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  1. Personality differences in two minnow populations that differ in their parasitism and predation risk

    Directory of Open Access Journals (Sweden)

    Raine eKortet

    2015-02-01

    Full Text Available Animals are often individually consistent in their behavior, not only over time, but also across different functional contexts. Recent research has focused on phenotypic and evolutionary mechanisms explaining such personality differences through selection. Parasitism and predation induce important mortality and fitness costs, and are thus the main candidates to create and maintain personality differences in the wild. Here, we present data on the behavioral consistency of the Eurasian minnow (Phoxinus phoxinus from two populations that live in different tributaries of the same river, but whose ecological environment differs fundamentally with regard to predation and parasitism. We experimentally demonstrate that minnow in both study populations are consistent in their boldness and activity. However, the two study populations differ notably: in the high predation and parasitism risk population fish show higher mean boldness, but tend to be less active than fish in low predation and parasitism risk population. Parasite (Diplostomum phoxini load was negatively, but not statistically significantly, associated with fish activity level. Our study suggests that parasitism and predation are likely important agents in the ecology and evolution of animal personalities.

  2. Social learning in a high-risk environment: incomplete disregard for the 'minnow that cried pike' results in culturally transmitted neophobia.

    Science.gov (United States)

    Crane, Adam L; Mathiron, Anthony G E; Ferrari, Maud C O

    2015-08-07

    Many prey species rely on conspecifics to gather information about unknown predation threats, but little is known about the role of varying environmental conditions on the efficacy of social learning. We examined predator-naive minnows that had the opportunity to learn about predators from experienced models that were raised in either a low- or high-risk environment. There were striking differences in behaviour among models; high-risk models showed a weaker response to the predator cue and became neophobic in response to the control cue (a novel odour, NO). Observers that were previously paired with low-risk models acquired a strong antipredator response only to the predator cue. However, observers that interacted with high-risk models, displayed a much weaker response to the predator odour and a weak neophobic response to the NO. This is the first study reporting such different outcomes of social learning under different environmental conditions, and suggests high-risk environments promote the cultural transmission of neophobia more so than social learning. If such a transfer can be considered similar to secondary traumatization in humans, culturally transmitted neophobia in minnows may provide a good model system for understanding more about the social ecology of fear disorders. © 2015 The Author(s).

  3. Gene prediction in the fathead minnow [Pimephales promelas] genome

    Science.gov (United States)

    The fathead minnow is a well-established model organism which has been widely used for regulatory ecotoxicity testing and research for over half century. While much information has been gathered on the organism over the years, the fathead minnow genome, a critical source of infor...

  4. The impact of long term exposure to phthalic acid esters on reproduction in Chinese rare minnow (Gobiocypris rarus)

    International Nuclear Information System (INIS)

    Guo, Yongyong; Yang, Yuanjin; Gao, Yong; Wang, Xianfeng; Zhou, Bingsheng

    2015-01-01

    The environmental risk of phthalic acid esters (PAEs) is of great concern. We investigated the reproductive impairment of di-(2-ethylhexyl)-phthalate (DEHP) on Chinese rare minnow, an endemic fish inhabiting the upper streams of the Yangtze River. Chinese rare minnow larvae were exposed to environmentally relevant concentrations of DEHP (0, 4.2, 13.3, and 40.8 μg/L) for 6 months. Plasma testosterone and 17β-estradiol levels decreased in females, accompanied by downregulation of cyp19a and cyp17 gene transcription in ovary. Increases in plasma testosterone concentration were observed in males, accompanied by downregulation of cyp19a gene transcription in testes. Hepatic VTG gene transcription was upregulated in males and females. Exposure to DEHP reduced egg production and inhibited oocyte maturation in females and retarded spermiation in males. Decreased egg protein content was measured in F1 embryos. These results indicate that long-term exposure to low concentrations of DEHP (13.3 μg/L) causes endocrine disruption and impairs fish reproduction. - Highlights: • PAEs in the aquatic environment may pose risk to endemic fish species. • Long-term exposure to DEHP affected sex hormone levels in rare minnow. • DEHP affected gonad development. • Long-term exposure caused reduction of fecundity, but not sex ratio. • Environmentally relevant concentrations of DEHP impair fish reproduction. - Long-term exposure to low concentrations of DEHP adversely impact Chinese rare minnow reproduction

  5. I. Effects of a Dopamine Receptor Antagonist on Fathead Minnow, Pimephales promelas ,Reproduction

    Science.gov (United States)

    This study used a 21 d fathead minnow (Pimephales promelas) reproduction assay to test the hypothesis that exposure to the dopamine 2 receptor (D2R) antagonist, haloperidol, would impair fish reproduction. Additionally, a 96 h experiment with fathead minnows and zebrafish (Danio ...

  6. Ecological diversification associated with the benthic-to-pelagic transition by North American minnows.

    Science.gov (United States)

    Burress, E D; Holcomb, J M; Tan, M; Armbruster, J W

    2017-03-01

    Ecological opportunity is often regarded as a key factor that explains why diversity is unevenly distributed across life. Colonization of novel environments or adaptive zones may promote diversification. North American minnows exhibit an ancestral benthic-to-pelagic habitat shift that coincided with a burst in diversification. Here, we evaluate the phenotypic and ecological implications of this habitat shift by assessing craniofacial and dietary traits among 34 species and testing for morphology-diet covariation, convergence and adaptive optima. There were several instances of morphology-diet covariation such as correlations between mouth angle and the consumption of terrestrial insects and between relative gut length and the consumption of algae. After accounting for size and phylogenetic nonindependence, benthic species had longer heads, longer snouts, eyes positioned higher on their head, smaller mouth angles and longer digestive tracts than pelagic minnows. Benthic minnows also consumed more algae but less terrestrial insects, by volume, than pelagic minnows. Lastly, there were three distinct evolutionary regimes and more convergence in morphology and dietary characteristics than expected under a Brownian motion model of evolution. These findings indicate that colonization of the pelagic zone by minnows involved myriad phenotypic and dietary changes associated with exploitation of terrestrial subsidies. Thus, minnows exhibit phenotype-dietary covariation, an expansion of ecological roles and a burst in diversification rates in response to the ecological opportunity afforded by the colonization of a novel habitat. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

  7. A computational model linking oocyte growth and spawning to the hypothalamic-pituitary-gonadal axis in fathead minnow (Pimephales promelas)

    Science.gov (United States)

    Reproduction is vital to the survival of all living organisms, and reproductive toxicity is an important outcome in determining the ecological risks of chemicals in the environment. To evaluate reproductive toxicity, fathead minnow fecundity, as measured by the average number of...

  8. Reproductive and health assessment of fathead minnows (Pimephales promelas) inhabiting a pond containing oil sands process-affected water

    International Nuclear Information System (INIS)

    Kavanagh, Richard J.; Frank, Richard A.; Solomon, Keith R.; Van Der Kraak, Glen

    2013-01-01

    Highlights: ► Fish were collected from a pond containing oil sands process-affected water (OSPW). ► They were compared to fish from two reference sites within the oil sands region. ► Differences in GSIs and tubercle numbers were observed in fish from the OSPW pond. ► Opercula, gills, and 11-KT concentrations also differed in fish from the OSPW pond. ► Black spot and tapeworms were not observed in any of the fish from the OSPW pond. -- Abstract: Previous laboratory based studies have shown that oil sands process-affected waters (OSPWs) containing high concentrations of naphthenic acids (>25 mg/l) have adverse effects on the reproductive physiology of fish. The purpose of this study was to assess the reproductive development and health of a wild population of fathead minnows (Pimephales promelas) inhabiting an OSPW pond that has moderate concentrations of naphthenic acids (∼10 mg/l). Fathead minnows were collected at various times during the period of 2006 through 2008 from Demonstration Pond (OSPW) located at Syncrude Canada Ltd., and two reference sites, Beaver Creek reservoir and Poplar Creek reservoir, which are all north of Fort McMurray, AB, Canada. Condition factor, gill histopathology, gonadosomatic indices, liver somatic indices, male secondary sexual characteristics, and plasma sex steroids were examined. Depending on the time of year that fathead minnows were collected, there were differences in the condition factor, gonadosomatic indices, liver somatic indices, and secondary sexual characteristics of fathead minnows (in males) from Demonstration Pond when compared to the fathead minnows from the reference sites. In comparison to reference fish, lower concentrations of 11-ketotestosterone were measured in the plasma of male fathead minnows collected from Demonstration Pond in June 2006 and July 2007. Black spot disease and Ligula intestinalis were prevalent in fathead minnows from the reference sites but were not observed in fathead minnows

  9. Reproductive and health assessment of fathead minnows (Pimephales promelas) inhabiting a pond containing oil sands process-affected water

    Energy Technology Data Exchange (ETDEWEB)

    Kavanagh, Richard J., E-mail: rkavanag@uoguelph.ca [Department of Integrative Biology, University of Guelph, Guelph, ON, Canada N1G 2W1 (Canada); Frank, Richard A.; Solomon, Keith R. [Centre for Toxicology, University of Guelph, Guelph, ON, Canada N1G 2W1 (Canada); Van Der Kraak, Glen [Department of Integrative Biology, University of Guelph, Guelph, ON, Canada N1G 2W1 (Canada)

    2013-04-15

    Highlights: ► Fish were collected from a pond containing oil sands process-affected water (OSPW). ► They were compared to fish from two reference sites within the oil sands region. ► Differences in GSIs and tubercle numbers were observed in fish from the OSPW pond. ► Opercula, gills, and 11-KT concentrations also differed in fish from the OSPW pond. ► Black spot and tapeworms were not observed in any of the fish from the OSPW pond. -- Abstract: Previous laboratory based studies have shown that oil sands process-affected waters (OSPWs) containing high concentrations of naphthenic acids (>25 mg/l) have adverse effects on the reproductive physiology of fish. The purpose of this study was to assess the reproductive development and health of a wild population of fathead minnows (Pimephales promelas) inhabiting an OSPW pond that has moderate concentrations of naphthenic acids (∼10 mg/l). Fathead minnows were collected at various times during the period of 2006 through 2008 from Demonstration Pond (OSPW) located at Syncrude Canada Ltd., and two reference sites, Beaver Creek reservoir and Poplar Creek reservoir, which are all north of Fort McMurray, AB, Canada. Condition factor, gill histopathology, gonadosomatic indices, liver somatic indices, male secondary sexual characteristics, and plasma sex steroids were examined. Depending on the time of year that fathead minnows were collected, there were differences in the condition factor, gonadosomatic indices, liver somatic indices, and secondary sexual characteristics of fathead minnows (in males) from Demonstration Pond when compared to the fathead minnows from the reference sites. In comparison to reference fish, lower concentrations of 11-ketotestosterone were measured in the plasma of male fathead minnows collected from Demonstration Pond in June 2006 and July 2007. Black spot disease and Ligula intestinalis were prevalent in fathead minnows from the reference sites but were not observed in fathead minnows

  10. Transcriptional expression analysis of ABC efflux transporters and xenobiotic-metabolizing enzymes in the Chinese rare minnow.

    Science.gov (United States)

    Yuan, Lilai; Lv, Biping; Zha, Jinmiao; Wang, Zijian

    2014-05-01

    In the present study, the cDNA fragments of five ABC transporter genes (ABCB1, ABCB11, ABCC1, ABCC2, and ABCG2) in the rare minnow were cloned, and their tissue-specific expression patterns were evaluated across eight rare minnow tissues (liver, gill, intestine, kidney, spleen, brain, skin, and muscle). Furthermore, the transcriptional effects on these ABC transporter genes and five xenobiotic-metabolizing enzyme genes (CYP1A, GSTm, GSTp1, GCLC, and UGT1a) were determined in the rare minnow liver after 12 days of pyrene exposure. Basal expression analysis showed that the tissues with high expression of the ABC transporters included the liver, kidney, and intestine. Moreover, the most highly expressed of the ABC genes were ABCB1 and ABCC2 in all eight of the tissues tested. The ABCB11 gene was almost exclusively expressed in the liver of the rare minnow, whereas ABCC1 and ABCG2 showed weak expression in all eight tissues compared to ABCB1 and ABCC2. Our results provide the first thorough examination of the expression patterns of toxicologically relevant ABC transporters in the rare minnow and serve as a necessary basis for further studies of these ABC transporters in fish. Furthermore, synergistic up-regulation of CYP1A, GSTp1, GCLC, UGT1a, and ABCC2 was observed in the rare minnow liver following pyrene exposure, while GSTm, ABCB1, ABCB11, ABCC1, and ABCG2 were not significantly affected (p ABC transporters by pyrene suggests a possible involvement and cooperation of these genes in the detoxification process in rare minnows. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. InP/ZnS QDs exposure induces developmental toxicity in rare minnow (Gobiocypris rarus) embryos.

    Science.gov (United States)

    Chen, Yao; Yang, Yang; Ou, Fang; Liu, Li; Liu, Xiao-Hong; Wang, Zhi-Jian; Jin, Li

    2018-04-05

    We investigated the in vivo toxicity of InP/ZnS quantum dots (QDs) in Chinese rare minnow (Gobiocypris rarus) embryos. The 72 h post-fertilization (hpf) LC 50 (median lethal concentration) was 1678.007 nmol/L. Rare minnows exposed to InP/ZnS QDs exhibited decreased spontaneous movement, decreased survival and hatchability rates, and an increased malformation rate. Pericardial edema, spinal curvature, bent tails and vitelline cysts were observed. Embryonic Wnt8a and Mstn mRNA levels were significantly up-regulated after InP/ZnS QDs treatment at 48 hpf (200 nmol/L) (p InP/ZnS QDs treatments did not significantly change the Olive tail moments (p > 0.05). Thus, InP/ZnS QDs caused teratogenic effects and death during the development of Chinese rare minnow embryos, but InP/ZnS QDs did not cause significant genetic toxicity during Chinese rare minnow development. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Alternative responses to predation in two headwater stream minnows is reflected in their contrasting diel activity patterns.

    Science.gov (United States)

    Kadye, Wilbert T; Booth, Anthony J

    2014-01-01

    Animals exhibit diel periodicity in their activity in part to meet energy requirements whilst evading predation. A competing hypothesis suggests that partitioning of diel activities is less important because animals capitalise on opportunity. To test these hypotheses we examined the diel activity patterns for two cyprinid minnows, chubbyhead barb Barbus anoplus and the Eastern Cape redfin minnow Pseudobarbus afer that both occur within headwater streams in the Eastern Cape, South Africa. Chubbyhead barbs exhibited consistent nocturnal activity based on both field and laboratory observations. Due to the absence of fish predators within its habitat, its nocturnal behaviour suggests a response to the cost associated with diurnal activity, such as predation risk by diving and wading birds. In contrast, redfin minnows showed high diurnal activity and a shoaling behaviour in the wild, whereas, in the laboratory, they showed high refuge use during the diel cycle. Despite their preference for refuge in the laboratory, they were diurnally active, a behaviour that was consistent with observations in the wild. The diurnal activity of this species suggests a response to the cost associated with nocturnal activity. Such a cost could be inferred from the presence of the longfin eel, a native predator that was active at night, whereas the daytime shoaling behaviour suggests an anti-predator mechanism to diurnal visual predators. The implications of these findings relate to the impacts associated with the potential invasions by non-native piscivores that occur in the mainstem sections. Diurnal activity patterns for redfin minnows, that are IUCN-listed as endangered, may, in part, explain their susceptibility to high predation by visual non-native piscivores, such as bass and trout. In contrast, the nocturnal habits of chubbyhead barbs suggest a probable pre-adaptation to visual predation. The likelihood of invasion by nocturnally-active sharptooth catfish Clarias gariepinus

  13. Alternative responses to predation in two headwater stream minnows is reflected in their contrasting diel activity patterns.

    Directory of Open Access Journals (Sweden)

    Wilbert T Kadye

    Full Text Available Animals exhibit diel periodicity in their activity in part to meet energy requirements whilst evading predation. A competing hypothesis suggests that partitioning of diel activities is less important because animals capitalise on opportunity. To test these hypotheses we examined the diel activity patterns for two cyprinid minnows, chubbyhead barb Barbus anoplus and the Eastern Cape redfin minnow Pseudobarbus afer that both occur within headwater streams in the Eastern Cape, South Africa. Chubbyhead barbs exhibited consistent nocturnal activity based on both field and laboratory observations. Due to the absence of fish predators within its habitat, its nocturnal behaviour suggests a response to the cost associated with diurnal activity, such as predation risk by diving and wading birds. In contrast, redfin minnows showed high diurnal activity and a shoaling behaviour in the wild, whereas, in the laboratory, they showed high refuge use during the diel cycle. Despite their preference for refuge in the laboratory, they were diurnally active, a behaviour that was consistent with observations in the wild. The diurnal activity of this species suggests a response to the cost associated with nocturnal activity. Such a cost could be inferred from the presence of the longfin eel, a native predator that was active at night, whereas the daytime shoaling behaviour suggests an anti-predator mechanism to diurnal visual predators. The implications of these findings relate to the impacts associated with the potential invasions by non-native piscivores that occur in the mainstem sections. Diurnal activity patterns for redfin minnows, that are IUCN-listed as endangered, may, in part, explain their susceptibility to high predation by visual non-native piscivores, such as bass and trout. In contrast, the nocturnal habits of chubbyhead barbs suggest a probable pre-adaptation to visual predation. The likelihood of invasion by nocturnally-active sharptooth catfish

  14. SURROGATE SPECIES IN ASSESSING CONTAMINANT RISK FOR ENDANGERED FISHES

    Science.gov (United States)

    Rainbow trout, fathead minnows, and sheepshead minnows were tested as surrogate species to assess contaminant risk for 17 endangered fishes and one toad species. Acute toxicity tests were conducted with carbaryl, copper, 4-nonylphenol, pentachlorophenol, and permethrin in accord...

  15. Conversion of environmental estrone to estradiol by male fathead minnows

    Data.gov (United States)

    U.S. Environmental Protection Agency — This data set describes experiments that were conducted to investigate whether exposure of male fathead minnows to environmentally-relevant estrone concentrations...

  16. Vinclozolin affects the interrenal system of the rare minnow (Gobiocypris rarus).

    Science.gov (United States)

    Yang, Lihua; Zha, Jinmiao; Li, Wei; Li, Zhaoli; Wang, Zijian

    2011-07-01

    Vinclozolin, a widely used fungicide, has been characterized as a potent androgen antagonist. In this study, the effects of vinclozolin on the interrenal system of the rare minnow (Gobiocypris rarus) were evaluated. The results revealed a decline of the renal somatic index (RSI) and the presence of histopathological effects, including shrinkage of the glomerulus and expansion of the Bowman's space in the kidneys, in rare minnows exposed to vinclozolin. Elevated plasma cortisol concentrations in females exposed to ≥ 2 μg/L vinclozolin and males exposed to ≥ 10 μg/L vinclozolin (pvinclozolin exposure. Significant decreases in mRNA levels of interrenal crf, pomc, gr, and nka in females and gr and nka in males were observed after exposure to ≥ 0.5 μg/L and 2 μg/L vinclozolin (pvinclozolin exposure. In conclusion, vinclozolin exposure evoked endocrine stress on the hypothalamic-pituitary-interrenal axis in the rare minnow, and the interrenal tissue was more sensitive than the brain tissue to stress caused by vinclozolin exposure. These results provide additional data about the modes of toxicological action of vinclozolin. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. First Generation Annotations for the Fathead Minnow (Pimephales promelas) Genome

    Data.gov (United States)

    U.S. Environmental Protection Agency — The fathead minnow (Pimephales promelas) is a laboratory model organism widely used in regulatory toxicity testing and ecotoxicology research. Despite, the wealth of...

  18. DEVELOPMENT OF MONOCLONAL ANTIBODIES AGAINST FATHEAD MINNOW (PIMEPHALES PROMELAS) VITELLOGENIN

    Science.gov (United States)

    We have obtained a panel of monoclonal antibodies directed against fathead minnow vitellogenin (Vtg) for use in sensitive ELISAs to quantify the response of exposure in vivo to estrogen or estrogen mimics.

  19. NMR analysis of male fathead minnow urinary metabolites: A potential approach for studying impacts of chemical exposures

    Energy Technology Data Exchange (ETDEWEB)

    Ekman, D.R. [Ecosystems Research Division, U.S. EPA, 960 College Station Road, Athens, GA 30605 (United States)], E-mail: ekman.drew@epa.gov; Teng, Q. [Ecosystems Research Division, U.S. EPA, 960 College Station Road, Athens, GA 30605 (United States); Jensen, K.M.; Martinovic, D.; Villeneuve, D.L.; Ankley, G.T. [Mid-Continent Ecology Division, U.S. EPA, 6201 Congdon Boulevard, Duluth, MN 55804 (United States); Collette, T.W. [Ecosystems Research Division, U.S. EPA, 960 College Station Road, Athens, GA 30605 (United States)

    2007-11-30

    The potential for profiling metabolites in urine from male fathead minnows (Pimephales promelas) to assess chemical exposures was explored using nuclear magnetic resonance (NMR) spectroscopy. Both one-dimensional (1D) and two-dimensional (2D) NMR spectroscopy was used for the assignment of metabolites in urine from unexposed fish. Because fathead minnow urine is dilute, we lyophilized these samples prior to analysis. Furthermore, 1D {sup 1}H NMR spectra of unlyophilized urine from unexposed male fathead minnow and Sprague-Dawley rat were acquired to qualitatively compare rat and fish metabolite profiles and to provide an estimate of the total urinary metabolite pool concentration difference. As a small proof-of-concept study, lyophilized urine samples from male fathead minnows exposed to three different concentrations of the antiandrogen vinclozolin were analyzed by 1D {sup 1}H NMR to assess exposure-induced changes. Through a combination of principal components analysis (PCA) and measurements of {sup 1}H NMR peak intensities, several metabolites were identified as changing with statistical significance in response to exposure. Among those changes occurring in response to exposure to the highest concentration (450 {mu}g/L) of vinclozolin were large increases in taurine, lactate, acetate, and formate. These increases coincided with a marked decrease in hippurate, a combination potentially indicative of hepatotoxicity. The results of these investigations clearly demonstrate the potential utility of an NMR-based approach for assessing chemical exposures in male fathead minnow, using urine collected from individual fish.

  20. NMR analysis of male fathead minnow urinary metabolites: A potential approach for studying impacts of chemical exposures

    International Nuclear Information System (INIS)

    Ekman, D.R.; Teng, Q.; Jensen, K.M.; Martinovic, D.; Villeneuve, D.L.; Ankley, G.T.; Collette, T.W.

    2007-01-01

    The potential for profiling metabolites in urine from male fathead minnows (Pimephales promelas) to assess chemical exposures was explored using nuclear magnetic resonance (NMR) spectroscopy. Both one-dimensional (1D) and two-dimensional (2D) NMR spectroscopy was used for the assignment of metabolites in urine from unexposed fish. Because fathead minnow urine is dilute, we lyophilized these samples prior to analysis. Furthermore, 1D 1 H NMR spectra of unlyophilized urine from unexposed male fathead minnow and Sprague-Dawley rat were acquired to qualitatively compare rat and fish metabolite profiles and to provide an estimate of the total urinary metabolite pool concentration difference. As a small proof-of-concept study, lyophilized urine samples from male fathead minnows exposed to three different concentrations of the antiandrogen vinclozolin were analyzed by 1D 1 H NMR to assess exposure-induced changes. Through a combination of principal components analysis (PCA) and measurements of 1 H NMR peak intensities, several metabolites were identified as changing with statistical significance in response to exposure. Among those changes occurring in response to exposure to the highest concentration (450 μg/L) of vinclozolin were large increases in taurine, lactate, acetate, and formate. These increases coincided with a marked decrease in hippurate, a combination potentially indicative of hepatotoxicity. The results of these investigations clearly demonstrate the potential utility of an NMR-based approach for assessing chemical exposures in male fathead minnow, using urine collected from individual fish

  1. First generation annotations for the fathead minnow (Pimephales promelas) genome

    Science.gov (United States)

    Ab initio gene prediction and evidence alignment were used to produce the first annotations for the fathead minnow SOAPdenovo genome assembly. Additionally, a genome browser hosted at genome.setac.org provides simplified access to the annotation data in context with fathead minno...

  2. Beneficial effect of a high number of copies of salivary amylase AMY1 gene on obesity risk in Mexican children.

    Science.gov (United States)

    Mejía-Benítez, María A; Bonnefond, Amélie; Yengo, Loïc; Huyvaert, Marlène; Dechaume, Aurélie; Peralta-Romero, Jesús; Klünder-Klünder, Miguel; García Mena, Jaime; El-Sayed Moustafa, Julia S; Falchi, Mario; Cruz, Miguel; Froguel, Philippe

    2015-02-01

    Childhood obesity is a major public health problem in Mexico, affecting one in every three children. Genome-wide association studies identified genetic variants associated with childhood obesity, but a large missing heritability remains to be elucidated. We have recently shown a strong association between a highly polymorphic copy number variant encompassing the salivary amylase gene (AMY1 also known as AMY1A) and obesity in European and Asian adults. In the present study, we aimed to evaluate the association between AMY1 copy number and obesity in Mexican children. We evaluated the number of AMY1 copies in 597 Mexican children (293 obese children and 304 normal weight controls) through highly sensitive digital PCR. The effect of AMY1 copy number on obesity status was assessed using a logistic regression model adjusted for age and sex. We identified a marked effect of AMY1 copy number on reduced risk of obesity (OR per estimated copy 0.84, with the number of copies ranging from one to 16 in this population; p = 4.25 × 10(-6)). The global association between AMY1 copy number and reduced risk of obesity seemed to be mostly driven by the contribution of the highest AMY1 copy number. Strikingly, all children with >10 AMY1 copies were normal weight controls. Salivary amylase initiates the digestion of dietary starch, which is highly consumed in Mexico. Our current study suggests putative benefits of high number of AMY1 copies (and related production of salivary amylase) on energy metabolism in Mexican children.

  3. FIELD VALIDATION OF A SHEEPSHEAD MINNOW ESTROGEN-RESPONSIVE CDNA MACROARRAY

    Science.gov (United States)

    Hemmer, Michael J., Iris Knoebl, Becky L. Hemmer, Patrick Larkin, Peggy S. Harris and Nancy D. Denslow. In press. Field Validation of a Sheepshead Minnow Estrogen-Responsive cDNA Macroarray (Abstract). To be presented at the SETAC Fourth World Congress, 14-18 November 2004, Portl...

  4. Effect of exposure to wastewater treatment plant effluent on fathead minnow reproduction

    Data.gov (United States)

    U.S. Environmental Protection Agency — Adult fathead minnows were exposed to dilutions of a historically estrogenic wastewater treatment plant effluent in a 21-d reproduction study. This dataset is...

  5. Early development and larval behaviour of a minnow, Barbus ...

    African Journals Online (AJOL)

    The chubbyhead barb, Barbus anoplus, underwent a population explosion in the early phases of filling of Lake be Roux on the Orange River. This successful colonization was possibly related to the survival strategy of the young stages of this minnow. It is suggested that some of the development traits of B. anoplus enabled ...

  6. Taxonomy Icon Data: fathead minnow [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available fathead minnow Pimephales promelas Chordata/Vertebrata/Pisciformes Pimephales_promela...s_L.png Pimephales_promelas_NL.png Pimephales_promelas_S.png Pimephales_promelas_NS.png http://bioscienced...bc.jp/taxonomy_icon/icon.cgi?i=Pimephales+promelas&t=L http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Pimephales+promela...s&t=NL http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Pimephales+promela...s&t=S http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Pimephales+promelas&t=NS ...

  7. EXPRESSION PROFILING OF ESTROGENIC COMPOUNDS USING A SHEEPSHEAD MINNOW CDNA MACROARRAY

    Science.gov (United States)

    Larkin, Patrick, Leroy C. Folmar, Michael J. Hemmer, Arianna J. Poston and Nancy D. Denslow. 2003. Expression Profiling of Estrogenic Compounds Using a Sheepshead Minnow cDNA Macroarray. Environ. Health Perspect. 111(6):839-846. (ERL,GB 1171). A variety of anthropogenic c...

  8. ASSOCIATIONS BETWEEN GENETIC DIVERSITY AND ANTHROPOGENIC DISTURBANCE IN MIDWESTERN STREAM-DWELLING MINNOWS

    Science.gov (United States)

    Anthropogenic disturbances may leave imprints on patterns of intraspecific genetic diversity through their effects on population size, adaptation, migration, and mutation. We examined patterns of genetic diversity for a stream-dwelling minnow (the central stoneroller, Campostoma...

  9. Environmental hormones and their impacts on sex differentiation in fathead minnows

    Science.gov (United States)

    Runoff from lands fertilized with animal manure from concentrated animal feeding operations (CAFOs) is a source of hormones to surface water. To test the hypothesis that juvenile fathead minnows exposed to sex steroids singly and in a “typical” CAFO mixture while undergoing sex...

  10. Bisphenol A induces spermatocyte apoptosis in rare minnow Gobiocypris rarus

    International Nuclear Information System (INIS)

    Zhang, Yingying; Cheng, Mengqian; Wu, Lang; Zhang, Guo; Wang, Zaizhao

    2016-01-01

    Highlights: • Adult male G. rarus were exposed to 225 μg/L BPA for 7, 21 and 63 days. • BPA could induce spermatocyte apoptosis in rare minnow testis. • The mitochondrial apoptotic pathway participated in the germ cell apoptosis. • The spermatocyte apoptosis was likely initiated by BPA induced meiosis arrest. - Abstract: Bisphenol A (BPA) is an endocrine disruptor, and could induce germ cells apoptosis in the testis of mammals. But whether it could affect fish in the same mechanism has not’ been studied till now. In the present study, to investigate the influence of BPA on testis germ cells in fish, adult male rare minnow Gobiocypris rarus were exposed to 225 μg L"−"1 (0.99 μM) BPA for 1, 3 and 9 weeks. Through TdT-mediated dUTP nick end labeling (TUNEL) and transmission electron microscope (TEM) analysis, we found that the amount of apoptotic spermatocytes significantly increased in a time dependent manner following BPA exposure. Western Blot results showed that the ratio of Bcl2/Bax, the important apoptosis regulators in intrinsic mitochondrial apoptotic pathway, was significantly decreased. qPCR showed that mRNA expression of several genes in mitochondrial apoptotic pathway including bcl2, bax, casp9, cytc and mcl1b were significantly changed following BPA exposure. In addition, mRNA expression of meiosis regulation genes (kpna7 and wee2), and genes involved in both apoptosis and meiosis (birc5, ccna1, and gsa1a) were also affected by BPA. Taken together, the present study demonstrated that BPA could induce spermatocytes apoptosis in rare minnow testis, and the apoptosis was probably under regulation of intrinsic mitochondrial apoptotic pathway. Moreover, the spermatocyte apoptosis was likely initiated by BPA induced meiosis arrest.

  11. Bisphenol A induces spermatocyte apoptosis in rare minnow Gobiocypris rarus

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yingying; Cheng, Mengqian; Wu, Lang; Zhang, Guo; Wang, Zaizhao, E-mail: zzwang@nwsuaf.edu.cn

    2016-10-15

    Highlights: • Adult male G. rarus were exposed to 225 μg/L BPA for 7, 21 and 63 days. • BPA could induce spermatocyte apoptosis in rare minnow testis. • The mitochondrial apoptotic pathway participated in the germ cell apoptosis. • The spermatocyte apoptosis was likely initiated by BPA induced meiosis arrest. - Abstract: Bisphenol A (BPA) is an endocrine disruptor, and could induce germ cells apoptosis in the testis of mammals. But whether it could affect fish in the same mechanism has not’ been studied till now. In the present study, to investigate the influence of BPA on testis germ cells in fish, adult male rare minnow Gobiocypris rarus were exposed to 225 μg L{sup −1} (0.99 μM) BPA for 1, 3 and 9 weeks. Through TdT-mediated dUTP nick end labeling (TUNEL) and transmission electron microscope (TEM) analysis, we found that the amount of apoptotic spermatocytes significantly increased in a time dependent manner following BPA exposure. Western Blot results showed that the ratio of Bcl2/Bax, the important apoptosis regulators in intrinsic mitochondrial apoptotic pathway, was significantly decreased. qPCR showed that mRNA expression of several genes in mitochondrial apoptotic pathway including bcl2, bax, casp9, cytc and mcl1b were significantly changed following BPA exposure. In addition, mRNA expression of meiosis regulation genes (kpna7 and wee2), and genes involved in both apoptosis and meiosis (birc5, ccna1, and gsa1a) were also affected by BPA. Taken together, the present study demonstrated that BPA could induce spermatocytes apoptosis in rare minnow testis, and the apoptosis was probably under regulation of intrinsic mitochondrial apoptotic pathway. Moreover, the spermatocyte apoptosis was likely initiated by BPA induced meiosis arrest.

  12. Sex-specific gonadal and gene expression changes throughout development in fathead minnow

    Science.gov (United States)

    Although fathead minnows (Pimephales promelas) are commonly used as a model fish in endocrine disruption studies, none have characterized sex-specific baseline expression of genes involved in sex differentiation during development in this species. Using a sex-linked DNA marker t...

  13. Comparison of catch per unit effort among four minnow trap models in the three-spined stickleback (Gasterosteus aculeatus) fishery.

    Science.gov (United States)

    Budria, Alexandre; DeFaveri, Jacquelin; Merilä, Juha

    2015-12-21

    Minnow traps are commonly used in the stickleback (Gasterostidae) fishery, but the potential differences in catch per unit effort (CPUE) among different minnow trap models are little studied. We compared the CPUE of four different minnow trap models in field experiments conducted with three-spined sticklebacks (Gasterosteus aculeatus). Marked (up to 26 fold) differences in median CPUE among different trap models were observed. Metallic uncoated traps yielded the largest CPUE (2.8 fish/h), followed by metallic black nylon-coated traps (1.3 fish/h). Collapsible canvas traps yielded substantially lower CPUEs (black: 0.7 fish/h; red: 0.1 fish/h) than the metallic traps. Laboratory trials further revealed significant differences in escape probabilities among the different trap models. While the differences in escape probability can explain at least part of the differences in CPUE among the trap models (e.g. high escape rate and low CPUE in red canvas traps), discrepancies between model-specific CPUEs and escape rates suggests that variation in entrance rate also contributes to the differences in CPUE. In general, and in accordance with earlier data on nine-spined stickleback (Pungitius pungitius) trapping, the results suggest that uncoated metallic (Gee-type) traps are superior to the other commonly used minnow trap models in stickleback fisheries.

  14. Free-to-play: About addicted Whales, at risk Dolphins and healthy Minnows. Monetarization design and Internet Gaming Disorder.

    Science.gov (United States)

    Dreier, M; Wölfling, K; Duven, E; Giralt, S; Beutel, M E; Müller, K W

    2017-01-01

    Video games are not only changing due to technical innovation, but also because of new game design and monetization approaches. Moreover, elite gamer groups with financial in-game-investments co-finance all users of free-to-play-games. Besides questions on youth protection, the growing popularity of free-to-play games has fostered discussions on supposed associations to Internet Gaming Disorder (IGD). Children and adolescents using free-to-play browser games were examined in a German school-based representative study (N=3967; age range 12 to 18). Based on a clinical self-report AICA-S (Wölfling et al., 2011), students were categorized into non-problematic, risky, and addicted users. Psycho-social problems (SDQ; Goodman, 1997), perceived stress (PSS; Cohen, Kamarck & Mermelstein, 1983), coping strategies (BriefCOPE; Carver, 1997), and Average Revenue per (Paying) User (ARPU) were investigated as dependent variables. Furthermore, an industry classification (Freeloaders, Minnows, Dolphins, and Whales) for free-to-play gamers was used for additional relations regarding IGD, SDQ, PSS, BriefCOPE, and ARPU. Among free-to-play gamers the prevalence of IGD amounted to 5.2%. Subjects classified with IGD displayed higher psycho-social symptoms than non-problematic users, reported higher degrees of perceived stress, and applied dysfunctional coping strategies more frequently. Additionally, we found a higher ARPU among subjects with IGD. ARPU is significantly associated with IGD. Whales share significant characteristics with addicted video gamers; Dolphins might be classified as risky consumers; Minnows and Freeloaders are rather non-pathological gamers. Vulnerability for stress, dysfunctional coping, and free-to-play gaming represent an unhealthy combination. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. A new bacilliform fathead minnow rhabdovirus that produces syncytia in tissue culture.

    Science.gov (United States)

    Iwanowicz, L R; Goodwin, A E

    2002-05-01

    A pathogenic bacilliform virus 130-180 nm in length and 31-47 nm in diameter was isolated from moribund fathead minnows (Pimephales promelas) exhibiting hemorrhages in their eyes and skin. A cytopathic effect of multifocal syncytia was observed in the epithelioma papulosum cyprini cell line after a 48 h incubation at 20 degrees C. A similar cytopathic effect was also observed in other cell lines tested, but not in bluegill fry, koi fin, or Chinook salmon embryo cells. The filterable agent was inactivated by exposure to 50 degrees C for 10 min, 20% ether, 2 and 50% chloroform, pH 3, and pH 10, was unaffected by 5'-iodo-2 deoxyuridine, and appeared bacilliform and occasionally bullet-shaped by electron microscopy. These results are consistent with those of rhabdoviruses. Immunodot blots performed with antisera against selected fish rhabdoviruses, an aquareovirus, and a birnavirus were all negative. River's postulates were fulfilled in fathead minnows, but the agent did not replicate or cause disease in other cyprinids or salmonids during challenge experiments. Hepatic, splenic, and renal lesions were observed during histological analysis of diseased fish from viral challenges and from the original case. Structural proteins resolved via SDS-PAGE had molecular weights similar to those reported in lyssaviruses of the family Rhabdoviridae; however, syncytia formation is not a typical cytopathic effect of rhabdoviruses. This virus, has tentatively been named the fathead minnow rhabdovirus (FHMRV) and is most similar to the members of the family Rhabdoviridae, but atypical properties like syncytia formation may justify the assignment to a novel taxon.

  16. SEQUENCING AND DE NOVO DRAFT ASSEMBLIES OF A FATHEAD MINNOW (Pimpehales promelas) reference genome

    Data.gov (United States)

    U.S. Environmental Protection Agency — The dataset provides the URLs for accessing the genome sequence data and two draft assemblies as well as fathead minnow genotyping data associated with estimating...

  17. Quantitative PCR Assays for Detecting Loach Minnow (Rhinichthys cobitis and Spikedace (Meda fulgida in the Southwestern United States.

    Directory of Open Access Journals (Sweden)

    Joseph C Dysthe

    Full Text Available Loach minnow (Rhinichthys cobitis and spikedace (Meda fulgida are legally protected with the status of Endangered under the U.S. Endangered Species Act and are endemic to the Gila River basin of Arizona and New Mexico. Efficient and sensitive methods for monitoring these species' distributions are critical for prioritizing conservation efforts. We developed quantitative PCR assays for detecting loach minnow and spikedace DNA in environmental samples. Each assay reliably detected low concentrations of target DNA without detection of non-target species, including other cyprinid fishes with which they co-occur.

  18. Mitochondrial DNA copy number and chronic lymphocytic leukemia/small lymphocytic lymphoma risk in two prospective studies

    NARCIS (Netherlands)

    Kim, Christopher; Bassig, Bryan A; Seow, Wei Jie; Hu, Wei; Purdue, Mark P; Huang, Wen-Yi; Liu, Chin-San; Cheng, Wen-Ling; Männistö, Satu; Vermeulen, Roel; Weinstein, Stephanie J; Lim, Unhee; Hosgood, H Dean; Bonner, Matthew R; Caporaso, Neil E; Albanes, Demetrius; Lan, Qing; Rothman, Nathaniel

    BACKGROUND: Mitochondrial DNA copy number (mtDNA CN) may be modified by mitochondria in response to oxidative stress. Previously, mtDNA CN was associated with non-Hodgkin lymphoma (NHL) risk, particularly chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). We conducted a replication

  19. FATHEAD MINNOW VITELLOGENIN: CDNA SEQUENCE AND MRNA AND PROTEIN EXPRESSION AFTER 17 BETA-ESTRADIOL TREATMENT

    Science.gov (United States)

    In the present study, a sensitive ribonuclease protection assay (RPA) for VTG mRNA was developed for the fathead minnow (Pimephales promelas), a species proposed for routine endocrine-disrupting chemical (EDC) screening.

  20. 75 FR 7625 - Endangered and Threatened Wildlife and Plants; Rio Grande Silvery Minnow (Hybognathus amarus...

    Science.gov (United States)

    2010-02-22

    ... modification of its habitat due to dewatering and diversion of water, water impoundment, and modification of... thorough knowledge of the Rio Grande silvery minnow's life history, ecology, and behavior, and the current...

  1. Alternative methods for toxicity assessments in fish: comparison of the fish embryo toxicity and the larval growth and survival tests in zebrafish and fathead minnows.

    Science.gov (United States)

    Jeffries, Marlo K Sellin; Stultz, Amy E; Smith, Austin W; Rawlings, Jane M; Belanger, Scott E; Oris, James T

    2014-11-01

    An increased demand for chemical toxicity evaluations has resulted in the need for alternative testing strategies that address animal welfare concerns. The fish embryo toxicity (FET) test developed for zebrafish (Danio rerio) is one such alternative, and the application of the FET test to other species such as the fathead minnow (Pimephales promelas) has been proposed. In the present study, the performances of the FET test and the larval growth and survival (LGS; a standard toxicity testing method) test in zebrafish and fathead minnows were evaluated. This required that testing methods for the fathead minnow FET and zebrafish LGS tests be harmonized with existing test methods and that the performance of these testing strategies be evaluated by comparing the median lethal concentrations of 2 reference toxicants, 3,4-dicholoraniline and ammonia, obtained via each of the test types. The results showed that procedures for the zebrafish FET test can be adapted and applied to the fathead minnow. Differences in test sensitivity were observed for 3,4-dicholoraniline but not ammonia; therefore, conclusions regarding which test types offer the least or most sensitivity could not be made. Overall, these results show that the fathead minnow FET test has potential as an alternative toxicity testing strategy and that further analysis with other toxicants is warranted in an effort to better characterize the sensitivity and feasibility of this testing strategy. © 2014 SETAC.

  2. Sequencing and De novo Draft Assemblies of the Fathead Minnow (Pimphales promelas)Reference Genome

    Science.gov (United States)

    This study was undertaken to develop genome-scale resources for the fathead minnow (Pimphales promelas) an important model organism widely used in both aquatic ecotoxicology research and in regulatory toxicity testing. We report on the first sequencing and two draft assemblies fo...

  3. Transcription of Key Genes Regulating Gonadal Steroidogenesis in Control and Ketoconazole- or Vinclozolin-exposed Fathead Minnows

    Science.gov (United States)

    This paper provides the first report on the effects of two endocrine-active fungicides, ketoconazole and vinclozolin, on the expression of steroidogenesis-related genes in the testis of male fathead minnows.

  4. Toxicogenomic analysis of the hepatic effects of perfluorooctanoic acid on rare minnows (Gobiocypris rarus)

    International Nuclear Information System (INIS)

    Wei Yanhong; Liu Yang; Wang Jianshe; Tao Yi; Dai Jiayin

    2008-01-01

    Perfluorooctanoic acid (PFOA) is a ubiquitous environmental contaminant that has been detected in a variety of terrestrial and aquatic organisms. To assess the effects of PFOA in fish and predict its potential mode of action, a toxicogenomic approach was applied to hepatic gene expression profile analysis in male and female rare minnows (Gobiocypris rarus) using a custom cDNA microarray containing 1773 unique genes. Rare minnows were treated with continuous flow-through exposure to PFOA at concentrations of 3, 10, and 30 mg/L for 28 days. Based on the observed histopathological changes, the livers from fish exposed to 10 mg/L PFOA were selected for further hepatic gene expression analysis. While 124 and 171 genes were significantly altered by PFOA in males and females, respectively, of which 43 genes were commonly regulated in both sexes. The affected genes are involved in multiple biological processes, including lipid metabolism and transport, hormone action, immune responses, and mitochondrial functions. PFOA exposure significantly suppressed genes involved in fatty acid biosynthesis and transport but induced genes associated with intracellular trafficking of cholesterol. Alterations in expression of genes associated with mitochondrial fatty acid β-oxidation were only observed in female rare minnows. In addition, PFOA inhibited genes responsible for thyroid hormone biosynthesis and significantly induced estrogen-responsive genes. These findings implicate PFOA in endocrine disruption. This work contributes not only to the elucidation of the potential mode of toxicity of PFOA to aquatic organisms but also to the use of toxicogenomic approaches to address issues in environmental toxicology

  5. Tissue lead concentration during chronic exposure of Pimephales promelas (fathead minnow) to lead nitrate in aquarium water.

    Science.gov (United States)

    Spokas, Eric G; Spur, Bernd W; Smith, Holly; Kemp, Francis W; Bogden, John D

    2006-11-01

    The fathead minnow is a useful species for evaluating the toxicity of wastewater effluents. While this fish is widely used for "survival" studies of metal toxicity, little or no work has been done on the tissue distribution of metals in fathead minnows. To determine the distribution of tissue lead, aquarium studies were conducted for several weeks with fish maintained in soft synthetic freshwater. Lead- (II) nitrate was added to three aquaria attaining concentrations of 20-30 ppb (aquarium B), 100-140 ppb (aquarium C), and roughly 200 ppb (aquarium D). Results were compared to controls (aquarium A). During the initial week, the majority of aquarium D fish died, whereas few deaths occurred in the other groups. Lead accumulation was dose- and tissue-dependent, with highest uptake by the gills. Gill concentrations of aquarium D fish averaged about 4-fold higherthan in skeleton or skin and muscle. In vitro, lead (2.5-25 ppm) caused dose-dependent reductions in the ratio of reduced glutathione/oxidized glutathione (GSH/GSSG) in gills incubated in physiological buffer. These findings demonstrate that fathead minnow gills bind and accumulate waterborne lead rapidly and preferentially and raise the possibility that gill lipid peroxidation contributes to lead toxicity at low water hardness.

  6. CHRONIC EFFECTS OF THE HERBICIDE DIURON ON FRESHWATER CLADOCERANS,AMPHIPODS,MIDGES,MINNOWS,WORMS, AND SNAILS

    Science.gov (United States)

    The chronic effects of the herbicide diuron on survival and reproduction of Daphnia pulex, and survival and growth of the amphipod Hyalella azteca, the midge Chironomus tentans, juvenile and embro/larval fathead minnows, Pimephales promelas, annelid worms, Lumbriculus variegatus,...

  7. Laboratory technique for obtaining fathead minnow eggs for use in toxicity experiments

    International Nuclear Information System (INIS)

    Till, J.E.

    1977-01-01

    A laboratory technique for collecting freshly fertilized eggs of the fathead minnow (Pimephales promelas) has been developed for use in toxicity testing of radioactive materials or other environmental pollutants. The fathead minnow egg was selected as a test organism because the period of embryogenesis is relatively short, the number of eggs per spawning is sufficiently large to provide a test group and a control group, and the size of the parent fish is compatible with laboratory facilities. Under a controlled laboratory environment, eggs are available all year. Nesting sites were constructed by cutting plastic pipe in half and covering the inside of the pipe with 1-mm-thick translucent polyethylene. The polyethylene with the eggs attached was removed from the shelter and cut into two pieces, each piece containing approximately the same number of eggs. One piece of polyethylene was floated in the test solution, and the other in spring water as a control. Hatching occurs in 168 h at 24 0 C. Toxicity of the test solution may be scored on the percentage of eggs hatching, the number of abnormal larvae produced, and larval survival

  8. Fathead minnows (Pimephales promelas) and goldfish (Carassius auratus) as standard fish in bioassays and their reaction to potential reference toxicants

    Energy Technology Data Exchange (ETDEWEB)

    Adelman, I.R.; Smith, L.L. Jr.

    1976-02-01

    Fathead minnows (Pimephales promelas) and goldfish (Carassius auratus) were compared for their suitability as standard bioassay fish. Both species showed the same variability of bioassay results when tested with four toxicants. Fathead minnows are recommended on the basis of their small size and on their capability for use in complete life cycle tests. On the basis of minimum variability of bioassay results, sodium chloride was superior for use as a reference toxicant. Both sodium chloride and pentachlorophenol seemed capable of detecting abnormal fish. On the basis of seven listed criteria either sodium chloride or pentachlorophenol would be acceptable as a reference toxicant.

  9. EVALUATING THE EFFECTS OF FLY ASH EXPOSURE ON FISH EARLY LIFE STAGES: FATHEAD MINNOW EMBRYO-LARVAL TESTS

    Energy Technology Data Exchange (ETDEWEB)

    Greeley Jr, Mark Stephen [ORNL; Elmore, Logan R [ORNL; McCracken, Kitty [ORNL

    2012-05-01

    current technical manuscript); (3) additional laboratory experimentation focused on the potential effects of long-term exposures to fly ash on fish survival and reproductive competence; and (4) a combined field and laboratory study examining the in vitro developmental success of embryos and larvae obtained from fish exposed in vivo for over two years to fly ash in the Emory and Clinch Rivers. These fish reproduction and early life-stage studies are being conducted in conjunction with a broader biological monitoring program administered by TVA that includes a field study of the condition of larval fish in the Emory and Clinch Rivers along with assessments of water quality, sediment composition, ecotoxicological studies, terrestrial wildlife studies, and human and ecological risk assessment. Information and data generated from these studies will provide direct input into risk assessment efforts and will also complement and help support other phases of the overall biomonitoring program. Fish eggs, in general, are known to be capable of concentrating heavy metals and other environmental contaminants from water-borne exposures during embryonic development (Jezierska and others 2009), and fathead minnow embryos in particular have been shown to concentrate methylmercury (Devlin 2006) as well as other chemical toxicants. This technical report focuses on the responses of fathead minnow embryos to simple contact exposures to fly ash in laboratory toxicity tests adapted from a standard fathead minnow (Pimephales promelas) 7-d embryo-larval survival and teratogenicity test (method 1001.0 in EPA 2002) with mortality, hatching success, and the incidences of developmental abnormalities as measured endpoints.

  10. MAXIMIZING GROWTH AND SEXUAL MATURATION OF SHEEPSHEAD MINNOWS IN SUPPORT OF MULTI-GENERATION TEST DEVELOPMENT

    Science.gov (United States)

    Hemmer, R.L., G.M. Cripe and L.R. Goodman. In press. Maximizing Growth and Sexual Maturation of Sheepshead Minnows (Cyprinodon variegatus) in Support of Multi-Generation Test Development (Abstract). To be presented at the SETAC Fourth World Congress, 14-18 November 2004, Portland...

  11. Predicting Adaptive Response to Fadrozole Exposure:Computational Model of the Fathead MinnowsHypothalamic-Pituitary-Gonadal Axis

    Science.gov (United States)

    Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We are developing a mechanistic mathematical model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict doseresponse and time-course (...

  12. Mitochondrial DNA copy number in peripheral blood cell and hypertension risk among mining workers: a case-control study in Chinese coal miners.

    Science.gov (United States)

    Lei, L; Guo, J; Shi, X; Zhang, G; Kang, H; Sun, C; Huang, J; Wang, T

    2017-09-01

    Alteration of mitochondrial DNA (mtDNA) copy number, which reflects oxidant-induced cell damage, has been observed in a wide range of human diseases. However, whether it correlates with hypertension has not been elucidated. We aimed to explore the association between mtDNA copy number and the risk of hypertension in Chinese coal miners. A case-control study was performed with 378 hypertension patients and 325 healthy controls in a large coal mining group located in North China. Face-to-face interviews were conducted by trained staffs with necessary medical knowledge. The mtDNA copy number was measured by a quantitative real-time PCR assay using DNA extracted from peripheral blood. No significant differences in mtDNA copy number were observed between hypertension patients and healthy controls. However, in both case and control groups, the mtDNA copy number was statistically significantly lower in the elder population (≥45 years old) compared with the younger subjects (associated with hypertension in coal miners.

  13. Predicting Adaptive Response to Fadrozole Exposure: Computational Model of the Fathead Minnow Hypothalamic-Pituitary-Gonadal Axis

    Science.gov (United States)

    Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We are developing a mechanistic mathematical model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict dose-response and time-course (...

  14. Probabilistic quantitative microbial risk assessment model of norovirus from wastewater irrigated vegetables in Ghana using genome copies and fecal indicator ratio conversion for estimating exposure dose.

    Science.gov (United States)

    Owusu-Ansah, Emmanuel de-Graft Johnson; Sampson, Angelina; Amponsah, Samuel K; Abaidoo, Robert C; Dalsgaard, Anders; Hald, Tine

    2017-12-01

    The need to replace the commonly applied fecal indicator conversions ratio (an assumption of 1:10 -5 virus to fecal indicator organism) in Quantitative Microbial Risk Assessment (QMRA) with models based on quantitative data on the virus of interest has gained prominence due to the different physical and environmental factors that might influence the reliability of using indicator organisms in microbial risk assessment. The challenges facing analytical studies on virus enumeration (genome copies or particles) have contributed to the already existing lack of data in QMRA modelling. This study attempts to fit a QMRA model to genome copies of norovirus data. The model estimates the risk of norovirus infection from the intake of vegetables irrigated with wastewater from different sources. The results were compared to the results of a corresponding model using the fecal indicator conversion ratio to estimate the norovirus count. In all scenarios of using different water sources, the application of the fecal indicator conversion ratio underestimated the norovirus disease burden, measured by the Disability Adjusted Life Years (DALYs), when compared to results using the genome copies norovirus data. In some cases the difference was >2 orders of magnitude. All scenarios using genome copies met the 10 -4 DALY per person per year for consumption of vegetables irrigated with wastewater, although these results are considered to be highly conservative risk estimates. The fecal indicator conversion ratio model of stream-water and drain-water sources of wastewater achieved the 10 -6 DALY per person per year threshold, which tends to indicate an underestimation of health risk when compared to using genome copies for estimating the dose. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Molecular characterization of cytochrome P450 1A and 3A and the effects of perfluorooctanoic acid on their mRNA levels in rare minnow (Gobiocypris rarus) gills

    Energy Technology Data Exchange (ETDEWEB)

    Liu Yong; Wang Jianshe; Wei Yanhong; Zhang Hongxia; Liu Yang [Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Datun Road, Beijing 100101 (China); Dai Jiayin [Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Datun Road, Beijing 100101 (China)], E-mail: daijy@ioz.ac.cn

    2008-07-07

    Perfluorooctanoic acid (PFOA), a potentially toxic perfluorinated compound (PFC), has been widely disseminated in the environment. In the present study, rare minnows (Gobiocypris rarus) exposed to PFOA exhibited histopathological gill damage, including epithelial hyperplasia of the lamellae, inflammatory cell infiltration, and lamellar fusion. Cytochrome P450s (CYPs) play a central role in the metabolism and biotransformation of a wide range of endogenous substrates and foreign compounds. Thus, we studied the CYPs and the effects of waterborne PFOA on their corresponding mRNA levels in the gills of rare minnows. Two novel CYP cDNAs (CYP1A and CYP3A) were identified in rare minnow and their mRNAs were ubiquitously expressed in all tissues examined. Upregulation of CYP3A mRNA was observed in the gills of male rare minnows exposed to 30 mg/L PFOA, while no significant changes occurred in exposed females. In contrast, down regulation of CYP1A mRNA was detected in the gills of male and female minnows exposed to PFOA. However, the effect of PFOA on gill mRNA levels of their potential regulators, aryl hydrocarbon receptor (AhR) for CYP1A, and pregnane X receptor (PXR) for CYP3A, were not consistent with the observed effects of PFOA on the corresponding CYP mRNA concentrations. This suggests a different or more complex transcriptional regulation of CYP expression following PFOA exposure.

  16. Effects of spray-dried Pseudomonas fluorescens, strain CL145A (Zequanox®) on reproduction and early development of the fathead minnow (Pimephales promelas).

    Science.gov (United States)

    Waller, Diane L.; Luoma, James A.

    2016-01-01

    The biopesticide, Zequanox®, is registered for dreissenid mussel control in open water systems. Previous toxicity trials with nontarget organisms, including young-of-the year of several fish species and invertebrates, demonstrated selectivity of Zequanox for dreissenids. However, data are lacking on its safety to reproductive and early life stages of fish. The present study evaluated the effects of Zequanox on spawning and early life stages of the fathead minnow, Pimephales promelas, at the maximum approved concentration (100 mg Zequanox active ingredient /L) and exposure duration (8 h) for open water application. The results showed no significant effect of Zequanox on survival, condition, or cumulative egg deposition (21 d) in adult fathead minnow. Eggs (<24-h old) exposed to Zequanox developed to the eyed-stage at a similar rate to that of unexposed eggs. Additionally, Zequanox did not have a significant effect on survival and growth (90 d) of newly hatched fry (<24-h old). The results indicate that Zequanox treatment will not affect survival, spawning, and early life development of fathead minnows when applied at the recommended treatment regime.

