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Sample records for 121ins2 heterozygosity reduced

  1. Surfactant protein-B 121ins2 heterozygosity, reduced pulmonary function, and chronic obstructive pulmonary disease in smokers

    Bækvad-Hansen, Marie; Dahl, Morten; Tybjaerg-Hansen, Anne; Nordestgaard, Børge G

    2010-01-01

    Hereditary surfactant protein-B deficiency is an autosomal recessive disorder that causes fatal respiratory distress syndrome in newborns. Seventy percent of the cases of hereditary surfactant protein-B deficiency are caused by homozygosity for the 121ins2 mutation in the surfactant protein-B gene...

  2. Reduced meiotic fitness in hybrids with heterozygosity for heterochromatin in the speciating Mus terricolor complex

    Tikaram Sharma; Amit Bardhan; Min Bahadur

    2003-03-01

    Mus terricolor I, II and III are the three chromosomal species which differ in stable autosomal short-arm heterochromatin variations established in homozygous condition. Analysis of meiosis in the laboratorygenerated F1 male hybrids from crosses (both ways) between M. terricolor I and II and between M. terricolor I and III shows high frequencies of pairing abnormalities at pachytene. The backcross (N3 generation) male hybrids between M. terricolor I and II have meiotic abnormalities as in the F1 male hybrids, though to a lesser extent. They show difference in pairing abnormalities in the different karyotypic forms; the backcross hybrids heterozygous for the heterochromatic short arms have more anomalies compared to the homokaryotypic hybrids. This suggests a negative influence of the heterochromatin heterozygosity in meiotic pairing. The results indicate a role for heterochromatin variations in the development of a reproductive barrier in the speciating M. terricolor complex.

  3. Imprinted survival genes preclude loss of heterozygosity of chromosome 7 in cancer cells.

    Boot, Arnoud; Oosting, Jan; de Miranda, Noel Fcc; Zhang, Yinghui; Corver, Willem E; van de Water, Bob; Morreau, Hans; van Wezel, Tom

    2016-09-01

    The genomes of a wide range of cancers, including colon, breast, and thyroid cancers, frequently show copy number gains of chromosome 7 and rarely show loss of heterozygosity. The molecular basis for this phenomenon is unknown. Strikingly, oncocytic follicular thyroid carcinomas can display an extreme genomic profile, with homozygosity of all chromosomes except for chromosome 7. The observation that homozygosity of chromosome 7 is never observed suggests that retention of heterozygosity is essential for cells. We hypothesized that cell survival genes are genetically imprinted on either of two copies of chromosome 7, which thwarts loss of heterozygosity at this chromosome in cancer cells. By employing a DNA methylation screen and gene expression analysis, we identified six imprinted genes that force retention of heterozygosity on chromosome 7. Subsequent knockdown of gene expression showed that CALCR, COPG2, GRB10, KLF14, MEST, and PEG10 were essential for cancer cell survival, resulting in reduced cell proliferation, G1 -phase arrest, and increased apoptosis. We propose that imprinted cell survival genes provide a genetic basis for retention of chromosome 7 heterozygosity in cancer cells. The monoallelically expressed cell survival genes identified in this study, and the cellular pathways that they are involved in, offer new therapeutic targets for the treatment of tumours showing retention of heterozygosity on chromosome 7. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:27265324

  4. A new method to detect loss of heterozygosity using cohort heterozygosity comparisons

    Loss of heterozygosity (LOH) is an important marker for one of the 'two-hits' required for tumor suppressor gene inactivation. Traditional methods for mapping LOH regions require the comparison of both tumor and patient-matched normal DNA samples. However, for many archival samples, patient-matched normal DNA is not available leading to the under-utilization of this important resource in LOH studies. Here we describe a new method for LOH analysis that relies on the genome-wide comparison of heterozygosity of single nucleotide polymorphisms (SNPs) between cohorts of cases and un-matched healthy control samples. Regions of LOH are defined by consistent decreases in heterozygosity across a genetic region in the case cohort compared to the control cohort. DNA was collected from 20 Follicular Lymphoma (FL) tumor samples, 20 Diffuse Large B-cell Lymphoma (DLBCL) tumor samples, neoplastic B-cells of 10 B-cell Chronic Lymphocytic Leukemia (B-CLL) patients and Buccal cell samples matched to 4 of these B-CLL patients. The cohort heterozygosity comparison method was developed and validated using LOH derived in a small cohort of B-CLL by traditional comparisons of tumor and normal DNA samples, and compared to the only alternative method for LOH analysis without patient matched controls. LOH candidate regions were then generated for enlarged cohorts of B-CLL, FL and DLBCL samples using our cohort heterozygosity comparison method in order to evaluate potential LOH candidate regions in these non-Hodgkin's lymphoma tumor subtypes. Using a small cohort of B-CLL samples with patient-matched normal DNA we have validated the utility of this method and shown that it displays more accuracy and sensitivity in detecting LOH candidate regions compared to the only alternative method, the Hidden Markov Model (HMM) method. Subsequently, using B-CLL, FL and DLBCL tumor samples we have utilised cohort heterozygosity comparisons to localise LOH candidate regions in these subtypes

  5. Heterozygosity at a single locus explains a large proportion of variation in two fitness-related traits in great tits: a general or a local effect?

    García-Navas, V; Cáliz-Campal, C; Ferrer, E S; Sanz, J J; Ortego, J

    2014-12-01

    In natural populations, mating between relatives can have important fitness consequences due to the negative effects of reduced heterozygosity. Parental level of inbreeding or heterozygosity has been also found to influence the performance of offspring, via direct and indirect parental effects that are independent of the progeny own level of genetic diversity. In this study, we first analysed the effects of parental heterozygosity and relatedness (i.e. an estimate of offspring genetic diversity) on four traits related to offspring viability in great tits (Parus major) using 15 microsatellite markers. Second, we tested whether significant heterozygosity-fitness correlations (HFCs) were due to 'local' (i.e. linkage to genes influencing fitness) and/or 'general' (genome-wide heterozygosity) effects. We found a significant negative relationship between parental genetic relatedness and hatching success, and maternal heterozygosity was positively associated with offspring body size. The characteristics of the studied populations (recent admixture, polygynous matings) together with the fact that we found evidence for identity disequilibrium across our set of neutral markers suggest that HFCs may have resulted from genome-wide inbreeding depression. However, one locus (Ase18) had disproportionately large effects on the observed HFCs: heterozygosity at this locus had significant positive effects on hatching success and offspring size. It suggests that this marker may lie near to a functional locus under selection (i.e. a local effect) or, alternatively, heterozygosity at this locus might be correlated to heterozygosity across the genome due to the extensive ID found in our populations (i.e. a general effect). Collectively, our results lend support to both the general and local effect hypotheses and reinforce the view that HFCs lie on a continuum from inbreeding depression to those strictly due to linkage between marker loci and genes under selection. PMID:25370831

  6. Genetic susceptibility to infectious disease in East African Shorthorn Zebu: a genome-wide analysis of the effect of heterozygosity and exotic introgression

    Murray, Gemma GR; Woolhouse, Mark EJ; Tapio, Miika; Mary N Mbole-Kariuki; Tad S. Sonstegard; Thumbi, Samuel M; Jennings, Amy E.; VAN WYK, ILANA CONRADIE; Chase-Topping, Margo; Kiara, Henry; TOYE, PHIL; Coetzer, Koos; deC Bronsvoort, Barend M; Hanotte, Olivier

    2013-01-01

    Background Positive multi-locus heterozygosity-fitness correlations have been observed in a number of natural populations. They have been explained by the correlation between heterozygosity and inbreeding, and the negative effect of inbreeding on fitness (inbreeding depression). Exotic introgression in a locally adapted population has also been found to reduce fitness (outbreeding depression) through the breaking-up of co-adapted genes, or the introduction of non-locally adapted gene variants...

  7. Genetic susceptibility to infectious disease in East African Shorthorn Zebu: a genome-wide analysis of the effect of heterozygosity and exotic introgression

    Murray, Gemma G. R.; Woolhouse, Mark; Tapio, Miika; Mbole-Kariuki, Mary Ndila; Thumbi, Samuel Mwangi; Jennings, Amy; Conradie van Wyk, Ilana; Kiara, Henry; Toye, Philip G.; Coetzer, J.A.W.; Bronsvoort, Mark; Hanotte, Olivier; Sonstegard, Tad; Chase-Topping, Margo

    2013-01-01

    BackgroundPositive multi-locus heterozygosity-fitness correlations have been observed in a number of natural populations. They have been explained by the correlation between heterozygosity and inbreeding, and the negative effect of inbreeding on fitness (inbreeding depression). Exotic introgression in a locally adapted population has also been found to reduce fitness (outbreeding depression) through the breaking-up of co-adapted genes, or the introduction of non-locally adapted gene variants....

  8. Inferring relationships between pairs of individuals from locus heterozygosities

    Spinetti Isabella

    2002-11-01

    Full Text Available Abstract Background The traditional exact method for inferring relationships between individuals from genetic data is not easily applicable in all situations that may be encountered in several fields of applied genetics. This study describes an approach that gives affordable results and is easily applicable; it is based on the probabilities that two individuals share 0, 1 or both alleles at a locus identical by state. Results We show that these probabilities (zi depend on locus heterozygosity (H, and are scarcely affected by variation of the distribution of allele frequencies. This allows us to obtain empirical curves relating zi's to H for a series of common relationships, so that the likelihood ratio of a pair of relationships between any two individuals, given their genotypes at a locus, is a function of a single parameter, H. Application to large samples of mother-child and full-sib pairs shows that the statistical power of this method to infer the correct relationship is not much lower than the exact method. Analysis of a large database of STR data proves that locus heterozygosity does not vary significantly among Caucasian populations, apart from special cases, so that the likelihood ratio of the more common relationships between pairs of individuals may be obtained by looking at tabulated zi values. Conclusions A simple method is provided, which may be used by any scientist with the help of a calculator or a spreadsheet to compute the likelihood ratios of common alternative relationships between pairs of individuals.

  9. Heterozygosity for a Bub1 mutation causes female-specific germ cell aneuploidy in mice

    Leland, Shawn; Nagarajan, Prabakaran; Polyzos, Aris; Thomas, Sharon; Samaan, George; Donnell, Robert; Marchetti, Francesco; Venkatachalam, Sundaresan

    2009-06-24

    Aneuploidy, the most common chromosomal abnormality at birth and the main ascertained cause of pregnancy loss in humans, originates primarily from chromosome segregation errors during oogenesis. Here we report that heterozygosity for a mutation in the mitotic checkpoint kinase gene, Bub1, induces aneuploidy in female germ cells of mice, and that the effect increases with advancing maternal age. Analysis of Bub1 heterozygous oocytes showed that aneuploidy occurred primarily during the first meiotic division and involved premature sister chromatid separation. Furthermore, aneuploidy was inherited in zygotes and resulted in the loss of embryos after implantation. The incidence of aneuploidy in zygotes was sufficient to explain the reduced litter size in matings with Bub1 heterozygous females. No effects were seen in germ cells from heterozygous males. These findings show that Bub1 dysfunction is linked to inherited aneuploidy in female germ cells and may contribute to the maternal age-related increase in aneuploidy and pregnancy loss.

  10. Multilocus Heterozygosity and Coronary Heart Disease: Nested Case-Control Studies in Men and Women

    Mukamal, Kenneth J.; Jensen, Majken K.; Pers, Tune Hannes;

    2015-01-01

    , homocysteine, adiponectin, or body-mass index. Conclusions: In these parallel nested case-control studies, we found no relationship of multilocus heterozygosity with risk of CHD or its major risk factors. Studies in other populations are needed to rule out associations with lower levels of heterozygosity....

  11. Heterozygosity for the classical galactosemia mutation does not affect ovarian reserve and menopausal age

    Knauff, Erik A. H.; Richardus, Renate; Eijkemans, Marinus J.; Broekinans, Frank J.; de Jong, Frank J.; Fauser, Bart C. J. M.; Bosch, Annet M.

    2007-01-01

    Female patients with classical galactosemia (galactose-1-phosphate uridyltransferase [GALT] deficiency) frequently suffer from premature ovarian failure, despite treatment with a galactose-restricted diet. Earlier research has suggested an association between heterozygosity for GALT mutations and ea

  12. Mechanisms of increased risk of tumorigenesis in Atm and Brca1 double heterozygosity

    Wang Jufang

    2011-08-01

    Full Text Available Abstract Background Both epidemiological and experimental studies suggest that heterozygosity for a single gene is linked with tumorigenesis and heterozygosity for two genes increases the risk of tumor incidence. Our previous work has demonstrated that Atm/Brca1 double heterozygosity leads to higher cell transformation rate than single heterozygosity. However, the underlying mechanisms have not been fully understood yet. In the present study, a series of pathways were investigated to clarify the possible mechanisms of increased risk of tumorigenesis in Atm and Brca1 heterozygosity. Methods Wild type cells, Atm or Brca1 single heterozygous cells, and Atm/Brca1 double heterozygous cells were used to investigate DNA damage and repair, cell cycle, micronuclei, and cell transformation after photon irradiation. Results Remarkable high transformation frequency was confirmed in Atm/Brca1 double heterozygous cells compared to wild type cells. It was observed that delayed DNA damage recognition, disturbed cell cycle checkpoint, incomplete DNA repair, and increased genomic instability were involved in the biological networks. Haploinsufficiency of either ATM or BRCA1 negatively impacts these pathways. Conclusions The quantity of critical proteins such as ATM and BRCA1 plays an important role in determination of the fate of cells exposed to ionizing radiation and double heterozygosity increases the risk of tumorigenesis. These findings also benefit understanding of the individual susceptibility to tumor initiation.

  13. Mechanisms of increased risk of tumorigenesis in Atm and Brca1 double heterozygosity

    Both epidemiological and experimental studies suggest that heterozygosity for a single gene is linked with tumorigenesis and heterozygosity for two genes increases the risk of tumor incidence. Our previous work has demonstrated that Atm/Brca1 double heterozygosity leads to higher cell transformation rate than single heterozygosity. However, the underlying mechanisms have not been fully understood yet. In the present study, a series of pathways were investigated to clarify the possible mechanisms of increased risk of tumorigenesis in Atm and Brca1 heterozygosity. Wild type cells, Atm or Brca1 single heterozygous cells, and Atm/Brca1 double heterozygous cells were used to investigate DNA damage and repair, cell cycle, micronuclei, and cell transformation after photon irradiation. Remarkable high transformation frequency was confirmed in Atm/Brca1 double heterozygous cells compared to wild type cells. It was observed that delayed DNA damage recognition, disturbed cell cycle checkpoint, incomplete DNA repair, and increased genomic instability were involved in the biological networks. Haploinsufficiency of either ATM or BRCA1 negatively impacts these pathways. The quantity of critical proteins such as ATM and BRCA1 plays an important role in determination of the fate of cells exposed to ionizing radiation and double heterozygosity increases the risk of tumorigenesis. These findings also benefit understanding of the individual susceptibility to tumor initiation

  14. Heterozygosity in an Isolated Population of a Large Mammal Founded by Four Individuals Is Predicted by an Individual-Based Genetic Model

    Kekkonen, Jaana; Wikström, Mikael; Brommer, Jon E

    2012-01-01

    Background Within-population genetic diversity is expected to be dramatically reduced if a population is founded by a low number of individuals. Three females and one male white-tailed deer Odocoileus virginianus, a North American species, were successfully introduced in Finland in 1934 and the population has since been growing rapidly, but remained in complete isolation from other populations. Methodology/Principal Findings Based on 14 microsatellite loci, the expected heterozygosity H was 0...

  15. Analysis of APC allelic imbalance/loss of heterozygosity and APC protein expression in cutaneous squamous cell carcinomas.

    Gray, Sarah E

    2012-02-01

    BACKGROUND: The adenomatous polyposis coli (APC) gene is a tumor suppressor gene which is mutated in the hereditary disease, familial adenomatous polyposis (FAP). Somatic mutations of the APC gene have also been identified in the majority of sporadic colorectal carcinomas, and mutation of the APC gene appears to be an early step in the initiation of colon cancer. Loss of heterozygosity (LOH) of APC has been described in a variety of other cancer types, including renal cell carcinoma, gastric cancer, non-small cell lung cancer, endometrial cancer and oral squamous cell carcinomas (SCC). AIM: To determine the role played by APC gene in the genesis of cutaneous SCC. MATERIALS AND METHODS: Allelic imbalance\\/loss of heterozygosity (AI\\/LOH) was examined in twenty-two histologically confirmed cutaneous squamous cell carcinomas (SCC) using microsatellite markers, proximal to the APC gene. Immunohistochemical analysis of APC protein expression was also examined in the cutaneous SCC. RESULTS: AI\\/LOH was detected in 60% of the SCC samples using D5S346 marker (proximal to the APC gene). Ninty-five percent of the SCC samples showed positive reduced APC expression, however the localization of the APC protein was abnormal. CONCLUSION: The abnormal expression of APC suggests that APC gene may play a role in cutaneous SCC development.

  16. Loss of heterozygosity on chromosome 3, bands q24----qter, in a diploid meningioma.

    Färber, U; Schneider, G; Schrell, U M; Fahlbusch, P; Adams, E F; Blin, N; Henn, W

    1991-01-01

    Cytogenetic analysis of a meningioma from a 46-year-old female patient exhibited as the sole cytogenetic aberration a deletion on the long arm of one chromosome 3 involving bands 3q24----qter. To verify this finding, RFLP analysis was performed with two polymorphic probes, MOX2 and D3S5. The patient was informative for both single copy probes and demonstrated loss of heterozygosity in the region above whereas chromosome 22 displayed no loss of heterozygosity as judged by a proximal and a distal probe. PMID:1680607

  17. Extremely Reduced Levels of Heterozygosity in the Vertebrate Pathogen Encephalitozoon cuniculi

    Selman, M.; Sak, Bohumil; Kváč, Martin; Farinelli, L.; Weiss, L.M.; Corradi, N.

    2013-01-01

    Roč. 12, č. 4 (2013), s. 496-502. ISSN 1535-9778 R&D Projects: GA ČR(CZ) GAP505/11/1163 Institutional support: RVO:60077344 Keywords : intracellular parasites * microsporidian genome * sexual reproduction * clonal diploids Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.179, year: 2013

  18. Wildlife translocation: the conservation implications of pathogen exposure and genetic heterozygosity

    Penedo M Cecilia T

    2011-02-01

    Full Text Available Abstract Background A key challenge for conservation biologists is to determine the most appropriate demographic and genetic management strategies for wildlife populations threatened by disease. We explored this topic by examining whether genetic background and previous pathogen exposure influenced survival of translocated animals when captive-bred and free-ranging bighorn sheep (Ovis canadensis were used to re-establish a population that had been extirpated in the San Andres Mountains in New Mexico, USA. Results Although the free-ranging source population had significantly higher multi-locus heterozygosity at 30 microsatellite loci than the captive bred animals, neither source population nor genetic background significantly influenced survival or cause of death. The presence of antibodies to a respiratory virus known to cause pneumonia was associated with increased survival, but there was no correlation between genetic heterozygosity and the presence of antibodies to this virus. Conclusions Although genetic theory predicts otherwise, increased heterozygosity was not associated with increased fitness (survival among translocated animals. While heterosis or genetic rescue effects may occur in F1 and later generations as the two source populations interbreed, we conclude that previous pathogen exposure was a more important marker than genetic heterozygosity for predicting survival of translocated animals. Every wildlife translocation is an experiment, and whenever possible, translocations should be designed and evaluated to test hypotheses that will further improve our understanding of how pathogen exposure and genetic variability influence fitness.

  19. Heterozygosity for R1141X in ABCC6 and risk of ischemic vascular disease

    Hornstrup, Louise S; Tybjærg-Hansen, Anne; Haase, Christiane L; Nordestgaard, Børge G; Sillesen, Henrik; Grande, Peer; Frikke-Schmidt, Ruth

    2011-01-01

    Pseudoxanthoma elasticum (PXE) is an autosomal recessive disease caused by loss-of-function mutations in ABCC6 and characterized by elastic calcification leading to dermal, ocular, and ischemic vascular disease. We tested the hypothesis that heterozygosity for R1141X, the most frequent PXE-causing...

  20. The Adaptive Response in p53 Cancer Prone Mice: Loss of heterozygosity and Genomic Instability

    Josee, Lavoie [McMaster Univ., Hamilton, ON (Canada). Medical Physics and Applied Radiation Sciences; Dolling, Jo-Anna [Credit Valley Hospital, Missassauga, ON (Canada); Mitchel, Ron E.J. [Atomic Energy of Canada (AECL), Limited, Chalk River, ON (Canada); Boreham, Douglas R. [McMaster Univ., Hamilton, ON (Canada). Medical Physics and Applied Radiation Sciences

    2004-09-28

    mice, only numerical aberrations were observed in 5 to 20% of the cells. There seem to be an age related increase in numerical aberrations as mice grow old. The results indicate that the presence of a defective copy of the Trp53 gene does not seem to affect spontaneous chromosomal instability or in response to chronic low dose exposure to g-radiation. In previous studies it was speculated that low dose and low dose rate in vivo exposure to g-radiation induces an adaptive response, which reduces the risk of cancer death generated by subsequent DNA damage from either spontaneous or radiation induced events due to enhanced recombinational repair. Induced recombination could result from reversion to homozygosity at Trp53 gene locus (Trp53 +/- to +/+) or loss of heterozygosity in unexposed mice (Trp53 +/- to -/-). This hypothesis was investigated using the quantitative real-time Polymerase Chain Reaction (QRT-PCR) quantification method and the novel Rolling Circle Amplification technique (RCA). For these purposes, spleenocytes and bone marrow cells from all the mice were isolated for cell fixation and DNA extraction. The defective Trp53 allele is generated by integration of a portion of the cloning vector pKONEO DNA into the coding sequence. Therefore, the genotypic changes are monitored based on the detection of the NEO allele and the normal Trp53 allele in the cells. To evaluate loss of heterozygosity at the Trp53 gene locus in a cell, detection of the NEO allele and the normal Trp53 allele using the dual color RCA was utilized. In our hands, this protocol did not give the required sensitivity. The gene signal enumeration was inconsistent and not reproducible. The protocol was modified and could not be optimized. Therefore, the QRT-PCR method was selected to evaluate the loss of heterozygosity with greater sensitivity and efficiency. A set of 4 primers was designed to target the NEO allele and the normal Trp53 allele in a PCR experiment using the LightCycler instrument

  1. Females prefer the scent of outbred males: good-genes-as-heterozygosity?

    Thoß Michaela

    2009-05-01

    Full Text Available Abstract Background There is increasing interest to determine the relative importance of non-additive genetic benefits as opposed to additive ones for the evolution of mating preferences and maintenance of genetic variation in sexual ornaments. The 'good-genes-as-heterozygosity' hypothesis predicts that females should prefer to mate with more heterozygous males to gain more heterozygous (and less inbred offspring. Heterozygosity increases males' sexual ornamentation, mating success and reproduction success, yet few experiments have tested whether females are preferentially attracted to heterozygous males, and none have tested whether females' own heterozygosity influences their preferences. Outbred females might have the luxury of being more choosey, but on the other hand, inbred females might have more to gain by mating with heterozygous males. We manipulated heterozygosity in wild-derived house mice (Mus musculus musculus through inbreeding and tested whether the females are more attracted to the scent of outbred versus inbred males, and whether females' own inbreeding status affects their preferences. We also tested whether infecting both inbred and outbred males with Salmonella would magnify females' preferences for outbred males. Results Females showed a significant preference for outbred males, and this preference was more pronounced among inbred females. We found no evidence that Salmonella infection increased the relative attractiveness of outbred versus inbred males; however, we found no evidence that inbreeding affected males' disease resistance in this study. Conclusion Our findings support the idea that females are more attracted to outbred males, and they suggest that such preferences may be stronger among inbred than outbred females, which is consistent with the 'good-genes-as-heterozygosity' hypothesis. It is unclear whether this odour preference reflects females' actual mating preferences, though it suggests that future studies

  2. A Successful Mother and Neonate Outcome for a Woman with Essential Thrombocytosis and FV Leiden Heterozygosity

    Marianna Politou

    2016-01-01

    Full Text Available Essential thrombocytosis (ET and FV Leiden heterozygosity represent an acquired and hereditable hypercoagulable state, respectively. An uncommon case of coexistence of ET and FV Leiden heterozygosity in a 36-year-old pregnant woman and her successful pregnancy outcome is described. She was considered to be at high risk of thrombosis during her pregnancy and she was treated with both prophylactic dose of LMWH and aspirin daily throughout her pregnancy and for a 6-week period postpartum. The efficacy of the anticoagulation treatment was monitored in various time points not only by measuring anti-Xa levels and D-Dimers but also with new coagulation methods such as rotation thromboelastometry and multiplate. Global assessment of coagulation using additional newer laboratory tests might prove useful in monitoring coagulation pregnancies at high risk for thrombosis.

  3. Size and heterozygosity influence partner selection in the Formosan subterranean termite

    Husseneder, Claudia; Simms, Dawn M.

    2008-01-01

    In monogamous species that exhibit extensive biparental investment, such as termites, both sexes are predicted to be selective when choosing a mate. Size-related traits are expected to be important in partner selection because the fat reserves of the colony founders sustain the incipient colony. Partner relatedness and heterozygosity determine the degree of inbreeding and genetic diversity within the colony and may thus also influence partner selection. To test these predictions, we investiga...

  4. Heterozygosity for the alpha1-antitrypsin Z allele may confer genetic risk of cholangiocarcinoma

    Mihalache, Florentina; HÖBLINGER, AKSANA; Grünhage, Frank; Krawczyk, Marcin; Gärtner, Barbara C.; Acalovschi, Monica; Sauerbruch, Tilman; Lammert, Frank; Zimmer, Vincent

    2010-01-01

    Abstract Background & Aim: Alpha1-antitrypsin (?1AT) deficiency caused by Z allele homozygosity represents a risk factor for hepatocellular carcinoma. Previous studies have implicated ?1AT Z heterozygosity in cholangiocarcinogenesis. We assessed the ?common? Z and S alleles as well as the promoter variant rs8004738 for association with cholangiocarcinoma (CCA). Patients & Methods: We genotyped 182 Caucasian patients and 350 controls for rs28929474 (Z), rs17580 (S) and the varia...

  5. Excess heterozygosity contributes to genetic map expansion in pea recombinant inbred populations.

    Knox, M.R.; Ellis, T. H. N.

    2002-01-01

    Several plant genetic maps presented in the literature are longer than expected from cytogenetic data. Here we compare F(2) and RI maps derived from a cross between the same two parental lines and show that excess heterozygosity contributes to map inflation. These maps have been constructed using a common set of dominant markers. Although not generally regarded as informative for F(2) mapping, these allowed rapid map construction, and the resulting data analysis has provided information not o...

  6. Developmental Stability Covaries with Genome-Wide and Single-Locus Heterozygosity in House Sparrows

    Carl Vangestel; Joachim Mergeay; Deborah A Dawson; Viki Vandomme; Luc Lens

    2011-01-01

    Fluctuating asymmetry (FA), a measure of developmental instability, has been hypothesized to increase with genetic stress. Despite numerous studies providing empirical evidence for associations between FA and genome-wide properties such as multi-locus heterozygosity, support for single-locus effects remains scant. Here we test if, and to what extent, FA co-varies with single- and multilocus markers of genetic diversity in house sparrow (Passer domesticus) populations along an urban gradient. ...

  7. Effect of ATM heterozygosity on heritable DNA damage in mice following paternal F0 germline irradiation

    The ataxia telangiectasia mutated (ATM) gene product maintains genome integrity and initiates cellular DNA repair pathways following exposures to genotoxic agents. ATM also plays a significant role in meiotic recombination during spermatogenesis. Fertilization with sperm carrying damaged DNA could lead to adverse effects in offspring including developmental defects or increased cancer susceptibility. Currently, there is little information regarding the effect of ATM heterozygosity on germline DNA repair and heritable effects of paternal germline-ionizing irradiation. We used neutral pH comet assays to evaluate spermatozoa 45 days after acute whole-body irradiation of male mice (0.1 Gy, attenuated 137Cs γ rays) to determine the effect of ATM heterozygosity on delayed DNA damage effects of Type A/B spermatogonial irradiation. Using the neutral pH sperm comet assay, significant irradiation-related differences were found in comet tail length, percent tail DNA and tail extent moment, but there were no observed differences in effect between wild-type and ATM +/- mice. However, evaluation of spermatozoa from third generation descendants of irradiated male mice for heritable chromatin effects revealed significant differences in DNA electrophoretic mobility in the F3 descendants that were based upon the irradiated F0 sire's genotype. In this study, radiation-induced chromatin alterations to Type A/B spermatogonia, detected in mature sperm 45 days post-irradiation, led to chromatin effects in mature sperm three generations later. The early cellular response to and repair of DNA damage is critical and appears to be affected by ATM zygosity. Our results indicate that there is potential for heritable genetic or epigenetic changes following Type A/B spermatogonial irradiation and that ATM heterozygosity increases this effect

  8. Oligonucleotide fingerprinting of free-ranging and captive rhesus macaques from Cayo Santiago: paternity assignment and comparison of heterozygosity.

    Nürnberg, P; Berard, J D; Bercovitch, F; Epplen, J T; Schmidtke, J; Krawczak, M

    1993-01-01

    Multilocus DNA fingerprinting with oligonucleotide probes (GTG)5, (GATA)4, and (CA)8 was applied in order to determine paternity in one birth cohort (15 infants) of social group (S) from the free-ranging colony of rhesus macaques (Macaca mulatta) on Cayo Santiago. While sires could be identified in 11 cases, all males tested (N = 19) could be excluded from paternity for the remaining four infants. Data revealed marked discrepancies between actual paternity and paternity as inferred from the observation of copulation behavior. Thus, a dominant social rank does not appear to be strongly associated with reproductive success. Furthermore, alternative reproductive strategies were found to yield comparable net benefits in reproduction. A second group of animals (M) was translocated from Cayo Santiago to the Sabana Seca Field Station in 1984. They have continuously resided together in a large outdoor enclosure since then. Here paternity assessment was seriously impeded by a reduced number of discriminating bands, i.e. offspring bands which were unequivocally derived from the sires. This was initially held to be indicative of a smaller degree of heterozygosity in Group M, and was attributed to inbreeding due to a lack of male immigration or extra-group fertilizations. However, a comparison of the DNA fingerprint patterns obtained in Group S and Group M lends only partial support to this idea. PMID:8400713

  9. Do females of the scarlet rosefinch (Carpodacus erythrinus) increase offspring heterozygosity through extra-pair matings?