  17. Targeting neurotrophic factors and their receptors, but not cholinesterase or neurotransmitter, in the neurotoxicity of TDCPP in Chinese rare minnow adults (Gobiocypris rarus)

    International Nuclear Information System (INIS)

    Yuan, Lilai; Li, Jiasu; Zha, Jinmiao; Wang, Zijian

    2016-01-01

    Organophosphate flame retardants (OPFRs) have been detected at high concentrations in various environmental and biotic samples, but little is known about their toxicity. In this study, the potential neurotoxicity of three OPFRs (TCEP, TDCPP, and TPP) and Chlorpyrifos (CPF, an organophosphate pesticide) were compared in Chinese rare minnow using an acute toxicity test and a 21-day fish assay. The acute test demonstrated significant inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) by CPF. Although significant AChE inhibition at high concentration of TPP was also observed, none of the OPFRs had effects similar to CPF on these enzymes, indicating that their acute toxicities to Chinese rare minnow may be unrelated to cholinesterase inhibition. In addition, the 21-day fish assay with TDCPP demonstrated no significant effects on cholinesterase activities or neurotransmitter levels. Nonetheless, this OPFR exhibited widespread effects on the neurotrophic factors and their receptors (e.g., ntf3, ntrk1, ntrk2, ngfr, and fgf2, fgf11, fgf22, fgfr4), indicating that TDCPP or other OPFRs may elicit neurological effects by targeting neurotrophic factors and their receptors in Chinese rare minnow. - Highlights: • Significant inhibition of AChE and BChE activities by CPF was observed. • None of the OPFRs had similar effects on the cholinesterase like the CPF. • TDCPP showed significant effects on the neurotrophic factor genes in rare minnow. - Although none of the tested OPFRs showed any significant effects on cholinesterase activities and neurotransmitter levels, TDCPP did elicit widespread effects on neurotrophic factor genes.

  18. Transcription of key genes regulating gonadal steroidogenesis in control and ketoconazole- or vinclozolin-exposed fathead minnows

    Energy Technology Data Exchange (ETDEWEB)

    Villeneuve, Daniel L.; Blake, Lindsey S.; Brodin, Jeffrey; Greene, Katie J.; Knoebl, Iris; Miracle, Ann L.; Martinovic, Dalma; Ankley, Gerald T.

    2007-08-01

    This study evaluated changes in the expression of steroidogenesis-related genes in male fathead minnows exposed to ketoconazole (KTC) or vinclozolin (VZ) for 21 days. The aim was to evaluate links between molecular changes and higher level outcomes after exposure to endocrine-active chemicals (EACs) with different modes of action. To aid our analysis and interpretation of EAC-related effects, we first examined variation in the relative abundance of steroidogenesis-related gene transcripts in the gonads of male and female fathead minnows as a function of age, gonad development, and spawning status, independent of EAC exposure. Gonadal expression of several genes varied with age and/or gonadal somatic index in either males or females. However, with the exception of aromatase, steroidogenesis-related gene expression did not vary with spawning status. Following the baseline experiments, expression of the selected genes in male fathead minnows exposed to KTC or VZ was evaluated in the context of effects observed at higher levels of organization. Exposure to KTC elicited changes in gene transcription that were consistent with an apparent compensatory response to the chemical's anticipated direct inhibition of steroidogenic enzyme activity. Exposure to VZ, an antiandrogen expected to indirectly impact steroidogenesis, increased pituitary expression of follicle-stimulating hormone beta-subunit as well as testis expression of 20beta-hydroxysteroid dehydrogenase and luteinizing hormone receptor transcripts. Results of this study contribute to ongoing research aimed at understanding responses of the teleost hypothalamic-pituitary-gonadal axis to different types of EACs and how changes in molecular endpoints translate into apical outcomes reflective of either adverse effect or compensation.

  19. Time-specific and population-level differences in physiological responses of fathead minnows (Pimephales promelas) and golden shiners (Notemigonus crysoleucas) exposed to copper.

    Science.gov (United States)

    Peles, John D; Pistole, David H; Moffe, Mickey C

    2012-03-01

    The influence of exposure time on gill Na+/K+ ATPase activity and metabolic rate in populations of fathead minnows (Pimephales promelas) and golden shiners (Notemigonus crysoleucas) hatcheries in Ohio (OH) and Pennsylvania (PA) when exposed to sublethal concentrations of copper (Cu) was examined. The pattern of change in gill Na+/K+ ATPase activity was similar in all species/populations and results support expectations based on the concept of acclimation. In all populations, Na+/K+ ATPase activity declined significantly compared to reference values within 24 h, recovered by 48 h, and then continued to increase before exceeding reference values by 192 h. With the exception of PA fathead minnows, Na+/K+ ATPase activities returned to reference levels by 384 h. Although metabolic rates of individual fish were not strongly correlated with Na+/K+ ATPase activities, the pattern of change in mean values of these physiological parameters was very similar. However, OH populations of both fathead minnows and golden shiners demonstrated much more dramatic changes in metabolic rate compared to PA fish. At 24 h, metabolic rate of PA fathead minnows had decreased by 16% compared to the reference value whereas the OH population had decreased by 31%; metabolic rate of PA golden shiners declined by 23% compared to 59% in OH shiners at 24 h. Similar differences were observed in the maximum metabolic rates achieved at 192 h. While the increased sensitivity of OH fish to Cu is not readily explainable by genetic or environmental factors, results suggest the need for considering population level differences when evaluating the physiological effects of toxicants. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Estimating the Probability of Traditional Copying, Conditional on Answer-Copying Statistics.

    Science.gov (United States)

    Allen, Jeff; Ghattas, Andrew

    2016-06-01

    Statistics for detecting copying on multiple-choice tests produce p values measuring the probability of a value at least as large as that observed, under the null hypothesis of no copying. The posterior probability of copying is arguably more relevant than the p value, but cannot be derived from Bayes' theorem unless the population probability of copying and probability distribution of the answer-copying statistic under copying are known. In this article, the authors develop an estimator for the posterior probability of copying that is based on estimable quantities and can be used with any answer-copying statistic. The performance of the estimator is evaluated via simulation, and the authors demonstrate how to apply the formula using actual data. Potential uses, generalizability to other types of cheating, and limitations of the approach are discussed.

  1. Toxicological effects of irregularly shaped and spherical microplastics in a marine teleost, the sheepshead minnow (Cyprinodon variegatus).

    Science.gov (United States)

    Choi, Jin Soo; Jung, Youn-Joo; Hong, Nam-Hui; Hong, Sang Hee; Park, June-Woo

    2018-04-01

    The increasing global contamination of plastics in marine environments is raising public concerns about the potential hazards of microplastics to environmental and human health. Microplastics formed by the breakdown of larger plastics are typically irregular in shape. The objective of this study was to compare the effects of spherical or irregular shapes of microplastics on changes in organ distribution, swimming behaviors, gene expression, and enzyme activities in sheepshead minnow (Cyprinodon variegatus). Both types of microplastics accumulated in the digestive system, causing intestinal distention. However, when compared to spherical microplastics, irregular microplastics decreased swimming behavior (i.e., total distance travelled and maximum velocity) of sheepshead minnow. Both microplastics generated cellular reactive oxygen species (ROS), while ROS-related molecular changes (i.e., transcriptional and enzymatic characteristics) differed. This study provides toxicological insights into the impacts of environmentally relevant (fragmented) microplastics on fish and improves our understanding of the environmental effects of microplastics in the ecosystem. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Observed and modeled effects of pH on bioconcentration of diphenhydramine, a weakly basic pharmaceutical, by fathead minnows

    Science.gov (United States)

    Understanding the influence of pH on uptake and accumulation of ionizable pharmaceuticals by fish was recently identified as a major research need. In the present study, fathead minnows were exposed to diphenhydramine (DPH), a weakly basic pharmaceutical (pKa = 9.1). Fish were ...

  3. Adaptive Response in Female Fathead Minnows Exposed to an Aromatase Inhibitor: Computational Modeling of the Hypothalamic-Pituitary-Gonadal Axis

    Science.gov (United States)

    Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We are developing a mechanistic computational model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict dose-response and time-course ...

  4. Modulation of estrogenic exposure effects via alterations in salinity and dissolved oxygen in male fathead minnows, Pimephales promelas

    Science.gov (United States)

    Laboratory exposure data indicate that estrogens and estrogen mimics can cause endocrine disruption in male fathead minnows (Pimephales promelas). In the wild, conditions are not static as is often the case in the laboratory. Changes in water quality parameters, such as salinity influx due to road s...

  5. Gauge field copies

    International Nuclear Information System (INIS)

    Bollini, C.G.; Giambiagi, J.J.; Tiomno, J.

    1979-01-01

    The construction of field strength copies without any gauge constraint is discussed. Several examples are given, one of which is not only a field strength copy but also (at the same time) a 'current copy'. (author) [pt

  6. Assessment of 17α-ethinylestradiol effects and underlying mechanisms in a continuous, multigeneration exposure of the Chinese rare minnow (Gobiocypris rarus)

    International Nuclear Information System (INIS)

    Zha Jinmiao; Sun Liwei; Zhou Yiqi; Spear, Philip A.; Ma, Mei; Wang Zijian

    2008-01-01

    17α-Ethinylestradiol (EE 2 ) is a synthetic estrogen used primarily in birth control pills and in hormone replacement therapy. Owing to its occurrence in surface waters at concentrations frequently greater than 1 ng/l and its projected future use, EE 2 is expected to pose a significant risk to aquatic organisms. This study was conducted to obtain long-term exposure data necessary for the establishment of water quality criteria and to investigate mechanisms associated with toxic effects. In a multigeneration experiment, Chinese rare minnows (Gobiocypris rarus) were constantly exposed to environmentally relevant concentrations of the synthetic estrogen EE 2 . Mortality, deformities, reproductive parameters, plasma vitellogenin and histopathology were assessed. The results showed that, in the F 0 generation, all endpoints were significantly affected at concentrations higher than 0.2 ng/l EE 2 . No F 1 phenotypic males developed to maturity at 0.2 ng/l and, when adult females of this exposure group were crossed with unexposed males, no F 2 fertile eggs were produced. Kidney histopathology and ultrastructure suggest anomalies possibly associated with increased vitellogenin accumulation. We concluded that the reproduction of the F 1 minnows was completely inhibited at the lowest concentration tested, 0.2 ng/l EE 2 , a concentration frequently detected in surface waters. Growth effects may be related to increased energy requirements including the energy used in VTG synthesis. Reproductive effects are presumably associated with male feminization and the occurrence of testis-ova in males; however, ovarian degeneration observed in females may also have contributed to reproductive failure

  7. Computational Modeling of Hypothalamic-Pituitary-Gonadal Axis to Predict Adaptive Responses in Female Fathead Minnows Exposed to an Aromatase Inhibitor

    Science.gov (United States)

    Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We are developing a mechanistic computational model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict dose response and time-course...

  8. Transcriptome analyses of sex differential gene expression in brains of rare minnow (Gobiocypris rarus and effects of tributyltin exposure

    Directory of Open Access Journals (Sweden)

    Ji-liang Zhang

    2018-06-01

    Full Text Available RNA-sequencing was used to identify sex-biased gene expression in brains of rare minnow (Gobiocypris rarus by comparing transcriptomic profiles between females and males. Furthermore, transcriptomic responses to 10 ng/L tributyltin (TBT in both male and female brains were also investigated to understand whether TBT affects the identified sex-biased genes. Differentially expressed genes (DEGs were identified using the IDEG6 web tool. In this article, we presented male- and female-biased DEGs, and up-regulated and down-regulated DEGs after TBT exposure. The raw reads data supporting the present analyses has been deposited in NCBI Sequence Read Archive (SRA, http://www.ncbi.nlm.nih.gov/Traces/sra with accession number PRJNA376634. The data presented in this article are related to the research article entitled “Transcriptomic analyses of sexual dimorphism of rare minnow (G. rarus brains and effects of tributyltin exposure” (doi: 10.1016/j.ecoenv.2018.02.049.

  9. Scaling up Copy Detection

    OpenAIRE

    Li, Xian; Dong, Xin Luna; Lyons, Kenneth B.; Meng, Weiyi; Srivastava, Divesh

    2015-01-01

    Recent research shows that copying is prevalent for Deep-Web data and considering copying can significantly improve truth finding from conflicting values. However, existing copy detection techniques do not scale for large sizes and numbers of data sources, so truth finding can be slowed down by one to two orders of magnitude compared with the corresponding techniques that do not consider copying. In this paper, we study {\\em how to improve scalability of copy detection on structured data}. Ou...

  10. Probabilistic quantitative microbial risk assessment model of norovirus from wastewater irrigated vegetables in Ghana using genome copies and fecal indicator ratio conversion for estimating exposure dose

    DEFF Research Database (Denmark)

    Owusu-Ansah, Emmanuel de-Graft Johnson; Sampson, Angelina; Amponsah, Samuel K.

    2017-01-01

    physical and environmental factors that might influence the reliability of using indicator organisms in microbial risk assessment. The challenges facing analytical studies on virus enumeration (genome copies or particles) have contributed to the already existing lack of data in QMRA modelling. This study......The need to replace the commonly applied fecal indicator conversions ratio (an assumption of 1:10− 5 virus to fecal indicator organism) in Quantitative Microbial Risk Assessment (QMRA) with models based on quantitative data on the virus of interest has gained prominence due to the different...... attempts to fit a QMRA model to genome copies of norovirus data. The model estimates the risk of norovirus infection from the intake of vegetables irrigated with wastewater from different sources. The results were compared to the results of a corresponding model using the fecal indicator conversion ratio...

  11. The effect of chronic exposure to 238Pu(IV) citrate on the embryonic development of carp and fathead minnow eggs

    International Nuclear Information System (INIS)

    Till, J.E.

    1978-01-01

    This study focused on the effects of plutonium to the developing fish egg. A quantitative analysis of the uptake of 238 Pu(IV) citrate by carp eggs indicated that plutonium is accumulated in the egg and reaches a concentration factor of approx 4 at hatching (72hr after exposure begins). Autoradiographs made from carp eggs that had been exposed to 238 Pu revealed that, although some plutonium was concentrated on the egg chorion, plutonium that penetrated the chorion was uniformly distri-buted throughout the perivitelline fluid, embryo and yolk sac. Using the uptake data for carp eggs, dose conversion factors were calculated for both carp eggs and fathead minnow eggs exposed to 238 Pu during embryological development. These values were 2100 rad/μCi/ml and 7500 rad/μCi/ml for carp and fathead minnows, respectively. Experiments were conducted in which both carp and fathead minnow eggs were exposed to plutonium in solution during embryogenesis; the percentage of eggs hatching, the number of abnormal larvae produced, and the survival of larvae were used as indicators of radiation toxicity. Concentrations in excess of 1 μCi/ml were required to prevent both species of eggs from hatching. It is concluded that fish eggs developing in natural aquatic ecosystems contaminated with plutonium probably do not receive a significant dose from the plutonium alpha radioactivity. Future analysis of fecundity and the production of abnormalities in the offspring of larvae exposed during embryological development would provide an additional degree of sensitivity to the toxicity test system used in this study. (author)

  12. An intergeneric hybrid of a native minnow, the golden shiner, and an exotic minnow, the rudd

    Science.gov (United States)

    Burkhead, N.M.; Williams, J.D.

    1991-01-01

    The hybrid golden shiner Notemigonus crysoleucas × rudd Scardinius erythrophthalmus is the first known nonsalmonid, intergeneric hybrid of an exotic species and a North American native species. The cross is also the first valid record of a viable hybrid involving the native golden shiner. Meristic and mensural characters of 30 artificially produced hybrids of male golden shiners and female rudds were analyzed. Forty-seven percent of the meristic traits exhibited character states intermediate between those of parents. Twenty-seven percent of the meristic characters were supernumerary, suggesting developmental instability of the hybrid genome. Mensural hybrid characters were significantly skewed to the golden shiner phenotype. The skewed mensural inheritance and other skewed patterns of morphological inheritance also suggest problems in canalization of the hybrid phenome or atypical patterns of dominance. All hybrids were identifiable by intermediate squamation of the cultrate abdomen: the keel was mostly scaled but exhibited a small fleshy ridge posteriorly. This minnow hybrid allows general inferences to be made about the phylogenetic affinity of the golden shiner to other cultrate cyprinids of Eurasia. The hybrid cross has important management and conservation implications for fishes in North America. The hybrid is an example of how an exotic species may negatively affect a native species.

  13. Application of endocrine disruptor screening program fish short-term reproduction assay: Reproduction and endocrine function in fathead minnow (Pimephales promelas) and killifish (Fundulus heteroclitus) exposed to Bermuda pond sediment.

    Science.gov (United States)

    Fort, Douglas J; Mathis, Michael; Fort, Chelsea E; Fort, Hayley M; Bacon, Jamie P

    2015-06-01

    A modified tier 1 Endocrine Disruptor Screening Program (EDSP) 21-d fish short-term reproduction assay (FSTRA) was used to evaluate the effects of sediment exposure from freshwater and brackish ponds in Bermuda on reproductive fecundity and endocrine function in fathead minnow (Pimephales promelas) and killifish (Fundulus heteroclitus). Reproductively active male and female fish were exposed to control sediment and sediment from 2 freshwater ponds (fathead minnow) and 2 marine ponds (killifish) contaminated with polyaromatic hydrocarbons and metals via flow-through exposure for 21 d. Reproductive fecundity was monitored daily. At termination, the status of the reproductive endocrine system was assessed by the gonadosomatic index, gonadal histology, plasma steroids (estrogen [E2], testosterone [T], and 11-ketotestosterone [11-KT]), steroidogenic enzymes (aromatase and combined 3β/17β -hydroxysteroid dehydrogenase [3β/17β-HSD]), and plasma vitellogenin (VTG). Decreased reproductive fecundity, lower male body weight, and altered endocrinological measures of reproductive status were observed in both species. Higher plasma T levels in female minnows and 11-KT levels in both male and female minnows and female killifish exposed to freshwater and brackish sediments, respectively. Decreased female E2 and VTG levels and gonadal cytochrome P19 (aromatase) activity were also found in sediment exposed females from both species. No effect on female 3β/17β-HSD activity was found in either species. The FSTRA provided a robust model capable of modification to evaluate reproductive effects of sediment exposure in fish. © 2015 SETAC.

  14. A study of temporal effects of the model anti-androgen flutamide on components of the hypothalamic-pituitary-gonadal axis in adult fathead minnows

    Data.gov (United States)

    U.S. Environmental Protection Agency — The aim of this study was to investigate temporal changes in the hypothalamic-pituitary-gonadal axis of fathead minnow treated with the model androgen receptor (AR)...

  15. High‐resolution mass spectrometry of skin mucus for monitoring physiological impacts and contaminant biotransformation products in fathead minnows exposed to wastewater effluent

    Science.gov (United States)

    High‐resolution mass spectrometry is advantageous for monitoring physiological impacts and contaminant biotransformation products in fish exposed to complex wastewater effluent. We evaluated this technique using skin mucus from male and female fathead minnows (Pimephales pr...

  16. Quantitative PCR assays for detecting loach minnow (Rhinichthys cobitis) and spikedace (Meda fulgida) in the southwestern United States

    Science.gov (United States)

    Joseph C. Dysthe; Kellie J. Carim; Yvette M. Paroz; Kevin S. McKelvey; Michael K. Young; Michael K. Schwartz

    2016-01-01

    Loach minnow (Rhinichthys cobitis) and spikedace (Meda fulgida) are legally protected with the status of Endangered under the U.S. Endangered Species Act and are endemic to the Gila River basin of Arizona and New Mexico. Efficient and sensitive methods for monitoring these species’ distributions are critical for prioritizing conservation efforts. We developed...

  17. Observed and modeled effects of pH on bioconcentration of diphenhydramine, a weakly basic pharmaceutical, in fathead minnows

    Science.gov (United States)

    Fathead minnows were exposed to diphenhydramine (DPH), a weakly basic pharmaceutical (pKa = 9.1), to examine pH effects on uptake and accumulation. Fish were exposed to 10 ìg/L DPH in water for up to 96 h at three nominal pH levels: 6.7, 7.7, and 8.7. In each case, an appa...

  18. Original Copies

    DEFF Research Database (Denmark)

    Sørensen, Tim Flohr

    2013-01-01

    of similarity by looking at artefactual similarity as the results of prototyping and as a production of simulacra. In this light, the concept of copying turns out to be more than simply a matter of trying to imitate an exotic or prestigious original, and it fundamentally raises the question how different a copy...

  19. A Time-course Analysis of Effects of the Steroidogenesis Inhibitor Ketoconazole on Components of the Hypothalamic-pituitary-gonadal Axis of Fathead Minnows

    Science.gov (United States)

    The objective of this study was to evaluate temporal effects of the model steroidogenesis inhibitor ketoconazole (KTC) on aspects of reproductive endocrine function controlled by the hypothalamic-pituitary-gonadal (HPG) axis in the fathead minnow (Pimephales promelas). Ketoconazo...

  20. Quantum copying: A review

    Directory of Open Access Journals (Sweden)

    Mark Hillery

    2000-07-01

    Full Text Available Quantum information is stored in two-level quantum systems known as qubits. The no-cloning theorem states that the state of an unknown qubit cannot be copied. This is in contrast to classical information which can be copied. If one drops the requirement that the copies be perfect it is possible to design quantum copiers. This paper presents a short review of the theory of quantum copying.

  1. Effects-based monitoring in the lower Green Bay/Fox River and Milwaukee Estuary Areas of Concern using caged Fathead Minnows (Pimephales promelas)

    Science.gov (United States)

    Within the Great Lakes there is an increased focus on contaminants of emerging concern (CECs) and their potential effects on aquatic organisms, including adverse reproductive effects. To further characterize the utility of caged fathead minnows (Pimephales promelas) for effects-b...

  2. Effects of a Short-term Exposure to the Fungicide Prochloraz on Endocrine Function and Gene Expression in Female Fathead Minnows (Pimephales promelas)

    Science.gov (United States)

    Prochloraz is a fungicide known to cause endocrine disruption through effects on the hypothalamic-pituitary-gonadal (HPG) axis. To determine the short-term impacts of prochloraz on gene expression and steroid production, adult female fathead minnows (Pimephales promelas) were exp...

  3. A time-course analysis of effects of the steroidogenesis inhibitor ketoconazole on components of the hypothalamic-pituitary-gonadal axis of fathead minnows (Presentation)

    Science.gov (United States)

    The objective of this study was to evaluate temporal effects of the model steroidogenesis inhibitor ketoconazole (KTC) on aspects of reproductive endocrine function controlled by the hypothalamic-pituitary-gonadal (HPG) axis in the fathead minnow (Pimephales promelas). Ketoconazo...

  4. Copy number variations of E2F1: a new genetic risk factor for testicular cancer.

    Science.gov (United States)

    Rocca, Maria Santa; Di Nisio, Andrea; Marchiori, Arianna; Ghezzi, Marco; Opocher, Giuseppe; Foresta, Carlo; Ferlin, Alberto

    2017-03-01

    Testicular germ cell tumor (TGCT) is one of the most heritable forms of cancer. In last years, many evidence suggested that constitutional genetic factors, mainly single nucleotide polymorphisms, can increase its risk. However, the possible contribution of copy number variations (CNVs) in TGCT susceptibility has not been substantially addressed. Indeed, an increasing number of studies have focused on the effect of CNVs on gene expression and on the role of these structural genetic variations as risk factors for different forms of cancer. E2F1 is a transcription factor that plays an important role in regulating cell growth, differentiation, apoptosis and response to DNA damage. Therefore, deficiency or overexpression of this protein might significantly influence fundamental biological processes involved in cancer development and progression, including TGCT. We analyzed E2F1 CNVs in 261 cases with TGCT and 165 controls. We found no CNVs in controls, but 17/261 (6.5%) cases showed duplications in E2F1 Blot analysis demonstrated higher E2F1 expression in testicular samples of TGCT cases with three copies of the gene. Furthermore, we observed higher phosphorylation of Akt and mTOR in samples with E2F1 duplication. Interestingly, normal, non-tumoral testicular tissue in patient with E2F1 duplication showed lower expression of E2F1 and lower AKT/mTOR phosphorylation with respect to adjacent tumor tissue. Furthermore, increased expression of E2F1 obtained in vitro in NTERA-2 testicular cell line induced increased AKT/mTOR phosphorylation. This study suggests for the first time an involvement of E2F1 CNVs in TGCT susceptibility and supports previous preliminary data on the importance of AKT/mTOR signaling pathway in this cancer. © 2017 Society for Endocrinology.

  5. Examining waterborne and dietborne routes of exposure and their contribution to biological response patterns in fathead minnow (Pimephales promelas)

    International Nuclear Information System (INIS)

    Rozon-Ramilo, Lisa D.; Dubé, Monique G.; Squires, Allison J.; Niyogi, Som

    2011-01-01

    Highlights: Objective (i) was achieved by isolating each route of exposure (diet, water and the combination of the two) and comparing it to a control. The metal mining effluent studied encompassed several different effluent types including: mine water, mill facility, tailing impoundment, treatment pond, treatment facility, seepage and surface drainage effluent. Experiment 1 examined exposure pathways by isolating effluent exposure through the diet, water or the combination of the two. Experiment 2 examined whether differences in Fathead minnow responses occurred when fish were fed a live or frozen (dead) diet of chironomids. Multiple trophic levels (consumers and carnivores) were placed in each artificial stream simultaneously. Primary route of exposure to Fathead minnow when held in control water and fed effluent-exposed chironomid larvae. - Abstract: The objectives of the current study were: (i) to gain a better understanding of the relative importance of water and diet as routes of exposure causing toxicity in fathead minnow (FHM) exposed to metal mining effluents (MME) using a full factorial water/food experimental design (Experiment 1), and (ii) to assess differences in the effects of food quality on toxicity by comparing FHM fed both a live and frozen diet of Chironomus dilutus (Experiment 2). The results showed significant increases in general water quality parameters (e.g., hardness, conductivity) and various metals in the effluent treatment waters compared to control waters, with maximum increase seen in the multi-trophic streams. Metals accumulation (Rb, Al, Se, Sr, Tl, Ce, Co, Cu, Pb) effects of both waterborne and multi-trophic exposures were significant in one or more fathead minnow tissue type (muscle, gonads, liver, larvae) relative to those in the control systems. Condition factor and liver somatic index (LSI) of FHM were also significantly affected in both exposures by one or both routes of exposure (water and/or diet). In addition, cumulative

  6. A study of temporal effects of the model anti-androgen flutamide on components of the hypothalamic-pituitary-gonadal axis in adult fathead minnows

    Science.gov (United States)

    The aim of this study was to investigate temporal changes in the hypothalamic-pituitary-gonadal (HPG) axis of fathead minnow (Pimephales promelas) treated with the model androgen receptor (AR) antagonist, flutamide. Reproductively-mature fish were exposed in a flow-through, meas...

  7. The Art of Copying

    DEFF Research Database (Denmark)

    Christensen, Hans Dam

    2017-01-01

    This article discusses copies within the field of art museums by way of mapping strategies for copy practices. This mapping leans heavily towards parts of the writings of Jacques Derrida (1930–2004). Against the backdrop of this theoretical premise, the article distinguishes five main strategies....... An informational copy is just as unique as an original object of art, and at the same time, it defines the original and is itself defined by this opposition. Lastly, the strategy for the imagined relation between original and copy follows. This strategy is dependent upon several of the previous approaches, and...

  8. Screening for common copy-number variants in cancer genes.

    Science.gov (United States)

    Tyson, Jess; Majerus, Tamsin M O; Walker, Susan; Armour, John A L

    2010-12-01

    For most cases of colorectal cancer that arise without a family history of the disease, it is proposed that an appreciable heritable component of predisposition is the result of contributions from many loci. Although progress has been made in identifying single nucleotide variants associated with colorectal cancer risk, the involvement of low-penetrance copy number variants is relatively unexplored. We have used multiplex amplifiable probe hybridization (MAPH) in a fourfold multiplex (QuadMAPH), positioned at an average resolution of one probe per 2 kb, to screen a total of 1.56 Mb of genomic DNA for copy number variants around the genes APC, AXIN1, BRCA1, BRCA2, CTNNB1, HRAS, MLH1, MSH2, and TP53. Two deletion events were detected, one upstream of MLH1 in a control individual and the other in APC in a colorectal cancer patient, but these do not seem to correspond to copy number polymorphisms with measurably high population frequencies. In summary, by means of our QuadMAPH assay, copy number measurement data were of sufficient resolution and accuracy to detect any copy number variants with high probability. However, this study has demonstrated a very low incidence of deletion and duplication variants within intronic and flanking regions of these nine genes, in both control individuals and colorectal cancer patients. Copyright © 2010 Elsevier Inc. All rights reserved.

  9. Robust Adaptable Video Copy Detection

    DEFF Research Database (Denmark)

    Assent, Ira; Kremer, Hardy

    2009-01-01

    in contrast). Our query processing combines filtering and indexing structures for efficient multistep computation of video copies under this model. We show that our model successfully identifies altered video copies and does so more reliably than existing models.......Video copy detection should be capable of identifying video copies subject to alterations e.g. in video contrast or frame rates. We propose a video copy detection scheme that allows for adaptable detection of videos that are altered temporally (e.g. frame rate change) and/or visually (e.g. change...

  10. In Silico analysis of perturbed steroidogenesis and gonad growth in fathead minnows (P. promelas) exposed to 17α-ethynylestradiol.

    Science.gov (United States)

    Hala, David; Petersen, Lene H; Martinović, Dalma; Huggett, Duane B

    2015-06-01

    The multi-factorial nature of adverse reproductive effects mediated by endocrine disrupting compounds (or EDCs) makes understanding the mechanistic basis of reproductive dysfunction a highly pertinent area of research. As a consequence, a main motivator for continued research is to integrate 'multi-leveled' complexity (i.e., from genes to phenotype) using mathematical methods capable of encapsulating properties of physiological relevance. In this study, an in silico stoichiometric model of piscine steroidogenesis was augmented with a 'biomass' reaction associating the underlying stoichiometry of steroidogenesis with a reaction representative of gonad growth. The ability of the in silico model to predict perturbed steroidogenesis and subsequent effects on gonad growth was tested by exposing reproductively active male and female fathead minnows (Pimephales promelas) to 88 ng/L of the synthetic estrogen, 17α-ethynylestradiol (EE2). The in silico model was parameterized (or constrained) with experimentally quantified concentrations of selected steroid hormones (using mass spectrometry) and fold changes in gene expression (using RT-qPCR) for selected steroidogenic enzyme genes, in gonads of male and female fish. Once constrained, the optimization framework of flux balance analysis (FBA) was used to calculate an optimal flux through the biomass reaction (analogous to gonad growth) and associated steroidogenic flux distributions required to generate biomass. FBA successfully predicted effects of EE2 exposure on fathead minnow gonad growth (%gonadosomatic index or %GSI) and perturbed production of steroid hormones. Specifically, FBA accurately predicted no effects of exposure on male %GSI and a significant reduction for female %GSI. Furthermore, in silico simulations accurately identified disrupted reaction fluxes catalyzing productions of androgens (in male fish) and progestogens (in female fish), an observation which agreed with in vivo experimentation. The analyses

  11. Hard-copy versus soft-copy with and without simple image manipulation for detection of pulmonary nodules and masses

    International Nuclear Information System (INIS)

    Kosuda, S.; Kaji, T.; Iwasaki, Y.; Kusano, S.; Kobayashi, H.; Watanabe, M.

    2000-01-01

    To compare interpretation performance on soft-copy presentations, with and without simple image manipulation, and on unmodified hard-copy presentations with regard to detection of pulmonary nodules and masses. Material and Methods: Fifty chest digital radiograph combinations of patients with a total of 60 nodules, 32 of which were 2.0 cm in diameter, were selected for the study. Three readers evaluated three separate image formats: unmodified hard- and soft-copies, and soft-copies with simple image manipulation of lung and mediastinum window settings, and zooming. The screen display was 1600x1200 pixels with 8 bits/pixel. Results: The sensitivity, accuracy, detectability, and Az value of the soft-copy systems were clearly inferior to hard-copy evaluation. The mean Az values were 0.921 for unmodified hard-copy, 0.820 for image-manipulated soft-copy, and 0.781 for unmodified soft-copy. Conclusion: Soft-copy interpretations were not as sensitive in detecting pulmonary nodules and masses as hard-copy evaluation

  12. CDNA CLONING OF FATHEAD MINNOW (PIMEPHALES PROMELAS) ESTROGEN AND ANDROGEN RECEPTORS FOR USE IN STEROID RECEPTOR EXTRAPOLATION STUDIES FOR ENDOCRINE DISRUPTING CHEMICALS

    Science.gov (United States)

    cDNA Cloning of Fathead minnow (Pimephales promelas) Estrogen and Androgen Receptors for Use in Steroid Receptor Extrapolation Studies for Endocrine Disrupting Chemicals. Wilson, V.S.1,, Korte, J.2, Hartig P. 1, Ankley, G.T.2, Gray, L.E., Jr 1, , and Welch, J.E.1. 1U.S...

  13. Toward an adverse outcome pathway for impaired growth: Mitochondrial dysfunction impairs growth in early life stages of the fathead minnow (Pimephales promelas).

    Science.gov (United States)

    Bolser, Derek G; Dreier, David A; Li, Erchao; Kroll, Kevin J; Martyniuk, Christopher J; Denslow, Nancy D

    2018-07-01

    Chemical contaminants present in the environment can affect mitochondrial bioenergetics in aquatic organisms and can have substantial effects on individual fitness. As early life stages of fish are particularly vulnerable to environmental contaminants, they are ideal models for examining the relationship between impaired mitochondrial bioenergetics (ATP-dependent respiration, basal oxidative respiration) and apical endpoints such as growth. Here, early life stages of the fathead minnow (Pimephales promelas), an ecologically relevant North American species, were used to investigate the relationship between mitochondrial bioenergetics and growth following perturbation with model mitochondrial toxicants 2,4-dinitrophenol and octylamine. Fathead minnows were exposed to 2,4-dinitrophenol and octylamine at 3 concentrations for 24 h and endpoints related to mitochondrial bioenergetics were measured with the Agilent Seahorse XFe24 Bioanalyzer. In order to link changes in mitochondrial bioenergetics to growth, fathead minnows were exposed to the same chemical contaminants for 7-14 days and growth was measured by measuring total length on a weekly basis. There was a significant correlation between decrease in average length at 14 days and basal respiration (r = 0.997, p = 0.050, n = 3), as well as maximal respiration (r = 0.998, p-value = 0.043, n = 3) for embryos exposed to 2,4 dinitrophenol. For octylamine, ATP production was highly correlated with average length at 7 days (p-value = 0.1) and spare respiratory capacity and average length at 14 days were highly correlated (p-value = 0.1). These data improve understanding of how mitochondrial toxicants impair growth in fish larvae and may be useful for developing an adverse outcome pathway for growth. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Extended fish short term reproduction assays with the fathead minnow and Japanese medaka: No evidence of impaired fecundity from exposure to atrazine.

    Science.gov (United States)

    Brain, Richard A; Schneider, Suzanne Z; Anderson, Julie C; Knopper, Loren D; Wolf, Jeffrey C; Hanson, Mark L

    2018-08-01

    Short-term reproduction assays were conducted with fathead minnow (Pimephales promelas) and Japanese medaka (Oryzias latipes) to evaluate responses from atrazine exposure at environmentally relevant concentrations and above. Breeding groups of fish with multiple males and females were exposed to atrazine under flow-through conditions. Fathead minnows were exposed to mean measured concentrations of 1.0, 10, 26, 52, and 105 μg atrazine/L for 28 days. Medaka were exposed to mean measured concentrations of 9.4, 48, 74, 97, and 244 μg atrazine/L for 28 or 29 days. Fish were evaluated for survival, fecundity, fertility, total length, wet weight, secondary sex characteristics, gonadosomatic index (GSI) (P. promelas only), plasma or hepatic vitellogenin (VTG), and histopathology of gonads. General observations of health and behaviour were also conducted. There were no statistically significant effects (i.e., p < 0.05) of atrazine on survival, size, reproduction, behaviour, GSI, VTG, or secondary sex characteristics in either species at any exposure level. In fathead minnows, there were no histopathological findings associated with atrazine exposure in male fish, but there was an increased proportion of Stage 4.0 ovaries accompanied by an increase in proportion of Grade 3 post-ovulatory follicles in females of the 105 μg/L treatment group. Without a concomitant increase in oocyte atresia, neither of these findings are considered adverse for the health of the fish. In medaka, there were no significant effects of atrazine exposure on histopathology in either sex. These data support current weight-of-evidence assessments that atrazine does not cause direct adverse effects on fish reproduction at environmentally realistic concentrations. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Acute toxicity of sodium chloride, pentachlorophenol, Guthion, and hexavalent chromium to fathead minnows (Pimephales promelas) and goldfish (Carassius auratus)

    Energy Technology Data Exchange (ETDEWEB)

    Adelman, I.R.; Smith, L.L. Jr.; Siesennop, G.D.

    1976-02-01

    The 96-h LC50's for sodium chloride were 7650 and 7341 mg/liter, for pentachlorophenol 0.21 and 0.22 mg/liter, for Guthion 1.9 and 2.4 mg/liter, and for hexavalent chromium 48 and 120 mg/liter, for fathead minnows (Pimephales promelas) and goldfish (Carassius auratus), respectively. Threshold LC50's were reached in 6 days for sodium chloride (7650 and 7322 mg/liter for fathead minnows and goldfish, respectively), and pentachlorophenol (0.21 and 0.21 mg/liter), but were not attained in 11 days (termination of testing) with Guthion (0.76 and 0.80 mg/liter) and hexavalent chromium (18 and 33 mg/liter). With pentachlorophenol and Guthion goldfish were initially more resistant, but by termination there was no significant difference in LC50's between the two species. With hexavalent chromium the goldfish were more resistant throughout the 11-day test, and with sodium chloride goldfish were initially more resistant but at attainment of a threshold LC50 were less resistant. Use of toxicity curves for assessment of acute mortality permits interpretation not possible in 96-h tests where LC50's are computed at 24-h intervals.

  16. Accurate measurement of gene copy number for human alpha-defensin DEFA1A3.

    Science.gov (United States)

    Khan, Fayeza F; Carpenter, Danielle; Mitchell, Laura; Mansouri, Omniah; Black, Holly A; Tyson, Jess; Armour, John A L

    2013-10-20

    Multi-allelic copy number variants include examples of extensive variation between individuals in the copy number of important genes, most notably genes involved in immune function. The definition of this variation, and analysis of its impact on function, has been hampered by the technical difficulty of large-scale but accurate typing of genomic copy number. The copy-variable alpha-defensin locus DEFA1A3 on human chromosome 8 commonly varies between 4 and 10 copies per diploid genome, and presents considerable challenges for accurate high-throughput typing. In this study, we developed two paralogue ratio tests and three allelic ratio measurements that, in combination, provide an accurate and scalable method for measurement of DEFA1A3 gene number. We combined information from different measurements in a maximum-likelihood framework which suggests that most samples can be assigned to an integer copy number with high confidence, and applied it to typing 589 unrelated European DNA samples. Typing the members of three-generation pedigrees provided further reassurance that correct integer copy numbers had been assigned. Our results have allowed us to discover that the SNP rs4300027 is strongly associated with DEFA1A3 gene copy number in European samples. We have developed an accurate and robust method for measurement of DEFA1A3 copy number. Interrogation of rs4300027 and associated SNPs in Genome-Wide Association Study SNP data provides no evidence that alpha-defensin copy number is a strong risk factor for phenotypes such as Crohn's disease, type I diabetes, HIV progression and multiple sclerosis.

  17. Effects of eutrophication on vitellogenin gene expression in male fathead minnows (Pimephales promelas) exposed to 17α-ethynylestradiol in field mesocosms

    International Nuclear Information System (INIS)

    Gordon, Denise A.; Toth, Gregory P.; Graham, David W.; Lazorchak, James M.; Reddy, Tirumuru V.; Knapp, Charles W.; Noyelles, Frank de; Campbell, Scott; Lattier, David L.

    2006-01-01

    This study evaluated the effect of aquatic secondary nutrient supply levels (nitrogen and phosphorus) on the subcellular response of adult male fathead minnows (Pimephales promelas) exposed to a single nominal concentration of 17α-ethynylestradiol (EE2), a potent synthetic estrogen, under quasi-natural field conditions. Outdoor mesocosms were maintained under low, medium, and high nutrient supply conditions as categorized by total phosphorus (TP) level (nominal 0.012, 0.025, and 0.045 mg TP/L, respectively), and treated with EE2 with and without a carrier solvent. Using reverse transcription-polymerase chain reaction methods, vitellogenin gene (Vg) expression was determined in the fish collected at 0 h, 8 h, 24 h, 4 d, 7 d, and 14 d post-exposure. Induction of Vg was detected as early as 8 h post-exposure, with and without the carrier solvent, and persisted through Day 14. Results showed Vg to be significantly greater at low nutrient levels (p < 0.05), suggesting that EE2 bioavailability to the fish was likely greater under less-turbid water conditions. - Nutrient condition in surface waters strongly influences vitellogenin gene expression in male fathead minnows

  18. Behavioral observations of the endangered Rio Grande silvery minnow in a conservation aquaculture facility

    Directory of Open Access Journals (Sweden)

    Tave Douglas

    2018-03-01

    Full Text Available A major reason why conservation aquaculture is needed to improve the success of aquaculture-assisted fisheries is that traditional production aquaculture produces fish with mal-adaptive behaviors. These behaviors can be produced via domestication and culture techniques, and preventing these mal-adaptive behaviors requires integrating improvements in genetic management and culture protocols. The genetic protocols needed to minimize hatchery-induced genetic changes have received considerable attention, but changing the way fish are raised has received less effort. Conservation aquaculture cultures fish in environments that resemble their native habitats so that when stocked, they behave like wild fish rather than hatchery fish. A purpose built-conservation aquaculture facility can also be used to learn about a species’ behavior and how it reacts to changes in the environment, something which can be difficult or expensive to study in the wild. These observations can then be used to help direct both propagation and recovery management. This paper provides the rationale for why genetic management, culture systems, and management practices need to be altered to produce fish that are behaviorally similar to wild fish for aquaculture-assisted fisheries programs. It then provides a description of some of the behaviors of the endangered Rio Grande silvery minnow Hybognathus amarus that were observed at the Los Lunas Silvery Minnow Refugium, a purpose-built conservation aquaculture facility, and explains how some of these behaviors can be used in culture and recovery management. Behaviors described are: schooling; predator avoidance; feeding behavior; use of vegetation for cover and predator avoidance; habitat use by bottom substrate; location in the water column; upstream movement via a fish ladder; movement upstream in a high-velocity channel; response to changes in water level; spawning behavior; seine avoidance; and Kaah-chee-nyee Srkaash, a behavior

  19. Dynamic Expansion and Contraction of cagA Copy Number in Helicobacter pylori Impact Development of Gastric Disease

    Directory of Open Access Journals (Sweden)

    Sungil Jang

    2017-02-01

    Full Text Available Infection with Helicobacter pylori is a major risk factor for development of gastric disease, including gastric cancer. Patients infected with H. pylori strains that express CagA are at even greater risk of gastric carcinoma. Given the importance of CagA, this report describes a new molecular mechanism by which the cagA copy number dynamically expands and contracts in H. pylori. Analysis of strain PMSS1 revealed a heterogeneous population in terms of numbers of cagA copies; strains carried from zero to four copies of cagA that were arranged as direct repeats within the chromosome. Each of the multiple copies of cagA was expressed and encoded functional CagA; strains with more cagA repeats exhibited higher levels of CagA expression and increased levels of delivery and phosphorylation of CagA within host cells. This concomitantly resulted in more virulent phenotypes as measured by cell elongation and interleukin-8 (IL-8 induction. Sequence analysis of the repeat region revealed three cagA homologous areas (CHAs within the cagA repeats. Of these, CHA-ud flanked each of the cagA copies and is likely important for the dynamic variation of cagA copy numbers. Analysis of a large panel of clinical isolates showed that 7.5% of H. pylori strains isolated in the United States harbored multiple cagA repeats, while none of the tested Korean isolates carried more than one copy of cagA. Finally, H. pylori strains carrying multiple cagA copies were differentially associated with gastric disease. Thus, the dynamic expansion and contraction of cagA copy numbers may serve as a novel mechanism by which H. pylori modulates gastric disease development.

  20. Effects of lipid-lowering pharmaceuticals bezafibrate and clofibric acid on lipid metabolism in fathead minnow (Pimephales promelas).

    Science.gov (United States)

    Weston, Anna; Caminada, Daniel; Galicia, Hector; Fent, Karl

    2009-12-01

    The lipid-lowering agents bezafibrate and clofibric acid, which occur at concentrations up to 3.1 and 1.6 microg/L, respectively, are among the most frequently found human pharmaceuticals in the aquatic environment. In contrast to knowledge about their environmental occurrence, little is known about their effects in the environment. The aim of the present study was to analyze effects of these lipid-lowering agents in fish by focusing on their modes of action, lipid metabolism. Fathead minnows were exposed in aquaria to measured concentrations of 0.1, 1.27, 10.18, 101.56, and 106.7 mg/L bezafibrate and to 1.07, 10.75, and 108.91 mg/L clofibric acid for 14 and 21 d, respectively. After exposure, fish liver was analyzed for expression of peroxisome proliferator-activated receptor alpha (PPARalpha) by quantitative polymerase chain reaction (PCR), and the PPAR-regulated enzyme fatty acyl-coenzyme-A oxidase (FAO) involved in fatty acid oxidation. Bezafibrate had no effect, either on PPARalpha expression or on FAO activity, at all concentrations. In contrast, clofibric acid induced FAO activity in male fathead minnows at 108.91 mg/L. No increase in expression of PPARalpha messenger ribonucleic acid was observed. Egg production was apparently decreased after 21 d of exposure to 108.91 mg/L clofibric acid. The present study demonstrates that bezafibrate has very little or no effect on PPARalpha expression and FAO activity, but clofibric acid affects FAO activity.

  1. Copy number increase of ACTN4 is a prognostic indicator in salivary gland carcinoma

    International Nuclear Information System (INIS)

    Watabe, Yukio; Mori, Taisuke; Yoshimoto, Seiichi; Nomura, Takeshi; Shibahara, Takahiko; Yamada, Tesshi; Honda, Kazufumi

    2014-01-01

    Copy number increase (CNI) of ACTN4 has been associated with poor prognosis and metastatic phenotypes in various human carcinomas. To identify a novel prognostic factor for salivary gland carcinoma, we investigated the copy number of ACTN4. We evaluated DNA copy number of ACTN4 in 58 patients with salivary gland carcinoma by using fluorescent in situ hybridization (FISH). CNI of ACTN4 was recognized in 14 of 58 patients (24.1%) with salivary gland carcinoma. The cases with CNI of ACTN4 were closely associated with histological grade (P = 0.047) and vascular invasion (P = 0.033). The patients with CNI of ACTN4 had a significantly worse prognosis than the patients with normal copy number of ACTN4 (P = 0.0005 log-rank test). Univariate analysis by the Cox proportional hazards model showed that histological grade, vascular invasion, and CNI of ACTN4 were independent risk factors for cancer death. Vascular invasion (hazard ratio [HR]: 7.46; 95% confidence interval [CI]: 1.98–28.06) and CNI of ACTN4 (HR: 3.23; 95% CI: 1.08–9.68) remained as risk factors for cancer death in multivariate analysis. Thus, CNI of ACTN4 is a novel indicator for an unfavorable outcome in patients with salivary gland carcinoma

  2. Local copying of orthogonal entangled quantum states

    International Nuclear Information System (INIS)

    Anselmi, Fabio; Chefles, Anthony; Plenio, Martin B

    2004-01-01

    In classical information theory one can, in principle, produce a perfect copy of any input state. In quantum information theory, the no cloning theorem prohibits exact copying of non-orthogonal states. Moreover, if we wish to copy multiparticle entangled states and can perform only local operations and classical communication (LOCC), then further restrictions apply. We investigate the problem of copying orthogonal, entangled quantum states with an entangled blank state under the restriction to LOCC. Throughout, the subsystems have finite dimension D. We show that if all of the states to be copied are non-maximally entangled, then novel LOCC copying procedures based on entanglement catalysis are possible. We then study in detail the LOCC copying problem where both the blank state and at least one of the states to be copied are maximally entangled. For this to be possible, we find that all the states to be copied must be maximally entangled. We obtain a necessary and sufficient condition for LOCC copying under these conditions. For two orthogonal, maximally entangled states, we provide the general solution to this condition. We use it to show that for D = 2, 3, any pair of orthogonal, maximally entangled states can be locally copied using a maximally entangled blank state. However, we also show that for any D which is not prime, one can construct pairs of such states for which this is impossible

  3. Patterns, correlates, and reduction of homework copying

    Directory of Open Access Journals (Sweden)

    David J. Palazzo

    2010-03-01

    Full Text Available Submissions to an online homework tutor were analyzed to determine whether they were copied. The fraction of copied submissions increased rapidly over the semester, as each weekly deadline approached and for problems later in each assignment. The majority of students, who copied less than 10% of their problems, worked steadily over the three days prior to the deadline, whereas repetitive copiers (those who copied >30% of their submitted problems exerted little effort early. Importantly, copying homework problems that require an analytic answer correlates with a 2(σ decline over the semester in relative score for similar problems on exams but does not significantly correlate with the amount of conceptual learning as measured by pretesting and post-testing. An anonymous survey containing questions used in many previous studies of self-reported academic dishonesty showed ∼1/3 less copying than actually was detected. The observed patterns of copying, free response questions on the survey, and interview data suggest that time pressure on students who do not start their homework in a timely fashion is the proximate cause of copying. Several measures of initial ability in math or physics correlated with copying weakly or not at all. Changes in course format and instructional practices that previous self-reported academic dishonesty surveys and/or the observed copying patterns suggested would reduce copying have been accompanied by more than a factor of 4 reduction of copying from ∼11% of all electronic problems to less than 3%. As expected (since repetitive copiers have approximately three times the chance of failing, this was accompanied by a reduction in the overall course failure rate. Survey results indicate that students copy almost twice as much written homework as online homework and show that students nationally admit to more academic dishonesty than MIT students.

  4. Chronic effect of low pH on fathead minnow survival, growth, and reproduction

    Energy Technology Data Exchange (ETDEWEB)

    Mount, D I

    1973-01-01

    Fathead minnows (Pimephales promelas rafinesque) were continuously exposed to reduced pH levels of 4.5, 5.2, 5.9, 6.6, and 7.5 (control) during a 13-month, one-generation test. Survival was not affected, even at the lowest pH tested. Fish behavior was abnormal, and fish were deformed at pH 4.5 and 5.2. Egg production and egg hatchability were reduced at pH 5.9 and lower, and all eggs were abnormal. A pH of 6.6 was marginal for vital life functions, but safe for continuous exposure. Free carbon dioxide, liberated by the addition of sulfuric acid to reduce the pH, may have had an unknown effect. The fish did not become acclimiated to low pH levels.

  5. Variability and condition of common minnow (Phoxinus phoxinus, Cyprinidae, Cypriniformes) on the Semipalatinsk range and out of its influence

    International Nuclear Information System (INIS)

    Mitrofanov, I.V.; Matmuratov, S.A.

    2003-01-01

    Populations of common minnow (Phoxinus phoxinus) from five rivers of Irtysh and Balkhash basins were investigated. Population from the Shagan river situated inside area of Semipalatinsk Range influence. This population has normal sexual structure and high growth rate. Condition factor of all fishes is high. Population from Semipalatinsk Range has increased variability of characteristics due to increasing of stochastic part of general variability. Abnormalities of external fish morphology are not observed in this area. Asymmetry of bilateral characteristics is low. (author)

  6. Detection of erbB2 copy number variations in plasma of patients with esophageal carcinoma

    International Nuclear Information System (INIS)

    Andolfo, Immacolata; Orditura, Michele; Ciardiello, Fortunato; De Vita, Fernando; Zollo, Massimo; Petrosino, Giuseppe; Vecchione, Loredana; De Antonellis, Pasqualino; Capasso, Mario; Montanaro, Donatella; Gemei, Marica; Troncone, Giancarlo; Iolascon, Achille

    2011-01-01

    Mortality is high in patients with esophageal carcinoma as tumors are rarely detected before the disease has progressed to an advanced stage. Here, we sought to isolate cell-free DNA released into the plasma of patients with esophageal carcinoma, to analyze copy number variations of marker genes in the search for early detection of tumor progression. Plasma of 41 patients with esophageal carcinoma was prospectively collected before tumor resection and chemotherapy. Our dataset resulted heterogeneous for clinical data, resembling the characteristics of the tumor. DNA from the plasma was extracted to analyze copy number variations of the erbB2 gene using real-time PCR assays. The real-time PCR assays for erbB2 gene showed significant (P = 0.001) copy number variations in the plasma of patients with esophageal carcinoma, as compared to healthy controls with high sensitivity (80%) and specificity (95%). These variations in erbB2 were negatively correlated to the progression free survival of these patients (P = 0.03), and revealed a further risk category stratification of patients with low VEGF expression levels. The copy number variation of erbB2 gene from plasma can be used as prognostic marker for early detection of patients at risk of worse clinical outcome in esophageal cancer

  7. Environmentally relevant exposure to 17{alpha}-ethinylestradiol affects the telencephalic proteome of male fathead minnows

    Energy Technology Data Exchange (ETDEWEB)

    Martyniuk, Christopher J., E-mail: cmartyn@unb.ca [Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL, 32611 (United States); Kroll, Kevin J.; Doperalski, Nicholas J.; Barber, David S.; Denslow, Nancy D. [Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL, 32611 (United States)

    2010-07-15

    Estrogens are key mediators of neuronal processes in vertebrates. As such, xenoestrogens present in the environment have the potential to alter normal central nervous system (CNS) function. The objectives of the present study were (1) to identify proteins with altered abundance in the male fathead minnow telencephalon as a result of low-level exposure to17{alpha}-ethinylestradiol (EE{sub 2}), and (2) to better understand the underlying mechanisms of 17{beta}-estradiol (E{sub 2}) feedback in this important neuroendocrine tissue. Male fathead minnows exposed to a measured concentration of 5.4 ng EE{sub 2}/L for 48 h showed decreased plasma E{sub 2} levels of approximately 2-fold. Of 77 proteins that were quantified statistically, 14 proteins were down-regulated after EE{sub 2} exposure, including four histone proteins, ATP synthase, H+ transporting subunits, and metabolic proteins (lactate dehydrogenase B4, malate dehydrogenase 1b). Twelve proteins were significantly induced by EE{sub 2} including microtubule-associated protein tau (Mapt), astrocytic phosphoprotein, ependymin precursor, and calmodulin. Mapt showed an increase in protein abundance but a decrease in mRNA expression after EE{sub 2} exposure{sub ,} suggesting there may be a negative feedback response in the telencephalon to decreased mRNA transcription with increasing Mapt protein abundance. These results demonstrate that a low, environmentally relevant exposure to EE{sub 2} can rapidly alter the abundance of proteins involved in cell differentiation and proliferation, neuron network morphology, and long-term synaptic potentiation. Together, these findings provide a better understanding of the molecular responses underlying E{sub 2} feedback in the brain and demonstrate that quantitative proteomics can be successfully used in ecotoxicology to characterize affected cellular pathways and endocrine physiology.

  8. Multiple-copy entanglement transformation and entanglement catalysis

    International Nuclear Information System (INIS)

    Duan Runyao; Feng Yuan; Li Xin; Ying Mingsheng

    2005-01-01

    We prove that any multiple-copy entanglement transformation [S. Bandyopadhyay, V. Roychowdhury, and U. Sen, Phys. Rev. A 65, 052315 (2002)] can be implemented by a suitable entanglement-assisted local transformation [D. Jonathan and M. B. Plenio, Phys. Rev. Lett. 83, 3566 (1999)]. Furthermore, we show that the combination of multiple-copy entanglement transformation and the entanglement-assisted one is still equivalent to the pure entanglement-assisted one. The mathematical structure of multiple-copy entanglement transformations then is carefully investigated. Many interesting properties of multiple-copy entanglement transformations are presented, which exactly coincide with those satisfied by the entanglement-assisted ones. Most interestingly, we show that an arbitrarily large number of copies of state should be considered in multiple-copy entanglement transformations

  9. Hard Copy Market Overview

    Science.gov (United States)

    Testan, Peter R.

    1987-04-01

    A number of Color Hard Copy (CHC) market drivers are currently indicating strong growth in the use of CHC technologies for the business graphics marketplace. These market drivers relate to product, software, color monitors and color copiers. The use of color in business graphics allows more information to be relayed than is normally the case in a monochrome format. The communicative powers of full-color computer generated output in the business graphics application area will continue to induce end users to desire and require color in their future applications. A number of color hard copy technologies will be utilized in the presentation graphics arena. Thermal transfer, ink jet, photographic and electrophotographic technologies are all expected to be utilized in the business graphics presentation application area in the future. Since the end of 1984, the availability of color application software packages has grown significantly. Sales revenue generated by business graphics software is expected to grow at a compound annual growth rate of just over 40 percent to 1990. Increased availability of packages to allow the integration of text and graphics is expected. Currently, the latest versions of page description languages such as Postscript, Interpress and DDL all support color output. The use of color monitors will also drive the demand for color hard copy in the business graphics market place. The availability of higher resolution screens is allowing color monitors to be easily used for both text and graphics applications in the office environment. During 1987, the sales of color monitors are expected to surpass the sales of monochrome monitors. Another major color hard copy market driver will be the color copier. In order to take advantage of the communications power of computer generated color output, multiple copies are required for distribution. Product introductions of a new generation of color copiers is now underway with additional introductions expected

  10. Pathway-based approaches for assessment of real-time exposure to an estrogenic wastewater treatment plant effluent on fathead minnow reproduction

    Science.gov (United States)

    Cavallin, Jenna E.; Jensen, Kathleen M.; Kahl, Michael D.; Villeneuve, Daniel L.; Lee, Kathy E.; Schroeder, Anthony L.; Mayasich, Joe; Eid, Evan P.; Nelson, Krysta R.; Milsk, Rebecca Y.; Blackwell, Brett R.; Berninger, Jason P.; LaLone, Carlie A.; Blanskma, Chad; Jicha, Terri M.; Elonen, Colleen M.; Johnson, Rodney C.; Ankley, Gerald T.

    2016-01-01

    Wastewater treatment plant (WWTP) effluents are known contributors of chemical mixtures into the environment. Of particular concern are endocrine-disrupting compounds, such as estrogens, which can affect the hypothalamic-pituitary-gonadal axis function in exposed organisms. The present study examined reproductive effects in fathead minnows exposed for 21 d to a historically estrogenic WWTP effluent. Fathead minnow breeding pairs were held in control water or 1 of 3 effluent concentrations (5%, 20%, and 100%) in a novel onsite, flow-through system providing real-time exposure. The authors examined molecular and biochemical endpoints representing key events along adverse outcome pathways linking estrogen receptor activation and other molecular initiating events to reproductive impairment. In addition, the authors used chemical analysis of the effluent to construct a chemical-gene interaction network to aid in targeted gene expression analyses and identifying potentially impacted biological pathways. Cumulative fecundity was significantly reduced in fish exposed to 100% effluent but increased in those exposed to 20% effluent, the approximate dilution factor in the receiving waters. Plasma vitellogenin concentrations in males increased in a dose-dependent manner with effluent concentration; however, male fertility was not impacted. Although in vitro analyses, analytical chemistry, and biomarker responses confirmed the effluent was estrogenic, estrogen receptor agonists were unlikely the primary driver of impaired reproduction. The results provide insights into the significance of pathway-based effects with regard to predicting adverse reproductive outcomes.

  11. Haplotype phasing and inheritance of copy number variants in nuclear families.

    Science.gov (United States)

    Palta, Priit; Kaplinski, Lauris; Nagirnaja, Liina; Veidenberg, Andres; Möls, Märt; Nelis, Mari; Esko, Tõnu; Metspalu, Andres; Laan, Maris; Remm, Maido

    2015-01-01

    DNA copy number variants (CNVs) that alter the copy number of a particular DNA segment in the genome play an important role in human phenotypic variability and disease susceptibility. A number of CNVs overlapping with genes have been shown to confer risk to a variety of human diseases thus highlighting the relevance of addressing the variability of CNVs at a higher resolution. So far, it has not been possible to deterministically infer the allelic composition of different haplotypes present within the CNV regions. We have developed a novel computational method, called PiCNV, which enables to resolve the haplotype sequence composition within CNV regions in nuclear families based on SNP genotyping microarray data. The algorithm allows to i) phase normal and CNV-carrying haplotypes in the copy number variable regions, ii) resolve the allelic copies of rearranged DNA sequence within the haplotypes and iii) infer the heritability of identified haplotypes in trios or larger nuclear families. To our knowledge this is the first program available that can deterministically phase null, mono-, di-, tri- and tetraploid genotypes in CNV loci. We applied our method to study the composition and inheritance of haplotypes in CNV regions of 30 HapMap Yoruban trios and 34 Estonian families. For 93.6% of the CNV loci, PiCNV enabled to unambiguously phase normal and CNV-carrying haplotypes and follow their transmission in the corresponding families. Furthermore, allelic composition analysis identified the co-occurrence of alternative allelic copies within 66.7% of haplotypes carrying copy number gains. We also observed less frequent transmission of CNV-carrying haplotypes from parents to children compared to normal haplotypes and identified an emergence of several de novo deletions and duplications in the offspring.

  12. Haplotype phasing and inheritance of copy number variants in nuclear families.

    Directory of Open Access Journals (Sweden)

    Priit Palta

    Full Text Available DNA copy number variants (CNVs that alter the copy number of a particular DNA segment in the genome play an important role in human phenotypic variability and disease susceptibility. A number of CNVs overlapping with genes have been shown to confer risk to a variety of human diseases thus highlighting the relevance of addressing the variability of CNVs at a higher resolution. So far, it has not been possible to deterministically infer the allelic composition of different haplotypes present within the CNV regions. We have developed a novel computational method, called PiCNV, which enables to resolve the haplotype sequence composition within CNV regions in nuclear families based on SNP genotyping microarray data. The algorithm allows to i phase normal and CNV-carrying haplotypes in the copy number variable regions, ii resolve the allelic copies of rearranged DNA sequence within the haplotypes and iii infer the heritability of identified haplotypes in trios or larger nuclear families. To our knowledge this is the first program available that can deterministically phase null, mono-, di-, tri- and tetraploid genotypes in CNV loci. We applied our method to study the composition and inheritance of haplotypes in CNV regions of 30 HapMap Yoruban trios and 34 Estonian families. For 93.6% of the CNV loci, PiCNV enabled to unambiguously phase normal and CNV-carrying haplotypes and follow their transmission in the corresponding families. Furthermore, allelic composition analysis identified the co-occurrence of alternative allelic copies within 66.7% of haplotypes carrying copy number gains. We also observed less frequent transmission of CNV-carrying haplotypes from parents to children compared to normal haplotypes and identified an emergence of several de novo deletions and duplications in the offspring.

  13. Mitochondrial DNA Copy Number in Peripheral Blood Is Independently Associated with Visceral Fat Accumulation in Healthy Young Adults

    Directory of Open Access Journals (Sweden)

    Jee-Yon Lee

    2014-01-01

    Full Text Available Aims. Visceral obesity is associated with an increased risk of cardiometabolic diseases and it is important to identify the underlying mechanisms. There is growing evidence that mitochondrial dysfunction is associated with metabolic disturbances related to visceral obesity. In addition, maintaining mitochondrial DNA (mtDNA copy number is important for preserving mitochondrial function. Therefore, we investigated the relationship between mtDNA copy number and visceral fat in healthy young adults. Methods. A total of 94 healthy young subjects were studied. Biomarkers of metabolic risk factors were assessed along with body composition by computed tomography. mtDNA copy number was measured in peripheral leukocytes using real-time polymerase chain reaction (PCR methods. Results. The mtDNA copy number correlated with BMI (r=-0.22, P=0.04, waist circumference (r=-0.23, P=0.03, visceral fat area (r=-0.28, P=-0.01, HDL-cholesterol levels (r=0.25, P=0.02, and hs-CRP (r=0.32, P=0.02 after adjusting for age and sex. Both stepwise and nonstepwise multiple regression analyses confirmed that visceral fat area was independently associated with mtDNA copy number (β=-0.33, P<0.01, β=0.32, and P=0.03, resp.. Conclusions. An independent association between mtDNA content and visceral adiposity was identified. These data suggest that mtDNA copy number is a potential predictive marker for metabolic disturbances. Further studies are required to understand the causality and clinical significance of our findings.

  14. Practical method for appearance match between soft copy and hard copy

    Science.gov (United States)

    Katoh, Naoya

    1994-04-01

    CRT monitors are often used as a soft proofing device for the hard copy image output. However, what the user sees on the monitor does not match its output, even if the monitor and the output device are calibrated with CIE/XYZ or CIE/Lab. This is especially obvious when correlated color temperature (CCT) of CRT monitor's white point significantly differs from ambient light. In a typical office environment, one uses a computer graphic monitor having a CCT of 9300K in a room of white fluorescent light of 4150K CCT. In such a case, human visual system is partially adapted to the CRT monitor's white point and partially to the ambient light. The visual experiments were performed on the effect of the ambient lighting. Practical method for soft copy color reproduction that matches the hard copy image in appearance is presented in this paper. This method is fundamentally based on a simple von Kries' adaptation model and takes into account the human visual system's partial adaptation and contrast matching.

  15. Chronic nitrate exposure alters reproductive physiology in fathead minnows.

    Science.gov (United States)

    Kellock, Kristen A; Moore, Adrian P; Bringolf, Robert B

    2018-01-01

    Nitrate is a ubiquitous aquatic pollutant that is commonly associated with eutrophication and dead zones in estuaries around the world. At high concentrations nitrate is toxic to aquatic life but at environmental concentrations it has also been purported as an endocrine disruptor in fish. To investigate the potential for nitrate to cause endocrine disruption in fish, we conducted a lifecycle study with fathead minnows (Pimephales promelas) exposed to nitrate (0, 11.3, and 56.5 mg/L (total nitrate-nitrogen (NO 3 -N)) from nitrate-exposed males both 11-KT and vitellogenin were significantly induced when compared with controls. No significant differences occurred for body mass, condition factor, or GSI among males and intersex was not observed in any of the nitrate treatments. Nitrate-exposed females also had significant increases in vitellogenin compared to controls but no significant differences for mass, condition factor, or GSI were observed in nitrate exposed groups. Estradiol was used as a positive control for vitellogenin induction. Our findings suggest that environmentally relevant nitrate levels may disrupt steroid hormone synthesis and/or metabolism in male and female fish and may have implications for fish reproduction, watershed management, and regulation of nutrient pollution. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Copy Counts

    Science.gov (United States)

    Beaumont, Lee R.

    1970-01-01

    The level of difficulty of straight copy, which is used to measure typewriting speed, is influenced by syllable intensity (the average number of syllables per word), stroke intensity (average number of strokes per word), and high-frequency words. (CH)

  17. Effects of a homologous series of linear alcohol ethoxylate surfactants on fathead minnow early life stages.

    Science.gov (United States)

    Lizotte, R E; Wong, D C; Dorn, P B; Rodgers, J H

    1999-11-01

    Effects of a homologous series of three primarily linear alcohol ethoxylate surfactants were studied in laboratory flow-through 28-day early-life-stage tests with fathead minnow (Pimephales promelas Rafinesque). Surfactants were a C(9-11), C(12-13), and C(14-15) with an average of 6, 6.5, and 7 ethylene oxide units per mole of alcohol, respectively. Average measured surfactant recoveries were 103%, 81%, and 79% of nominal concentrations for the C(9-11) EO 6, C(12-13) EO 6.5, and C(14-15) EO 7 studies, respectively. Embryo survival at 48 h was not adversely affected at any of the concentrations tested. Impaired hatching and deformed fry were observed only in the C(12-13) EO 6.5 study. The 28-day LC50 values were 4.87, 2.39, and 1.02 mg/L for the C(9-11) EO 6, C(12-13) EO 6.5, and C(14-15) EO 7 surfactants, respectively. The corresponding NOECs for survival were 1.01, 1.76, and 0.74 mg/L. Posthatch fry growth was more sensitive than survival for the C(12-13) EO 6.5 and C(14-15) EO 7 surfactants. Survival of posthatch fry decreased with increasing surfactant alkyl chain length. Twenty-eight-day laboratory data were compared to 96-h laboratory, 10-day laboratory and 30-day stream mesocosm data for fathead minnow previously determined for these surfactants. Survival endpoints from the different exposures were comparable and only varied within a factor of two. Similarity of results suggests that it is possible to effectively use 96-h, 10-day, or 28-day laboratory data to predict environmental effects concentrations of these surfactants for fish. http://link.springer-ny. com/link/service/journals/00244/bibs/37n4p536.html

  18. Development of a methodology for successful multigeneration life-cycle testing of the estuarine sheepshead minnow, Cyprinodon variegatus.

    Science.gov (United States)

    Cripe, G M; Hemmer, B L; Goodman, L R; Vennari, J C

    2009-04-01

    Evaluation of effects on fish reproduction and development during chemical exposures lasting for multiple generations is sometimes limited by variable reproductive responses and the time required for the exposure. Established testing methods and the short life cycle of the sheepshead minnow, Cyprinodon variegatus, make this species particularly suitable for use in identifying potential impacts of contaminants in estuarine and marine environments. This study describes the refinement of life-cycle exposure methods that increased the reliability of reproduction in sheepshead minnows and reduced the time to maturation for larvae and juvenile fishes. A test of three spawning chamber designs, three sex ratios, and two photoperiods identified conditions that reduced the coefficient of variation in egg production from >100% to as little as 32%. The most reliable results were produced with groups of three female and two male fishes (all of similar size) when they were placed in a rectangular chamber and acclimated for 12 days. A test water temperature of 26.5 +/- 2 degrees C and a 14L:10D photoperiod resulted in fish producing a mean of 74 embryos per female per day, with a coefficient of variation of 31.8%. Egg fertility exceeded 90%, with a hatch rate of 95% for normal embryos (>or=80% yolk) and a hatch rate of size (>or=2.7 cm standard length) was critical for spawning readiness. Adult fish were prepared for the spawning assessment by adding frozen brine shrimp to their diet. Results of these experiments provide methods that are of particular interest in assessment of endocrine-disrupting chemicals that are known to affect reproduction.

  19. Distribution of Eurasian minnows (Phoxinus: Cypriniformes in the Western Balkans

    Directory of Open Access Journals (Sweden)

    Vucić Matej

    2018-01-01

    Full Text Available The Eurasian minnows of the genus Phoxinus are small cyprinid species, widely distributed across Europe and Asia. Currently, there are at least 15 species in Phoxinus, with preliminary data suggesting more to be described. Despite the discernible increase in research integrating molecular phylogenetic approaches with traditional taxonomy and systematics, inter- and intraspecific relationships in the genus Phoxinus are still poorly known. The aims of this research were to: (i compile data on the distribution of Phoxinus species in Croatia and Bosnia and Herzegovina from the sampling conducted by authors from 2006 to 2016 and from literature sources, and (ii provide a detailed insight on distribution ranges of genetic clades and species of Phoxinus in the western Balkans. Additional 118 localities in Croatia and 8 locations in Bosnia and Herzegovina were added to already known 160 localities from the literature data. Molecular analyses of mitochondrial DNA indicate: (i the presence of Phoxinus marsilii in Croatia (Drava drainage, the Papuk Mountain, around 260 km south of its known distribution range in Hungary, and (ii an exceptional genetic variability of P. lumaireul in the Western Balkans.

  20. Life-cycle toxicity of bis(tributyltin) oxide to the sheepshead minnow (Cyprinodon variegatus).

    Science.gov (United States)

    Manning, C S; Lytle, T F; Walker, W W; Lytle, J S

    1999-08-01

    The effects of tributyltin (TBT) to the life cycle of the estuarine fish Cyprinodon variegatus were examined in a 180-day flow-through exposure. The study was initiated with embryos less than 24 h postfertilization and monitored through hatch, maturation, growth, and reproduction under continuous exposure to mean measured TBT concentrations of 5.4, 3.2, 1.3, 0.66, and 0.41 microg TBT/L. Progeny isolated at the onset of reproduction by the parental generation (F0) were monitored for survival as embryos, survival as fry/juveniles, and growth 30 days postisolation. TBT, at a concentration of 5.4 microg/L, significantly reduced embryo survival of the F0 generation sheepshead minnows. By day 145 of the exposure, significant effects to the survival of this generation increased and included all test concentrations >/=0.66 microg/L. Survival of 0.66 microg/L was reduced 59% relative to control survival by termination of the F0 generation. Growth of F0 generation organisms as measured by standard length was significantly reduced only on day 90 at 3.2 microg/L, however no significant reductions of wet or dry weight related to treatment concentration were detected. Due to complete mortality of organisms exposed to 5.4 microg/L by study day 7, effects to fecundity and progeny were monitored at measured concentrations of 3.2, 1.3, 0.66, and 0.41 microg TBT/L. Fecundity, as measured by the production of viable eggs produced per female per day, was unaffected by any of the test treatments. All F1 generation embryos isolated from treatment chambers into 3.2 microg/L died. Survival, standard length, wet and dry weight of the F1 generation at the remaining treatment concentrations were unaffected. The results of this study indicate that exposure to TBT reduced survival of the F0 generation sheepshead minnow and establishes the lowest observed effect concentration (LOEC) as 0.66 microg TBT/L, and the no observed effect concentration (NOEC) as 0.41 microg TBT/L for this species

  1. 36 CFR 1290.6 - Originals and copies.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Originals and copies. 1290.6... ASSASSINATION RECORDS COLLECTION ACT OF 1992 (JFK ACT) § 1290.6 Originals and copies. (a) For purposes of determining whether originals or copies of assassination records will be made part of the President John F...

  2. Preservation Copying Endangered Historic Negative Collections

    DEFF Research Database (Denmark)

    Kejser, Ulla Bøgvad

    2008-01-01

    This article discusses preservation copying of unstable B&W nitrate and acetate still photographic negatives. It focuses on evaluating two different strategies for preserving the copies from a point of view of quality and cost-effectiveness. The evaluated strategies are preservation of the master...... by describing essential characteristics of negatives, which must be passed on to the copies, and the required metadata and technical imaging specifications. Next the paper discusses strategies for preservation and makes an analysis with the LIFE2 Costing Model. The paper concludes that the most beneficial...... and cost-effective preservation solution for large format negatives is to keep the preservation copies as digital files. However, it also acknowledges that it is important to revisit such strategies regularly to monitor changes in user expectations, technologies and costs....

  3. COPI is required for enterovirus 71 replication.

    Directory of Open Access Journals (Sweden)

    Jianmin Wang

    Full Text Available Enterovirus 71 (EV71, a member of the Picornaviridae family, is found in Asian countries where it causes a wide range of human diseases. No effective therapy is available for the treatment of these infections. Picornaviruses undergo RNA replication in association with membranes of infected cells. COPI and COPII have been shown to be involved in the formation of picornavirus-induced vesicles. Replication of several picornaviruses, including poliovirus and Echovirus 11 (EV11, is dependent on COPI or COPII. Here, we report that COPI, but not COPII, is required for EV71 replication. Replication of EV71 was inhibited by brefeldin A and golgicide A, inhibitors of COPI activity. Furthermore, we found EV71 2C protein interacted with COPI subunits by co-immunoprecipitation and GST pull-down assay, indicating that COPI coatomer might be directed to the viral replication complex through viral 2C protein. Additionally, because the pathway is conserved among different species of enteroviruses, it may represent a novel target for antiviral therapies.

  4. Copy-Editing: The Cambridge Handbook.

    Science.gov (United States)

    Butcher, Judith

    This handbook is designed as a reference manual for copy editors who prepare typescript for printing. It deals with the following topics: the copy editor's function; the work to be done at each stage in the production process; some difficult points of spelling, capitalization, and other features collectively known as "house style"; the parts of a…

  5. Single-copy insertion of transgenes in Caenorhabditis elegans

    DEFF Research Database (Denmark)

    Frøkjaer-Jensen, Christian; Davis, M Wayne; Hopkins, Christopher E

    2008-01-01

    developed a method that inserts a single copy of a transgene into a defined site. Mobilization of a Mos1 transposon generates a double-strand break in noncoding DNA. The break is repaired by copying DNA from an extrachromosomal template into the chromosomal site. Homozygous single-copy insertions can...... be obtained in less than 2 weeks by injecting approximately 20 worms. We have successfully inserted transgenes as long as 9 kb and verified that single copies are inserted at the targeted site. Single-copy transgenes are expressed at endogenous levels and can be expressed in the female and male germlines....

  6. Genome-Wide Association of Copy Number Polymorphisms and Kidney Function.

    Directory of Open Access Journals (Sweden)

    Man Li

    Full Text Available Genome-wide association studies (GWAS using single nucleotide polymorphisms (SNPs have identified more than 50 loci associated with estimated glomerular filtration rate (eGFR, a measure of kidney function. However, significant SNPs account for a small proportion of eGFR variability. Other forms of genetic variation have not been comprehensively evaluated for association with eGFR. In this study, we assess whether changes in germline DNA copy number are associated with GFR estimated from serum creatinine, eGFRcrea. We used hidden Markov models (HMMs to identify copy number polymorphic regions (CNPs from high-throughput SNP arrays for 2,514 African (AA and 8,645 European ancestry (EA participants in the Atherosclerosis Risk in Communities (ARIC study. Separately for the EA and AA cohorts, we used Bayesian Gaussian mixture models to estimate copy number at regions identified by the HMM or previously reported in the HapMap Project. We identified 312 and 464 autosomal CNPs among individuals of EA and AA, respectively. Multivariate models adjusted for SNP-derived covariates of population structure identified one CNP in the EA cohort near genome-wide statistical significance (Bonferroni-adjusted p = 0.067 located on chromosome 5 (876-880kb. Overall, our findings suggest a limited role of CNPs in explaining eGFR variability.

  7. The Stepwise Behavioral Responses: Behavioral Adjustment of the Chinese Rare Minnow (Gobiocypris rarus in the Exposure of Carbamate Pesticides

    Directory of Open Access Journals (Sweden)

    Zongming Ren

    2013-01-01

    Full Text Available In order to illustrate the behavioral regulation in environmental stress, the behavioral responses of the Chinese rare minnow (Gobiocypris rarus to arprocarb, carbofuran, and oxamyl were analyzed with an online monitoring system. The Self-Organizing Map (SOM was used to define the patterns of the behavioral data obtained from treatments at concentrations of 0.1 toxic unit (TU, 1 TU, 2 TU, 5 TU, 10 TU, and 20 TU and a control. In certain cases, differences among the carbamate pesticides (CPs tested were observed. The profiles of behavioral strength (BS in SOM varied according to the concentration used. The time of the first significant decrease of the BS varied inversely with the CP concentrations. The results suggested that the behavioral regulation in the stepwise behavioral responses (SBR was evident. The primary movement behaviors shown by the SBR model included no effect, stimulation, acclimation, adjustment (readjustment, and toxic effect, especially at the lower concentrations. However, higher stress (10 TU and 20 TU might limit the function of the behavioral adjustment produced by the intrinsic response mechanisms. It was concluded that SBR, which were affected by both the concentration and the exposure time, could be used as a suitable indicator in the ecotoxicological risk assessment of CPs.

  8. Copies, Concepts and Time

    Directory of Open Access Journals (Sweden)

    Anne Eriksen

    2017-09-01

    Full Text Available Copies are defined by their relation to an original. The understanding and evaluation of this relationship has been changing over time. A main argument of this article is that originals and copies are phenomena with no "natural" or essential meaning outside of their specific historical settings. The idea to be explored is how changing historicity regimes have transformed notions of originals and copies over time and how these differences also are reflected in the intrinsically temporal relation between the two concepts. The discussion will be framed by two theory sets. The first is Alexander Nagel and Christopher Woods investigation of two kinds of temporality that vied for dominance in works of art in the late Middle Ages and the Renaissance. The second is Walter Benjamins discussion of artwork in the "age of mechanical reproduction", i.e. the twentieth century. The second half of the article seeks to add to the historical complexity described by both theory sets by introducing a concept of tradition and discussing the early modern ideals of exemplarity, emulation and copiousness.

  9. The influence of food quantity on metal bioaccumulation and reproduction in fathead minnows (Pimephales promelas) during chronic exposures to a metal mine effluent.

    Science.gov (United States)

    Ouellet, Jacob D; Dubé, Monique G; Niyogi, Som

    2013-05-01

    Metal mine effluents can impact fish in the receiving environment via both direct effects from exposure as well as indirect effects via food web. The main objective of the present study was to assess whether an indirect effect such as reduced food (prey) availability could influence metal accumulation and reproductive capacity in fish during chronic exposure to a metal mine effluent. Breeding pairs of fathead minnows (Pimephales promelas) were exposed to either reference water (RW) or an environmentally relevant metal mine effluent [45 percent process water effluent (PWE)] for 21 days and fed either low food quantities [LF (a daily ration of 6-10 percent body weight)] or normal food quantities [NF (a daily ration of 20-30 percent body weight)] in artificial stream systems. Fish in RW treatments were fed Chironomus dilutus larvae cultured in RW (Treatments: RW-NF or RW-LF), while fish in PWE treatments were fed C. dilutus larvae cultured in PWE (Treatments: PWE-NF or PWE-LF). Tissue-specific (gill, liver, gonad and carcass) metal accumulation, egg production, and morphometric parameters in fish were analyzed. Fathead minnows that were exposed to LF rations had significantly smaller body, gonad and liver sizes, and were in a relatively poor condition compared to fathead minnows exposed to NF rations, regardless of the treatment water type (RW or PWE) (two-way ANOVA; pmetal-contaminated food in the PWE-NF treatment, tissue metal accumulation pattern were almost similar between the PWE-NF and PWE-LF treatments, except for higher liver barium, cobalt and manganese concentrations in the latter treatment. This indicated that a higher food ration could help reduce the tissue burden of at least some metals and thereby ameliorate the toxicity of metal-mine effluents in fish. More importantly, cumulative egg production in fish was found to be lowest in the PWE-LF treatment, whereas fish egg production in the PWE-NF treatment was not impacted. Overall, these findings suggest

  10. Integration of copy number and transcriptomics provides risk stratification in prostate cancer: A discovery and validation cohort study

    Science.gov (United States)

    Ross-Adams, H.; Lamb, A.D.; Dunning, M.J.; Halim, S.; Lindberg, J.; Massie, C.M.; Egevad, L.A.; Russell, R.; Ramos-Montoya, A.; Vowler, S.L.; Sharma, N.L.; Kay, J.; Whitaker, H.; Clark, J.; Hurst, R.; Gnanapragasam, V.J.; Shah, N.C.; Warren, A.Y.; Cooper, C.S.; Lynch, A.G.; Stark, R.; Mills, I.G.; Grönberg, H.; Neal, D.E.

    2015-01-01

    Background Understanding the heterogeneous genotypes and phenotypes of prostate cancer is fundamental to improving the way we treat this disease. As yet, there are no validated descriptions of prostate cancer subgroups derived from integrated genomics linked with clinical outcome. Methods In a study of 482 tumour, benign and germline samples from 259 men with primary prostate cancer, we used integrative analysis of copy number alterations (CNA) and array transcriptomics to identify genomic loci that affect expression levels of mRNA in an expression quantitative trait loci (eQTL) approach, to stratify patients into subgroups that we then associated with future clinical behaviour, and compared with either CNA or transcriptomics alone. Findings We identified five separate patient subgroups with distinct genomic alterations and expression profiles based on 100 discriminating genes in our separate discovery and validation sets of 125 and 103 men. These subgroups were able to consistently predict biochemical relapse (p = 0.0017 and p = 0.016 respectively) and were further validated in a third cohort with long-term follow-up (p = 0.027). We show the relative contributions of gene expression and copy number data on phenotype, and demonstrate the improved power gained from integrative analyses. We confirm alterations in six genes previously associated with prostate cancer (MAP3K7, MELK, RCBTB2, ELAC2, TPD52, ZBTB4), and also identify 94 genes not previously linked to prostate cancer progression that would not have been detected using either transcript or copy number data alone. We confirm a number of previously published molecular changes associated with high risk disease, including MYC amplification, and NKX3-1, RB1 and PTEN deletions, as well as over-expression of PCA3 and AMACR, and loss of MSMB in tumour tissue. A subset of the 100 genes outperforms established clinical predictors of poor prognosis (PSA, Gleason score), as well as previously published gene

  11. The Hegemony of the Copy

    DEFF Research Database (Denmark)

    Graulund, Rune

    2017-01-01

    This essay questions when the creative process leading tothe original can be said to be complete. When does the series of a pupil’sbotched attempts at perfection leading to “the” singular and unique object,text, tool, or artwork we recognise as the original expression of themaster craftsman stop......? Where is the cut-off point between the differentversions (copies) of earlier inferior iterations in the gestation process thatlead to the original, and final, superior original? This essay chiefly examinesthe manner in which text has been copied and stored in one particulartype of object, namely...... that of the book, in order to provide some fairlywell-known arguments regarding pre-mechanical as well as mechanical reproduction.In particular, it examines the differences between manuscriptculture and print culture as we see them expressed in the production (andreproduction) of master copies and subsequent...

  12. 40 CFR 264.53 - Copies of contingency plan.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Copies of contingency plan. 264.53... Contingency Plan and Emergency Procedures § 264.53 Copies of contingency plan. A copy of the contingency plan... called upon to provide emergency services. [Comment: The contingency plan must be submitted to the...

  13. 40 CFR 265.53 - Copies of contingency plan.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Copies of contingency plan. 265.53... DISPOSAL FACILITIES Contingency Plan and Emergency Procedures § 265.53 Copies of contingency plan. A copy of the contingency plan and all revisions to the plan must be: (a) Maintained at the facility; and (b...

  14. Predator avoidance performance of larval fathead minnows (Pimephales promelas) following short-term exposure to estrogen mixtures

    Science.gov (United States)

    McGee, M.R.; Julius, M.L.; Vajda, A.M.; Norris, D.O.; Barber, L.B.; Schoenfuss, H.L.

    2009-01-01

    Aquatic organisms exposed to endocrine disrupting compounds (EDCs) at early life-stages may have reduced reproductive fitness via disruption of reproductive and non-reproductive behavioral and physiological pathways. Survival to reproductive age relies upon optimal non-reproductive trait expression, such as adequate predator avoidance responses, which may be impacted through EDC exposure. During a predator–prey confrontation, larval fish use an innate C-start escape behavior to rapidly move away from an approaching threat. We tested the hypotheses that (1) larval fathead minnows exposed to estrogens, a primary class of EDCs, singularly or in mixture, suffer a reduced ability to perform an innate C-start behavior when faced with a threat stimulus; (2) additive effects will cause greater reductions in C-start behavior; and (3) effects will differ among developmental stages. In this study, embryos (post-fertilization until hatching) were exposed for 5 days to environmentally relevant concentrations of estrone (E1), 17β-estradiol (E2), and 17α-ethinylestradiol (EE2) singularly and in mixture. Exposed embryos were allowed to hatch and grow in control well water until 12 days old. Similarly, post-hatch fathead minnows were exposed for 12 days to these compounds. High-speed (1000 frames/s) video recordings of escape behavior were collected and transferred to National Institutes of Health Image for frame-by-frame analysis of latency period, escape velocity, and total escape response (combination of latency period and escape velocity). When tested 12 days post-hatch, only E1 adversely affected C-start performance of larvae exposed as embryos. Conversely, larvae exposed for 12 days post-hatch did not exhibit altered escape responses when exposed to E1, while adverse responses were seen in E2 and the estrogen mixture. Ethinylestradiol exposure did not elicit changes in escape behaviors at either developmental stage. The direct impact of reduced C-start performance on

  15. Gauge and non-gauge curvature tensor copies

    International Nuclear Information System (INIS)

    Srivastava, P.P.

    1982-10-01

    A procedure for constructing curvature tensor copies is discussed using the anholonomic geometrical framework. The corresponding geometries are compared and the notion of gauge copy is elucidated. An explicit calculation is also made. (author)

  16. Preliminary studies into the effects of the human pharmaceutical Clofibric acid on sperm parameters in adult Fathead minnow.

    Science.gov (United States)

    Runnalls, Tamsin J; Hala, David N; Sumpter, John P

    2007-08-15

    The effects of Clofibric acid (a persistent environmental metabolite of Clofibrate, a human pharmaceutical), on Fathead minnows were studied. Fibrates are used to prevent cardiovascular disease through their antilipidemic activity. In a series of experiments, in which fish were exposed to waterborne Clofibric acid, no convincing, reproducible antilipidemic effects were observed. In contrast, in three separate experiments, Clofibric acid affected the reproductive axis of fish. Spermatogenesis was apparently impaired, leading to a marked reduction in sperm count in two of the three experiments. Various measures of sperm motility were also reduced, although only significantly so at the highest concentration of Clofibric acid tested (1mg/L). There were also indications that plasma androgen concentrations were reduced. These effects of Clofibric acid on the reproductive axis of fish are similar to those that occur in some mammals as a side-effect of the drug. Taken together, a weight-of-evidence argument would suggest that the main discernable effect of Clofibric acid on fish is likely to be a reproductive, not an antilipidemic, one. Although some of these reproductive effects of Clofibric acid occurred only at a high concentration (1mg/L), others occurred at lower concentrations (microg/litre), near or similar to those reported in the aquatic environment (ng to low microg/litre range). Although we recognise that this is not a definitive study of the effects of Clofibric acid on fish reproduction, the results strongly suggest that Clofibric acid could adversely affect sperm parameters and androgen concentrations in adult Fathead minnows. Further studies are warranted. This may be an example of a drug in which an accidentally discovered side-effect found in mammals turns out to be the most important effect in a different vertebrate group, namely fish.

  17. Associations of common copy number variants in glutathione S-transferase mu 1 and D-dopachrome tautomerase-like protein genes with risk of schizophrenia in a Japanese population.

    Science.gov (United States)

    Nakamura, Toru; Ohnuma, Tohru; Hanzawa, Ryo; Takebayashi, Yuto; Takeda, Mayu; Nishimon, Shohei; Sannohe, Takahiro; Katsuta, Narimasa; Higashiyama, Ryoko; Shibata, Nobuto; Arai, Heii

    2015-10-01

    Oxidative-stress, genetic regions of interest (1p13 and 22q11), and common copy number variations (CNVs) may play roles in the pathophysiology of schizophrenia. In the present study, we confirmed associations between schizophrenia and the common CNVs in the glutathione (GSH)-related genes GSTT1, DDTL, and GSTM1 using quantitative real-time polymerase chain reaction analyses of 620 patients with schizophrenia and in 622 controls. No significant differences in GSTT1 copy number distributions were found between patient groups. However, frequencies of characterized CNVs and assumed gain alleles of DDTL and GSTM1 were significantly higher in patients with schizophrenia. In agreement with a previous report, the present data indicate that gains in the CNV alleles DDTL and GSTM1 are genetic risk factors in Japanese patients with schizophrenia, and suggest involvement of micro-inflammation and oxidative stress in the pathophysiology of schizophrenia. © 2015 Wiley Periodicals, Inc.

  18. Gauge field copies and Higgs mechanism

    International Nuclear Information System (INIS)

    Gleiser, M.

    1982-07-01

    From the algebric classification of the possible solutions of the necessary and sufficient condition for the existence of gauge field copies in two possible classes the Higgs mechanism for the potential obtained from the difference between two copied potentials is applied. It is shown that for class I 'electric type' it is possible to construct a vector field that satisfies an electromagnetic wave equation. For class I 'magnetic type', a vector field that satisfies a non-linear equation as a consequence of the non-abelianity of the theory, is obtained. It is shown that for class II it's not possible to apply the Higgs mechanism. A possible physical interpretation for the 'gauge field copies' phenomenon, is obtained. (author) [pt

  19. Partitioning of copy-number genotypes in pedigrees

    Directory of Open Access Journals (Sweden)

    Andelfinger Gregor U

    2010-05-01

    Full Text Available Abstract Background Copy number variations (CNVs and polymorphisms (CNPs have only recently gained the genetic community's attention. Conservative estimates have shown that CNVs and CNPs might affect more than 10% of the genome and that they may be at least as important as single nucleotide polymorphisms in assessing human variability. Widely used tools for CNP analysis have been implemented in Birdsuite and PLINK for the purpose of conducting genetic association studies based on the unpartitioned total number of CNP copies provided by the intensities from Affymetrix's Genome-Wide Human SNP Array. Here, we are interested in partitioning copy number variations and polymorphisms in extended pedigrees for the purpose of linkage analysis on familial data. Results We have developed CNGen, a new software for the partitioning of copy number polymorphism using the integrated genotypes from Birdsuite with the Affymetrix platform. The algorithm applied to familial trios or extended pedigrees can produce partitioned copy number genotypes with distinct parental alleles. We have validated the algorithm using simulations on a complex pedigree structure using frequencies calculated from a real dataset of 300 genotyped samples from 42 pedigrees segregating a congenital heart defect phenotype. Conclusions CNGen is the first published software for the partitioning of copy number genotypes in pedigrees, making possible the use CNPs and CNVs for linkage analysis. It was implemented with the Python interpreter version 2.5.2. It was successfully tested on current Linux, Windows and Mac OS workstations.

  20. Measurement methods and accuracy in copy number variation: failure to replicate associations of beta-defensin copy number with Crohn's disease

    Science.gov (United States)

    Aldhous, Marian C.; Abu Bakar, Suhaili; Prescott, Natalie J.; Palla, Raquel; Soo, Kimberley; Mansfield, John C.; Mathew, Christopher G.; Satsangi, Jack; Armour, John A.L.

    2010-01-01

    The copy number variation in beta-defensin genes on human chromosome 8 has been proposed to underlie susceptibility to inflammatory disorders, but presents considerable challenges for accurate typing on the scale required for adequately powered case–control studies. In this work, we have used accurate methods of copy number typing based on the paralogue ratio test (PRT) to assess beta-defensin copy number in more than 1500 UK DNA samples including more than 1000 cases of Crohn's disease. A subset of 625 samples was typed using both PRT-based methods and standard real-time PCR methods, from which direct comparisons highlight potentially serious shortcomings of a real-time PCR assay for typing this variant. Comparing our PRT-based results with two previous studies based only on real-time PCR, we find no evidence to support the reported association of Crohn's disease with either low or high beta-defensin copy number; furthermore, it is noteworthy that there are disagreements between different studies on the observed frequency distribution of copy number states among European controls. We suggest safeguards to be adopted in assessing and reporting the accuracy of copy number measurement, with particular emphasis on integer clustering of results, to avoid reporting of spurious associations in future case–control studies. PMID:20858604

  1. Measurement methods and accuracy in copy number variation: failure to replicate associations of beta-defensin copy number with Crohn's disease.

    Science.gov (United States)

    Aldhous, Marian C; Abu Bakar, Suhaili; Prescott, Natalie J; Palla, Raquel; Soo, Kimberley; Mansfield, John C; Mathew, Christopher G; Satsangi, Jack; Armour, John A L

    2010-12-15

    The copy number variation in beta-defensin genes on human chromosome 8 has been proposed to underlie susceptibility to inflammatory disorders, but presents considerable challenges for accurate typing on the scale required for adequately powered case-control studies. In this work, we have used accurate methods of copy number typing based on the paralogue ratio test (PRT) to assess beta-defensin copy number in more than 1500 UK DNA samples including more than 1000 cases of Crohn's disease. A subset of 625 samples was typed using both PRT-based methods and standard real-time PCR methods, from which direct comparisons highlight potentially serious shortcomings of a real-time PCR assay for typing this variant. Comparing our PRT-based results with two previous studies based only on real-time PCR, we find no evidence to support the reported association of Crohn's disease with either low or high beta-defensin copy number; furthermore, it is noteworthy that there are disagreements between different studies on the observed frequency distribution of copy number states among European controls. We suggest safeguards to be adopted in assessing and reporting the accuracy of copy number measurement, with particular emphasis on integer clustering of results, to avoid reporting of spurious associations in future case-control studies.

  2. 75 FR 30106 - Terrorism Risk Insurance Program; Litigation Management Submissions

    Science.gov (United States)

    2010-05-28

    ... DEPARTMENT OF THE TREASURY Terrorism Risk Insurance Program; Litigation Management Submissions... U.S.C. 3506(c)(2)(A)). Currently, the Terrorism Risk Insurance Program Office is seeking comments... or by mail (if hard copy, preferably an original and two copies) to: Terrorism Risk Insurance Program...

  3. The double copy: Bremsstrahlung and accelerating black holes

    CERN Document Server

    Luna, Andres; Nicholson, Isobel; O'Connell, Donal; White, Chris D

    2016-01-01

    Advances in our understanding of perturbation theory suggest the existence of a correspondence between classical general relativity and Yang-Mills theory. A concrete example of this correspondence, which is known as the double copy, was recently introduced for the case of stationary Kerr-Schild spacetimes. Building on this foundation, we examine the simple time-dependent case of an accelerating, radiating point source. The gravitational solution, which generalises the Schwarzschild solution, includes a non-trivial stress-energy tensor. This stress-energy tensor corresponds to a gauge theoretic current in the double copy. We interpret both of these sources as representing the radiative part of the field. Furthermore, in the simple example of Bremsstrahlung, we determine a scattering amplitude describing the radiation, maintaining the double copy throughout. Our results provide the strongest evidence yet that the classical double copy is directly related to the BCJ double copy for scattering amplitudes.

  4. The λ transformation and gravitational copies

    International Nuclear Information System (INIS)

    Silva, M.R. da.

    1984-01-01

    An Abelian symmetry already considered by Einstein with respect to his asymmetrical field theories is related to the gravitational and gauge field copy phenomenon. It is shown that gauge field copies arise out of a straightforward generalization of the λ - map. The connection between Einstein's work on the λ-transformation and the copy phenomenon is obtained with the help of the Frobenius Theorem on the existence of foliations on a differentiable manifold. A problem like the one above is usually treated within the language of (intrinsic) Differential Geometry; General Relativity and classical unified field theories are traditionally developed in a classical style, that gap, a long introduction is prepared where the same structures are studied from the traditional and from the more recent point of view. (author)

  5. Assessing the sublethal effects of in-river concentrations of parameters contributing to cumulative effects in the Athabasca river basin using a fathead minnow bioassay.

    Science.gov (United States)

    Squires, Allison J; Dubé, Monique G; Rozon-Ramilo, Lisa D

    2013-03-01

    The Athabasca River basin, located in Alberta, Canada, covers 157, 000 km(2) and holds significant cultural and economic importance. Recent research assessed changes in several water quality and quantity parameters that have changed both spatially (along the river continuum) and temporally (pre-development and present day) in the Athabasca River Basin. In particular, parameters such as salinity and dissolved sulphate have changed significantly across the Athabasca River mainstem over the past five decades. Further laboratory testing has linked concentrations of these parameters to changes in fathead minnow reproduction. Research is required to determine whether these changes observed in the laboratory can be applied to actual in-river conditions. The objectives of the present study were to twofold: assess changes in fathead minnow response metrics (i.e., condition, liver and gonad size, egg production, and gill histology) associated with increasing concentrations of salinity and dissolved sulphate and determine whether sublethal effect thresholds established in laboratory experiments correspond to actual in-river concentrations using water from the mouth and headwaters of the Athabasca River. Three dose-response experiments (NaCl, SO4, and water sampled from the mouth of the Athabasca River) were conducted at Jasper National Park, Alberta, Canada. Significant increases in mean eggs per female per day occurred at the 50% treatment for the mouth experiment and thresholds previously developed in the laboratory were verified. Copyright © 2012 SETAC.

  6. DNA replication stress restricts ribosomal DNA copy number.

    Science.gov (United States)

    Salim, Devika; Bradford, William D; Freeland, Amy; Cady, Gillian; Wang, Jianmin; Pruitt, Steven C; Gerton, Jennifer L

    2017-09-01

    Ribosomal RNAs (rRNAs) in budding yeast are encoded by ~100-200 repeats of a 9.1kb sequence arranged in tandem on chromosome XII, the ribosomal DNA (rDNA) locus. Copy number of rDNA repeat units in eukaryotic cells is maintained far in excess of the requirement for ribosome biogenesis. Despite the importance of the repeats for both ribosomal and non-ribosomal functions, it is currently not known how "normal" copy number is determined or maintained. To identify essential genes involved in the maintenance of rDNA copy number, we developed a droplet digital PCR based assay to measure rDNA copy number in yeast and used it to screen a yeast conditional temperature-sensitive mutant collection of essential genes. Our screen revealed that low rDNA copy number is associated with compromised DNA replication. Further, subculturing yeast under two separate conditions of DNA replication stress selected for a contraction of the rDNA array independent of the replication fork blocking protein, Fob1. Interestingly, cells with a contracted array grew better than their counterparts with normal copy number under conditions of DNA replication stress. Our data indicate that DNA replication stresses select for a smaller rDNA array. We speculate that this liberates scarce replication factors for use by the rest of the genome, which in turn helps cells complete DNA replication and continue to propagate. Interestingly, tumors from mini chromosome maintenance 2 (MCM2)-deficient mice also show a loss of rDNA repeats. Our data suggest that a reduction in rDNA copy number may indicate a history of DNA replication stress, and that rDNA array size could serve as a diagnostic marker for replication stress. Taken together, these data begin to suggest the selective pressures that combine to yield a "normal" rDNA copy number.

  7. DNA replication stress restricts ribosomal DNA copy number

    Science.gov (United States)

    Salim, Devika; Bradford, William D.; Freeland, Amy; Cady, Gillian; Wang, Jianmin

    2017-01-01

    Ribosomal RNAs (rRNAs) in budding yeast are encoded by ~100–200 repeats of a 9.1kb sequence arranged in tandem on chromosome XII, the ribosomal DNA (rDNA) locus. Copy number of rDNA repeat units in eukaryotic cells is maintained far in excess of the requirement for ribosome biogenesis. Despite the importance of the repeats for both ribosomal and non-ribosomal functions, it is currently not known how “normal” copy number is determined or maintained. To identify essential genes involved in the maintenance of rDNA copy number, we developed a droplet digital PCR based assay to measure rDNA copy number in yeast and used it to screen a yeast conditional temperature-sensitive mutant collection of essential genes. Our screen revealed that low rDNA copy number is associated with compromised DNA replication. Further, subculturing yeast under two separate conditions of DNA replication stress selected for a contraction of the rDNA array independent of the replication fork blocking protein, Fob1. Interestingly, cells with a contracted array grew better than their counterparts with normal copy number under conditions of DNA replication stress. Our data indicate that DNA replication stresses select for a smaller rDNA array. We speculate that this liberates scarce replication factors for use by the rest of the genome, which in turn helps cells complete DNA replication and continue to propagate. Interestingly, tumors from mini chromosome maintenance 2 (MCM2)-deficient mice also show a loss of rDNA repeats. Our data suggest that a reduction in rDNA copy number may indicate a history of DNA replication stress, and that rDNA array size could serve as a diagnostic marker for replication stress. Taken together, these data begin to suggest the selective pressures that combine to yield a “normal” rDNA copy number. PMID:28915237

  8. DNA replication stress restricts ribosomal DNA copy number.

    Directory of Open Access Journals (Sweden)

    Devika Salim

    2017-09-01

    Full Text Available Ribosomal RNAs (rRNAs in budding yeast are encoded by ~100-200 repeats of a 9.1kb sequence arranged in tandem on chromosome XII, the ribosomal DNA (rDNA locus. Copy number of rDNA repeat units in eukaryotic cells is maintained far in excess of the requirement for ribosome biogenesis. Despite the importance of the repeats for both ribosomal and non-ribosomal functions, it is currently not known how "normal" copy number is determined or maintained. To identify essential genes involved in the maintenance of rDNA copy number, we developed a droplet digital PCR based assay to measure rDNA copy number in yeast and used it to screen a yeast conditional temperature-sensitive mutant collection of essential genes. Our screen revealed that low rDNA copy number is associated with compromised DNA replication. Further, subculturing yeast under two separate conditions of DNA replication stress selected for a contraction of the rDNA array independent of the replication fork blocking protein, Fob1. Interestingly, cells with a contracted array grew better than their counterparts with normal copy number under conditions of DNA replication stress. Our data indicate that DNA replication stresses select for a smaller rDNA array. We speculate that this liberates scarce replication factors for use by the rest of the genome, which in turn helps cells complete DNA replication and continue to propagate. Interestingly, tumors from mini chromosome maintenance 2 (MCM2-deficient mice also show a loss of rDNA repeats. Our data suggest that a reduction in rDNA copy number may indicate a history of DNA replication stress, and that rDNA array size could serve as a diagnostic marker for replication stress. Taken together, these data begin to suggest the selective pressures that combine to yield a "normal" rDNA copy number.

  9. Hacking DNA copy number for circuit engineering.

    Science.gov (United States)

    Wu, Feilun; You, Lingchong

    2017-07-27

    DNA copy number represents an essential parameter in the dynamics of synthetic gene circuits but typically is not explicitly considered. A new study demonstrates how dynamic control of DNA copy number can serve as an effective strategy to program robust oscillations in gene expression circuits.

  10. Physiological Responses in Chinese Rare Minnow Larvae Following Exposure to Low-Dose Tributyltin.

    Science.gov (United States)

    Li, Ping; Li, Zhi-Hua

    2015-11-01

    In the present study, the antioxidant response and acetylcholinesterase (AChE) activity were measured in Chinese rare minnow larvae (Gobiocypris rarus) after exposure to tributyltin (TBT) (0, 100, 400 and 800 ngL(-1)) for 7 days, as well as the expression of a series of genes, including cr, aptase and prl genes involved in the ion-regulatory process and igfbp3 and gh related to growth rate. Results shows that oxidative stress was generated in fish exposed to TBT, as evidenced by elevated malondialdehyde levels and the inhibition of antioxidant parameters. The activity of acetylcholinesterase (AChE) was also inhibited in fish under higher TBT stress. Moreover, genes involved in ion regulation and growth were affected, based on the regulated transcription of the cr, atpase, gh, prl and igfbp3 genes in the treated groups. The observed effects of TBT upon antioxidant responses and altered expression of genes provides insight into the use of these molecular biomarkers in evaluating mechanisms of TBT toxicity in fish.

  11. GSTM1 copy number and promoter haplotype as predictors for risk of recurrence and/or second primary tumor in patients with head and neck cancer

    Directory of Open Access Journals (Sweden)

    Zhang X

    2013-03-01

    Full Text Available Xuemei Zhang,1 Maosheng Huang,2 Xifeng Wu,2 Susan Kadlubar,1 Jie Lin,2 Xinfeng Yu,1 Chunyang Fan,3 Baitang Ning,4 Fred F Kadlubar1†1University of Arkansas for Medical Sciences, Little Rock, Arkansas, 2The University of Texas MD Anderson Cancer Center, Houston, Texas, 3VA hospital, Little Rock, Arkansas, 4National Center for Toxicological Research, US Food and Drug Administration, Jefferson, Arkansas, USA†Fred F Kadlubar passed away on December 4, 2010.Abstract: The objective of this study was to determine copy number variant (CNV and promoter genetic variants in glutathione S-transferase Mu class 1 (GSTM1 and the risk of recurrence (REC/second primary tumor (SPT in patients with previously diagnosed early stage head and neck cancer. Among 441 subjects, 133 experienced REC and/or an SPT, while 308 had single primary disease. TaqMan real-time polymerase chain reaction was used to measure the exact copy number of GSTM1 and direct sequencing was used to determine genetic variants in the GSTM1 promoter region. Multivariate Cox regression analysis was performed to estimate hazard ratios (HRs and 95% confidence intervals (95% CIs associated with copy number and genetic variants. REC/SPT-free survival times were compared by constructing Kaplan–Meier curves and differences between curves were tested by logrank test. Results showed a significantly decreased REC/SPT (HR = 0.57; 95% CI = 0.35–0.95 and longer REC/SPT-free survival in subjects with at least two copies of GSTM1 compared with the GSTM1 homozygous deletion, but not in those with one copy of GSTM1. The −498G, −426G, and −339T alleles were significantly associated with REC/SPT, with HRs of 0.11 (0.02–0.85, 0.28 (0.11–0.74 and 2.02 (1.07–3.82, respectively. Kaplan–Meier survival analysis showed that the −498G, −426G, and −339C alleles were also significantly associated with increased REC/SPT-free survival. Further haplotype analysis showed the haplotype P-498G--426G--339

  12. Readability as a Factor in Magazine Ad Copy Recall.

    Science.gov (United States)

    Wesson, David A.

    1989-01-01

    Examines the relationship between advertising copy readability and advertising effectiveness. Finds that recall is improved when the copy style is either fairly easy or fairly hard to read. Suggests the value of considering copy readability as a potential contributor, though a minor one, to the success of magazine advertising. (RS)

  13. Elimination of Parallel Copies using Code Motion on Data Dependence Graphs

    DEFF Research Database (Denmark)

    Brandner, Florian; Colombet, Quentin

    2013-01-01

    , while at the same time a valid register assignment is preserved. Our results show that even after traditional register allocation with coalescing our technique is able to eliminate an additional 3% (up to 9%) of the remaining copies and reduce the weighted costs of register copies by up to 25......Register allocation regained much interest in recent years due to the development of decoupled strategies that split the problem into separate phases: spilling, register assignment, and copy elimination. Traditional approaches to copy elimination during register allocation are based on interference......% for the SPECINT 2000 benchmarks. In comparison to Parallel Copy Motion, our technique removes 11% (up to 20%) more copies and up to 39% more of the copy costs....

  14. Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects

    DEFF Research Database (Denmark)

    Marshall, Christian R.; Howrigan, Daniel P.; Merico, Daniele

    2017-01-01

    Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline...

  15. A comprehensive profile of DNA copy number variations in a Korean population: identification of copy number invariant regions among Koreans.

    Science.gov (United States)

    Jeon, Jae Pil; Shim, Sung Mi; Jung, Jong Sun; Nam, Hye Young; Lee, Hye Jin; Oh, Berm Seok; Kim, Kuchan; Kim, Hyung Lae; Han, Bok Ghee

    2009-09-30

    To examine copy number variations among the Korean population, we compared individual genomes with the Korean reference genome assembly using the publicly available Korean HapMap SNP 50 k chip data from 90 individuals. Korean individuals exhibited 123 copy number variation regions (CNVRs) covering 27.2 mb, equivalent to 1.0% of the genome in the copy number variation (CNV) analysis using the combined criteria of P value (Por= 0.25) among study subjects. In contrast, when compared to the Affymetrix reference genome assembly from multiple ethnic groups, considerably more CNVRs (n=643) were detected in larger proportions (5.0%) of the genome covering 135.1 mb even by more stringent criteria (Por=0.25), reflecting ethnic diversity of structural variations between Korean and other populations. Some CNVRs were validated by the quantitative multiplex PCR of short fluorescent fragment (QMPSF) method, and then copy number invariant regions were detected among the study subjects. These copy number invariant regions would be used as good internal controls for further CNV studies. Lastly, we demonstrated that the CNV information could stratify even a single ethnic population with a proper reference genome assembly from multiple heterogeneous populations.

  16. Copy-number and gene dependency analysis reveals partial copy loss of wild-type SF3B1 as a novel cancer vulnerability. | Office of Cancer Genomics

    Science.gov (United States)

    Genomic instability is a hallmark of human cancer, and results in widespread somatic copy number alterations. We used a genome-scale shRNA viability screen in human cancer cell lines to systematically identify genes that are essential in the context of particular copy-number alterations (copy-number associated gene dependencies). The most enriched class of copy-number associated gene dependencies was CYCLOPS (Copy-number alterations Yielding Cancer Liabilities Owing to Partial losS) genes, and spliceosome components were the most prevalent.

  17. Vocal copying of individually distinctive signature whistles in bottlenose dolphins

    Science.gov (United States)

    King, Stephanie L.; Sayigh, Laela S.; Wells, Randall S.; Fellner, Wendi; Janik, Vincent M.

    2013-01-01

    Vocal learning is relatively common in birds but less so in mammals. Sexual selection and individual or group recognition have been identified as major forces in its evolution. While important in the development of vocal displays, vocal learning also allows signal copying in social interactions. Such copying can function in addressing or labelling selected conspecifics. Most examples of addressing in non-humans come from bird song, where matching occurs in an aggressive context. However, in other animals, addressing with learned signals is very much an affiliative signal. We studied the function of vocal copying in a mammal that shows vocal learning as well as complex cognitive and social behaviour, the bottlenose dolphin (Tursiops truncatus). Copying occurred almost exclusively between close associates such as mother–calf pairs and male alliances during separation and was not followed by aggression. All copies were clearly recognizable as such because copiers consistently modified some acoustic parameters of a signal when copying it. We found no evidence for the use of copying in aggression or deception. This use of vocal copying is similar to its use in human language, where the maintenance of social bonds appears to be more important than the immediate defence of resources. PMID:23427174

  18. "Dear Teacher, Johnny Copied."

    Science.gov (United States)

    Jackson, Louise A.; And Others

    1987-01-01

    Presents the problem of intentional or unintentional plagiarism on the part of young students, several possible causes for it, and offers ways teachers can help students avoid copying and understand the value of owning one's writing. (JC)

  19. 38 CFR 1.526 - Copies of records and papers.

    Science.gov (United States)

    2010-07-01

    ... papers. 1.526 Section 1.526 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... Copies of records and papers. (a) Any person desiring a copy of any record or document in the custody of... plain one-sided paper copies of a standard size (81/2″ × 11″; 81/2″ × 14″; 11″ × 14″) $0.15 per page...

  20. The classical double copy for Taub–NUT spacetime

    Energy Technology Data Exchange (ETDEWEB)

    Luna, Andrés, E-mail: a.luna-godoy.1@research.gla.ac.uk [School of Physics and Astronomy, University of Glasgow, Glasgow G12 8QQ, Scotland (United Kingdom); Monteiro, Ricardo, E-mail: monteiro@maths.ox.ac.uk [Mathematical Institute, University of Oxford, Oxford OX2 6GG, England (United Kingdom); O' Connell, Donal, E-mail: donal@staffmail.ed.ac.uk [Higgs Centre for Theoretical Physics, School of Physics and Astronomy, The University of Edinburgh, Edinburgh EH9 3JZ, Scotland (United Kingdom); Kavli Institute for Theoretical Physics, University of California, Santa Barbara, CA 93106-4030 (United States); White, Chris D., E-mail: Christopher.White@glasgow.ac.uk [School of Physics and Astronomy, University of Glasgow, Glasgow G12 8QQ, Scotland (United Kingdom)

    2015-11-12

    The double copy is a much-studied relationship between gauge theory and gravity amplitudes. Recently, this was generalised to an infinite family of classical solutions to Einstein's equations, namely stationary Kerr–Schild geometries. In this paper, we extend this to the Taub–NUT solution in gravity, which has a double Kerr–Schild form. The single copy of this solution is a dyon, whose electric and magnetic charges are related to the mass and NUT charge in the gravity theory. Finally, we find hints that the classical double copy extends to curved background geometries.

  1. Ammonia causes decreased brain monoamines in fathead minnows (Pimephales promelas)

    Science.gov (United States)

    Ronan, Patrick J.; Gaikowski, Mark P.; Hamilton, Steven J.; Buhl, Kevin J.; Summers, Cliff H.