    Poláková, Radka; Vinkler, Michal; Schnitzer, J.; Bryja, Josef; Munclinger, P.; Albrecht, Tomáš

    Brno: Ústav biologie obratlovců AV ČR, 2008 - (Bryja, J.; Nedvěd, O.; Sedláček, F.; Zukal, J.). s. 163 ISBN 978-80-87189-00-9. [Zoologické dny. 14.02.2008-15.02.2008, České Budějovice] R&D Projects: GA ČR GA206/06/0851 Institutional research plan: CEZ:AV0Z60930519 Keywords : scarlet rosefinch * heterozygosity * extrapair paternity Subject RIV: EB - Genetics ; Molecular Biology

  10. Osteogenesis imperfecta due to compound heterozygosity for the LEPRE1 gene.

    Moul, Adrienne; Alladin, Amanda; Navarrete, Cristina; Abdenour, George; Rodriguez, Maria M

    2013-10-01

    Osteogenesis imperfecta is a rare connective tissue disorder characterized by bone fragility and low bone density. Most cases are caused by an autosomal dominant mutation in either COL1A1 or COL1A2 gene encoding type I collagen. However, autosomal recessive forms have been identified. We present a patient with severe respiratory distress due to osteogenesis imperfecta simulating type II, born to a non-consanguineous couple with mixed African-American and African-Hispanic ethnicity. Cultured skin fibroblasts demonstrated compound heterozygosity for mutations in the LEPRE1 gene encoding prolyl 3-hydroxylase 1 confirming the diagnosis of autosomal recessive osteogenesis imperfecta type VIII, perinatal lethal type. PMID:23301918

  11. Loss of heterozygosity analyzed by single nucleotide polymorphisrn array in cancer

    HaiTao Zheng; ZhiHai Peng; Sheng Li; Lin He

    2005-01-01

    Neoplastic progression is generally characterized by the accumulation of multiple genetic alterations including loss of tumor suppression gene function.Loss of heterozygosity (LOH) has been used to identify genomic regions that harbor tumor suppressor genes and to characterize different tumor types, pathological stages and progression. LOH pattern has been detected by allelotyping using restriction fragment length polymorphism, and later by simple sequence length polymorphisms (SSLPs or microsatellite) for 10 years.This paper reviews the detection of LOH by recently developed single nucleotide polymorphism (SNP) arrays (all analyzed by Affymetrix array); furthermore, its advantage and disadvantage were analyzed in several kinds of cancer.

  12. No correlation between multi-locus heterozygosity and fitness in the common buzzard despite heterozygote advantage for plumage colour.

    Boerner, M; Hoffman, J I; Amos, W; Chakarov, N; Kruger, O

    2013-10-01

    Correlations between heterozygosity and fitness are frequently found but rarely well understood. Fitness can be affected by single loci of large effect which correlate with neutral markers via linkage disequilibrium, or as a result of variation in genome-wide heterozygosity following inbreeding. We explored these alternatives in the common buzzard, a raptor species in which three colour morphs differ in their lifetime reproductive success. Using 18 polymorphic microsatellite loci, we evaluated potential genetic differences among the morphs which may lead to subpopulation structuring and tested for correlations between three fitness-related traits and heterozygosity, both genome wide and at each locus separately. Despite their assortative mating pattern, the buzzard morphs were found to be genetically undifferentiated. Multilocus heterozygosity was only found to be correlated with a single fitness-related trait, infection with the blood parasite, Leucocytozoon buteonis, and this was via interactions with vole abundance and age. One locus also showed a significant relationship with blood parasite infection and ectoparasite infestation. The vicinity of this locus contains two genes, one of which is potentially implicated in the immune system of birds. We conclude that genome-wide heterozygosity is unlikely to be a major determinant of parasite burden and body condition in the polymorphic common buzzard. PMID:23980596

  13. Excess heterozygosity contributes to genetic map expansion in pea recombinant inbred populations.

    Knox, M R; Ellis, T H N

    2002-10-01

    Several plant genetic maps presented in the literature are longer than expected from cytogenetic data. Here we compare F(2) and RI maps derived from a cross between the same two parental lines and show that excess heterozygosity contributes to map inflation. These maps have been constructed using a common set of dominant markers. Although not generally regarded as informative for F(2) mapping, these allowed rapid map construction, and the resulting data analysis has provided information not otherwise obvious when examining a population from only one generation. Segregation distortion, a common feature of most populations and marker systems, found in the F(2) but not the RI, has identified excess heterozygosity. A few markers with a deficiency of heterozygotes were found to map to linkage group V (chromosome 3), which is known to form rod bivalents in this cross. Although the final map length was longer for the F(2) population, the mapped order of markers was generally the same in the F(2) and RI maps. The data presented in this analysis reconcile much of the inconsistency between map length estimates from chiasma counts and genetic data. PMID:12399396

  14. Calculation of breed direct and maternal genetic fractions and breed specific direct and maternal heterozygosity for crossbreeding data

    L.D. Van Vleck

    1997-12-01

    Full Text Available Teaching, research, and herd breeding applications may require calculation of breed additive contributions for direct and maternal genetic effects and fractions of heterozygosity associated with breed specific direct and maternal heterosis effects. These coefficients can be obtained from the first NB rows of a pseudo numerator relationship matrix where the first NB rows represent fractional contributions by breed to each animal or group representing a specific breed cross. The table begins with an NB x NB identity matrix representing pure breeds. Initial animals or representative crosses must be purebreds or two-breed crosses. Parents of initial purebreds are represented by the corresponding column and initial two-breed cross progeny by the two corresponding columns of the identity matrix. After that, usual rules are used to calculate the NB column entries corresponding to breeds for each animal. The NB entries are fractions of genes expected to be contributed by each of the pure breeds and correspond to the breed additive direct fractions. Entries in the column corresponding to the dam represent breed additive maternal fractions. Breed specific direct heterozygosity coefficients are entries of an NB x NB matrix formed by the outer product of the two NB by 1 columns associated with sire and dam of the animal. One minus sum of the diagonals represents total direct heterozygosity. Similarly, the NB x NB matrix formed by the outer product of columns associated with sire of dam and dam of dam contains breed specific maternal heterozygosity coefficients. These steps can be programmed to create covariates to merge with data. If X represents these coefficients for all unique breed crosses, then the reduced row echelon form function of MATLAB or SAS can be used on X to determine estimable functions of additive breed direct and maternal effects and breed specific direct and maternal heterosis effectsO ensino, a pesquisa e a criação de gado podem

  15. The imprecision of heterozygosity-fitness correlations hinders the detection of inbreeding and inbreeding depression in a threatened species.

    Grueber, Catherine E; Waters, Jonathan M; Jamieson, Ian G

    2011-01-01

    In nonpedigreed wild populations, inbreeding depression is often quantified through the use of heterozygosity-fitness correlations (HFCs), based on molecular estimates of relatedness. Although such correlations are typically interpreted as evidence of inbreeding depression, by assuming that the marker heterozygosity is a proxy for genome-wide heterozygosity, theory predicts that these relationships should be difficult to detect. Until now, the vast majority of empirical research in this area has been performed on generally outbred, nonbottlenecked populations, but differences in population genetic processes may limit extrapolation of results to threatened populations. Here, we present an analysis of HFCs, and their implications for the interpretation of inbreeding, in a free-ranging pedigreed population of a bottlenecked species: the endangered takahe (Porphyrio hochstetteri). Pedigree-based inbreeding depression has already been detected in this species. Using 23 microsatellite loci, we observed only weak evidence of the expected relationship between multilocus heterozygosity and fitness at individual life-history stages (such as survival to hatching and fledging), and parameter estimates were imprecise (had high error). Furthermore, our molecular data set could not accurately predict the inbreeding status of individuals (as 'inbred' or 'outbred', determined from pedigrees), nor could we show that the observed HFCs were the result of genome-wide identity disequilibrium. These results may be attributed to high variance in heterozygosity within inbreeding classes. This study is an empirical example from a free-ranging endangered species, suggesting that even relatively large numbers (>20) of microsatellites may give poor precision for estimating individual genome-wide heterozygosity. We argue that pedigree methods remain the most effective method of quantifying inbreeding in wild populations, particularly those that have gone through severe bottlenecks. PMID

  16. AB170. Loss of heterozygosity in child with multiple congenital anomaly

    Aswin, Yulia Ariani; Sjarif, Damayanti Rusli

    2015-01-01

    Background Multiple congenital anomaly (MCA) has become an increasing problem in worldwide, since it significantly contributes to infant mortality rate (IMR) and caused many morbidities during neonatal until childhood period. Prevention has to be done to decrease the incidence through prenatal diagnosis, hence a proper postnatal definitive diagnosis should be established as a reference. Microaray system is one of the leading technique in order to detect copy number variations (CNV’s) and loss of heterozygosities (LOH’s) which may responsible to phenotype. This report is aimed to demonstrate a case of MCA with normal G-banding result, no pathologic CNV’s, with wide area of LOH’s contain several genes which may responsible to the phenotype. Methods Using Online Mendelian Inheritance in Man (OMIM) and Pictures of Standard Syndromes and Undiagnosed Malformation (POSSUM) databases, certain syndrome were tried to identify. Chromosome analysis were performed to detect large aberration. Microarray examination was done using Infinium CytoSNP-850K DNA analysis bead chip kit from Illumina. Chip was scanned using Hi-scan scanner from Illumina. Data were extracted using genome studio software. Data were analyzed using Nexus software. Results A 8-year-old girl was brought by parents to hospital with a chief complains dyspnea and looks cyanosis since 1 month prior to admission. She was born spontaneously, full term, no cyanosis, with distinctive face. Birth weight was 2,800 g. Her growth was retarded, but her development was normal. There is no history of seizure. Patient was a student in 3rd grade of elementary school, with an average level of intelligence. Physical examination reveals tachypnea and cyanosis. There was pansystolic mur-mur without gallop. Clubbing fingers were noticed. There are several dysmorphic feature such as frontal bossing, wide frontal, depressed nasal bridge, hypertelorism, down slanting palpebrae, asymetric face (hemi hypoplasia), midfacial

  17. LOSS OF HETEROZYGOSITY FOR MARKERS ON 22CHROMOSOME IN SPORADIC SCHWANNOMA

    2000-01-01

    Objective To analyze the loss of heterozygosity ( LOH) for markers on chromosome 22 ( CHR 22 ) and its significance with their clinical behaviors. Methods The frequency of CHR22 LOH in 36 schwannomas was observed by dena tured polyacrylamide gels and silver staining, and the proliferative index of schwannoma was calculated by Ki-67 and PCNA im munohistochemistry. Results 15 schwannomas (41.6%) showed allele loss. The proliferative index of schwannomas with LOH were significantly higher than those without LOH (P<0.05). In acoustic neuromas, patients with LOH were younger at the age of diagnosis, larger size of tumor, shorter history and higher growth rate than those without LOH, but with no signifi cance. Conclusion CHR22 LOH was the frequent event in the tumorigenesis of sporadic schwannoma. There were some links between CHR22 LOH and clinical behavior.

  18. Frequent loss of heterozygosity at 8p22 chromosomal region in diffuse type of gastric cancer

    Hedayat Allah Hosseini; Ali Ahani; Hamid Galehdari; Ali Mohammad Froughmand; Masoud Hosseini; Abdolrahim Masjedizadeh; Mohammad Reza Zali

    2007-01-01

    AIM: To study the loss of heterozygosity (LOH) at 8p21-23 locus in diffuse gastric cancer.METHODS: To evaluate the involvement of this region in gastric cancer, we used eight microsatellite markers covering two Mb of mentioned region, to perform a high-resolution analysis of allele loss in 42 cases of late diffuse gastric adenocarcinoma.RESULTS: Six of these STS makers: D8S1149, D8S1645,D8S1643, D8S1508, D8S1591, and D8S1145 showed 36%, 28%, 37%, 41%, 44% and 53% LOH, respectively.CONCLUSION: A critical region of loss, close to the NAT2 locus and relatively far from FEZ1 gene currently postulated as tumor suppressor gene in this region.

  19. LOSS OF HETEROZYGOSITY ON CHROMOSOME 17p13.3 IN OVARIAN CANCER AND CERVICAL CANCER

    Zhang Guoling; Yang Huijian; Xu Kaili; Zhou Jin; Qin Ruidi; Lu Minghua

    1998-01-01

    Objective:To identify the loss of heterozygosity (LOH) on chromosome 17p13.3 in ovarian cancer and cervical cancer. Methods: The frequency of LOH on chromosome 17p13.3 in DNA samples from 24 ovarian cancers, 9 cervical cancers, and 13 non-malignant gynecological diseases were determined respectively, using Southern blot method with probe PYNZ.22. Results:LOH on 17p13.3 was found in 12 of 24 (50.0%) ovarian cancers (including a borderline mucinous cystadenoma), 4of 9 (44.4%) cervical carcinomas, and 1 of 13 (7.7%) nonmalignant gynecological diseases, which was cervical intraepithelial neoplasm HI (CIN Ⅲ) (P<0.01).Conclusion: These results show that LOH on 17p13.3 is associated with ovarian cancer and cervical cancer,suggesting that detection of LOH on 17p13.3 may be helpful to understand the molecular pathogenesis of ovarian cancer and cervical cancer.

  20. Radiosensitivity to high energy iron ions is influenced by heterozygosity for Atm, Rad9 and Brca1

    Zhou, G.; Smilenov, L. B.; Lieberman, H. B.; Ludwig, T.; Hall, E. J.

    2010-09-01

    Loss of function of DNA repair genes has been implicated in the development of many types of cancer. In the last several years, heterozygosity leading to haploinsufficiency for proteins involved in DNA repair was shown to play a role in genomic instability and carcinogenesis after DNA damage is induced, for example by ionizing radiation. Since the effect of heterozygosity for one gene is relatively small, we hypothesize that predisposition to cancer could be a result of the additive effect of heterozygosity for two or more genes critical to pathways that control DNA damage signaling, repair or apoptosis. We investigated the role of heterozygosity for Atm, Rad9 and Brca1 on cell oncogenic transformation and cell survival induced by 1 GeV/ n56Fe ions. Our results show that cells heterozygous for both Atm and Rad9 or Atm and Brca1 have high survival rates and are more sensitive to transformation by high energy iron ions when compared with wild-type controls or cells haploinsufficient for only one of these proteins. Since mutations or polymorphisms for similar genes exist in a small percentage of the human population, we have identified a radiosensitive sub-population. This finding has several implications. First, the existence of a radiosensitive sub-population may distort the shape of the dose-response relationship. Second, it would not be ethical to put exceptionally radiosensitive individuals into a setting where they may potentially be exposed to substantial doses of radiation.

  1. LOSS OF HETEROZYGOSITY OF ER GENE IN BREAST CANCER AND ITS CLINICAL SIGNIFICANCE

    郑唯强; 郑建明; 卢建; 胡凤仙

    2002-01-01

    Objective: Clinically, the reason of resistance for breast cancer to endocrine therapy has not been well known. The current study attempted to examine loss of heterozygosity (LOH) on the estrogen receptor (ER) gene in breast cancer and its relationship to clinicopathologic findings. Methods: DNAs of tumor tissues and blood lymphocytes were collected from 40 cases of primary breast cancer patients and LOH were detected using the microsatellite repeat assay and combined with other ER immunohistochemical assays. Results: ER-positive staining was observed in 65% of breast cancer. Heterogeneity of ER expression was found. Seven of the patients (17.5%) showed LOH. In three of the seven cases, there was total loss, and there was a marked reduction in the intensity of signal in the other four cases. LOH was associated with histologic grade, occurring more frequently in ER-negative and lymph node metastasis group, but not with tumor size and patient ages. Conclusion: This result implied that LOH of the ER gene may have an important role in the progression of breast cancer. It was postulated that the lack of ER function induced by LOH may contributed to endocrine therapy resistance of breast cancer since the tumor clone would escape from the ER regulation, obtain growth predisposition and finally lost response to therapy.

  2. LOSS OF HETEROZYGOSITY ON CHROMOSOME 13 IN SQUAMOUS CELL CARCINOMAS OF THE LARYNX

    Bai Sujuan; Zhang Xue; Wang Jun; Sun Kailai; Fei Shengzhong

    1998-01-01

    Objective: To locate lost region of tumor suppressor gene on chromosome 13q in squamous cell carcinoma of the larynx (LSCC) and to provide clues and evidence for discovering and locating new suppressor gene.Methods: Loss of heterozygosity (LOH) on chromosome 13q was analyzed in 58 LSCC patients by microsatellite polymorphic sequences in loci D13S765 (13q13), RB1.20(13q14.2), D13S133 (13q14.3) and D13S318 (13q21) on chromosome 13 by PCR. Results: There weren't any LOH on chromosome 13q in 3 cases with preinvasive LSCC. Forty-five percentage (24/53) of the 53 invasive LSCC cases showed LOH at one or more loci on chromosome 13q region. The highest percentage of LOH on chromosome 13q was 52% (22/53) at D13S765locus. Conclusion: The deletion region on chromosome 13q was located near by D13S765 locus which is centromeric to RB1. In this region there is suppressor gene, which is related to the genesis and development of LSCC, possibly including RB1. The inactivation of these suppressor genes may be related to the genesis and development of invasive LSCC.

  3. Developmental stability covaries with genome-wide and single-locus heterozygosity in house sparrows.

    Carl Vangestel

    Full Text Available Fluctuating asymmetry (FA, a measure of developmental instability, has been hypothesized to increase with genetic stress. Despite numerous studies providing empirical evidence for associations between FA and genome-wide properties such as multi-locus heterozygosity, support for single-locus effects remains scant. Here we test if, and to what extent, FA co-varies with single- and multilocus markers of genetic diversity in house sparrow (Passer domesticus populations along an urban gradient. In line with theoretical expectations, FA was inversely correlated with genetic diversity estimated at genome level. However, this relationship was largely driven by variation at a single key locus. Contrary to our expectations, relationships between FA and genetic diversity were not stronger in individuals from urban populations that experience higher nutritional stress. We conclude that loss of genetic diversity adversely affects developmental stability in P. domesticus, and more generally, that the molecular basis of developmental stability may involve complex interactions between local and genome-wide effects. Further study on the relative effects of single-locus and genome-wide effects on the developmental stability of populations with different genetic properties is therefore needed.

  4. Loss of heterozygosity drives clonal diversity of Phytophthora capsici in China.

    Jian Hu

    Full Text Available Phytophthora capsici causes significant loss to pepper (Capsicum annum in China and our goal was to develop single nucleotide polymorphism (SNP markers for P. capsici and characterize genetic diversity nationwide. Eighteen isolates of P. capsici from locations worldwide were re-sequenced and candidate nuclear and mitochondrial SNPs identified. From 2006 to 2012, 276 isolates of P. capsici were recovered from 136 locations in 27 provinces and genotyped using 45 nuclear and 2 mitochondrial SNPs. There were two main mitochondrial haplotypes and 95 multi-locus genotypes (MLGs identified. Genetic diversity was geographically structured with a high level of genotypic diversity in the north and on Hainan Island in the south, suggesting outcrossing contributes to diversity in these areas. The remaining areas of China are dominated by four clonal lineages that share mitochondrial haplotypes, are almost exclusively the A1 or A2 mating type and appear to exhibit extensive diversity based on loss of heterozygosity (LOH. Analysis of SNPs directly from infected peppers confirmed LOH in field populations. One clonal lineage is dominant throughout much of the country. The overall implications for long-lived genetically diverse clonal lineages amidst a widely dispersed sexual population are discussed.

  5. Exploring Heterozygosity-Survival Correlations in a Wild Songbird Population: Contrasting Effects between Juvenile and Adult Stages

    David Canal; David Serrano; Jaime Potti

    2014-01-01

    The relationship between genetic diversity and fitness, a major issue in evolutionary and conservation biology, is expected to be stronger in traits affected by many loci and those directly influencing fitness. Here we explore the influence of heterozygosity measured at 15 neutral markers on individual survival, one of the most important parameters determining individual fitness. We followed individual survival up to recruitment and during subsequent adult life of 863 fledgling pied flycatche...

  6. Compound Heterozygosity for Mutations in PAX6 in Patient with Complex Brain Anomaly, Neonatal Diabetes Mellitus, and Microophthalmia

    Solomon, Benjamin D.; Pineda-Alvarez, Daniel E.; Balog, Joan Z.; Hadley, Donald; Gropman, Andrea L.; Nandagopal, Radha; Han, Joan C.; Hahn, Jin S; BLAIN, DELPHINE; Brooks, Brian; Muenke, Maximilian

    2009-01-01

    We report on a patient with trisomy 21, microophthalmia, neonatal diabetes mellitus, hypopituitarism, and a complex structural brain anomaly who was a member of a large bilineal family with eye anomalies. The patient inherited a different mutation in PAX6 from each parent and is the only known living and second reported patient with compound heterozygosity for mutations in PAX6. PAX6 is a transcription factor involved in eye and brain development, and has roles in pancreatic and pituitary dev...

  7. Clinical significance of chromosome 1p/19q loss of heterozygosity and Sox17 expression in oligodendrogliomas

    Li, Junzhi; Miao, Na; Liu, Ming; Cui, Wenli; Liu, Xia; Li, Xinxia; Xiaoli SHI; Qing, Song; Ma, Yuqing; Zhang, Wei; Biekemituofu, Hadeti

    2014-01-01

    Objective: To study chromosome 1p/19q loss of heterozygosity (LOH) and Sox17 protein expression in oligodendrogliomas and correlate this loss with clinicopathological features. Methods: This study included 100 cases of oligodendrogliomas at the First Affiliated Hospital of Xinjiang Medical University from 2003 to 2014. The cases included paraffin-embedded tissues from 50 low-grade oligodendrogliomas and 50 anaplastic oligodendrogliomas. Chromosome 1p/19q LOH was detected by fluorescence in si...

  8. Copy number and loss of heterozygosity detected by SNP array of formalin-fixed tissues using whole-genome amplification.

    Angela Stokes

    Full Text Available The requirement for large amounts of good quality DNA for whole-genome applications prohibits their use for small, laser capture micro-dissected (LCM, and/or rare clinical samples, which are also often formalin-fixed and paraffin-embedded (FFPE. Whole-genome amplification of DNA from these samples could, potentially, overcome these limitations. However, little is known about the artefacts introduced by amplification of FFPE-derived DNA with regard to genotyping, and subsequent copy number and loss of heterozygosity (LOH analyses. Using a ligation adaptor amplification method, we present data from a total of 22 Affymetrix SNP 6.0 experiments, using matched paired amplified and non-amplified DNA from 10 LCM FFPE normal and dysplastic oral epithelial tissues, and an internal method control. An average of 76.5% of SNPs were called in both matched amplified and non-amplified DNA samples, and concordance was a promising 82.4%. Paired analysis for copy number, LOH, and both combined, showed that copy number changes were reduced in amplified DNA, but were 99.5% concordant when detected, amplifications were the changes most likely to be 'missed', only 30% of non-amplified LOH changes were identified in amplified pairs, and when copy number and LOH are combined ∼50% of gene changes detected in the unamplified DNA were also detected in the amplified DNA and within these changes, 86.5% were concordant for both copy number and LOH status. However, there are also changes introduced as ∼20% of changes in the amplified DNA are not detected in the non-amplified DNA. An integrative network biology approach revealed that changes in amplified DNA of dysplastic oral epithelium localize to topologically critical regions of the human protein-protein interaction network, suggesting their functional implication in the pathobiology of this disease. Taken together, our results support the use of amplification of FFPE-derived DNA, provided sufficient samples are used

  9. No Evidence for Association of SCO2 Heterozygosity with High-Grade Myopia or Other Diseases with Possible Mitochondrial Dysfunction.

    Piekutowska-Abramczuk, Dorota; Kocyła-Karczmarewicz, Beata; Małkowska, Maja; Łuczak, Sylwia; Iwanicka-Pronicka, Katarzyna; Siegmund, Stephanie; Yang, Hua; Wen, Quan; Hoang, Quan V; Silverman, Ronald H; Kowalski, Paweł; Szczypińska, Olga; Czornak, Kamila; Zimowski, Janusz; Płoski, Rafał; Pilch, Jacek; Ciara, Elżbieta; Zaremba, Jacek; Krajewska-Walasek, Małgorzata; Schon, Eric A; Pronicka, Ewa

    2016-01-01

    SCO2 mutations cause recessively inherited cytochrome c oxidase deficiency. Recently Tran-Viet et al. proposed that heterozygosity for pathogenic SCO2 variants, including the common E140K variant, causes high-grade myopia. To investigate the association of SCO2 mutations with myopia, ophthalmic examinations were performed on 35 E140K carriers, one homozygous infant, and on a mouse model of Sco2 deficiency. Additionally, a screen for other putative effects of SCO2 heterozygosity was carried out by comparing the prevalence of the common E140K variant in a population of patients with undiagnosed diseases compatible with SCO2-related pathogenesis to that in a general population sample. High-grade myopia was not identified in any of the studied individuals. Of the carriers, 17 were emmetropic, and 18 possessed refractive errors. Additionally, no significant axial elongation indicative of high-grade myopia was found in mice carrying E129K (corresponding to E140K in humans) knock-in mutations. The prevalence of E140K carriers in the symptomatic cohort was evaluated as 1:103 (CI: 0.44-2.09) and did not differ significantly from the population prevalence (1:147, CI: 0.45-1.04).Our study demonstrates that heterozygosity for pathogenic SCO2 variants is not associated with high-grade myopia in either human patients or in mice. PMID:26427993

  10. No correlation between neonatal fitness and heterozygosity in a reintroduced population of Père David's deer

    Yan ZENG; Chunwang LI; Linyuan ZHANG; Zhenyu ZHONG; Zhigang JIANG

    2013-01-01

    Considering the severe impacts of genetic bottlenecks and small numbers of founders in populations of reintroduced animals,it is necessary to study inbreeding and its effect on fitness in species of conservation concern.Père David's deer is one of few large mammal species extinct in the wild but safely preserved in captivity.Its specific background gives us the opportunity to study the relationships between heterozygosity and neonatal fitness in relocated populations.We employed five microsatellite loci to explore heterozygosity-fitness correlations in a population of Père David's deer at the Beijing Milu Ecological Research Center.We observed associations between microsatellite-based variables sMLH,IR,MD2 and HL,and two components of fitness expressed early in life (birth weight and the neonatal mortality of 123 Père David's deer calves born over six consecutive years).We found that neonatal mortality was 19.1% ± 7.6%,not higher than the 19% or 18% reported in other ungulates.The heterozygosity of calves was not associated with neonatal mortality,nor birth weight.Our study implies that low genetic variability of microsatellite loci has no overt effect on birth weight and neonatal mortality in reintroduced populations of Père David's deer.

  11. No correlation between neonatal fitness and heterozygosity in a reintroduced population of Père David's deer

    Yan ZENG, Chunwang LI, Linyuan ZHANG, Zhenyu ZHONG, Zhigang JIANG

    2013-04-01

    Full Text Available Considering the severe impacts of genetic bottlenecks and small numbers of founders in populations of reintroduced animals, it is necessary to study inbreeding and its effect on fitness in species of conservation concern. Père David’s deer is one of few large mammal species extinct in the wild but safely preserved in captivity. Its specific background gives us the opportunity to study the relationships between heterozygosity and neonatal fitness in relocated populations. We employed five microsatellite loci to explore heterozygosity-fitness correlations in a population of Père David’s deer at the Beijing Milu Ecological Research Center. We observed associations between microsatellite-based variables sMLH, IR, MD2 and HL, and two components of fitness expressed early in life (birth weight and the neonatal mortality of 123 Père David’s deer calves born over six consecutive years. We found that neonatal mortality was 19.1 ± 7.6%, not higher than the 19% or 18% reported in other ungulates. The heterozygosity of calves was not associated with neonatal mortality, nor birth weight. Our study implies that low genetic variability of microsatellite loci has no overt effect on birth weight and neonatal mortality in reintroduced populations of Père David’s deer [Current Zoology 59 (2: 249–256, 2013].

  12. TP53 Codon 72 Heterozygosity May Promote MicrosatelliteInstability in Sporadic Colorectal Cancer

    Mehdi Nikbahkt Dastjerdi

    2010-01-01

    Full Text Available Objective: The polymorphic variants at codon 72 of the p53 gene, encoding prolineor arginine at residue 72, produce marked changes in the p53 structure. From theevidence that the DNA mismatch repair system and p53 interact to maintain genomicintegrity, we hypothesized that codon 72 variations may influence the prevalence ofmicrosatellite instability (MSI, a feature of malignancies associated with mismatchrepair deficiency in sporadic colorectal cancer.Materials and Methods: We investigated the frequency of MSI in three P53 codon72 genotypes using genomic DNAs from 144 paraffin blocks of sporadic colorectaladenocarcinomas by testing the BAT-26 poly(A marker. We used PCR-SSCP analysisto detect tumor sample MSI for the nonisotopic detection of deletions in the BAT-26 poly (A mononucleotide repeat. Associations between qualitative variables wereevaluated using the χ2-test. Statistical significance level was set to p ≤ 0.05.Results: MSI analysis revealed that 24.3% of the tumors (n=35 were MSI-positiveand 75.7% (n=109 were MSI-negative. The frequency of microsatellite instability inthe arginine/arginine, arginine/proline and proline/proline genotypes were 11 (16.9%,22 (36.1% and 2 (11.1% respectively. A significant difference in distribution of MSIwas found for the arginine/proline genotype compared with the grouped arginine/arginineand proline/proline genotypes (p=0.05.Conclusion: Our findings suggested that colorectal adenocarcinomas arising in individualswith the p53 codon 72 arginine/proline heterozygosity are more prone tomicrosatellite instability than those with other p53 genotypes. In our study, MSI wasimportant in the carcinogenesis of sporadic colorectal cancer arising in pro/arg heterozygotes.

  13. HbD Punjab/HbQ India compound heterozygosity: An unusual association.

    Stacy Colaco

    2014-11-01

    Full Text Available Background: Haemoglobinopathies are the commonest hereditary disorders in India and pose a major health problem. Both beta thalassaemia and structural haemoglobin variants are relatively common in north western India. Here we report a 29 year old Sindhi female who was referred to us for a haemoglobinopathy work up and genetic counseling since her spouse was a classical beta thalassaemia carrier. Method: A complete blood count was done on an automated cell counter. Haemoglobin analysis was carried out using HPLC Variant Haemoglobin Testing System.  The cellulose acetate electrophoresis was carried out [pH 8.9]. Confirmation of mutations was done by automated DNA sequencing. Results: HPLC analysis showed four major peaks, HbA0, a peak in the HbD window, an unknown peak [retention time 4.74 minutes] and a peak in the HbC window. The HbA2 level was 2.2% and the HbF level was 0.7%.Cellulose acetate electrophoresis at alkaline pH, a slow moving band was seen at the HbS/D position along with a prominent band at the HbA2 position. DNA sequencing of the β and α genes showed presence of the 2 hemoglobin variants :Hb D [b 121GAA à CAA] and Hb Q [a 64 AAG à GAG]. The δ globin gene was normal. The additional peak in the HbC window was due to the formation of a heterodimer hybrid. Conclusion: Both HbD Punjab and HbQ India are relatively common in India but their co-inheritance has not been described in the country. This is the second report of compound heterozygosity for HbQ India/HbD Punjab haemoglobinopathy globally, and the first one from India.

  14. Heterozygosity, gender, and the growth-defense trade-off in quaking aspen.

    Cole, Christopher T; Stevens, Michael T; Anderson, Jon E; Lindroth, Richard L

    2016-06-01

    Although plant growth is generally recognized to be influenced by allocation to defense, genetic background (e.g., inbreeding), and gender, rarely have those factors been addressed collectively. In quaking aspen (Populus tremuloides Michx.), phenolic glycosides (PGs) and condensed tannins (CTs) constitute up to 30 % of leaf dry weight. To quantify the allocation cost of this chemical defense, we measured growth, defense chemistry, and individual heterozygosity (H obs at 16 microsatellite loci) for male and female trees in both controlled and natural environments. The controlled environment consisted of 12 juvenile genets grown for 3 years in a common garden, with replication. The natural environment consisted of 51 mature genets in wild populations, from which we sampled multiple ramets (trees) per genet. Concentrations of PGs and CTs were negatively correlated. PGs were uncorrelated with growth, but CT production represented a major cost. Across the range of CT levels found in wild-grown trees, growth rates varied by 2.6-fold, such that a 10 % increase in CT concentration occurred with a 38.5 % decrease in growth. H obs had a marked effect on aspen growth: for wild trees, a 10 % increase in H obs corresponded to a 12.5 % increase in growth. In wild trees, this CT effect was significant only in females, in which reproduction seems to exacerbate the cost of defense, while the H obs effect was significant only in males. Despite the lower growth rate of low-H obs trees, their higher CT levels may improve survival, which could account for the deficit of heterozygotes repeatedly found in natural aspen populations. PMID:26886130

  15. The contribution of recombination to heterozygosity differs among plant evolutionary lineages and life-forms

    Verdú Miguel

    2010-01-01

    Full Text Available Abstract Background Despite its role as a generator of haplotypic variation, little is known about how the rates of recombination evolve across taxa. Recombination is a very labile force, susceptible to evolutionary and life trait related processes, which have also been correlated with general levels of genetic diversity. For example, in plants, it has been shown that long-lived outcrossing taxa, such as trees, have higher heterozygosity (He at SSRs and allozymes than selfing or annual species. However, some of these tree taxa have surprisingly low levels of nucleotide diversity at the DNA sequence level, which points to recombination as a potential generator of genetic diversity in these organisms. In this study, we examine how genome-wide and within-gene rates of recombination evolve across plant taxa, determine whether such rates are influenced by the life-form adopted by species, and evaluate if higher genome-wide rates of recombination translate into higher He values, especially in trees. Results Estimates of genome-wide (cM/Mb recombination rates from 81 higher plants showed a significant phylogenetic signal. The use of different comparative phylogenetic models demonstrated that there is a positive correlation between recombination rate and He (0.83 ± 0.29, and that trees have higher rates of genome-wide recombination than short-lived herbs and shrubs. A significant taxonomic component was further made evident by our models, as conifers exhibited lower recombination rates than angiosperms. This trend was also found at the within-gene level. Conclusions Altogether, our results illustrate how both common ancestry and life-history traits have to be taken into account for understanding the evolution of genetic diversity and genomic rates of recombination across plant species, and highlight the relevance of species life forms to explain general levels of diversity and recombination.

  16. Analysis of APC allelic imbalance/loss of heterozygosity and APC protein expression in cutaneous squamous cell carcinomas.

    Gray, Sarah E

    2011-05-01

    The adenomatous polyposis coli (APC) gene is a tumor suppressor gene which is mutated in the hereditary disease, familial adenomatous polyposis (FAP). Somatic mutations of the APC gene have also been identified in the majority of sporadic colorectal carcinomas, and mutation of the APC gene appears to be an early step in the initiation of colon cancer. Loss of heterozygosity (LOH) of APC has been described in a variety of other cancer types, including renal cell carcinoma, gastric cancer, non-small cell lung cancer, endometrial cancer and oral squamous cell carcinomas (SCC).

  17. Compound heterozygosity for mutations in PAX6 in a patient with complex brain anomaly, neonatal diabetes mellitus, and microophthalmia.

    Solomon, Benjamin D; Pineda-Alvarez, Daniel E; Balog, Joan Z; Hadley, Donald; Gropman, Andrea L; Nandagopal, Radha; Han, Joan C; Hahn, Jin S; Blain, Delphine; Brooks, Brian; Muenke, Maximilian

    2009-11-01

    We report on a patient with trisomy 21, microophthalmia, neonatal diabetes mellitus, hypopituitarism, and a complex structural brain anomaly who was a member of a large bilineal family with eye anomalies. The patient inherited a different mutation in PAX6 from each parent and is the only known living and second reported patient with compound heterozygosity for mutations in PAX6. PAX6 is a transcription factor involved in eye and brain development and has roles in pancreatic and pituitary development. Clinical evaluation of the propositus and his parents demonstrated the effects of mutations of differing severity in multiple individuals. PMID:19876904

  18. Compound Heterozygosity for Mutations in PAX6 in Patient with Complex Brain Anomaly, Neonatal Diabetes Mellitus, and Microophthalmia

    Solomon, Benjamin D.; Pineda-Alvarez, Daniel E.; Balog, Joan Z.; Hadley, Donald; Gropman, Andrea L.; Nandagopal, Radha; Han, Joan C.; Hahn, Jin S.; Blain, Delphine; Brooks, Brian; Muenke, Maximilian

    2009-01-01

    We report on a patient with trisomy 21, microophthalmia, neonatal diabetes mellitus, hypopituitarism, and a complex structural brain anomaly who was a member of a large bilineal family with eye anomalies. The patient inherited a different mutation in PAX6 from each parent and is the only known living and second reported patient with compound heterozygosity for mutations in PAX6. PAX6 is a transcription factor involved in eye and brain development, and has roles in pancreatic and pituitary development. Clinical evaluation of the propositus and his parents demonstrated the effects of mutations of differing severity in multiple individuals. PMID:19876904

  19. Combination of Complement-Dependent Cytotoxicity and Relative Fluorescent Quantification of HLA Length Polymorphisms Facilitates the Detection of a Loss of Heterozygosity

    Klaus Witter

    2014-01-01

    Full Text Available Loss of heterozygosity (LOH is a common event in malignant cells. In this work we introduce a new approach to identify patients with loss of heterozygosity in the HLA region either at first diagnosis or after HLA mismatched allogeneic HSCT. Diagnosis of LOH requires a high purity of recipient target cells. FACS is time consuming and also frequently prevented by rather nonspecific or unknown immune phenotype. The approach for recipient cell enrichment is based on HLA targeted complement-dependent cytotoxicity (CDC. Relative fluorescent quantification (RFQ analysis of HLA intron length polymorphisms then allows analysis of HLA heterozygosity. The approach is exemplified in recent clinical cases illustrating the detection of an acquired allele loss. As illustrated in one case with DPB1, distinct HLA loci in donor and patient were sufficient for both proof of donor cell removal and evaluation of allele loss in the patient's leukemic cells. Results were confirmed using HLA-B RFQ analysis and leukemia-associated aberrant immunophenotype (LAIP based cell sort. Both results confirmed suspected loss of HLA heterozygosity. Our approach complements or substitutes for FACS-based cell enrichment; hence it may be further developed as novel routine diagnostic tool. This allows rapid recipient cell purification and testing for loss of HLA heterozygosity before and after allogeneic HSCT in easily accessible peripheral blood samples.

  20. High incidence of microsatellite instability and loss of heterozygosity in three loci in breast cancer patients receiving chemotherapy: a prospective study

    The aim of the study was to evaluate potential chemotherapy-induced microsatellite instability, loss of heterozygosity, loss of expression in mismatch repair proteins and associations with clinical findings in breast cancer patients, especially resistance to chemotherapy and/or development of other tumors in the four years following chemotherapy treatment. A comprehensive study of chemotherapy-related effects with a follow-up period of 48 months post treatment was conducted. A total of 369 peripheral blood samples were collected from 123 de novo breast cancer patients. Microsatellite instability and loss of heterozygosity in five commonly used marker loci (including Tp53-Alu of the tumor suppressor gene TP53) were analyzed in blood samples. Sampling was conducted on three occasions; 4–5 weeks prior to the first chemotherapy session (pre-treatment), to serve as a baseline, followed by two consecutive draws at 12 weeks intervals from the first collection. Mismatch repair protein expression was evaluated in cancer tissues using immunohistochemistry for three mismatch-repair related proteins. A total of 70.7% of the patients showed microsatellite instability for at least one locus, including 18.6% marked as high-positive and 52.1% as low-positive; 35.8% showed loss of heterozygosity in addition to microsatellite instability, while 29.3% exhibited microsatellite stability. The following incidence rates for microsatellite instability and loss of heterozygosity were detected: 39.1% positive for Tp53-Alu, 31.1% for locus Mfd41, and 25.3% for locus Mfd28. A higher occurrence of loss of heterozygosity was noted with alleles 399 and 404 of Tp53-Alu. The mismatch repair protein expression analysis showed that the chemotherapy caused a loss of 29.3% in hMLH1 expression, and 18.7% and 25.2% loss in hMSH2 and P53 expression, respectively. A strong correlation between low or deficient hMSH2 protein expression and occurrence of mismatch repair/loss of heterozygosity events in Mfd

  1. E-cadherin and loss of heterozygosity at chromosome 16 in breast carcinogenesis: different genetic pathways in ductal and lobular breast cancer?

    Loss of heterozygosity at the long arm of chromosome 16 is one of the most frequent genetic events in breast cancer. In the search for tumour suppressor genes that are the target of loss of heterozygosity at 16q, the E-cadherin gene CDH1 was unveiled by the identification of truncating mutations in the retained copy. However, only lobular tumours showed E-cadherin mutations. Whereas investigations are still devoted to finding the target genes in the more frequent ductal breast cancers, other studies suspect the E-cadherin gene to also be the target in this tumour type. The present article discusses the plausibility of those two lines of thought

  2. Cohesin Rad21 Mediates Loss of Heterozygosity and Is Upregulated via Wnt Promoting Transcriptional Dysregulation in Gastrointestinal Tumors

    Huiling Xu

    2014-12-01

    Full Text Available Loss of heterozygosity (LOH of the adenomatous polyposis coli (APC gene triggers a series of molecular events leading to intestinal adenomagenesis. Haploinsufficiency of the cohesin Rad21 influences multiple initiating events in colorectal cancer (CRC. We identify Rad21 as a gatekeeper of LOH and a β-catenin target gene and provide evidence that Wnt pathway activation drives RAD21 expression in human CRC. Genome-wide analyses identified Rad21 as a key transcriptional regulator of critical CRC genes and long interspersed element (LINE-1 or L1 retrotransposons. Elevated RAD21 expression tracks with reactivation of L1 expression in human sporadic CRC, implicating cohesin-mediated L1 expression in global genomic instability and gene dysregulation in cancer.

  3. Genetic variants in the HER2 gene: Influence on HER2 overexpression and loss of heterozygosity in breast cancer.

    Cresti, Nicola; Lee, Joanne; Rourke, Emma; Televantou, Despina; Jamieson, David; Verrill, Mark; Boddy, Alan V

    2016-03-01

    Human epidermal growth factor receptor 2 (HER2) overexpression in breast cancer is an indicator of poor prognosis and is the pre-requisite for treatment with the agents targeting this member of the epidermal growth factor receptor family. In order to determine the influence of these common single-nucleotide polymorphisms (SNPs) in the HER2 gene, genomic DNA was obtained from 361 patients with breast cancer, aged between 29 and 82 years. Samples of tumour tissue were obtained from 241 (66%) patients and material for extraction of DNA is isolated from surrounding normal tissue by laser capture microdissection. Genotyping was performed using the Taqman fluorogenic 5' nuclease assay. Of the 360 patients with definitive determination of HER2 status, 49% were positive. The Ile655Val SNP had no influence on the frequency of HER2 expression. However, the proline allele of the Ala1170Pro SNP was associated with a higher frequency of HER2 overexpression (56% versus 43%, p = 0.015). Where the germline genotype was homozygous, the tumour genotype was identical in every case and for both SNPs. In HER2-positive tumours, heterozygosity was maintained in only 15% and 18% of the Ile655Val and Ala1170Pro SNPs, respectively. This was lower than in the HER2-negative tumours (46% and 43%, respectively). Normal breast tissue (n = 23) retained the germline genotype in all but one case. The underlying link between the Ala1170Pro SNP and HER2 positivity is not known, nor is the significance of HER2 overexpression and loss of heterozygosity in breast cancer. However, these results illustrate the complexity of HER2 genotype and overexpression in this disease. PMID:26773371

  4. Loss-of-heterozygosity on chromosome 19q in early-stage serous ovarian cancer is associated with recurrent disease

    Ovarian cancer is a heterogeneous disease and prognosis for apparently similar cases of ovarian cancer varies. Recurrence of the disease in early stage (FIGO-stages I-II) serous ovarian cancer results in survival that is comparable to those with recurrent advanced-stage disease. The aim of this study was to investigate if there are specific genomic aberrations that may explain recurrence and clinical outcome. Fifty-one women with early stage serous ovarian cancer were included in the study. DNA was extracted from formalin fixed samples containing tumor cells from ovarian tumors. Tumor samples from thirty-seven patients were analysed for allele-specific copy numbers using OncoScan single nucleotide polymorphism arrays from Affymetrix and the bioinformatic tool Tumor Aberration Prediction Suite. Genomic gains, losses, and loss-of-heterozygosity that associated with recurrent disease were identified. The most significant differences (p < 0.01) in Loss-of-heterozygosity (LOH) were identified in two relatively small regions of chromosome 19; 8.0-8,8 Mbp (19 genes) and 51.5-53.0 Mbp (37 genes). Thus, 56 genes on chromosome 19 were potential candidate genes associated with clinical outcome. LOH at 19q (51-56 Mbp) was associated with shorter disease-free survival and was an independent prognostic factor for survival in a multivariate Cox regression analysis. In particular LOH on chromosome 19q (51-56 Mbp) was significantly (p < 0.01) associated with loss of TP53 function. The results of our study indicate that presence of two aberrations in TP53 on 17p and LOH on 19q in early stage serous ovarian cancer is associated with recurrent disease. Further studies related to the findings of chromosomes 17 and 19 are needed to elucidate the molecular mechanism behind the recurring genomic aberrations and the poor clinical outcome

  5. Single Nucleotide Polymorphism (SNP)-Based Loss of Heterozygosity (LOH) Testing by Real Time PCR in Patients Suspect of Myeloproliferative Disease.

    Huijsmans, C.J.; Poodt, J.; Damen, J.; Linden, J.C. van der; Savelkoul, P.H.; Pruijt, J.F.M.; Hilbink, M.; Hermans, M.H.

    2012-01-01

    During tumor development, loss of heterozygosity (LOH) often occurs. When LOH is preceded by an oncogene activating mutation, the mutant allele may be further potentiated if the wild-type allele is lost or inactivated. In myeloproliferative neoplasms (MPN) somatic acquisition of JAK2V617F may be fol

  6. Molecular genetic characterization and urinary excretion pattern of metabolites in two families with MCAD deficiency due to compound heterozygosity with a 13 base pair insertion in one allele

    Gregersen, N; Winter, V; Lyonnet, S; Saudubray, J M; Wendel, U; Jensen, T G; Andresen, B S; Kølvraa, S; Lehnert, W; Bolund, L

    1994-01-01

    Two families with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency due to compound heterozygosity are described. All patients have a 13 bp insertion in exon 11 of one allele at the MCAD gene locus. In the other allele patients in one of the families harbour the prevalent G985 mutation, and t...

  7. A map of nuclear matrix attachment regions within the breast cancer loss-of-heterozygosity region on human chromosome 16q22.1

    Shaposhnikov, Sergey A.; Akopov, Sergey B.; Chernov, Igor P.;

    2007-01-01

    There is abundant evidence that the DNA in eukaryotic cells is organized into loop domains that represent basic structural and functional units of chromatin packaging. To explore the DNA domain organization of the breast cancer loss-of-heterozygosity region on human chromosome 16q22.1, we have id...

  8. Start of reproduction and allozyme heterozygosity in Pinus sibirica under different techniques of artificial forest stand establishment

    S.N. Velisevich

    2013-12-01

    Full Text Available Siberian stone pine (Pinus sibirica Du Tour is one of the main forest-forming tree species in boreal forests of Eurasia. Large edibleseeds of this species have an important resource value because of their high nutritious properties. Development of approaches toestablishment of early cone producing Siberian stone pine stands including utilization of corresponding genetic background is one of the priorities of forest resource management. The goal of our study was to evaluate the effect of stand density on the differentiation of trees bythe age of first reproduction and the relationship of allozyme heterozygosity and morphological traits variability in Siberian stone pine.Morphological and allozyme variability in artificial Pinus sibirica stands with high and low density was investigated. In the high-densitystand the distance between trees was 0.7 and 3 meters (4080 trees per ha while in the lowdensity stand it was 8 and 8 meters (144 treesper ha. Age of formation of first male and female cones was evaluated by retrospective method based on analysis of tracks of cones ona shoot bark. Tree height, diameter and number of male, female and vegetative shoots in a crown of model trees were measured.Genotypes of the trees were determined by 29 isozyme loci coding for 16 enzymes (ADH, FDH, FEST, GDH, GOT, IDH, LAP, MDH, MNR, PEPCA, 6-PGD, PGI, PGM, SDH, SKDH, SOD. In the low-density stand, the portion of generative trees was higher and differentiation of trees by age of reproduction starting was lower in spite of the smaller age of trees as compared to the high-density stand. Inboth samples, the age of formation of first generative organs was related negatively with stem height, stem diameter and number offemale shoots. In the high-density stand, positive relation of age of first reproduction with total number of shoots and number ofmale shoots was found. In both samples nonreproductive trees were less heterozygous at

  9. Comparative genomic hybridization in childhood acute lymphoblastic leukemia: correlation with interphase cytogenetics and loss of heterozygosity analysis.

    Scholz, I; Popp, S; Granzow, M; Schoell, B; Holtgreve-Grez, H; Takeuchi, S; Schrappe, M; Harbott, J; Teigler-Schlegel, A; Zimmermann, M; Fischer, C; Koeffler, H P; Bartram, C R; Jauch, A

    2001-01-15

    We used comparative genomic hybridization (CGH) to study DNA copy number changes in 71 children with acute lymphoblastic leukemia (ALL) including 50 B-lineage and 21 T-ALLs. Forty-two patients (59%) showed genomic imbalances whereby gains were more frequently observed than losses (127 vs. 29). Gains most commonly affected the entire chromosomes 21 and 10 (19.7% each), 6, 14, 18, X (15.5% each), 17 (14.1%) and 4 (11.3%). Highly hyperdiploid karyotypes (chromosome number >50) occurred more frequently in B-lineage than in T-lineage ALL (24% vs. 4.8%). In both cell lineages deletions were mainly detected on 9p (14.1%) and 12p (8.4%), and on 6q in T-lineage ALL (4.2%). These findings were compared with loss of heterozygosity (LOH) of 6q, 9p, 11q, and 12p previously performed in 56 of the 71 patients. Among 54 sites of LOH, CGH revealed losses of the respective chromosome arms in 17 LOH-positive regions (31.5%). G-banding analysis and interphase cytogenetics with subregional probes for 14 loci confirmed the presence of genomic imbalances as detected by CGH. We, therefore, conclude that, in the absence of cytogenetic data, CGH represents a suitable method for identifying hyperdiploid karyotypes as well as prognostically relevant deletions in ALL patients. PMID:11172898

  10. Loss-of-heterozygosity on chromosome 19q in early-stage serous ovarian cancer is associated with recurrent disease

    Skirnisdottir Ingiridur

    2012-09-01

    Full Text Available Abstract Background Ovarian cancer is a heterogeneous disease and prognosis for apparently similar cases of ovarian cancer varies. Recurrence of the disease in early stage (FIGO-stages I-II serous ovarian cancer results in survival that is comparable to those with recurrent advanced-stage disease. The aim of this study was to investigate if there are specific genomic aberrations that may explain recurrence and clinical outcome. Methods Fifty-one women with early stage serous ovarian cancer were included in the study. DNA was extracted from formalin fixed samples containing tumor cells from ovarian tumors. Tumor samples from thirty-seven patients were analysed for allele-specific copy numbers using OncoScan single nucleotide polymorphism arrays from Affymetrix and the bioinformatic tool Tumor Aberration Prediction Suite. Genomic gains, losses, and loss-of-heterozygosity that associated with recurrent disease were identified. Results The most significant differences (p  Conclusions The results of our study indicate that presence of two aberrations in TP53 on 17p and LOH on 19q in early stage serous ovarian cancer is associated with recurrent disease. Further studies related to the findings of chromosomes 17 and 19 are needed to elucidate the molecular mechanism behind the recurring genomic aberrations and the poor clinical outcome.

  11. Mutations in PTCH and XPA heterozygosity in x-irradiated subjects with high multiplicity of basal cell carcinomas

    Burns, F.J.; Zhao, P.; Roy, N.; Shore, R.; Loomis, C. [NYU, New York, NY (United States). School of Medicine

    2000-07-01

    Basal cell carcinomas (BCCs) were obtained from subjects who had been treated with x-ray for tinea capitis at mean age 8 yr (average dose 3.0 Gy) and who have developed multiple (>5) skin cancers 35-40 years later. By allelic loss analysis, 9/10 tumors from 3 patients exhibited loss of heterozygosity (LOH) in one or more microsatellite markers in chromosome location 9q22.3. The xeroderma pigmentosum A (XPA) and PTCH (nevoid BCC syndrome (NBCCS)) genes are located in region 9q22.3, and often LOH in the region means that alleles of both genes are lost. Mutations were found in the undeleted PTCH allele in 2/9 BCCs, which is consistent with the two-allele inactivation model. A similar analysis for the XPA gene showed 5/9 BCCs with probable inactivating mutations. In 1 patient 5/5 cancers and normal blood showed the same 14 base deletion in codon 256-260 indicating this person was an XPA heterozygote. The same 5 cancers exhibited LOH in region 9q22.3 making it likely that 1 allele of both PTCH and XPA were lost. These results suggest how 2 genes could combine to produce an increase in susceptibility to X-ray-induced carcinogenesis in connection with UV as a second exogenous carcinogen (Supported by NIEHS and NCI). (author)

  12. Genome Sequencing and Mapping Reveal Loss of Heterozygosity as a Mechanism for Rapid Adaptation in the Vegetable Pathogen Phytophthora capsici

    Lamour, Kurt H.; Mudge, Joann; Gobena, Daniel; Hurtado-Gonzales, Oscar P.; Schmutz, Jeremy; Kuo, Alan; Miller, Neil A.; Rice, Brandon J.; Raffaele, Sylvain; Cano, Liliana M.; Bharti, Arvind K.; Donahoo, Ryan S.; Finely, Sabra; Huitema, Edgar; Hulvey, Jon; Platt, Darren; Salamov, Asaf; Savidor, Alon; Sharma, Rahul; Stam, Remco; Sotrey, Dylan; Thines, Marco; Win, Joe; Haas, Brian J.; Dinwiddie, Darrell L.; Jenkins, Jerry; Knight, James R.; Affourtit, Jason P.; Han, Cliff S.; Chertkov, Olga; Lindquist, Erika A.; Detter, Chris; Grigoriev, Igor V.; Kamoun, Sophien; Kingsmore, Stephen F.

    2012-02-07

    The oomycete vegetable pathogen Phytophthora capsici has shown remarkable adaptation to fungicides and new hosts. Like other members of this destructive genus, P. capsici has an explosive epidemiology, rapidly producing massive numbers of asexual spores on infected hosts. In addition, P. capsici can remain dormant for years as sexually recombined oospores, making it difficult to produce crops at infested sites, and allowing outcrossing populations to maintain significant genetic variation. Genome sequencing, development of a high-density genetic map, and integrative genomic or genetic characterization of P. capsici field isolates and intercross progeny revealed significant mitotic loss of heterozygosity (LOH) in diverse isolates. LOH was detected in clonally propagated field isolates and sexual progeny, cumulatively affecting >30percent of the genome. LOH altered genotypes for more than 11,000 single-nucleotide variant sites and showed a strong association with changes in mating type and pathogenicity. Overall, it appears that LOH may provide a rapid mechanism for fixing alleles and may be an important component of adaptability for P. capsici.

  13. Compound heterozygosity for a novel and a recurrent MFRP gene mutation in a family with the nanophthalmos-retinitis pigmentosa complex

    Zenteno, Juan Carlos; Buentello-Volante, Beatriz; Quiroz-González, Miguel A.; Quiroz-Reyes, Miguel A.

    2009-01-01

    Purpose To report a new familial case of the recently described autosomal recessive syndrome of nanophthalmos-retinitis pigmentosa-foveoschisis-optic disc drusen, which arises from compound heterozygosity for Membrane Frizzled-Related Protein (MFRP) mutations in a sibling pair of Mexican origin. Methods Ophthalmological assessment included slit-lamp and dilated fundus examination, applanation tonometry, fundus photography, A-mode and B-mode ultrasound examination, electroretinogram, fluoresce...

  14. Partial protective effect of CCR5-Delta 32 heterozygosity in a cohort of heterosexual Italian HIV-1 exposed uninfected individuals

    Cauda Roberto

    2006-09-01

    Full Text Available Abstract Despite multiple sexual exposure to HIV-1 virus, some individuals remain HIV-1 seronegative (exposed seronegative, ESN. The mechanisms underlying this resistance remain still unclear, although a multifactorial pathogenesis can be hypothesised. Although several genetic factors have been related to HIV-1 resistance, the homozigosity for a mutation in CCR5 gene (the 32 bp deletion, i.e. CCR5-Delta32 allele is presently considered the most relevant one. In the present study we analysed the genotype at CCR5 locus of 30 Italian ESN individuals (case group who referred multiple unprotected heterosexual intercourse with HIV-1 seropositive partner(s, for at least two years. One hundred and twenty HIV-1 infected patients and 120 individuals representative of the general population were included as control groups. Twenty percent of ESN individuals had heterozygous CCR5-Delta 32 genotype, compared to 7.5% of HIV-1 seropositive and 10% of individuals from the general population, respectively. None of the analysed individuals had CCR5-Delta 32 homozygous genotype. Sequence analysis of the entire open reading frame of CCR5 was performed in all ESN subjects and no polymorphisms or mutations were identified. Moreover, we determined the distribution of C77G variant in CD45 gene, which has been previously related to HIV-1 infection susceptibility. The frequency of the C77G variant showed no significant difference between ESN subjects and the two control groups. In conclusion, our data show a significantly higher frequency of CCR5-Delta 32 heterozygous genotype (p = 0.04 among the Italian heterosexual ESN individuals compared to HIV-1 seropositive patients, suggesting a partial protective role of CCR5-Delta 32 heterozygosity in this cohort.

  15. Loss of heterozygosity of Kras2 gene on 12p12-13 in Chinese colon carcinoma patients

    Jun Wan; Hong Li; Yuan Li; Mei-Ling Zhu; Po Zhao

    2006-01-01

    AIM: To study the loss of heterozygosity (LOH) on 12p12-13 in Chinese colon carcinoma patients.METHODS: DNA was extracted from 10 specimens of cancer tissue, 10 specimens of adjacent tissue and 10specimens of normal tissue, respectively. LOH of Kras2gene was analyzed by polymerase chain reaction (PCR)and denaturing polyacrylamide gel electrophoresis using 11 microsatellite markers on 12p-12-13.RESULTS: LOH of Kras gene was detected at least on one marker of 12p-12-13 in 30% (3/10) of adjacent tissue specimens. The highest frequency of LOH was identified on D12S1034 in 28.57% (2/7) of adjacent tissue specimens. LOH was detected at least on one marker of 12p12-13 in 60% (6/10) of carcinoma tissue specimens, the most frequent LOH was found on D12S1034 and D12S1591 in 42.86% (3/7) of carcinoma tissue specimens. LOH was detected in 30% (3/10) of carcinoma tissue specimens, 30% (3/10) of adjacent tissue specimens, and no signal in 1% (1/0) carcinoma tissue specimen. The occurrence of LOH did not correlate with sex, age, tumor size and lymph node metastasis.CONCLUSION: Genomic instability may occur on 12p-12-13 of Kras2 gene in the development and progression of colon carcinoma. The high LOH of Kras2 gene may directly influence the transcription and translation of wild type Kras2 gene.

  16. Conflicting HLA assignment by three different typing methods due to the apparent loss of heterozygosity in the MHC region.

    Linjama, T; Impola, U; Niittyvuopio, R; Kuittinen, O; Kaare, A; Rimpiläinen, J; Volin, L; Peräsaari, J; Jaatinen, T; Lauronen, J; Saarinen, T; Juvonen, E; Partanen, J; Koskela, S

    2016-05-01

    Loss of heterozygosity (LOH) has been reported to cause false human leukocyte antigen (HLA) homozygous typing results in pre-transplant patients suffering from haematological malignancies, who in fact are HLA heterozygous. This poses a challenge for histocompatibility testing, as a stem cell graft from a genuinely HLA homozygous donor to a mistyped patient may lead to acute life-threatening graft-vs-host disease. LOH in the HLA region on chromosome 6 is known to be quite common in solid tumours, helping malignant cells to escape T-cell surveillance, but the incidence in haematological malignancies is less well known and the estimates vary. Here we report LOH in the HLA region of five patients with haematological malignancy. We found considerable differences in sensitivity between the three different HLA typing methods used in our laboratory: SSP was clearly the most sensitive method for detecting the lost haplotype, followed by rSSO, while SBT was the least sensitive technique. A subsequent, retrospective genotyping of 65 HLA homozygous haematological patients by SSP method showed no mistyped LOH cases in our laboratory in the past 10 years. The frequency of HLA homozygosity was found to be similar between haematological patients and control groups. It is important for an HLA laboratory to be aware of the differences in various HLA typing techniques' sensitivity for detecting an under-represented haplotype between HLA typing techniques when genotyping patients with haematological diseases. It is advisable for HLA laboratories to have at least two different methods with different sensitivities in their repertoire to be able to retype samples when a false homozygous result is suspected. PMID:26969202

  17. Heterozygosity for Tay-Sachs and Sandhoff diseases in non-Jewish Americans with ancestry from Ireland, Great Britain, or Italy.

    Branda, Kelly Johnston; Tomczak, Jerzy; Natowicz, Marvin R

    2004-01-01

    Previous reports have found that non-Jewish Americans with ancestry from Ireland have an increased frequency of heterozygosity for Tay-Sachs disease (TSD), although frequency estimates are substantially different. Our goal in this study was to determine the frequency of heterozygosity for TSD and Sandhoff diseases (SD) among Irish Americans, as well as in persons of English, Scottish, and/or Welsh ancestry and in individuals with Italian heritage, who were referred for determination of their heterozygosity status and who had no known family history of TSD or SD or of heterozygosity for these conditions. Of 610 nonpregnant subjects with Irish background, 24 TSD heterozygotes were identified by biochemical testing, corresponding to a heterozygote frequency of 1 in 25 (4%; 95% CI, 1/39-1/17). In comparison, of 322 nonpregnant individuals with ancestry from England, Scotland, or Wales, two TSD heterozygotes were identified (1 in 161 or 0.62%; 95% CI, 1/328-1/45), and three TSD heterozygotes were ascertained from 436 nonpregnant individuals with Italian heritage (1 in 145 or 0.69%; 95% CI, 1/714-1/50). Samples from 21 Irish heterozygotes were analyzed for HEXA gene mutations. Two (9.5%) Irish heterozygotes had the lethal + 1 IVS-9 G --> A mutation, whereas 9 (42.8%) had a benign pseudodeficiency mutation. No mutation was found in 10 (47.6%) heterozygotes. These data allow for a frequency estimate of deleterious alleles for TSD among Irish Americans of 1 in 305 (95% CI, 1/2517-1/85) to 1 in 41 (95% CI, 1/72-1/35), depending on whether one, respectively, excludes or includes enzyme-defined heterozygotes lacking a defined deleterious mutation. Pseudodeficiency mutations were identified in both of the heterozygotes with ancestry from other countries in the British Isles, suggesting that individuals with ancestry from these countries do not have an increased rate of TSD heterozygosity. Four SD heterozygotes were found among individuals of Italian descent, a frequency of 1 in

  18. Loss of Heterozygosity

    sprotocols

    2014-01-01

    Author: Molecular Profiling Initiative, NCI *This method was successful in our lab using prostate tissue and for our specific objectives. Investigators must be aware that they will need to tailor the following protocol for their own research objectives and tissue under study*. This method is used to detect genomic DNA deletions in tumor cells. For a more detailed discussion of applying this approach to microdissected samples, see [Allelic Loss Studies](http://cgap-mf.nih.gov/ProstateE...