    2007-01-01

    Hyperammonemia, arising from variety of disorders, leads to severe neurological dysfunction. The mechanisms of ammonia toxicity in brain are not completely understood. This study investigated the effects of ammonia on monoaminergic systems in brains of fathead minnows (Pimephales promelas). Fish serve as a good model system to investigate hyperammonemic effects on brain function since no liver manipulations are necessary to increase endogenous ammonia concentrations. Using high performance liquid chromatography with electrochemical detection, monoamines and some associated metabolites were measured from whole brain homogenate. Adult males were exposed for 48 h to six different concentrations of ammonia (0.01–2.36 mg/l unionized) which bracketed the 96-h LC50 for this species. Ammonia concentration-dependent decreases were found for the catecholamines (norepinephrine and dopamine) and the indoleamine serotonin (5-HT). After an initial increase in the 5-HT precursor 5-hydroxytryptophan it too decreased with increasing ammonia concentrations. There were also significant increases in the 5-HIAA/5-HT and DOPAC/DA ratios, often used as measures of turnover. There were no changes in epinephrine (Epi) or monoamine catabolites (DOPAC, 5-HIAA) at any ammonia concentrations tested. Results suggest that ammonia causes decreased synthesis while also causing increased release and degradation. Increased release may underlie behavioral reactions to ammonia exposure in fish. This study adds weight to a growing body of evidence demonstrating that ammonia leads to dysfunctional monoaminergic systems in brain which may underlie neurological symptoms associated with human disorders such as hepatic encephalopathy.

  2. 29 CFR 1956.84 - Location of plan for inspection and copying.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Location of plan for inspection and copying. 1956.84... PLANS Illinois § 1956.84 Location of plan for inspection and copying. A copy of the plan may be inspected and copied during normal business hours at the following locations: Office of State Programs, U.S...

  3. Changes of hematological and biochemical parameters revealed genotoxicity and immunotoxicity of neonicotinoids on Chinese rare minnows (Gobiocypris rarus).

    Science.gov (United States)

    Hong, Xiangsheng; Zhao, Xu; Tian, Xue; Li, Jiasu; Zha, Jinmiao

    2018-02-01

    Adverse impacts of immunity in terrestrial non-target organisms exposed to neonicotinoid insecticides have been reported, but the causal link between insecticide exposure and possible immune alterations in fish remains limited. In the present study, the potential genotoxicity and immunotoxicity of three neonicotinoids (imidacloprid, nitenpyram, and dinotefuran) were assessed in Chinese rare minnows by using a 60-day chronic toxicity test. The hematological and biochemical parameters of juvenile Chinese rare minnows and changes in the transcription of six inflammation-related genes were determined after exposure to neonicotinoids at 0.1, 0.5, or 2.0 mg/L. A clear difference in the frequency of erythrocytes with micronuclei (MN) was observed after treatment with 2.0 mg/L imidacloprid (p < .05). Additionally, exposure to 0.5 or 2.0 mg/L imidacloprid significantly increased the binucleated (BN) erythrocytes and those with notched nuclei (NT) (p < .05). A serum protein electrophoresis (SPE) assay showed significant alterations in the serum protein in all treatments (p < .05), and further analysis indicated decreases in immunoglobulin (Ig) in treatments with 0.5 or 2.0 mg/L imidacloprid or dinotefuran or with 0.1 mg/L nitenpyram (p < .05). Moreover, a biochemical assay confirmed that immunoglobulin M (IgM) levels were indeed significantly decreased upon treatment with imidacloprid or dinotefuran at 0.5 or 2.0 mg/L (p < .05). In addition, the transcriptional levels of the inflammatory cytokines IL-6, INF-α, TNF-α, and IL-1β were markedly down-regulated after all imidacloprid treatments (p < .05), whereas the expression levels of only TNF-α and IL-1β were significantly down-regulated following the 0.5 and 2.0 mg/L dinotefuran treatments (p < .05). Taken together, our results clearly demonstrate that imidacloprid, rather than nitenpyram and dinotefuran, can induce genotoxicity. The responsiveness of these immune indicators

  4. 29 CFR 1956.64 - Location of plan for inspection and copying.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Location of plan for inspection and copying. 1956.64... PLANS New Jersey § 1956.64 Location of plan for inspection and copying. A copy of the plan may be inspected and copied during normal business hours at the following locations: Office of State Programs, U.S...

  5. Quantum copying and simplification of the quantum Fourier transform

    Science.gov (United States)

    Niu, Chi-Sheng

    Theoretical studies of quantum computation and quantum information theory are presented in this thesis. Three topics are considered: simplification of the quantum Fourier transform in Shor's algorithm, optimal eavesdropping in the BB84 quantum cryptographic protocol, and quantum copying of one qubit. The quantum Fourier transform preceding the final measurement in Shor's algorithm is simplified by replacing a network of quantum gates with one that has fewer and simpler gates controlled by classical signals. This simplification results from an analysis of the network using the consistent history approach to quantum mechanics. The optimal amount of information which an eavesdropper can gain, for a given level of noise in the communication channel, is worked out for the BB84 quantum cryptographic protocol. The optimal eavesdropping strategy is expressed in terms of various quantum networks. A consistent history analysis of these networks using two conjugate quantum bases shows how the information gain in one basis influences the noise level in the conjugate basis. The no-cloning property of quantum systems, which is the physics behind quantum cryptography, is studied by considering copying machines that generate two imperfect copies of one qubit. The best qualities these copies can have are worked out with the help of the Bloch sphere representation for one qubit, and a quantum network is worked out for an optimal copying machine. If the copying machine does not have additional ancillary qubits, the copying process can be viewed using a 2-dimensional subspace in a product space of two qubits. A special representation of such a two-dimensional subspace makes possible a complete characterization of this type of copying. This characterization in turn leads to simplified eavesdropping strategies in the BB84 and the B92 quantum cryptographic protocols.

  6. Determination of beta-defensin genomic copy number in different populations

    DEFF Research Database (Denmark)

    Fode, Peder; Jespersgaard, Cathrine; Hardwick, Robert J

    2011-01-01

    There have been conflicting reports in the literature on association of gene copy number with disease, including CCL3L1 and HIV susceptibility, and ß-defensins and Crohn's disease. Quantification of precise gene copy numbers is important in order to define any association of gene copy number with...

  7. Catchment-scale determinants of nonindigenous minnow richness in the eastern United States

    Science.gov (United States)

    Peoples, Brandon K.; Midway, Stephen R.; DeWeber, Jefferson T.; Wagner, Tyler

    2018-01-01

    Understanding the drivers of biological invasions is critical for preserving aquatic biodiversity. Stream fishes make excellent model taxa for examining mechanisms driving species introduction success because their distributions are naturally limited by catchment boundaries. In this study, we compared the relative importance of catchment-scale abiotic and biotic predictors of native and nonindigenous minnow (Cyprinidae) richness in 170 catchments throughout the eastern United States. We compared historic and contemporary cyprinid distributional data to determine catchment-wise native/nonindigenous status for 152 species. Catchment-scale model predictor variables described natural (elevation, precipitation, flow accumulation) and anthropogenic (developed land cover, number of dams) abiotic features, as well as native congener richness. Native congener richness may represent either biotic resistance via interspecific competition, or trait preadaptation according to Darwin's naturalisation hypothesis. We used generalised linear mixed models to examine evidence supporting the relative roles of abiotic and biotic predictors of cyprinid introduction success. Native congener richness was positively correlated with nonindigenous cyprinid richness and was the most important variable predicting nonindigenous cyprinid richness. Mean elevation had a weak positive effect, and effects of other abiotic factors were insignificant and less important. Our results suggest that at this spatial scale, trait preadaptation may be more important than intrageneric competition for determining richness of nonindigenous fishes.

  8. Hard copies for digital medical images: an overview

    Science.gov (United States)

    Blume, Hartwig R.; Muka, Edward

    1995-04-01

    This paper is a condensed version of an invited overview on the technology of film hard-copies used in radiology. Because the overview was given to an essentially nonmedical audience, the reliance on film hard-copies in radiology is outlined in greater detail. The overview is concerned with laser image recorders generating monochrome prints on silver-halide films. The basic components of laser image recorders are sketched. The paper concentrates on the physical parameters - characteristic function, dynamic range, digitization resolution, modulation transfer function, and noise power spectrum - which define image quality and information transfer capability of the printed image. A preliminary approach is presented to compare the printed image quality with noise in the acquired image as well as with the noise of state-of- the-art cathode-ray-tube display systems. High-performance laser-image- recorder/silver-halide-film/light-box systems are well capable of reproducing acquired radiologic information. Most recently development was begun toward a display function standard for soft-copy display systems to facilitate similarity of image presentation between different soft-copy displays as well as between soft- and hard-copy displays. The standard display function is based on perceptional linearization. The standard is briefly reviewed to encourage the printer industry to adopt it, too.

  9. Assessing the potential impact of non-proprietary drug copies on quality of medicine and treatment in patients with relapsing multiple sclerosis: the experience with fingolimod

    Directory of Open Access Journals (Sweden)

    Correale J

    2014-06-01

    Full Text Available Jorge Correale,1 Erwin Chiquete,2 Snezana Milojevic,3 Nadina Frider,3 Imre Bajusz31Raúl Carrea Institute for Neurological Research, Foundation for the Fight against Infant Neurological Illnesses, Buenos Aires, Argentina; 2Department of Neurology and Psychiatry, Salvador Zubirán National Institute of Medical Science and Nutrition, Mexico City, Mexico; 3Novartis Pharma AG, Basel, SwitzerlandBackground: Fingolimod is a once-daily oral treatment for relapsing multiple sclerosis, the proprietary production processes of which are tightly controlled, owing to its susceptibility to contamination by impurities, including genotoxic impurities. Many markets produce nonproprietary medicines; assessing their efficacy and safety is difficult as regulators may approve nonproprietary drugs without bioequivalence data, genotoxic evaluation, or risk management plans (RMPs. This assessment is especially important for fingolimod given its solubility/bioavailability profile, genotoxicity risk, and low-dose final product (0.5 mg. This paper presents an evaluation of the quality of proprietary and nonproprietary fingolimod variants.Methods: Proprietary fingolimod was used as a reference substance against which eleven nonproprietary fingolimod copies were assessed. The microparticle size distribution of each compound was assessed by laser light diffraction, and inorganic impurity content by sulfated ash testing. Heavy metals content was quantified using inductively coupled plasma optical emission spectrometry, and levels of unspecified impurities by high-performance liquid chromatography. Solubility was assessed in a range of solvents at different pH values. Key information from the fingolimod RMP is also presented.Results: Nonproprietary fingolimod variants exhibited properties out of proprietary or internationally accepted specifications, including differences in particle size distribution and levels of impurities such as heavy metals. For microparticle size and

  10. Does the survival motor neuron copy number variation play a role in the onset and severity of sporadic amyotrophic lateral sclerosis in Malians?

    Science.gov (United States)

    Sangare, Modibo; Dicko, Ilo; Guinto, Cheick Oumar; Sissoko, Adama; Dembele, Kekouta; Coulibaly, Youlouza; Coulibaly, Siaka Y; Landoure, Guida; Diallo, Abdallah; Dolo, Mamadou; Dolo, Housseini; Maiga, Boubacar; Traore, Moussa; Karembe, Mamadou; Traore, Kadiatou; Toure, Amadou; Sylla, Mariam; Togora, Arouna; Coulibaly, Souleymane; Traore, Sékou Fantamady; Hendrickson, Brant; Bricceno, Katherine; Schindler, Alice B; Kokkinis, Angela; Meilleur, Katherine G; Sangho, Hammadoun Ali; Diakite, Brehima; Kassogue, Yaya; Coulibaly, Yaya Ibrahim; Burnett, Barrington; Maiga, Youssoufa; Doumbia, Seydou; Fischbeck, Kenneth H

    2016-06-01

    Spinal muscular atrophy (SMA) and sporadic amyotrophic lateral sclerosis (SALS) are both motor neuron disorders. SMA results from the deletion of the survival motor neuron ( SMN ) 1 gene. High or low SMN1 copy number and the absence of SMN2 have been reported as risk factors for the development or severity of SALS. To investigate the role of SMN gene copy number in the onset and severity of SALS in Malians. We determined the SMN1 and SMN2 copy number in genomic DNA samples from 391 Malian adult volunteers, 120 Yoruba from Nigeria, 120 Luyha from Kenya and 74 U.S. Caucasians using a Taqman quantitative PCR assay. We evaluated the SALS risk based on the estimated SMA protein level using the Veldink formula ( SMN1 copy number + 0.2 ∗  SMN2 copy number). We also characterized the disease natural history in 15 ALS patients at the teaching hospital of Point G, Bamako, Mali. We found that 131 of 391 (33.5%) had an estimated SMN protein expression of ≤ 2.2; 60 out of 391 (15.3%) had an estimated SMN protein expression < 2 and would be at risk of ALS and the disease onset was as early as 16 years old. All 15 patients were male and some were physically handicapped within 1-2 years in the disease course. Because of the short survival time of our patients, family histories and sample DNA for testing were not done. However, our results show that sporadic ALS is of earlier onset and shorter survival time as compared to patients elsewhere. We plan to establish a network of neurologists and researchers for early screening of ALS.

  11. 39 CFR 955.23 - Copies of papers, withdrawal of exhibits.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Copies of papers, withdrawal of exhibits. 955.23... SERVICE BOARD OF CONTRACT APPEALS § 955.23 Copies of papers, withdrawal of exhibits. (a) When books, records, papers, or documents have been received in evidence, a true copy thereof or of such part thereof...

  12. 19 CFR 210.55 - Content of service copies.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 3 2010-04-01 2010-04-01 false Content of service copies. 210.55 Section 210.55 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION INVESTIGATIONS OF UNFAIR PRACTICES IN IMPORT TRADE ADJUDICATION AND ENFORCEMENT Temporary Relief § 210.55 Content of service copies. (a) Any...

  13. aCNViewer: Comprehensive genome-wide visualization of absolute copy number and copy neutral variations.

    Directory of Open Access Journals (Sweden)

    Victor Renault

    Full Text Available Copy number variations (CNV include net gains or losses of part or whole chromosomal regions. They differ from copy neutral loss of heterozygosity (cn-LOH events which do not induce any net change in the copy number and are often associated with uniparental disomy. These phenomena have long been reported to be associated with diseases and particularly in cancer. Losses/gains of genomic regions are often correlated with lower/higher gene expression. On the other hand, loss of heterozygosity (LOH and cn-LOH are common events in cancer and may be associated with the loss of a functional tumor suppressor gene. Therefore, identifying recurrent CNV and cn-LOH events can be important as they may highlight common biological components and give insights into the development or mechanisms of a disease. However, no currently available tools allow a comprehensive whole-genome visualization of recurrent CNVs and cn-LOH in groups of samples providing absolute quantification of the aberrations leading to the loss of potentially important information.To overcome these limitations, we developed aCNViewer (Absolute CNV Viewer, a visualization tool for absolute CNVs and cn-LOH across a group of samples. aCNViewer proposes three graphical representations: dendrograms, bi-dimensional heatmaps showing chromosomal regions sharing similar abnormality patterns, and quantitative stacked histograms facilitating the identification of recurrent absolute CNVs and cn-LOH. We illustrated aCNViewer using publically available hepatocellular carcinomas (HCCs Affymetrix SNP Array data (Fig 1A. Regions 1q and 8q present a similar percentage of total gains but significantly different copy number gain categories (p-value of 0.0103 with a Fisher exact test, validated by another cohort of HCCs (p-value of 5.6e-7 (Fig 2B.aCNViewer is implemented in python and R and is available with a GNU GPLv3 license on GitHub https://github.com/FJD-CEPH/aCNViewer and Docker https://hub.docker.com/r/fjdceph/acnviewer/.aCNViewer@cephb.fr.

  14. aCNViewer: Comprehensive genome-wide visualization of absolute copy number and copy neutral variations.

    Science.gov (United States)

    Renault, Victor; Tost, Jörg; Pichon, Fabien; Wang-Renault, Shu-Fang; Letouzé, Eric; Imbeaud, Sandrine; Zucman-Rossi, Jessica; Deleuze, Jean-François; How-Kit, Alexandre

    2017-01-01

    Copy number variations (CNV) include net gains or losses of part or whole chromosomal regions. They differ from copy neutral loss of heterozygosity (cn-LOH) events which do not induce any net change in the copy number and are often associated with uniparental disomy. These phenomena have long been reported to be associated with diseases and particularly in cancer. Losses/gains of genomic regions are often correlated with lower/higher gene expression. On the other hand, loss of heterozygosity (LOH) and cn-LOH are common events in cancer and may be associated with the loss of a functional tumor suppressor gene. Therefore, identifying recurrent CNV and cn-LOH events can be important as they may highlight common biological components and give insights into the development or mechanisms of a disease. However, no currently available tools allow a comprehensive whole-genome visualization of recurrent CNVs and cn-LOH in groups of samples providing absolute quantification of the aberrations leading to the loss of potentially important information. To overcome these limitations, we developed aCNViewer (Absolute CNV Viewer), a visualization tool for absolute CNVs and cn-LOH across a group of samples. aCNViewer proposes three graphical representations: dendrograms, bi-dimensional heatmaps showing chromosomal regions sharing similar abnormality patterns, and quantitative stacked histograms facilitating the identification of recurrent absolute CNVs and cn-LOH. We illustrated aCNViewer using publically available hepatocellular carcinomas (HCCs) Affymetrix SNP Array data (Fig 1A). Regions 1q and 8q present a similar percentage of total gains but significantly different copy number gain categories (p-value of 0.0103 with a Fisher exact test), validated by another cohort of HCCs (p-value of 5.6e-7) (Fig 2B). aCNViewer is implemented in python and R and is available with a GNU GPLv3 license on GitHub https://github.com/FJD-CEPH/aCNViewer and Docker https

  15. Fc-Gamma Receptor 3B Copy Number Variation Is Not a Risk Factor for Behçet’s Disease

    Directory of Open Access Journals (Sweden)

    Rachel Black

    2012-01-01

    Full Text Available Behçet’s disease (BD is an immune-mediated systemic vasculitis associated with HLAB51. Other gene associations are likely and may provide further insight into the pathogenesis of this disease. Fc-gamma receptors play an important role in regulating immune function. Copy number variation (CNV of the Fc-gamma receptor 3B (FCGR3B gene is associated with other inflammatory conditions and may also play a role in BD. The aim of this study was to determine whether CNV of the FCGR3B gene is associated with BD or its clinical features. FCGR3B copy number was determined for 187 Iranian patients and 178 ethnicity-matched controls using quantitative real-time PCR. The genotype frequencies were comparable in both BD patients and controls. The odds ratio for low copy number (2CN was 0.75 (=0.50. There was no association found between high or low CN of the FCGR3B gene and BD or its clinical features in this Iranian population. We are the first to report this finding which, when looked at in the context of other genetic studies, gives us further insight into the complex pathogenesis of BD.

  16. Accuracy and differential bias in copy number measurement of CCL3L1 in association studies with three auto-immune disorders.

    Science.gov (United States)

    Carpenter, Danielle; Walker, Susan; Prescott, Natalie; Schalkwijk, Joost; Armour, John Al

    2011-08-18

    Copy number variation (CNV) contributes to the variation observed between individuals and can influence human disease progression, but the accurate measurement of individual copy numbers is technically challenging. In the work presented here we describe a modification to a previously described paralogue ratio test (PRT) method for genotyping the CCL3L1/CCL4L1 copy variable region, which we use to ascertain CCL3L1/CCL4L1 copy number in 1581 European samples. As the products of CCL3L1 and CCL4L1 potentially play a role in autoimmunity we performed case control association studies with Crohn's disease, rheumatoid arthritis and psoriasis clinical cohorts. We evaluate the PRT methodology used, paying particular attention to accuracy and precision, and highlight the problems of differential bias in copy number measurements. Our PRT methods for measuring copy number were of sufficient precision to detect very slight but systematic differential bias between results from case and control DNA samples in one study. We find no evidence for an association between CCL3L1 copy number and Crohn's disease, rheumatoid arthritis or psoriasis. Differential bias of this small magnitude, but applied systematically across large numbers of samples, would create a serious risk of false positive associations in copy number, if measured using methods of lower precision, or methods relying on single uncorroborated measurements. In this study the small differential bias detected by PRT in one sample set was resolved by a simple pre-treatment by restriction enzyme digestion.

  17. Accuracy and differential bias in copy number measurement of CCL3L1 in association studies with three auto-immune disorders

    Directory of Open Access Journals (Sweden)

    Carpenter Danielle

    2011-08-01

    Full Text Available Abstract Background Copy number variation (CNV contributes to the variation observed between individuals and can influence human disease progression, but the accurate measurement of individual copy numbers is technically challenging. In the work presented here we describe a modification to a previously described paralogue ratio test (PRT method for genotyping the CCL3L1/CCL4L1 copy variable region, which we use to ascertain CCL3L1/CCL4L1 copy number in 1581 European samples. As the products of CCL3L1 and CCL4L1 potentially play a role in autoimmunity we performed case control association studies with Crohn's disease, rheumatoid arthritis and psoriasis clinical cohorts. Results We evaluate the PRT methodology used, paying particular attention to accuracy and precision, and highlight the problems of differential bias in copy number measurements. Our PRT methods for measuring copy number were of sufficient precision to detect very slight but systematic differential bias between results from case and control DNA samples in one study. We find no evidence for an association between CCL3L1 copy number and Crohn's disease, rheumatoid arthritis or psoriasis. Conclusions Differential bias of this small magnitude, but applied systematically across large numbers of samples, would create a serious risk of false positive associations in copy number, if measured using methods of lower precision, or methods relying on single uncorroborated measurements. In this study the small differential bias detected by PRT in one sample set was resolved by a simple pre-treatment by restriction enzyme digestion.

  18. Advantage of using allele-specific copy numbers when testing for association in regions with common copy number variants.

    Directory of Open Access Journals (Sweden)

    Gaëlle Marenne

    Full Text Available Copy number variants (CNV can be called from SNP-arrays; however, few studies have attempted to combine both CNV and SNP calls to test for association with complex diseases. Even when SNPs are located within CNVs, two separate association analyses are necessary, to compare the distribution of bi-allelic genotypes in cases and controls (referred to as SNP-only strategy and the number of copies of a region (referred to as CNV-only strategy. However, when disease susceptibility is actually associated with allele specific copy-number states, the two strategies may not yield comparable results, raising a series of questions about the optimal analytical approach. We performed simulations of the performance of association testing under different scenarios that varied genotype frequencies and inheritance models. We show that the SNP-only strategy lacks power under most scenarios when the SNP is located within a CNV; frequently it is excluded from analysis as it does not pass quality control metrics either because of an increased rate of missing calls or a departure from fitness for Hardy-Weinberg proportion. The CNV-only strategy also lacks power because the association testing depends on the allele which copy number varies. The combined strategy performs well in most of the scenarios. Hence, we advocate the use of this combined strategy when testing for association with SNPs located within CNVs.

  19. Copying of holograms by spot scanning approach.

    Science.gov (United States)

    Okui, Makoto; Wakunami, Koki; Oi, Ryutaro; Ichihashi, Yasuyuki; Jackin, Boaz Jessie; Yamamoto, Kenji

    2018-05-20

    To replicate holograms, contact copying has conventionally been used. In this approach, a photosensitive material is fixed together with a master hologram and illuminated with a coherent beam. This method is simple and enables high-quality copies; however, it requires a large optical setup for large-area holograms. In this paper, we present a new method of replicating holograms that uses a relatively compact optical system even for the replication of large holograms. A small laser spot that irradiates only part of the hologram is used to reproduce the hologram by scanning the spot over the whole area of the hologram. We report on the results of experiments carried out to confirm the copy quality, along with a guide to design scanning conditions. The results show the potential effectiveness of the large-area hologram replication technology using a relatively compact apparatus.

  20. Re-thinking copyright through the copy in Russia

    NARCIS (Netherlands)

    Sezneva, O.

    2013-01-01

    How one copy of a film or a single is made illegal, while its identical twin is treated as legitimate? By drawing from the material collected in Russia on the illegal copying and distribution of video and musical contents, this paper moves beyond the definition of media piracy in legal terms, and

  1. 1 CFR 18.1 - Original and copies required.

    Science.gov (United States)

    2010-01-01

    ... 1 General Provisions 1 2010-01-01 2010-01-01 false Original and copies required. 18.1 Section 18.1... PROCESSING OF DOCUMENTS PREPARATION AND TRANSMITTAL OF DOCUMENTS GENERALLY § 18.1 Original and copies... agency submitting a document to be filed and published in the Federal Register shall send an original and...

  2. Mitochondrial DNA Copy Number in Sleep Duration Discordant Monozygotic Twins

    DEFF Research Database (Denmark)

    Wrede, Joanna E; Mengel-From, Jonas; Buchwald, Dedra

    2015-01-01

    STUDY OBJECTIVES: Mitochondrial DNA (mtDNA) copy number is an important component of mitochondrial function and varies with age, disease, and environmental factors. We aimed to determine whether mtDNA copy number varies with habitual differences in sleep duration within pairs of monozygotic twins...... structure to assess within-pair effects of sleep duration on mtDNA copy number. MEASUREMENTS AND RESULTS: Mean within-pair sleep duration difference per 24 hours was 94.3 minutes (SD 62.6 min). We found reduced sleep duration (β = 0.06; 95% CI 0.004, 0.12; P sleep efficiency (β = 0.51; 95% CI 0.......06, 0.95; P DNA copy number within twin pairs. Thus every 1-minute decrease in actigraphy-defined sleep duration was associated with a decrease in mtDNA copy number of 0.06. Likewise, a 1% decrease in actigraphy-defined sleep efficiency was associated...

  3. 25 CFR 571.13 - Copies of audit reports.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false Copies of audit reports. 571.13 Section 571.13 Indians... MONITORING AND INVESTIGATIONS Audits § 571.13 Copies of audit reports. (a) Each tribe shall prepare and.../or reports as a result of the audit setting forth the results of each fiscal year. The submission...

  4. The Art of Copying: Five strategies for Transforming Originals in the Art Museum

    Directory of Open Access Journals (Sweden)

    Hans Dam Christensen

    2017-09-01

    Full Text Available This article discusses copies within the field of art museums by way of mapping strategies for copy practices. This mapping leans heavily towards parts of the wri-tings of Jacques Derrida (1930-2004. Against the backdrop of this theoretical premise, the article distinguishes five main strategies. Firstly, the copies which of-ten are considered to be typical museum copies, characterize the strategy for the disseminating relation between original and copy, that is, reproductions, magnets, etc. This strategy implies how copy practices are closely integrated into museum practices in general. Secondly, the supplementing relation between original and copy will be introduced. This strategy frames, for example, artists' citations of other works and forgeries. Both show that copy practices often lead to new originals, in principle, ad infinitum. Thirdly, this leads to the strategy for the displacing relation between original and copy which encompasses, for example, artistic reworkings of other artists' originals and conservatorial restorations. This approach partly ex-cludes the copy and partly displaces the original, while still, unavoidably, referring to the latter. In general, this strategy signifies the latent instability of the origi-nal. Fourthly, the strategy for the informational relation between original and copy will be discussed as it has a vital function in terms of talking about museum originals and copies. This is the strategy which grants the original artifacts their status as museum objects. An informational copy is just as unique as an original object of art, and at the same time, it defines the original and is itself defined by this opposition. Lastly, the strategy for the imagined relation between original and copy follows. This strategy is dependent upon several of the previous approaches, and, in addition, handles signs that exist without explicit originals, as the strategy covers copies referring to originals which have disappeared

  5. The Role of Constitutional Copy Number Variants in Breast Cancer

    Science.gov (United States)

    Walker, Logan C.; Wiggins, George A.R.; Pearson, John F.

    2015-01-01

    Constitutional copy number variants (CNVs) include inherited and de novo deviations from a diploid state at a defined genomic region. These variants contribute significantly to genetic variation and disease in humans, including breast cancer susceptibility. Identification of genetic risk factors for breast cancer in recent years has been dominated by the use of genome-wide technologies, such as single nucleotide polymorphism (SNP)-arrays, with a significant focus on single nucleotide variants. To date, these large datasets have been underutilised for generating genome-wide CNV profiles despite offering a massive resource for assessing the contribution of these structural variants to breast cancer risk. Technical challenges remain in determining the location and distribution of CNVs across the human genome due to the accuracy of computational prediction algorithms and resolution of the array data. Moreover, better methods are required for interpreting the functional effect of newly discovered CNVs. In this review, we explore current and future application of SNP array technology to assess rare and common CNVs in association with breast cancer risk in humans. PMID:27600231

  6. A spatial haplotype copying model with applications to genotype imputation.

    Science.gov (United States)

    Yang, Wen-Yun; Hormozdiari, Farhad; Eskin, Eleazar; Pasaniuc, Bogdan

    2015-05-01

    Ever since its introduction, the haplotype copy model has proven to be one of the most successful approaches for modeling genetic variation in human populations, with applications ranging from ancestry inference to genotype phasing and imputation. Motivated by coalescent theory, this approach assumes that any chromosome (haplotype) can be modeled as a mosaic of segments copied from a set of chromosomes sampled from the same population. At the core of the model is the assumption that any chromosome from the sample is equally likely to contribute a priori to the copying process. Motivated by recent works that model genetic variation in a geographic continuum, we propose a new spatial-aware haplotype copy model that jointly models geography and the haplotype copying process. We extend hidden Markov models of haplotype diversity such that at any given location, haplotypes that are closest in the genetic-geographic continuum map are a priori more likely to contribute to the copying process than distant ones. Through simulations starting from the 1000 Genomes data, we show that our model achieves superior accuracy in genotype imputation over the standard spatial-unaware haplotype copy model. In addition, we show the utility of our model in selecting a small personalized reference panel for imputation that leads to both improved accuracy as well as to a lower computational runtime than the standard approach. Finally, we show our proposed model can be used to localize individuals on the genetic-geographical map on the basis of their genotype data.

  7. 44 CFR 5.85 - Authentication and attestation of copies.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Authentication and attestation of copies. 5.85 Section 5.85 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT... Authentication and attestation of copies. The Administrator, Deputy Administrators, Regional Administrators...

  8. The genetic effect of copy number variations on the risk of alcoholism in a Korean population.

    Science.gov (United States)

    Bae, Joon Seol; Jung, Myung Hun; Lee, Boung Chul; Cheong, Hyun Sub; Park, Byung Lae; Kim, Lyoung Hyo; Kim, Jeong-Hyun; Pasaje, Charisse Flerida A; Lee, Jin Sol; Jung, Kyoung Hwa; Chai, Young Gyu; Shin, Hyoung Doo; Choi, Ihn-Geun

    2012-01-01

    Alcoholism, a chronic behavioral disorder characterized by excessive alcohol consumption, has been a leading cause of morbidity and premature death. This condition is believed to be influenced by genetic factors. As copy number variation (CNV) has been recently discovered in human genome, genomic diversity of human genome is more frequent than previously thought. Many studies have reported evidences that CNV is associated with the development of complex diseases. In this study, we hypothesized that CNV can predict the risk of alcoholism. Using the Illumina HumanHap660W-Quad BeadChip (∼660 k markers), genome-wide genotyping was performed to obtain signal and allelic intensities from 116 alcoholic cases and 1,022 healthy controls (total n = 1,138) in a Korean population. To identify alcoholism-associated CNV regions, we performed a genome-wide association analysis, using multivariate logistic regression model controlling for age and gender. We identified a total of 255,732 individual CNVs and 3,261 CNV regions (1,067 common CNV regions, frequency > 1%) in this study. Results from multivariate logistic regression showed that the chr20:61195302-61195978 regions were significantly associated with the risk of alcoholism after multiple corrections (p = 5.02E-05, p(corr) = 0.04). Most of the identified variations in this study overlapped with the previously reported CNVs in the Database of Genomic Variants (95.3%). The identified CNVs, which encompassed 3,226 functional genes, were significantly enriched in the cellular part, in the membrane-bound organelle, in the cell part, in developmental processes, in cell communication, in neurological system process, in sensory perception of smell and chemical stimulus, and in olfactory receptor activity. This is the first genome-wide association study to investigate the relationship between common CNV and alcoholism. Our results suggest that the newly identified CNV regions may contribute to the development of alcoholism

  9. Novel association strategy with copy number variation for identifying new risk Loci of human diseases.

    Directory of Open Access Journals (Sweden)

    Xianfeng Chen

    2010-08-01

    Full Text Available Copy number variations (CNV are important causal genetic variations for human disease; however, the lack of a statistical model has impeded the systematic testing of CNVs associated with disease in large-scale cohort.Here, we developed a novel integrated strategy to test CNV-association in genome-wide case-control studies. We converted the single-nucleotide polymorphism (SNP signal to copy number states using a well-trained hidden Markov model. We mapped the susceptible CNV-loci through SNP site-specific testing to cope with the physiological complexity of CNVs. We also ensured the credibility of the associated CNVs through further window-based CNV-pattern clustering. Genome-wide data with seven diseases were used to test our strategy and, in total, we identified 36 new susceptible loci that are associated with CNVs for the seven diseases: 5 with bipolar disorder, 4 with coronary artery disease, 1 with Crohn's disease, 7 with hypertension, 9 with rheumatoid arthritis, 7 with type 1 diabetes and 3 with type 2 diabetes. Fifteen of these identified loci were validated through genotype-association and physiological function from previous studies, which provide further confidence for our results. Notably, the genes associated with bipolar disorder converged in the phosphoinositide/calcium signaling, a well-known affected pathway in bipolar disorder, which further supports that CNVs have impact on bipolar disorder.Our results demonstrated the effectiveness and robustness of our CNV-association analysis and provided an alternative avenue for discovering new associated loci of human diseases.

  10. 48 CFR 6302.25 - Copies of papers (Rule 25).

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Copies of papers (Rule 25). 6302.25 Section 6302.25 Federal Acquisition Regulations System DEPARTMENT OF TRANSPORTATION BOARD OF CONTRACT APPEALS RULES OF PROCEDURE 6302.25 Copies of papers (Rule 25). When books, records, papers, or...

  11. Peer-to-peer computing for secure high performance data copying

    International Nuclear Information System (INIS)

    Hanushevsky, A.; Trunov, A.; Cottrell, L.

    2001-01-01

    The BaBar Copy Program (bbcp) is an excellent representative of peer-to-peer (P2P) computing. It is also a pioneering application of its type in the P2P arena. Built upon the foundation of its predecessor, Secure Fast Copy (sfcp), bbcp incorporates significant improvements performance and usability. As with sfcp, bbcp uses ssh for authentication; providing an elegant and simple working model--if you can ssh to a location, you can copy files to or from that location. To fully support this notion, bbcp transparently supports 3rd party copy operations. The program also incorporates several mechanism to deal with firewall security; the bane of P2P computing. To achieve high performance in a wide area network, bbcp allows a user to independently specify, the number of parallel network streams, tcp window size, and the file I/O blocking factor. Using these parameters, data is pipelined from source to target to provide a uniform traffic pattern that maximizes router efficiency. For improved recoverability, bbcp also keeps track of copy operations so that an operation can be restarted from the point of failure at a later time; minimizing the amount of network traffic in the event of a copy failure. Here, the authors present the bbcp architecture, it's various features, and the reasons for their inclusion

  12. Peer-to-Peer Computing for Secure High Performance Data Copying

    International Nuclear Information System (INIS)

    2002-01-01

    The BaBar Copy Program (bbcp) is an excellent representative of peer-to-peer (P2P) computing. It is also a pioneering application of its type in the P2P arena. Built upon the foundation of its predecessor, Secure Fast Copy (sfcp), bbcp incorporates significant improvements performance and usability. As with sfcp, bbcp uses ssh for authentication; providing an elegant and simple working model -- if you can ssh to a location, you can copy files to or from that location. To fully support this notion, bbcp transparently supports 3rd party copy operations. The program also incorporates several mechanism to deal with firewall security; the bane of P2P computing. To achieve high performance in a wide area network, bbcp allows a user to independently specify, the number of parallel network streams, tcp window size, and the file I/O blocking factor. Using these parameters, data is pipelined from source to target to provide a uniform traffic pattern that maximizes router efficiency. For improved recoverability, bbcp also keeps track of copy operations so that an operation can be restarted from the point of failure at a later time; minimizing the amount of network traffic in the event of a copy failure. Here, we preset the bbcp architecture, it's various features, and the reasons for their inclusion

  13. Mitochondrial DNA Copy Number in Sleep Duration Discordant Monozygotic Twins.

    Science.gov (United States)

    Wrede, Joanna E; Mengel-From, Jonas; Buchwald, Dedra; Vitiello, Michael V; Bamshad, Michael; Noonan, Carolyn; Christiansen, Lene; Christensen, Kaare; Watson, Nathaniel F

    2015-10-01

    Mitochondrial DNA (mtDNA) copy number is an important component of mitochondrial function and varies with age, disease, and environmental factors. We aimed to determine whether mtDNA copy number varies with habitual differences in sleep duration within pairs of monozygotic twins. Academic clinical research center. 15 sleep duration discordant monozygotic twin pairs (30 twins, 80% female; mean age 42.1 years [SD 15.0]). Sleep duration was phenotyped with wrist actigraphy. Each twin pair included a "normal" (7-9 h/24) and "short" (sleeping twin. Fasting peripheral blood leukocyte DNA was assessed for mtDNA copy number via the n-fold difference between qPCR measured mtDNA and nuclear DNA creating an mtDNA measure without absolute units. We used generalized estimating equation linear regression models accounting for the correlated data structure to assess within-pair effects of sleep duration on mtDNA copy number. Mean within-pair sleep duration difference per 24 hours was 94.3 minutes (SD 62.6 min). We found reduced sleep duration (β = 0.06; 95% CI 0.004, 0.12; P sleep efficiency (β = 0.51; 95% CI 0.06, 0.95; P sleep duration was associated with a decrease in mtDNA copy number of 0.06. Likewise, a 1% decrease in actigraphy-defined sleep efficiency was associated with a decrease in mtDNA copy number of 0.51. Reduced sleep duration and sleep efficiency were associated with reduced mitochondrial DNA copy number in sleep duration discordant monozygotic twins offering a potential mechanism whereby short sleep impairs health and longevity through mitochondrial stress. © 2015 Associated Professional Sleep Societies, LLC.

  14. 49 CFR 512.5 - How many copies should I submit?

    Science.gov (United States)

    2010-10-01

    ... must send the following in hard copy or electronic format to the Chief Counsel when making a claim for... format, a copy of any special software required to review materials for which confidential treatment is...

  15. SULT1A1 copy number variation: ethnic distribution analysis in an Indian population.

    Science.gov (United States)

    Almal, Suhani; Padh, Harish

    2017-11-01

    Cytosolic sulfotransferases (SULTs) are phase II detoxification enzymes involved in metabolism of numerous xenobiotics, drugs and endogenous compounds. Interindividual variation in sulfonation capacity is important for determining an individual's response to xenobiotics. SNPs in SULTs, mainly SULT1A1 have been associated with cancer risk and also with response to therapeutic agents. Copy number variation (CNVs) in SULT1A1 is found to be correlated with altered enzyme activity. This short report primarily focuses on CNV in SULT1A1 and its distribution among different ethnic populations around the globe. Frequency distribution of SULT1A1 copy number (CN) in 157 healthy Indian individuals was assessed using florescent-based quantitative PCR assay. A range of 1 to >4 copies, with a frequency of SULT1A1 CN =2 (64.9%) the highest, was observed in our (Indian) population. Upon comparative analysis of frequency distribution of SULT1A1 CN among diverse population groups, a statistically significant difference was observed between Indians (our data) and African-American (AA) (p = 0.0001) and South African (Tswana) (p populations. Distribution of CNV in the Indian population was found to be similar to that in European-derived populations of American and Japanese. CNV of SULT1A1 varies significantly among world populations and may be one of the determinants of health and diseases.

  16. DNA copy number, including telomeres and mitochondria, assayed using next-generation sequencing

    Directory of Open Access Journals (Sweden)

    Jackson Stuart

    2010-04-01

    Full Text Available Abstract Background DNA copy number variations occur within populations and aberrations can cause disease. We sought to develop an improved lab-automatable, cost-efficient, accurate platform to profile DNA copy number. Results We developed a sequencing-based assay of nuclear, mitochondrial, and telomeric DNA copy number that draws on the unbiased nature of next-generation sequencing and incorporates techniques developed for RNA expression profiling. To demonstrate this platform, we assayed UMC-11 cells using 5 million 33 nt reads and found tremendous copy number variation, including regions of single and homogeneous deletions and amplifications to 29 copies; 5 times more mitochondria and 4 times less telomeric sequence than a pool of non-diseased, blood-derived DNA; and that UMC-11 was derived from a male individual. Conclusion The described assay outputs absolute copy number, outputs an error estimate (p-value, and is more accurate than array-based platforms at high copy number. The platform enables profiling of mitochondrial levels and telomeric length. The assay is lab-automatable and has a genomic resolution and cost that are tunable based on the number of sequence reads.

  17. Incidental copy-number variants identified by routine genome testing in a clinical population

    Science.gov (United States)

    Boone, Philip M.; Soens, Zachry T.; Campbell, Ian M.; Stankiewicz, Pawel; Cheung, Sau Wai; Patel, Ankita; Beaudet, Arthur L.; Plon, Sharon E.; Shaw, Chad A.; McGuire, Amy L.; Lupski, James R.

    2013-01-01

    Purpose Mutational load of susceptibility variants has not been studied on a genomic scale in a clinical population, nor has the potential to identify these mutations as incidental findings during clinical testing been systematically ascertained. Methods Array comparative genomic hybridization, a method for genome-wide detection of DNA copy-number variants, was performed clinically on DNA from 9,005 individuals. Copy-number variants encompassing or disrupting single genes were identified and analyzed for their potential to confer predisposition to dominant, adult-onset disease. Multigene copy-number variants affecting dominant, adult-onset cancer syndrome genes were also assessed. Results In our cohort, 83 single-gene copy-number variants affected 40 unique genes associated with dominant, adult-onset disorders and unrelated to the patients’ referring diagnoses (i.e., incidental) were found. Fourteen of these copy-number variants are likely disease-predisposing, 25 are likely benign, and 44 are of unknown clinical consequence. When incidental copy-number variants spanning up to 20 genes were considered, 27 copy-number variants affected 17 unique genes associated with dominant, adult-onset cancer predisposition. Conclusion Copy-number variants potentially conferring susceptibility to adult-onset disease can be identified as incidental findings during routine genome-wide testing. Some of these mutations may be medically actionable, enabling disease surveillance or prevention; however, most incidentally observed single-gene copy-number variants are currently of unclear significance to the patient. PMID:22878507

  18. Associations of mitochondrial haplogroups and mitochondrial DNA copy numbers with end-stage renal disease in a Han population.

    Science.gov (United States)

    Zhang, Yuheng; Zhao, Ying; Wen, Shuzhen; Yan, Rengna; Yang, Qinglan; Chen, Huimei

    2017-09-01

    Mitochondrial DNA (mtDNA) is closely related to mitochondrion function, and variations have been suggested to be involved in pathogenesis of complex diseases. The present study sought to elucidate mitochondrial haplogroups and mtDNA copy number in end-stage renal disease (ESRD) in a Han population. First, the mitochondrial haplogroups of 37 ESRD patients were clustered into several haplogroups, and haplogroup A & D were taken as the candidate risk haplogroups for ESRD. Second, the frequencies of A and D were assessed in 344 ESRD patients and 438 healthy controls, respectively. Haplogroup D was found to be risk maker for ESRD in young subjects (numbers were evaluated with quantitative-PCR. The ESRD patients exhibited greater cell-free mtDNA contents than the healthy controls but less intracellular mtDNA. Haplogroup D exhibited a further increase in cell-free mtDNA content and a decrease in intracellular mtDNA content among the ESRDs patients. Our findings suggest that mtNDA haplogroup D may contributes to pathogenesis of early-onset ESRD through alterations of mtDNA copy numbers.

  19. The double copy: gravity from gluons

    Science.gov (United States)

    White, C. D.

    2018-04-01

    Three of the four fundamental forces in nature are described by so-called gauge theories, which include the effects of both relativity and quantum mechanics. Gravity, on the other hand, is described by General Relativity, and the lack of a well-behaved quantum theory - believed to be relevant at the centre of black holes, and at the Big Bang itself - remains a notorious unsolved problem. Recently a new correspondence, the double copy, has been discovered between scattering amplitudes (quantities related to the probability for particles to interact) in gravity, and their gauge theory counterparts. This has subsequently been extended to other quantities, providing gauge theory analogues of e.g. black holes. We here review current research on the double copy, and describe some possible applications.

  20. Video copy protection and detection framework (VPD) for e-learning systems

    Science.gov (United States)

    ZandI, Babak; Doustarmoghaddam, Danial; Pour, Mahsa R.

    2013-03-01

    This Article reviews and compares the copyright issues related to the digital video files, which can be categorized as contended based and Digital watermarking copy Detection. Then we describe how to protect a digital video by using a special Video data hiding method and algorithm. We also discuss how to detect the copy right of the file, Based on expounding Direction of the technology of the video copy detection, and Combining with the own research results, brings forward a new video protection and copy detection approach in terms of plagiarism and e-learning systems using the video data hiding technology. Finally we introduce a framework for Video protection and detection in e-learning systems (VPD Framework).

  1. A genomic copy number signature predicts radiation exposure in post-Chernobyl breast cancer.

    Science.gov (United States)

    Wilke, Christina M; Braselmann, Herbert; Hess, Julia; Klymenko, Sergiy V; Chumak, Vadim V; Zakhartseva, Liubov M; Bakhanova, Elena V; Walch, Axel K; Selmansberger, Martin; Samaga, Daniel; Weber, Peter; Schneider, Ludmila; Fend, Falko; Bösmüller, Hans C; Zitzelsberger, Horst; Unger, Kristian

    2018-04-16

    Breast cancer is the second leading cause of cancer death among women worldwide and besides life style, age and genetic risk factors, exposure to ionizing radiation is known to increase the risk for breast cancer. Further, DNA copy number alterations (CNAs), which can result from radiation-induced double-strand breaks, are frequently occurring in breast cancer cells. We set out to identify a signature of CNAs discriminating breast cancers from radiation-exposed and non-exposed female patients. We analyzed resected breast cancer tissues from 68 exposed female Chernobyl clean-up workers and evacuees and 68 matched non-exposed control patients for CNAs by array comparative genomic hybridization analysis (aCGH). Using a stepwise forward-backward selection approach a non-complex CNA signature, that is, less than ten features, was identified in the training data set, which could be subsequently validated in the validation data set (p value < 0.05). The signature consisted of nine copy number regions located on chromosomal bands 7q11.22-11.23, 7q21.3, 16q24.3, 17q21.31, 20p11.23-11.21, 1p21.1, 2q35, 2q35, 6p22.2. The signature was independent of any clinical characteristics of the patients. In all, we identified a CNA signature that has the potential to allow identification of radiation-associated breast cancer at the individual level. © 2018 UICC.

  2. Does Visual Attention Span Relate to Eye Movements during Reading and Copying?

    Science.gov (United States)

    Bosse, Marie-Line; Kandel, Sonia; Prado, Chloé; Valdois, Sylviane

    2014-01-01

    This research investigated whether text reading and copying involve visual attention-processing skills. Children in grades 3 and 5 read and copied the same text. We measured eye movements while reading and the number of gaze lifts (GL) during copying. The children were also administered letter report tasks that constitute an estimation of the…

  3. 29 CFR 1921.17 - Service; copies of documents and pleadings.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 7 2010-07-01 2010-07-01 false Service; copies of documents and pleadings. 1921.17 Section 1921.17 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION... LONGSHOREMEN'S AND HARBOR WORKERS' COMPENSATION ACT Miscellaneous § 1921.17 Service; copies of documents and...

  4. Systematic biases in DNA copy number originate from isolation procedures

    NARCIS (Netherlands)

    van Heesch, S.; Mokry, M.; Boskova, V.; Junker, W.; Mehon, R.; Toonen, P.; de Bruijn, E.; Shull, J.D.; Aitman, T.J.; Cuppen, E.; Guryev, V.

    2013-01-01

    BACKGROUND: The ability to accurately detect DNA copy number variation in both a sensitive and quantitative manner is important in many research areas. However, genome-wide DNA copy number analyses are complicated by variations in detection signal. RESULTS: While GC content has been used to correct

  5. Conservatism and "copy-if-better" in chimpanzees (Pan troglodytes).

    Science.gov (United States)

    van Leeuwen, Edwin J C; Call, Josep

    2017-05-01

    Social learning is predicted to evolve in socially living animals provided the learning process is not random but biased by certain socio-ecological factors. One bias of particular interest for the emergence of (cumulative) culture is the tendency to forgo personal behaviour in favour of relatively better variants observed in others, also known as the "copy-if-better" strategy. We investigated whether chimpanzees employ copy-if-better in a simple token-exchange paradigm controlling for individual and random social learning. After being trained on one token-type, subjects were confronted with a conspecific demonstrator who either received the same food reward as the subject (control condition) or a higher value food reward than the subject (test condition) for exchanging another token-type. In general, the chimpanzees persisted in exchanging the token-type they were trained on individually, indicating a form of conservatism consistent with previous studies. However, the chimpanzees were more inclined to copy the demonstrator in the test compared to the control condition, indicating a tendency to employ a copy-if-better strategy. We discuss the validity of our results by considering alternative explanations and relate our findings to the emergence of cumulative culture.

  6. Scattering on plane waves and the double copy

    Science.gov (United States)

    Adamo, Tim; Casali, Eduardo; Mason, Lionel; Nekovar, Stefan

    2018-01-01

    Perturbatively around flat space, the scattering amplitudes of gravity are related to those of Yang–Mills by colour-kinematic duality, under which gravitational amplitudes are obtained as the ‘double copy’ of the corresponding gauge theory amplitudes. We consider the question of how to extend this relationship to curved scattering backgrounds, focusing on certain ‘sandwich’ plane waves. We calculate the 3-point amplitudes on these backgrounds and find that a notion of double copy remains in the presence of background curvature: graviton amplitudes on a gravitational plane wave are the double copy of gluon amplitudes on a gauge field plane wave. This is non-trivial in that it requires a non-local replacement rule for the background fields and the momenta and polarization vectors of the fields scattering on the backgrounds. It must also account for new ‘tail’ terms arising from scattering off the background. These encode a memory effect in the scattering amplitudes, which naturally double copies as well.

  7. Copy number variation in glutathione-S-transferase T1 and M1 predicts incidence and 5-year survival from prostate and bladder cancer, and incidence of corpus uteri cancer in the general population

    DEFF Research Database (Denmark)

    Nørskov, M S; Frikke-Schmidt, R; Bojesen, S E

    2011-01-01

    Glutathione-S-transferase T1 (GSTT1) and GSTM1 detoxify carcinogens and thus potentially contribute to inter-individual susceptibility to cancer. We determined the ability of GST copy number variation (CNV) to predict the risk of cancer in the general population. Exact copy numbers of GSTT1 and G...

  8. Larval exposure to environmentally relevant mixtures of alkylphenolethoxylates reduces reproductive competence in male fathead minnows

    Science.gov (United States)

    Bistodeau, T.J.; Barber, L.B.; Bartell, S.E.; Cediel, R.A.; Grove, K.J.; Klaustermeier, J.; Woodard, J.C.; Lee, K.E.; Schoenfuss, H.L.

    2006-01-01

    The ubiquitous presence of nonylphenolethoxylate/octylphenolethoxylate (NPE/OPE) compounds in aquatic environments adjacent to wastewater treatment plants (WWTP) warrants an assessment of the endocrine disrupting potential of these complex mixtures on aquatic vertebrates. In this study, fathead minnow larvae were exposed for 64 days to a mixture of NPE/OPE, which closely models the NPE/OPE composition of a major metropolitan WWTP effluent. Target exposure concentrations included a total NPE/OPE mixture load of 200% of the WWTP effluent concentration (148 ??g/L), 100% of the WWTP effluent concentration (74 ??g/L) and 50% of the WWTP effluent concentration (38 ??g/L). The NPE/OPE mixture contained 0.2% 4-t-octylphenol, 2.8% 4-nonylphenol, 5.1% 4-nonylphenolmonoethoxylate, 9.3% 4-nonylphenoldiethoxylate, 0.9% 4-t-octylphenolmonoethoxylate, 3.1% 4-t-octylphenoldiethoxylate, 33.8% 4-nonylphenolmonoethoxycarboxylate, and 44.8% 4-nonylphenoldiethoxycarboxylate. An additional exposure of 5 ??g/L 4-nonylphenol (nominal) was conducted. The exposure utilized a flow-through system supplied by ground water and designed to deliver consistent concentrations of applied chemicals. Following exposure, larvae were raised to maturity. Upon sexual maturation, exposed male fish were allowed to compete with control males in a competitive spawning assay. Nest holding ability of control and exposed fish was carefully monitored for 7 days. All male fish were then sacrificed and analyzed for plasma vitellogenin, developmental changes in gonadal tissues, alterations in the development of secondary sexual characters, morphometric changes, and changes to reproductive behavior. When exposed to the 200% NPE/OPE treatment most larvae died within the first 4 weeks of exposure. Both the 100% and 50% NPE/OPE exposures caused a significant decrease in reproductive behavior, as indicated by an inability of many of the previously exposed males to acquire and hold a nest site required for reproduction

  9. Genomic copy concentrations of selected waterborne viruses in a slum environment in Kampala, Uganda.

    Science.gov (United States)

    Katukiza, A Y; Temanu, H; Chung, J W; Foppen, J W A; Lens, P N L

    2013-06-01

    The presence of viruses in a slum environment where sanitation is poor is a major concern. However, little is known of their occurrence and genomic copy concentration in the slum environment. The main objective of this study was to determine the genomic copy concentrations of human adenoviruses F and G, Rotavirus (RV), Hepatitis A virus (HAV), Hepatitis E virus (HEV) and human adenovirus species A,C,D,E, and F (HAdV-ACDEF) in Bwaise III, a typical slum in Kampala, Uganda. Forty-one samples from surface water, grey water and ground water were collected from 30 sampling locations. The virus particles were recovered by glass wool filtration with elution using beef extract. DNA and RNA viruses were detected by the real time quantitative polymerase chain reaction (qPCR) and the reverse transcription-qPCR (RT-qPCR), respectively. HAdV-F and G were detected in 70.7% of the samples with concentrations up to 2.65 × 10(1) genomic copies per mL (gc mL(-1)). RV and HAV were detected in 60.9% and 17.1% of the samples, respectively. The maximum concentration of RV was 1.87 × 10(2)gc mL(-1). In addition, 78% of the samples tested positive for the HAdV-ACDEF, but all samples tested negative for HEV. These new data are essential for quantitative microbial risk assessment, and for understanding the effects of environmental pollution in slums.

  10. A Reusable Software Copy Protection Using Hash Result and Asymetrical Encryption

    Directory of Open Access Journals (Sweden)

    Aswin Wibisurya

    2014-12-01

    Full Text Available Desktop application is one of the most popular types of application being used in computer due to the one time install simplicity and the quick accessibility from the moment the computer being turned on. Limitation of the copy and usage of desktop applications has long been an important issue to application providers. For security concerns, software copy protection is usually integrated with the application. However, developers seek to reuse the copy protection component of the software. This paper proposes an approach of reusable software copy protection which consists of a certificate validator on the client computer and a certificate generator on the server. The certificate validator integrity is protected using hashing result while all communications are encrypted using asymmetrical encryption to ensure the security of this approach.

  11. How bio-questionable are the different recombinant human erythropoietin copy products in Thailand?

    Science.gov (United States)

    Halim, Liem Andhyk; Brinks, Vera; Jiskoot, Wim; Romeijn, Stefan; Praditpornsilpa, Kearkiat; Assawamakin, Anunchai; Schellekens, Huub

    2014-05-01

    The high prevalence of pure red cell aplasia in Thailand has been associated with the sharp increase in number of recombinant human erythropoietin (rhEPO) copy products, based on a classical generic regulatory pathway, which have entered the market. This study aims to assess the quality of rhEPO copy products being used in Thailand. Twelve rhEPO copy products were purchased from pharmacies in Thailand, shipped under controlled cold chain conditions to the Netherlands and characterized using (1) high performance size-exclusion chromatography, (2) asymmetrical flow field-flow fractionation, (3) sodium dodecyl sulfate polyacrylamide gel electrophoresis in combination with (4) Western blotting and additionally tested for (5) host cell protein impurities as well as (6) endotoxin contamination. Some of the tested rhEPO copy products showed high aggregate levels and contained a substantial amount of protein fragments. Also, one of rhEPO copy products had a high endotoxin level, exceeding the FDA limit. Our observations show that some of the tested copy products on the Thai market differ significantly from the originator rhEPO product, Epogen®. This comparison study supports a link between the quality attributes of copy rhEPO products and their immunogenicity.

  12. Imitation, Inspiration, and Creation: Cognitive Process of Creative Drawing by Copying Others' Artworks.

    Science.gov (United States)

    Okada, Takeshi; Ishibashi, Kentaro

    2017-09-01

    To investigate the cognitive processes underlying creative inspiration, we tested the extent to which viewing or copying prior examples impacted creative output in art. In Experiment 1, undergraduates made drawings under three conditions: (a) copying an artist's drawing, then producing an original drawing; (b) producing an original drawing without having seen another's work; and (c) copying another artist's work, then reproducing that artist's style independently. We discovered that through copying unfamiliar abstract drawings, participants were able to produce creative drawings qualitatively different from the model drawings. Process analyses suggested that participants' cognitive constraints became relaxed, and new perspectives were formed from copying another's artwork. Experiment 2 showed that exposure to styles of artwork considered unfamiliar facilitated creativity in drawing, while styles considered familiar did not do so. Experiment 3 showed that both copying and thoroughly viewing artwork executed using an unfamiliar style facilitated creativity in drawing, whereas merely thinking about alternative styles of artistic representation did not do so. These experiments revealed that deep encounters with unfamiliar artworks-whether through copying or prolonged observation-change people's cognitive representations of the act of drawing to produce novel artwork. Copyright © 2016 Cognitive Science Society, Inc.