  19. Integrated analysis of copy number and loss of heterozygosity in primary breast carcinomas using high-density SNP array.

    Ching, Ho Ching; Naidu, Rakesh; Seong, Mun Kein; Har, Yip Cheng; Taib, Nur Aishah Mohd

    2011-09-01

    Breast cancer is a heterogeneous disease, marked by extensive chromosomal aberrations. In this study, we aimed to explicate the underlying chromosomal copy number (CN) alterations and loss of heterozygosity (LOH) implicated in a cohort of Malaysian hospital-based primary breast carcinoma samples using a single nucleotide polymorphism (SNP) array platform. The analysis was conducted by hybridizing the extracted DNA of 70 primary breast carcinomas and 37 normal peripheral blood samples to the Affymetrix 250K Sty SNP arrays. Locus-specific CN aberrations and LOH were statistically summarized using the binary segmentation algorithm and hidden Markov model. Selected genes from the SNP array analysis were also validated using quantitative real-time PCR. The merging of CN and LOH data fabricated distinctive integrated alteration profiles, which were comprised of finely demarcated minimal sites of aberrations. The most prevalent gains (≥ 30%) were detected at the 8q arm: 8q23.1, 8q23.3, 8q24.11, 8q24.13, 8q24.21, 8q24.22, 8q24.23 and 8q24.3, whilst the most ubiquitous losses (≥ 20%) were noted at the 8p12, 8p21.1, 8p21.2, 8p21.1-p21.2, 8p21.3, 8p22, 8p23.1, 8p23.1‑p23.2, 8p23.3, 17p11.2, 17p12, 17p11.2-p12, 17p13.1 and 17p13.2 regions. Copy-neutral LOH was characterized as the most prevailing LOH event, in which the most frequent distributions (≥ 30%) were revealed at 3p21.31, 5q33.2, 12q24.12, 12q24.12‑q24.13 and 14q23.1. These findings offer compre-hensive genome-wide views on breast cancer genomic changes, where the most recurrent gain, loss and copy-neutral LOH events were harboured within the 8q24.21, 8p21.1 and 14q23.1 loci, respectively. This will facilitate the uncovering of true driver genes pertinent to breast cancer biology and the develop-ment of prospective therapeutics. PMID:21687935

  20. Partial loss of heterozygosity events at the mutated gene in tumors from MLH1/MSH2 large genomic rearrangement carriers

    Depending on the population studied, large genomic rearrangements (LGRs) of the mismatch repair (MMR) genes constitute various proportions of the germline mutations that predispose to hereditary non-polyposis colorectal cancer (HNPCC). It has been reported that loss of heterozygosity (LOH) at the LGR region occurs through a gene conversion mechanism in tumors from MLH1/MSH2 deletion carriers; however, the converted tracts were delineated only by extragenic microsatellite markers. We sought to determine the frequency of LGRs in Slovak HNPCC patients and to study LOH in tumors from LGR carriers at the LGR region, as well as at other heterozygous markers within the gene to more precisely define conversion tracts. The main MMR genes responsible for HNPCC, MLH1, MSH2, MSH6, and PMS2, were analyzed by MLPA (multiplex ligation-dependent probe amplification) in a total of 37 unrelated HNPCC-suspected patients whose MLH1/MSH2 genes gave negative results in previous sequencing experiments. An LOH study was performed on six tumors from LGR carriers by combining MLPA to assess LOH at LGR regions and sequencing to examine LOH at 28 SNP markers from the MLH1 and MSH2 genes. We found six rearrangements in the MSH2 gene (five deletions and dup5-6), and one aberration in the MLH1 gene (del5-6). The MSH2 deletions were of three types (del1, del1-3, del1-7). We detected LOH at the LGR region in the single MLH1 case, which was determined in a previous study to be LOH-negative in the intragenic D3S1611 marker. Three tumors displayed LOH of at least one SNP marker, including two cases that were LOH-negative at the LGR region. LGRs accounted for 25% of germline MMR mutations identified in 28 Slovakian HNPCC families. A high frequency of LGRs among the MSH2 mutations provides a rationale for a MLPA screening of the Slovakian HNPCC families prior scanning by DNA sequencing. LOH at part of the informative loci confined to the MLH1 or MSH2 gene (heterozygous LGR region, SNP, or

  1. p53 polymorphisms associated with mutations in and loss of heterozygosity of the p53 gene in male oral squamous cell carcinomas in Taiwan

    Hsieh, L-L; Huang, T-H; Chen, I-H; Liao, C-T; Wang, H-M; Lai, C-H; Liou, S-H; Chang, J T-C; Cheng, A-J

    2004-01-01

    The present study was designed to examine whether different p53 haplotypes of exon 4–intron 3–intron 6 affect the frequency of mutations and loss of heterozygosity (LOH) of the p53 gene in male oral squamous cell carcinomas (OSCCs) in Taiwan. We found that individuals without two Pro-W-G alleles had significantly higher frequency of p53 mutations than those with two Pro-W-G alleles (odds ratio (OR)=1.98; 95% confidence interval (CI), 1.10–3.56). Out of the 172 p53 gene exon 4 informative male...

  2. Heterozygosity of Knob-Associated Tandem Repeats and Knob Instability in Mitotic Chromosomes of Zea (Zea mays L. and Z. diploperennis Iltis Doebley)

    Zhi-Yong XIONG; Yong LIU; Yong-Gang HE; Yun-Chun SONG; Ke-Xiu LI; Guan-Yuan HE

    2005-01-01

    Knobs are blocks of heterochromatin present on chromosomes of maize (Zea mays L.) and its relatives that have effects on the frequency of genetic recombination, as well as on chromosome behavior.Knob heterozygosity and instability in six maize inbred lines and one Z. diploperennis Iltis Doebley line were investigated using the fluorescence in situ hybridization (FISH) technique with knob-associated tandem repeats (180 bp and 350 bp (TR-1)) as probes. Signals of seven heterozygous knobs containing 180-bp repeats and of one heterozygous knob containing TR- 1 were captured in chromosomes of all materials tested according to the results of FISH, which demonstrates that the 180-bp repeat is the main contributor to knob heterozygosity compared with the TR-1 element. In addition, one target cell with two TR-1 signals on one homolog of chromosome 2L, which was different from the normal cells in the maize inbred line GB57,was observed, suggesting knob duplication and an instability phenomenon in the maize genome.

  3. Glucose-dependent insulinotropic peptide receptor overexpression in adrenocortical hyperplasia in MEN1 syndrome without loss of heterozygosity at the 11q13 locus

    Marcia Helena Soares Costa

    2011-01-01

    Full Text Available BACKGROUND: The molecular mechanisms involved in the genesis of the adrenocortical lesions seen in MEN1 syndrome (ACL-MEN1 remain poorly understood; loss of heterozygosity at 11q13 and somatic mutations of MEN1 are not usually found in these lesions. Thus, additional genes must be involved in MEN1 adrenocortical disorders. Overexpression of the glucose-dependent insulinotropic peptide receptor has been shown to promote adrenocortical tumorigenesis in a mice model and has also been associated with ACTH-independent Cushing syndrome in humans. However, to our knowledge, the status of glucose-dependent insulinotropic peptide receptor expression in adrenocortical lesions in MEN1 has not been previously investigated. OBJECTIVE: To evaluate glucose-dependent insulinotropic peptide receptor expression in adrenocortical hyperplasia associated with MEN1 syndrome. MATERIALS/METHODS: Three adrenocortical tissue samples were obtained from patients with previously known MEN1 germline mutations and in whom the presence of a second molecular event (a new MEN1 somatic mutation or an 11q13 loss of heterozygosity had been excluded. The expression of the glucose-dependent insulinotropic peptide receptor was quantified by qPCR using the DDCT method, and b-actin was used as an endogenous control. RESULTS: The median of glucose-dependent insulinotropic peptide receptor expression in the adrenocortical lesions associated with MEN1 syndrome was 2.6-fold (range 1.2 to 4.8 higher than the normal adrenal controls (p = 0.02. CONCLUSION: The current study represents the first investigation of glucose-dependent insulinotropic peptide receptor expression in adrenocortical lesions without 11q13 loss of heterozygosity in MEN1 syndrome patients. Although we studied a limited number of cases of MEN1 adrenocortical lesions retrospectively, our preliminary data suggest an involvement of glucose-dependent insulinotropic peptide receptor overexpression in the etiology of

  4. The role of proteases, endoplasmic reticulum stress and SERPINA1 heterozygosity in lung disease and alpha-1 anti-trypsin deficiency.

    Greene, Catherine M

    2012-02-01

    The serine proteinase inhibitor alpha-1 anti-trypsin (AAT) provides an antiprotease protective screen throughout the body. Mutations in the AAT gene (SERPINA1) that lead to deficiency in AAT are associated with chronic obstructive pulmonary diseases. The Z mutation encodes a misfolded variant of AAT that is not secreted effectively and accumulates intracellularly in the endoplasmic reticulum of hepatocytes and other AAT-producing cells. Until recently, it was thought that loss of antiprotease function was the major cause of ZAAT-related lung disease. However, the contribution of gain-of-function effects is now being recognized. Here we describe how both loss- and gain-of-function effects can contribute to ZAAT-related lung disease. In addition, we explore how SERPINA1 heterozygosity could contribute to smoking-induced chronic obstructive pulmonary diseases and consider the consequences.

  5. DNA studies are necessary for accurate patient diagnosis in compound heterozygosity for Hb Adana (HBA2:c.179>A) with deletional or nondeletional α-thalassaemia.

    Tan, Jin Ai Mary Anne; Kho, Siew Leng; Ngim, Chin Fang; Chua, Kek Heng; Goh, Ai Sim; Yeoh, Seoh Leng; George, Elizabeth

    2016-01-01

    Haemoglobin (Hb) Adana (HBA2:c.179>A) interacts with deletional and nondeletional α-thalassaemia mutations to produce HbH disorders with varying clinical manifestations from asymptomatic to severe anaemia with significant hepatosplenomegaly. Hb Adana carriers are generally asymptomatic and haemoglobin subtyping is unable to detect this highly unstable α-haemoglobin variant. This study identified 13 patients with compound heterozygosity for Hb Adana with either the 3.7 kb gene deletion (-α(3.7)), Hb Constant Spring (HbCS) (HBA2:c.427T>C) or Hb Paksé (HBA2:429A>T). Multiplex Amplification Refractory Mutation System was used for the detection of five deletional and six nondeletional α-thalassaemia mutations. Duplex-PCR was used to confirm Hb Paksé and HbCS. Results showed 84.6% of the Hb Adana patients were Malays. Using DNA studies, compound heterozygosity for Hb Adana and HbCS (α(codon 59)α/α(CS)α) was confirmed in 11 patients. A novel point in this investigation was that DNA studies confirmed Hb Paksé for the first time in a Malaysian patient (α(codon 59)α/α(Paksé)α) after nine years of being misdiagnosis with Hb Adana and HbCS (α(codon 59)α/α(CS)α). Thus, the reliance on haematology studies and Hb subtyping to detect Hb variants is inadequate in countries where thalassaemia is prevalent and caused by a wide spectrum of mutations. PMID:27271331

  6. Frequent loss of heterozygosity and altered expression of the candidate tumor suppressor gene 'FAT' in human astrocytic tumors

    We had earlier used the comparison of RAPD (Random Amplification of Polymorphic DNA) DNA fingerprinting profiles of tumor and corresponding normal DNA to identify genetic alterations in primary human glial tumors. This has the advantage that DNA fingerprinting identifies the genetic alterations in a manner not biased for locus. In this study we used RAPD-PCR to identify novel genomic alterations in the astrocytic tumors of WHO grade II (Low Grade Diffuse Astrocytoma) and WHO Grade IV (Glioblastoma Multiforme). Loss of heterozygosity (LOH) of the altered region was studied by microsatellite and Single Nucleotide Polymorphism (SNP) markers. Expression study of the gene identified at the altered locus was done by semi-quantitative reverse-transcriptase-PCR (RT-PCR). Bands consistently altered in the RAPD profile of tumor DNA in a significant proportion of tumors were identified. One such 500 bp band, that was absent in the RAPD profile of 33% (4/12) of the grade II astrocytic tumors, was selected for further study. Its sequence corresponded with a region of FAT, a putative tumor suppressor gene initially identified in Drosophila. Fifty percent of a set of 40 tumors, both grade II and IV, were shown to have Loss of Heterozygosity (LOH) at this locus by microsatellite (intragenic) and by SNP markers. Semi-quantitative RT-PCR showed low FAT mRNA levels in a major subset of tumors. These results point to a role of the FAT in astrocytic tumorigenesis and demonstrate the use of RAPD analysis in identifying specific alterations in astrocytic tumors

  7. Mild Microcytic Anemia in an Infant with a Compound Heterozygosity for Hb C (HBB: c.19G > A) and Hb Osu Christiansborg (HBB: c.157G > A).

    Boucher, Maria O; Chui, David H K; Woda, Bruce A; Newburger, Peter E

    2016-06-01

    We report an infant with a compound heterozygosity for Hb C (HBB: c.19G > A) and Hb Osu Christiansborg (HBB: c.157G > A) and a phenotype of mild microcytic anemia with target cell morphology but without overt hemolysis. PMID:27117572

  8. α₁-Antitrypsin protease inhibitor MZ heterozygosity is associated with airflow obstruction in two large cohorts

    Sørheim, Inga-Cecilie; Bakke, Per; Gulsvik, Amund; Pillai, Sreekumar G; Johannessen, Ane; Gaarder, Per I; Campbell, Edward J; Agustí, Alvar; Calverley, Peter M A; Donner, Claudio F; Make, Barry J; Rennard, Stephen I; Vestbo, Jørgen; Wouters, Emiel F M; Paré, Peter D; Levy, Robert D; Coxson, Harvey O; Lomas, David A; Hersh, Craig P; Silverman, Edwin K

    2010-01-01

    Severe α₁-antitrypsin deficiency is a known genetic risk factor for COPD. Heterozygous (protease inhibitor [PI] MZ) individuals have moderately reduced serum levels of α₁-antitrypsin, but whether they have an increased risk of COPD is uncertain....

  9. Genome-wide loss of heterozygosity and copy number alteration in esophageal squamous cell carcinoma using the Affymetrix GeneChip Mapping 10 K array

    Goldstein Alisa M

    2006-11-01

    Full Text Available Abstract Background Esophageal squamous cell carcinoma (ESCC is a common malignancy worldwide. Comprehensive genomic characterization of ESCC will further our understanding of the carcinogenesis process in this disease. Results Genome-wide detection of chromosomal changes was performed using the Affymetrix GeneChip 10 K single nucleotide polymorphism (SNP array, including loss of heterozygosity (LOH and copy number alterations (CNA, for 26 pairs of matched germ-line and micro-dissected tumor DNA samples. LOH regions were identified by two methods – using Affymetrix's genotype call software and using Affymetrix's copy number alteration tool (CNAT software – and both approaches yielded similar results. Non-random LOH regions were found on 10 chromosomal arms (in decreasing order of frequency: 17p, 9p, 9q, 13q, 17q, 4q, 4p, 3p, 15q, and 5q, including 20 novel LOH regions (10 kb to 4.26 Mb. Fifteen CNA-loss regions (200 kb to 4.3 Mb and 36 CNA-gain regions (200 kb to 9.3 Mb were also identified. Conclusion These studies demonstrate that the Affymetrix 10 K SNP chip is a valid platform to integrate analyses of LOH and CNA. The comprehensive knowledge gained from this analysis will enable improved strategies to prevent, diagnose, and treat ESCC.

  10. Clonal evolution and clinical significance of copy number neutral loss of heterozygosity of chromosome arm 6p in acquired aplastic anemia.

    Betensky, Marisol; Babushok, Daria; Roth, Jacquelyn J; Mason, Philip J; Biegel, Jaclyn A; Busse, Tracy M; Li, Yimei; Lind, Curt; Papazoglou, Anna; Monos, Dimitri; Podsakoff, Gregory; Bessler, Monica; Olson, Timothy S

    2016-01-01

    Acquired aplastic anemia (aAA) results from the T cell-mediated autoimmune destruction of hematopoietic stem cells. Factors predicting response to immune suppression therapy (IST) or development of myelodysplastic syndrome (MDS) are beginning to be elucidated. Our recent data suggest most patients with aAA treated with IST develop clonal somatic genetic alterations in hematopoietic cells. One frequent acquired abnormality is copy-number neutral loss of heterozygosity on chromosome 6p (6p CN-LOH) involving the human leukocyte antigen (HLA) locus. We hypothesized that because 6p CN-LOH clones may arise from selective pressure to escape immune surveillance through deletion of HLA alleles, the development of 6p CN-LOH may affect response to IST. We used single nucleotide polymorphism array genotyping and targeted next-generation sequencing of HLA alleles to assess frequency of 6p CN-LOH, identity of HLA alleles lost through 6p CN-LOH, and impact of 6p CN-LOH on response to IST. 6p CN-LOH clones were present in 11.3% of patients, remained stable over time, and were not associated with development of MDS-defining cytogenetic abnormalities. Notably, no patient with 6p CN-LOH treated with IST achieved a complete response. In summary, clonal 6p CN-LOH in aAA defines a unique subgroup of patients that may provide insights into hematopoietic clonal evolution. PMID:26702937

  11. A map of nuclear matrix attachment regions within the breast cancer loss-of-heterozygosity region on human chromosome 16q22.1.

    Shaposhnikov, Sergey A; Akopov, Sergey B; Chernov, Igor P; Thomsen, Preben D; Joergensen, Claus; Collins, Andrew R; Frengen, Eirik; Nikolaev, Lev G

    2007-03-01

    There is abundant evidence that the DNA in eukaryotic cells is organized into loop domains that represent basic structural and functional units of chromatin packaging. To explore the DNA domain organization of the breast cancer loss-of-heterozygosity region on human chromosome 16q22.1, we have identified a significant portion of the scaffold/matrix attachment regions (S/MARs) within this region. Forty independent putative S/MAR elements were assigned within the 16q22.1 locus. More than 90% of these S/MARs are AT rich, with GC contents as low as 27% in 2 cases. Thirty-nine (98%) of the S/MARs are located within genes and 36 (90%) in gene introns, of which 15 are in first introns of different genes. The clear tendency of S/MARs from this region to be located within the introns suggests their regulatory role. The S/MAR resource constructed may contribute to an understanding of how the genes in the region are regulated and of how the structural architecture and functional organization of the DNA are related. PMID:17188460

  12. Analysis of two single nucleotide polymorphisms and loss of heterozygosity detection in the VHL gene in Chinese patients with sporadic renal cell carcinoma

    LIU Ning; GONG Kan; NA Xi; WU Guan; NA Yan-qun

    2005-01-01

    @@ Renal cell carcinoma (RCC) is the most common malignant tumour in the adult kidney.Recent studies have shown that inactivation of the tumour suppressor gene VHL located in chromosome 3p25-26 region is responsible for sporadic RCCs.1 According to Kundson's two hit theory,the mechanism of inactivation of a tumour suppressor gene involves mutation,hyper-methylation and loss of heterozygosity (LOH).Mutations and hypermethylation of the VHL gene have been well analysed in RCC,but due to the deficiency of specific gene markers in the VHL region,the exact LOH frequency of the VHL gene in RCC is still unknown.Single nucleotide polymorphisms (SNPs) are regarded as the third generation of human gene markers and are appropriate for LOH analysis.We searched the SNP database in the National Centre for Biotechnology Information,and selected two SNP sites located within the VHL gene region as gene markers.We analysed these two SNP sites in 79 Chinese sporadic RCC patients by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) to detect LOH frequency of the VHL gene and analyse the relationship between VHL LOH and the pathological parameters of RCC.

  13. Loss of heterozygosity on chromosome 10q23 and mutation of the phosphatase and tensin homolog deleted from chromosome 10 tumor suppressor gene in Korean hepatocellular carcinoma patients.

    Bae, Jei-Jun; Rho, Jin-Woo; Lee, Tae-Jin; Yun, Sung-Su; Kim, Hong-Jin; Choi, Joon-Hyuk; Jeong, Daewon; Jang, Byeong-Churl; Lee, Tae-Yoon

    2007-10-01

    Loss of heterozygosity (LOH) in the 10q23 chromosomal region was analyzed in 18 tissue samples from Korean hepatocellular carcinoma (HCC) patients. LOH at the phosphatase and tensin homolog deleted from chromosome 10 (PTEN) region (D10S215, AFMa086wg9 and D10S541) was found in 8 of the 18 (44.4%) HCCs. LOH (20%) and microsatellite instability (26.7%) were also frequently found at the D10S2177 locus, which is located on the telomere side of the PTEN region. LOH was found in other loci, such as AFM280we1 and D10S2281. The presence of LOH in regions other than the PTEN region on chromosome 10q23 suggested the presence of additional tumor suppressor gene(s). PTEN mutation was found in only a subset of HCCs: A single base insertion at the end of the 5'-end splice signal (AG-GUAAGUU) in intron 5 and a silent mutation in exon 6 (codon 188, CTG-Val to CTA). Our data collectively suggest that the genetic alterations of chromosome 10q23, including the PTEN gene, could be important in hepatocarcinogenesis in the Korean population. PMID:17786367

  14. A hypothesis on the origin of genetic heterozygosity in diploids and triploids in Japanese Cayratia japonica species complex (Vitaceae).

    Tsukaya, Hirokazu; Ishikawa, Naoko; Okada, Hiroshi

    2012-07-01

    We previously reported the occurrence of triploid strains in Japanese populations of Cayratia japonica (Thunb.) Gagnep. Interestingly, the triploid and most diploid strains had variably reduced pollen fertility. Two questions emerged from this earlier work: (1) How do triploids arise, and are they allotriploids or autotriploids? and (2) Why is there low pollen fertility in some diploid plants? We used a molecular genetic approach to determine the phylogenetic origins of triploids in C. japonica and the closely related species Cayratia tenuifolia (Wight & Arn.) Gagnep. In our analysis, we compared the sequences of the nuclear single-copy genes LEAFY and ASYMMETRIC LEAVES1. As a result, most triploids and diploids were heterozygous for the loci examined; the triploid genome shared an allele with the diploid genome, but other alleles differed between the ploidies. Therefore, Japanese populations of C. japonica and C. tenuifolia almost certainly arose from repeated hybridization events among genetically differentiated strains. Using our sequence data, we discuss possible scenarios accounting for the occurrence of triploids in the two species of Cayratia. PMID:22200910

  15. Detailed deletion mapping of loss of heterozygosity on 9p13-23 in laryngeal squamous cell carcinoma by microsatellite analysis

    徐先发; 高燕宁; 程书鈞

    2004-01-01

    Background This study was designed to investigate the hot spots of microsatellite loss of heterozygosity (LOH) on 9p13-23 in laryngeal squamous cell carcinoma and to find out the correlation between the incidence of microsatellite LOH and the clinicopathological parameters.Methods Tumor tissues were obtained from paraffin embedded sections with microdissection. Genomic DNA was extracted from tumor tissues and peripheral blood lymphocytes with the phenol-chloroform. Polymerase chain reaction (PCR) amplification and denaturing gel electrophoresis were carried out in a set of 42 squamous cell carcinoma (SCC) of larynx and corresponding peripheral blood lymphocytes using 13 highly polymorphic microsatellite markers on 9p13-23. The correlation was analyzed between microsatellite LOH at the high frequency on 9p13-23 and clinicopathological parameters in the patients with squamous cell carcinoma of larynx.Results Of the 42 laryngeal cancers, 41 (97.6%) showed LOH in at least one of the microsatellite markers tested on 9p13-23. The most frequently deleted marker was D9S162 in 17 of the 19 (89.5%) informative samples. The marker D9S171, which is located on 9p21, had LOH detected in 12 of the 15 informative cases (80.0%). LOH at the D9S1748 marker (closest to the p16 gene locus) was detected in 18 of the 36 informative cases (50.0%). Allelic deletion mapping revealed two minimal regions of LOH encompassing markers D9S161-D9S171 on 9p21 and IFNA-D9S162 on 9p22-23. Multiple LOH (≥4) on 9p21-23 was found more frequently in the patients under 60 years, with supraglottic SCC or cervical lymph node metastasis than those over 60 years, with glottic SCC or without cervical lymph node metastasis (P<0.01 or 0.01, 0.05, respectively). On the contrary, there was no correlation between T stages or pathologic classification and the frequency of LOH on 9p21-23 in 42 SCC of Larynx.Conclusions These findings imply the presence of at least two putative tumor suppressor genes on 9p13-23 in

  16. delta beta-Thalassaemia in Sicily: report of a case of double heterozygosity for A gamma delta beta-thalassaemia and A gamma G gamma delta beta-thalassaemia.

    Musumeci,S; Romeo, M A; Pizzarelli, G.; Schilirò, G; Russo, G.

    1983-01-01

    A case of double heterozygosity for A gamma delta beta-thalassaemia and A gamma G gamma delta beta-thalassaemia was found during a screening programme in Sicily. The proband, a 4-year-old girl, showed a clinical picture of thalassaemia intermedia. Hb F (85.12% by the Singer method) was G gamma A gamma type. The parents and the brother were delta beta-thalassaemia carriers. Structural analysis of Hb F showed both G gamma and A gamma chains in the father, but only A gamma chains in the mother.

  17. A Non-Invasive Droplet Digital PCR (ddPCR) Assay to Detect Paternal CFTR Mutations in the Cell-Free Fetal DNA (cffDNA) of Three Pregnancies at Risk of Cystic Fibrosis via Compound Heterozygosity

    Debrand, Emmanuel; Lykoudi, Alexandra; Bradshaw, Elizabeth; Allen, Stephanie K.

    2015-01-01

    Introduction Non-invasive prenatal diagnosis (NIPD) makes use of cell-free fetal DNA (cffDNA) in the mother’s bloodstream as an alternative to invasive sampling methods such as amniocentesis or CVS, which carry a 0.5–1% risk of fetal loss. We describe a droplet digital PCR (ddPCR) assay designed to inform the testing options for couples whose offspring are at risk of suffering from cystic fibrosis via compound heterozygosity. By detecting the presence or absence of the paternal mutation in th...

  18. CHEK2*1100delC Heterozygosity in Women With Breast Cancer Associated With Early Death, Breast Cancer-Specific Death, and Increased Risk of a Second Breast Cancer

    Weischer, Maren; Nordestgaard, Børge G; Pharoah, Paul; Bolla, Manjeet K; Nevanlinna, Heli; Van't Veer, Laura J; Garcia-Closas, Montserrat; Hopper, John L; Hall, Per; Andrulis, Irene L; Devilee, Peter; Fasching, Peter A; Anton-Culver, Hoda; Lambrechts, Diether; Hooning, Maartje; Cox, Angela; Giles, Graham G; Burwinkel, Barbara; Lindblom, Annika; Couch, Fergus J; Mannermaa, Arto; Grenaker Alnæs, Grethe; John, Esther M; Dörk, Thilo; Flyger, Henrik; Dunning, Alison M; Wang, Qin; Muranen, Taru A; van Hien, Richard; Figueroa, Jonine; Southey, Melissa C; Czene, Kamila; Knight, Julia A; Tollenaar, Rob A E M; Beckmann, Matthias W; Ziogas, Argyrios; Christiaens, Marie-Rose; Collée, Johanna Margriet; Reed, Malcolm W R; Severi, Gianluca; Marme, Frederik; Margolin, Sara; Olson, Janet E; Kosma, Veli-Matti; Kristensen, Vessela N; Miron, Alexander; Bogdanova, Natalia; Shah, Mitul; Blomqvist, Carl; Broeks, Annegien; Sherman, Mark; Phillips, Kelly-Anne; Li, Jingmei; Liu, Jianjun; Glendon, Gord; Seynaeve, Caroline; Ekici, Arif B; Leunen, Karin; Kriege, Mieke; Cross, Simon S; Baglietto, Laura; Sohn, Christof; Wang, Xianshu; Kataja, Vesa; Børresen-Dale, Anne-Lise; Meyer, Andreas; Easton, Douglas F; Schmidt, Marjanka K; Bojesen, Stig E

    2012-01-01

    PURPOSE We tested the hypotheses that CHEK2*1100delC heterozygosity is associated with increased risk of early death, breast cancer-specific death, and risk of a second breast cancer in women with a first breast cancer. PATIENTS AND METHODS From 22 studies participating in the Breast Cancer...... Association Consortium, 25,571 white women with invasive breast cancer were genotyped for CHEK2*1100delC and observed for up to 20 years (median, 6.6 years). We examined risk of early death and breast cancer-specific death by estrogen receptor status and risk of a second breast cancer after a first breast...... cancer in prospective studies. Results CHEK2*1100delC heterozygosity was found in 459 patients (1.8%). In women with estrogen receptor-positive breast cancer, multifactorially adjusted hazard ratios for heterozygotes versus noncarriers were 1.43 (95% CI, 1.12 to 1.82; log-rank P = .004) for early death...

  19. Reducing costs by reducing size

    The present paper discusses briefly the many factors, including capital cost, which have to be taken into account in determining whether a series of power stations based on a small nuclear plant can be competitive with a series based on traditional large unit sizes giving the guaranteed level of supply. The 320 MWe UK/US Safe Integral Reactor is described as a good example of how the factors discussed can be beneficially incorporated into a design using proven technology. Finally it goes on to illustrate how the overall costs of a generating system can indeed by reduced by use of the 320 MWe Safe Integral Reactor rather than conventional units of around 1200 MWe. (author). 9 figs

  20. Compound heterozygosity for COL7A1 mutations in twins with dystrophic epidermolysis bullosa: A recessive paternal deletion/insertion mutation and a dominant negative maternal glycine substitution result in a severe phenotype

    Christiano, A.M.; Uitto, J. [Thomas Jefferson Univ., Philadelphia, PA (United States); Anton-Lamprecht, I.; Ebschner, U. [Universitaet Heidelberg (Germany); Amano, S.; Burgeson, R.E. [Harvard Medical School, Charlestown, MA (United States)

    1996-04-01

    We have previously demonstrated genetic linkage between the type VII collagen gene (COL7A1) and the dominant (DDEB) and recessive (RDEB) forms of dystrophic epidermolysis bullosa (DEB) and have subsequently identified pathogenetic mutations in several families. Mutations in DDEB identified thus far are glycine substitutions in the collagenous domain of COL7A1, while the most severe forms of RDEB result from premature termination codon (PTC) mutations on both alleles. In this study, we performed mutation analysis in the COL7A1 gene in twins who displayed a severe DEB phenotype. Mutational analysis revealed a paternal 2-bp deletion/1-bp insertion in exon 56, designated 5103CC{yields}G, which results in a frameshift and downstream PTC. Analysis of the maternal COL7A1 allele revealed a glycine-to-arginine substitution in exon 91 (G2351R). Careful questioning of the mother revealed that she and her father had a history of shedding of toenails and occasional poorly heating erosions, consistent with a mild form of DDEB. Immunoprecipitation of type VII collagen from fibroblasts of the twins revealed a marked reduction in intracellular protein production, consistent with the drastic reduction in mRNA transcript from the paternal mutant allele, while the majority of polypeptides bearing the glycine substitution appeared to be degraded intracellularly. Thus, the severe RDEB phenotype in the probands results from compound heterozygosity for one glycine substitution and one PTC mutation in COL7A1. 40 refs., 7 figs.