  13. Late Print Culture’s Social Media Revolution: Authorship, Collaboration and Copy Machines

    Directory of Open Access Journals (Sweden)

    Kate Eichhorn

    2013-05-01

    Full Text Available This article examines the impact of copy machines on late twentieth-century print cultures. Specifically, this article makes a case for “dry copying,” the method of print reproduction perfected by Xerox in the late 1950s, as a unique medium rather than a weak imitation of other printing methods. Following the claim that the widespread availability of copy machines in the late twentieth century represented the arrival of a new medium, this article further examines how understandings of authorship, established with print culture, came undone in the era of the copy machine. Finally, this paper makes a case for understanding copy machines as a form of “social media” that opened up opportunities for writers, readers and publishers to create, share, exchange and comment on texts and images in communities and networks of their own making in the decades preceding the development of the web.

  14. 20 CFR 404.707 - Original records or copies as evidence.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Original records or copies as evidence. 404... DISABILITY INSURANCE (1950- ) Evidence General § 404.707 Original records or copies as evidence. (a) General... original document or record. These original records or documents will be returned to you after we have...

  15. 1 CFR 15.4 - Reproduction and certification of copies of acts and documents.

    Science.gov (United States)

    2010-01-01

    ... 1 General Provisions 1 2010-01-01 2010-01-01 false Reproduction and certification of copies of... Reproduction and certification of copies of acts and documents. The Director of the Federal Register shall furnish to requesting agencies, at cost, reproductions or certified copies of original acts and documents...

  16. Decreases in average bacterial community rRNA operon copy number during succession.

    Science.gov (United States)

    Nemergut, Diana R; Knelman, Joseph E; Ferrenberg, Scott; Bilinski, Teresa; Melbourne, Brett; Jiang, Lin; Violle, Cyrille; Darcy, John L; Prest, Tiffany; Schmidt, Steven K; Townsend, Alan R

    2016-05-01

    Trait-based studies can help clarify the mechanisms driving patterns of microbial community assembly and coexistence. Here, we use a trait-based approach to explore the importance of rRNA operon copy number in microbial succession, building on prior evidence that organisms with higher copy numbers respond more rapidly to nutrient inputs. We set flasks of heterotrophic media into the environment and examined bacterial community assembly at seven time points. Communities were arrayed along a geographic gradient to introduce stochasticity via dispersal processes and were analyzed using 16 S rRNA gene pyrosequencing, and rRNA operon copy number was modeled using ancestral trait reconstruction. We found that taxonomic composition was similar between communities at the beginning of the experiment and then diverged through time; as well, phylogenetic clustering within communities decreased over time. The average rRNA operon copy number decreased over the experiment, and variance in rRNA operon copy number was lowest both early and late in succession. We then analyzed bacterial community data from other soil and sediment primary and secondary successional sequences from three markedly different ecosystem types. Our results demonstrate that decreases in average copy number are a consistent feature of communities across various drivers of ecological succession. Importantly, our work supports the scaling of the copy number trait over multiple levels of biological organization, ranging from cells to populations and communities, with implications for both microbial ecology and evolution.

  17. From Copy-and-Paste to Trace-and-Learn

    DEFF Research Database (Denmark)

    Klitgård, Ida

    2009-01-01

    of them even use the term ‹copy-and-paste› to illustrate this, suggesting that their perception is closely linked to their use of the internet. This generally one-dimensional perception calls for immediate repair work in the teaching of English academic writing in International Study Programmes......This paper presents an investigation of both Danish and international second-semester BA-students' perceptions of the problem of plagiarism. Surprisingly, the investigation proves that the students unanimously perceive plagiarism as directly copying other people's texts or entire works. Some...

  18. Mate-choice copying, social information processing, and the roles of oxytocin.

    Science.gov (United States)

    Kavaliers, Martin; Matta, Richard; Choleris, Elena

    2017-01-01

    Social and sexual behaviors, including that of mate choice, are dependent on social information. Mate choice can be modified by prior and ongoing social factors and experience. The mate choice decisions of one individual can be influenced by either the actual or potential mate choice of another female or male. Such non-independent mate choice, where individuals gain social information and socially learn about and recognizes potential mates by observing the choices of another female or male, has been termed "mate-choice copying". Here we first briefly review how, why, and under what circumstances individuals engage in mate-choice copying. Secondly, we review the neurobiological mechanisms underlying mate-choice copying. In particular, we consider the roles of the nonapeptide, oxytocin, in the processing of social information and the expression of mate-choice copying. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. 18 CFR 45.7 - Form of application; number of copies.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Form of application; number of copies. 45.7 Section 45.7 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... in accordance with § 131.60 of this chapter. Each copy shall bear the date and signature that appear...

  20. Identification of rare recurrent copy number variants in high-risk autism families and their prevalence in a large ASD population.

    Directory of Open Access Journals (Sweden)

    Nori Matsunami

    Full Text Available Structural variation is thought to play a major etiological role in the development of autism spectrum disorders (ASDs, and numerous studies documenting the relevance of copy number variants (CNVs in ASD have been published since 2006. To determine if large ASD families harbor high-impact CNVs that may have broader impact in the general ASD population, we used the Affymetrix genome-wide human SNP array 6.0 to identify 153 putative autism-specific CNVs present in 55 individuals with ASD from 9 multiplex ASD pedigrees. To evaluate the actual prevalence of these CNVs as well as 185 CNVs reportedly associated with ASD from published studies many of which are insufficiently powered, we designed a custom Illumina array and used it to interrogate these CNVs in 3,000 ASD cases and 6,000 controls. Additional single nucleotide variants (SNVs on the array identified 25 CNVs that we did not detect in our family studies at the standard SNP array resolution. After molecular validation, our results demonstrated that 15 CNVs identified in high-risk ASD families also were found in two or more ASD cases with odds ratios greater than 2.0, strengthening their support as ASD risk variants. In addition, of the 25 CNVs identified using SNV probes on our custom array, 9 also had odds ratios greater than 2.0, suggesting that these CNVs also are ASD risk variants. Eighteen of the validated CNVs have not been reported previously in individuals with ASD and three have only been observed once. Finally, we confirmed the association of 31 of 185 published ASD-associated CNVs in our dataset with odds ratios greater than 2.0, suggesting they may be of clinical relevance in the evaluation of children with ASDs. Taken together, these data provide strong support for the existence and application of high-impact CNVs in the clinical genetic evaluation of children with ASD.

  1. Copy number variants and VNTR length polymorphisms of the carboxyl-ester lipase (CEL) gene as risk factors in pancreatic cancer.

    Science.gov (United States)

    Dalva, Monica; El Jellas, Khadija; Steine, Solrun J; Johansson, Bente B; Ringdal, Monika; Torsvik, Janniche; Immervoll, Heike; Hoem, Dag; Laemmerhirt, Felix; Simon, Peter; Lerch, Markus M; Johansson, Stefan; Njølstad, Pål R; Weiss, Frank U; Fjeld, Karianne; Molven, Anders

    We have recently described copy number variants (CNVs) of the human carboxyl-ester lipase (CEL) gene, including a recombined deletion allele (CEL-HYB) that is a genetic risk factor for chronic pancreatitis. Associations with pancreatic disease have also been reported for the variable number of tandem repeat (VNTR) region located in CEL exon 11. Here, we examined if CEL CNVs and VNTR length polymorphisms affect the risk for developing pancreatic cancer. CEL CNVs and VNTR were genotyped in a German family with non-alcoholic chronic pancreatitis and pancreatic cancer, in 265 German and 197 Norwegian patients diagnosed with pancreatic adenocarcinoma, and in 882 controls. CNV screening was performed using PCR assays followed by agarose gel electrophoresis whereas VNTR lengths were determined by DNA fragment analysis. The investigated family was CEL-HYB-positive. However, an association of CEL-HYB or a duplication CEL allele with pancreatic cancer was not seen in our two patient cohorts. The frequency of the 23-repeat VNTR allele was borderline significant in Norwegian cases compared to controls (1.2% vs. 0.3%; P = 0.05). For all other VNTR lengths, no statistically significant difference in frequency was observed. Moreover, no association with pancreatic cancer was detected when CEL VNTR lengths were pooled into groups of short, normal or long alleles. We could not demonstrate an association between CEL CNVs and pancreatic cancer. An association is also unlikely for CEL VNTR lengths, although analyses in larger materials are necessary to completely exclude an effect of rare VNTR alleles. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  2. Does testing with feedback improve adult spelling skills relative to copying and reading?

    Science.gov (United States)

    Pan, Steven C; Rubin, Benjamin R; Rickard, Timothy C

    2015-12-01

    We examined testing's ability to enhance adult spelling acquisition, relative to copying and reading. Across 3 experiments in which testing with feedback was compared with copying, the spelling improvement after testing matched that following the same amount of time spent copying. A potent testing advantage, however, was observed for spelling words free-recalled. In the fourth experiment, a large testing advantage for both word free recall and spelling was observed, versus reading. Subjects also generally preferred testing and rated it as more effective than copying or reading. The equivalent performance of testing and copying for spelling contrasts with prior work involving children and suggests that retrieval practice may not be the only effective mechanism for spelling skill acquisition. Rather, we suggest that the critical learning event for spelling is focused study on phoneme-to-grapheme mappings for previously unlearned letter sequences. For adults with extensive spelling expertise, focused study is more automatic during both copying and testing with feedback than for individuals with beginning spelling skills. Reading, however, would not be expected to produce efficient focused study of phoneme-to-grapheme mappings, regardless of expertise level. Overall, adult spelling skill acquisition benefits both from testing and copying, and substantially less from reading. (c) 2015 APA, all rights reserved).

  3. Using DMA for copying performance counter data to memory

    Science.gov (United States)

    Gara, Alan; Salapura, Valentina; Wisniewski, Robert W

    2013-12-31

    A device for copying performance counter data includes hardware path that connects a direct memory access (DMA) unit to a plurality of hardware performance counters and a memory device. Software prepares an injection packet for the DMA unit to perform copying, while the software can perform other tasks. In one aspect, the software that prepares the injection packet runs on a processing core other than the core that gathers the hardware performance data.

  4. 20 CFR 416.804 - Certified copy in lieu of original.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Certified copy in lieu of original. 416.804... AGED, BLIND, AND DISABLED Determination of Age § 416.804 Certified copy in lieu of original. In lieu of the original of any record, except a Bible or other family record, there may be submitted as evidence...

  5. Copy-writing Post-Soviet Russia. Viktor Pelevin's work in Postcolonial Terms

    NARCIS (Netherlands)

    Noordenbos, Boris; Brouwer, S

    2008-01-01

    The copywriters and creatives in Viktor Pelevin's novel Generation "II" (1999) both 'copy' and 'write' Russian identity. Through advertising texts, video scripts, and written scenario's for Russia's stage-set democracy, the commercial elite makes Russia into a superficial and virtual copy of 'the

  6. Statistical Methods for the detection of answer copying on achievement tests

    NARCIS (Netherlands)

    Sotaridona, Leonardo

    2003-01-01

    This thesis contains a collection of studies where statistical methods for the detection of answer copying on achievement tests in multiple-choice format are proposed and investigated. Although all methods are suited to detect answer copying, each method is designed to address specific

  7. CopyNumber450kCancer: baseline correction for accurate copy number calling from the 450k methylation array.

    Science.gov (United States)

    Marzouka, Nour-Al-Dain; Nordlund, Jessica; Bäcklin, Christofer L; Lönnerholm, Gudmar; Syvänen, Ann-Christine; Carlsson Almlöf, Jonas

    2016-04-01

    The Illumina Infinium HumanMethylation450 BeadChip (450k) is widely used for the evaluation of DNA methylation levels in large-scale datasets, particularly in cancer. The 450k design allows copy number variant (CNV) calling using existing bioinformatics tools. However, in cancer samples, numerous large-scale aberrations cause shifting in the probe intensities and thereby may result in erroneous CNV calling. Therefore, a baseline correction process is needed. We suggest the maximum peak of probe segment density to correct the shift in the intensities in cancer samples. CopyNumber450kCancer is implemented as an R package. The package with examples can be downloaded at http://cran.r-project.org nour.marzouka@medsci.uu.se Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press.

  8. Human mate-choice copying is domain-general social learning.

    Science.gov (United States)

    Street, Sally E; Morgan, Thomas J H; Thornton, Alex; Brown, Gillian R; Laland, Kevin N; Cross, Catharine P

    2018-01-29

    Women appear to copy other women's preferences for men's faces. This 'mate-choice copying' is often taken as evidence of psychological adaptations for processing social information related to mate choice, for which facial information is assumed to be particularly salient. No experiment, however, has directly investigated whether women preferentially copy each other's face preferences more than other preferences. Further, because prior experimental studies used artificial social information, the effect of real social information on attractiveness preferences is unknown. We collected attractiveness ratings of pictures of men's faces, men's hands, and abstract art given by heterosexual women, before and after they saw genuine social information gathered in real time from their peers. Ratings of faces were influenced by social information, but no more or less than were images of hands and abstract art. Our results suggest that evidence for domain-specific social learning mechanisms in humans is weaker than previously suggested.

  9. 47 CFR 1.359 - Proof of official record; authentication of copy.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Proof of official record; authentication of copy. 1.359 Section 1.359 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL PRACTICE AND PROCEDURE Hearing Proceedings Evidence § 1.359 Proof of official record; authentication of copy. An official...

  10. 47 CFR 1.735 - Copies; service; separate filings against multiple defendants.

    Science.gov (United States)

    2010-10-01

    ... overnight delivery service such as, or comparable to, the US Postal Service Express Mail, United Parcel... 47 Telecommunication 1 2010-10-01 2010-10-01 false Copies; service; separate filings against... Complaints § 1.735 Copies; service; separate filings against multiple defendants. (a) Complaints may...

  11. Generalized hedgehog ansatz and Gribov copies in regions with nontrivial topologies

    Science.gov (United States)

    Canfora, Fabrizio; Salgado-Rebolledo, Patricio

    2013-02-01

    In this paper the arising of Gribov copies both in Landau and Coulomb gauges in regions with nontrivial topologies but flat metric, (such as closed tubes S1×D2, or R×T2) will be analyzed. Using a novel generalization of the hedgehog ansatz beyond spherical symmetry, analytic examples of Gribov copies of the vacuum will be constructed. Using such ansatz, we will also construct the elliptic Gribov pendulum. The requirement of absence of Gribov copies of the vacuum satisfying the strong boundary conditions implies geometrical constraints on the shapes and sizes of the regions with nontrivial topologies.

  12. [Application of rational ant colony optimization to improve the reproducibility degree of laser three-dimensional copy].

    Science.gov (United States)

    Cui, Xiao-Yan; Huo, Zhong-Gang; Xin, Zhong-Hua; Tian, Xiao; Zhang, Xiao-Dong

    2013-07-01

    Three-dimensional (3D) copying of artificial ears and pistol printing are pushing laser three-dimensional copying technique to a new page. Laser three-dimensional scanning is a fresh field in laser application, and plays an irreplaceable part in three-dimensional copying. Its accuracy is the highest among all present copying techniques. Reproducibility degree marks the agreement of copied object with the original object on geometry, being the most important index property in laser three-dimensional copying technique. In the present paper, the error of laser three-dimensional copying was analyzed. The conclusion is that the data processing to the point cloud of laser scanning is the key technique to reduce the error and increase the reproducibility degree. The main innovation of this paper is as follows. On the basis of traditional ant colony optimization, rational ant colony optimization algorithm proposed by the author was applied to the laser three-dimensional copying as a new algorithm, and was put into practice. Compared with customary algorithm, rational ant colony optimization algorithm shows distinct advantages in data processing of laser three-dimensional copying, reducing the error and increasing the reproducibility degree of the copy.

  13. Curvature tensor copies in affine geometry

    International Nuclear Information System (INIS)

    Srivastava, P.P.

    1981-01-01

    The sets of space-time and spin-connections which give rise to the same curvature tensor are constructed. The corresponding geometries are compared. Results are illustrated by an explicit calculation and comment on the copies in Einstein-Cartan and Weyl-Cartan geometries. (Author) [pt

  14. 1 CFR 19.3 - Routing and certification of originals and copies.

    Science.gov (United States)

    2010-01-01

    ... 1 General Provisions 1 2010-01-01 2010-01-01 false Routing and certification of originals and... certification of originals and copies. (a) If the order or proclamation is signed by the President, the original...: “Certified to be a true copy of the original.” ...

  15. Inferring Variation in Copy Number Using High Throughput Sequencing Data in R.

    Science.gov (United States)

    Knaus, Brian J; Grünwald, Niklaus J

    2018-01-01

    Inference of copy number variation presents a technical challenge because variant callers typically require the copy number of a genome or genomic region to be known a priori . Here we present a method to infer copy number that uses variant call format (VCF) data as input and is implemented in the R package vcfR . This method is based on the relative frequency of each allele (in both genic and non-genic regions) sequenced at heterozygous positions throughout a genome. These heterozygous positions are summarized by using arbitrarily sized windows of heterozygous positions, binning the allele frequencies, and selecting the bin with the greatest abundance of positions. This provides a non-parametric summary of the frequency that alleles were sequenced at. The method is applicable to organisms that have reference genomes that consist of full chromosomes or sub-chromosomal contigs. In contrast to other software designed to detect copy number variation, our method does not rely on an assumption of base ploidy, but instead infers it. We validated these approaches with the model system of Saccharomyces cerevisiae and applied it to the oomycete Phytophthora infestans , both known to vary in copy number. This functionality has been incorporated into the current release of the R package vcfR to provide modular and flexible methods to investigate copy number variation in genomic projects.

  16. Improved Ordinary Measure and Image Entropy Theory based intelligent Copy Detection Method

    Directory of Open Access Journals (Sweden)

    Dengpan Ye

    2011-10-01

    Full Text Available Nowadays, more and more multimedia websites appear in social network. It brings some security problems, such as privacy, piracy, disclosure of sensitive contents and so on. Aiming at copyright protection, the copy detection technology of multimedia contents becomes a hot topic. In our previous work, a new computer-based copyright control system used to detect the media has been proposed. Based on this system, this paper proposes an improved media feature matching measure and an entropy based copy detection method. The Levenshtein Distance was used to enhance the matching degree when using for feature matching measure in copy detection. For entropy based copy detection, we make a fusion of the two features of entropy matrix of the entropy feature we extracted. Firstly,we extract the entropy matrix of the image and normalize it. Then, we make a fusion of the eigenvalue feature and the transfer matrix feature of the entropy matrix. The fused features will be used for image copy detection. The experiments show that compared to use these two kinds of features for image detection singly, using feature fusion matching method is apparent robustness and effectiveness. The fused feature has a high detection for copy images which have been received some attacks such as noise, compression, zoom, rotation and so on. Comparing with referred methods, the method proposed is more intelligent and can be achieved good performance.

  17. Evaluation of tributyltin toxicity in Chinese rare minnow larvae by abnormal behavior, energy metabolism and endoplasmic reticulum stress.

    Science.gov (United States)

    Li, Zhi-Hua; Li, Ping

    2015-02-05

    Tributyltin (TBT) is a ubiquitous contaminant in aquatic environment, but the detailed mechanisms underlying the toxicity of TBT have not been fully understood. In this study, the effects of TBT on behavior, energy metabolism and endoplasmic reticulum (ER) stress were investigated by using Chinese rare minnow larvae. Fish larvae were exposed at sublethal concentrations of TBT (100, 400 and 800 ng/L) for 7 days. Compared with the control, energy metabolic parameters (RNA/DNA ratio, Na(+)-K(+)-ATPase) were significantly inhibited in fish exposed at highest concentration (800 ng/L), as well as abnormal behaviors observed. Moreover, we found that the PERK (PKR-like ER kinase)-eIF2α (eukaryotic translation initiation factor 2α) pathway, as the main branch was activated by TBT exposure in fish larvae. In short, TBT-induced physiological, biochemical and molecular responses in fish larvae were reflected in parameters measured in this study, which suggest that these biomarkers could be used as potential indicators for monitoring organotin compounds present in aquatic environment. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Chimpanzees copy dominant and knowledgeable individuals: implications for cultural diversity.

    Science.gov (United States)

    Kendal, Rachel; Hopper, Lydia M; Whiten, Andrew; Brosnan, Sarah F; Lambeth, Susan P; Schapiro, Steven J; Hoppitt, Will

    2015-01-01

    Evolutionary theory predicts that natural selection will fashion cognitive biases to guide when, and from whom, individuals acquire social information, but the precise nature of these biases, especially in ecologically valid group contexts, remains unknown. We exposed four captive groups of chimpanzees ( Pan troglodytes ) to a novel extractive foraging device and, by fitting statistical models, isolated four simultaneously operating transmission biases. These include biases to copy (i) higher-ranking and (ii) expert individuals, and to copy others when (iii) uncertain or (iv) of low rank. High-ranking individuals were relatively un-strategic in their use of acquired knowledge, which, combined with the bias for others to observe them, may explain reports that high innovation rates (in juveniles and subordinates) do not generate a correspondingly high frequency of traditions in chimpanzees. Given the typically low rank of immigrants in chimpanzees, a 'copying dominants' bias may contribute to the observed maintenance of distinct cultural repertoires in neighboring communities despite sharing similar ecology and knowledgeable migrants. Thus, a copying dominants strategy may, as often proposed for conformist transmission, and perhaps in concert with it, restrict the accumulation of traditions within chimpanzee communities whilst maintaining cultural diversity.

  19. Association of MYCN copy number with clinical features, tumor biology, and outcomes in neuroblastoma: A report from the Children's Oncology Group.

    Science.gov (United States)

    Campbell, Kevin; Gastier-Foster, Julie M; Mann, Meegan; Naranjo, Arlene H; Van Ryn, Collin; Bagatell, Rochelle; Matthay, Katherine K; London, Wendy B; Irwin, Meredith S; Shimada, Hiroyuki; Granger, M Meaghan; Hogarty, Michael D; Park, Julie R; DuBois, Steven G

    2017-11-01

    High-level MYCN amplification (MNA) is associated with poor outcome and unfavorable clinical and biological features in patients with neuroblastoma. To the authors' knowledge, less is known regarding these associations in patients with low-level MYCN copy number increases. In this retrospective study, the authors classified patients has having tumors with MYCN wild-type tumors, MYCN gain (2-4-fold increase in MYCN signal compared with the reference probe), or MNA (>4-fold increase). Tests of trend were used to investigate ordered associations between MYCN copy number category and features of interest. Log-rank tests and Cox models compared event-free survival and overall survival by subgroup. Among 4672 patients, 3694 (79.1%) had MYCN wild-type tumors, 133 (2.8%) had MYCN gain, and 845 (18.1%) had MNA. For each clinical/biological feature, the percentage of patients with an unfavorable feature was lowest in the MYCN wild-type category, intermediate in the MYCN gain category, and highest in the MNA category (PNeuroblastoma Staging System) and patients with non-high-risk disease with MYCN gain had a significantly increased risk for death, a finding confirmed on multivariable testing. Increasing MYCN copy number is associated with an increasingly higher rate of unfavorable clinical/biological features, with 11q aberration being an exception. Patients with MYCN gain appear to have inferior outcomes, especially in otherwise more favorable groups. Cancer 2017;123:4224-4235. © 2017 American Cancer Society. © 2017 American Cancer Society.

  20. Multi-centered N=2 BPS black holes: a double copy description

    Energy Technology Data Exchange (ETDEWEB)

    Cardoso, G.L.; Nagy, S.; Nampuri, S. [Center for Mathematical Analysis, Geometry and Dynamical Systems,Department of Mathematics, Instituto Superior Técnico, Universidade de Lisboa,Av. Rovisco Pais, Lisboa, 1049-001 (Portugal)

    2017-04-07

    We present the on-shell double copy dictionary for linearised N=2 supergravity coupled to an arbitrary number of vector multiplets in four dimensions. Subsequently, we use it to construct a double copy description of multi-centered BPS black hole solutions in these theories in the weak-field approximation.

  1. Allelic recombination between distinct genomic locations generates copy number diversity in human β-defensins

    Science.gov (United States)

    Bakar, Suhaili Abu; Hollox, Edward J.; Armour, John A. L.

    2009-01-01

    β-Defensins are small secreted antimicrobial and signaling peptides involved in the innate immune response of vertebrates. In humans, a cluster of at least 7 of these genes shows extensive copy number variation, with a diploid copy number commonly ranging between 2 and 7. Using a genetic mapping approach, we show that this cluster is at not 1 but 2 distinct genomic loci ≈5 Mb apart on chromosome band 8p23.1, contradicting the most recent genome assembly. We also demonstrate that the predominant mechanism of change in β-defensin copy number is simple allelic recombination occurring in the interval between the 2 distinct genomic loci for these genes. In 416 meiotic transmissions, we observe 3 events creating a haplotype copy number not found in the parent, equivalent to a germ-line rate of copy number change of ≈0.7% per gamete. This places it among the fastest-changing copy number variants currently known. PMID:19131514

  2. Getting DNA copy numbers without control samples.

    Science.gov (United States)

    Ortiz-Estevez, Maria; Aramburu, Ander; Rubio, Angel

    2012-08-16

    The selection of the reference to scale the data in a copy number analysis has paramount importance to achieve accurate estimates. Usually this reference is generated using control samples included in the study. However, these control samples are not always available and in these cases, an artificial reference must be created. A proper generation of this signal is crucial in terms of both noise and bias.We propose NSA (Normality Search Algorithm), a scaling method that works with and without control samples. It is based on the assumption that genomic regions enriched in SNPs with identical copy numbers in both alleles are likely to be normal. These normal regions are predicted for each sample individually and used to calculate the final reference signal. NSA can be applied to any CN data regardless the microarray technology and preprocessing method. It also finds an optimal weighting of the samples minimizing possible batch effects. Five human datasets (a subset of HapMap samples, Glioblastoma Multiforme (GBM), Ovarian, Prostate and Lung Cancer experiments) have been analyzed. It is shown that using only tumoral samples, NSA is able to remove the bias in the copy number estimation, to reduce the noise and therefore, to increase the ability to detect copy number aberrations (CNAs). These improvements allow NSA to also detect recurrent aberrations more accurately than other state of the art methods. NSA provides a robust and accurate reference for scaling probe signals data to CN values without the need of control samples. It minimizes the problems of bias, noise and batch effects in the estimation of CNs. Therefore, NSA scaling approach helps to better detect recurrent CNAs than current methods. The automatic selection of references makes it useful to perform bulk analysis of many GEO or ArrayExpress experiments without the need of developing a parser to find the normal samples or possible batches within the data. The method is available in the open-source R package

  3. Molecular subtypes in stage II-III colon cancer defined by genomic instability: early recurrence-risk associated with a high copy-number variation and loss of RUNX3 and CDKN2A.

    Directory of Open Access Journals (Sweden)

    Marianne Berg

    Full Text Available We sought to investigate various molecular subtypes defined by genomic instability that may be related to early death and recurrence in colon cancer.We sought to investigate various molecular subtypes defined by instability at microsatellites (MSI, changes in methylation patterns (CpG island methylator phenotype, CIMP or copy number variation (CNV in 8 genes. Stage II-III colon cancers (n = 64 were investigated by methylation-specific multiplex ligated probe amplification (MS-MLPA. Correlation of CNV, CIMP and MSI, with mutations in KRAS and BRAFV600E were assessed for overlap in molecular subtypes and early recurrence risk by uni- and multivariate regression.The CIMP phenotype occurred in 34% (22/64 and MSI in 27% (16/60 of the tumors, with noted CIMP/MSI overlap. Among the molecular subtypes, a high CNV phenotype had an associated odds ratio (OR for recurrence of 3.2 (95% CI 1.1-9.3; P = 0.026. Losses of CACNA1G (OR of 2.9, 95% CI 1.4-6.0; P = 0.001, IGF2 (OR of 4.3, 95% CI 1.1-15.8; P = 0.007, CDKN2A (p16 (OR of 2.0, 95% CI 1.1-3.6; P = 0.024, and RUNX3 (OR of 3.4, 95% CI 1.3-8.7; P = 0.002 were associated with early recurrence, while MSI, CIMP, KRAS or BRAF V600E mutations were not. The CNV was significantly higher in deceased patients (CNV in 6 of 8 compared to survivors (CNV in 3 of 8. Only stage and loss of RUNX3 and CDKN2A were significant in the multivariable risk-model for early recurrence.A high copy number variation phenotype is a strong predictor of early recurrence and death, and may indicate a dose-dependent relationship between genetic instability and outcome. Loss of tumor suppressors RUNX3 and CDKN2A were related to recurrence-risk and warrants further investigation.

  4. Genomic copy number variations in three Southeast Asian populations.

    Science.gov (United States)

    Ku, Chee-Seng; Pawitan, Yudi; Sim, Xueling; Ong, Rick T H; Seielstad, Mark; Lee, Edmund J D; Teo, Yik-Ying; Chia, Kee-Seng; Salim, Agus

    2010-07-01

    Research on the role of copy number variations (CNVs) in the genetic risk of diseases in Asian populations has been hampered by a relative lack of reference CNV maps for Asian populations outside the East Asians. In this article, we report the population characteristics of CNVs in Chinese, Malay, and Asian Indian populations in Singapore. Using the Illumina Human 1M Beadchip array, we identify 1,174 CNV loci in these populations that corroborated with findings when the same samples were typed on the Affymetrix 6.0 platform. We identify 441 novel loci not previously reported in the Database of Genomic Variations (DGV). We observe a considerable number of loci that span all three populations and were previously unreported, as well as population-specific loci that are quite common in the respective populations. From this we observe the distribution of CNVs in the Asian Indian population to be considerably different from the Chinese and Malay populations. About half of the deletion loci and three-quarters of duplication loci overlap UCSC genes. Tens of loci show population differentiation and overlap with genes previously known to be associated with genetic risk of diseases. One of these loci is the CYP2A6 deletion, previously linked to reduced susceptibility to lung cancer. (c) 2010 Wiley-Liss, Inc.

  5. TEGS-CN: A Statistical Method for Pathway Analysis of Genome-wide Copy Number Profile.

    Science.gov (United States)

    Huang, Yen-Tsung; Hsu, Thomas; Christiani, David C

    2014-01-01

    The effects of copy number alterations make up a significant part of the tumor genome profile, but pathway analyses of these alterations are still not well established. We proposed a novel method to analyze multiple copy numbers of genes within a pathway, termed Test for the Effect of a Gene Set with Copy Number data (TEGS-CN). TEGS-CN was adapted from TEGS, a method that we previously developed for gene expression data using a variance component score test. With additional development, we extend the method to analyze DNA copy number data, accounting for different sizes and thus various numbers of copy number probes in genes. The test statistic follows a mixture of X (2) distributions that can be obtained using permutation with scaled X (2) approximation. We conducted simulation studies to evaluate the size and the power of TEGS-CN and to compare its performance with TEGS. We analyzed a genome-wide copy number data from 264 patients of non-small-cell lung cancer. With the Molecular Signatures Database (MSigDB) pathway database, the genome-wide copy number data can be classified into 1814 biological pathways or gene sets. We investigated associations of the copy number profile of the 1814 gene sets with pack-years of cigarette smoking. Our analysis revealed five pathways with significant P values after Bonferroni adjustment (number data, and causal mechanisms of the five pathways require further study.

  6. Copy-Move Forgery Detection Technique for Forensic Analysis in Digital Images

    Directory of Open Access Journals (Sweden)

    Toqeer Mahmood

    2016-01-01

    Full Text Available Due to the powerful image editing tools images are open to several manipulations; therefore, their authenticity is becoming questionable especially when images have influential power, for example, in a court of law, news reports, and insurance claims. Image forensic techniques determine the integrity of images by applying various high-tech mechanisms developed in the literature. In this paper, the images are analyzed for a particular type of forgery where a region of an image is copied and pasted onto the same image to create a duplication or to conceal some existing objects. To detect the copy-move forgery attack, images are first divided into overlapping square blocks and DCT components are adopted as the block representations. Due to the high dimensional nature of the feature space, Gaussian RBF kernel PCA is applied to achieve the reduced dimensional feature vector representation that also improved the efficiency during the feature matching. Extensive experiments are performed to evaluate the proposed method in comparison to state of the art. The experimental results reveal that the proposed technique precisely determines the copy-move forgery even when the images are contaminated with blurring, noise, and compression and can effectively detect multiple copy-move forgeries. Hence, the proposed technique provides a computationally efficient and reliable way of copy-move forgery detection that increases the credibility of images in evidence centered applications.

  7. 18 CFR 385.2004 - Original and copies of filings (Rule 2004).

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Original and copies of... Requirements for Filings in Proceedings Before the Commission § 385.2004 Original and copies of filings (Rule 2004). Any person filing under this chapter must provide an original of the filing and fourteen exact...

  8. 17 CFR 270.24b-2 - Filing copies of sales literature.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Filing copies of sales literature. 270.24b-2 Section 270.24b-2 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... literature. Copies of material filed with the Commission for the sole purpose of complying with section 24(b...

  9. 20 CFR 703.105 - Copies of forms of policies to be submitted with application.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Copies of forms of policies to be submitted... REGULATIONS Authorization of Insurance Carriers § 703.105 Copies of forms of policies to be submitted with... of the Office copies of the forms of policies which the applicant proposes to issue in writing...

  10. Tributyltin affects shoaling and anxiety behavior in female rare minnow (Gobiocypris rarus).

    Science.gov (United States)

    Zhang, Jiliang; Zhang, Chunnuan; Sun, Ping; Shao, Xian

    2016-09-01

    Effects of tributyltin (TBT) on reproduction are well established in many fish species. However, few studies report the effects of TBT on non-reproductive behaviors, which is a novel aspect of endocrine disruption in fish. Thus, the present study used rare minnow (Gobiocypris rarus) to investigate the effects of TBT, at environmental concentrations of 1, 10 and 100ng/L, on shoaling and anxiety behaviors. The results showed that fish exposed to TBT had less group cohesion during the course of the 10-min observation period as compared with the control fish. Further, TBT altered the shoaling in the Novel tank test, where shoaling is determined as the tendency to leave a shoal of littermates trapped behind a Plexiglas barrier at one end of the test tank. Fish exposed to TBT had shorter latency before leaving shoal mates and spent more time away from shoal than control fish. In addition, we also used Novel tanks to study the anxiety behavior as the tendency to stay at the bottom when introduced into an unfamiliar environment. The fish exposed to TBT showed increased anxiety, manifested as increased latency to enter the upper half and decreased time in upper half when compared with the control fish. TBT exposure increased the levels of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid, and decreased the levels of 5-hydroxytryptamine and its metabolite 5-hydroxy indole acetic acid in the brain. Thus, the hypofunction of the dopaminergic system or of the serotoninergic system or the combination of the two may underlie the observed behavioral change, which might affect the fitness of fish in their natural environment. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Agency Researchers' Perception of the Users and Uses of Copy Research.

    Science.gov (United States)

    Reid, Leonard N.; Salmon, Charles T.

    A survey of 30 advertising agency researchers sought to determine (1) whether there are differences between agency researchers' perception of who benefits most from copy research and who should benefit most, and (2) whether there are differences between their perception of how copy research is used and how it should be used. Consistent with…

  12. Influence of elevated alkalinity and natural organic matter (NOM) on tissue-specific metal accumulation and reproductive performance in fathead minnows during chronic, multi-trophic exposures to a metal mine effluent.

    Science.gov (United States)

    Ouellet, Jacob D; Dubé, Monique G; Niyogi, Som

    2013-09-01

    Metal bioavailability in aquatic organisms is known to be influenced by various water chemistry parameters. The present study examined the influence of alkalinity and natural organic matter (NOM) on tissue-specific metal accumulation and reproductive performance of fathead minnows (Pimephales promelas) during environmentally relevant chronic exposures to a metal mine effluent (MME). Sodium bicarbonate (NaHCO3) or NOM (as commercial humic acid) were added to a Canadian MME [45 percent process water effluent (PWE)] in order to evaluate whether increases in alkalinity (3-4 fold) or NOM (~1.5-3mg/L dissolved organic carbon) would reduce metal accumulation and mitigate reproductive toxicity in fathead minnows during a 21-day multi-trophic exposure. Eleven metals (barium, boron, cobalt, copper, lithium, manganese, molybdenum, nickel, rubidium, selenium, and strontium) were elevated in the 45 percent PWE relative to the reference water. Exposure to the unmodified 45 percent PWE resulted in a decrease of fathead minnow egg production (~300 fewer eggs/pair) relative to the unmodified reference water, over the 21-day exposure period. Water chemistry modifications produced a modest decrease in free ion activity of some metals (as shown by MINTEQ, Version 3) in the 45 percent PWE exposure water, but did not alter the metal burden in the treatment-matched larval Chironomus dilutus (the food source of fish during exposure). The tissue-specific metal accumulation increased in fish exposed to the 45 percent PWE relative to the reference water, irrespective of water chemistry modifications, and the tissue metal concentrations were found to be similar between fish in the unmodified and modified 45 percent PWE (higher alkalinity or NOM) treatments. Interestingly however, increased alkalinity and NOM markedly improved fish egg production both in the reference water (~500 and ~590 additional eggs/pair, respectively) and 45 percent PWE treatments (~570 and ~260 additional eggs

  13. SU(3) lattice gauge fixing with overrelaxation and Gribov copies

    Energy Technology Data Exchange (ETDEWEB)

    Paciello, M.L.; Taglienti, B. (INFN La Sapienza, Rome (Italy)); Parrinello, C. (Physics Dept., New York Univ., NY (United States)); Petrarca, S. (Theory Div., CERN, Geneva (Switzerland)); Vladikas, A. (Dipt. di Fisica, Univ. Tor Vergata, Rome (Italy) INFN Tor Vergata, Rome (Italy))

    1992-02-06

    We report on the phenomenology of SU(3) lattice Landau gauge fixing as obtained by using an overrelaxation algorithm. An interesting result obtained using this very efficient algorithm is that distinct Gribov copies are generated by simply modifying the value {omega} of the overrelaxation parameter for a fixed starting configuration. By generating random gauge equivalent configurations, we study the variation of the number of copies with the lattice volume and gauge coupling. (orig.).

  14. The copying power of one-state tree transducers

    DEFF Research Database (Denmark)

    Engelfriet, Joost; Skyum, Sven

    1982-01-01

    One-state deterministic top-down tree transducers (or, tree homomorphisms) cannot handle “prime copying,” i.e., their class of output (string) languages is not closed under the operation L → {$(w$)f(n) short parallel w ε L, f(n) greater-or-equal, slanted 1}, where f is any integer function whose...... range contains numbers with arbitrarily large prime factors (such as a polynomial). The exact amount of nonclosure under these copying operations is established for several classes of input (tree) languages. These results are relevant to the extended definable (or, restricted parallel level) languages......, to the syntax-directed translation of context-free languages, and to the tree transducer hierarchy....

  15. Exploiting rRNA operon copy number to investigate bacterial reproductive strategies.

    Science.gov (United States)

    Roller, Benjamin R K; Stoddard, Steven F; Schmidt, Thomas M

    2016-09-12

    The potential for rapid reproduction is a hallmark of microbial life, but microbes in nature must also survive and compete when growth is constrained by resource availability. Successful reproduction requires different strategies when resources are scarce and when they are abundant 1,2 , but a systematic framework for predicting these reproductive strategies in bacteria has not been available. Here, we show that the number of ribosomal RNA operons (rrn) in bacterial genomes predicts two important components of reproduction-growth rate and growth efficiency-which are favoured under contrasting regimes of resource availability 3,4 . We find that the maximum reproductive rate of bacteria doubles with a doubling of rrn copy number, and the efficiency of carbon use is inversely related to maximal growth rate and rrn copy number. We also identify a feasible explanation for these patterns: the rate and yield of protein synthesis mirror the overall pattern in maximum growth rate and growth efficiency. Furthermore, comparative analysis of genomes from 1,167 bacterial species reveals that rrn copy number predicts traits associated with resource availability, including chemotaxis and genome streamlining. Genome-wide patterns of orthologous gene content covary with rrn copy number, suggesting convergent evolution in response to resource availability. Our findings imply that basic cellular processes adapt in contrasting ways to long-term differences in resource availability. They also establish a basis for predicting changes in bacterial community composition in response to resource perturbations using rrn copy number measurements 5 or inferences 6,7 .

  16. Dietary Variation and Evolution of Gene Copy Number among Dog Breeds.

    Directory of Open Access Journals (Sweden)

    Taylor Reiter

    Full Text Available Prolonged human interactions and artificial selection have influenced the genotypic and phenotypic diversity among dog breeds. Because humans and dogs occupy diverse habitats, ecological contexts have likely contributed to breed-specific positive selection. Prior to the advent of modern dog-feeding practices, there was likely substantial variation in dietary landscapes among disparate dog breeds. As such, we investigated one type of genetic variant, copy number variation, in three metabolic genes: glucokinase regulatory protein (GCKR, phytanol-CoA 2-hydroxylase (PHYH, and pancreatic α-amylase 2B (AMY2B. These genes code for proteins that are responsible for metabolizing dietary products that originate from distinctly different food types: sugar, meat, and starch, respectively. After surveying copy number variation among dogs with diverse dietary histories, we found no correlation between diet and positive selection in either GCKR or PHYH. Although it has been previously demonstrated that dogs experienced a copy number increase in AMY2B relative to wolves during or after the dog domestication process, we demonstrate that positive selection continued to act on amylase copy number in dog breeds that consumed starch-rich diets in time periods after domestication. Furthermore, we found that introgression with wolves is not responsible for deterioration of positive selection on AMY2B among diverse dog breeds. Together, this supports the hypothesis that the amylase copy number expansion is found universally in dogs.

  17. Association testing of copy number variants in schizophrenia and autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Crespi Bernard J

    2012-05-01

    Full Text Available Abstract Background Autism spectrum disorders and schizophrenia have been associated with an overlapping set of copy number variant loci, but the nature and degree of overlap in copy number variants (deletions compared to duplications between these two disorders remains unclear. Methods We systematically evaluated three lines of evidence: (1 the statistical bases for associations of autism spectrum disorders and schizophrenia with a set of the primary CNVs thus far investigated, from previous studies; (2 data from case series studies on the occurrence of these CNVs in autism spectrum disorders, especially among children, and (3 data on the extent to which the CNVs were associated with intellectual disability and developmental, speech, or language delays. We also conducted new analyses of existing data on these CNVs in autism by pooling data from seven case control studies. Results Four of the CNVs considered, dup 1q21.1, dup 15q11-q13, del 16p11.2, and dup 22q11.21, showed clear statistical evidence as autism risk factors, whereas eight CNVs, del 1q21.1, del 3q29, del 15q11.2, del 15q13.3, dup 16p11.2, dup 16p13.1, del 17p12, and del 22q11.21, were strongly statistically supported as risk factors for schizophrenia. Three of the CNVs, dup 1q21.1, dup 16p11.2, and dup 16p13.1, exhibited statistical support as risk factors for both autism and schizophrenia, although for each of these CNVs statistical significance was nominal for tests involving one of the two disorders. For the CNVs that were statistically associated with schizophrenia but were not statistically associated with autism, a notable number of children with the CNVs have been diagnosed with autism or ASD; children with these CNVs also demonstrate a high incidence of intellectual disability and developmental, speech, or language delays. Conclusions These findings suggest that although CNV loci notably overlap between autism and schizophrenia, the degree of strongly statistically

  18. 46 CFR Sec. 5 - Responsibility for duplicating copies of NSA-WORKSMALREP Contract.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false Responsibility for duplicating copies of NSA-WORKSMALREP Contract. Sec. 5 Section 5 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION A-NATIONAL... INDIVIDUAL CONTRACT FOR MINOR REPAIRS-NSA-WORKSMALREP Sec. 5 Responsibility for duplicating copies of NSA...

  19. Measurement of locus copy number by hybridisation with amplifiable probes

    Science.gov (United States)

    Armour, John A. L.; Sismani, Carolina; Patsalis, Philippos C.; Cross, Gareth

    2000-01-01

    Despite its fundamental importance in genome analysis, it is only recently that systematic approaches have been developed to assess copy number at specific genetic loci, or to examine genomic DNA for submicroscopic deletions of unknown location. In this report we show that short probes can be recovered and amplified quantitatively following hybridisation to genomic DNA. This simple observation forms the basis of a new approach to determining locus copy number in complex genomes. The power and specificity of multiplex amplifiable probe hybridisation is demonstrated by the simultaneous assessment of copy number at a set of 40 human loci, including detection of deletions causing Duchenne muscular dystrophy and Prader–Willi/Angelman syndromes. Assembly of other probe sets will allow novel, technically simple approaches to a wide variety of genetic analyses, including the potential for extension to high resolution genome-wide screens for deletions and amplifications. PMID:10606661

  20. Measurement of locus copy number by hybridisation with amplifiable probes.

    Science.gov (United States)

    Armour, J A; Sismani, C; Patsalis, P C; Cross, G

    2000-01-15

    Despite its fundamental importance in genome analysis, it is only recently that systematic approaches have been developed to assess copy number at specific genetic loci, or to examine genomic DNA for submicro-scopic deletions of unknown location. In this report we show that short probes can be recovered and amplified quantitatively following hybridisation to genomic DNA. This simple observation forms the basis of a new approach to determining locus copy number in complex genomes. The power and specificity of multiplex amplifiable probe hybridisation is demonstrated by the simultaneous assessment of copy number at a set of 40 human loci, including detection of deletions causing Duchenne muscular dystrophy and Prader-Willi/Angelman syndromes. Assembly of other probe sets will allow novel, technically simple approaches to a wide variety of genetic analyses, including the potential for extension to high resolution genome-wide screens for deletions and amplifications.

  1. 77 FR 27125 - Periodicals-Recognition of Distribution of Periodicals via Electronic Copies

    Science.gov (United States)

    2012-05-09

    ... Electronic Copies AGENCY: Postal Service\\TM\\. ACTION: Final rule. SUMMARY: The Postal Service will revise the Mailing Standards of the United States Postal Service, Domestic Mail Manual (DMM[supreg]) 707.6 to permit limited reporting of electronic copies of Periodicals publications to satisfy the circulation standards...

  2. Getting DNA copy numbers without control samples

    Directory of Open Access Journals (Sweden)

    Ortiz-Estevez Maria

    2012-08-01

    Full Text Available Abstract Background The selection of the reference to scale the data in a copy number analysis has paramount importance to achieve accurate estimates. Usually this reference is generated using control samples included in the study. However, these control samples are not always available and in these cases, an artificial reference must be created. A proper generation of this signal is crucial in terms of both noise and bias. We propose NSA (Normality Search Algorithm, a scaling method that works with and without control samples. It is based on the assumption that genomic regions enriched in SNPs with identical copy numbers in both alleles are likely to be normal. These normal regions are predicted for each sample individually and used to calculate the final reference signal. NSA can be applied to any CN data regardless the microarray technology and preprocessing method. It also finds an optimal weighting of the samples minimizing possible batch effects. Results Five human datasets (a subset of HapMap samples, Glioblastoma Multiforme (GBM, Ovarian, Prostate and Lung Cancer experiments have been analyzed. It is shown that using only tumoral samples, NSA is able to remove the bias in the copy number estimation, to reduce the noise and therefore, to increase the ability to detect copy number aberrations (CNAs. These improvements allow NSA to also detect recurrent aberrations more accurately than other state of the art methods. Conclusions NSA provides a robust and accurate reference for scaling probe signals data to CN values without the need of control samples. It minimizes the problems of bias, noise and batch effects in the estimation of CNs. Therefore, NSA scaling approach helps to better detect recurrent CNAs than current methods. The automatic selection of references makes it useful to perform bulk analysis of many GEO or ArrayExpress experiments without the need of developing a parser to find the normal samples or possible batches within the

  3. 28 CFR 5.1101 - Copies of the Report of the Attorney General.

    Science.gov (United States)

    2010-07-01

    ... Attorney General. Copies of the Report of the Attorney General to the Congress on the Administration of the... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Copies of the Report of the Attorney General. 5.1101 Section 5.1101 Judicial Administration DEPARTMENT OF JUSTICE ADMINISTRATION AND...

  4. The Home Copying Loophole Widens: Sony & Others v . Easyinternetcafé

    OpenAIRE

    Free, Dominic; Garnett, Nic

    2003-01-01

    The record industry is engaged in a determined campaign to stop the unlawful copying of music files downloaded via the Internet. In Sony & Others v. Easyinternetcafé [2003] All ER(D) 249 proceedings were brought by several major record companies to prevent Easyinternetcafé from providing a service copying music files onto CDs for its customers. The claimants succeeded in their aim. However the summary judgment which they obtained had a sting in the tail. It supports the proposition that t...

  5. Evidence for the existence of Gribov copies in Landau gauge lattice QCD

    Energy Technology Data Exchange (ETDEWEB)

    Marinari, E.; Ricci, R. (Rome-2 Univ. (Italy). Dipt. di Fisica INFN, Rome (Italy)); Parrinello, C. (New York Univ., NY (USA). Physics Dept.)

    1991-09-16

    We unambiguously show the existence of Gribov copies in a pure SU(3) gauge lattice model, with Wilson action. We show that the usual steepest-descent algorithms used for implementing the lattice Landau gauge lead to ambiguities, which are related to the existence of Gribov copies in the model. (orig.).

  6. 40 CFR 267.53 - Who must have copies of the contingency plan?

    Science.gov (United States)

    2010-07-01

    ... contingency plan? 267.53 Section 267.53 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... UNDER A STANDARDIZED PERMIT Contingency Plan and Emergency Procedures § 267.53 Who must have copies of the contingency plan? (a) You must maintain a copy of the plan with all revisions at the facility; and...

  7. Local Reasoning about a Copying Garbage Collector

    DEFF Research Database (Denmark)

    Torp-Smith, Noah; Birkedal, Lars; Reynolds, John C.

    2008-01-01

    We present a programming language, model, and logic appropriate for implementing and reasoning about a memory management system. We state semantically what is meant by correctness of a copying garbage collector, and employ a variant of the novel separation logics to formally specify partial corre...

  8. Genome Architecture and Its Roles in Human Copy Number Variation

    Directory of Open Access Journals (Sweden)

    Lu Chen

    2014-12-01

    Full Text Available Besides single-nucleotide variants in the human genome, large-scale genomic variants, such as copy number variations (CNVs, are being increasingly discovered as a genetic source of human diversity and the pathogenic factors of diseases. Recent experimental findings have shed light on the links between different genome architectures and CNV mutagenesis. In this review, we summarize various genomic features and discuss their contributions to CNV formation. Genomic repeats, including both low-copy and high-copy repeats, play important roles in CNV instability, which was initially known as DNA recombination events. Furthermore, it has been found that human genomic repeats can also induce DNA replication errors and consequently result in CNV mutations. Some recent studies showed that DNA replication timing, which reflects the high-order information of genomic organization, is involved in human CNV mutations. Our review highlights that genome architecture, from DNA sequence to high-order genomic organization, is an important molecular factor in CNV mutagenesis and human genomic instability.

  9. Low copy numbers of complement C4 and homozygous deficiency of C4A may predispose to severe disease and earlier disease onset in patients with systemic lupus erythematosus.

    Science.gov (United States)

    Jüptner, M; Flachsbart, F; Caliebe, A; Lieb, W; Schreiber, S; Zeuner, R; Franke, A; Schröder, J O

    2018-04-01

    Objectives Low copy numbers and deletion of complement C4 genes are potent risk factors for systemic lupus erythematosus (SLE). However, it is not known whether this genetic association affects the clinical outcome. We investigated C4 copy number variation and its relationship to clinical and serological features in a Northern European lupus cohort. Methods We genotyped the C4 gene locus using polymerase chain reaction (PCR)-based TaqMan assays in 169 patients with SLE classified according to the 1997 revised American College of Rheumatology (ACR) criteria and in 520 matched controls. In the patient group the mean C4 serum protein concentrations nephelometrically measured during a 12-month period prior to genetic analysis were compared to C4 gene copy numbers. Severity of disease was classified according to the intensity of the immunosuppressive regimens applied and compared to C4 gene copy numbers, too. In addition, we performed a TaqMan based analysis of three lupus-associated single-nucleotide polymorphisms (SNPs) located inside the major histocompatibility complex (MHC) to investigate the independence of complement C4 in association with SLE. Results Homozygous deficiency of the C4A isotype was identified as the strongest risk factor for SLE (odds ratio (OR) = 5.329; p = 7.7 × 10 -3 ) in the case-control comparison. Moreover, two copies of total C4 were associated with SLE (OR = 3.699; p = 6.8 × 10 -3 ). C4 serum levels were strongly related to C4 gene copy numbers in patients, the mean concentration ranging from 0.110 g/l (two copies) to 0.256 g/l (five to six copies; p = 4.9 × 10 -6 ). Two copies of total C4 and homozygous deletion of C4A were associated with a disease course requiring cyclophosphamide therapy (OR = 4.044; p = 0.040 and OR = 5.798; p = 0.034, respectively). Homozygous deletion of C4A was associated with earlier onset of SLE (median 24 vs. 34 years; p = 0.019) but not significant after

  10. 37 CFR 202.20 - Deposit of copies and phonorecords for copyright registration.

    Science.gov (United States)

    2010-07-01

    ... published in both hard copy, i.e., in a physically tangible format, and also in an electronic format, the current Library of Congress Best Edition Statement requirements pertaining to the hard copy format apply... registration in digital formats. A ‘complete’ electronically filed work is one which is embodied in a digital...

  11. Accurate, high-throughput typing of copy number variation using paralogue ratios from dispersed repeats.

    Science.gov (United States)

    Armour, John A L; Palla, Raquel; Zeeuwen, Patrick L J M; den Heijer, Martin; Schalkwijk, Joost; Hollox, Edward J

    2007-01-01

    Recent work has demonstrated an unexpected prevalence of copy number variation in the human genome, and has highlighted the part this variation may play in predisposition to common phenotypes. Some important genes vary in number over a high range (e.g. DEFB4, which commonly varies between two and seven copies), and have posed formidable technical challenges for accurate copy number typing, so that there are no simple, cheap, high-throughput approaches suitable for large-scale screening. We have developed a simple comparative PCR method based on dispersed repeat sequences, using a single pair of precisely designed primers to amplify products simultaneously from both test and reference loci, which are subsequently distinguished and quantified via internal sequence differences. We have validated the method for the measurement of copy number at DEFB4 by comparison of results from >800 DNA samples with copy number measurements by MAPH/REDVR, MLPA and array-CGH. The new Paralogue Ratio Test (PRT) method can require as little as 10 ng genomic DNA, appears to be comparable in accuracy to the other methods, and for the first time provides a rapid, simple and inexpensive method for copy number analysis, suitable for application to typing thousands of samples in large case-control association studies.

  12. Small Vocabulary with Saliency Matching for Video Copy Detection

    DEFF Research Database (Denmark)

    Ren, Huamin; Moeslund, Thomas B.; Tang, Sheng

    2013-01-01

    The importance of copy detection has led to a substantial amount of research in recent years, among which Bag of visual Words (BoW) plays an important role due to its ability to effectively handling occlusion and some minor transformations. One crucial issue in BoW approaches is the size of vocab......The importance of copy detection has led to a substantial amount of research in recent years, among which Bag of visual Words (BoW) plays an important role due to its ability to effectively handling occlusion and some minor transformations. One crucial issue in BoW approaches is the size...... matching algorithm based on salient visual words selection. More specifically, the variation of visual words across a given video are represented as trajectories and those containing locally asymptotically stable points are selected as salient visual words. Then we attempt to measure the similarity of two...... videos through saliency matching merely based on the selected salient visual words to remove false positives. Our experiments show that a small codebook with saliency matching is quite competitive in video copy detection. With the incorporation of the proposed saliency matching, the precision can...

  13. Tragedy and Delirium in Montevideo: The Theater of Copi

    Directory of Open Access Journals (Sweden)

    Stefano Casi

    2017-11-01

    Full Text Available Nelle sue pièces comiche il drammaturgo franco-argentino Copi (1939-1987 si confronta con la tragedia, immergendo riferimenti e forme tragiche nell’umorismo e nel camp, all’interno di una cornice caratterizzata dal relativismo più estremo, in cui vita e morte coincidono e in cui ogni personaggio (spesso transgender afferma e nega la propria identità. Gli ‘eroi’ di Copi mostrano un difetto di volontà, che porta i loro sforzi titanici a diventare perdenti e a infrangersi contro risultati ridicoli o contro lo stallo. Le pièces oscillano tra «circo» e «tragedia», come dice il protagonista di Cachafaz (1981, definita dall’autore «tragedia barbara», in cui la tradizione del gauchesco argentino si coniuga con una visione cruenta e soprannaturale della tragedia, tra Macbeth e Le baccanti. Il linguaggio della commedia umoristica e camp è la base per la ricostruzione di un nuovo linguaggio tragico, e l’intero corpus teatrale di Copi non si presenta come parodia o dissacrazione, bensì come ‘riattivazione’ della tragedia nel secolo della sua ‘morte’ (Steiner.

  14. 37 CFR 360.25 - Copies of claims.

    Science.gov (United States)

    2010-07-01

    ... Section 360.25 Patents, Trademarks, and Copyrights COPYRIGHT ROYALTY BOARD, LIBRARY OF CONGRESS SUBMISSION OF ROYALTY CLAIMS FILING OF CLAIMS TO ROYALTY FEES COLLECTED UNDER COMPULSORY LICENSE Digital Audio Recording Devices and Media Royalty Claims § 360.25 Copies of claims. A claimant shall, for each claim...

  15. 37 CFR 360.5 - Copies of claims.

    Science.gov (United States)

    2010-07-01

    ... Section 360.5 Patents, Trademarks, and Copyrights COPYRIGHT ROYALTY BOARD, LIBRARY OF CONGRESS SUBMISSION OF ROYALTY CLAIMS FILING OF CLAIMS TO ROYALTY FEES COLLECTED UNDER COMPULSORY LICENSE Cable Claims... hand delivery or by mail, file an original and one copy of the claim to cable royalty fees. ...

  16. 37 CFR 203.5 - Inspection and copying.

    Science.gov (United States)

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Inspection and copying. 203.5 Section 203.5 Patents, Trademarks, and Copyrights COPYRIGHT OFFICE, LIBRARY OF CONGRESS COPYRIGHT OFFICE AND PROCEDURES FREEDOM OF INFORMATION ACT: POLICIES AND PROCEDURES Availability of Information § 203.5...

  17. Performance of Molecular Inversion Probes (MIP) in Allele CopyNumber Determination

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yuker; Moorhead, Martin; Karlin-Neumann, George; Wang,Nicolas J.; Ireland, James; Lin, Steven; Chen, Chunnuan; Heiser, LauraM.; Chin, Koei; Esserman, Laura; Gray, Joe W.; Spellman, Paul T.; Faham,Malek

    2007-05-14

    We have developed a new protocol for using MolecularInversion Probes (MIP) to accurately and specifically measure allele copynumber (ACN). The new protocol provides for significant improvementsincluding the reduction of input DNA (from 2?g) by more than 25 fold (to75ng total genomic DNA), higher overall precision resulting in one orderof magnitude lower false positive rate, and greater dynamic range withaccurate absolute copy number up to 60 copies.

  18. Copy-number variants in neurodevelopmental disorders: promises and challenges.

    LENUS (Irish Health Repository)

    Merikangas, Alison K

    2012-02-01

    Copy-number variation (CNV) is the most prevalent type of structural variation in the human genome. There is emerging evidence that copy-number variants (CNVs) provide a new vista on understanding susceptibility to neuropsychiatric disorders. Some challenges in the interpretation of current CNV studies include the use of overlapping samples, differing phenotypic definitions, an absence of population norms for CNVs and a lack of consensus in methods for CNV detection and analysis. Here, we review current CNV association study methods and results in autism spectrum disorders (ASD) and schizophrenia, and provide suggestions for design approaches to future studies that might maximize the translation of this work to etiological understanding.

  19. [Relationship between mitochondrial DNA copy number, membrane potential of human embryo and embryo morphology].

    Science.gov (United States)

    Zhao, H; Teng, X M; Li, Y F

    2017-11-25

    Objective: To explore the relationship between the embryo with the different morphological types in the third day and its mitochondrial copy number, the membrane potential. Methods: Totally 117 embryos with poor development after normal fertilization and were not suitable transferred in the fresh cycle and 106 frozen embryos that were discarded voluntarily by infertility patients with in vitro fertilization-embryo transfer after successful pregnancy were selected. According to evaluation of international standard in embryos, all cleavage stage embryos were divided into class Ⅰ frozen embryo group ( n= 64), class Ⅱ frozen embryo group ( n= 42) and class Ⅲ fresh embryonic group (not transplanted embryos; n= 117). Real-time PCR and confocal microscopy methods were used to detect mitochondrial DNA (mtDNA) copy number and the mitochondrial membrane potential of a single embryo. The differences between embryo quality and mtDNA copy number and membrane potential of each group were compared. Results: The copy number of mtDNA and the mitochondrial membrane potential in class Ⅲ fresh embryonic group [(1.7±1.0)×10(5) copy/μl, 1.56±0.32] were significantly lower than those in class Ⅰ frozen embryo group [(3.4±1.7)×10(5) copy/μl, 2.66±0.21] and class Ⅱ frozen embryo group [(2.6±1.2)×10(5) copy/μl, 1.80±0.32; all Pembryo group were significantly higher than those in classⅡ frozen embryo group (both Pembryos of the better quality embryo are higher.

  20. Accurate measure of transgene copy number in crop plants using droplet digital PCR

    Science.gov (United States)

    Genetic transformation is a powerful means for the improvement of crop plants, but requires labor- and resource-intensive methods. An efficient method for identifying single-copy transgene insertion events from a population of independent transgenic lines is desirable. Currently, transgene copy numb...

  1. Investigation of Copy Number Variation in Children with Conotruncal Heart Defects

    International Nuclear Information System (INIS)

    Campos, Carla Marques Rondon; Zanardo, Evelin Aline; Dutra, Roberta Lelis; Kulikowski, Leslie Domenici; Kim, Chong Ae

    2015-01-01

    Congenital heart defects (CHD) are the most prevalent group of structural abnormalities at birth and one of the main causes of infant morbidity and mortality. Studies have shown a contribution of the copy number variation in the genesis of cardiac malformations. Investigate gene copy number variation (CNV) in children with conotruncal heart defect. Multiplex ligation-dependent probe amplification (MLPA) was performed in 39 patients with conotruncal heart defect. Clinical and laboratory assessments were conducted in all patients. The parents of the probands who presented abnormal findings were also investigated. Gene copy number variation was detected in 7/39 patients: 22q11.2 deletion, 22q11.2 duplication, 15q11.2 duplication, 20p12.2 duplication, 19p deletion, 15q and 8p23.2 duplication with 10p12.31 duplication. The clinical characteristics were consistent with those reported in the literature associated with the encountered microdeletion/microduplication. None of these changes was inherited from the parents. Our results demonstrate that the technique of MLPA is useful in the investigation of microdeletions and microduplications in conotruncal congenital heart defects. Early diagnosis of the copy number variation in patients with congenital heart defect assists in the prevention of morbidity and decreased mortality in these patients

  2. Investigation of Copy Number Variation in Children with Conotruncal Heart Defects

    Energy Technology Data Exchange (ETDEWEB)

    Campos, Carla Marques Rondon, E-mail: carlamcampos@uol.com.br [Universidade Federal de Mato Grosso, Cuiabá, MT (Brazil); Zanardo, Evelin Aline; Dutra, Roberta Lelis [Departamento de Patologia - Laboratório de Citogenômica - LIM 03 - Universidade de São Paulo, São Paulo, SP (Brazil); Kulikowski, Leslie Domenici [Universidade de São Paulo, São Paulo, SP (Brazil); Departamento de Patologia - Laboratório de Citogenômica - LIM 03 - Universidade de São Paulo, São Paulo, SP (Brazil); Kim, Chong Ae [Universidade de São Paulo, São Paulo, SP (Brazil)

    2015-01-15

    Congenital heart defects (CHD) are the most prevalent group of structural abnormalities at birth and one of the main causes of infant morbidity and mortality. Studies have shown a contribution of the copy number variation in the genesis of cardiac malformations. Investigate gene copy number variation (CNV) in children with conotruncal heart defect. Multiplex ligation-dependent probe amplification (MLPA) was performed in 39 patients with conotruncal heart defect. Clinical and laboratory assessments were conducted in all patients. The parents of the probands who presented abnormal findings were also investigated. Gene copy number variation was detected in 7/39 patients: 22q11.2 deletion, 22q11.2 duplication, 15q11.2 duplication, 20p12.2 duplication, 19p deletion, 15q and 8p23.2 duplication with 10p12.31 duplication. The clinical characteristics were consistent with those reported in the literature associated with the encountered microdeletion/microduplication. None of these changes was inherited from the parents. Our results demonstrate that the technique of MLPA is useful in the investigation of microdeletions and microduplications in conotruncal congenital heart defects. Early diagnosis of the copy number variation in patients with congenital heart defect assists in the prevention of morbidity and decreased mortality in these patients.

  3. Transcriptomic analyses of tributyltin-induced sexual dimorphisms in rare minnow (Gobiocypris rarus) brains.

    Science.gov (United States)

    Zhang, Ji-Liang; Liu, Min; Zhang, Chun-Nuan; Li, Er-Chao; Fan, Ming-Zhen; Huang, Mao-Xian

    2018-07-30

    The brain of fish displays sexual dimorphisms and exhibits remarkable sexual plasticity throughout their life span. Although reproductive toxicity of tributyltin (TBT) in fish is well documented in fish, it remains unknown whether TBT interrupts sexual dimorphisms of fish brains. In this work, brain transcriptomic profiles of rare minnow (Gobiocypris rarus) was characterized and sex-biased genes were identified using RNA sequencing. Functional annotation and enrichment analysis were performed to reveal differences of gene products and pathways between the brains of male and female fish. Furthermore, transcriptomic responses of male and female brains to TBT at 10 ng/L were also investigated to understand effects of TBT on brain sexual dimorphisms. Only 345 male-biased and 273 female-biased genes were found in the brains. However, significant female-biased pathways of circadian rhythm and phototransduction were identified in the brains by enrichment analysis. Interestingly, following TBT exposure in the female fish, the circadian rhythm pathway was significantly disrupted based on enrichment analysis, while in the male fish, the phototransduction pathway was significantly disrupted. In the female fish, expression of genes (Per, Cry, Rev-Erb α, Ror, Dec and CK1δ/ε) in the circadian rhythm pathway was down-regulated after TBT exposure; while in the male fish, expression of genes (Rec, GNAT1_2, GNGT1, Rh/opsin, PDE and Arr) in the phototransduction pathway was up-regulated after TBT exposure. Overall, our results not only provide key data on the molecular basis of brain sexual dimorphisms in fish, but also offer valuable resources for investigating molecular mechanisms by which environmental chemicals might influence brain sexual plasticity. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Copy-number analysis and inference of subclonal populations in cancer genomes using Sclust.

    Science.gov (United States)

    Cun, Yupeng; Yang, Tsun-Po; Achter, Viktor; Lang, Ulrich; Peifer, Martin

    2018-06-01

    The genomes of cancer cells constantly change during pathogenesis. This evolutionary process can lead to the emergence of drug-resistant mutations in subclonal populations, which can hinder therapeutic intervention in patients. Data derived from massively parallel sequencing can be used to infer these subclonal populations using tumor-specific point mutations. The accurate determination of copy-number changes and tumor impurity is necessary to reliably infer subclonal populations by mutational clustering. This protocol describes how to use Sclust, a copy-number analysis method with a recently developed mutational clustering approach. In a series of simulations and comparisons with alternative methods, we have previously shown that Sclust accurately determines copy-number states and subclonal populations. Performance tests show that the method is computationally efficient, with copy-number analysis and mutational clustering taking Linux/Unix command-line syntax should be able to carry out analyses of subclonal populations.

  5. Gauged Supergravities and Spontaneous Supersymmetry Breaking from the Double Copy Construction

    Science.gov (United States)

    Chiodaroli, M.; Günaydin, M.; Johansson, H.; Roiban, R.

    2018-04-01

    Supergravities with gauged R symmetry and Minkowski vacua allow for spontaneous supersymmetry breaking and, as such, provide a framework for building supergravity models of phenomenological relevance. In this Letter, we initiate the study of double copy constructions for these supergravities. We argue that, on general grounds, we expect their scattering amplitudes to be described by a double copy of the type (spontaneously broken gauge theory)⊗ (gauge theory with broken supersymmetry). We present a simple realization in which the resulting supergravity has U (1 )R gauge symmetry, spontaneously broken N =2 supersymmetry, and massive gravitini. This is the first instance of a double copy construction of a gauged supergravity and of a theory with spontaneously broken supersymmetry. The construction extends in a straightforward manner to a large family of gauged Yang-Mills-Einstein supergravity theories with or without spontaneous gauge-symmetry breaking.

  6. rRNA Operon Copy Number Can Explain the Distinct Epidemiology of Hospital-Associated Methicillin-Resistant Staphylococcus aureus

    Science.gov (United States)

    Jansen, M. D.; Bosch, T.; Jansen, W. T. M.; Schouls, L.; Jonker, M. J.; Boel, C. H. E.

    2016-01-01

    The distinct epidemiology of original hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) and early community-associated MRSA (CA-MRSA) is largely unexplained. S. aureus carries either five or six rRNA operon copies. Evidence is provided for a scenario in which MRSA has adapted to the hospital environment by rRNA operon loss (six to five copies) due to antibiotic pressure. Early CA-MRSA, in contrast, results from wild-type methicillin-susceptible S. aureus (MSSA) that acquired mecA without loss of an rRNA operon. Of the HA-MRSA isolates (n = 77), 67.5% had five rRNA operon copies, compared to 23.2% of the CA-MRSA isolates (n = 69) and 7.7% of MSSA isolates (n = 195) (P operon copies. For all subsets, a correlation between resistance profile and rRNA copy number was found. Furthermore, we showed that in vitro antibiotic pressure may result in rRNA operon copy loss. We also showed that without antibiotic pressure, S. aureus isolates containing six rRNA copies are more fit than isolates with five copies. We conclude that HA-MRSA and cystic fibrosis isolates most likely have adapted to an environment with high antibiotic pressure by the loss of an rRNA operon copy. This loss has facilitated resistance development, which promoted survival in these niches. However, strain fitness decreased, which explains their lack of success in the community. In contrast, CA-MRSA isolates retained six rRNA operon copies, rendering them fitter and thereby able to survive and spread in the community. PMID:27671073

  7. Beta-defensin genomic copy number is not a modifier locus for cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Burgess Juliana

    2005-12-01

    Full Text Available Abstract Human beta-defensin 2 (DEFB4, also known as DEFB2 or hBD-2 is a salt-sensitive antimicrobial protein that is expressed in lung epithelia. Previous work has shown that it is encoded in a cluster of beta-defensin genes at 8p23.1, which varies in copy number between 2 and 12 in different individuals. We determined the copy number of this locus in 355 patients with cystic fibrosis (CF, and tested for correlation between beta-defensin cluster genomic copy number and lung disease associated with CF. No significant association was found.

  8. 8q24 allelic imbalance and MYC gene copy number in primary prostate cancer.

    Science.gov (United States)

    Chen, H; Liu, W; Roberts, W; Hooker, S; Fedor, H; DeMarzo, A; Isaacs, W; Kittles, R A

    2010-09-01

    Four independent regions within 8q24 near the MYC gene are associated with risk for prostate cancer (Pca). Here, we investigated allelic imbalance (AI) at 8q24 risk variants and MYC gene DNA copy number (CN) in 27 primary Pcas. Heterozygotes were observed in 24 of 27 patients at one or more 8q24 markers and 27% of the loci exhibited AI in tumor DNA. The 8q24 risk alleles were preferentially favored in the tumors. Increased MYC gene CN was observed in 33% of tumors, and the co-existence of increased MYC gene CN with AI at risk loci was observed in 86% (P<0.004 exact binomial test) of the informative tumors. No AI was observed in tumors, which did not reveal increased MYC gene CN. Higher Gleason score was associated with tumors exhibiting AI (P=0.04) and also with increased MYC gene CN (P=0.02). Our results suggest that AI at 8q24 and increased MYC gene CN may both be related to high Gleason score in Pca. Our findings also suggest that these two somatic alterations may be due to the same preferential chromosomal duplication event during prostate tumorigenesis.

  9. Low AMY1 Gene Copy Number Is Associated with Increased Body Mass Index in Prepubertal Boys.

    Directory of Open Access Journals (Sweden)

    M Loredana Marcovecchio

    Full Text Available Genome-wide association studies have identified more than 60 single nucleotide polymorphisms associated with Body Mass Index (BMI. Additional genetic variants, such as copy number variations (CNV, have also been investigated in relation to BMI. Recently, the highly polymorphic CNV in the salivary amylase (AMY1 gene, encoding an enzyme implicated in the first step of starch digestion, has been associated with obesity in adults and children. We assessed the potential association between AMY1 copy number and a wide range of BMI in a population of Italian school-children.744 children (354 boys, 390 girls, mean age (±SD: 8.4±1.4years underwent anthropometric assessments (height, weight and collection of saliva samples for DNA extraction. AMY1 copies were evaluated by quantitative PCR.A significant increase of BMI z-score by decreasing AMY1 copy number was observed in boys (β: -0.117, p = 0.033, but not in girls. Similarly, waist circumference (β: -0.155, p = 0.003, adjusted for age was negatively influenced by AMY1 copy number in boys. Boys with 8 or more AMY1 copy numbers presented a significant lower BMI z-score (p = 0.04 and waist circumference (p = 0.01 when compared to boys with less than 8 copy numbers.In this pediatric-only, population-based study, a lower AMY1 copy number emerged to be associated with increased BMI in boys. These data confirm previous findings from adult studies and support a potential role of a higher copy number of the salivary AMY1 gene in protecting from excess weight gain.

  10. 27 CFR 478.95 - Certified copy of license.

    Science.gov (United States)

    2010-04-01

    ... for copies. The fee may be paid by (a) cash, or (b) money order or check made payable to the Bureau of Alcohol, Tobacco, Firearms, and Explosives. (Approved by the Office of Management and Budget under control...

  11. Multiple-copy state discrimination: Thinking globally, acting locally

    International Nuclear Information System (INIS)

    Higgins, B. L.; Pryde, G. J.; Wiseman, H. M.; Doherty, A. C.; Bartlett, S. D.

    2011-01-01

    We theoretically investigate schemes to discriminate between two nonorthogonal quantum states given multiple copies. We consider a number of state discrimination schemes as applied to nonorthogonal, mixed states of a qubit. In particular, we examine the difference that local and global optimization of local measurements makes to the probability of obtaining an erroneous result, in the regime of finite numbers of copies N, and in the asymptotic limit as N→∞. Five schemes are considered: optimal collective measurements over all copies, locally optimal local measurements in a fixed single-qubit measurement basis, globally optimal fixed local measurements, locally optimal adaptive local measurements, and globally optimal adaptive local measurements. Here an adaptive measurement is one in which the measurement basis can depend on prior measurement results. For each of these measurement schemes we determine the probability of error (for finite N) and the scaling of this error in the asymptotic limit. In the asymptotic limit, it is known analytically (and we verify numerically) that adaptive schemes have no advantage over the optimal fixed local scheme. Here we show moreover that, in this limit, the most naive scheme (locally optimal fixed local measurements) is as good as any noncollective scheme except for states with less than 2% mixture. For finite N, however, the most sophisticated local scheme (globally optimal adaptive local measurements) is better than any other noncollective scheme for any degree of mixture.

  12. Cognitive profile of patients with rotated drawing at copy or recall: a controlled group study.

    Science.gov (United States)

    Molteni, Federica; Traficante, Debora; Ferri, Francesca; Isella, Valeria

    2014-03-01

    When copying or recalling a figure from memory, some patient with dementia or focal brain lesions may rotate the drawing through ±90° or 180°. We have tried to clarify the nature of this phenomenon by investigating the cognitive profile of 22 patients who rotated the copy of the Rey-Osterrieth Complex Figure and 27 who rotated (only) the recall, and two control groups of cases with the same neuropsychiatric diagnoses, but no misorientation deficit. Brain MRI and FDG-PET images were also analysed. Predictor of rotation at the copy versus rotation at the recall was visuospatial impairment as measured by the copy of the Rey Figure; predictors of rotation at the copy versus no rotation were, again, visuospatial deficits, in addition to an abnormal performance at the task of selective attention. No specific profile of cognitive impairment distinguished patients with and without rotation at the recall. Disproportionate temporo-parieto-occipital atrophy or hypometabolism were evident in cases with misorientation of the copy, while predominant frontal abnormalities were found in cases of rotated recall. Based on these findings, rotated drawing at the copy is interpreted as a dorsal visual stream deficit, whose occurrence is more probable when attentional control is impaired. Rotation at recall seems to have a distinct, more anterior, neural substrate, but its dysexecutive nature has yet to be demonstrated. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Molecular initiating events of the intersex phenotype: Low-dose exposure to 17α-ethinylestradiol rapidly regulates molecular networks associated with gonad differentiation in the adult fathead minnow testis

    International Nuclear Information System (INIS)

    Feswick, April; Loughery, Jennifer R.; Isaacs, Meghan A.; Munkittrick, Kelly R.; Martyniuk, Christopher J.

    2016-01-01

    Highlights: • Male fathead minnow were exposed to 17alpha ethinylestradiol (EE2). • Both 11-ketotestosterone and testosterone production was decreased relative to controls. • A gene network associated with doublesex and mab-3 related transcription factor 1 were suppressed. • Genes involved in granulosa cell development were increased and sensitive to EE2 exposure. • Molecular initiating events that may be related to the intersex condition were identified. - Abstract: Intersex, or the presence of oocytes in the testes, has been documented in fish following exposure to wastewater effluent and estrogenic compounds. However, the molecular networks underlying the intersex condition are not completely known. To address this, we exposed male fathead minnows to a low, environmentally-relevant concentration of 17alpha-ethinylestradiol (EE2) (15 ng/L) and measured the transcriptome response in the testis after 96 h to identify early molecular initiating events that may proceed the intersex condition. The short-term exposure to EE2 did not affect gonadosomatic index and proportion of gametes within the testes. However, the production of 11-ketotestosterone and testosterone from the testis in vitro was decreased relative to controls. Expression profiling using a 8 × 60 K fathead minnow microarray identified 10 transcripts that were differentially expressed in the testes, the most dramatic change being that of coagulation factor XIII A chain (20-fold increase). Transcripts that included guanine nucleotide binding protein (Beta Polypeptide 2), peroxisome proliferator-activated receptor delta, and WNK lysine deficient protein kinase 1a, were down-regulated by EE2. Subnetwork enrichment analysis revealed that EE2 suppressed transcriptional networks associated with steroid metabolism, hormone biosynthesis, and sperm mobility. Most interesting was that gene networks associated with doublesex and mab-3 related transcription factor 1 (dmrt1) were suppressed in the adult

  14. Molecular initiating events of the intersex phenotype: Low-dose exposure to 17α-ethinylestradiol rapidly regulates molecular networks associated with gonad differentiation in the adult fathead minnow testis

    Energy Technology Data Exchange (ETDEWEB)

    Feswick, April; Loughery, Jennifer R.; Isaacs, Meghan A.; Munkittrick, Kelly R.; Martyniuk, Christopher J., E-mail: cmartyni@yahoo.ca

    2016-12-15

    Highlights: • Male fathead minnow were exposed to 17alpha ethinylestradiol (EE2). • Both 11-ketotestosterone and testosterone production was decreased relative to controls. • A gene network associated with doublesex and mab-3 related transcription factor 1 were suppressed. • Genes involved in granulosa cell development were increased and sensitive to EE2 exposure. • Molecular initiating events that may be related to the intersex condition were identified. - Abstract: Intersex, or the presence of oocytes in the testes, has been documented in fish following exposure to wastewater effluent and estrogenic compounds. However, the molecular networks underlying the intersex condition are not completely known. To address this, we exposed male fathead minnows to a low, environmentally-relevant concentration of 17alpha-ethinylestradiol (EE2) (15 ng/L) and measured the transcriptome response in the testis after 96 h to identify early molecular initiating events that may proceed the intersex condition. The short-term exposure to EE2 did not affect gonadosomatic index and proportion of gametes within the testes. However, the production of 11-ketotestosterone and testosterone from the testis in vitro was decreased relative to controls. Expression profiling using a 8 × 60 K fathead minnow microarray identified 10 transcripts that were differentially expressed in the testes, the most dramatic change being that of coagulation factor XIII A chain (20-fold increase). Transcripts that included guanine nucleotide binding protein (Beta Polypeptide 2), peroxisome proliferator-activated receptor delta, and WNK lysine deficient protein kinase 1a, were down-regulated by EE2. Subnetwork enrichment analysis revealed that EE2 suppressed transcriptional networks associated with steroid metabolism, hormone biosynthesis, and sperm mobility. Most interesting was that gene networks associated with doublesex and mab-3 related transcription factor 1 (dmrt1) were suppressed in the adult

  15. Accurate measurement of transgene copy number in crop plants using droplet digital PCR.

    Science.gov (United States)

    Collier, Ray; Dasgupta, Kasturi; Xing, Yan-Ping; Hernandez, Bryan Tarape; Shao, Min; Rohozinski, Dominica; Kovak, Emma; Lin, Jeanie; de Oliveira, Maria Luiza P; Stover, Ed; McCue, Kent F; Harmon, Frank G; Blechl, Ann; Thomson, James G; Thilmony, Roger

    2017-06-01

    Genetic transformation is a powerful means for the improvement of crop plants, but requires labor- and resource-intensive methods. An efficient method for identifying single-copy transgene insertion events from a population of independent transgenic lines is desirable. Currently, transgene copy number is estimated by either Southern blot hybridization analyses or quantitative polymerase chain reaction (qPCR) experiments. Southern hybridization is a convincing and reliable method, but it also is expensive, time-consuming and often requires a large amount of genomic DNA and radioactively labeled probes. Alternatively, qPCR requires less DNA and is potentially simpler to perform, but its results can lack the accuracy and precision needed to confidently distinguish between one- and two-copy events in transgenic plants with large genomes. To address this need, we developed a droplet digital PCR-based method for transgene copy number measurement in an array of crops: rice, citrus, potato, maize, tomato and wheat. The method utilizes specific primers to amplify target transgenes, and endogenous reference genes in a single duplexed reaction containing thousands of droplets. Endpoint amplicon production in the droplets is detected and quantified using sequence-specific fluorescently labeled probes. The results demonstrate that this approach can generate confident copy number measurements in independent transgenic lines in these crop species. This method and the compendium of probes and primers will be a useful resource for the plant research community, enabling the simple and accurate determination of transgene copy number in these six important crop species. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  16. Copy number variation analysis of matched ovarian primary tumors and peritoneal metastasis.

    Directory of Open Access Journals (Sweden)

    Joel A Malek

    Full Text Available Ovarian cancer is the most deadly gynecological cancer. The high rate of mortality is due to the large tumor burden with extensive metastatic lesion of the abdominal cavity. Despite initial chemosensitivity and improved surgical procedures, abdominal recurrence remains an issue and results in patients' poor prognosis. Transcriptomic and genetic studies have revealed significant genome pathologies in the primary tumors and yielded important information regarding carcinogenesis. There are, however, few studies on genetic alterations and their consequences in peritoneal metastatic tumors when compared to their matched ovarian primary tumors. We used high-density SNP arrays to investigate copy number variations in matched primary and metastatic ovarian cancer from 9 patients. Here we show that copy number variations acquired by ovarian tumors are significantly different between matched primary and metastatic tumors and these are likely due to different functional requirements. We show that these copy number variations clearly differentially affect specific pathways including the JAK/STAT and cytokine signaling pathways. While many have shown complex involvement of cytokines in the ovarian cancer environment we provide evidence that ovarian tumors have specific copy number variation differences in many of these genes.

  17. Investigation of Copy Number Variation in Children with Conotruncal Heart Defects

    Directory of Open Access Journals (Sweden)

    Carla Marques Rondon Campos

    2015-01-01

    Full Text Available Background: Congenital heart defects (CHD are the most prevalent group of structural abnormalities at birth and one of the main causes of infant morbidity and mortality. Studies have shown a contribution of the copy number variation in the genesis of cardiac malformations. Objectives: Investigate gene copy number variation (CNV in children with conotruncal heart defect. Methods: Multiplex ligation-dependent probe amplification (MLPA was performed in 39 patients with conotruncal heart defect. Clinical and laboratory assessments were conducted in all patients. The parents of the probands who presented abnormal findings were also investigated. Results: Gene copy number variation was detected in 7/39 patients: 22q11.2 deletion, 22q11.2 duplication, 15q11.2 duplication, 20p12.2 duplication, 19p deletion, 15q and 8p23.2 duplication with 10p12.31 duplication. The clinical characteristics were consistent with those reported in the literature associated with the encountered microdeletion/microduplication. None of these changes was inherited from the parents. Conclusions: Our results demonstrate that the technique of MLPA is useful in the investigation of microdeletions and microduplications in conotruncal congenital heart defects. Early diagnosis of the copy number variation in patients with congenital heart defect assists in the prevention of morbidity and decreased mortality in these patients.

  18. Reduction in the copy number and expression level of the recurrent human papillomavirus integration gene fragile histidine triad (FHIT predicts the transition of cervical lesions.

    Directory of Open Access Journals (Sweden)

    Liming Wang

    Full Text Available Cervical cancer is the second most common cancer and the third leading cause of cancer death in females worldwide, especially in developing countries. High risk human papillomavirus (HR-HPV infection causes cervical cancer and precancerous cervical intraepithelial neoplasia (CIN. Integration of the HR-HPV genome into the host chromatin is an important step in cervical carcinogenesis. The detection of integrated papillomavirus sequences-PCR (DIPS-PCR allowed us to explore HPV integration in the human genome and to determine the pattern of this integration. We performed DIPS-PCR for 4 cell lines including 3 cervical cancer cell lines and 40 tissue samples. Overall, 32 HR-HPV integration loci were detected in the clinical samples and the HeLa and SiHa cell lines. Among all the integration loci, we identified three recurrent integration loci: 3p14.2 (3 samples, 13q22.1 (2 samples and a SiHa cell line and 8q24 (1 sample and a HeLa cell line. To further explore the effect of HR-HPV integration in the 3p14.2 locus, we used fluorescence in situ hybridization (FISH to determine the copy number of the 3p14.2 locus and immunohistochemistry (IHC to determine the protein expression levels of the related FHIT gene in the clinical samples. Both the 3p14.2 locus copy number and FHIT protein expression levels showed significant decreases when CIN transitioned to cervical cancer. HPV copy number was also evaluated in these clinical samples, and the copy number of HPV increased significantly between CIN and cervical cancer samples. Finally, we employed receiver operating characteristic curve (ROC curve analysis to evaluate the potential of all these indexes in distinguishing CIN and cervical cancer, and the HPV copy number, FHIT copy number and FHIT protein expression levels have good diagnostic efficiencies.

  19. The cost of copy number in a selfish genetic element: the 2-μm plasmid of Saccharomyces cerevisiae.

    Science.gov (United States)

    Harrison, Ellie; Koufopanou, V; Burt, A; MacLean, R C

    2012-11-01

    Many autonomously replicating genetic elements exist as multiple copies within the cell. The copy number of these elements is often assumed to have important fitness consequences for both element and host, yet the forces shaping its evolution are not well understood. The 2 μm is a multicopy plasmid of Saccharomyces yeasts, encoding just four genes that are solely involved in plasmid replication. One simple model for the fitness relationship between yeasts and 2 μm is that plasmid copy number evolves as a trade-off between selection for increased vertical transmission, favouring high copy number, and selection for decreased virulence, favouring low copy number. To test this model, we experimentally manipulated the copy number of the plasmid and directly measured the fitness cost, in terms of growth rate reduction, associated with high plasmid copy number. We find that the fitness burden imposed by the 2 μm increases with plasmid copy number, such that each copy imposes a fitness burden of 0.17% (± 0.008%), greatly exceeding the cost expected for it to be stably maintained in yeast populations. Our results demonstrate the crucial importance of copy number in the evolution of yeast per 2 μm associations and pave the way for future studies examining how selection can shape the cost of multicopy elements. © 2012 The Authors. Journal of Evolutionary Biology © 2012 European Society For Evolutionary Biology.

  20. 1 CFR 3.3 - Reproduction and certification of copies of acts and documents.

    Science.gov (United States)

    2010-01-01

    ... 1 General Provisions 1 2010-01-01 2010-01-01 false Reproduction and certification of copies of... GENERAL SERVICES TO THE PUBLIC § 3.3 Reproduction and certification of copies of acts and documents. The... furnishing of reproductions of acts and documents and certificates of authentication for them. Section 1258...

  1. Sparse representation and Bayesian detection of genome copy number alterations from microarray data.

    Science.gov (United States)

    Pique-Regi, Roger; Monso-Varona, Jordi; Ortega, Antonio; Seeger, Robert C; Triche, Timothy J; Asgharzadeh, Shahab

    2008-02-01

    Genomic instability in cancer leads to abnormal genome copy number alterations (CNA) that are associated with the development and behavior of tumors. Advances in microarray technology have allowed for greater resolution in detection of DNA copy number changes (amplifications or deletions) across the genome. However, the increase in number of measured signals and accompanying noise from the array probes present a challenge in accurate and fast identification of breakpoints that define CNA. This article proposes a novel detection technique that exploits the use of piece wise constant (PWC) vectors to represent genome copy number and sparse Bayesian learning (SBL) to detect CNA breakpoints. First, a compact linear algebra representation for the genome copy number is developed from normalized probe intensities. Second, SBL is applied and optimized to infer locations where copy number changes occur. Third, a backward elimination (BE) procedure is used to rank the inferred breakpoints; and a cut-off point can be efficiently adjusted in this procedure to control for the false discovery rate (FDR). The performance of our algorithm is evaluated using simulated and real genome datasets and compared to other existing techniques. Our approach achieves the highest accuracy and lowest FDR while improving computational speed by several orders of magnitude. The proposed algorithm has been developed into a free standing software application (GADA, Genome Alteration Detection Algorithm). http://biron.usc.edu/~piquereg/GADA

  2. A Carbapenem-Resistant Pseudomonas aeruginosa Isolate Harboring Two Copies of blaIMP-34 Encoding a Metallo-β-Lactamase.

    Directory of Open Access Journals (Sweden)

    Tatsuya Tada

    Full Text Available A carbapenem-resistant strain of Pseudomonas aeruginosa, NCGM1984, was isolated in 2012 from a hospitalized patient in Japan. Immunochromatographic assay showed that the isolate was positive for IMP-type metallo-β-lactamase. Complete genome sequencing revealed that NCGM1984 harbored two copies of blaIMP-34, located at different sites on the chromosome. Each blaIMP-34 was present in the same structures of the class 1 integrons, tnpA(ISPa7-intI1-qacG-blaIMP-34-aac(6'-Ib-qacEdelta1-sul1-orf5-tniBdelta-tniA. The isolate belonged to multilocus sequence typing ST235, one of the international high-risk clones. IMP-34, with an amino acid substitution (Glu126Gly compared with IMP-1, hydrolyzed all β-lactamases tested except aztreonam, and its catalytic activities were similar to IMP-1. This is the first report of a clinical isolate of an IMP-34-producing P. aeruginosa harboring two copies of blaIMP-34 on its chromosome.

  3. Non-fluent speech following stroke is caused by impaired efference copy.

    Science.gov (United States)

    Feenaughty, Lynda; Basilakos, Alexandra; Bonilha, Leonardo; den Ouden, Dirk-Bart; Rorden, Chris; Stark, Brielle; Fridriksson, Julius

    2017-09-01

    Efference copy is a cognitive mechanism argued to be critical for initiating and monitoring speech: however, the extent to which breakdown of efference copy mechanisms impact speech production is unclear. This study examined the best mechanistic predictors of non-fluent speech among 88 stroke survivors. Objective speech fluency measures were subjected to a principal component analysis (PCA). The primary PCA factor was then entered into a multiple stepwise linear regression analysis as the dependent variable, with a set of independent mechanistic variables. Participants' ability to mimic audio-visual speech ("speech entrainment response") was the best independent predictor of non-fluent speech. We suggest that this "speech entrainment" factor reflects integrity of internal monitoring (i.e., efference copy) of speech production, which affects speech initiation and maintenance. Results support models of normal speech production and suggest that therapy focused on speech initiation and maintenance may improve speech fluency for individuals with chronic non-fluent aphasia post stroke.

  4. Two new statistics to detect answer copying

    NARCIS (Netherlands)

    Meijer, R.R.; Sotaridona, Leonardo

    2001-01-01

    Two new indices to detect answer copying on a multiple-choice test, S(1) and S(2) (subscripts), are proposed. The S(1) index is similar to the K-index (P. Holland, 1996) and the K-overscore(2), (K2) index (L. Sotaridona and R. Meijer, in press), but the distribution of the number of matching

  5. Two new indices to detect answer copying

    NARCIS (Netherlands)

    Sotaridona, Leonardo; Meijer, R.R.

    2003-01-01

    Two new indices to detect answer copying on a multiple-choice test—S1 and S2—were proposed. The S1 index is similar to the K index (Holland, 1996) and the K2 index (Sotaridona & Meijer, 2002) but the distribution of the number of matching incorrect answers of the source and the copier is modeled by

  6. Inferring mechanisms of copy number change from haplotype structures at the human DEFA1A3 locus

    OpenAIRE

    Black, Holly A; Khan, Fayeza F; Tyson, Jess; Armour, John AL

    2014-01-01

    Background The determination of structural haplotypes at copy number variable regions can indicate the mechanisms responsible for changes in copy number, as well as explain the relationship between gene copy number and expression. However, obtaining spatial information at regions displaying extensive copy number variation, such as the DEFA1A3 locus, is complex, because of the difficulty in the phasing and assembly of these regions. The DEFA1A3 locus is intriguing in that it falls within a reg...

  7. 75 FR 30106 - Terrorism Risk Insurance Program; Recordkeeping Requirements for Insurers Compensated Under the...

    Science.gov (United States)

    2010-05-28

    ... DEPARTMENT OF THE TREASURY Terrorism Risk Insurance Program; Recordkeeping Requirements for... Budget. The Terrorism Risk Insurance Program Office within the Department of the Treasury is soliciting... original and two copies) to: Terrorism Risk Insurance Program, Public Comment Record, Suite 2100...

  8. On quasi-conformal (in-) compatibility of satellite copies of the Mandelbrot set: I

    DEFF Research Database (Denmark)

    Lomonaco, Luna; Petersen, Carsten Lunde

    2017-01-01

    Douady and Hubbard (Ann Sci Ec Norm Suppl 4 18(2):287–343, 1985) introduced the notion of polynomial-like maps. They used it to identify homeomorphic copies M of the Mandelbrot set inside the Mandelbrot set M. These copies can be primitive (with a root cusp) or satellite (without a root cusp). Th...

  9. Transcriptional and physiological response of fathead minnows (Pimephales promelas) exposed to urban waters entering into wildlife protected areas

    International Nuclear Information System (INIS)

    Rodriguez-Jorquera, Ignacio A.; Kroll, Kevin J.; Toor, Gurpal S.; Denslow, Nancy D.

    2015-01-01

    The mission of protected areas is to conserve biodiversity and improve human welfare. To assess the effect of urban waters entering into protected areas, we performed 48-h whole-effluent exposures with fathead minnows, analyzing changes in steady state levels of mRNAs in the livers of exposed fish. Raw wastewater, treated city wastewater, and treated wastewater from a university were collected for exposures. All exposed fish showed altered mRNA levels of DNA damage-repair genes. Fish exposed to raw and treated wastewaters showed down-regulation of transcripts for key intermediates of cholesterol biosynthesis and elevated plasma cholesterol. The type of wastewater treatment influenced the response of gene transcription. Because of the relevance of some of the altered cellular pathways, we suggest that these effluents may cause deleterious effects on fish inside protected areas that receive these waters. Inclusion of research and mitigation efforts for this type of threat in protected areas management is advised. - Highlights: • Wastewater entering wildlife preserves alters gene expression in exposed fish. • DNA repair mechanisms and cholesterol metabolism were altered in fish. • Effects on cholesterol genes were in agreement with fish hypercholesterolemia. - Urban wastewaters released into protected areas altered gene transcription of key genes such as DNA repair and cholesterol biosynthesis and produced hypercholesterolemia in fish

  10. 75 FR 28848 - Culturally Significant Objects Imported for Exhibition Determinations: “The Original Copy...

    Science.gov (United States)

    2010-05-24

    ... DEPARTMENT OF STATE [Public Notice 7027] Culturally Significant Objects Imported for Exhibition Determinations: ``The Original Copy: Photography of Sculpture, 1839 to Today'' SUMMARY: Notice is hereby given of... included in the exhibition ``The Original Copy: Photography of Sculpture, 1839 to Today,'' imported from...

  11. Finding-specific display presets for computed radiography soft-copy reading.

    Science.gov (United States)

    Andriole, K P; Gould, R G; Webb, W R

    1999-05-01

    Much work has been done to optimize the display of cross-sectional modality imaging examinations for soft-copy reading (i.e., window/level tissue presets, and format presentations such as tile and stack modes, four-on-one, nine-on-one, etc). Less attention has been paid to the display of digital forms of the conventional projection x-ray. The purpose of this study is to assess the utility of providing presets for computed radiography (CR) soft-copy display, based not on the window/level settings, but on processing applied to the image optimized for visualization of specific findings, pathologies, etc (i.e., pneumothorax, tumor, tube location). It is felt that digital display of CR images based on finding-specific processing presets has the potential to: speed reading of digital projection x-ray examinations on soft copy; improve diagnostic efficacy; standardize display across examination type, clinical scenario, important key findings, and significant negatives; facilitate image comparison; and improve confidence in and acceptance of soft-copy reading. Clinical chest images are acquired using an Agfa-Gevaert (Mortsel, Belgium) ADC 70 CR scanner and Fuji (Stamford, CT) 9000 and AC2 CR scanners. Those demonstrating pertinent findings are transferred over the clinical picture archiving and communications system (PACS) network to a research image processing station (Agfa PS5000), where the optimal image-processing settings per finding, pathologic category, etc, are developed in conjunction with a thoracic radiologist, by manipulating the multiscale image contrast amplification (Agfa MUSICA) algorithm parameters. Soft-copy display of images processed with finding-specific settings are compared with the standard default image presentation for 50 cases of each category. Comparison is scored using a 5-point scale with the positive scale denoting the standard presentation is preferred over the finding-specific processing, the negative scale denoting the finding

  12. Identification of copy number variants defining genomic differences among major human groups.

    Directory of Open Access Journals (Sweden)

    Lluís Armengol

    Full Text Available BACKGROUND: Understanding the genetic contribution to phenotype variation of human groups is necessary to elucidate differences in disease predisposition and response to pharmaceutical treatments in different human populations. METHODOLOGY/PRINCIPAL FINDINGS: We have investigated the genome-wide profile of structural variation on pooled samples from the three populations studied in the HapMap project by comparative genome hybridization (CGH in different array platforms. We have identified and experimentally validated 33 genomic loci that show significant copy number differences from one population to the other. Interestingly, we found an enrichment of genes related to environment adaptation (immune response, lipid metabolism and extracellular space within these regions and the study of expression data revealed that more than half of the copy number variants (CNVs translate into gene-expression differences among populations, suggesting that they could have functional consequences. In addition, the identification of single nucleotide polymorphisms (SNPs that are in linkage disequilibrium with the copy number alleles allowed us to detect evidences of population differentiation and recent selection at the nucleotide variation level. CONCLUSIONS: Overall, our results provide a comprehensive view of relevant copy number changes that might play a role in phenotypic differences among major human populations, and generate a list of interesting candidates for future studies.

  13. Slatan Dudow, Bulles de savon (1934) et la Suisse, ou Le mouvement des copies

    OpenAIRE

    Cosandey, Roland

    2011-01-01

    Observations à partir des deux copies de Bulles de savon conservées à la Cinémathèque suisse (35mm sonore et 16mm muette) dans le Fonds CSEO/SABZ dont le directeur de l’époque, Hans Neumann fit l’acquisition auprès du cinéaste. A discussion based on the two copies of Dudow’s Soap Bubbles held at the Cinémathèque suisse (sound 35mm and silent 16mm) in the CSEO/SABZ collection, whose director at the time, Hans Neumann, acquired the copies from the filmmaker....

  14. Chronic effects assessment and plasma concentrations of the {beta}-blocker propranolol in fathead minnows (Pimephales promelas)

    Energy Technology Data Exchange (ETDEWEB)

    Giltrow, Emma [Institute for the Environment, Brunel University, Uxbridge, Middlesex UB8 3PH (United Kingdom); Eccles, Paul D. [Institute for the Environment, Brunel University, Uxbridge, Middlesex UB8 3PH (United Kingdom); Biosciences, School of Health Sciences and Social Care, Brunel University, Uxbridge, Middlesex UB8 3PH (United Kingdom); Winter, Matthew J.; McCormack, Paul J. [AstraZeneca Safety, Health and Environment, Brixham Environmental Laboratory, Freshwater Quarry, Brixham, Devon TQ5 8BA (United Kingdom); Rand-Weaver, Mariann [Biosciences, School of Health Sciences and Social Care, Brunel University, Uxbridge, Middlesex UB8 3PH (United Kingdom); Hutchinson, Thomas H. [Natural Environmental Research Council, Plymouth Marine Laboratory, Prospect Place, The Hoe, Plymouth PL1 3DH (United Kingdom); Sumpter, John P., E-mail: john.sumpter@brunel.ac.uk [Institute for the Environment, Brunel University, Uxbridge, Middlesex UB8 3PH (United Kingdom)

    2009-11-27

    The presence of many human pharmaceuticals in the aquatic environment is now a worldwide concern, yet little is known of the chronic effects that these bioactive substances may be having on aquatic organisms. Propranolol, a non-specific beta adrenoreceptor blocker ({beta}-blocker), is used to treat high blood pressure and heart disease in humans. Propranolol has been found in surface waters worldwide at concentrations ranging from 12 to 590 ng/L. To test the potential for ecologically relevant effects in fish in receiving waters, short-term (21 days) adult reproduction studies were conducted, in which fathead minnows were exposed to nominal concentrations of propranolol hydrochloride [CAS number 318-98-9] ranging from 0.001 to 10 mg/L (measured concentrations typically from 78 to 130%). Exposure of fish to 3.4 mg/L (measured) over 3 days caused 100% mortality or severe toxicity requiring euthanasia. The most sensitive endpoints from the studies were a decrease in hatchability (with regard to the number of days to hatch) and a concentration-related increase in female gonadal somatic index (GSI), giving LOEC{sup hatchability} and LOEC{sup female} {sup GSI} values of 0.1 mg/L. Concentration-related decreases in weights of male fish were also observed, with LOEC{sup m}ale wet weight value of 1.0 mg/L, and the LOEC{sup r}eproduction value was 1.0 mg/L. Collectively, these data do not suggest that propranolol was acting as a reproductive toxin. Plasma concentrations of propranolol in male fish exposed to nominal concentrations of 0.1 and 1.0 mg/L were 0.34 and 15.00 mg/L, respectively, which constitutes 436 and 1546% of measured water concentrations. These compare with predicted concentrations of 0.07 and 0.84 mg/L, and thus to a degree support the use of partition coefficient models for predicting concentrations in plasma in fish. In addition, propranolol plasma concentrations in fish exposed to water concentrations of 0.1 and 1.0 mg/L were greater than the human

  15. Chronic effects assessment and plasma concentrations of the β-blocker propranolol in fathead minnows (Pimephales promelas)

    International Nuclear Information System (INIS)

    Giltrow, Emma; Eccles, Paul D.; Winter, Matthew J.; McCormack, Paul J.; Rand-Weaver, Mariann; Hutchinson, Thomas H.; Sumpter, John P.

    2009-01-01

    The presence of many human pharmaceuticals in the aquatic environment is now a worldwide concern, yet little is known of the chronic effects that these bioactive substances may be having on aquatic organisms. Propranolol, a non-specific beta adrenoreceptor blocker (β-blocker), is used to treat high blood pressure and heart disease in humans. Propranolol has been found in surface waters worldwide at concentrations ranging from 12 to 590 ng/L. To test the potential for ecologically relevant effects in fish in receiving waters, short-term (21 days) adult reproduction studies were conducted, in which fathead minnows were exposed to nominal concentrations of propranolol hydrochloride [CAS number 318-98-9] ranging from 0.001 to 10 mg/L (measured concentrations typically from 78 to 130%). Exposure of fish to 3.4 mg/L (measured) over 3 days caused 100% mortality or severe toxicity requiring euthanasia. The most sensitive endpoints from the studies were a decrease in hatchability (with regard to the number of days to hatch) and a concentration-related increase in female gonadal somatic index (GSI), giving LOEC hatchability and LOEC female GSI values of 0.1 mg/L. Concentration-related decreases in weights of male fish were also observed, with LOEC m ale wet weight value of 1.0 mg/L, and the LOEC r eproduction value was 1.0 mg/L. Collectively, these data do not suggest that propranolol was acting as a reproductive toxin. Plasma concentrations of propranolol in male fish exposed to nominal concentrations of 0.1 and 1.0 mg/L were 0.34 and 15.00 mg/L, respectively, which constitutes 436 and 1546% of measured water concentrations. These compare with predicted concentrations of 0.07 and 0.84 mg/L, and thus to a degree support the use of partition coefficient models for predicting concentrations in plasma in fish. In addition, propranolol plasma concentrations in fish exposed to water concentrations of 0.1 and 1.0 mg/L were greater than the human therapeutic plasma concentration

  16. Deteksi Pemalsuan Citra dengan Teknik Copy-Move Menggunakan Metode Ordinal Measure dari Koefisien Discrete Cosine Transform

    Directory of Open Access Journals (Sweden)

    Zulfan

    2016-07-01

    Full Text Available This article discusses a new method for the detection of forgery images generated by copy-move technique. Copy-move technique is one of image forgery techniques which taking a particular object from its original image and add it on that image for the purpose of increasing the number of or changing the same object in the original image. This study aims to detect the forged image generated by the copy-move techniques and copy-move forged image that has been modified by the rotation operation and histogram equalization. Detection feature used is Ordinal Measure of Discrete Cosine Transform coefficient (OM-DCT. Detection starts with division of the image into a block size of BXB (B = 16x16, 32x32 and 64x64 and two-dimensional DCT was performed to each of blocks. The feature distance from the original to the fake image, was calculated by the Euclidian distance and each feature has a distance of less than or equal to the threshold value (T according to the observations will be marked as a forged part. The results show that there are blocks detected on the copy-move image, whether on the unmodified copy-move forge image or those which modified by the rotation operation and histogram equalization. The number of blocks that are found in the copy-move object varies according to the size of the detection block used.

  17. Research on copying system of dynamic multiplex holographic stereograms

    Science.gov (United States)

    Fu, Huaiping; Yang, Hong; Zheng, Tong

    2003-05-01

    The most important advantage of holographic stereograms over conventional hologram is that they can produce 3D images at any desired scale with movement, holographers in many countries involved in the studies towards it. We began our works in the early 80's and accomplished two research projects automatic system for making synthetic holograms and multiplex synthetic rainbow holograms, Based on these works, a large scale holographic stereogram of an animated goldfish was made by us for practical advertisement. In order to meet the needs of the market, a copying system for making multiplex holographic stereograms, and a special kind of silver halide holographic film developed by us recently. The characteristic of the copying system and the property of the special silver-halide emulsion are introduced in this paper.

  18. Copy Number Alterations and Methylation in Ewing's Sarcoma

    Science.gov (United States)

    Jahromi, Mona S.; Jones, Kevin B.; Schiffman, Joshua D.

    2011-01-01

    Ewing's sarcoma is the second most common bone malignancy affecting children and young adults. The prognosis is especially poor in metastatic or relapsed disease. The cell of origin remains elusive, but the EWS-FLI1 fusion oncoprotein is present in the majority of cases. The understanding of the molecular basis of Ewing's sarcoma continues to progress slowly. EWS-FLI1 affects gene expression, but other factors must also be at work such as mutations, gene copy number alterations, and promoter methylation. This paper explores in depth two molecular aspects of Ewing's sarcoma: copy number alterations (CNAs) and methylation. While CNAs consistently have been reported in Ewing's sarcoma, their clinical significance has been variable, most likely due to small sample size and tumor heterogeneity. Methylation is thought to be important in oncogenesis and balanced karyotype cancers such as Ewing's, yet it has received only minimal attention in prior studies. Future CNA and methylation studies will help to understand the molecular basis of this disease. PMID:21437220

  19. Copy Number Alterations and Methylation in Ewing's Sarcoma

    Directory of Open Access Journals (Sweden)

    Mona S. Jahromi

    2011-01-01

    Full Text Available Ewing's sarcoma is the second most common bone malignancy affecting children and young adults. The prognosis is especially poor in metastatic or relapsed disease. The cell of origin remains elusive, but the EWS-FLI1 fusion oncoprotein is present in the majority of cases. The understanding of the molecular basis of Ewing's sarcoma continues to progress slowly. EWS-FLI1 affects gene expression, but other factors must also be at work such as mutations, gene copy number alterations, and promoter methylation. This paper explores in depth two molecular aspects of Ewing's sarcoma: copy number alterations (CNAs and methylation. While CNAs consistently have been reported in Ewing's sarcoma, their clinical significance has been variable, most likely due to small sample size and tumor heterogeneity. Methylation is thought to be important in oncogenesis and balanced karyotype cancers such as Ewing's, yet it has received only minimal attention in prior studies. Future CNA and methylation studies will help to understand the molecular basis of this disease.

  20. Imitation, Inspiration, and Creation: Cognitive Process of Creative Drawing by Copying Others' Artworks

    Science.gov (United States)

    Okada, Takeshi; Ishibashi, Kentaro

    2017-01-01

    To investigate the cognitive processes underlying creative inspiration, we tested the extent to which viewing or copying prior examples impacted creative output in art. In Experiment 1, undergraduates made drawings under three conditions: (a) copying an artist's drawing, then producing an original drawing; (b) producing an original drawing without…

  1. Mefloquine resistance in Plasmodium falciparum and increased pfmdr1 gene copy number.

    Science.gov (United States)

    Price, Ric N; Uhlemann, Anne-Catrin; Brockman, Alan; McGready, Rose; Ashley, Elizabeth; Phaipun, Lucy; Patel, Rina; Laing, Kenneth; Looareesuwan, Sornchai; White, Nicholas J; Nosten, François; Krishna, Sanjeev

    The borders of Thailand harbour the world's most multidrug resistant Plasmodium falciparum parasites. In 1984 mefloquine was introduced as treatment for uncomplicated falciparum malaria, but substantial resistance developed within 6 years. A combination of artesunate with mefloquine now cures more than 95% of acute infections. For both treatment regimens, the underlying mechanisms of resistance are not known. The relation between polymorphisms in the P falciparum multidrug resistant gene 1 (pfmdr1) and the in-vitro and in-vivo responses to mefloquine were assessed in 618 samples from patients with falciparum malaria studied prospectively over 12 years. pfmdr1 copy number was assessed by a robust real-time PCR assay. Single nucleotide polymorphisms of pfmdr1, P falciparum chloroquine resistance transporter gene (pfcrt) and P falciparum Ca2+ ATPase gene (pfATP6) were assessed by PCR-restriction fragment length polymorphism. Increased copy number of pfmdr1 was the most important determinant of in-vitro and in-vivo resistance to mefloquine, and also to reduced artesunate sensitivity in vitro. In a Cox regression model with control for known confounders, increased pfmdr1 copy number was associated with an attributable hazard ratio (AHR) for treatment failure of 6.3 (95% CI 2.9-13.8, p<0.001) after mefloquine monotherapy and 5.4 (2.0-14.6, p=0.001) after artesunate-mefloquine therapy. Single nucleotide polymorphisms in pfmdr1 were associated with increased mefloquine susceptibility in vitro, but not in vivo. Amplification in pfmdr1 is the main cause of resistance to mefloquine in falciparum malaria. Multidrug resistant P falciparum malaria is common in southeast Asia, but difficult to identify and treat. Genes that encode parasite transport proteins maybe involved in export of drugs and so cause resistance. In this study we show that increase in copy number of pfmdr1, a gene encoding a parasite transport protein, is the best overall predictor of treatment failure with

  2. Integrating Tenascin-C protein expression and 1q25 copy number status in pediatric intracranial ependymoma prognostication: A new model for risk stratification.

    Science.gov (United States)

    Andreiuolo, Felipe; Le Teuff, Gwénaël; Bayar, Mohamed Amine; Kilday, John-Paul; Pietsch, Torsten; von Bueren, André O; Witt, Hendrik; Korshunov, Andrey; Modena, Piergiorgio; Pfister, Stefan M; Pagès, Mélanie; Castel, David; Giangaspero, Felice; Chimelli, Leila; Varlet, Pascale; Rutkowski, Stefan; Frappaz, Didier; Massimino, Maura; Grundy, Richard; Grill, Jacques

    2017-01-01

    Despite multimodal therapy, prognosis of pediatric intracranial ependymomas remains poor with a 5-year survival rate below 70% and frequent late deaths. This multicentric European study evaluated putative prognostic biomarkers. Tenascin-C (TNC) immunohistochemical expression and copy number status of 1q25 were retained for a pooled analysis of 5 independent cohorts. The prognostic value of TNC and 1q25 on the overall survival (OS) was assessed using a Cox model adjusted to age at diagnosis, tumor location, WHO grade, extent of resection, radiotherapy and stratified by cohort. Stratification on a predictor that did not satisfy the proportional hazards assumption was considered. Model performance was evaluated and an internal-external cross validation was performed. Among complete cases with 5-year median follow-up (n = 470; 131 deaths), TNC and 1q25 gain were significantly associated with age at diagnosis and posterior fossa tumor location. 1q25 status added independent prognostic value for death beyond the classical variables with a hazard ratio (HR) = 2.19 95%CI = [1.29; 3.76] (p = 0.004), while TNC prognostic relation was tumor location-dependent with HR = 2.19 95%CI = [1.29; 3.76] (p = 0.004) in posterior fossa and HR = 0.64 [0.28; 1.48] (p = 0.295) in supratentorial (interaction p value = 0.015). The derived prognostic score identified 3 different robust risk groups. The omission of upfront RT was not associated with OS for good and intermediate prognostic groups while the absence of upfront RT was negatively associated with OS in the poor risk group. Integrated TNC expression and 1q25 status are useful to better stratify patients and to eventually adapt treatment regimens in pediatric intracranial ependymoma.

  3. Integrating Tenascin-C protein expression and 1q25 copy number status in pediatric intracranial ependymoma prognostication: A new model for risk stratification.