  1. First Spanish case of thalassemia major due to a compound heterozygosity for the IVS-II-848 (C --> A) and codon 39 (C --> T) mutations of the beta-globin gene.

    Ropero, Paloma; Villegas, Ana; Muñoz, Juan; Briceño, Olga; Mora, Asunción; Salvador, María; Polo, Marta; González, Fernando A

    2006-01-01

    This report describes the first case in Spain of a severe form of beta-thalassemia (thal) due to a compound heterozygosity for the IVS-II-848 (C --> A) and the nonsense codon 39 (C --> T) mutations. Five members of a family from Cadiz (southern Spain) were studied. The proband was an 8-year-old girl diagnosed as anemic at the age of 13 months. Her father had the codon 39 (C --> T) mutation and her mother the C --> A change at nucleotide (nt) 848 of IVS-II. Haplotype analysis showed that the proband was a compound heterozygote for haplotypes I [+ --> + +] and VII [+ --> +]. This is the first description in Spain of the IVS-II-848 (C --> A) mutation. It appears, from restriction fragment length polymorphism (RFLP) analysis, that this mutation has a different origin in the various populations, where it was found. This observation shows that in this case the association of a beta(0)- and a beta(+)-thal mutation does not lead to a thalassemia intermedia but to a severe thalassemia with very low hemoglobin (Hb) levels. From a therapeutic point of view, early introduction of a transfusion regimen may improve the clinical picture of these children, allowing for better development and growth. PMID:16540410

  2. A Non-Invasive Droplet Digital PCR (ddPCR Assay to Detect Paternal CFTR Mutations in the Cell-Free Fetal DNA (cffDNA of Three Pregnancies at Risk of Cystic Fibrosis via Compound Heterozygosity.

    Emmanuel Debrand

    Full Text Available Non-invasive prenatal diagnosis (NIPD makes use of cell-free fetal DNA (cffDNA in the mother's bloodstream as an alternative to invasive sampling methods such as amniocentesis or CVS, which carry a 0.5-1% risk of fetal loss. We describe a droplet digital PCR (ddPCR assay designed to inform the testing options for couples whose offspring are at risk of suffering from cystic fibrosis via compound heterozygosity. By detecting the presence or absence of the paternal mutation in the cffDNA, it is possible to predict whether the fetus will be an unaffected carrier (absence or whether further invasive testing is indicated (presence.We selected a family in which the parents were known to carry different mutated CFTR alleles as our test system. NIPD was performed for three of their pregnancies during the first trimester (at around 11-12 weeks of gestation. Taqman probes were designed against an amplicon in exon 11 of the CFTR gene, to quantify the proportion of mutant (ΔF508-MUT; FAM and normal (ΔF508-NOR; VIC alleles at position c.1521_1523 of the CFTR gene.The assay correctly and unambiguously recognized the ΔF508-MUT CFTR allele in the cffDNA of all three proband fetuses and none of the six unaffected control fetuses. In conclusion, the Bio-Rad QX100 was found to be a cost-effective and technically undemanding platform for designing bespoke NIPD assays.

  3. A Non-Invasive Droplet Digital PCR (ddPCR) Assay to Detect Paternal CFTR Mutations in the Cell-Free Fetal DNA (cffDNA) of Three Pregnancies at Risk of Cystic Fibrosis via Compound Heterozygosity

    Debrand, Emmanuel; Lykoudi, Alexandra; Bradshaw, Elizabeth; Allen, Stephanie K.

    2015-01-01

    Introduction Non-invasive prenatal diagnosis (NIPD) makes use of cell-free fetal DNA (cffDNA) in the mother’s bloodstream as an alternative to invasive sampling methods such as amniocentesis or CVS, which carry a 0.5–1% risk of fetal loss. We describe a droplet digital PCR (ddPCR) assay designed to inform the testing options for couples whose offspring are at risk of suffering from cystic fibrosis via compound heterozygosity. By detecting the presence or absence of the paternal mutation in the cffDNA, it is possible to predict whether the fetus will be an unaffected carrier (absence) or whether further invasive testing is indicated (presence). Methods We selected a family in which the parents were known to carry different mutated CFTR alleles as our test system. NIPD was performed for three of their pregnancies during the first trimester (at around 11–12 weeks of gestation). Taqman probes were designed against an amplicon in exon 11 of the CFTR gene, to quantify the proportion of mutant (ΔF508-MUT; FAM) and normal (ΔF508-NOR; VIC) alleles at position c.1521_1523 of the CFTR gene. Discussion The assay correctly and unambiguously recognized the ΔF508-MUT CFTR allele in the cffDNA of all three proband fetuses and none of the six unaffected control fetuses. In conclusion, the Bio-Rad QX100 was found to be a cost-effective and technically undemanding platform for designing bespoke NIPD assays. PMID:26561302

  4. 甲状腺肿瘤3号染色体短臂杂合性缺失的研究%Loss of heterozygosity on chromosome 3p in thyroid tumors

    胡孟钧; 徐航娣; 周韧; 郦秀芳; 张海勇

    2008-01-01

    目的 探讨甲状腺肿瘤中3号染色体短臂(3p)杂合性缺失(LOH)状态及其临床意义.方法 收集74例甲状腺肿瘤标本,包括20例甲状腺腺瘤(FA)、24例滤泡性甲状腺癌(FTC)和30例乳头状甲状腺癌(Prc).通过PCR扩增和银染分析其3p上11个微卫星位点的杂合性缺失状态.结果 FFC的LOH频率达到71%(17/24),PTC中30%(9/30),FA中10%(2/20).FFC的3p LOH频率显著高于FA和PTC(P<0.01).FTC中存在两个最小共同缺失区,分别位于3p26-pter和3p14.2-3p22.PTC上存在一个最小共同缺失区,位于3p 25.2-26.1.结论 FTC的3p LOH频率显著高于FA和PTC.3p的3个最小缺失区上可能存在着与FTC和PTC发生发展相关的肿瘤抑制基因.%Objective To study the loss of heterozygosity(LOH)on chromosome 3p in thyroid tumors. Methods LOH at 11 microsatellite loci Wag analyzed in 74 cases of thyroid tumors(including 20 follicular adenomas, 24 follicular thyroid carcinomas and 30 papillary thyroid carcinomas)by polymerase chain reaction and silver stain. Results LOH on chromosome 3p Wag detected in 71% of follicular thyroid carcinoma(17/24), 30%of the papillary thyroid carcinoma(9/30) and 10%of the follicular adenoma (2/20)case. Two minimal common deleted regions(CDR)(3p26-pter and 3p14. 2-3p22)involving significant sites of LOH has identified in follicular thyroid carcinoma. There Was also one CDR(3p25. 2-26. 1)in papilhry thyroid careinoma. Conclusions LOH is more frequently identified in follicular thyroid careinoma than in papillary thyroid carcinoma and follicular adenoma. The 3 CDR on chromosome 3p may harbor tumor suppressor genes involved in the pathogenesis of follicular thyroid carcinoma and papillary thyroid carcinoma.

  5. Reduced Rank Regression

    Johansen, Søren

    2008-01-01

    The reduced rank regression model is a multivariate regression model with a coefficient matrix with reduced rank. The reduced rank regression algorithm is an estimation procedure, which estimates the reduced rank regression model. It is related to canonical correlations and involves calculating...... eigenvalues and eigenvectors. We give a number of different applications to regression and time series analysis, and show how the reduced rank regression estimator can be derived as a Gaussian maximum likelihood estimator. We briefly mention asymptotic results...

  6. Association between the impulsive aggressive behaviors and the heterozygosity of 1 7 short tandem repeats loci%17个短串联重复序列基因座杂合度与冲动攻击行为的相关性

    何益民; 巴华杰; 杨春; 余海鹰; 赵汉清; 张书友

    2014-01-01

    目的:探讨短串联重复序列( STR )基因座杂合度与冲动攻击行为的关系。方法运用 PowerPlex 18 D System 荧光标记复合扩增试剂盒对249例冲动攻击行为军人个体与313例非攻击行为对照个体样本进行 PCR 复合扩增,然后应用 ABI3130 XL 型基因分析系统对扩增产物进行基因检测。比较两个群体中杂合子比率及17个 STR 基因座杂度性的差异。结果17个 STR 基因座在两个群体均符合 Hardy-Weinberg 平衡;两个群体中的杂合子比率差异无统计学意义( P =0.533);在 CSF 1 PO 基因座冲动攻击行为组的杂合度显著低于对照组(P =0.035);其余 STR 基因座两组的杂合度无统计学意义(P >0.05)。结论 CSF1PO 基因座杂合性降低可能与冲动攻击行为的发生相关。%Objective To investigate the relationship of the impulsive aggressive behavior and the heterozygosity of 1 7 short tandem repeats ( STRs ) loci .Methods The biological samples of 2 4 9 army-men with impulsive aggressive behavior and 3 1 3 healthy armymen without aggressive behavior were collect-ed .Then all of the sample were amplified by PowerPlex 1 8 D System and separated by electrophoresis to obtain the heterozygosity of 1 7 STRs loci in both groups .Results All the 1 7 STRs loci in both groups were found to coincide with Hardy-Weinberg equilibrium; The ratios of heterozygotes with in the 1 7 STR loci in both groups were not different ( P =0.5 3 3 );The heterozygosity of CSF 1 PO locus within armymen with impulsive aggressive behavior was lower than control group ( P =0.0 3 5 ); The heterozygosity of both groups was not different in the other STR loci ( P >0.0 5 ) .Conclusion The reduction in heterozygosity of CSF 1 PO might associated with impulsive aggressive behavior .

  7. Pipeline Drag Reducers

    Pipeline drag reducers have proven to be an extremely powerful tool in fluid transportation. High molecular weight polymers are used to reduce the frictional pressure loss ratio in crude oil pipelines, refined fuel and aqueous pipelines. Chemical structure of the main used pipeline drag reducers is one of the following polymers and copolymers classified according to the type of fluid to ; low density polyethylene, copolymer of I-hexane cross linked with divinyl benzene, polyacrylamide, polyalkylene oxide polymers and their copolymers, fluorocarbons, polyalkyl methacrylates and terpolymer of styrene, alkyl acrylate and acrylic acid. Drag reduction is the increase in pump ability of a fluid caused by the addition of small amounts of an additive to the fluid. The effectiveness of a drag reducer is normally expressed in terms of percent drag reduction. Frictional pressure loss in a pipeline system is a waste of energy and it costly. The drag reducing additive minimizes the flow turbulence, increases throughput and reduces the energy costs. The Flow can be increased by more than 80 % with existing assets. The effectiveness of the injected drag reducer in Mostorod to Tanta crude oil pipeline achieved 35.4 % drag reduction and 23.2 % flow increase of the actual performance The experimental application of DRA on Arab Petroleum Pipeline Company (Summed) achieved a flow increase ranging from 9-32 %

  8. Reducing Erosion and Runoff

    Relf, Diane

    2009-01-01

    By caring for and improving your soil, you will help it absorb water more readily, reducing runoff and erosion as well as improving plant health. This publication gives the homeowner tips to help prevent runoff and erosion on their property.

  9. Reducing Childhood Obesity

    ... Bar Home Current Issue Past Issues Reducing Childhood Obesity Past Issues / Summer 2007 Table of Contents For ... Ga. were the first three We Can! cities. Obesity Research: A New Approach The percentage of children ...

  10. Reducing Childhood Obesity

    ... Navigation Bar Home Current Issue Past Issues Reducing Childhood Obesity Past Issues / Summer 2007 Table of Contents For ... page please turn Javascript on. The We Can! childhood obesity-prevention program involves parents, caregivers, and community leaders ...

  11. Reduced Extended MHD

    Morrison, P. J.; Abdelhamid, H. M.; Grasso, D.; Hazeltine, R. D.; Lingam, M.; Tassi, E.

    2015-11-01

    Over the years various reduced fluid models have been obtained for modeling plasmas, with the goal of capturing important physics while maintaining computability. Such models have included the physics contained in various generalizations of Ohm's law, including Hall drift and electron inertia. In a recent publication it was shown that full 3D extended MHD is a Hamiltonian system by finding its noncanonical Poisson bracket. Subsequently, this bracket was shown to be derivable from that for Hall MHD by a series of remarkable transformations, which greatly simplifies the proof of the Jacobi identity and allows one to immediately obtain generalizations of the helicity and cross helicity. In this poster we use this structure to obtain exact reduced fluid models with the effects of full two-fluid theory. Results of numerical computations of collisionless reconnection using an exact reduced 4-field model will be presented and analytical comparisons of mode structure of previous reduced models will be made.

  12. Reduced shear power spectrum

    Dodelson, Scott; /Fermilab /Chicago U., Astron. Astrophys. Ctr. /Northwestern U.; Shapiro, Charles; /Chicago U. /KICP, Chicago; White, Martin J.; /UC, Berkeley, Astron.

    2005-08-01

    Measurements of ellipticities of background galaxies are sensitive to the reduced shear, the cosmic shear divided by (1-{kappa}) where {kappa} is the projected density field. They compute the difference between shear and reduced shear both analytically and with simulations. The difference becomes more important an smaller scales, and will impact cosmological parameter estimation from upcoming experiments. A simple recipe is presented to carry out the required correction.

  13. Tank closure reducing grout

    A reducing grout has been developed for closing high level waste tanks at the Savannah River Site in Aiken, South Carolina. The grout has a low redox potential, which minimizes the mobility of Sr90, the radionuclide with the highest dose potential after closure. The grout also has a high pH which reduces the solubility of the plutonium isotopes. The grout has a high compressive strength and low permeability, which enhances its ability to limit the migration of contaminants after closure. The grout was designed and tested by Construction Technology Laboratories, Inc. Placement methods were developed by the Savannah River Site personnel

  14. Tank closure reducing grout

    Caldwell, T.B.

    1997-04-18

    A reducing grout has been developed for closing high level waste tanks at the Savannah River Site in Aiken, South Carolina. The grout has a low redox potential, which minimizes the mobility of Sr{sup 90}, the radionuclide with the highest dose potential after closure. The grout also has a high pH which reduces the solubility of the plutonium isotopes. The grout has a high compressive strength and low permeability, which enhances its ability to limit the migration of contaminants after closure. The grout was designed and tested by Construction Technology Laboratories, Inc. Placement methods were developed by the Savannah River Site personnel.

  15. Reduced Braginskii equations

    A set of reduced Braginskii equations is derived without assuming flute ordering and the Boussinesq approximation. These model equations conserve the physical energy. It is crucial at finite β that we solve the perpendicular component of Ohm's law to conserve the physical energy while ensuring the relation ∇ · j = 0

  16. Reduced Multiplication Modules

    Karim Samei

    2011-05-01

    An -module is called a multiplication module if for each submodule of , = for some ideal of . As defined for a commutative ring , an -module is said to be reduced if the intersection of prime submodules of is zero. The prime spectrum and minimal prime submodules of the reduced module are studied. Essential submodules of are characterized via a topological property. It is shown that the Goldie dimension of is equal to the Souslin number of Spec (). Also a finitely generated module is a Baer module if and only if Spec () is an extremally disconnected space; if and only if it is a -module. It is proved that a prime submodule is minimal in if and only if for each $x\\in N,\\mathrm{Ann}(x)\

  17. Reducing conspiracy theory beliefs

    Stojanov Ana

    2015-01-01

    Full Text Available This study aimed to look at possible ways to reduce beliefs in conspiracy theories and increase the intention to have a fictitious child vaccinated. One hundred and sixty participants answered an online questionnaire. Three groups were used. The control group did not read any text prior to answering whereas the two experimental groups read either only debunking information or information about the motives of the conspiracists and the fallacy in their reasoning in addition to the debunking paragraph. The second experimental manipulation was effective in reducing medical conspiracy theories beliefs, but not belief in conspiracy theories in general. Neither intervention was effective in increasing the likelihood to have a fictitious child vaccinated. Those not intending to vaccinate a fictitious child endorsed conspiracy theories to a greater degree. A positive correlation between beliefs in conspiracy theories and the experiential/intuitive information processing system was found.

  18. Reducing rotor weight

    Cheney, M.C. [PS Enterprises, Inc., Glastonbury, CT (United States)

    1997-12-31

    The cost of energy for renewables has gained greater significance in recent years due to the drop in price in some competing energy sources, particularly natural gas. In pursuit of lower manufacturing costs for wind turbine systems, work was conducted to explore an innovative rotor designed to reduce weight and cost over conventional rotor systems. Trade-off studies were conducted to measure the influence of number of blades, stiffness, and manufacturing method on COE. The study showed that increasing number of blades at constant solidity significantly reduced rotor weight and that manufacturing the blades using pultrusion technology produced the lowest cost per pound. Under contracts with the National Renewable Energy Laboratory and the California Energy Commission, a 400 kW (33m diameter) turbine was designed employing this technology. The project included tests of an 80 kW (15.5m diameter) dynamically scaled rotor which demonstrated the viability of the design.

  19. Risk-reducing mastectomy.

    Chiesa, Federica; Sacchini, Virgilio S

    2016-10-01

    Mastectomy rates have significantly increased over the last decades, likely due to the rising trend of risk-reducing mastectomies (RRM) in the treatment and prevention of breast cancer. Growing evidence suggests that aggressive risk-reducing surgical strategies are only justified in high-risk breast cancer situations. Notably, in this selected cohort of women, prophylactic mastectomies offer evident benefit for local and contralateral disease control, and may also provide a survival benefit. Nevertheless, the extent of the increasing frequency of this operation is not explained by the broadening of the medical indications alone. Here we analyze the current evidence regarding RRM, its clinical practice, and possible explanations for the rising phenomenon of aggressive surgical locoregional control strategies. PMID:26785281

  20. Reducing volcanic risk

    Decker, R.; Decker, B.

    1991-01-01

    The last two decades have brought major advances in research on how volcanoes work and how to monitor their changing habits. Geologic mapping as well as studies of earthquake patterns and surface deformation associated with underground movement of magma have given scientists a better view of the inner structure and dynamics of active volcanoes. With the next decade, the time has come to focuses more on applying this knowledge toward reducing the risk from volcanic activity on a worldwide basis. 

  1. Awareness Reduces Racial Bias

    Pope, Devin G.; Price, Joseph; Wolfers, Justin

    2014-01-01

    Can raising awareness of racial bias subsequently reduce that bias? We address this question by exploiting the widespread media attention highlighting racial bias among professional basketball referees that occurred in May 2007 following the release of an academic study. Using new data, we confirm that racial bias persisted in the years after the study's original sample, but prior to the media coverage. Subsequent to the media coverage though, the bias completely disappeared. We examine poten...

  2. Reducing conspiracy theory beliefs

    Stojanov Ana

    2015-01-01

    This study aimed to look at possible ways to reduce beliefs in conspiracy theories and increase the intention to have a fictitious child vaccinated. One hundred and sixty participants answered an online questionnaire. Three groups were used. The control group did not read any text prior to answering whereas the two experimental groups read either only debunking information or information about the motives of the conspiracists and the fallacy in their reason...

  3. Reducing Children's Media Viewing

    Erin Clyne; Jason, Leonard A.

    2011-01-01

    This case study evaluates the use of a Restrictive aide and the complementary use of parental mediation techniques to reduce media viewing among children. A family was provided a TV Token Timer, which involved a positive reward in exchange for participating in activities outside of watching television. Media viewing habits decreased from the baseline to the completion of the intervention at week 8 for both children. The parent reported high levels of Instructive mediation and positively evalu...

  4. Does democracy reduce corruption?

    Ivar Kolstad; Arne Wiig

    2011-01-01

    While democracy is commonly believed to reduce corruption, there are obvious endogeneity problems in measuring the impact of democracy on corruption. This paper addresses the endogeneity of democracy by exploiting the common observation that democracies seldom go to war against each other. We instrument for democracy using a dummy variable reflecting whether a country has been at war with a democracy in the period 1946-2009, while controlling for the extent to which countries have been at war...

  5. Coupling Reduces Noise

    Kia, Behnam; Kia, Sarvenaz; Lindner, John. F.; Sinha, Sudeshna; Ditto, William L.

    2014-01-01

    We demonstrate how coupling nonlinear dynamical systems can reduce the effects of noise. For simplicity we investigate noisy coupled map lattices. Noise from different lattice nodes can diffuse across the lattice and lower the noise level of individual nodes. We develop a theoretical model that explains this observed noise evolution and show how the coupled dynamics can naturally function as an averaging filter. Our numerical simulations are in excellent agreement with the model predictions.

  6. Gradual extinction reduces Reinstatement

    Youssef eShiban

    2015-09-01

    Full Text Available The current study investigated whether gradually reducing the frequency of aversive stimuli during extinction can prevent the return of fear. Thirty-one participants of a three-stage procedure (acquisition, extinction and a reinstatement test on day two were randomly assigned to a standard extinction (SE and gradual extinction (GE procedure. The two groups differed only in the extinction procedure. While the SE group ran through a regular extinction process without any negative events, the frequency of the aversive stimuli during the extinction phase was gradually reduced for the GE group. The unconditioned stimulus was an air blast (5 bar, 10 ms. A spider and a scorpion were used as conditioned stimuli. The outcome variables were contingency ratings and physiological measures (skin conductance response and startle response. There were no differences found between the two groups for the acquisition and extinction phases concerning contingency ratings, SCR, or startle response. Gradual extinction compared to standard extinction significantly reduced the return of fear in the reinstatement test for the startle response but not for skin conductance response or contingency ratings. This study was successful in translating the findings in rodent to humans. The results suggest that the gradual extinction process is suitable for increasing the efficacy of fear extinction.

  7. Coating Reduces Ice Adhesion

    Smith, Trent; Prince, Michael; DwWeese, Charles; Curtis, Leslie

    2008-01-01

    The Shuttle Ice Liberation Coating (SILC) has been developed to reduce the adhesion of ice to surfaces on the space shuttle. SILC, when coated on a surface (foam, metal, epoxy primer, polymer surfaces), will reduce the adhesion of ice by as much as 90 percent as compared to the corresponding uncoated surface. This innovation is a durable coating that can withstand several cycles of ice growth and removal without loss of anti-adhesion properties. SILC is made of a binder composed of varying weight percents of siloxane(s), ethyl alcohol, ethyl sulfate, isopropyl alcohol, and of fine-particle polytetrafluoroethylene (PTFE). The combination of these components produces a coating with significantly improved weathering characteristics over the siloxane system alone. In some cases, the coating will delay ice formation and can reduce the amount of ice formed. SILC is not an ice prevention coating, but the very high water contact angle (greater than 140 ) causes water to readily run off the surface. This coating was designed for use at temperatures near -170 F (-112 C). Ice adhesion tests performed at temperatures from -170 to 20 F (-112 to -7 C) show that SILC is a very effective ice release coating. SILC can be left as applied (opaque) or buffed off until the surface appears clear. Energy dispersive spectroscopy (EDS) and x-ray photoelectron spectroscopy (XPS) data show that the coating is still present after buffing to transparency. This means SILC can be used to prevent ice adhesion even when coating windows or other objects, or items that require transmission of optical light. Car windshields are kept cleaner and SILC effectively mitigates rain and snow under driving conditions.

  8. Reduced Google matrix

    Frahm, K M

    2016-01-01

    Using parallels with the quantum scattering theory, developed for processes in nuclear and mesoscopic physics and quantum chaos, we construct a reduced Google matrix $G_R$ which describes the properties and interactions of a certain subset of selected nodes belonging to a much larger directed network. The matrix $G_R$ takes into account effective interactions between subset nodes by all their indirect links via the whole network. We argue that this approach gives new possibilities to analyze effective interactions in a group of nodes embedded in a large directed networks. Possible efficient numerical methods for the practical computation of $G_R$ are also described.

  9. A genome-wide survey of genetic variation in gorillas using reduced representation sequencing.

    Aylwyn Scally

    Full Text Available All non-human great apes are endangered in the wild, and it is therefore important to gain an understanding of their demography and genetic diversity. Whole genome assembly projects have provided an invaluable foundation for understanding genetics in all four genera, but to date genetic studies of multiple individuals within great ape species have largely been confined to mitochondrial DNA and a small number of other loci. Here, we present a genome-wide survey of genetic variation in gorillas using a reduced representation sequencing approach, focusing on the two lowland subspecies. We identify 3,006,670 polymorphic sites in 14 individuals: 12 western lowland gorillas (Gorilla gorilla gorilla and 2 eastern lowland gorillas (Gorilla beringei graueri. We find that the two species are genetically distinct, based on levels of heterozygosity and patterns of allele sharing. Focusing on the western lowland population, we observe evidence for population substructure, and a deficit of rare genetic variants suggesting a recent episode of population contraction. In western lowland gorillas, there is an elevation of variation towards telomeres and centromeres on the chromosomal scale. On a finer scale, we find substantial variation in genetic diversity, including a marked reduction close to the major histocompatibility locus, perhaps indicative of recent strong selection there. These findings suggest that despite their maintaining an overall level of genetic diversity equal to or greater than that of humans, population decline, perhaps associated with disease, has been a significant factor in recent and long-term pressures on wild gorilla populations.

  10. A genome-wide survey of genetic variation in gorillas using reduced representation sequencing.

    Scally, Aylwyn; Yngvadottir, Bryndis; Xue, Yali; Ayub, Qasim; Durbin, Richard; Tyler-Smith, Chris

    2013-01-01

    All non-human great apes are endangered in the wild, and it is therefore important to gain an understanding of their demography and genetic diversity. Whole genome assembly projects have provided an invaluable foundation for understanding genetics in all four genera, but to date genetic studies of multiple individuals within great ape species have largely been confined to mitochondrial DNA and a small number of other loci. Here, we present a genome-wide survey of genetic variation in gorillas using a reduced representation sequencing approach, focusing on the two lowland subspecies. We identify 3,006,670 polymorphic sites in 14 individuals: 12 western lowland gorillas (Gorilla gorilla gorilla) and 2 eastern lowland gorillas (Gorilla beringei graueri). We find that the two species are genetically distinct, based on levels of heterozygosity and patterns of allele sharing. Focusing on the western lowland population, we observe evidence for population substructure, and a deficit of rare genetic variants suggesting a recent episode of population contraction. In western lowland gorillas, there is an elevation of variation towards telomeres and centromeres on the chromosomal scale. On a finer scale, we find substantial variation in genetic diversity, including a marked reduction close to the major histocompatibility locus, perhaps indicative of recent strong selection there. These findings suggest that despite their maintaining an overall level of genetic diversity equal to or greater than that of humans, population decline, perhaps associated with disease, has been a significant factor in recent and long-term pressures on wild gorilla populations. PMID:23750230

  11. KCTD11 Tumor Suppressor Gene Expression Is Reduced in Prostate Adenocarcinoma

    Francesca Zazzeroni

    2014-01-01

    Full Text Available Prostate cancer is the most common noncutaneous cancer among men in the United States. A genetic contribution to prostate cancer risk has been documented, but knowledge of the molecular mechanisms involved in prostate cancer initiation is still not well understood. Loss of heterozygosity (LOH of chromosomal regions is crucial in tumor progression. In human prostate cancer, several chromosomal regions demonstrating a high frequency of LOH have been previously identified. KCTD11 (REN is a tumor suppressor gene mapping on human chromosome 17p13.2, whose expression is frequently lost in human medulloblastoma and in several other cancer types. KCTD11 acts as a negative regulator of the Hedgehog (Hh signaling. Here, we demonstrated that KCTD11 LOH is a common genetic lesion in human prostate adenocarcinoma. Indeed, nuclear KCTD11 protein expression is strongly reduced in primary prostate cancer, and this event correlated with overexpression of proteins acting into the Hedgehog pathway. Low levels of KCTD11 mRNA have been also observed in prostatic cancer cells, and ectopic overexpression of KCTD11 led to growth arrest. Our study demonstrates and supports that KCTD11, as well as negatively regulated downstream effectors belonging to Hh signaling, plays a role in prostate cancer pathogenesis. This could be suitable to characterize new diagnostic and therapeutic markers.

  12. KCTD11 tumor suppressor gene expression is reduced in prostate adenocarcinoma.

    Zazzeroni, Francesca; Nicosia, Daniela; Tessitore, Alessandra; Gallo, Rita; Verzella, Daniela; Fischietti, Mariafausta; Vecchiotti, Davide; Ventura, Luca; Capece, Daria; Gulino, Alberto; Alesse, Edoardo

    2014-01-01

    Prostate cancer is the most common noncutaneous cancer among men in the United States. A genetic contribution to prostate cancer risk has been documented, but knowledge of the molecular mechanisms involved in prostate cancer initiation is still not well understood. Loss of heterozygosity (LOH) of chromosomal regions is crucial in tumor progression. In human prostate cancer, several chromosomal regions demonstrating a high frequency of LOH have been previously identified. KCTD11 (REN) is a tumor suppressor gene mapping on human chromosome 17p13.2, whose expression is frequently lost in human medulloblastoma and in several other cancer types. KCTD11 acts as a negative regulator of the Hedgehog (Hh) signaling. Here, we demonstrated that KCTD11 LOH is a common genetic lesion in human prostate adenocarcinoma. Indeed, nuclear KCTD11 protein expression is strongly reduced in primary prostate cancer, and this event correlated with overexpression of proteins acting into the Hedgehog pathway. Low levels of KCTD11 mRNA have been also observed in prostatic cancer cells, and ectopic overexpression of KCTD11 led to growth arrest. Our study demonstrates and supports that KCTD11, as well as negatively regulated downstream effectors belonging to Hh signaling, plays a role in prostate cancer pathogenesis. This could be suitable to characterize new diagnostic and therapeutic markers. PMID:25045667

  13. Reducing Outdoor Advertising

    Patrice de Rendinger

    2006-05-01

    Full Text Available The fundamental concept is that public space is not a private property. So, a facade (the outer skin, the last millimeter belongs to the town, not to the owner of the building. Changing the rendering, a window, adding or removing anything from a facade requires a permission delivered by the town's authority.In places like Paris, Bordeaux, Marseilles, Lyon, Strasbourg… everywhere one can find a registrated building such as a cathedral, a castle, or a group of ancient buildings, a national administration is controlling this permission. This administration is called «historical monuments administration» and is locally lead by a specialized architect.In the late seventies, French government decided to reduce advertising on the roads and on the city walls. Advertising on the road was leading to a confusion reducing the efficacy of the roadsigns and direction signs, which is dangerous. The reduction was under control of a national administration: the ministry of equipment in charge of the roads design. Advertising on the walls with publicity boards was under control of the cities. Every city has a townplanning regulation. Many cities included forbidding advertisement boards on the walls in this regulation.A couple of firms, but mainly once (Decaux found clever to give a hand to the cities to control advertising. Decaux developed a line of bus stop shelters including advertisements and advertising panels and paid the cities the right to put rather smaller publicities on the public domain.Now Decaux is no more alone on this market and the cities are comparing offers.Marseille turned to a foreign advertising firm who pays three times the price Decaux paid… for half of the advertising surface. Freiburg erased totally the public domain advertisements, selling the tramways and bus coachwork as advertising spaces. Paris is reopening the advertising market before the end of Deacaux's contract and will pay Deacaux a huge amount

  14. Reducing GWAS Complexity.

    Hazelett, Dennis J; Conti, David V; Han, Ying; Al Olama, Ali Amin; Easton, Doug; Eeles, Rosalind A; Kote-Jarai, Zsofia; Haiman, Christopher A; Coetzee, Gerhard A

    2016-01-01

    Genome-wide association studies (GWAS) have revealed numerous genomic 'hits' associated with complex phenotypes. In most cases these hits, along with surrogate genetic variation as measure by numerous single nucleotide polymorphisms (SNPs) that are in linkage disequilibrium, are not in coding genes making assignment of functionality or causality intractable. Here we propose that fine-mapping along with the matching of risk SNPs at chromatin biofeatures lessen this complexity by reducing the number of candidate functional/causal SNPs. For example, we show here that only on average 2 SNPs per prostate cancer risk locus are likely candidates for functionality/causality; we further propose that this manageable number should be taken forward in mechanistic studies. The candidate SNPs can be looked up for each prostate cancer risk region in 2 recent publications in 2015 (1,2) from our groups. PMID:26771711

  15. Reduced Order Podolsky Model

    Thibes, Ronaldo

    2016-01-01

    We perform the canonical and path integral quantizations of a lower-order derivatives model describing Podolsky's generalized electrodynamics. The physical content of the model shows an auxiliary massive vector field coupled to the usual electromagnetic field. The equivalence with Podolsky's original model is studied at classical and quantum levels. Concerning the dynamical time evolution we obtain a theory with two first-class and two second-class constraints in phase space. We calculate explicitly the corresponding Dirac brackets involving both vector fields. We use the Senjanovic procedure to implement the second-class constraints and the Batalin-Fradkin-Vilkovisky path integral quantization scheme to deal with the symmetries generated by the first-class constraints. The physical interpretation of the results turns out to be simpler due to the reduced derivatives order permeating the equations of motion, Dirac brackets and effective action.