    Directory of Open Access Journals (Sweden)

    Felipe Andreiuolo

    Full Text Available Despite multimodal therapy, prognosis of pediatric intracranial ependymomas remains poor with a 5-year survival rate below 70% and frequent late deaths.This multicentric European study evaluated putative prognostic biomarkers. Tenascin-C (TNC immunohistochemical expression and copy number status of 1q25 were retained for a pooled analysis of 5 independent cohorts. The prognostic value of TNC and 1q25 on the overall survival (OS was assessed using a Cox model adjusted to age at diagnosis, tumor location, WHO grade, extent of resection, radiotherapy and stratified by cohort. Stratification on a predictor that did not satisfy the proportional hazards assumption was considered. Model performance was evaluated and an internal-external cross validation was performed.Among complete cases with 5-year median follow-up (n = 470; 131 deaths, TNC and 1q25 gain were significantly associated with age at diagnosis and posterior fossa tumor location. 1q25 status added independent prognostic value for death beyond the classical variables with a hazard ratio (HR = 2.19 95%CI = [1.29; 3.76] (p = 0.004, while TNC prognostic relation was tumor location-dependent with HR = 2.19 95%CI = [1.29; 3.76] (p = 0.004 in posterior fossa and HR = 0.64 [0.28; 1.48] (p = 0.295 in supratentorial (interaction p value = 0.015. The derived prognostic score identified 3 different robust risk groups. The omission of upfront RT was not associated with OS for good and intermediate prognostic groups while the absence of upfront RT was negatively associated with OS in the poor risk group.Integrated TNC expression and 1q25 status are useful to better stratify patients and to eventually adapt treatment regimens in pediatric intracranial ependymoma.

  4. Assessment of copy number variations in 120 patients with Poland syndrome.

    Science.gov (United States)

    Vaccari, Carlotta Maria; Tassano, Elisa; Torre, Michele; Gimelli, Stefania; Divizia, Maria Teresa; Romanini, Maria Victoria; Bossi, Simone; Musante, Ilaria; Valle, Maura; Senes, Filippo; Catena, Nunzio; Bedeschi, Maria Francesca; Baban, Anwar; Calevo, Maria Grazia; Acquaviva, Massimo; Lerone, Margherita; Ravazzolo, Roberto; Puliti, Aldamaria

    2016-11-25

    Poland Syndrome (PS) is a rare congenital disorder presenting with agenesis/hypoplasia of the pectoralis major muscle variably associated with thoracic and/or upper limb anomalies. Most cases are sporadic, but familial recurrence, with different inheritance patterns, has been observed. The genetic etiology of PS remains unknown. Karyotyping and array-comparative genomic hybridization (CGH) analyses can identify genomic imbalances that can clarify the genetic etiology of congenital and neurodevelopmental disorders. We previously reported a chromosome 11 deletion in twin girls with pectoralis muscle hypoplasia and skeletal anomalies, and a chromosome six deletion in a patient presenting a complex phenotype that included pectoralis muscle hypoplasia. However, the contribution of genomic imbalances to PS remains largely unknown. To investigate the prevalence of chromosomal imbalances in PS, standard cytogenetic and array-CGH analyses were performed in 120 PS patients. Following the application of stringent filter criteria, 14 rare copy number variations (CNVs) were identified in 14 PS patients in different regions outside known common copy number variations: seven genomic duplications and seven genomic deletions, enclosing the two previously reported PS associated chromosomal deletions. These CNVs ranged from 0.04 to 4.71 Mb in size. Bioinformatic analysis of array-CGH data indicated gene enrichment in pathways involved in cell-cell adhesion, DNA binding and apoptosis processes. The analysis also provided a number of candidate genes possibly causing the developmental defects observed in PS patients, among others REV3L, a gene coding for an error-prone DNA polymerase previously associated with Möbius Syndrome with variable phenotypes including pectoralis muscle agenesis. A number of rare CNVs were identified in PS patients, and these involve genes that represent candidates for further evaluation. Rare inherited CNVs may contribute to, or represent risk factors of PS

  5. Erlotinib and the Risk of Oral Cancer

    Science.gov (United States)

    William, William N.; Papadimitrakopoulou, Vassiliki; Lee, J. Jack; Mao, Li; Cohen, Ezra E.W.; Lin, Heather Y.; Gillenwater, Ann M.; Martin, Jack W.; Lingen, Mark W.; Boyle, Jay O.; Shin, Dong M.; Vigneswaran, Nadarajah; Shinn, Nancy; Heymach, John V.; Wistuba, Ignacio I.; Tang, Ximing; Kim, Edward S.; Saintigny, Pierre; Blair, Elizabeth A.; Meiller, Timothy; Gutkind, J. Silvio; Myers, Jeffrey; El-Naggar, Adel; Lippman, Scott M.

    2016-01-01

    IMPORTANCE Standard molecularly based strategies to predict and/or prevent oral cancer development in patients with oral premalignant lesions (OPLs) are lacking. OBJECTIVE To test if the epidermal growth factor receptor inhibitor erlotinib would reduce oral cancer development in patients with high-risk OPLs defined by specific loss of heterozygosity (LOH) profiles. Secondary objectives included prospective determination of LOH as a prognostic marker in OPLs. DESIGN The Erlotinib Prevention of Oral Cancer (EPOC) study was a randomized, placebo-controlled, double-bind trial. Accrual occurred from November 2006 through July 2012, with a median follow-up time of 35 months in an ambulatory care setting in 5 US academic referral institutions. Patients with OPLs were enrolled in the protocol, and each underwent LOH profiling (N = 379); they were classified as high-risk (LOH-positive) or low-risk (LOH-negative) patients based on their LOH profiles and oral cancer history. The randomized sample consisted of 150 LOH-positive patients. INTERVENTIONS Oral erlotinib treatment (150mg/d) or placebo for 12 months. MAIN OUTCOMES AND MEASURES Oral cancer–free survival (CFS). RESULTS A total of 395 participants were classified with LOH profiles, and 254 were classified LOH positive. Of these, 150 (59%) were randomized, 75 each to the placebo and erlotinib groups. The 3-year CFS rates in placebo- and erlotinib-treated patients were 74%and 70%, respectively (hazard ratio [HR], 1.27; 95%CI, 0.68–2.38; P = .45). The 3-year CFS was significantly lower for LOH-positive compared with LOH-negative groups (74%vs 87%, HR, 2.19; 95%CI, 1.25–3.83; P = .01). Increased EGFR gene copy number correlated with LOH-positive status (P < .001) and lower CFS (P = .01). The EGFR gene copy number was not predictive of erlotinib efficacy. Erlotinib-induced skin rash was associated with improved CFS (P = .01). CONCLUSIONS AND RELEVANCE In this trial, LOH was validated as a marker of oral cancer risk and

  6. Engineered promoters enable constant gene expression at any copy number in bacteria.

    Science.gov (United States)

    Segall-Shapiro, Thomas H; Sontag, Eduardo D; Voigt, Christopher A

    2018-04-01

    The internal environment of growing cells is variable and dynamic, making it difficult to introduce reliable parts, such as promoters, for genetic engineering. Here, we applied control-theoretic ideas to design promoters that maintained constant levels of expression at any copy number. Theory predicts that independence to copy number can be achieved by using an incoherent feedforward loop (iFFL) if the negative regulation is perfectly non-cooperative. We engineered iFFLs into Escherichia coli promoters using transcription-activator-like effectors (TALEs). These promoters had near-identical expression in different genome locations and plasmids, even when their copy number was perturbed by genomic mutations or changes in growth medium composition. We applied the stabilized promoters to show that a three-gene metabolic pathway to produce deoxychromoviridans could retain function without re-tuning when the stabilized-promoter-driven genes were moved from a plasmid into the genome.

  7. Modulation of Mitochondrial DNA Copy Number to Induce Hepatocytic Differentiation of Human Amniotic Epithelial Cells.

    Science.gov (United States)

    Vaghjiani, Vijesh; Cain, Jason E; Lee, William; Vaithilingam, Vijayaganapathy; Tuch, Bernard E; St John, Justin C

    2017-10-15

    Mitochondrial deoxyribonucleic acid (mtDNA) copy number is tightly regulated during pluripotency and differentiation. There is increased demand of cellular adenosine triphosphate (ATP) during differentiation for energy-intensive cell types such as hepatocytes and neurons to meet the cell's functional requirements. During hepatocyte differentiation, mtDNA copy number should be synchronously increased to generate sufficient ATP through oxidative phosphorylation. Unlike bone marrow mesenchymal cells, mtDNA copy number failed to increase by 28 days of differentiation of human amniotic epithelial cells (hAEC) into hepatocyte-like cells (HLC) despite their expression of some end-stage hepatic markers. This was due to higher levels of DNA methylation at exon 2 of POLGA, the mtDNA-specific replication factor. Treatment with a DNA demethylation agent, 5-azacytidine, resulted in increased mtDNA copy number, reduced DNA methylation at exon 2 of POLGA, and reduced hepatic gene expression. Depletion of mtDNA followed by subsequent differentiation did not increase mtDNA copy number, but reduced DNA methylation at exon 2 of POLGA and increased expression of hepatic and pluripotency genes. We encapsulated hAEC in barium alginate microcapsules and subsequently differentiated them into HLC. Encapsulation resulted in no net increase of mtDNA copy number but a significant reduction in DNA methylation of POLGA. RNAseq analysis showed that differentiated HLC express hepatocyte-specific genes but also increased expression of inflammatory interferon genes. Differentiation in encapsulated cells showed suppression of inflammatory genes as well as increased expression of genes associated with hepatocyte function pathways and networks. This study demonstrates that an increase in classical hepatic gene expression can be achieved in HLC through encapsulation, although they fail to effectively regulate mtDNA copy number.

  8. A sparse regulatory network of copy-number driven gene expression reveals putative breast cancer oncogenes.

    Science.gov (United States)

    Yuan, Yinyin; Curtis, Christina; Caldas, Carlos; Markowetz, Florian

    2012-01-01

    Copy number aberrations are recognized to be important in cancer as they may localize to regions harboring oncogenes or tumor suppressors. Such genomic alterations mediate phenotypic changes through their impact on expression. Both cis- and transacting alterations are important since they may help to elucidate putative cancer genes. However, amidst numerous passenger genes, trans-effects are less well studied due to the computational difficulty in detecting weak and sparse signals in the data, and yet may influence multiple genes on a global scale. We propose an integrative approach to learn a sparse interaction network of DNA copy-number regions with their downstream transcriptional targets in breast cancer. With respect to goodness of fit on both simulated and real data, the performance of sparse network inference is no worse than other state-of-the-art models but with the advantage of simultaneous feature selection and efficiency. The DNA-RNA interaction network helps to distinguish copy-number driven expression alterations from those that are copy-number independent. Further, our approach yields a quantitative copy-number dependency score, which distinguishes cis- versus trans-effects. When applied to a breast cancer data set, numerous expression profiles were impacted by cis-acting copy-number alterations, including several known oncogenes such as GRB7, ERBB2, and LSM1. Several trans-acting alterations were also identified, impacting genes such as ADAM2 and BAGE, which warrant further investigation. An R package named lol is available from www.markowetzlab.org/software/lol.html.

  9. Copy number determination of genetically-modified hematopoietic stem cells.

    Science.gov (United States)

    Schuesler, Todd; Reeves, Lilith; Kalle, Christof von; Grassman, Elke

    2009-01-01

    Human gene transfer with gammaretroviral, murine leukemia virus (MLV) based vectors has been shown to effectively insert and express transgene sequences at a level of therapeutic benefit. However, there are numerous reports of disruption of the normal cellular processes caused by the viral insertion, even of replication deficient gammaretroviral vectors. Current gammaretroviral and lentiviral vectors do not control the site of insertion into the genome, hence, the possibility of disruption of the target cell genome. Risk related to viral insertions is linked to the number of insertions of the transgene into the cellular DNA, as has been demonstrated for replication competent and replication deficient retroviruses in experiments. At high number of insertions per cell, cell transformation due to vector induced activation of proto-oncogenes is more likely to occur, in particular since more than one transforming event is needed for oncogenesis. Thus, determination of the vector copy number in bulk transduced populations, individual colony forming units, and tissue from the recipient of the transduced cells is an increasingly important safety assay and has become a standard, though not straightforward assay, since the inception of quantitative PCR.

  10. Population-genetic nature of copy number variations in the human genome.

    Science.gov (United States)

    Kato, Mamoru; Kawaguchi, Takahisa; Ishikawa, Shumpei; Umeda, Takayoshi; Nakamichi, Reiichiro; Shapero, Michael H; Jones, Keith W; Nakamura, Yusuke; Aburatani, Hiroyuki; Tsunoda, Tatsuhiko

    2010-03-01

    Copy number variations (CNVs) are universal genetic variations, and their association with disease has been increasingly recognized. We designed high-density microarrays for CNVs, and detected 3000-4000 CNVs (4-6% of the genomic sequence) per population that included CNVs previously missed because of smaller sizes and residing in segmental duplications. The patterns of CNVs across individuals were surprisingly simple at the kilo-base scale, suggesting the applicability of a simple genetic analysis for these genetic loci. We utilized the probabilistic theory to determine integer copy numbers of CNVs and employed a recently developed phasing tool to estimate the population frequencies of integer copy number alleles and CNV-SNP haplotypes. The results showed a tendency toward a lower frequency of CNV alleles and that most of our CNVs were explained only by zero-, one- and two-copy alleles. Using the estimated population frequencies, we found several CNV regions with exceptionally high population differentiation. Investigation of CNV-SNP linkage disequilibrium (LD) for 500-900 bi- and multi-allelic CNVs per population revealed that previous conflicting reports on bi-allelic LD were unexpectedly consistent and explained by an LD increase correlated with deletion-allele frequencies. Typically, the bi-allelic LD was lower than SNP-SNP LD, whereas the multi-allelic LD was somewhat stronger than the bi-allelic LD. After further investigation of tag SNPs for CNVs, we conclude that the customary tagging strategy for disease association studies can be applicable for common deletion CNVs, but direct interrogation is needed for other types of CNVs.

  11. Students Write, Then "Sell" Ad Copy to Class.

    Science.gov (United States)

    Galician, Mary Lou

    1986-01-01

    Describes a course in commercial copywriting for electronic media in which students must also present orally their copy to the class to drive home two points: (1) the writing has to sell products, and (2) the writer has to sell the spot or campaign to the client or employers. (HTH)

  12. Selection of Suitable Endogenous Reference Genes for Relative Copy Number Detection in Sugarcane

    Directory of Open Access Journals (Sweden)

    Bantong Xue

    2014-05-01

    Full Text Available Transgene copy number has a great impact on the expression level and stability of exogenous gene in transgenic plants. Proper selection of endogenous reference genes is necessary for detection of genetic components in genetically modification (GM crops by quantitative real-time PCR (qPCR or by qualitative PCR approach, especially in sugarcane with polyploid and aneuploid genomic structure. qPCR technique has been widely accepted as an accurate, time-saving method on determination of copy numbers in transgenic plants and on detection of genetically modified plants to meet the regulatory and legislative requirement. In this study, to find a suitable endogenous reference gene and its real-time PCR assay for sugarcane (Saccharum spp. hybrids DNA content quantification, we evaluated a set of potential “single copy” genes including P4H, APRT, ENOL, CYC, TST and PRR, through qualitative PCR and absolute quantitative PCR. Based on copy number comparisons among different sugarcane genotypes, including five S. officinarum, one S. spontaneum and two S. spp. hybrids, these endogenous genes fell into three groups: ENOL-3—high copy number group, TST-1 and PRR-1—medium copy number group, P4H-1, APRT-2 and CYC-2—low copy number group. Among these tested genes, P4H, APRT and CYC were the most stable, while ENOL and TST were the least stable across different sugarcane genotypes. Therefore, three primer pairs of P4H-3, APRT-2 and CYC-2 were then selected as the suitable reference gene primer pairs for sugarcane. The test of multi-target reference genes revealed that the APRT gene was a specific amplicon, suggesting this gene is the most suitable to be used as an endogenous reference target for sugarcane DNA content quantification. These results should be helpful for establishing accurate and reliable qualitative and quantitative PCR analysis of GM sugarcane.

  13. Unselective Overimitators: The Evolutionary Implications of Children's Indiscriminate Copying of Successful and Prestigious Models

    Science.gov (United States)

    Chudek, Maciej; Baron, Andrew S.; Birch, Susan

    2016-01-01

    Children are both shrewd about whom to copy--they selectively learn from certain adults--and overimitators--they copy adults' obviously superfluous actions. Is overimitation also selective? Does selectivity change with age? In two experiments, 161 two- to seven-year-old children saw videos of one adult receiving better payoffs or more bystander…

  14. [Risk factors of schizophrenia].

    Science.gov (United States)

    Suvisaari, Jaana

    2010-01-01

    Schizophrenia is a multifactorial, neurodevelopmental disorder caused by a combination of genetic and environmental risk factors. Disturbances of brain development begin prenatally, while different environmental insults further affect postnatal brain maturation during childhood and adolescence. Genome-wide association studies (GWAS) have succeeded in identifying hundreds of new risk variants for common, multifactorial diseases. In schizophrenia research, GWAS have found several rare copy number variants that considerably increase the risk of schizophrenia, and have shown an association between schizophrenia and the major histocompatibility complex. Research on environmental risk factors in recent years has provided new information particularly on risk factors related to pregnancy and childhood rearing environment. Gene-environment interactions have become a central research topic. There is evidence that genetically susceptible children are more vulnerable to the effects of unstable childhood rearing environment and other environmental risk factors.

  15. Relation between catalyst-assisted transformation and multiple-copy transformation for bipartite pure states

    International Nuclear Information System (INIS)

    Feng Yuan; Duan Runyao; Ying Mingsheng

    2006-01-01

    We show that in some cases, catalyst-assisted entanglement transformation cannot be implemented by multiple-copy transformation for pure states. This fact, together with the result we obtained in R. Y. Duan, Y. Feng, X. Li, and M. S. Ying, Phys. Rev. A 71, 042319 (2005), namely that the latter can be completely implemented by the former, indicates that catalyst-assisted transformation is strictly more powerful than multiple-copy transformation. For the purely probabilistic setting we find, however, these two kinds of transformations are geometrically equivalent in the sense that the sets of pure states that can be converted into a given pure state with maximal probabilities not less than a given value have the same closure, regardless of whether catalyst-assisted transformation or multiple-copy transformation is used

  16. Pfmdr1 copy number and arteminisin derivatives combination therapy failure in falciparum malaria in Cambodia

    Directory of Open Access Journals (Sweden)

    Wongsrichanalai Chansuda

    2009-01-01

    Full Text Available Abstract Background The combination of artesunate and mefloquine was introduced as the national first-line treatment for Plasmodium falciparum malaria in Cambodia in 2000. However, recent clinical trials performed at the Thai-Cambodian border have pointed to the declining efficacy of both artesunate-mefloquine and artemether-lumefantrine. Since pfmdr1 modulates susceptibility to mefloquine and artemisinin derivatives, the aim of this study was to assess the link between pfmdr1 copy number, in vitro susceptibility to individual drugs and treatment failure to combination therapy. Methods Blood samples were collected from P. falciparum-infected patients enrolled in two in vivo efficacy studies in north-western Cambodia: 135 patients were treated with artemether-lumefantrine (AL group in Sampovloun in 2002 and 2003, and 140 patients with artesunate-mefloquine (AM group in Sampovloun and Veal Veng in 2003 and 2004. At enrollment, the in vitro IC50 was tested and the strains were genotyped for pfmdr1 copy number by real-time PCR. Results The pfmdr1 copy number was analysed for 115 isolates in the AM group, and for 109 isolates in the AL group. Parasites with increased pfmdr1 copy number had significantly reduced in vitro susceptibility to mefloquine, lumefantrine and artesunate. There was no association between pfmdr1 polymorphisms and in vitro susceptibilities. In the patients treated with AM, the mean pfmdr1copy number was lower in subjects with adequate clinical and parasitological response compared to those who experienced late treatment failure (n = 112, p p = 0.364. The presence of three or more copies of pfmdr1 were associated with recrudescence in artesunate-mefloquine treated patients (hazard ratio (HR = 7.80 [95%CI: 2.09–29.10], N = 115, p = 0.002 but not with recrudescence in artemether-lumefantrine treated patients (HR = 1.03 [95%CI: 0.24–4.44], N = 109, p = 0.969. Conclusion This study shows that pfmdr1 copy number is a molecular

  17. Classical gluon and graviton radiation from the bi-adjoint scalar double copy

    Science.gov (United States)

    Goldberger, Walter D.; Prabhu, Siddharth G.; Thompson, Jedidiah O.

    2017-09-01

    We find double-copy relations between classical radiating solutions in Yang-Mills theory coupled to dynamical color charges and their counterparts in a cubic bi-adjoint scalar field theory which interacts linearly with particles carrying bi-adjoint charge. The particular color-to-kinematics replacements we employ are motivated by the Bern-Carrasco-Johansson double-copy correspondence for on-shell amplitudes in gauge and gravity theories. They are identical to those recently used to establish relations between classical radiating solutions in gauge theory and in dilaton gravity. Our explicit bi-adjoint solutions are constructed to second order in a perturbative expansion, and map under the double copy onto gauge theory solutions which involve at most cubic gluon self-interactions. If the correspondence is found to persist to higher orders in perturbation theory, our results suggest the possibility of calculating gravitational radiation from colliding compact objects, directly from a scalar field with vastly simpler (purely cubic) Feynman vertices.

  18. rDNA Copy Number Variants Are Frequent Passenger Mutations in Saccharomyces cerevisiae Deletion Collections and de Novo Transformants

    Directory of Open Access Journals (Sweden)

    Elizabeth X. Kwan

    2016-09-01

    Full Text Available The Saccharomyces cerevisiae ribosomal DNA (rDNA locus is known to exhibit greater instability relative to the rest of the genome. However, wild-type cells preferentially maintain a stable number of rDNA copies, suggesting underlying genetic control of the size of this locus. We performed a screen of a subset of the Yeast Knock-Out (YKO single gene deletion collection to identify genetic regulators of this locus and to determine if rDNA copy number correlates with yeast replicative lifespan. While we found no correlation between replicative lifespan and rDNA size, we identified 64 candidate strains with significant rDNA copy number differences. However, in the process of validating candidate rDNA variants, we observed that independent isolates of our de novo gene deletion strains had unsolicited but significant changes in rDNA copy number. Moreover, we were not able to recapitulate rDNA phenotypes from the YKO yeast deletion collection. Instead, we found that the standard lithium acetate transformation protocol is a significant source of rDNA copy number variation, with lithium acetate exposure being the treatment causing variable rDNA copy number events after transformation. As the effects of variable rDNA copy number are being increasingly reported, our finding that rDNA is affected by lithium acetate exposure suggested that rDNA copy number variants may be influential passenger mutations in standard strain construction in S. cerevisiae.

  19. rDNA Copy Number Variants Are Frequent Passenger Mutations in Saccharomyces cerevisiae Deletion Collections and de Novo Transformants.

    Science.gov (United States)

    Kwan, Elizabeth X; Wang, Xiaobin S; Amemiya, Haley M; Brewer, Bonita J; Raghuraman, M K

    2016-09-08

    The Saccharomyces cerevisiae ribosomal DNA (rDNA) locus is known to exhibit greater instability relative to the rest of the genome. However, wild-type cells preferentially maintain a stable number of rDNA copies, suggesting underlying genetic control of the size of this locus. We performed a screen of a subset of the Yeast Knock-Out (YKO) single gene deletion collection to identify genetic regulators of this locus and to determine if rDNA copy number correlates with yeast replicative lifespan. While we found no correlation between replicative lifespan and rDNA size, we identified 64 candidate strains with significant rDNA copy number differences. However, in the process of validating candidate rDNA variants, we observed that independent isolates of our de novo gene deletion strains had unsolicited but significant changes in rDNA copy number. Moreover, we were not able to recapitulate rDNA phenotypes from the YKO yeast deletion collection. Instead, we found that the standard lithium acetate transformation protocol is a significant source of rDNA copy number variation, with lithium acetate exposure being the treatment causing variable rDNA copy number events after transformation. As the effects of variable rDNA copy number are being increasingly reported, our finding that rDNA is affected by lithium acetate exposure suggested that rDNA copy number variants may be influential passenger mutations in standard strain construction in S. cerevisiae. Copyright © 2016 Kwan et al.

  20. Inferring mechanisms of copy number change from haplotype structures at the human DEFA1A3 locus.

    Science.gov (United States)

    Black, Holly A; Khan, Fayeza F; Tyson, Jess; Al Armour, John

    2014-07-21

    The determination of structural haplotypes at copy number variable regions can indicate the mechanisms responsible for changes in copy number, as well as explain the relationship between gene copy number and expression. However, obtaining spatial information at regions displaying extensive copy number variation, such as the DEFA1A3 locus, is complex, because of the difficulty in the phasing and assembly of these regions. The DEFA1A3 locus is intriguing in that it falls within a region of high linkage disequilibrium, despite its high variability in copy number (n = 3-16); hence, the mechanisms responsible for changes in copy number at this locus are unclear. In this study, a region flanking the DEFA1A3 locus was sequenced across 120 independent haplotypes with European ancestry, identifying five common classes of DEFA1A3 haplotype. Assigning DEFA1A3 class to haplotypes within the 1000 Genomes project highlights a significant difference in DEFA1A3 class frequencies between populations with different ancestry. The features of each DEFA1A3 class, for example, the associated DEFA1A3 copy numbers, were initially assessed in a European cohort (n = 599) and replicated in the 1000 Genomes samples, showing within-class similarity, but between-class and between-population differences in the features of the DEFA1A3 locus. Emulsion haplotype fusion-PCR was used to generate 61 structural haplotypes at the DEFA1A3 locus, showing a high within-class similarity in structure. Structural haplotypes across the DEFA1A3 locus indicate that intra-allelic rearrangement is the predominant mechanism responsible for changes in DEFA1A3 copy number, explaining the conservation of linkage disequilibrium across the locus. The identification of common structural haplotypes at the DEFA1A3 locus could aid studies into how DEFA1A3 copy number influences expression, which is currently unclear.

  1. Copy Number Analysis of 24 Oncogenes: MDM4 Identified as a Putative Marker for Low Recurrence Risk in Non Muscle Invasive Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Samanta Salvi

    2014-07-01

    Full Text Available Patients with non-muscle invasive bladder cancer (NMIBC generally have a high risk of relapsing locally after primary tumor resection. The search for new predictive markers of local recurrence thus represents an important goal for the management of this disease. We studied the copy number variations (CNVs of 24 oncogenes (MDM4, MYCN, ALK, PDGFRA, KIT, KDR, DHFR, EGFR, MET, SMO, FGFR1, MYC, ABL1, RET, CCND1, CCND2, CDK4, MDM2, AURKB, ERBB2, TOP2A, AURKA, AR and BRAF using multiplex ligation probe amplification technique to verify their role as predictive markers of recurrence. Formalin-fixed paraffin-embedded tissue samples from 43 patients who underwent transurethral resection of the bladder (TURB were used; 23 patients had relapsed and 20 were disease-free after 5 years. Amplification frequencies were analyzed for all genes and MDM4 was the only gene that showed significantly higher amplification in non recurrent patients than in recurrent ones (0.65 vs. 0.3; Fisher’s test p = 0.023. Recurrence-free survival analysis confirmed the predictive role of MDM4 (log-rank test p = 0.041. Our preliminary results indicate a putative role for the MDM4 gene in predicting local recurrence of bladder cancer. Confirmation of this hypothesis is needed in a larger cohort of NMIBC patients.

  2. High Glucose-Induced Oxidative Stress Increases the Copy Number of Mitochondrial DNA in Human Mesangial Cells

    Directory of Open Access Journals (Sweden)

    Ghada Al-Kafaji

    2013-01-01

    Full Text Available Oxidative damage to mitochondrial DNA (mtDNA has been linked to the pathogenicity of diabetic nephropathy. We tested the hypothesis that mtDNA copy number may be increased in human mesangial cells in response to high glucose-induced reactive oxygen species (ROS to compensate for damaged mtDNA. The effect of manganese superoxide dismutase mimetic (MnTBAP on glucose-induced mtDNA copy number was also examined. The copy number of mtDNA was determined by real-time PCR in human mesangial cells cultured in 5 mM glucose, 25 mM glucose, and mannitol (osmotic control, as well as in cells cultured in 25 mM glucose in the presence and absence of 200 μM MnTBAP. Intracellular ROS was assessed by confocal microscopy and flow cytometry in human mesangial cells. The copy number of mtDNA was significantly increased when human mesangial cells were incubated with 25 mM glucose compared to 5 mM glucose and mannitol. In addition, 25 mM glucose rapidly generated ROS in the cells, which was not detected in 5 mM glucose. Furthermore, mtDNA copy number was significantly decreased and maintained to normal following treatment of cells with 25 mM glucose and MnTBAP compared to 25 mM glucose alone. Inclusion of MnTBAP during 25 mM glucose incubation inhibited mitochondrial superoxide in human mesangial cells. Increased mtDNA copy number in human mesangial cells by high glucose could contribute to increased mitochondrial superoxide, and prevention of mtDNA copy number could have potential in retarding the development of diabetic nephropathy.

  3. 41 CFR 102-75.405 - What responsibilities does the Federal Aviation Administration (FAA) have after receiving a copy...

    Science.gov (United States)

    2010-07-01

    ... does the Federal Aviation Administration (FAA) have after receiving a copy of the notice (and a copy of... responsibilities does the Federal Aviation Administration (FAA) have after receiving a copy of the notice (and a..., the FAA must inform the disposal agency of its determination. Then, the FAA must provide assistance to...

  4. The standardised copy of pentagons test

    Directory of Open Access Journals (Sweden)

    Terzoglou Vassiliki A

    2011-04-01

    Full Text Available Abstract Background The 'double-diamond copy' task is a simple paper and pencil test part of the Bender-Gestalt Test and the Mini Mental State Examination (MMSE. Although it is a widely used test, its method of scoring is crude and its psychometric properties are not adequately known. The aim of the present study was to develop a sensitive and reliable method of administration and scoring. Methods The study sample included 93 normal control subjects (53 women and 40 men aged 35.87 ± 12.62 and 127 patients suffering from schizophrenia (54 women and 73 men aged 34.07 ± 9.83. Results The scoring method was based on the frequencies of responses of healthy controls and proved to be relatively reliable with Cronbach's α equal to 0.61, test-retest correlation coefficient equal to 0.41 and inter-rater reliability equal to 0.52. The factor analysis produced two indices and six subscales of the Standardised Copy of Pentagons Test (SCPT. The total score as well as most of the individual items and subscales distinguished between controls and patients. The discriminant function correctly classified 63.44% of controls and 75.59% of patients. Discussion The SCPT seems to be a satisfactory, reliable and valid instrument, which is easy to administer, suitable for use in non-organic psychiatric patients and demands minimal time. Further research is necessary to test its psychometric properties and its usefulness and applications as a neuropsychological test.

  5. Differential Effects of Motor Efference Copies and Proprioceptive Information on Response Evaluation Processes

    Science.gov (United States)

    Stock, Ann-Kathrin; Wascher, Edmund; Beste, Christian

    2013-01-01

    It is well-kown that sensory information influences the way we execute motor responses. However, less is known about if and how sensory and motor information are integrated in the subsequent process of response evaluation. We used a modified Simon Task to investigate how these streams of information are integrated in response evaluation processes, applying an in-depth neurophysiological analysis of event-related potentials (ERPs), time-frequency decomposition and sLORETA. The results show that response evaluation processes are differentially modulated by afferent proprioceptive information and efference copies. While the influence of proprioceptive information is mediated via oscillations in different frequency bands, efference copy based information about the motor execution is specifically mediated via oscillations in the theta frequency band. Stages of visual perception and attention were not modulated by the interaction of proprioception and motor efference copies. Brain areas modulated by the interactive effects of proprioceptive and efference copy based information included the middle frontal gyrus and the supplementary motor area (SMA), suggesting that these areas integrate sensory information for the purpose of response evaluation. The results show how motor response evaluation processes are modulated by information about both the execution and the location of a response. PMID:23658624

  6. Nutritional strategies to reduce falls risk in older people.

    Science.gov (United States)

    Nash, Louise; Bergin, Nick

    2018-03-23

    A literature review found an association between increased falls risk and malnutrition, sarcopenia, vitamin D deficiency and dehydration. Strategies to identify, prevent and treat these conditions can help to reduce falls risk in at-risk groups such as frail, older people. Nurses can reduce falls risk in older people by raising awareness of risk factors and embedding nutritional strategies in local falls reduction strategies. ©2018 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.

  7. Quadruplex MAPH: improvement of throughput in high-resolution copy number screening.

    Science.gov (United States)

    Tyson, Jess; Majerus, Tamsin Mo; Walker, Susan; Armour, John Al

    2009-09-28

    Copy number variation (CNV) in the human genome is recognised as a widespread and important source of human genetic variation. Now the challenge is to screen for these CNVs at high resolution in a reliable, accurate and cost-effective way. Multiplex Amplifiable Probe Hybridisation (MAPH) is a sensitive, high-resolution technology appropriate for screening for CNVs in a defined region, for a targeted population. We have developed MAPH to a highly multiplexed format ("QuadMAPH") that allows the user a four-fold increase in the number of loci tested simultaneously. We have used this method to analyse a genomic region of 210 kb, including the MSH2 gene and 120 kb of flanking DNA. We show that the QuadMAPH probes report copy number with equivalent accuracy to simplex MAPH, reliably demonstrating diploid copy number in control samples and accurately detecting deletions in Hereditary Non-Polyposis Colorectal Cancer (HNPCC) samples. QuadMAPH is an accurate, high-resolution method that allows targeted screening of large numbers of subjects without the expense of genome-wide approaches. Whilst we have applied this technique to a region of the human genome, it is equally applicable to the genomes of other organisms.

  8. 36 CFR 1012.7 - Can I get an authenticated copy of a Presidio Trust record?

    Science.gov (United States)

    2010-07-01

    ... copy of a Presidio Trust record, for purposes of admissibility under Federal, State or Tribal law. We... copy of a Presidio Trust record? 1012.7 Section 1012.7 Parks, Forests, and Public Property PRESIDIO TRUST LEGAL PROCESS: TESTIMONY BY EMPLOYEES AND PRODUCTION OF RECORDS Responsibilities of Requesters...

  9. Edge Antimagic Total Labeling on Two Copies of Path

    Science.gov (United States)

    Nurdin; Abrar, A. M.; Bhayangkara, A. R. M.; Muliani; Samsir, A. U.; Nahdi, M. R. An

    2018-03-01

    A graph G = (V(G), E(G)) denotes the vertex set and the edge set, respectively. A (p,q)-graph G is a graph such that |V(G) | = p and |E(G) | = q. Graph of order p and size q is called (a,d)-edge-anti magic total if there exists a bijection f : V(G) U E(G)→ {1,2,..., p + q} such that the edge weights w(u,v) = f(u) + f(uv) + f(v) form an arithmetic sequence {a, a + d, a + 2d,...,a + (q - 1)d} with the first term a and common difference d. Two copies of path is disjoint union of two path graph with same order (Pn ∪Pn ) denoted by 2Pn . In this paper we construct the (a,d)-edge-anti magic total labeling in two copies of path for some differences d.

  10. Identification of copy number variants in horses

    KAUST Repository

    Doan, R.

    2012-03-01

    Copy number variants (CNVs) represent a substantial source of genetic variation in mammals. However, the occurrence of CNVs in horses and their subsequent impact on phenotypic variation is unknown. We performed a study to identify CNVs in 16 horses representing 15 distinct breeds (Equus caballus) and an individual gray donkey (Equus asinus) using a whole-exome tiling array and the array comparative genomic hybridization methodology. We identified 2368 CNVs ranging in size from 197 bp to 3.5 Mb. Merging identical CNVs from each animal yielded 775 CNV regions (CNVRs), involving 1707 protein- and RNA-coding genes. The number of CNVs per animal ranged from 55 to 347, with median and mean sizes of CNVs of 5.3 kb and 99.4 kb, respectively. Approximately 6% of the genes investigated were affected by a CNV. Biological process enrichment analysis indicated CNVs primarily affected genes involved in sensory perception, signal transduction, and metabolism. CNVs also were identified in genes regulating blood group antigens, coat color, fecundity, lactation, keratin formation, neuronal homeostasis, and height in other species. Collectively, these data are the first report of copy number variation in horses and suggest that CNVs are common in the horse genome and may modulate biological processes underlying different traits observed among horses and horse breeds.

  11. Multiply to conquer: Copy number variations at Ppd-B1 and Vrn-A1 facilitate global adaptation in wheat.

    Science.gov (United States)

    Würschum, Tobias; Boeven, Philipp H G; Langer, Simon M; Longin, C Friedrich H; Leiser, Willmar L

    2015-07-29

    Copy number variation was found to be a frequent type of DNA polymorphism in the human genome often associated with diseases but its importance in crops and the effects on agronomic traits are still largely unknown. Here, we employed a large worldwide panel of 1110 winter wheat varieties to assess the frequency and the geographic distribution of copy number variants at the Photoperiod-B1 (Ppd-B1) and the Vernalization-A1 (Vrn-A1) loci as well as their effects on flowering time under field conditions. We identified a novel four copy variant of Vrn-A1 and based on the phylogenetic relationships among the lines show that the higher copy variants at both loci are likely to have arisen independently multiple times. In addition, we found that the frequency of the different copy number variants at both loci reflects the environmental conditions in the varieties' region of origin and based on multi-location field trials show that Ppd-B1 copy number has a substantial effect on the fine-tuning of flowering time. In conclusion, our results show the importance of copy number variation at Ppd-B1 and Vrn-A1 for the global adaptation of wheat making it a key factor for wheat success in a broad range of environments and in a wider context substantiate the significant role of copy number variation in crops.

  12. Selective uptake and biological consequences of environmentally relevant antidepressant pharmaceutical exposures on male fathead minnows

    Science.gov (United States)

    Schultz, Melissa M.; Painter, Meghan M.; Bartell, Stephen E.; Logue, Amanda; Furlong, Edward T.; Werner, Stephen L.; Schoenfuss, Heiko L.

    2011-01-01

    Antidepressant pharmaceuticals have been reported in wastewater effluent at the nanogram to low microgram-per-liter range, and include bupropion (BUP), fluoxetine (FLX), sertraline (SER), and venlafaxine (VEN). To assess the effects of antidepressants on reproductive anatomy, physiology, and behavior, adult male fathead minnows (Pimeplwles promelas) were exposed for 21 days either to a single concentration of the antidepressants FLX, SER, VEN, or BUP, or to an antidepressant mixture. The data demonstrated that exposure to VEN (305 ng/L and 1104 ng/L) and SER (5.2 ng/L) resulted in mortality. Anatomical alterations were noted within the testes of fish exposed to SER and FLX, both modulators of the neurotransmitter serotonin. Additionally, FLX at 28 ng/L induced vitellogenin in male fish—a common endpoint for estrogenic endocrine disruption. Significant alterations in male secondary sex characteristics were noted with single exposures. Effects of single compound exposures neither carried over, nor became additive in the antidepressant mixtures, and reproductive behavior was not affected. Analysis of brain tissues from the exposed fish suggested increased uptake of FLX, SER and BUP and minimal uptake of VEN when compared to exposure water concentrations. Furthermore, the only metabolite detected consistently in the brain tissues was norfluoxetine. Similar trends of uptake by brain tissue were observed when fish were exposed to antidepressant mixtures. The present study demonstrates that anatomy and physiology, but not reproductive behavior, can be disrupted by exposure to environmental concentrations of some antidepressants. The observation that antidepressant uptake into fish tissues is selective may have consequences on assessing the mode-of-action and effects of these compounds in future studies.

  13. Using a risk assessment approach to handle 'hot spot' remediation in an environmentally-sensitive habitat

    International Nuclear Information System (INIS)

    BenKinney, M.T.; Guiseppi-Eli, A.; Novick, N.J.; Naro, P.A.

    1993-01-01

    A number of different approaches have been used to address site restoration following an accidental discharge or spill. Removal of all contamination with subsequent site restoration has been a favored approach. The authors' presentation will focus on a case study where a risk assessment approach was used to establish the criteria for is the restoration. Waste oil from a gasoline service station had leaked, over time, into a swale system in an ecologically-sensitive coastal forested habitat. The initial regulatory recommendation was to excavate all soils and restore the area. Their initial investigations revealed that only a limited area was heavily contaminated, predominantly with paraffinic hydrocarbons. They used a risk assessment approach coupled with sediment elutriate testing to demonstrate that leaving the lightly contaminated material in place would not present an environmental hazard from the waste oil, while causing less damage to the swale bed and forested area. Bioassay tests were conducted on sediments collected along the length of the swale from the areas with the highest remaining hydrocarbon concentrations using fathead minnow and Daphnia magna. The bioassay studies confirmed the results of the risk assessment which determined that no environmental toxicity would be expected from allowing lightly contaminated material to remain in-place at this site

  14. 75 FR 4031 - Streamlining Hard-Copy Postage Statement Processing

    Science.gov (United States)

    2010-01-26

    ... finalized postage statements from PostalOne! facilities are available online at the Business Customer...! facilities only. Copies of finalized postage statements are available online at the Business Customer Gateway... postage statements from PostalOne! facilities are available online at the Business Customer Gateway. 2. At...

  15. Whole genome DNA copy number changes identified by high density oligonucleotide arrays

    Directory of Open Access Journals (Sweden)

    Huang Jing

    2004-05-01

    Full Text Available Abstract Changes in DNA copy number are one of the hallmarks of the genetic instability common to most human cancers. Previous micro-array-based methods have been used to identify chromosomal gains and losses; however, they are unable to genotype alleles at the level of single nucleotide polymorphisms (SNPs. Here we describe a novel algorithm that uses a recently developed high-density oligonucleotide array-based SNP genotyping method, whole genome sampling analysis (WGSA, to identify genome-wide chromosomal gains and losses at high resolution. WGSA simultaneously genotypes over 10,000 SNPs by allele-specific hybridisation to perfect match (PM and mismatch (MM probes synthesised on a single array. The copy number algorithm jointly uses PM intensity and discrimination ratios between paired PM and MM intensity values to identify and estimate genetic copy number changes. Values from an experimental sample are compared with SNP-specific distributions derived from a reference set containing over 100 normal individuals to gain statistical power. Genomic regions with statistically significant copy number changes can be identified using both single point analysis and contiguous point analysis of SNP intensities. We identified multiple regions of amplification and deletion using a panel of human breast cancer cell lines. We verified these results using an independent method based on quantitative polymerase chain reaction and found that our approach is both sensitive and specific and can tolerate samples which contain a mixture of both tumour and normal DNA. In addition, by using known allele frequencies from the reference set, statistically significant genomic intervals can be identified containing contiguous stretches of homozygous markers, potentially allowing the detection of regions undergoing loss of heterozygosity (LOH without the need for a matched normal control sample. The coupling of LOH analysis, via SNP genotyping, with copy number

  16. Genetic transformation and gene silencing mediated by multiple copies of a transgene in eastern white pine.

    Science.gov (United States)

    Tang, Wei; Newton, Ronald J; Weidner, Douglas A

    2007-01-01

    An efficient transgenic eastern white pine (Pinus strobus L.) plant regeneration system has been established using Agrobacterium tumefaciens strain GV3850-mediated transformation and the green fluorescent protein (gfp) gene as a reporter in this investigation. Stable integration of transgenes in the plant genome of pine was confirmed by polymerase chain reaction (PCR), Southern blot, and northern blot analyses. Transgene expression was analysed in pine T-DNA transformants carrying different numbers of copies of T-DNA insertions. Post-transcriptional gene silencing (PTGS) was mostly obtained in transgenic lines with more than three copies of T-DNA, but not in transgenic lines with one copy of T-DNA. In situ hybridization chromosome analysis of transgenic lines demonstrated that silenced transgenic lines had two or more T-DNA insertions in the same chromosome. These results suggest that two or more T-DNA insertions in the same chromosome facilitate efficient gene silencing in transgenic pine cells expressing green fluorescent protein. There were no differences in shoot differentiation and development between transgenic lines with multiple T-DNA copies and transgenic lines with one or two T-DNA copies.

  17. Copy number variation in salivary amylase: A participant-based study on genetic variation.

    Directory of Open Access Journals (Sweden)

    Phillips, E.

    2017-07-01

    Full Text Available Amylase (AMY1 is an enzyme found in the mouth that is used to help digest carbohydrates. It has been found that the copy number of AMY1 has been positively associated with protein levels within an individual and also that individual’s population. This information can correspond to the positive ancestral linkage of high starch consumption within agricultural and hunter-gatherer societies. A high starch consumption means that the AMY1 enzyme will be more prevalent within their bodies, and the presence of AMY1 could both help bodies process starches better and prevent future conditions or intestinal diseases. The amylase gene is conclusively connected to the AMY1 copy number production. I hypothesized that individuals within a population will have a similar copy number of the AMY1 gene to each other. Twenty-five high school students located in Norman, Oklahoma were asked to retrieve buccal swabs from the inside of their cheek. DNA then was abstracted from these samples, and a quantitative polymerase chain reaction (qPCR, a machine used to detect the amount of genetic material found in the DNA, was completed in order to determine the copy number within each salivary sample. The qPCR was completed two different times in order to ensure correct results when the data was presented. Results indicated that the copy number within the population were similar to each other, and ranged from 1-12. This means that individuals located in this population have a lower production of amylase, and this provides indication that they are more likely to become obese than in previous research papers located in Arizona. Research shows that a smaller production of AMY1 may contribute to the chances of obesity in the future.

  18. FabV/Triclosan Is an Antibiotic-Free and Cost-Effective Selection System for Efficient Maintenance of High and Medium-Copy Number Plasmids in Escherichia coli.

    Science.gov (United States)

    Ali, Syed A; Chew, Yik Wei

    2015-01-01

    Antibiotic resistance genes and antibiotics are frequently used to maintain plasmid vectors in bacterial hosts such as Escherichia coli. Due to the risk of spread of antibiotic resistance, the regulatory authorities discourage the use of antibiotic resistance genes/antibiotics for the maintenance of plasmid vectors in certain biotechnology applications. Overexpression of E. coli endogenous fabI gene and subsequent selection on Triclosan has been proposed as a practical alternative to traditional antibiotic selection systems. Unfortunately, overexpression of fabI cannot be used to select medium-copy number plasmids, typically used for the expression of heterologous proteins in E. coli. Here we report that Vibrio cholera FabV, a functional homologue of E. coli FabI, can be used as a suitable marker for the selection and maintenance of both high and medium-copy number plasmid vectors in E. coli.

  19. Clinical findings and genetic screening for copy number variation ...

    African Journals Online (AJOL)

    to the Unified Parkinson's Disease Rating Scale (UPDRS), and patients were classified according to motor features. Genomic DNA was extracted and multiplex ligation-dependent probe amplification was used for detection of copy number variation (CNV) mutations in the known PD-causing genes. Results. Sixteen patients ...

  20. Rsp5 ubiquitin ligase is required for protein trafficking in Saccharomyces cerevisiae COPI mutants.

    Directory of Open Access Journals (Sweden)

    Katarzyna Jarmoszewicz

    Full Text Available Retrograde trafficking from the Golgi to the endoplasmic reticulum (ER depends on the formation of vesicles coated with the multiprotein complex COPI. In Saccharomyces cerevisiae ubiquitinated derivatives of several COPI subunits have been identified. The importance of this modification of COPI proteins is unknown. With the exception of the Sec27 protein (β'COP neither the ubiquitin ligase responsible for ubiquitination of COPI subunits nor the importance of this modification are known. Here we find that the ubiquitin ligase mutation, rsp5-1, has a negative effect that is additive with ret1-1 and sec28Δ mutations, in genes encoding α- and ε-COP, respectively. The double ret1-1 rsp5-1 mutant is also more severely defective in the Golgi-to-ER trafficking compared to the single ret1-1, secreting more of the ER chaperone Kar2p, localizing Rer1p mostly to the vacuole, and increasing sensitivity to neomycin. Overexpression of ubiquitin in ret1-1 rsp5-1 mutant suppresses vacuolar accumulation of Rer1p. We found that the effect of rsp5 mutation on the Golgi-to-ER trafficking is similar to that of sla1Δ mutation in a gene encoding actin cytoskeleton proteins, an Rsp5p substrate. Additionally, Rsp5 and Sla1 proteins were found by co-immunoprecipitation in a complex containing COPI subunits. Together, our results show that Rsp5 ligase plays a role in regulating retrograde Golgi-to-ER trafficking.

  1. Mitochondrial DNA copy number in peripheral blood cells declines with age and is associated with general health among elderly

    DEFF Research Database (Denmark)

    Mengel-From, Jonas; Thinggaard, Mikael; Dalgård, Christine

    2014-01-01

    compared to nuclear DNA, i.e. the mitochondrial DNA copy number, was measured by PCR technology and used as a proxy for the content of mitochondria copies. In 1,067 Danish twins and singletons (18-93 years of age), with the majority being elderly individuals, the estimated mean mitochondrial DNA copy...

  2. Prevalence of HIV-1 drug resistance in treated patients with viral load >50 copies/mL: a 2014 French nationwide study.

    Science.gov (United States)

    Assoumou, L; Charpentier, C; Recordon-Pinson, P; Grudé, M; Pallier, C; Morand-Joubert, L; Fafi-Kremer, S; Krivine, A; Montes, B; Ferré, V; Bouvier-Alias, M; Plantier, J-C; Izopet, J; Trabaud, M-A; Yerly, S; Dufayard, J; Alloui, C; Courdavault, L; Le Guillou-Guillemette, H; Maillard, A; Amiel, C; Vabret, A; Roussel, C; Vallet, S; Guinard, J; Mirand, A; Beby-Defaux, A; Barin, F; Allardet-Servent, A; Ait-Namane, R; Wirden, M; Delaugerre, C; Calvez, V; Chaix, M-L; Descamps, D; Reigadas, S

    2017-06-01

    Surveillance of HIV-1 resistance in treated patients with a detectable viral load (VL) is important to monitor, in order to assess the risk of spread of resistant viruses and to determine the proportion of patients who need new antiretroviral drugs with minimal cross-resistance. The HIV-1 protease and reverse transcriptase (RT) and integrase genes were sequenced in plasma samples from 782 consecutive patients on failing antiretroviral regimens, seen in 37 specialized centres in 2014. The genotyping results were interpreted using the ANRS v24 algorithm. Prevalence rates were compared with those obtained during a similar survey conducted in 2009. The protease and RT sequences were obtained in 566 patients, and the integrase sequence in 382 patients. Sequencing was successful in 60%, 78%, 78% and 87% of patients with VLs of 51-200, 201-500, 501-1000 and >1000 copies/mL, respectively. Resistance to at least one antiretroviral drug was detected in 56.3% of samples. Respectively, 3.9%, 8.7%, 1.5% and 3.4% of patients harboured viruses that were resistant to any NRTI, NNRTI, PI and integrase inhibitor (INI). Resistance rates were lower in 2014 than in 2009. Resistance was detected in 48.5% of samples from patients with a VL between 51 and 200 copies/mL. In France in 2014, 90.0% of patients in AIDS care centres were receiving antiretroviral drugs and 12.0% of them had VLs >50 copies/mL. Therefore, this study suggests that 6.7% of treated patients in France might transmit resistant strains. Resistance testing may be warranted in all treated patients with VL > 50 copies/mL. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Genomic copy number analysis of a spectrum of blue nevi identifies recurrent aberrations of entire chromosomal arms in melanoma ex blue nevus.

    Science.gov (United States)

    Chan, May P; Andea, Aleodor A; Harms, Paul W; Durham, Alison B; Patel, Rajiv M; Wang, Min; Robichaud, Patrick; Fisher, Gary J; Johnson, Timothy M; Fullen, Douglas R

    2016-03-01

    Blue nevi may display significant atypia or undergo malignant transformation. Morphologic diagnosis of this spectrum of lesions is notoriously difficult, and molecular tools are increasingly used to improve diagnostic accuracy. We studied copy number aberrations in a cohort of cellular blue nevi, atypical cellular blue nevi, and melanomas ex blue nevi using Affymetrix's OncoScan platform. Cases with sufficient DNA were analyzed for GNAQ, GNA11, and HRAS mutations. Copy number aberrations were detected in 0 of 5 (0%) cellular blue nevi, 3 of 12 (25%) atypical cellular blue nevi, and 6 of 9 (67%) melanomas ex blue nevi. None of the atypical cellular blue nevi displayed more than one aberration, whereas complex aberrations involving four or more regions were seen exclusively in melanomas ex blue nevi. Gains and losses of entire chromosomal arms were identified in four of five melanomas ex blue nevi with copy number aberrations. In particular, gains of 1q, 4p, 6p, and 8q, and losses of 1p and 4q were each found in at least two melanomas. Whole chromosome aberrations were also common, and represented the sole finding in one atypical cellular blue nevus. When seen in melanomas, however, whole chromosome aberrations were invariably accompanied by partial aberrations of other chromosomes. Three melanomas ex blue nevi harbored aberrations, which were absent or negligible in their precursor components, suggesting progression in tumor biology. Gene mutations involving GNAQ and GNA11 were each detected in two of eight melanomas ex blue nevi. In conclusion, copy number aberrations are more common and often complex in melanomas ex blue nevi compared with cellular and atypical cellular blue nevi. Identification of recurrent gains and losses of entire chromosomal arms in melanomas ex blue nevi suggests that development of new probes targeting these regions may improve detection and risk stratification of these lesions.

  4. Chromosome 17 alterations identify good-risk and poor-risk tumors independently of clinical factors in medulloblastoma

    Science.gov (United States)

    McCabe, Martin G.; Bäcklund, L. Magnus; Leong, Hui Sun; Ichimura, Koichi; Collins, V. Peter

    2011-01-01

    Current risk stratification schemas for medulloblastoma, based on combinations of clinical variables and histotype, fail to accurately identify particularly good- and poor-risk tumors. Attempts have been made to improve discriminatory power by combining clinical variables with cytogenetic data. We report here a pooled analysis of all previous reports of chromosomal copy number related to survival data in medulloblastoma. We collated data from previous reports that explicitly quoted survival data and chromosomal copy number in medulloblastoma. We analyzed the relative prognostic significance of currently used clinical risk stratifiers and the chromosomal aberrations previously reported to correlate with survival. In the pooled dataset metastatic disease, incomplete tumor resection and severe anaplasia were associated with poor outcome, while young age at presentation was not prognostically significant. Of the chromosomal variables studied, isolated 17p loss and gain of 1q correlated with poor survival. Gain of 17q without associated loss of 17p showed a trend to improved outcome. The most commonly reported alteration, isodicentric chromosome 17, was not prognostically significant. Sequential multivariate models identified isolated 17p loss, isolated 17q gain, and 1q gain as independent prognostic factors. In a historical dataset, we have identified isolated 17p loss as a marker of poor outcome and 17q gain as a novel putative marker of good prognosis. Biological markers of poor-risk and good-risk tumors will be critical in stratifying treatment in future trials. Our findings should be prospectively validated independently in future clinical studies. PMID:21292688

  5. Down the Rabbit Hole of Reality: Abbas Kiarostami’s Certified Copy

    Directory of Open Access Journals (Sweden)

    Anna Maria McMurray

    2011-08-01

    Full Text Available This article discusses how Iranian director Abbas Kiarostami’s 2010 film Certified Copy treats themes of originality, experience, perception, and memory.  The main character’s thesis about art—that copies are not merely inferior versions of originals—is applied to everyday experience of love, life and human relationships.  While the film seems to privilege the subjectivity of experience and reinforces the idea that value is found in individual interpretation rather than any one true or original meaning, it ultimately asks more questions than it answers, and while it sets out on a quest for truth, it, in the end, places responsibility on the audience to fill in the blanks and make meaning for themselves.

  6. The potential role for use of mitochondrial DNA copy number as predictive biomarker in presbycusis.

    Science.gov (United States)

    Falah, Masoumeh; Houshmand, Massoud; Najafi, Mohammad; Balali, Maryam; Mahmoudian, Saeid; Asghari, Alimohamad; Emamdjomeh, Hessamaldin; Farhadi, Mohammad

    2016-01-01

    Age-related hearing impairment, or presbycusis, is the most common communication disorder and neurodegenerative disease in the elderly. Its prevalence is expected to increase, due to the trend of growth of the elderly population. The current diagnostic test for detection of presbycusis is implemented after there has been a change in hearing sensitivity. Identification of a pre-diagnostic biomarker would raise the possibility of preserving hearing sensitivity before damage occurs. Mitochondrial dysfunction, including the production of reactive oxygen species and induction of expression of apoptotic genes, participates in the progression of presbycusis. Mitochondrial DNA sequence variation has a critical role in presbycusis. However, the nature of the relationship between mitochondrial DNA copy number, an important biomarker in many other diseases, and presbycusis is undetermined. Fifty-four subjects with presbycusis and 29 healthy controls were selected after ear, nose, throat examination and pure-tone audiometry. DNA was extracted from peripheral blood samples. The copy number of mitochondrial DNA relative to the nuclear genome was measured by quantitative real-time polymerase chain reaction. Subjects with presbycusis had a lower median mitochondrial DNA copy number than healthy subjects and the difference was statistically significant ( P =0.007). Mitochondrial DNA copy number was also significantly associated with degree of hearing impairment ( P =0.025) and audiogram configuration ( P =0.022). The findings of this study suggest that lower mitochondrial DNA copy number is responsible for presbycusis through alteration of mitochondrial function. Moreover, the significant association of mitochondrial DNA copy number in peripheral blood samples with the degree of hearing impairment and audiogram configuration has potential for use as a standard test for presbycusis, providing the possibility of the development of an easy-to-use biomarker for the early detection of

  7. 29 CFR 1905.7 - Form of documents; subscription; copies.