  16. Stewarding a Reduced Stockpile

    Goodwin, B T; Mara, G

    2008-04-18

    The future of the US nuclear arsenal continues to be guided by two distinct drivers: the preservation of world peace and the prevention of further proliferation through our extended deterrent umbrella. Timely implementation of US nuclear policy decisions depends, in part, on the current state of stockpile weapons, their delivery systems, and the supporting infrastructure within the Department of Defense (DoD) and the Department of Energy's National Nuclear Security Administration (NNSA). In turn, the present is a product of past choices and world events. Now more than ever, the nuclear weapons program must respond to the changing global security environment and to increasing budget pressures with innovation and sound investments. As the nation transitions to a reduced stockpile, the successes of the Stockpile Stewardship Program (SSP) present options to transition to a sustainable complex better suited to stockpile size, national strategic goals and budgetary realities. Under any stockpile size, we must maintain essential human capital, forefront capabilities, and have a right-sized effective production capacity. We present new concepts for maintaining high confidence at low stockpile numbers and to effectively eliminate the reserve weapons within an optimized complex. We, as a nation, have choices to make on how we will achieve a credible 21st century deterrent.

  17. Reducing maintenance costs

    The increasingly more expensive maintenance measures, cuts in the cost budget, and the loss of know-how on the part of vendors all require a change of policy with respect to maintenance concepts of the part of operators. This also applies to the existing valve concepts, the drives included. Under these aspects, the current drive, which is self-actuated and actuated by outside media, for a parallel-plate valve of a nomial width of 700 was reconsidered. The effort served to reduce maintenance costs and, at the same time, simplify the drive concept as well as cut back on the number of in-service inspections. Moreover, the number of active components were to be minimized and installation conditions in the plant were to be improved. When the boundary conditions to be observed with respect to process technology had been laid down, the competent technical department developed a concept of modification of the drive. A major constituent part was the demonstration of the functioning capability of the new drive under accident conditions. It was achieved mainly by an analytical approach. In the resultant drive concept, the same control valves are employed to actuate a driving cylinder by means of self-actuation or by an outside medium as a function of pressure. (orig.)

  18. Cancer Reduces Transcriptome Specialization

    Martínez, Octavio; Reyes-Valdés, M. Humberto; Herrera-Estrella, Luis

    2010-01-01

    A central goal of cancer biology is to understand how cells from this family of genetic diseases undergo specific morphological and physiological changes and regress to a de-regulated state of the cell cycle. The fact that tumors are unable to perform most of the specific functions of the original tissue led us to hypothesize that the degree of specialization of the transcriptome of cancerous tissues must be less than their normal counterparts. With the aid of information theory tools, we analyzed four datasets derived from transcriptomes of normal and tumor tissues to quantitatively test the hypothesis that cancer reduces transcriptome specialization. Here, we show that the transcriptional specialization of a tumor is significantly less than the corresponding normal tissue and comparable with the specialization of dedifferentiated embryonic stem cells. Furthermore, we demonstrate that the drop in specialization in cancerous tissues is largely due to a decrease in expression of genes that are highly specific to the normal organ. This approach gives us a better understanding of carcinogenesis and offers new tools for the identification of genes that are highly influential in cancer progression. PMID:20454660

  19. Generalized reduced magnetohydrodynamic equations

    A new derivation of reduced magnetohydrodynamic (MHD) equations is presented. A multiple-time-scale expansion is employed. It has the advantage of clearly separating the three time scales of the problem associated with (1) MHD equilibrium, (2) fluctuations whose wave vector is aligned perpendicular to the magnetic field, and (3) those aligned parallel to the magnetic field. The derivation is carried out without relying on a large aspect ratio assumption; therefore this model can be applied to any general configuration. By accounting for the MHD equilibrium and constraints to eliminate the fast perpendicular waves, equations are derived to evolve scalar potential quantities on a time scale associated with the parallel wave vector (shear-Alfven wave time scale), which is the time scale of interest for MHD instability studies. Careful attention is given in the derivation to satisfy energy conservation and to have manifestly divergence-free magnetic fields to all orders in the expansion parameter. Additionally, neoclassical closures and equilibrium shear flow effects are easily accounted for in this model. Equations for the inner resistive layer are derived which reproduce the linear ideal and resistive stability criterion of Glasser, Greene, and Johnson. The equations have been programmed into a spectral initial value code and run with shear flow that is consistent with the equilibrium input into the code. Linear results of tearing modes with shear flow are presented which differentiate the effects of shear flow gradients in the layer with the effects of the shear flow decoupling multiple harmonics

  20. Shrinkage Reducing Admixture for Concrete

    ECT Team, Purdue

    2007-01-01

    Concrete shrinkage cracking is a common problem in all types of concrete structures, especially for structures and environments where the cracks are prevalent and the repercussions are most severe. A liquid shrinkage reducing admixture for concrete, developed by GRACE Construction Products and ARCO Chemical Company, that reduces significantly the shrinkage during concrete drying and potentially reduces overall cracking over time.

  1. Oxygen-reducing catalyst layer

    O'Brien, Dennis P.; Schmoeckel, Alison K.; Vernstrom, George D.; Atanasoski, Radoslav; Wood, Thomas E.; Yang, Ruizhi; Easton, E. Bradley; Dahn, Jeffrey R.; O'Neill, David G.

    2011-03-22

    An oxygen-reducing catalyst layer, and a method of making the oxygen-reducing catalyst layer, where the oxygen-reducing catalyst layer includes a catalytic material film disposed on a substrate with the use of physical vapor deposition and thermal treatment. The catalytic material film includes a transition metal that is substantially free of platinum. At least one of the physical vapor deposition and the thermal treatment is performed in a processing environment comprising a nitrogen-containing gas.

  2. THz spectrum of reduced glutathione

    WANG; Weining; YAN; Haitao; YUE; Weiwei; ZHAO; Guozhong; Z

    2005-01-01

    The optical characteristics of reduced glutathione molecules between 0.2 THz and 2.4 THz have been investigated by THz time-domain spectroscopy (THz-TDS). The absorption characteristics and optical parameters of the reduced glutathione purged with Nitrogen at room temperature were obtained experimentally. The measured results were fitted well with the theoretical results computed by using Density Functional Theory (DFT) in far-infrared range. Also the conformation of the reduced glutathione molecule was simulated by Gaussian 03. This work has demonstrated significantly that THz-TDS spectroscopy can further be used to study other biological molecules in biological and biomedical engineering.

  3. Reducible braids and Garside theory

    Gonzalez-Meneses, Juan

    2010-01-01

    We show that reducible braids which are, in a Garside-theoretical sense, as simple as possible within their conjugacy class, are also as simple as possible in a geometric sense. More precisely, if a braid belongs to a certain subset of its conjugacy class which we call the stabilized set of sliding circuits, and if it is reducible, then its reducibility is geometrically obvious: it has a round or almost round reducing curve. Moreover, for any given braid, an element of its stabilized set of sliding circuits can be found using the well-known cyclic sliding operation. This leads to a polynomial time algorithm for deciding the Nielsen-Thurston type of any braid, modulo one well-known conjecture on the speed of convergence of the cyclic sliding operation.

  4. Reduced-Dimension Multiuser Detection

    Xie, Yao; Goldsmith, Andrea

    2011-01-01

    We explore several reduced-dimension multiuser detection (RD-MUD) structures that significantly decrease the number of required correlation branches at the receiver front-end, while still achieving performance similar to that of the conventional matched-filter (MF) bank. RD-MUD exploits the fact that the number of active users is typically small relative to the total number of users in the system and relies on ideas of analog compressed sensing to reduce the number of correlators. We first develop a general framework for both linear and nonlinear RD-MUD detectors. We then present theoretical performance analysis for two specific detectors: the linear reduced-dimension decorrelating (RDD) detector, which combines subspace projection and thresholding to determine active users and sign detection for data recovery, and the nonlinear reduced-dimension decision-feedback (RDDF) detector, which combines decision-feedback orthogonal matching pursuit for active user detection and sign detection for data recovery. The t...

  5. Reducing energy with asynchronous circuits

    Rivas Barragan, Daniel

    2012-01-01

    Reducing energy consumption using asynchronous circuits. The elastic clocks approach has been implemented along with a closed-feedback loop in order to achieve a lower energy consumption along with more reliability in integrated circuits.

  6. Determining Reduced Order Models for Optimal Stochastic Reduced Order Models

    Bonney, Matthew S. [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Brake, Matthew R.W. [Sandia National Lab. (SNL-CA), Livermore, CA (United States)

    2015-08-01

    The use of parameterized reduced order models(PROMs) within the stochastic reduced order model (SROM) framework is a logical progression for both methods. In this report, five different parameterized reduced order models are selected and critiqued against the other models along with truth model for the example of the Brake-Reuss beam. The models are: a Taylor series using finite difference, a proper orthogonal decomposition of the the output, a Craig-Bampton representation of the model, a method that uses Hyper-Dual numbers to determine the sensitivities, and a Meta-Model method that uses the Hyper-Dual results and constructs a polynomial curve to better represent the output data. The methods are compared against a parameter sweep and a distribution propagation where the first four statistical moments are used as a comparison. Each method produces very accurate results with the Craig-Bampton reduction having the least accurate results. The models are also compared based on time requirements for the evaluation of each model where the Meta- Model requires the least amount of time for computation by a significant amount. Each of the five models provided accurate results in a reasonable time frame. The determination of which model to use is dependent on the availability of the high-fidelity model and how many evaluations can be performed. Analysis of the output distribution is examined by using a large Monte-Carlo simulation along with a reduced simulation using Latin Hypercube and the stochastic reduced order model sampling technique. Both techniques produced accurate results. The stochastic reduced order modeling technique produced less error when compared to an exhaustive sampling for the majority of methods.

  7. Municipal actions to reduce mercury

    NONE

    2005-03-15

    This paper presented proper management practices for products containing mercury. The measures can help reduce mercury releases, occupational exposure and mercury spills, thereby preventing impacts on human health and the environment. Despite mercury's toxic nature, many common products that contain mercury are commercially available. These include thermostats, thermometers, fluorescent lamps, pressure measuring devices, electrical switches and relays, and dental amalgam. Mercury emissions are also associated with base metal smelting, waste incineration and coal-fired power generation. Mercury in the environment is a global issue, because it can travel in the atmosphere on wind currents. The actions taken by municipalities to address the issue include reducing or eliminating mercury releases from internal municipal operations and sources within the community. This document provided guidance on how to develop a Municipal Mercury Elimination Policy and Plan that will help reduce mercury releases. It presented information and case studies that will help municipalities manage mercury-containing products found in municipal buildings and street lighting. Information on sources of mercury from within the community was presented along with case studies that can help municipalities determine where community action is needed to reduce mercury releases. The 5 modules of this document were intended to help municipalities identify priorities, timelines and budget requirements for mercury initiatives. It was emphasized that municipalities that adopt a Municipal Mercury Elimination Policy and Plan formally commit to reducing and eliminating mercury from the environment. tabs., figs.

  8. Flexure Bearing Reduces Startup Friction

    Clingman, W. Dean

    1991-01-01

    Design concept for ball bearing incorporates small pieces of shim stock, wire spokes like those in bicycle wheels, or other flexing elements to reduce both stiction and friction slope. In flexure bearing, flexing elements placed between outer race of ball bearing and outer ring. Elements flex when ball bearings encounter small frictional-torque "bumps" or even larger ones when bearing balls encounter buildups of grease on inner or outer race. Flexure of elements reduce high friction slopes of "bumps", helping to keep torque between outer ring and inner race low and more nearly constant. Concept intended for bearings in gimbals on laser and/or antenna mirrors.

  9. National compacts to reduce deforestation

    Santilli, M. [Instituto Socioambiental ISA., Brasilia DF (Brazil); Moutinho, P.; Nepstad, D. [Instituto de Pesquisa Ambiental da Amazonia IPAM, Belem (Brazil)

    2005-07-01

    Finding ways for developing countries with tropical forests to participate more effectively in international efforts to reduce greenhouse gas (GHG) emissions has become central to the success of any future international agreement. The most obvious means would be the reduction of tropical deforestation and the emissions associated with it. Unless tropical deforestation is reduced it will not be possible to avoid 'dangerous anthropogenic interference' in the planet's climate. In this chapter the necessary conditions for these countries to use reduced deforestation, in the context of 'compensated reduction of deforestation', as an internationally recognized, valid form of mitigation of global climate change and, in return, receive compensation for demonstrated reductions. The proposal for compensated reduction suggests that countries that reduce their emissions from tropical deforestation during a Kyoto Protocol commitment period, in relation to an agreed baseline in accordance with historical deforestation rates, be remunerated with credits equivalent to the volume of emissions avoided, tradable in subsequent commitment periods. As we know, under the current terms of the Kyoto Protocol, covering the first commitment period, there are no means to offer incentives for reducing deforestation, which are a recognized factor in global emissions (25%). Eligible forestry projects in the Clean Development Mechanism (CDM) include only carbon sequestration. Since tropical deforestation is a problem occurring in non-Annex 1 developing countries, and is associated with development strategies historically linked to global markets, international instruments to encourage reduction of deforestation emissions should consider the objective conditions of these countries in a manner consistent with the principle of mutual, but differentiated responsibilities. The compensated reduction proposal emerges in this context: more effective participation of these

  10. Reducing ammonia emissions in Europe

    Jacobsen, Brian H.

    The NEC directive has set targets for the 2010 ammonia emissions from a number of European countries. The target will be reached by most EU-countries and the total emission for EU-27 has been reduced by 22% from 1990 to 2007. Denmark is one of the countries with the largest reductions since 1990...... not lived up to the high expectations at the outset. Despite this, the paper concludes that Denmark is likely to reduce emission by 50% from 1990 to 2020 and reach the likely 2020 NEC ceiling....

  11. Ways to reduce miner absenteeism

    1989-11-01

    Discussion is presented of the use of attendance programs at mines, to reduce interruptions to production, decrease labour costs, and to improve safety. Techniques described include use of absentee charts, frequency of attendance charts, and rewards for good attendance. 3 figs.

  12. Does Microfinance Reduce Income Inequality?

    Hermes, Niels

    2014-01-01

    This study addresses the question whether participation of the poor in microfinance contributes to reducing a country’s level of income inequality. Using data from 70 developing countries, we show that higher levels of microfinance participation are indeed associated with a reduction of the income g

  13. Solitons reduced from Heterotic fivebranes

    La, H S

    1992-01-01

    In view of the expectation that the solitonic sector of the lower dimensional world may be originated from the solitonic sector of string theory, various solitonic solutions are reduced from the heterotic fivebrane solutions in the ten-dimensional heterotic string theory. These solitons in principle can appear after proper compactifications, {\\it e.g.} toroidal compactifications.

  14. Reduced False Memory after Sleep

    Fenn, Kimberly M.; Gallo, David A.; Margoliash, Daniel; Roediger, Henry L., III; Nusbaum, Howard C.

    2009-01-01

    Several studies have shown that sleep contributes to the successful maintenance of previously encoded information. This research has focused exclusively on memory for studied events, as opposed to false memories. Here we report three experiments showing that sleep reduces false memories in the Deese-Roediger-McDermott (DRM) memory illusion. False…

  15. Reducing chlorination of niobium pentoxide

    Studies of cylindric briquettes of Nb2O5 and carbon are presented. The effects of chlorine flow, dimension of the briquettes, porosity, percentage of the reducing agent in the mixture and temperature are analysed. The volatilization aspect of Nb2O5 by the briquettes and the structural transformations of the samples are described. (M.A.C.)

  16. Breastfeeding reduces postpartum weight retention

    Baker, Jennifer Lyn; Gamborg, Michael; Heitmann, Berit L;

    2008-01-01

    BACKGROUND: Weight gained during pregnancy and not lost postpartum may contribute to obesity in women of childbearing age. OBJECTIVE: We aimed to determine whether breastfeeding reduces postpartum weight retention (PPWR) in a population among which full breastfeeding is common and breastfeeding d...

  17. Reducing Developing Country Debt Reducing Developing Country Debt

    Paul Krugman

    1989-03-01

    Full Text Available This paper offers a brief primer on the economics of debt reduction for developing countries. It begins by considering the case of unilateral debt forgiveness; such forgiveness is only in the mutual interest of creditors and debtors if the country is on the wrong side of fhe "debt Laffer curve". Current empirical estimafes suggest that problem debtors are in a very flat region of the debt Laffer curve where large changes in face value of debf have only small effcts in expected payments. The paper then considers a variety of market-based debt reduction schemes. It shows that the widespread belief that the markt offers a cheap way to reduce debt is incorrect; unless new market instruments can be made credibly senior to existing debt, debt reductions that impose only small costs to creditors would be very expensive if achieved through buy back. Reducing Developing Country Debt

  18. A reduced-turbulence, reduced-entrainment electrostatic precipitator

    Bahner, Mark A.

    1990-01-01

    This thesis describes testing of an electrostatic precipitator that has a portion of the main precipitator flow drawn through a porous (fabric) collecting surface. Tests investigated effects of flow through the collecting surface (side flow) on precipitator turbulence and particulate removal efficiency. Particulate removal tests were conducted at both ambient temperature and boiler slipstream conditions. Side flow was shown to reduce turbulence in the boundary layers of the collecting plat...

  19. Structural reducibility of multilayer networks

    de Domenico, Manlio; Nicosia, Vincenzo; Arenas, Alexandre; Latora, Vito

    2015-04-01

    Many complex systems can be represented as networks consisting of distinct types of interactions, which can be categorized as links belonging to different layers. For example, a good description of the full protein-protein interactome requires, for some organisms, up to seven distinct network layers, accounting for different genetic and physical interactions, each containing thousands of protein-protein relationships. A fundamental open question is then how many layers are indeed necessary to accurately represent the structure of a multilayered complex system. Here we introduce a method based on quantum theory to reduce the number of layers to a minimum while maximizing the distinguishability between the multilayer network and the corresponding aggregated graph. We validate our approach on synthetic benchmarks and we show that the number of informative layers in some real multilayer networks of protein-genetic interactions, social, economical and transportation systems can be reduced by up to 75%.

  20. Reduced graphene oxide molecular sensors.

    Robinson, Jeremy T; Perkins, F Keith; Snow, Eric S; Wei, Zhongqing; Sheehan, Paul E

    2008-10-01

    We demonstrate reduced graphene oxide as the active material for high-performance molecular sensors. Sensors are fabricated from exfoliated graphene oxide platelets that are deposited to form an ultrathin continuous network. These graphene oxide networks are tunably reduced toward graphene by varying the exposure time to a hydrazine hydrate vapor. The conductance change of the networks upon exposure to trace levels of vapor is measured as a function of the chemical reduction. The level of reduction affects both the sensitivity and the level of 1/ f noise. The sensors are capable of detecting 10 s exposures to simulants of the three main classes of chemical-warfare agents and an explosive at parts-per-billion concentrations. PMID:18763832

  1. Reduced modified Chaplygin gas cosmology

    Lu, Jianbo; Geng, Danhua; Xu, Lixin; Wu, Yabo; Liu, Molin

    2015-02-01

    In this paper, we study cosmologies containing the reduced modified Chaplygin gas (RMCG) fluid which is reduced from the modified Chaplygin gas p = Aρ - Bρ -α for the value of α = -1 /2. In this special case, dark cosmological models can be realized for different values of model parameter A. We investigate the viabilities of these dark cosmological models by discussing the evolutions of cosmological quantities and using the currently available cosmic observations. It is shown that the special RMCG model ( A = 0 or A = 1) which unifies the dark matter and dark energy should be abandoned. For A = 1 /3, RMCG which unifies the dark energy and dark radiation is the favorite model according to the objective Akaike information criteria. In the case of A , RMCG can achieve the features of the dynamical quintessence and phantom models, where the evolution of the universe is not sensitive to the variation of model parameters.

  2. Ferroelectric capacitor with reduced imprint

    Evans, Jr., Joseph T. (13609 Verbena Pl., NE., Albuquerque, NM 87112); Warren, William L. (7716 Wm. Moyers Ave., NE., Albuquerque, NM 87122); Tuttle, Bruce A. (12808 Lillian Pl., NE., Albuquerque, NM 87122); Dimos, Duane B. (6105 Innsbrook Ct., NE., Albuquerque, NM 87111); Pike, Gordon E. (1609 Cedar Ridge, NE., Albuquerque, NM 87112)

    1997-01-01

    An improved ferroelectric capacitor exhibiting reduced imprint effects in comparison to prior art capacitors. A capacitor according to the present invention includes top and bottom electrodes and a ferroelectric layer sandwiched between the top and bottom electrodes, the ferroelectric layer comprising a perovskite structure of the chemical composition ABO.sub.3 wherein the B-site comprises first and second elements and a dopant element that has an oxidation state greater than +4. The concentration of the dopant is sufficient to reduce shifts in the coercive voltage of the capacitor with time. In the preferred embodiment of the present invention, the ferroelectric element comprises Pb in the A-site, and the first and second elements are Zr and Ti, respectively. The preferred dopant is chosen from the group consisting of Niobium, Tantalum, and Tungsten. In the preferred embodiment of the present invention, the dopant occupies between 1 and 8% of the B-sites.

  3. Correlated Electrons in Reduced Dimensions

    Bonesteel, Nicholas E [Florida State Univ., Tallahassee, FL (United States)

    2015-01-31

    This report summarizes the work accomplished under the support of US DOE grant # DE-FG02-97ER45639, "Correlated Electrons in Reduced Dimensions." The underlying hypothesis of the research supported by this grant has been that studying the unique behavior of correlated electrons in reduced dimensions can lead to new ways of understanding how matter can order and how it can potentially be used. The systems under study have included i) fractional quantum Hall matter, which is realized when electrons are confined to two-dimensions and placed in a strong magnetic field at low temperature, ii) one-dimensional chains of spins and exotic quasiparticle excitations of topologically ordered matter, and iii) electrons confined in effectively ``zero-dimensional" semiconductor quantum dots.

  4. Reduced Deforestation and Economic Growth

    Patrick Doupe

    2014-01-01

    The clearing of forests for agricultural land and other marketable purposes is a well-trodden path of economic development. With these private benefits from deforestation come external costs: emissions from deforestation currently account for 12 per cent of global carbon emissions. A widespread intervention in reducing emissions from deforestation will affect the paths of agricultural expansion and economic growth of lower income nations. To investigate these processes, this paper presents a ...

  5. Numbers for reducible cubic scrolls

    Israel Vainsencher

    2004-12-01

    Full Text Available We show how to compute the number of reducible cubic scrolls of codimension 2 in (math blackboard symbol Pn incident to the appropriate number of linear spaces.Mostramos como calcular o número de rolos cúbicos redutíveis de codimensão 2 em (math blackboard symbol Pn incidentes a espaços lineares apropriados.

  6. Reducing the addictiveness of cigarettes

    HENNINGFIELD, J.; Benowitz, N.; Slade, J.; Houston, T; DAVIS, R.; Deitchman, S.

    1998-01-01

    OBJECTIVE—To assess the feasibility of reducing tobacco-caused disease by gradually removing nicotine from cigarettes until they would not be effective causes of nicotine addiction.
DATA SOURCES—Issues posed by such an approach, and potential solutions, were identified from analysis of literature published by the US Food and Drug Administration (FDA) in its 1996 Tobacco Rule, comments of the tobacco industry and other institutions and individuals on the rule, review of the reference lists of ...

  7. Reducing consumption through communal living

    Herring, Horace [The Open Univ., Milton Keynes (United Kingdom). Energy and Environment Research Unit

    2003-07-01

    This paper examines ways consumers and communities can voluntarily adopt a low consumption (or low carbon) lifestyle, often termed 'voluntary simplicity' or a policy of 'sufficiency'. There is an increasing academic literature within Europe in the last five years on the whole question of 'sustainable consumption', and the relationship between income levels and consumption particularly at the household. This debate has moved beyond 'green consumerism' to look at building 'new concepts of prosperity' through local community actions, or reducing working time to allow more time for the creation of social capital. The paper will concentrate on one aspect of the quest for sustainable communities, the relevance of communal living to reducing consumption through examining energy consumption (both direct and indirect) in one such community in the UK. The results from this preliminary study reveal that it is not the sharing of resources that reduces consumption but the mutual reinforcement of attitudes towards a low consumption lifestyle. Thus it is the creation of social capital in a community that is its key to its ecological lifestyle.

  8. Observation of HPV infection and loss of heterozygosity, micro satellite instabilityon FHIT gene in vulvar squamous cell carcinoma tissue%外阴鳞癌组织中HPV检测及FHIT基因杂合性缺失、微卫星不稳定性观察

    范余娟; 蒙亚晴; 杨开选; 徐红

    2012-01-01

    目的 观察外阴鳞癌( VSCC)组织中HPV感染情况及脆性组氨酸三联体(FHIT)基因的杂合性缺失(LOH)、微卫星不稳定性(MSI),并探讨其意义.方法 选取VSCC组织24例、外阴尖锐湿疣(VCA)42例、正常外阴组织20例,用PCR法检测上述组织中的HPV6、11、16、18、31、33亚型,用PCR-单链构像多态性分析(PCR-SSCP)法检测FHIT基因D3S1300位点的LOH和MSI.结果 在正常外阴、VCA、VSCC组织中低危型HPV( HPV6/11)阳性分别为2、38、21例,高危型HPV(HPV16/18/31/33)阳性分别为0、13、10例;VCA、VSCC组织与正常外阴组织比较,P均<0.05.在正常外阴、VCA、VSCC组织中,FHIT基因D3S1300位点上LOH、MSI阳性分别为0、9、13例,VSCC与VCA、正常外阴组织比较,P均<0.05.VSCC组织中HR-HPV感染与FHIT基因D3 S1300位点LOH/MSI相关(r =0.438,P<0.05).结论 VSCC组织中存在较高的低危型、高危型HPV复合感染及FHIT基因LOH和(或)MSI;二者在VSCC的发生发展中发挥重要作用.%Objective To observe HPV infection and loss of heterozygosity ( LOH) , micro satellite instability (MSI) on FHIT gene in vulvar squamous cell carcinoma tissue, and explore its significance. Methods HPV DNA 6,11,16,18,31, 33 were detected by PCR in VSCC(24 cases) ,VCA(42 cases) and normal vulva(20 cases). PCR-SSCP was used to detect the LOH, MSI for amplification with D3S1300 on FHIT gene. Results In normal vulva,VCA and VSCC groups,the number of patients with LR-HPV (HPV6/11) were 2,38 and 21 cases,and HR-HPV( HPV16,18 ,31,33) infection were 0,13 and 10 cases, there were statistics significant differences between normal vulva and VCA, normal vulva and VSCC(all P<0. 05). In normal vulva, VCA and VSCC groups, the number of LOH andMSI positive on D3S1300 were 0,9,13 cases respectively, there were statistics significant differences between VSCC and VCA, VSCC and normal vulva (all P<0.05). HR-HPV infections were possibly relevant to the LOH and/or MSI on FHIT gene (the related

  9. Welfare-Reducing Trade Liberalization

    Schröder, Philipp J.H.; Jørgensen, Jan G.

    Recent literature on the workhorse model of intra-industry trade has explored heterogeneous cost structures at the firm level. These approaches have proven to add realism and predictive power. This note shows, however, that this added realism also implies that there may exist a positive bilateral...... tariff that maximizes national and world welfare. Applying one of the simplest specifications possible, namely a symmetric two-country intra-industry trade model with fixed export costs that are heterogeneous across firms, we find that the reciprocal reduction of small tariffs reduces welfare. We explore...

  10. On nonlinear reduced order modeling

    When applied to a model that receives n input parameters and predicts m output responses, a reduced order model estimates the variations in the m outputs of the original model resulting from variations in its n inputs. While direct execution of the forward model could provide these variations, reduced order modeling plays an indispensable role for most real-world complex models. This follows because the solutions of complex models are expensive in terms of required computational overhead, thus rendering their repeated execution computationally infeasible. To overcome this problem, reduced order modeling determines a relationship (often referred to as a surrogate model) between the input and output variations that is much cheaper to evaluate than the original model. While it is desirable to seek highly accurate surrogates, the computational overhead becomes quickly intractable especially for high dimensional model, n ≫ 10. In this manuscript, we demonstrate a novel reduced order modeling method for building a surrogate model that employs only 'local first-order' derivatives and a new tensor-free expansion to efficiently identify all the important features of the original model to reach a predetermined level of accuracy. This is achieved via a hybrid approach in which local first-order derivatives (i.e., gradient) of a pseudo response (a pseudo response represents a random linear combination of original model’s responses) are randomly sampled utilizing a tensor-free expansion around some reference point, with the resulting gradient information aggregated in a subspace (denoted by the active subspace) of dimension much less than the dimension of the input parameters space. The active subspace is then sampled employing the state-of-the-art techniques for global sampling methods. The proposed method hybridizes the use of global sampling methods for uncertainty quantification and local variational methods for sensitivity analysis. In a similar manner to

  11. Welfare-Reducing Trade Liberalization

    Schröder, Philipp J.H.; Jørgensen, Jan G.

    Recent literature on the workhorse model of intra-industry trade has explored heterogeneous cost structures at the firm level. These approaches have proven to add realism and predictive power. This paper shows, however, that this added realism also implies that there may exist a positive bilateral...... tariff that maximizes national and world welfare. Applying one of the simplest specifications possible, namely a symmetric two-country intra-industry trade model with fixed export costs that are heterogeneous across firms, we find that the reciprocal reduction of small tariffs reduces welfare....

  12. FIREhose: Reducing Data from FIRE

    Fica, Haley Diane; Lambrides, Erini; Faherty, Jackie; Cruz, Kelle L.; BDNYC

    2016-01-01

    Brown dwarfs are stellar objects that do not have enough mass to ignite hydrogen fusion in their core. Their mass is between 0.08 solar masses and the mass of our sun. Brown dwarfs are very bright in the near-infrared wavelength band (0.8- 2.5 microns). We reduced data from the Folded-port InfraRed Echellette (FIRE) instrument on the Magellan Telescope at the Las Campanas Observatory. FIRE is a medium-resolution echelle spectrometer, whose data reduction results in a spectrum of a star. When reducing FIRE data, it is important to account for inconsistencies in the data, such as bad pixels, cosmic rays, and the effects of our atmosphere. Using the FIREhose pipeline, these inconsistencies can be accounted for and corrected using a A0 telluric with a known spectrum. After telluric correcting, the data reduction results in a primed spectrum for an object, which can then be used to determine an object's physical properties, such as atmospheric composition, radial velocity, effective temperature and surface gravity.

  13. Soldering Tested in Reduced Gravity

    Struk, Peter M.; Pettegrew, Richard D.; Watson, J. Kevin; Down, Robert S.; Haylett, Daniel R.

    2005-01-01

    Whether used occasionally for contingency repair or routinely in nominal repair operations, soldering will become increasingly important to the success of future long-duration human space missions. As a result, it will be critical to have a thorough understanding of the service characteristics of solder joints produced in reduced-gravity environments. The National Center for Space Exploration Research (via the Research for Design program), the NASA Glenn Research Center, and the NASA Johnson Space Center are conducting an experimental program to explore the influence of reduced gravity environments on the soldering process. Solder joint characteristics that are being considered include solder fillet geometry, porosity, and microstructural features. Both through-hole (see the drawing and image on the preceding figure) and surface-mounted devices are being investigated. This effort (the low-gravity portion being conducted on NASA s KC-135 research aircraft) uses the soldering hardware currently available on the International Space Station. The experiment involves manual soldering by a contingent of test operators, including both highly skilled technicians and less skilled individuals to provide a skill mix that might be encountered in space mission crews. The experiment uses both flux-cored solder and solid-core solder with an externally applied flux. Other experimental parameters include the type of flux, gravitational level (nominally zero,

  14. Moral Violations Reduce Oral Consumption.

    Chan, Cindy; Van Boven, Leaf; Andrade, Eduardo B; Ariely, Dan

    2014-07-01

    Consumers frequently encounter moral violations in everyday life. They watch movies and television shows about crime and deception, hear news reports of corporate fraud and tax evasion, and hear gossip about cheaters and thieves. How does exposure to moral violations influence consumption? Because moral violations arouse disgust and because disgust is an evolutionarily important signal of contamination that should provoke a multi-modal response, we hypothesize that moral violations affect a key behavioral response to disgust: reduced oral consumption. In three experiments, compared with those in control conditions, people drank less water and chocolate milk while (a) watching a film portraying the moral violations of incest, (b) writing about moral violations of cheating or theft, and (c) listening to a report about fraud and manipulation. These findings imply that "moral disgust" influences consumption in ways similar to core disgust, and thus provide evidence for the associations between moral violations, emotions, and consumer behavior. PMID:25125931

  15. Reducing catalytic converter pressure loss

    NONE

    1996-06-01

    This article examines why approximately 30--40% of total exhaust-system pressure loss occurs in the catalytic converter and what can be done to reduce pressure loss. High exhaust-system backpressure is of concern in the design of power trains for passenger cars and trucks because it penalizes fuel economy and limits peak power. Pressure losses occur due to fluid shear and turning during turbulent flow in the converter headers and in entry separation and developing laminar-flow boundary layers within the substrate flow passages. Some of the loss mechanisms are coupled. For example, losses in the inlet header are influenced by the presence of the flow resistance of a downstream substrate. Conversely, the flow maldistribution and pressure loss of the substrate(s) depend on the design of the inlet header.

  16. Reduced vibration motor winding arrangement

    Slavik, Charles J. (Rexford, NY); Rhudy, Ralph G. (Scotia, NY); Bushman, Ralph E. (Lathem, NY)

    1997-01-01

    An individual phase winding arrangement having a sixty electrical degree phase belt width for use with a three phase motor armature includes a delta connected phase winding portion and a wye connected phase winding portion. Both the delta and wye connected phase winding portions have a thirty electrical degree phase belt width. The delta and wye connected phase winding portions are each formed from a preselected number of individual coils each formed, in turn, from an unequal number of electrical conductor turns in the approximate ratio of .sqroot.3. The individual coils of the delta and wye connected phase winding portions may either be connected in series or parallel. This arrangement provides an armature winding for a three phase motor which retains the benefits of the widely known and utilized thirty degree phase belt concept, including improved mmf waveform and fundamental distribution factor, with consequent reduced vibrations and improved efficiency.

  17. Reduced gravity multibody dynamics testing

    Sillanpaa, Meija

    1993-01-01

    The Final Report on reduced gravity multibody dynamics testing is presented. Tests were conducted on board the NASA KC-135 RGA in Houston, Texas. The objective was to analyze the effects of large angle rotations on flexible, multi-segmented structures. The flight experiment was conducted to provide data which will be compared to the data gathered from ground tests of the same configurations. The flight and ground tested data will be used to validate the TREETOPS software, software which models dynamic multibody systems, and other multibody codes. The flight experiment consisted of seven complete flights on board the KC-135 RGA during two one-week periods. The first period of testing was 4-9 Apr. 1993. The second period of testing was 13-18 Jun. 1993.

  18. Interventions to reduce school bullying.

    Smith, Peter K; Ananiadou, Katerina; Cowie, Helen

    2003-10-01

    In the last 2 decades, school bullying has become a topic of public concern and research around the world. This has led to action to reduce the problem. We review interventions targeted at the school level (for example, whole school policy, classroom climate, peer support, school tribunal, and playground improvement), at the class level (for example, curriculum work), and at the individual level (for example, working with specific pupils). Effectiveness of interventions has been sporadically assessed. We review several systematically evaluated, large-scale, school-based intervention programs. Their effectiveness has varied, and we consider reasons for this. We suggest ways to improve the evaluation and comparability of studies, as well as the effectiveness of future interventions. PMID:14631879

  19. Variational Integrators for Reduced Magnetohydrodynamics

    Kraus, Michael; Grasso, Daniela

    2015-01-01

    Reduced magnetohydrodynamics is a simplified set of magnetohydrodynamics equations with applications to both fusion and astrophysical plasmas, possessing a noncanonical Hamiltonian structure and consequently a number of conserved functionals. We propose a new discretisation strategy for these equations based on a discrete variational principle applied to a formal Lagrangian. The resulting integrator preserves important quantities like the total energy, magnetic helicity and cross helicity exactly (up to machine precision). As the integrator is free of numerical resistivity, spurious reconnection along current sheets is absent in the ideal case. If effects of electron inertia are added, reconnection of magnetic field lines is allowed, although the resulting model still possesses a noncanonical Hamiltonian structure. After reviewing the conservation laws of the model equations, the adopted variational principle with the related conservation laws are described both at the continuous and discrete level. We verify...

  20. Periocular Recognition Using Reduced Features

    Ambika D R,

    2013-08-01

    Full Text Available Biometrics is science of measuring and statistically analyzing biological data. Biometric system establishes identity of a person based on unique physical or behavioural characteristic possessed by an individual. Behavioural biometrics measures characteristics which are acquired naturally over time. Physical biometrics measures inherent physical characteristics on a n individual. Over the last few decades enormous attention is drawn towards ocular biometrics. Cues provided by ocular region have led to exploration of newer traits. Feasibility of periocular region as a useful biometric trait has been explored recently. With the promising results of preliminary examination, research towards periocular region is currently gaining lot of prominence. Researchers have analyzed various techniques of feature extraction and classification in the periocular region. The current paper investigates the effect of using Lower Central Periocular Region (LCPR for identification. The results obtained are comparable with those acquired for the entire periocular region with an advantage of reduced periocular area.

  1. The Gambling Reducing Slot Machine

    Callesen, Mette Buhl; Thomsen, Kristine Rømer; Linnet, Jakob;

    2007-01-01

      The Gambling Reducing Slot Machine - Preliminary results Mette Buhl Callesen, Kristine Rømer Thomsen, Jakob Linnet and Arne Møller The PET Centre, Aarhus University Hospital and Centre of Functionally Integrative Neuroscience, Aarhus, Denmark   Slot machines are among the most addictive forms of...... gambling due to their specific structural characteristics. These include a high event frequency (number of games per minute), a high frequency of small wins and near misses, and auditory as well as visual feedback that reinforce extended gambling behavior [1].   This study focused on gambling behavior in...... pathological gamblers and healthy controls, using one of the most popular slot machines in Denmark, ’Orient Expressen‘. The study included 20 pathological gamblers (10 females) and 20 healthy non-gambling controls (10 females). While being videotaped the subjects played two versions of the slot machine in...

  2. The ITER reduced cost design

    Six years of joint work under the international thermonuclear experimental reactor (ITER) EDA agreement yielded a mature design for ITER which met the objectives set for it (ITER final design report (FDR)), together with a corpus of scientific and technological data, large/full scale models or prototypes of key components/systems and progress in understanding which both validated the specific design and are generally applicable to a next step, reactor-oriented tokamak on the road to the development of fusion as an energy source. In response to requests from the parties to explore the scope for addressing ITER's programmatic objective at reduced cost, the study of options for cost reduction has been the main feature of ITER work since summer 1998, using the advances in physics and technology databases, understandings, and tools arising out of the ITER collaboration to date. A joint concept improvement task force drawn from the joint central team and home teams has overseen and co-ordinated studies of the key issues in physics and technology which control the possibility of reducing the overall investment and simultaneously achieving the required objectives. The aim of this task force is to achieve common understandings of these issues and their consequences so as to inform and to influence the best cost-benefit choice, which will attract consensus between the ITER partners. A report to be submitted to the parties by the end of 1999 will present key elements of a specific design of minimum capital investment, with a target cost saving of about 50% the cost of the ITER FDR design, and a restricted number of design variants. Outline conclusions from the work of the task force are presented in terms of physics, operations, and design of the main tokamak systems. Possible implications for the way forward are discussed

  3. KCTD11 Tumor Suppressor Gene Expression Is Reduced in Prostate Adenocarcinoma

    Francesca Zazzeroni; Daniela Nicosia; Alessandra Tessitore; Rita Gallo; Daniela Verzella; Mariafausta Fischietti; Davide Vecchiotti; Luca Ventura; Daria Capece; Alberto Gulino; Edoardo Alesse

    2014-01-01

    Prostate cancer is the most common noncutaneous cancer among men in the United States. A genetic contribution to prostate cancer risk has been documented, but knowledge of the molecular mechanisms involved in prostate cancer initiation is still not well understood. Loss of heterozygosity (LOH) of chromosomal regions is crucial in tumor progression. In human prostate cancer, several chromosomal regions demonstrating a high frequency of LOH have been previously identified. KCTD11 (REN) is a tum...

  4. Bioventing reduces soil cleanup costs

    An offshoot technology from soil venting, bioventing offers a win-win solution for soils contaminated with volatile organic compounds (VOCs) and nonvolatile contaminants such as diesel and fuel oil. Using low air flowrates through permeable soils, bioventing injects sufficient oxygen to support naturally-occurring bacteria, which biodegraded the VOCs and other contaminants into benign byproducts. Waste gas can be directly discharged to atmosphere without further treatment. This results in no offgas treatment required. Bioventing is a cost-effective alternative to traditional soil-venting techniques. Soil venting uses air to volatilize organic-compound contamination from the vadose zone, the unsaturated soil layer above groundwater. Unfortunately, this simple-and-fast approach creates a waste offgas that requires further treatment before discharge, thus adding significantly to overall project costs. In contrast, bioventing uses low air flowrates, which require lower capital and operating costs. No offgas treatment further reduces equipment and operating costs and often eliminates air permitting. As in all treatment strategies, the process must meet the cleanup objectives. Bioventing is an alternative technique making inroads into refining and petrochemical soil-remediation applications

  5. Hamiltonian formulation of reduced magnetohydrodynamics

    Reduced magnetohydrodynamics (RMHD) has become a principal tool for understanding nonlinear processes, including disruptions, in tokamak plasmas. Although analytical studies of RMHD turbulence have been useful, the model's impressive ability to simulate tokamak fluid behavior has been revealed primarily by numerical solution. The present work describes a new analytical approach, not restricted to turbulent regimes, based on Hamiltonian field theory. It is shown that the nonlinear (ideal) RMHD system, in both its high-beta and low-beta versions, can be expressed in Hanmiltonian form. Thus a Poisson bracket, [ , ], is constructed such that each RMHD field quantitity, xi/sub i/, evolves according to xi/sub i/ = [xi/sub i/,H], where H is the total field energy. The new formulation makes RMHD accessible to the methodology of Hamiltonian mechanics; it has lead, in particular, to the recognition of new RMHD invariants and even exact, nonlinear RMHD solutions. A canonical version of the Poisson bracket, which requires the introduction of additional fields, leads to a nonlinear variational principle for time-dependent RMHD

  6. The benefits of reduced morbidity

    Morbidity benefits refer to increases in utility arising from reductions in incidents of acute health impairments and from increases in the probability of developing chronic diseases. The impairments would run the gamut from a cough-day to a bed-disability-day, while the chronic diseases include classic pollution-related diseases, such as cancer, to in utero effects and learning disabilities. As with mortality benefits, there could be benefits to oneself and family and friends as well as benefits based on altruism. A major difference between the mortality and morbidity valuation literatures is that while estimates of the former are always based on risk (one is never trying to obtain values for avoiding certain death), estimates of the latter generally are not. That is, most of the theory and empirical estimates are based on models where the effect to be avoided is certain. This assumption holds reasonably well for estimating common acute effects, for example, the willingness to pay (WTP) for one less cough-day. It works less well, if at all, for chronic illness endpoints, where benefits seem to be appropriately expressed in terms of reduced risk of developing a disease or impairment

  7. Neuromuscular Adaptations to Reduced Use

    Ploutz-Snyder, Lori

    2009-01-01

    This viewgraph presentation reviews the studies done to reduce neuromuscular strength loss during unilateral lower limb suspension (ULLS). Since there are animals that undergo fairly long periods of muscular disuse without any or minimal muscular atrophy, there is an answer to that might be applicable to human in situations that require no muscular use to diminish the effects of muscular atrophy. Three sets of ULLS studies were reviewed indicated that muscle strength decreased more than the muscle mass. The study reviewed exercise countermeasures to combat the atrophy, including: ischemia maintained during Compound muscle action potential (CMAP), ischemia and low load exercise, Japanese kaatsu, and the potential for rehabilitation or situations where heavy loading is undesirable. Two forms of countermeasures to unloading have been successful, (1) high-load resistance training has maintained muscle mass and strength, and low load resistance training with blood flow restriction (LL(sub BFR)). The LL(sub BFR) has been shown to increase muscle mass and strength. There has been significant interest in Tourniquet training. An increase in Growth Hormone(GH) has been noted for LL(sub BFR) exercise. An experimental study with 16 subjects 8 of whom performed ULLS, and 8 of whom performed ULLS and LL(sub BFR) exercise three times per week during the ULLS. Charts show the results of the two groups, showing that performing LL(sub BFR) exercise during 30 days of ULLS can maintain muscle size and strength and even improve muscular endurance.

  8. Regulating environments to reduce obesity.

    Hayne, Cheryl L; Moran, Patricia A; Ford, Mary M

    2004-01-01

    The marked increase in the prevalence of obesity appears to be attributable to environmental conditions that implicitly discourage physical activity while explicitly encouraging the consumption of greater quantities of energy-dense, low-nutrient foods. In the United States food environment, consumers are bombarded with advertising for unhealthy food, and receive inadequate nutritional information, especially at restaurants. In the US school environment children have access to sugary sodas and unhealthy a la carte foods in their cafeterias, at the same time getting inadequate physical activity and nutrition education. In the built environment, sprawl has reduced active living. We describe these environments and explore the potential effects of regulatory measures on these environments. In the United States, regulatory opportunities exist at the national, state and local levels to mandate action and to allocate funds for promising health-promoting strategies. Regulatory approaches, much like litigation, can transform the entire environment in which corporations operate. Even with incomplete enforcement of rules, they send a public message about what is acceptable behavior for corporations and individuals. Additionally, because the United States is party to many multilateral and bilateral trade agreements and is an active participant in the GATT/WTO framework, US regulatory actions promise to have a beneficial impact both domestically and globally. PMID:15683074

  9. Meditation Helps Reduce Hardened Arteries

    Sue; Pleming; 林兆佩

    2000-01-01

    沉思冥想可以减少人体冠状动脉内壁的厚度、降低心脏病和中风的危险。这话听上去有点玄乎,可是,这是事实。而且,这不是崇尚气功的国人的结论,而是美国医生的实验所证实的事实。 简称为TM(由Transcendental[超然的;超验的]Meditation的首字母所组成)的方法每日进行两次,每次20分钟。同时还得使用所谓a specific sound or“mental vehicle”(精神媒介物)。其目的是:…enabled the person to experiencequieter states of thinking.其背后的原因是:…heart disease was associated withpsychological stress and that meditating could reduce this。以下一句间接告诉我们:所谓TM,并非一两句话就能交代明白: The meditation group was given five to eight hours of tuition on TM tech—niques… 美国的研究人员常运用“对比法”来作下结论。本文也不例外。 本文给我们的重要启示是:…heart disease was associated with psychologicalstress.而quieter states of thinking是强身健体之关键。

  10. Reducing carbon-in-ash

    Nigel S. Dong [IEA Clean Coal Centre, London (United Kingdom)

    2010-05-15

    High levels of carbon-in-ash lead to reduced power plant efficiency and higher fuel costs, degrade the performance of electrostatic precipitators and increase emissions of particulates. Increased carbon levels in the fly ash can lead to problems with ash use in cement/concrete production. This report reviews current measures and technologies that can be used to prevent excessive carbon-in-ash in pulverised coal combustion (PCC) power plants. These include coal cleaning, coal fineness improvement, reduction of distribution imbalance of coal among burners, increasing coal-air mixing rates at both burner and OFA levels and optimising excess air ratios. A plasma-assisted combustion enhancement technology can help achieve better ignition and more stable flame for coals that are normally difficult to burn. Computer-based combustion optimisation using expert systems, neural network systems and coal combustion simulation is becoming an invaluable means to tackle the carbon-in-ash issue. This report also reviews the regulations in nine major coal-consuming countries, which stipulate the maximum unburnt carbon levels permitted for fly ash for use in concrete/cement production. The Loss on Ignition (LOI) parameter is used in all national standards, although it is considered inadequate and may exclude some usable fly ash from being utilised. Performance-based regulations are more appropriate and have been adopted by Canada and USA. The EU and Canada now permit the use of fly ash produced from co-combustion of coal and biomass. China and Russia allow very high LOI levels for certain fly ash but the other countries require similar LOI limits for fly ash for use in concrete. Finally, this report discusses measures and technologies for reduction of carbon-in-ash, including classification, froth flotation, triboelectrostatic separators, thermal processes and carbon surface modification. 146 refs., 19 figs., 15 tabs.

  11. Clinicopathologic significance of β-catenin protein and loss of heterozygosity on 10q in medulloblastoma%髓母细胞瘤β-catenin蛋白表达与10q杂合性缺失检测及其临床意义

    李俊芝; 王成辉; 周福安; 苗娜; 古丽那尔·阿布拉江; 张巍

    2012-01-01

    目的 探讨髓母细胞瘤β-catenin蛋白的表达及10q杂合性缺失与临床病理特征的关系.方法 选择新疆医科大学第一附属医院2002至2011年间,经病理组织学诊断为不同类型的髓母细胞瘤合计50例,包括经典型髓母细胞瘤32例,促纤维增生型13例,结节型5例,采用免疫组织化学EnVision法对50例髓母细胞瘤石蜡切片β-catenin蛋白进行半定量分析,荧光原位杂交技术检测10q杂合性缺失,Kaplan-Meien和Cox回归分析β-catenin蛋白、10q杂合性缺失与临床病理特征及预后关系.结果 β-catenin蛋白在经典型髓母细胞瘤胞质中阳性率为53.1% (17/32),促纤维增生型为4/13,广泛结节型为1/5;经典髓母细胞瘤10q杂合性缺失率为33.3%(8/24),促纤维增生型为2/11,结节型未见10q杂合性缺失(0/5);三种类型间比较,差异均无统计学意义(P>0.05).单因素分析β-catenin蛋白阳性表达者(P=0.022)、无10q杂合性缺失(P=0.020)、肿瘤切除范围(P<0.01)、放疗(P =0.002)、化疗(P<0.01)与髓母细胞瘤患者预后相关.结论 β-catenin蛋白阳性表达者、无10q杂合性缺失者预后较好.检测髓母细胞瘤染色体β-catenin蛋白表达和10q杂合性缺失,有助于预后判断.%Objective To study the expression of β-catenin protein and the status of loss of heterozygosity (LOH) on chromsome 10q in medulloblastoma,with clinical correlation.Methods Immunohistochemical study for β-catenin protein was carried out in 50 cases of medulloblastoma encountered in the First Affiliated Hospital of Xinjiang Medical University during the period from 2002 to 2011,including 32 cases of classic medulloblastoma,13 cases of desmoplastic medulloblastoma and 5 cases of medulloblastoma with extensive nodularity.The status of LOH on 10q was also detected by fluorescence in-situ hybridization.The clinicopathologic characteristics and prognostic parameters were studied by Kaplan-Meien and Cox analysis.Results The

  12. Loss of heterozygosity of chromosome 1p/19q and p53 protein expression in oligodendroglioma%少突胶质细胞瘤染色体1p/19 q杂合性缺失与p53蛋白表达的相关性研究

    熊佶; 刘颖; 李超; 朱静静; 叶诸榕; 毛颖; 汪寅

    2009-01-01

    Objective To study the status of loss of heterozygosity ( LOH) of chromosome lp/19q and p53 protein expression in oligodendroglioma,as compared to astrocytoma.Methods One hundred and ninety-one cases of glioma of different histologic types and grades,including 116 cases of low-grade of oligodendroglioma ( 86 paraffin-embedded and 30 fresh tissues) ,45 cases of anaplastic oligodendroglioma (all paraffin-embedded tissues) and 30 cases of astrocytoma of various grades ( all paraffin-embedded tissues),were enrolled into the study.The LOH of chromosome lp/19q was investigated by polymerase chain reaction ( PCR) -based microsatellite analysis.The p53 protein expression was demonstrated by immunohistochemical staining.Results The rates of lp loss, 19q loss and lp/19q loss were 69.8% ,64%,and 57.0% respectively in the 86 paraffin-embedded low-grade oligodendroglioma samples,as compared to 71.1%,60.0% and 55.6% respectively in the 45 paraffin-embedded anaplastic oligodendroglioma samples.There was no difference of LOH of lp/19q between low-grade oligodendroglioma and anaplastic oligodendroglioma (P > 0.05).In the 30 cases of low-grade oligodendroglioma with fresh tissues available,the rates of lp loss,19q loss and lp/19q loss were 70.0%,63.3% and 60.0% respectively.The LOH of lp/19q between paraffin-embedded and fresh samples was not statistically significant (P >0.05).In the 30 cases of astrocytoma,the rates of lp loss,19q loss and lp/19q loss were 23.3%,33.3% and 20.0% respectively,which were significantly less than those in oligodendroglioma (P 0.05).30例WHO Ⅱ级少突胶质细胞瘤新鲜标本染色体1p缺失率为70.0%(21/30)、19q缺失率为63.3%(19/30)、1p/19q联合缺失率为60.0%(18/30),与石蜡标本的缺失率比较差异无统计学意义(P>0.05).30例星形细胞起源的肿瘤染色体对应三种缺失率分别为23.3%(7/30)、33.3%(10/30)及20.0%(6/30),与少突胶质细胞瘤差异有统计学意义(P<0.05).86例WHO Ⅱ

  13. Generalized Reduced Order Model Generation Project

    National Aeronautics and Space Administration — M4 Engineering proposes to develop a generalized reduced order model generation method. This method will allow for creation of reduced order aeroservoelastic state...

  14. Microwave Antenna With Reduced Noise Leakage

    Cha, A. G.

    1986-01-01

    Gain or gain-to-temperature ratio of dual-shaped subreflector receiving antenna increased when illumination is tapered near aperture edge. Taper imposed in antenna feed reduces spillover in transmitting mode and reduces noise pickup in receiving mode.

  15. Interpretation of the reduced density gradient

    Boto, Roberto A.; Contreras-García, Julia; Tierny, Julien; Piquemal, Jean-Philip

    2015-01-01

    An interpretation of the reduced density gradient in terms of the bosonic kinetic energy density is presented. Contrary to other bonding indicators based on the kinetic energy density such as the localised orbital locator (LOL) or the electron localization function (ELF), the reduced density gradient is not only able to identify covalent bondings, but also ionic and non-covalent interactions. This study reveals that the critical points of the reduced density gradient are closely connected wit...

  16. Characterization of (per)chlorate-reducing bacteria

    Wolterink, A.F.W.M.

    2004-01-01

    Some bacteria can use (per)chlorateas terminal electron acceptor for growth. These bacteria convert perchlorate via chlorate and chlorite into chloride and molecular oxygen. Oxygen formation in microbial respiration is unique. In this study two chlorate-reducing strains belonging to the species Pseudomonas chloritidismutans and a (per)chlorate-reducing strain Dechloromonas hortensis were isolated. The characterization of the chlorate-reducing strain AW-1, which was isolated from a bioreactor ...

  17. Microprocessor Protection of Power Reducing Transformers

    F. A. Romanuk; Korolev, S. P.; M. S. Loman

    2011-01-01

    The paper contains analysis of advantages and disadvantages of existing differential protection terminals of power reducing transformers. The paper shows that there are good reasons to develop microprocessor protection of power reducing transformer which contains required functions and settings and which is based on Belarusian principles of relay protection system construction. The paper presents functional structure of microprocessor terminal of power reducing transformer which is developed. 

  18. Microprocessor Protection of Power Reducing Transformers

    F. A. Romanuk

    2011-01-01

    Full Text Available The paper contains analysis of advantages and disadvantages of existing differential protection terminals of power reducing transformers. The paper shows that there are good reasons to develop microprocessor protection of power reducing transformer which contains required functions and settings and which is based on Belarusian principles of relay protection system construction. The paper presents functional structure of microprocessor terminal of power reducing transformer which is developed. 

  19. Study on high Tc superconducting ripple reducer

    This paper presents study on application of high Tc superconductors as a ripple reducer for reduction of the toroidal field (TF) ripple without changing the design of TF coils. The feasibility of the ripple reducer is first demonstrated on the basis of experiments. Next, parameter survey of the ripple reducer is performed for the configuration of the outline design of ITER, and a guideline for the design of the ripple reducer is presented with the consideration of constraints from the technological viewpoint of the fusion reactor. (orig.)

  20. Reduced, tame and exotic fusion systems

    Andersen, K.K.S.; Oliver, Bob; Ventura, Joana

    We define here two new classes of saturated fusion systems, reduced fusion systems and tame fusion systems. These are motivated by our attempts to better understand and search for exotic fusion systems: fusion systems which are not the fusion systems of any finite group. Our main theorems say that...... every saturated fusion system reduces to a reduced fusion system which is tame only if the original one is realizable, and that every reduced fusion system which is not tame is the reduction of some exotic (nonrealizable) fusion system....

  1. Reduced, tame and exotic fusion systems

    Andersen, Kasper K. S.; Oliver, Bob; Ventura, Joana

    2010-01-01

    We define here two new classes of saturated fusion systems, reduced fusion systems and tame fusion systems. These are motivated by our attempts to better understand and search for exotic fusion systems: fusion systems which are not the fusion systems of any finite group. Our main theorems say that every saturated fusion system reduces to a reduced fusion system which is tame only if the original one is realizable, and that every reduced fusion system which is not tame is the reduction of some...

  2. Does beekeeping reduce genetic variability in Melipona scutellaris (Apidae, Meliponini)?

    Carvalho-Zilse, G A; Costa-Pinto, M F F; Nunes-Silva, C G; Kerr, W E

    2009-01-01

    Many factors have contributed to reductions in wild populations of stingless bees, such as: deforestation, displacement and destruction of nests by honey gatherers, as well as use of insecticides and other agrochemicals. All of these can potentially affect the populational structure of native species. We analyzed genetic variability and populational structure of Melipona scutellaris, based on five microsatellite loci, using heterologous primers of M. bicolor. Samples were taken from 43 meliponaries distributed among 30 sites of four northeastern states of Brazil (Pernambuco, Alagoas, Sergipe, and Bahia). Thirty-one alleles were found to be well distributed among the populations, with sizes ranging from 85 to 146 bp. In general, there was a variable distribution and frequency of alleles among populations, with either exclusive and/or fixed alleles at some sites. The population of Pernambuco was the most polymorphic, followed by Bahia, Alagoas and Sergipe. The heterozygosity was Ho = 0.36 on average, much lower than what has been reported for M. bicolor (Ho = 0.65). Most populations were not under Hardy-Weinberg equilibrium. We found a higher variation within rather than among populations, indicating no genetic structuring in those bees maintained in meliponaries. This apparent homogenization may be due to intense beekeeping activity, including exchange of genetic material among beekeepers. Based on our findings, we recommend more studies of meliponaries and of wild populations in order to help orient management and conservation of these native pollinators. PMID:19681027

  3. Soluble calcium amendments: reducing pathogen losses

    Flue gas desulfurization (FGD) gypsum is a byproduct of coal-fired power plants. Its application to agricultural fields may increase water infiltration, reduce soil erosion, and decrease nutrient losses from applications of animal manures. It may also reduce fecal bacterial contamination of surface ...

  4. A small town reduces its energy expenses

    Vissac, G.

    1993-12-31

    Langeac, a 4 300 inhabitants community in France, has relied on its resinous forest and on the local wood industry to save energy, reduce its energy expenses and protect environment. A wood-fired heat network exists, supplied by regional manufacturers. On top of that the charges are reduced in the field of energy. (TEC). 1 fig.

  5. Simple Potentiometric Determination of Reducing Sugars

    Moresco, Henry; Sanson, Pedro; Seoane, Gustavo

    2008-01-01

    In this article a potentiometric method for reducing sugar quantification is described. Copper(II) ion reacts with the reducing sugar (glucose, fructose, and others), and the excess is quantified using a copper wire indicator electrode. In order to accelerate the kinetics of the reaction, working conditions such as pH and temperature must be…

  6. Biplots in Reduced-Rank Regression

    Braak, ter C.J.F.; Looman, C.W.N.

    1994-01-01

    Regression problems with a number of related response variables are typically analyzed by separate multiple regressions. This paper shows how these regressions can be visualized jointly in a biplot based on reduced-rank regression. Reduced-rank regression combines multiple regression and principal c

  7. Chitosan-supported Borohydride Reducing Agent

    2001-01-01

    A new chitosan-supported borohydride reducing reagent (CBER) was prepared by treatment of KBH4 with the resin of chitosan derivative, which was first synthesized fiom the reaction of cross-linked chitosan microsphere with glycidyl trimethylammonium chloride. CBER could reduce aromatic carbonyl compound to corresponding alcohol.

  8. Genus Reducing Knots in 3-Manifolds

    Rieck, Yo’av

    2001-01-01

    A genus reducing knot is a knot that has infinitely many surgeries after which the Heegaard genus of the manifold reduces. We study certain aspects of this question, in particular solving it for totally orientable Seifert Fibered Spaces, where we find examples of manifolds of arbitrarily high genus containing no such knot.

  9. An intervention to reduce playground equipment hazards

    Roseveare, C.; Brown, J.; McIntosh, J.; Chalmers, D

    1999-01-01

    Objectives—A community intervention trial was carried out to evaluate the relative effectiveness of two methods of reducing playground hazards in schools. The study hypotheses were: (1) a health promotion programme addressing barriers to implementing the New Zealand Playground Safety Standard will reduce playground hazards and (2) the intervention programme will be more successful than providing information alone.

  10. Sulfate-reducing prokaryotes in river floodplains

    Miletto, M.

    2007-01-01

    This thesis constitutes a pioneer attempt at elucidating the ecology of sulfate-reducing prokaryotes in river floodplains. These are non-typical sulfate-reducing environmental settings, given the generally low sulfate concentration that characterize freshwater habitats, and river flow regulation tha

  11. Welfare Reform and Reducing Teen Pregnancy.

    Sawhill, Isabel V.

    2000-01-01

    Most adolescent mothers are unmarried and on welfare. Congress enacted new welfare legislation that emphasizes reducing teen pregnancy and requiring work, but states are reluctant to meet this challenge. Discusses child poverty's new face, public policy and culture wars, welfare reform, and social norms. Concludes that reducing unwed parenthood…

  12. Method and container for reducing pertechnetate

    A method of reducing the pertechnetate in TcO4- comprises mixing together an aqueous solution of pertechnetate, e.g. the eluant from a technetium generator, metallic tin or an alloy thereof as a reducing agent for the pertechnetate, and a soluble salt of a metal below tin in the electrochemical series, e.g. copper, as an activator for the tin metal reducing agent. A complexing agent for the reduced technetium or a colloid stabiliser may also be included. The pH is preferably 3 to 12. Also claimed is a closed container containing the tin reducing agent, the activator, and the complexant or colloid stabiliser if used, preferably in a freeze-dried sterile state, to which the pertechnetate solution may be added. (author)

  13. Multiclass Reduced-Set Support Vector Machines

    Tang, Benyang; Mazzoni, Dominic

    2006-01-01

    There are well-established methods for reducing the number of support vectors in a trained binary support vector machine, often with minimal impact on accuracy. We show how reduced-set methods can be applied to multiclass SVMs made up of several binary SVMs, with significantly better results than reducing each binary SVM independently. Our approach is based on Burges' approach that constructs each reduced-set vector as the pre-image of a vector in kernel space, but we extend this by recomputing the SVM weights and bias optimally using the original SVM objective function. This leads to greater accuracy for a binary reduced-set SVM, and also allows vectors to be 'shared' between multiple binary SVMs for greater multiclass accuracy with fewer reduced-set vectors. We also propose computing pre-images using differential evolution, which we have found to be more robust than gradient descent alone. We show experimental results on a variety of problems and find that this new approach is consistently better than previous multiclass reduced-set methods, sometimes with a dramatic difference.

  14. Novel Reduced Parts Online Uninterruptible Power Supply

    Bahram Ashrafi

    2012-01-01

    Full Text Available This paper presents design consideration and performance analysis of novel reduced parts online three-phase uninterruptible power supply (UPS system. The proposed UPS system is based on reduced switch count dual bridge matrix converter. It employs only six power switches and results in reducing the cost of the system compared to conventional online UPS topologies, while achieving excellent performance. The performance of the proposed system is evaluated through simulation in terms of input/output waveforms quality and shows the viability of topology.

  15. Reduced Baroclinicity During Martian Global Dust Storms

    Battalio, Joseph; Szunyogh, Istvan; Lemmon, Mark

    2015-11-01

    The eddy kinetic energy equation is applied to the Mars Analysis Correction Data Assimilation (MACDA) dataset during the pre-winter solstice period for the northern hemisphere of Mars. Traveling waves are triggered by geopotential flux convergence, grow baroclinically, and decay barotropically. Higher optical depth increases the static stability, which reduces vertical and meridional heat fluxes. Traveling waves during a global dust storm year develop a mixed baroclinic/barotropic growth phase before decaying barotropically. Baroclinic energy conversion is reduced during the global dust storm, but eddy intensity is undiminished. Instead, the frequency of storms is reduced due to a stabilized vertical profile.

  16. Reducing urinary tract infections in catheterised patients.

    Howe, Pam; Adams, John

    2015-01-20

    Urinary tract infections in catheterised patients continue to present a challenge in reducing healthcare-associated infection. In this article, an infection prevention and control team in one NHS trust reports on using audit results to focus attention on measures to reduce bacterial infections. Educational initiatives have an important role in reducing infection, but there is no single solution to the problem. Practice can be improved using a multi-targeted approach, peer review and clinical audit to allow for shared learning and experiences. These, along with informal education in the clinical area and more formal classroom lectures, can ultimately lead to improved patient outcomes. PMID:25585767

  17. Goal directed fluid therapy reduces major

    Dina Y. Kassim

    2016-04-01

    Conclusion: A restrictive strategy of fluid maintenance during optimization of oxygen delivery with early treatment directed to maintain oxygen extraction ratio estimate (O2ERe at <27% reduces major complications and hospital stay of surgical patients undergo abdominal aortic aneurysm.

  18. Electronic states in systems of reduced dimensionality

    This report briefly discusses the following research: magnetically modulated systems, inelastic magnetotunneling, ballistic transport review, screening in reduced dimensions, raman and electron energy loss spectroscopy; and ballistic quantum interference effects. (LSP)

  19. REDUCING TOXICITY CHEMICALS PLANT PROTECTION PRODUCTS

    Litvishko, Valery; Myaskovskaya, Tatiana

    2014-01-01

    The samples of microencapsulated pesticide have been investigated in acute experiments on laboratory animals. The results of the research have determined that microencapsulation can reduce toxicity of plant protection chemicals.

  20. Vaccine Reduces HPV Infections in Young Men

    An international randomized clinical trial has shown that the vaccine Gardasil can reduce the incidence of anogenital human papillomavirus (HPV) infections in young men 16 to 26 years of age at the time of vaccination.

  1. Reducing nitrogen oxides from power stations

    The report contains 17 individual lectures of the seminar included in databanks. The lectures concern combustion and waste gas measures for reducing the sulfur dioxide and nitrogen oxide emission from coal-fired and gas-fired power stations. (PW)

  2. Spontaneously reduced isolated orbital roof fracture.

    Itinteang, Tinte; Lambe, Gerald Francis; MacKinnon, Craig; Agir, Hakan

    2012-07-01

    We report a case of a spontaneously reduced isolated orbital roof blow-in fracture with resolution of associated diplopia and blepharoptosis highlighting the need for a low threshold for reimaging this cohort of facial fracture patients. PMID:22801127

  3. 76 FR 6123 - Reducing Regulatory Burden

    2011-02-03

    ... Reducing Regulatory Burden AGENCY: Office of the General Counsel, Department of Energy. ACTION: Request for... FURTHER INFORMATION CONTACT: Daniel Cohen, Assistant General Counsel for Legislation, Regulation, and..., the President issued Executive Order 13563, ``Improving Regulation and Regulatory Review,'' to...

  4. Cogeneration, renewables and reducing greenhouse gas emissions

    The MENSA model is used to assess the potential role of cogeneration and selected new renewable energy technologies in cost-effectively reducing Greenhouse gas emissions. The model framework for analyzing these issues is introduced, together with an account of relevant aspects of its application. In the discussion of selected new renewable energy technologies, it is shown how microeconomic reform may encourage these technologies and fuels, and thereby reduce sector wide carbon dioxide emissions. Policy scenarios modelled are described and the simulation results are presented. Certain interventions in microeconomic reform may result in economic benefits while also reducing emissions: no regrets' opportunities. Some renewable energy technologies are also shown to be cost-effective in the event that targets and timetables for reducing Greenhouse gas emissions are imposed. However, ad hoc interventions in support of particular renewables options are unlikely to be consistent with a least cost approach to achieving environmental objectives. (author). 5 tabs., 5 figs., 21 refs

  5. Do conditional benefits reduce equilibrium unemployment?

    F. van der Ploeg

    2006-01-01

    Although unconditional unemployment benefits destroy jobs in competitive and noncompetitive labor markets, conditional benefits can spur job growth in noncompetitive labor markets. Unconditional benefits reduce the penalty of shirking and misconduct, while conditional benefits increase this penalty.

  6. Deep brain stimulation to reduce sexual drive

    Fuss, Johannes; Auer, Matthias K.; Biedermann, Sarah V.; Briken, Peer; Hacke, Werner

    2015-01-01

    To date there are few treatment options to reduce high sexual drive or sexual urges in paraphilic patients with a risk for sexual offending. Pharmacological therapy aims to reduce sexual drive by lowering testosterone at the cost of severe side effects. We hypothesize that high sexual drive could also be reduced with deep brain stimulation (DBS) of circuits that generate sexual drive. This approach would help to avoid systemic side effects of antiandrogenic drug therapies. So far the best investigated target to reduce sexual drive is the ventromedial hypothalamus, which was lesioned unilaterally and bilaterally by stereotaxic interventions in paraphilic patients in the 1970s. Here, we discuss DBS as a treatment strategy in patients with severe paraphilic disorders with a serious risk of sexual offending. There are profound ethical and practical issues associated with DBS treatment of paraphilic patients that must be solved before considering such a treatment approach. PMID:26057198

  7. Multiple polylogarithms and linearly reducible Feynman graphs

    Bogner, Christian

    2013-01-01

    We review an approach for the computation of Feynman integrals by use of multiple polylogarithms, with an emphasis on the related criterion of linear reducibility of the graph. We show that the set of graphs which satisfies the linear reducibility with respect to both Symanzik polynomials is closed under taking minors. As a step towards a classification of Feynman integrals, we discuss the concept of critical minors and exhibit an example at three loops with four on-shell legs.

  8. Acetate reduces microglia inflammatory signaling in vitro

    Soliman, Mahmoud L; Puig, Kendra L.; Combs, Colin K.; Rosenberger, Thad A.

    2012-01-01

    Acetate supplementation increases brain acetyl-CoA and histone acetylation and reduces lipopolysaccharide (LPS)-induced neuroglial activation and interleukin (IL)-1β expression in vivo. To determine how acetate imparts these properties, we tested the hypothesis that acetate metabolism reduces inflammatory signaling in microglia. To test this, we measured the effect acetate treatment had on cytokine expression, mitogen-activated protein kinase (MAPK) signaling, histone H3 at lysine 9 acetylati...

  9. IHadoop: Asynchronous iterations for MapReduce

    Elnikety, Eslam Mohamed Ibrahim

    2011-11-01

    MapReduce is a distributed programming frame-work designed to ease the development of scalable data-intensive applications for large clusters of commodity machines. Most machine learning and data mining applications involve iterative computations over large datasets, such as the Web hyperlink structures and social network graphs. Yet, the MapReduce model does not efficiently support this important class of applications. The architecture of MapReduce, most critically its dataflow techniques and task scheduling, is completely unaware of the nature of iterative applications; tasks are scheduled according to a policy that optimizes the execution for a single iteration which wastes bandwidth, I/O, and CPU cycles when compared with an optimal execution for a consecutive set of iterations. This work presents iHadoop, a modified MapReduce model, and an associated implementation, optimized for iterative computations. The iHadoop model schedules iterations asynchronously. It connects the output of one iteration to the next, allowing both to process their data concurrently. iHadoop\\'s task scheduler exploits inter-iteration data locality by scheduling tasks that exhibit a producer/consumer relation on the same physical machine allowing a fast local data transfer. For those iterative applications that require satisfying certain criteria before termination, iHadoop runs the check concurrently during the execution of the subsequent iteration to further reduce the application\\'s latency. This paper also describes our implementation of the iHadoop model, and evaluates its performance against Hadoop, the widely used open source implementation of MapReduce. Experiments using different data analysis applications over real-world and synthetic datasets show that iHadoop performs better than Hadoop for iterative algorithms, reducing execution time of iterative applications by 25% on average. Furthermore, integrating iHadoop with HaLoop, a variant Hadoop implementation that caches

  10. Biplots in Reduced-Rank Regression

    Braak, ter, C.J.F.; Looman, C.W.N.

    1994-01-01

    Regression problems with a number of related response variables are typically analyzed by separate multiple regressions. This paper shows how these regressions can be visualized jointly in a biplot based on reduced-rank regression. Reduced-rank regression combines multiple regression and principal components analysis and can therefore be carried out with standard statistical packages. The proposed biplot highlights the major aspects of the regressions by displaying the least-squares approxima...

  11. How Stress Can Reduce Dissipation in Glasses

    Wu, Jiansheng; Yu, Clare C.

    2011-01-01

    We propose that stress can decrease the internal friction of amorphous solids, either by increasing the potential barriers of defects, thus reducing their tunneling and thermal activation that produce loss, or by decreasing the coupling between defects and phonons. This stress can be from impurities, atomic bonding constraints, or externally applied stress. Externally applied stress also reduces mechanical loss through dissipation dilution. Our results are consistent with the experiments, and...

  12. Programming MapReduce with Scalding

    Chalkiopoulos, Antonios

    2014-01-01

    This book is an easy-to-understand, practical guide to designing, testing, and implementing complex MapReduce applications in Scala using the Scalding framework. It is packed with examples featuring log-processing, ad-targeting, and machine learning. This book is for developers who are willing to discover how to effectively develop MapReduce applications. Prior knowledge of Hadoop or Scala is not required; however, investing some time on those topics would certainly be beneficial.

  13. Evaluating Active Interventions to Reduce Student Procrastination

    Martin, Joshua Deckert

    2015-01-01

    Procrastination is a pervasive problem in education. In computer science, procrastination and lack of necessary time management skills to complete programming projects are viewed as primary causes of student attrition. The most effective techniques known to reduce procrastination are resource-intensive and do not scale well to large classrooms. In this thesis, we examine three course interventions designed to both reduce procrastination and be scalable for large classrooms. Reflective writ...

  14. Laser welding in a reduced gravity environment

    Workman, Gary L.; Kaukler, William F.

    1992-01-01

    Preliminary results on the effects of reduced gravity on laser welding of stainless steel and other materials are reported. Laser welding experiments using a low power (10-18 watts) Nd-YAG laser have been performed on the NASA KC-135, which flies parabolic maneuvers to simulate reduced gravity conditions. Experiments on 0.005-0.010 inch thick stainless steel samples displayed a pronounced change in weld bead width, depth of penetration and surface ripple with changes in gravity level.

  15. Reducing stereotype threat by blurring intergroup boundaries.

    Rosenthal, H. E. S.; Crisp, R. J.

    2006-01-01

    The authors aimed to establish whether interventions designed to reduce intergroup bias could be applied to the stereotype threat domain. In three experiments, the hypothesis was tested that blurring intergroup boundaries would reduce stereotype threat. In the first study, it was found that female participants who thought about characteristics shared between the genders tended to show less preference for stereotypical female careers than did participants in the baseline condition. In. Experim...

  16. Reduced span spray – Part 1: Retention

    Massinon, Mathieu; De Cock, Nicolas; Ouled Taleb Salah, Sofiene; Lebeau, Frédéric

    2016-01-01

    Maximising treatment efficiency for a given target lies mainly on depositing a maximum part of the spray volume within an optimal droplet size range, which has to be as narrow as possible to reduce retention variability and drift issues. The present work focuses on exploring the effect of span factor of the droplet size distribution on the final retention by a 3D target plant using a modelling approach with the final aim of guiding the development of a reduced span nozzle (Redu...

  17. A Reducing Resistance to Change Model

    Daniela Braduţanu

    2015-01-01

    The aim of this scientific paper is to present an original reducing resistance to change model. After analyzing the existent literature, I have concluded that the resistance to change subject has gained popularity over the years, but there are not too many models that could help managers implement more smoothly an organizational change process and at the same time, reduce effectively employees’ resistance. The proposed model is very helpful for managers and change agents who are c...

  18. Reduced sulfur compound oxidation by Thiobacillus caldus.

    Hallberg, K. B.; Dopson, M; Lindström, E B

    1996-01-01

    The oxidation of reduced inorganic sulfur compounds was studied by using resting cells of the moderate thermophile Thiobacillus caldus strain KU. The oxygen consumption rate and total oxygen consumed were determined for the reduced sulfur compounds thiosulfate, tetrathionate, sulfur, sulfide, and sulfite in the absence and in the presence of inhibitors and uncouplers. The uncouplers 2,4-dinitrophenol and carbonyl cyanide m-chlorophenyl-hydrazone had no affect on the oxidation of thiosulfate, ...

  19. Reduced form of a Mueller matrix

    Gil, Jose J.; Jose, Ignacio San

    2015-01-01

    Through a simple procedure based on the Lu-Chipman decomposition [S-Y. Lu and R. C. Chipman, J. Opt. Soc. Am A 13, 1106 (1996)] any depolarizing Mueller matrix can be transformed into a reduced form which accumulates the depolarization and polarizance properties into a set of six parameters. The simple structure of this reduced form provides straightforward ways for the general characterization of Mueller matrices as well as for the analysis of singular Mueller matrices.

  20. Reduced form of a Mueller matrix

    Gil, Jose J

    2015-01-01

    Through a simple procedure based on the Lu-Chipman decomposition [S-Y. Lu and R. C. Chipman, J. Opt. Soc. Am A 13, 1106 (1996)] any depolarizing Mueller matrix can be transformed into a reduced form which accumulates the depolarization and polarizance properties into a set of seven parameters. The simple structure of this reduced form provides straightforward ways for the general characterization of Mueller matrices as well as for the analysis of singular Mueller matrices.

  1. Boiler burden reduced at Bedford site.

    Horsley, Chris

    2011-10-01

    With the NHS aiming to reduce its 2007 carbon footprint by 10% by 2015, Chris Horsley, managing director of Babcock Wanson UK, a provider of industrial boilers and burners, thermal oxidisers, air treatment, water treatment, and associated services, looks at how one NHS Trust has approached the challenge, and considerably reduced its carbon emissions, by refurbishing its boiler house and moving from oil to gas-fired steam generation. PMID:22049674

  2. Reduced waste generation technical work plan

    The United States Department of Energy has established policies for avoiding plutonium losses to the waste streams and minimizing the generation of wastes produced at its nuclear facilities. This policy is evidenced in DOE Order 5820.2, which states ''Technical and administrative controls shall be directed towards reducing the gross volume of TRU waste generated and the amount of radioactivity in such waste.'' To comply with the DOE directive, the Defense Transuranic Waste Program (DTWP) supports and provides funding for specific research and development tasks at the various DOE sites to reduce the generation of waste. This document has been prepared to give an overview of current and past Reduced Waste Generation task activities which are to be based on technical and cost/benefit factors. The document is updated annually, or as needed, to reflect the status of program direction. Reduced Waste Generation (RWG) tasks encompass a wide range of goals which are basically oriented toward (1) avoiding the generation of waste, (2) changing processes or operations to reduce waste, (3) converting TRU waste into LLW by sorting or decontamination, and (4) reducing volumes through operations such as incineration or compaction

  3. Contralateral Risk-Reducing Mastectomy: Review of Risk Factors and Risk-Reducing Strategies

    Basu, N. N.; Barr, L; Ross, G. L.; Evans, D. G.

    2015-01-01

    Rates of contralateral risk-reducing mastectomy have increased substantially over the last decade. Surgical oncologists are often in the frontline, dealing with requests for this procedure. This paper reviews the current evidence base regarding contralateral breast cancer, assesses the various risk-reducing strategies, and evaluates the cost-effectiveness of contralateral risk-reducing mastectomy.

  4. Evolution of technetium speciation in reducing grout

    Lukens, Wayne W.; Bucher, Jerome J.; Shuh, David K.; Edelstein,Norman M.

    2003-11-24

    Cementitious waste forms (CWFs) are an important component of the strategy to immobilize high-level nuclear waste resulting from plutonium production by the U.S. Department of Energy (DOE). Technetium (99Tc) is an abundant fission product of particular concern in CWFs due to the high solubility and mobility of pertechnetate, TcO4-, the stable form of technetium in aerobic environments. CWFs can more effectively immobilize 99Tc if they contain additives that reduce mobile TcO4- to immobile Tc(IV) species. Leaching of 99Tc from reducing CWFs that contain Tc(IV) is much slower than for CWFs containing TcO4-. Previous X-ray absorption fine structure (XAFS) studies showed that the Tc(IV) species were oxidized to TcO4- in reducing grout samples prepared on a laboratory scale. Whether the oxidizer was atmospheric O2 or NO3- in the waste simulant was not determined. In actual CWFs, rapid oxidation of Tc(IV) by NO3- would be a concern, whereas oxidation by atmospheric O2 would be of less concern due to the slow diffusion and reaction of O2 with the reducing CWF. To address this uncertainty, two series of reducing grouts were prepared using TcO4- containing waste simulants with and without NO3-. In the first series of samples, the TcO4- was completely reduced using Na2S, and the samples were placed in containers that permitted O2 diffusion. In these samples, all of the technetium was initially present as aTc(IV) sulfide compound, TcSx, which was characterized using extended X-ray absorption fine structure (EXAFS) spectroscopy, and is likely Tc2S7. The TcSx initially present in the grout samples was steadily oxidized over 4 years. In the second series of samples, all of the TcO4- was not initially reduced, and the grout samples were placed in airtight containers. In these samples, the remaining TcO4- continued to be reduced as the samples aged, presumably due to the presence of reducing blast furnace slag. When samples in the second series were exposed to atmosphere, the

  5. Evolution of technetium speciation in reducing grout

    Cementitious waste forms (CWFs) are an important component of the strategy to immobilize high-level nuclear waste resulting from plutonium production by the U.S. Department of Energy (DOE). Technetium (99Tc) is an abundant fission product of particular concern in CWFs due to the high solubility and mobility of pertechnetate, TcO4-, the stable form of technetium in aerobic environments. CWFs can more effectively immobilize 99Tc if they contain additives that reduce mobile TcO4- to immobile Tc(IV) species. Leaching of 99Tc from reducing CWFs that contain Tc(IV) is much slower than for CWFs containing TcO4-. Previous X-ray absorption fine structure (XAFS) studies showed that the Tc(IV) species were oxidized to TcO4- in reducing grout samples prepared on a laboratory scale. Whether the oxidizer was atmospheric O2 or NO3- in the waste simulant was not determined. In actual CWFs, rapid oxidation of Tc(IV) by NO3- would be a concern, whereas oxidation by atmospheric O2 would be of less concern due to the slow diffusion and reaction of O2 with the reducing CWF. To address this uncertainty, two series of reducing grouts were prepared using TcO4- containing waste simulants with and without NO3-. In the first series of samples, the TcO4- was completely reduced using Na2S, and the samples were placed in containers that permitted O2 diffusion. In these samples, all of the technetium was initially present as aTc(IV) sulfide compound, TcSx, which was characterized using extended X-ray absorption fine structure (EXAFS) spectroscopy, and is likely Tc2S7. The TcSx initially present in the grout samples was steadily oxidized over 4 years. In the second series of samples, all of the TcO4- was not initially reduced, and the grout samples were placed in airtight containers. In these samples, the remaining TcO4- continued to be reduced as the samples aged, presumably due to the presence of reducing blast furnace slag. When samples in the second series were exposed to atmosphere, the

  6. Bioremediation: Effectiveness in reducing the ecological impact

    Bioremediation becomes an important technique in oil spill combat programmes. The purpose is to shorten the exposure time of biota to oil compounds, in order to reduce long term environmental effects. Although bioremediation products have the advantage of stimulating the natural capacity to degrade oil, there are some limitations to be considered. Application as a technique for first emergency actions following an oil spill is not effective, and can therefore be no alternative for dispersion or mechanical removal of floating or freshly stranded oil slicks. Acute toxic effects are related to the short term exposure to unweathered oils. An immediate removal of oil is necessary to reduce the extent of the environmental impact of an oil spill. Physical processes (transport, dilution and evaporation) are determining the initial fate of environmentally released oil. Biodegradation only becomes important as a process of removing oil in the next phase. It is the only effective way to further reduce the concentration of oil that is left in (intertidal) coastal areas. Bioremediation thus reduces the duration of the environmental impact of an oil spill. This is especially important in ecosystems with a low recovery potential (e.g., salt marshes, rocky shores). The experimental evaluation of bioremediation products is mainly based on the capacity to reduce fresh oil and the acute toxicity of the product itself, rather than on the capacity to enhance the further reduction of weathered oil and the toxicological consequences of higher release rates of intermediate metabolites produced during the biotransformation processes

  7. Understanding Uranium Behavior in a Reduced Aquifer

    Janot, N.; Lezama-Pacheco, J. S.; Williams, K. H.; Bernier-Latmani, R.; Long, P. E.; Davis, J. A.; Fox, P. M.; Yang, L.; Giammar, D.; Cerrato, J. M.; Bargar, J.

    2012-12-01

    Uranium contamination of groundwater is a concern at several US Department of Energy sites, such Old Rifle, CO. Uranium transport in the environment is mainly controlled by its oxidation state, since oxidized U(VI) is relatively mobile, whereas U(IV) is relatively insoluble. Bio-remediation of contaminated aquifers aims at immobilizing uranium in a reduced form. Previous laboratory and field studies have shown that adding electron donor (lactate, acetate, ethanol) to groundwater stimulates the activity of metal- and sulfate-reducing bacteria, which promotes U(VI) reduction in contaminated aquifers. However, obtaining information on chemical and physical forms of U, Fe and S species for sediments biostimulated in the field, as well as kinetic parameters such as U(VI) reduction rate, is challenging due to the low concentration of uranium in the aquifers (typically bio-remediation experiment at the Old Rifle site, CO, from early iron-reducing conditions to the transition to sulfate-reducing conditions. Several in-well chromatographic columns packed with sediment were deployed and were sampled at different days after the start of bio-reduction. X-ray absorption spectroscopy and X-ray microscopy were used to obtain information on Fe, S and U speciation and distribution. Chemical extractions of the reduced sediments have also been performed, to determine the rate of Fe(II) and U(IV) accumulation.

  8. The LMNA mutation p.Arg321Ter associated with dilated cardiomyopathy leads to reduced expression and a skewed ratio of lamin A and lamin C proteins

    Dilated cardiomyopathy (DCM) is a disease of the heart muscle characterized by cardiac chamber enlargement and reduced systolic function of the left ventricle. Mutations in the LMNA gene represent the most frequent known genetic cause of DCM associated with disease of the conduction systems. The LMNA gene generates two major transcripts encoding the nuclear lamina major components lamin A and lamin C by alternative splicing. Both haploinsuffiency and dominant negative effects have been proposed as disease mechanism for premature termination codon (PTC) mutations in LMNA. These mechanisms however are still not clearly established. In this study, we used a representative LMNA nonsense mutation, p.Arg321Ter, to shed light on the molecular disease mechanisms. Cultured fibroblasts from three DCM patients carrying this mutation were analyzed. Quantitative reverse transcriptase PCR and sequencing of these PCR products indicated that transcripts from the mutant allele were degraded by the nonsense-mediated mRNA decay (NMD) mechanism. The fact that no truncated mutant protein was detectable in western blot (WB) analysis strengthens the notion that the mutant transcript is efficiently degraded. Furthermore, WB analysis showed that the expression of lamin C protein was reduced by the expected approximately 50%. Clearly decreased lamin A and lamin C levels were also observed by immunofluorescence microscopy analysis. However, results from both WB and nano-liquid chromatography/mass spectrometry demonstrated that the levels of lamin A protein were more reduced suggesting an effect on expression of lamin A from the wild type allele. PCR analysis of the ratio of lamin A to lamin C transcripts showed unchanged relative amounts of lamin A transcript suggesting that the effect on the wild type allele was operative at the protein level. Immunofluorescence microscopy analysis showed no abnormal nuclear morphology of patient fibroblast cells. Based on these data, we propose that

  9. The LMNA mutation p.Arg321Ter associated with dilated cardiomyopathy leads to reduced expression and a skewed ratio of lamin A and lamin C proteins

    Al-Saaidi, Rasha [Research Unit for Molecular Medicine, Aarhus University and Aarhus University Hospital, Aarhus (Denmark); Rasmussen, Torsten B. [Department of Cardiology, Aarhus University Hospital, Aarhus (Denmark); Palmfeldt, Johan [Research Unit for Molecular Medicine, Aarhus University and Aarhus University Hospital, Aarhus (Denmark); Nissen, Peter H. [Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus (Denmark); Beqqali, Abdelaziz [Heart Failure Research Center, Academic Medical Center, Amsterdam (Netherlands); Hansen, Jakob [Department of Forensic Medicine, Bioanalytical Unit, University of Aarhus (Denmark); Pinto, Yigal M. [Heart Failure Research Center, Academic Medical Center, Amsterdam (Netherlands); Boesen, Thomas [Department of Molecular Biology and Genetics, University of Aarhus (Denmark); Mogensen, Jens [Department of Cardiology, Odense University Hospital, Odense (Denmark); Bross, Peter, E-mail: peter.bross@ki.au.dk [Research Unit for Molecular Medicine, Aarhus University and Aarhus University Hospital, Aarhus (Denmark)

    2013-11-15

    Dilated cardiomyopathy (DCM) is a disease of the heart muscle characterized by cardiac chamber enlargement and reduced systolic function of the left ventricle. Mutations in the LMNA gene represent the most frequent known genetic cause of DCM associated with disease of the conduction systems. The LMNA gene generates two major transcripts encoding the nuclear lamina major components lamin A and lamin C by alternative splicing. Both haploinsuffiency and dominant negative effects have been proposed as disease mechanism for premature termination codon (PTC) mutations in LMNA. These mechanisms however are still not clearly established. In this study, we used a representative LMNA nonsense mutation, p.Arg321Ter, to shed light on the molecular disease mechanisms. Cultured fibroblasts from three DCM patients carrying this mutation were analyzed. Quantitative reverse transcriptase PCR and sequencing of these PCR products indicated that transcripts from the mutant allele were degraded by the nonsense-mediated mRNA decay (NMD) mechanism. The fact that no truncated mutant protein was detectable in western blot (WB) analysis strengthens the notion that the mutant transcript is efficiently degraded. Furthermore, WB analysis showed that the expression of lamin C protein was reduced by the expected approximately 50%. Clearly decreased lamin A and lamin C levels were also observed by immunofluorescence microscopy analysis. However, results from both WB and nano-liquid chromatography/mass spectrometry demonstrated that the levels of lamin A protein were more reduced suggesting an effect on expression of lamin A from the wild type allele. PCR analysis of the ratio of lamin A to lamin C transcripts showed unchanged relative amounts of lamin A transcript suggesting that the effect on the wild type allele was operative at the protein level. Immunofluorescence microscopy analysis showed no abnormal nuclear morphology of patient fibroblast cells. Based on these data, we propose that

  10. Active structures to reduce torsional vibrations

    Matthias, M.; Schlote, D.; Atzrodt, H.

    2013-03-01

    This paper describes the development of different active measures to reduce torsional vibrations in power trains. The measures are based on concepts developed for active mounts to reduce the transmission of structure-borne sound. To show the potential of these active measures and investigate their mode of operation to influence torsional vibrations, numerical simulations of powertrains with different active measures were done. First experimental results from tests on an experimental (reduced size) power train were used to align the numerical models. The work was done within the project 'LOEWE-Zentrum AdRIA: Adaptronik - Research, Innovation, Application' funded by the German federal state of Hessen, and the Project AKTos: 'Active control of torsional vibrations by coupling elements' placed in the research Framework program 'Navigation and Maritime Technology for the 21st Century' funded by the German Federal Ministry of Economics and Technology.