    Science.gov (United States)

    2010-07-01

    ... UNDER THE WILLIAMS-STEIGER OCCUPATIONAL SAFETY AND HEALTH ACT OF 1970 General § 1905.7 Form of documents... 29 Labor 5 2010-07-01 2010-07-01 false Form of documents; subscription; copies. 1905.7 Section 1905.7 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION...

  8. 12 CFR 563g.21 - Filing of copies of offering circulars in certain exempt offerings.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Filing of copies of offering circulars in certain exempt offerings. 563g.21 Section 563g.21 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY SECURITIES OFFERINGS § 563g.21 Filing of copies of offering circulars in certain...

  9. Using toxicokinetic-toxicodynamic modeling as an acute risk assessment refinement approach in vertebrate ecological risk assessment.

    Science.gov (United States)

    Ducrot, Virginie; Ashauer, Roman; Bednarska, Agnieszka J; Hinarejos, Silvia; Thorbek, Pernille; Weyman, Gabriel

    2016-01-01

    Recent guidance identified toxicokinetic-toxicodynamic (TK-TD) modeling as a relevant approach for risk assessment refinement. Yet, its added value compared to other refinement options is not detailed, and how to conduct the modeling appropriately is not explained. This case study addresses these issues through 2 examples of individual-level risk assessment for 2 hypothetical plant protection products: 1) evaluating the risk for small granivorous birds and small omnivorous mammals of a single application, as a seed treatment in winter cereals, and 2) evaluating the risk for fish after a pulsed treatment in the edge-of-field zone. Using acute test data, we conducted the first tier risk assessment as defined in the European Food Safety Authority (EFSA) guidance. When first tier risk assessment highlighted a concern, refinement options were discussed. Cases where the use of models should be preferred over other existing refinement approaches were highlighted. We then practically conducted the risk assessment refinement by using 2 different models as examples. In example 1, a TK model accounting for toxicokinetics and relevant feeding patterns in the skylark and in the wood mouse was used to predict internal doses of the hypothetical active ingredient in individuals, based on relevant feeding patterns in an in-crop situation, and identify the residue levels leading to mortality. In example 2, a TK-TD model accounting for toxicokinetics, toxicodynamics, and relevant exposure patterns in the fathead minnow was used to predict the time-course of fish survival for relevant FOCUS SW exposure scenarios and identify which scenarios might lead to mortality. Models were calibrated using available standard data and implemented to simulate the time-course of internal dose of active ingredient or survival for different exposure scenarios. Simulation results were discussed and used to derive the risk assessment refinement endpoints used for decision. Finally, we compared the

  10. Quadruplex MAPH: improvement of throughput in high-resolution copy number screening

    Directory of Open Access Journals (Sweden)

    Walker Susan

    2009-09-01

    Full Text Available Abstract Background Copy number variation (CNV in the human genome is recognised as a widespread and important source of human genetic variation. Now the challenge is to screen for these CNVs at high resolution in a reliable, accurate and cost-effective way. Results Multiplex Amplifiable Probe Hybridisation (MAPH is a sensitive, high-resolution technology appropriate for screening for CNVs in a defined region, for a targeted population. We have developed MAPH to a highly multiplexed format ("QuadMAPH" that allows the user a four-fold increase in the number of loci tested simultaneously. We have used this method to analyse a genomic region of 210 kb, including the MSH2 gene and 120 kb of flanking DNA. We show that the QuadMAPH probes report copy number with equivalent accuracy to simplex MAPH, reliably demonstrating diploid copy number in control samples and accurately detecting deletions in Hereditary Non-Polyposis Colorectal Cancer (HNPCC samples. Conclusion QuadMAPH is an accurate, high-resolution method that allows targeted screening of large numbers of subjects without the expense of genome-wide approaches. Whilst we have applied this technique to a region of the human genome, it is equally applicable to the genomes of other organisms.

  11. 36 CFR 1254.76 - What procedures do I follow to copy formerly national security-classified documents?

    Science.gov (United States)

    2010-07-01

    ... to copy formerly national security-classified documents? 1254.76 Section 1254.76 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION PUBLIC AVAILABILITY AND USE USING RECORDS... § 1254.76 What procedures do I follow to copy formerly national security-classified documents? (a) We...

  12. Written object naming, spelling to dictation, and immediate copying: Different tasks, different pathways?

    Science.gov (United States)

    Bonin, Patrick; Méot, Alain; Lagarrigue, Aurélie; Roux, Sébastien

    2015-01-01

    We report an investigation of cross-task comparisons of handwritten latencies in written object naming, spelling to dictation, and immediate copying. In three separate sessions, adults had to write down a list of concrete nouns from their corresponding pictures (written naming), from their spoken (spelling to dictation) and from their visual presentation (immediate copying). Linear mixed models without random slopes were performed on the latencies in order to study and compare within-task fixed effects. By-participants random slopes were then included to investigate individual differences within and across tasks. Overall, the findings suggest that written naming, spelling to dictation, and copying all involve a lexical pathway, but that written naming relies on this pathway more than the other two tasks do. Only spelling to dictation strongly involves a nonlexical pathway. Finally, the analyses performed at the level of participants indicate that, depending on the type of task, the slower participants are more or less influenced by certain psycholinguistic variables.

  13. Familial cases of Norrie disease detected by copy number analysis.

    Science.gov (United States)

    Arai, Eisuke; Fujimaki, Takuro; Yanagawa, Ai; Fujiki, Keiko; Yokoyama, Toshiyuki; Okumura, Akihisa; Shimizu, Toshiaki; Murakami, Akira

    2014-09-01

    Norrie disease (ND, MIM#310600) is an X-linked disorder characterized by severe vitreoretinal dysplasia at birth. We report the results of causative NDP gene analysis in three male siblings with Norrie disease and describe the associated phenotypes. Three brothers with suspected Norrie disease and their mother presented for clinical examination. After obtaining informed consent, DNA was extracted from the peripheral blood of the proband, one of his brothers and his unaffected mother. Exons 1-3 of the NDP gene were amplified by polymerase chain reaction (PCR), and direct sequencing was performed. Multiplex ligation-dependent probe amplification (MLPA) was also performed to search for copy number variants in the NDP gene. The clinical findings of the three brothers included no light perception, corneal opacity, shallow anterior chamber, leukocoria, total retinal detachment and mental retardation. Exon 2 of the NDP gene was not amplified in the proband and one brother, even when the PCR primers for exon 2 were changed, whereas the other two exons showed no mutations by direct sequencing. MLPA analysis showed deletion of exon 2 of the NDP gene in the proband and one brother, while there was only one copy of exon 2 in the mother. Norrie disease was diagnosed in three patients from a Japanese family by clinical examination and was confirmed by genetic analysis. To localize the defect, confirmation of copy number variation by the MLPA method was useful in the present study.

  14. Assessing Mitochondrial DNA Variation and Copy Number in Lymphocytes of ~2,000 Sardinians Using Tailored Sequencing Analysis Tools.

    Directory of Open Access Journals (Sweden)

    Jun Ding

    2015-07-01

    Full Text Available DNA sequencing identifies common and rare genetic variants for association studies, but studies typically focus on variants in nuclear DNA and ignore the mitochondrial genome. In fact, analyzing variants in mitochondrial DNA (mtDNA sequences presents special problems, which we resolve here with a general solution for the analysis of mtDNA in next-generation sequencing studies. The new program package comprises 1 an algorithm designed to identify mtDNA variants (i.e., homoplasmies and heteroplasmies, incorporating sequencing error rates at each base in a likelihood calculation and allowing allele fractions at a variant site to differ across individuals; and 2 an estimation of mtDNA copy number in a cell directly from whole-genome sequencing data. We also apply the methods to DNA sequence from lymphocytes of ~2,000 SardiNIA Project participants. As expected, mothers and offspring share all homoplasmies but a lesser proportion of heteroplasmies. Both homoplasmies and heteroplasmies show 5-fold higher transition/transversion ratios than variants in nuclear DNA. Also, heteroplasmy increases with age, though on average only ~1 heteroplasmy reaches the 4% level between ages 20 and 90. In addition, we find that mtDNA copy number averages ~110 copies/lymphocyte and is ~54% heritable, implying substantial genetic regulation of the level of mtDNA. Copy numbers also decrease modestly but significantly with age, and females on average have significantly more copies than males. The mtDNA copy numbers are significantly associated with waist circumference (p-value = 0.0031 and waist-hip ratio (p-value = 2.4×10-5, but not with body mass index, indicating an association with central fat distribution. To our knowledge, this is the largest population analysis to date of mtDNA dynamics, revealing the age-imposed increase in heteroplasmy, the relatively high heritability of copy number, and the association of copy number with metabolic traits.

  15. Perturbative quantum gravity as a double copy of gauge theory.

    Science.gov (United States)

    Bern, Zvi; Carrasco, John Joseph M; Johansson, Henrik

    2010-08-06

    In a previous paper we observed that (classical) tree-level gauge-theory amplitudes can be rearranged to display a duality between color and kinematics. Once this is imposed, gravity amplitudes are obtained using two copies of gauge-theory diagram numerators. Here we conjecture that this duality persists to all quantum loop orders and can thus be used to obtain multiloop gravity amplitudes easily from gauge-theory ones. As a nontrivial test, we show that the three-loop four-point amplitude of N=4 super-Yang-Mills theory can be arranged into a form satisfying the duality, and by taking double copies of the diagram numerators we obtain the corresponding amplitude of N=8 supergravity. We also remark on a nonsupersymmetric two-loop test based on pure Yang-Mills theory resulting in gravity coupled to an antisymmetric tensor and dilaton.

  16. Complex mixtures, complex responses: Assessing pharmaceutical mixtures using field and laboratory approaches

    Science.gov (United States)

    Schoenfuss, Heiko L.; Furlong, Edward T.; Phillips, Patrick J.; Scott, Tia-Marie; Kolpin, Dana W.; Cetkovic-Cvrlje, Marina; Lesteberg, Kelsey E.; Rearick, Daniel C.

    2016-01-01

    Pharmaceuticals are present in low concentrations (pharmaceutical formulation facilities. Using existing concentration data, the authors assessed pharmaceuticals in laboratory exposures of fathead minnows (Pimephales promelas) and added environmental complexity through effluent exposures. In the laboratory, larval and mature minnows were exposed to a simple opioid mixture (hydrocodone, methadone, and oxycodone), an opioid agonist (tramadol), a muscle relaxant (methocarbamol), a simple antidepressant mixture (fluoxetine, paroxetine, venlafaxine), a sleep aid (temazepam), or a complex mixture of all compounds. Larval minnow response to effluent exposure was not consistent. The 2010 exposures resulted in shorter exposed minnow larvae, whereas the larvae exposed in 2012 exhibited altered escape behavior. Mature minnows exhibited altered hepatosomatic indices, with the strongest effects in females and in mixture exposures. In addition, laboratory-exposed, mature male minnows exposed to all pharmaceuticals (except the selective serotonin reuptake inhibitor mixture) defended nest sites less rigorously than fish in the control group. Tramadol or antidepressant mixture exposure resulted in increased splenic T lymphocytes. Only male minnows exposed to whole effluent responded with increased plasma vitellogenin concentrations. Female minnows exposed to pharmaceuticals (except the opioid mixture) had larger livers, likely as a compensatory result of greater prominence of vacuoles in liver hepatocytes. The observed alteration of apical endpoints central to sustaining fish populations confirms that effluents containing waste streams from pharmaceutical formulation facilities can adversely impact fish populations but that the effects may not be temporally consistent. The present study highlights the importance of including diverse biological endpoints spanning levels of biological organization and life stages when assessing contaminant interactions.

  17. Dynamics in copy numbers of five plasmids of a dairy Lactococcus lactis in dairy-related conditions including near-zero growth rates.

    Science.gov (United States)

    van Mastrigt, Oscar; Lommers, Marcel M A N; de Vries, Yorick C; Abee, Tjakko; Smid, Eddy J

    2018-03-23

    Lactic acid bacteria can carry multiple plasmids affecting their performance in dairy fermentations. The expression of plasmid-encoded genes and the activity of the corresponding proteins is severely affected by changes in the number of plasmid copies. We studied the impact of growth rate on dynamics of plasmid copy numbers at high growth rates in chemostat cultures and down to near-zero growth rates in retentostat cultures. Five plasmids of the dairy strain Lactococcus lactis FM03-V1 were selected which varied in size (3 to 39 kb), in replication mechanism (theta or rolling-circle) and in putative (dairy-associated) functions. Copy numbers ranged from 1.5 to 40.5 and the copy number of theta-type replicating plasmids were negatively correlated to the plasmid size. Despite the extremely wide range of growth rates (0.0003 h -1 to 0.6 h -1 ), copy numbers of the five plasmids were stable and only slightly increased at near-zero growth rates showing that the plasmid replication rate was strictly controlled. One low-copy number plasmid, carrying a large exopolysaccharide gene cluster, was segregationally unstable during retentostat cultivations reflected in complete loss of the plasmid in one of the retentostat cultures. The copy number of the five plasmids was also hardly affected by varying the pH value, nutrient limitation or presence of citrate (maximum 2.2-fold) signifying the stability in copy number of the plasmids. Importance Lactococcus lactis is extensively used in starter cultures for dairy fermentations. Important traits for growth and survival of L. lactis in dairy fermentations are encoded by genes located on plasmids, such as genes involved in lactose and citrate metabolism, protein degradation and oligopeptide uptake and bacteriophage resistance. Because the number of plasmid copies could affect the expression of plasmid-encoded genes, it is important to know the factors that influence the plasmid copy numbers. We monitored plasmid copy numbers of L

  18. Short and long term bystander effect induction by fathead minnows (Pimephales promelas, Rafinesque, 1820) injected with environmentally relevant whole body doses of 226Ra

    International Nuclear Information System (INIS)

    Smith, Richard W.; Seymour, Colin B.; Mothersill, Carmel E.

    2013-01-01

    Bystander effect induction by fathead minnows injected with environmentally relevant doses of 226 Ra was investigated. Twenty four h and 6 months after injection with a single dose of 21, 210 or 2100 μBq, fin tissue samples emitted a pro-apoptotic signal, which reduced the clonogenic survival of an apoptosis sensitive reporter cell line. Twenty four h and 10 weeks after injection explants from non-injected bystander fish, swum with the injected fish, also emitted a pro-apoptotic signal. However 6 months after injection the bystander fish to 21 and 210 μBq injected fish emitted an anti-apoptotic signal. This demonstrates that extremely low dose irradiation can have effects outside of the irradiated fish. This has implications for population and ecosystem responses to contamination. -- Highlights: • Non-injected fish, swum with injected fish, gave the same response for up to 10 weeks. • After 6 months this response by non-injected fish changed to an anti-apoptotic signal. • This shows that 226 Ra contamination can have effects outside of the irradiated fish

  19. 4 CFR 22.7 - Copies and Service Thereof [Rule 7].

    Science.gov (United States)

    2010-01-01

    ...)], shall be provided to the Board by e-mail at [email protected], with a courtesy copy of the submission provided... delivery, express or priority mail, or approved commercial carrier (e.g., UPS or FedEx) within 2 business...

  20. Dietary fat-dependent transcriptional architecture and copy number alterations associated with modifiers of mammary cancer metastasis

    DEFF Research Database (Denmark)

    Gordon, Ryan A; Merrill, Michele La; Hunter, Kent W

    2010-01-01

    Breast cancer is a complex disease resulting from a combination of genetic and environmental factors. Among environmental factors, body composition and intake of specific dietary components like total fat are associated with increased incidence of breast cancer and metastasis. We previously showed...... fat. To elucidate diet-dependent genetic modifiers of mammary cancer and metastasis risk, global gene expression profiles and copy number alterations from mammary cancers were measured and expression quantitative trait loci (eQTL) identified. Functional candidate genes that colocalized with previously...... detected metastasis modifiers were identified. Additional analyses, such as eQTL by dietary fat interaction analysis, causality and database evaluations, helped to further refine the candidate loci to produce an enriched list of genes potentially involved in the pathogenesis of metastatic mammary cancer...

  1. Considering the role of time budgets on copy-error rates in material culture traditions: an experimental assessment.

    Science.gov (United States)

    Schillinger, Kerstin; Mesoudi, Alex; Lycett, Stephen J

    2014-01-01

    Ethnographic research highlights that there are constraints placed on the time available to produce cultural artefacts in differing circumstances. Given that copying error, or cultural 'mutation', can have important implications for the evolutionary processes involved in material culture change, it is essential to explore empirically how such 'time constraints' affect patterns of artefactual variation. Here, we report an experiment that systematically tests whether, and how, varying time constraints affect shape copying error rates. A total of 90 participants copied the shape of a 3D 'target handaxe form' using a standardized foam block and a plastic knife. Three distinct 'time conditions' were examined, whereupon participants had either 20, 15, or 10 minutes to complete the task. One aim of this study was to determine whether reducing production time produced a proportional increase in copy error rates across all conditions, or whether the concept of a task specific 'threshold' might be a more appropriate manner to model the effect of time budgets on copy-error rates. We found that mean levels of shape copying error increased when production time was reduced. However, there were no statistically significant differences between the 20 minute and 15 minute conditions. Significant differences were only obtained between conditions when production time was reduced to 10 minutes. Hence, our results more strongly support the hypothesis that the effects of time constraints on copying error are best modelled according to a 'threshold' effect, below which mutation rates increase more markedly. Our results also suggest that 'time budgets' available in the past will have generated varying patterns of shape variation, potentially affecting spatial and temporal trends seen in the archaeological record. Hence, 'time-budgeting' factors need to be given greater consideration in evolutionary models of material culture change.

  2. Copy-move forgery detection utilizing Fourier-Mellin transform log-polar features

    Science.gov (United States)

    Dixit, Rahul; Naskar, Ruchira

    2018-03-01

    In this work, we address the problem of region duplication or copy-move forgery detection in digital images, along with detection of geometric transforms (rotation and rescale) and postprocessing-based attacks (noise, blur, and brightness adjustment). Detection of region duplication, following conventional techniques, becomes more challenging when an intelligent adversary brings about such additional transforms on the duplicated regions. In this work, we utilize Fourier-Mellin transform with log-polar mapping and a color-based segmentation technique using K-means clustering, which help us to achieve invariance to all the above forms of attacks in copy-move forgery detection of digital images. Our experimental results prove the efficiency of the proposed method and its superiority to the current state of the art.

  3. Atrazine affects kidney and adrenal hormones (AHs) related genes expressions of rare minnow (Gobiocypris rarus).

    Science.gov (United States)

    Yang, Lihua; Zha, Jinmiao; Li, Wei; Li, Zhaoli; Wang, Zijian

    2010-05-05

    Atrazine, one of the most widely used herbicides, has been proved to interfere with sexual hormones. However few studies have considered the effects of atrazine on adrenal hormones (AH). In this study, rare minnow (Gobiocypris rarus) was exposed to 0, 3, 10, 33, 100 and 333microg/l atrazine for 28 days. The histopathology of kidney and gill was examined and the expressions of AHs-related genes including Na(+),K(+)-ATPase, glucocorticoid receptor (gr), heat shock protein 70 (hsp70), and heat shock protein 90 (hsp90) in kidney and gill were quantitatively determined. Histopathological observation revealed obvious lesions in gill including hyperplasia, necrosis in epithelium region, aneurysm and lamellar fusion at concentrations as low as 10microg/l. The observed lesions in kidney included extensive expansion in the lumen, degenerative and necrotic changes of the tubular epithelia, shrinkage of the glomerulus as well as increase of the Bowman's space at concentrations as low as 10microg/l. The expressions of Na(+),K(+)-ATPase, gr, hsp70 and hsp90 in the kidney of females were significantly decreased at all concentrations. For males, the expressions of hsp90 in the kidney of all treated groups were significantly down-regulated, while gr at all concentrations and hsp70 at 10, 33, 100microg/l were significantly up-regulated. However in the gill, the expressions of these genes were not significantly different from the control. These results indicated that exposure to atrazine caused impairments of kidney and gill of fish at environmental related concentrations. Histopathological lesions could partly attribute to the changes of the expressions of AHs-related genes in kidney. We concluded also that atrazine is a potential AHs-disruptor and AHs-related genes in kidney of fish could be used as sensitive molecular biomarkers.

  4. Atrazine affects kidney and adrenal hormones (AHs) related genes expressions of rare minnow (Gobiocypris rarus)

    Energy Technology Data Exchange (ETDEWEB)

    Yang Lihua; Zha Jinmiao; Li Wei; Li Zhaoli [State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Shuangqing Road 18, P.O. Box 2871, Beijing 100085 (China); Wang Zijian, E-mail: wangzj@rcees.ac.cn [State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Shuangqing Road 18, P.O. Box 2871, Beijing 100085 (China)

    2010-05-05

    Atrazine, one of the most widely used herbicides, has been proved to interfere with sexual hormones. However few studies have considered the effects of atrazine on adrenal hormones (AH). In this study, rare minnow (Gobiocypris rarus) was exposed to 0, 3, 10, 33, 100 and 333 {mu}g/l atrazine for 28 days. The histopathology of kidney and gill was examined and the expressions of AHs-related genes including Na{sup +},K{sup +}-ATPase, glucocorticoid receptor (gr), heat shock protein 70 (hsp70), and heat shock protein 90 (hsp90) in kidney and gill were quantitatively determined. Histopathological observation revealed obvious lesions in gill including hyperplasia, necrosis in epithelium region, aneurysm and lamellar fusion at concentrations as low as 10 {mu}g/l. The observed lesions in kidney included extensive expansion in the lumen, degenerative and necrotic changes of the tubular epithelia, shrinkage of the glomerulus as well as increase of the Bowman's space at concentrations as low as 10 {mu}g/l. The expressions of Na{sup +},K{sup +}-ATPase, gr, hsp70 and hsp90 in the kidney of females were significantly decreased at all concentrations. For males, the expressions of hsp90 in the kidney of all treated groups were significantly down-regulated, while gr at all concentrations and hsp70 at 10, 33, 100 {mu}g/l were significantly up-regulated. However in the gill, the expressions of these genes were not significantly different from the control. These results indicated that exposure to atrazine caused impairments of kidney and gill of fish at environmental related concentrations. Histopathological lesions could partly attribute to the changes of the expressions of AHs-related genes in kidney. We concluded also that atrazine is a potential AHs-disruptor and AHs-related genes in kidney of fish could be used as sensitive molecular biomarkers.

  5. Atrazine affects kidney and adrenal hormones (AHs) related genes expressions of rare minnow (Gobiocypris rarus)

    International Nuclear Information System (INIS)

    Yang Lihua; Zha Jinmiao; Li Wei; Li Zhaoli; Wang Zijian

    2010-01-01

    Atrazine, one of the most widely used herbicides, has been proved to interfere with sexual hormones. However few studies have considered the effects of atrazine on adrenal hormones (AH). In this study, rare minnow (Gobiocypris rarus) was exposed to 0, 3, 10, 33, 100 and 333 μg/l atrazine for 28 days. The histopathology of kidney and gill was examined and the expressions of AHs-related genes including Na + ,K + -ATPase, glucocorticoid receptor (gr), heat shock protein 70 (hsp70), and heat shock protein 90 (hsp90) in kidney and gill were quantitatively determined. Histopathological observation revealed obvious lesions in gill including hyperplasia, necrosis in epithelium region, aneurysm and lamellar fusion at concentrations as low as 10 μg/l. The observed lesions in kidney included extensive expansion in the lumen, degenerative and necrotic changes of the tubular epithelia, shrinkage of the glomerulus as well as increase of the Bowman's space at concentrations as low as 10 μg/l. The expressions of Na + ,K + -ATPase, gr, hsp70 and hsp90 in the kidney of females were significantly decreased at all concentrations. For males, the expressions of hsp90 in the kidney of all treated groups were significantly down-regulated, while gr at all concentrations and hsp70 at 10, 33, 100 μg/l were significantly up-regulated. However in the gill, the expressions of these genes were not significantly different from the control. These results indicated that exposure to atrazine caused impairments of kidney and gill of fish at environmental related concentrations. Histopathological lesions could partly attribute to the changes of the expressions of AHs-related genes in kidney. We concluded also that atrazine is a potential AHs-disruptor and AHs-related genes in kidney of fish could be used as sensitive molecular biomarkers.

  6. mtDNA copy number in oocytes of different sizes from individual pre- and post-pubertal pigs

    DEFF Research Database (Denmark)

    Pedersen, Hanne Skovsgaard; Løvendahl, Peter; Larsen, Knud Erik

    2014-01-01

    from ovaries of 10 pre- and 10 post-pubertal pigs. Cumulus cells were removed and the oocytes were measured (inside-ZP-diameter). Oocytes were transferred to DNAase-free tubes, snap-frozen, and stored at –80°C. The genes ND1 and COX1 were used to determine the mtDNA copy number. Plasmid preparations...... Reproduction 131, 233–245). However, the correlation between size and mtDNA copy number in single oocytes has not been determined. This study describes the relation between oocytes of defined diameters from individual pre- and postpubertal pigs and mtDNA copy number. Cumulus-oocyte complexes were aspirated...

  7. Industrial relevance of chromosomal copy number variation in Saccharomyces yeasts

    NARCIS (Netherlands)

    Gorter de Vries, A.R.; Pronk, J.T.; Daran, J.G.

    2017-01-01

    Chromosomal copy number variation (CCNV) plays a key role in evolution and health of eukaryotes. The unicellular yeast Saccharomyces cerevisiae is an important model for studying the generation, physiological impact, and evolutionary significance of CCNV. Fundamental studies of this yeast have

  8. Breast tumor copy number aberration phenotypes and genomic instability

    International Nuclear Information System (INIS)

    Fridlyand, Jane; Jain, Ajay N; McLennan, Jane; Ziegler, John; Chin, Koei; Devries, Sandy; Feiler, Heidi; Gray, Joe W; Waldman, Frederic; Pinkel, Daniel; Albertson, Donna G; Snijders, Antoine M; Ylstra, Bauke; Li, Hua; Olshen, Adam; Segraves, Richard; Dairkee, Shanaz; Tokuyasu, Taku; Ljung, Britt Marie

    2006-01-01

    Genomic DNA copy number aberrations are frequent in solid tumors, although the underlying causes of chromosomal instability in tumors remain obscure. Genes likely to have genomic instability phenotypes when mutated (e.g. those involved in mitosis, replication, repair, and telomeres) are rarely mutated in chromosomally unstable sporadic tumors, even though such mutations are associated with some heritable cancer prone syndromes. We applied array comparative genomic hybridization (CGH) to the analysis of breast tumors. The variation in the levels of genomic instability amongst tumors prompted us to investigate whether alterations in processes/genes involved in maintenance and/or manipulation of the genome were associated with particular types of genomic instability. We discriminated three breast tumor subtypes based on genomic DNA copy number alterations. The subtypes varied with respect to level of genomic instability. We find that shorter telomeres and altered telomere related gene expression are associated with amplification, implicating telomere attrition as a promoter of this type of aberration in breast cancer. On the other hand, the numbers of chromosomal alterations, particularly low level changes, are associated with altered expression of genes in other functional classes (mitosis, cell cycle, DNA replication and repair). Further, although loss of function instability phenotypes have been demonstrated for many of the genes in model systems, we observed enhanced expression of most genes in tumors, indicating that over expression, rather than deficiency underlies instability. Many of the genes associated with higher frequency of copy number aberrations are direct targets of E2F, supporting the hypothesis that deregulation of the Rb pathway is a major contributor to chromosomal instability in breast tumors. These observations are consistent with failure to find mutations in sporadic tumors in genes that have roles in maintenance or manipulation of the genome

  9. DR-Integrator: a new analytic tool for integrating DNA copy number and gene expression data.

    Science.gov (United States)

    Salari, Keyan; Tibshirani, Robert; Pollack, Jonathan R

    2010-02-01

    DNA copy number alterations (CNA) frequently underlie gene expression changes by increasing or decreasing gene dosage. However, only a subset of genes with altered dosage exhibit concordant changes in gene expression. This subset is likely to be enriched for oncogenes and tumor suppressor genes, and can be identified by integrating these two layers of genome-scale data. We introduce DNA/RNA-Integrator (DR-Integrator), a statistical software tool to perform integrative analyses on paired DNA copy number and gene expression data. DR-Integrator identifies genes with significant correlations between DNA copy number and gene expression, and implements a supervised analysis that captures genes with significant alterations in both DNA copy number and gene expression between two sample classes. DR-Integrator is freely available for non-commercial use from the Pollack Lab at http://pollacklab.stanford.edu/ and can be downloaded as a plug-in application to Microsoft Excel and as a package for the R statistical computing environment. The R package is available under the name 'DRI' at http://cran.r-project.org/. An example analysis using DR-Integrator is included as supplemental material. Supplementary data are available at Bioinformatics online.

  10. Géneros y cuerpos "degenerados" en la narrativa de Copi

    Directory of Open Access Journals (Sweden)

    Antonio Rojas

    2011-01-01

    Full Text Available El presente trabajo tiene como objetivo poner en relación el género literario y el género sexual mediante el estudio del funcionamiento del cronotopo en dos piezas narrativas de Copi (1939-1987. Siguiendo un método comparatista y con la ayuda de diferentes conceptos de teoría literaria, teoría queer y filosofía postestructuralista, se llevará a cabo un análisis, en primer lugar, de los medios con que Copi pretende transgredir las normas de género (literario y sexual; en segundo lugar, de los objetos imitados que son reapropiados según códigos no heterocentrados; por último, del modo en que el espaciamiento del tiempo en la novelística y la cuentística del escritor argentino privilegia una concepción del gender primordialmente prostética.

  11. Copy number variation of KIR genes influences HIV-1 control

    DEFF Research Database (Denmark)

    Pelak, Kimberly; Need, Anna C; Fellay, Jacques

    2011-01-01

    A genome-wide screen for large structural variants showed that a copy number variant (CNV) in the region encoding killer cell immunoglobulin-like receptors (KIR) associates with HIV-1 control as measured by plasma viral load at set point in individuals of European ancestry. This CNV encompasses...... the KIR3DL1-KIR3DS1 locus, encoding receptors that interact with specific HLA-Bw4 molecules to regulate the activation of lymphocyte subsets including natural killer (NK) cells. We quantified the number of copies of KIR3DS1 and KIR3DL1 in a large HIV-1 positive cohort, and showed that an increase in KIR3...... amounts of these activating and inhibitory KIR play a role in regulating the peripheral expansion of highly antiviral KIR3DS1+ NK cells, which may determine differences in HIV-1 control following infection....

  12. One Method for Inhibiting the Copying of Online Homework

    Science.gov (United States)

    Busch, Hauke

    2017-10-01

    Over the last several years online homework solutions have become ever more accessible to students. This is due in part to programs like Yahoo Answers, Chegg, publisher solution manuals, and other web resources that are readily available online. The student can easily search any physics homework problem posted on the web in a matter of seconds and have the solution. The results of this are an apparent increase in students copying the answers without solving the problem, which may lead to an increase in homework scores but a reduction in exam scores and an overall lower grade in the class. A secondary effect that may be observed is that tutoring centers, recitations, and supplemental instructor sessions have reduced student attendance. Some might say that the readily available solutions for homework systems such as MasteringPhysics (MP), WebAssign, etc. have greatly diminished them as a teaching tool, and for grading and assessing students' performance in a course. It is the purpose of this paper to offer a possible solution for preventing students from potentially copying online homework solutions.

  13. The role of copy number variation in susceptibility to amyotrophic lateral sclerosis: genome-wide association study and comparison with published loci.

    Directory of Open Access Journals (Sweden)

    Louise V Wain

    2009-12-01

    Full Text Available The genetic contribution to sporadic amyotrophic lateral sclerosis (ALS has not been fully elucidated. There are increasing efforts to characterise the role of copy number variants (CNVs in human diseases; two previous studies concluded that CNVs may influence risk of sporadic ALS, with multiple rare CNVs more important than common CNVs. A little-explored issue surrounding genome-wide CNV association studies is that of post-calling filtering and merging of raw CNV calls. We undertook simulations to define filter thresholds and considered optimal ways of merging overlapping CNV calls for association testing, taking into consideration possibly overlapping or nested, but distinct, CNVs and boundary estimation uncertainty.In this study we screened Illumina 300K SNP genotyping data from 730 ALS cases and 789 controls for copy number variation. Following quality control filters using thresholds defined by simulation, a total of 11321 CNV calls were made across 575 cases and 621 controls. Using region-based and gene-based association analyses, we identified several loci showing nominally significant association. However, the choice of criteria for combining calls for association testing has an impact on the ranking of the results by their significance. Several loci which were previously reported as being associated with ALS were identified here. However, of another 15 genes previously reported as exhibiting ALS-specific copy number variation, only four exhibited copy number variation in this study. Potentially interesting novel loci, including EEF1D, a translation elongation factor involved in the delivery of aminoacyl tRNAs to the ribosome (a process which has previously been implicated in genetic studies of spinal muscular atrophy were identified but must be treated with caution due to concerns surrounding genomic location and platform suitability.Interpretation of CNV association findings must take into account the effects of filtering and combining

  14. TTT and PIKK Complex Genes Reverted to Single Copy Following Polyploidization and Retain Function Despite Massive Retrotransposition in Maize.

    Science.gov (United States)

    Garcia, Nelson; Messing, Joachim

    2017-01-01

    The TEL2, TTI1, and TTI2 proteins are co-chaperones for heat shock protein 90 (HSP90) to regulate the protein folding and maturation of phosphatidylinositol 3-kinase-related kinases (PIKKs). Referred to as the TTT complex, the genes that encode them are highly conserved from man to maize. TTT complex and PIKK genes exist mostly as single copy genes in organisms where they have been characterized. Members of this interacting protein network in maize were identified and synteny analyses were performed to study their evolution. Similar to other species, there is only one copy of each of these genes in maize which was due to a loss of the duplicated copy created by ancient allotetraploidy. Moreover, the retained copies of the TTT complex and the PIKK genes tolerated extensive retrotransposon insertion in their introns that resulted in increased gene lengths and gene body methylation, without apparent effect in normal gene expression and function. The results raise an interesting question on whether the reversion to single copy was due to selection against deleterious unbalanced gene duplications between members of the complex as predicted by the gene balance hypothesis, or due to neutral loss of extra copies. Uneven alteration of dosage either by adding extra copies or modulating gene expression of complex members is being proposed as a means to investigate whether the data supports the gene balance hypothesis or not.

  15. TTT and PIKK Complex Genes Reverted to Single Copy Following Polyploidization and Retain Function Despite Massive Retrotransposition in Maize

    Directory of Open Access Journals (Sweden)

    Nelson Garcia

    2017-11-01

    Full Text Available The TEL2, TTI1, and TTI2 proteins are co-chaperones for heat shock protein 90 (HSP90 to regulate the protein folding and maturation of phosphatidylinositol 3-kinase-related kinases (PIKKs. Referred to as the TTT complex, the genes that encode them are highly conserved from man to maize. TTT complex and PIKK genes exist mostly as single copy genes in organisms where they have been characterized. Members of this interacting protein network in maize were identified and synteny analyses were performed to study their evolution. Similar to other species, there is only one copy of each of these genes in maize which was due to a loss of the duplicated copy created by ancient allotetraploidy. Moreover, the retained copies of the TTT complex and the PIKK genes tolerated extensive retrotransposon insertion in their introns that resulted in increased gene lengths and gene body methylation, without apparent effect in normal gene expression and function. The results raise an interesting question on whether the reversion to single copy was due to selection against deleterious unbalanced gene duplications between members of the complex as predicted by the gene balance hypothesis, or due to neutral loss of extra copies. Uneven alteration of dosage either by adding extra copies or modulating gene expression of complex members is being proposed as a means to investigate whether the data supports the gene balance hypothesis or not.

  16. The positioning logic and copy number control of genes in bacteria under stress

    Science.gov (United States)

    Zhang, Qiucen; Austin, Robert; Vyawahare, Saurabh; Lau, Alexandra

    2013-03-01

    Escherichia coli (E. coli) cells when challenged with sublethal concentrations of the genotoxic antibiotic ciprofloxacin cease to divide and form long filaments which contain multiple bacterial chromosomes. These filaments are individual mesoscopic environmental niches which provide protection for a community of chromosomes (as opposed to cells) under mutagenic stress and can provide an evolutionary fitness advantage within the niche. We use comparative genomic hybridization to show that the mesoscopic niche evolves within 20 minutes of ciprofloxacin exposure via replication of multiple copies of genes expressing ATP dependent transporters. We show that this rapid genomic amplification is done in a time efficient manner via placement of the genes encoding the pumps near the origin of replication on the bacterial chromosome. The de-amplification of multiple copies back to the wild type number is a function of the duration is a function of the ciprofloxacin exposure duration: the longer the exposure, the slower the removal of the multiple copies. The project described was supported by the National Science Foundation and the National Cancer Institute

  17. High incidence of recurrent copy number variants in patients with isolated and syndromic Müllerian aplasia.

    Science.gov (United States)

    Nik-Zainal, Serena; Strick, Reiner; Storer, Mekayla; Huang, Ni; Rad, Roland; Willatt, Lionel; Fitzgerald, Tomas; Martin, Vicki; Sandford, Richard; Carter, Nigel P; Janecke, Andreas R; Renner, Stefan P; Oppelt, Patricia G; Oppelt, Peter; Schulze, Christine; Brucker, Sara; Hurles, Matthew; Beckmann, Matthias W; Strissel, Pamela L; Shaw-Smith, Charles

    2011-03-01

    Congenital malformations involving the Müllerian ducts are observed in around 5% of infertile women. Complete aplasia of the uterus, cervix, and upper vagina, also termed Müllerian aplasia or Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome, occurs with an incidence of around 1 in 4500 female births, and occurs in both isolated and syndromic forms. Previous reports have suggested that a proportion of cases, especially syndromic cases, are caused by variation in copy number at different genomic loci. In order to obtain an overview of the contribution of copy number variation to both isolated and syndromic forms of Müllerian aplasia, copy number assays were performed in a series of 63 cases, of which 25 were syndromic and 38 isolated. A high incidence (9/63, 14%) of recurrent copy number variants in this cohort is reported here. These comprised four cases of microdeletion at 16p11.2, an autism susceptibility locus not previously associated with Müllerian aplasia, four cases of microdeletion at 17q12, and one case of a distal 22q11.2 microdeletion. Microdeletions at 16p11.2 and 17q12 were found in 4/38 (10.5%) cases with isolated Müllerian aplasia, and at 16p11.2, 17q12 and 22q11.2 (distal) in 5/25 cases (20%) with syndromic Müllerian aplasia. The finding of microdeletion at 16p11.2 in 2/38 (5%) of isolated and 2/25 (8%) of syndromic cases suggests a significant contribution of this copy number variant alone to the pathogenesis of Müllerian aplasia. Overall, the high incidence of recurrent copy number variants in all forms of Müllerian aplasia has implications for the understanding of the aetiopathogenesis of the condition, and for genetic counselling in families affected by it.

  18. Isolation and characterization of novel mutations in the pSC101 origin that increase copy number

    DEFF Research Database (Denmark)

    Thompson, Mitchell G.; Sedaghatian, Nima; Barajas, Jesus F.

    2018-01-01

    /cell) based plasmids, respectively. The mutant copy number variants retained compatibility with p15a, pBBR, and ColE1 origins of replication. These pSC101 variants may be useful in future metabolic engineering efforts that require medium or high-copy vectors compatible with p15a- and ColE1-based plasmids....

  19. Copy number variation of human AMY1 is a minor contributor to variation in salivary amylase expression and activity.

    Science.gov (United States)

    Carpenter, Danielle; Mitchell, Laura M; Armour, John A L

    2017-02-20

    Salivary amylase in humans is encoded by the copy variable gene AMY1 in the amylase gene cluster on chromosome 1. Although the role of salivary amylase is well established, the consequences of the copy number variation (CNV) at AMY1 on salivary amylase protein production are less well understood. The amylase gene cluster is highly structured with a fundamental difference between odd and even AMY1 copy number haplotypes. In this study, we aimed to explore, in samples from 119 unrelated individuals, not only the effects of AMY1 CNV on salivary amylase protein expression and amylase enzyme activity but also whether there is any evidence for underlying difference between the common haplotypes containing odd numbers of AMY1 and even copy number haplotypes. AMY1 copy number was significantly correlated with the variation observed in salivary amylase production (11.7% of variance, P structure may affect expression, but this was not significant in our data.

  20. Diversity in copy number and structure of a silkworm morphogenetic gene as a result of domestication.

    Science.gov (United States)

    Sakudoh, Takashi; Nakashima, Takeharu; Kuroki, Yoko; Fujiyama, Asao; Kohara, Yuji; Honda, Naoko; Fujimoto, Hirofumi; Shimada, Toru; Nakagaki, Masao; Banno, Yutaka; Tsuchida, Kozo

    2011-03-01

    The carotenoid-binding protein (CBP) of the domesticated silkworm, Bombyx mori, a major determinant of cocoon color, is likely to have been substantially influenced by domestication of this species. We analyzed the structure of the CBP gene in multiple strains of B. mori, in multiple individuals of the wild silkworm, B. mandarina (the putative wild ancestor of B. mori), and in a number of other lepidopterans. We found the CBP gene copy number in genomic DNA to vary widely among B. mori strains, ranging from 1 to 20. The copies of CBP are of several types, based on the presence of a retrotransposon or partial deletion of the coding sequence. In contrast to B. mori, B. mandarina was found to possess a single copy of CBP without the retrotransposon insertion, regardless of habitat. Several other lepidopterans were found to contain sequences homologous to CBP, revealing that this gene is evolutionarily conserved in the lepidopteran lineage. Thus, domestication can generate significant diversity of gene copy number and structure over a relatively short evolutionary time. © 2011 by the Genetics Society of America

  1. Microarray MAPH: accurate array-based detection of relative copy number in genomic DNA

    Directory of Open Access Journals (Sweden)

    Chan Alan

    2006-06-01

    Full Text Available Abstract Background Current methods for measurement of copy number do not combine all the desirable qualities of convenience, throughput, economy, accuracy and resolution. In this study, to improve the throughput associated with Multiplex Amplifiable Probe Hybridisation (MAPH we aimed to develop a modification based on the 3-Dimensional, Flow-Through Microarray Platform from PamGene International. In this new method, electrophoretic analysis of amplified products is replaced with photometric analysis of a probed oligonucleotide array. Copy number analysis of hybridised probes is based on a dual-label approach by comparing the intensity of Cy3-labelled MAPH probes amplified from test samples co-hybridised with similarly amplified Cy5-labelled reference MAPH probes. The key feature of using a hybridisation-based end point with MAPH is that discrimination of amplified probes is based on sequence and not fragment length. Results In this study we showed that microarray MAPH measurement of PMP22 gene dosage correlates well with PMP22 gene dosage determined by capillary MAPH and that copy number was accurately reported in analyses of DNA from 38 individuals, 12 of which were known to have Charcot-Marie-Tooth disease type 1A (CMT1A. Conclusion Measurement of microarray-based endpoints for MAPH appears to be of comparable accuracy to electrophoretic methods, and holds the prospect of fully exploiting the potential multiplicity of MAPH. The technology has the potential to simplify copy number assays for genes with a large number of exons, or of expanded sets of probes from dispersed genomic locations.

  2. Microarray MAPH: accurate array-based detection of relative copy number in genomic DNA.

    Science.gov (United States)

    Gibbons, Brian; Datta, Parikkhit; Wu, Ying; Chan, Alan; Al Armour, John

    2006-06-30

    Current methods for measurement of copy number do not combine all the desirable qualities of convenience, throughput, economy, accuracy and resolution. In this study, to improve the throughput associated with Multiplex Amplifiable Probe Hybridisation (MAPH) we aimed to develop a modification based on the 3-Dimensional, Flow-Through Microarray Platform from PamGene International. In this new method, electrophoretic analysis of amplified products is replaced with photometric analysis of a probed oligonucleotide array. Copy number analysis of hybridised probes is based on a dual-label approach by comparing the intensity of Cy3-labelled MAPH probes amplified from test samples co-hybridised with similarly amplified Cy5-labelled reference MAPH probes. The key feature of using a hybridisation-based end point with MAPH is that discrimination of amplified probes is based on sequence and not fragment length. In this study we showed that microarray MAPH measurement of PMP22 gene dosage correlates well with PMP22 gene dosage determined by capillary MAPH and that copy number was accurately reported in analyses of DNA from 38 individuals, 12 of which were known to have Charcot-Marie-Tooth disease type 1A (CMT1A). Measurement of microarray-based endpoints for MAPH appears to be of comparable accuracy to electrophoretic methods, and holds the prospect of fully exploiting the potential multiplicity of MAPH. The technology has the potential to simplify copy number assays for genes with a large number of exons, or of expanded sets of probes from dispersed genomic locations.

  3. The copy of the Essays of Jean Rey, used by Bayen and Gobet, at the BIU Sante, pole Pharmacie.

    Science.gov (United States)

    Lafont, Olivier

    2016-06-01

    The copy of the innovative book written by Jean Rey in 1630, entitied : The Essays on the reasons why the weight of stain and lead increased when they were burnt, which is nowadays kept in the BIU Sante, pole Pharmacie, proved to be the authentic copy which had been used by Pierre Bayer when he rediscovered Jean Rey's Works. It was also the same copy that Gobey used when he real- ized his new edition of the Essays in 1777. This copy first belonged to M. de Villars from La Rochelle, and then was acquired by M. de Villiers, who accepted to lend it to Bayen. The probes for this identification were detailed in the article.

  4. Why copy others? Insights from the social learning strategies tournament.

    Science.gov (United States)

    Rendell, L; Boyd, R; Cownden, D; Enquist, M; Eriksson, K; Feldman, M W; Fogarty, L; Ghirlanda, S; Lillicrap, T; Laland, K N

    2010-04-09

    Social learning (learning through observation or interaction with other individuals) is widespread in nature and is central to the remarkable success of humanity, yet it remains unclear why copying is profitable and how to copy most effectively. To address these questions, we organized a computer tournament in which entrants submitted strategies specifying how to use social learning and its asocial alternative (for example, trial-and-error learning) to acquire adaptive behavior in a complex environment. Most current theory predicts the emergence of mixed strategies that rely on some combination of the two types of learning. In the tournament, however, strategies that relied heavily on social learning were found to be remarkably successful, even when asocial information was no more costly than social information. Social learning proved advantageous because individuals frequently demonstrated the highest-payoff behavior in their repertoire, inadvertently filtering information for copiers. The winning strategy (discountmachine) relied nearly exclusively on social learning and weighted information according to the time since acquisition.

  5. Industrial Relevance of Chromosomal Copy Number Variation in Saccharomyces Yeasts

    Science.gov (United States)

    Gorter de Vries, Arthur R.; Pronk, Jack T.

    2017-01-01

    ABSTRACT Chromosomal copy number variation (CCNV) plays a key role in evolution and health of eukaryotes. The unicellular yeast Saccharomyces cerevisiae is an important model for studying the generation, physiological impact, and evolutionary significance of CCNV. Fundamental studies of this yeast have contributed to an extensive set of methods for analyzing and introducing CCNV. Moreover, these studies provided insight into the balance between negative and positive impacts of CCNV in evolutionary contexts. A growing body of evidence indicates that CCNV not only frequently occurs in industrial strains of Saccharomyces yeasts but also is a key contributor to the diversity of industrially relevant traits. This notion is further supported by the frequent involvement of CCNV in industrially relevant traits acquired during evolutionary engineering. This review describes recent developments in genome sequencing and genome editing techniques and discusses how these offer opportunities to unravel contributions of CCNV in industrial Saccharomyces strains as well as to rationally engineer yeast chromosomal copy numbers and karyotypes. PMID:28341679

  6. Dosage sensitivity shapes the evolution of copy-number varied regions.

    Directory of Open Access Journals (Sweden)

    Benjamin Schuster-Böckler

    2010-03-01

    Full Text Available Dosage sensitivity is an important evolutionary force which impacts on gene dispensability and duplicability. The newly available data on human copy-number variation (CNV allow an analysis of the most recent and ongoing evolution. Provided that heterozygous gene deletions and duplications actually change gene dosage, we expect to observe negative selection against CNVs encompassing dosage sensitive genes. In this study, we make use of several sources of population genetic data to identify selection on structural variations of dosage sensitive genes. We show that CNVs can directly affect expression levels of contained genes. We find that genes encoding members of protein complexes exhibit limited expression variation and overlap significantly with a manually derived set of dosage sensitive genes. We show that complexes and other dosage sensitive genes are underrepresented in CNV regions, with a particular bias against frequent variations and duplications. These results suggest that dosage sensitivity is a significant force of negative selection on regions of copy-number variation.

  7. Do laboratory species protect endangered species? Interspecies variation in responses to 17β-estradiol, a model endocrine active compound

    Science.gov (United States)

    Jorgenson, Zachary G.; Buhl, Kevin J.; Bartell, Stephen E.; Schoenfuss, Heiko L.

    2015-01-01

    Although the effects of estrogens on model laboratory species are well documented, their utility as surrogates for other species, including those listed as endangered, are less clear. Traditionally, conservation policies are evaluated based on model organism responses but are intended to protect all species in an environment. We tested the hypothesis that the endangered Rio Grande silvery minnow (Hybognathus amarus) is more vulnerable to endocrine disruption—as assessed through its larval predator-escape performance, survival, juvenile sex ratios, and whole-body vitellogenin concentration—than the commonly used toxicological model species fathead minnow (Pimephales promelas) and the bluegill sunfish (Lepomis macrochirus). Fish were exposed concurrently for 21 days to the model endocrine active compound (EAC) 17ß-estradiol (E2) at 10 ng E2/L and 30 ng E2/L in a flow-through system using reconstituted water that simulated the physicochemical conditions of the Middle Rio Grande in New Mexico, USA. No significant differences were observed between the fathead and silvery minnow in larval predator-escape response or juvenile sex ratio. Rio Grande silvery minnow survival decreased significantly at day 14 compared with the other two species; by day 21, both cyprinid species (silvery minnow and fathead minnow) exhibited a significant decrease in survival compared with bluegill sunfish, a member of the family Centrarchidae. Male Rio Grande silvery minnow showed a significant increase in whole-body vitellogenin concentration in the 10 ng/L treatment, whereas fathead minnow and bluegill sunfish showed no significant increases in vitellogenin concentrations across treatments. Our study showed response differences to estrogen exposures between the two cyprinid species and further divergence in responses between the families Cyprinidae and Centrarchidae. These results suggest that commonly used laboratory model organisms may be less sensitive to EACs than the endangered

  8. Do laboratory species protect endangered species? Interspecies variation in responses to 17β-estradiol, a model endocrine active compound.

    Science.gov (United States)

    Jorgenson, Z G; Buhl, K; Bartell, S E; Schoenfuss, H L

    2015-01-01

    Although the effects of estrogens on model laboratory species are well documented, their utility as surrogates for other species, including those listed as endangered, are less clear. Traditionally, conservation policies are evaluated based on model organism responses but are intended to protect all species in an environment. We tested the hypothesis that the endangered Rio Grande silvery minnow (Hybognathus amarus) is more vulnerable to endocrine disruption-as assessed through its larval predator-escape performance, survival, juvenile sex ratios, and whole-body vitellogenin concentration-than the commonly used toxicological model species fathead minnow (Pimephales promelas) and the bluegill sunfish (Lepomis macrochirus). Fish were exposed concurrently for 21 days to the model endocrine active compound (EAC) 17ß-estradiol (E2) at 10 ng E2/L and 30 ng E2/L in a flow-through system using reconstituted water that simulated the physicochemical conditions of the Middle Rio Grande in New Mexico, USA. No significant differences were observed between the fathead and silvery minnow in larval predator-escape response or juvenile sex ratio. Rio Grande silvery minnow survival decreased significantly at day 14 compared with the other two species; by day 21, both cyprinid species (silvery minnow and fathead minnow) exhibited a significant decrease in survival compared with bluegill sunfish, a member of the family Centrarchidae. Male Rio Grande silvery minnow showed a significant increase in whole-body vitellogenin concentration in the 10 ng/L treatment, whereas fathead minnow and bluegill sunfish showed no significant increases in vitellogenin concentrations across treatments. Our study showed response differences to estrogen exposures between the two cyprinid species and further divergence in responses between the families Cyprinidae and Centrarchidae. These results suggest that commonly used laboratory model organisms may be less sensitive to EACs than the endangered Rio

  9. Increased mitochondrial DNA deletions and copy number in transfusion-dependent thalassemia

    Science.gov (United States)

    Calloway, Cassandra

    2016-01-01

    BACKGROUND. Iron overload is the primary cause of morbidity in transfusion-dependent thalassemia. Increase in iron causes mitochondrial dysfunction under experimental conditions, but the occurrence and significance of mitochondrial damage is not understood in patients with thalassemia. METHODS. Mitochondrial DNA (mtDNA) to nuclear DNA copy number (Mt/N) and frequency of the common 4977-bp mitochondrial deletion (ΔmtDNA4977) were quantified using a quantitative PCR assay on whole blood samples from 38 subjects with thalassemia who were receiving regular transfusions. RESULTS. Compared with healthy controls, Mt/N and ΔmtDNA4977 frequency were elevated in thalassemia (P = 0.038 and P 15 mg/g dry-weight or splenectomy, with the highest levels observed in subjects who had both risk factors (P = 0.003). Myocardial iron (MRI T2* 40/1 × 107 mtDNA, respectively (P = 0.025). Subjects with Mt/N values below the group median had significantly lower Matsuda insulin sensitivity index (5.76 ± 0.53) compared with the high Mt/N group (9.11 ± 0.95, P = 0.008). CONCLUSION. Individuals with transfusion-dependent thalassemia demonstrate age-related increase in mtDNA damage in leukocytes. These changes are markedly amplified by splenectomy and are associated with extrahepatic iron deposition. Elevated mtDNA damage in blood cells may predict the risk of iron-associated organ damage in thalassemia. FUNDING. This project was supported by Children’s Hospital & Research Center Oakland Institutional Research Award and by the National Center for Advancing Translational Sciences, NIH, through UCSF-CTSI grant UL1 TR000004. PMID:27583305

  10. Genome-wide copy number variation (CNV) in patients with autoimmune Addison's disease

    Science.gov (United States)

    2011-01-01

    Background Addison's disease (AD) is caused by an autoimmune destruction of the adrenal cortex. The pathogenesis is multi-factorial, involving genetic components and hitherto unknown environmental factors. The aim of the present study was to investigate if gene dosage in the form of copy number variation (CNV) could add to the repertoire of genetic susceptibility to autoimmune AD. Methods A genome-wide study using the Affymetrix GeneChip® Genome-Wide Human SNP Array 6.0 was conducted in 26 patients with AD. CNVs in selected genes were further investigated in a larger material of patients with autoimmune AD (n = 352) and healthy controls (n = 353) by duplex Taqman real-time polymerase chain reaction assays. Results We found that low copy number of UGT2B28 was significantly more frequent in AD patients compared to controls; conversely high copy number of ADAM3A was associated with AD. Conclusions We have identified two novel CNV associations to ADAM3A and UGT2B28 in AD. The mechanism by which this susceptibility is conferred is at present unclear, but may involve steroid inactivation (UGT2B28) and T cell maturation (ADAM3A). Characterization of these proteins may unravel novel information on the pathogenesis of autoimmunity. PMID:21851588

  11. Genome-wide copy number variation (CNV in patients with autoimmune Addison's disease

    Directory of Open Access Journals (Sweden)

    Brønstad Ingeborg

    2011-08-01

    Full Text Available Abstract Background Addison's disease (AD is caused by an autoimmune destruction of the adrenal cortex. The pathogenesis is multi-factorial, involving genetic components and hitherto unknown environmental factors. The aim of the present study was to investigate if gene dosage in the form of copy number variation (CNV could add to the repertoire of genetic susceptibility to autoimmune AD. Methods A genome-wide study using the Affymetrix GeneChip® Genome-Wide Human SNP Array 6.0 was conducted in 26 patients with AD. CNVs in selected genes were further investigated in a larger material of patients with autoimmune AD (n = 352 and healthy controls (n = 353 by duplex Taqman real-time polymerase chain reaction assays. Results We found that low copy number of UGT2B28 was significantly more frequent in AD patients compared to controls; conversely high copy number of ADAM3A was associated with AD. Conclusions We have identified two novel CNV associations to ADAM3A and UGT2B28 in AD. The mechanism by which this susceptibility is conferred is at present unclear, but may involve steroid inactivation (UGT2B28 and T cell maturation (ADAM3A. Characterization of these proteins may unravel novel information on the pathogenesis of autoimmunity.

  12. Sequence diversity and copy number variation of Mutator-like transposases in wheat

    Directory of Open Access Journals (Sweden)

    Nobuaki Asakura

    2008-01-01

    Full Text Available Partial transposase-coding sequences of Mutator-like elements (MULEs were isolated from a wild einkorn wheat, Triticum urartu, by degenerate PCR. The isolated sequences were classified into a MuDR or Class I clade and divided into two distinct subclasses (subclass I and subclass II. The average pair-wise identity between members of both subclasses was 58.8% at the nucleotide sequence level. Sequence diversity of subclass I was larger than that of subclass II. DNA gel blot analysis showed that subclass I was present as low copy number elements in the genomes of all Triticum and Aegilops accessions surveyed, while subclass II was present as high copy number elements. These two subclasses seemed uncapable of recognizing each other for transposition. The number of copies of subclass II elements was much higher in Aegilops with the S, Sl and D genomes and polyploid Triticum species than in diploid Triticum with the A genome, indicating that active transposition occurred in S, Sl and D genomes before polyploidization. DNA gel blot analysis of six species selected from three subfamilies of Poaceae demonstrated that only the tribe Triticeae possessed both subclasses. These results suggest that the differentiation of these two subclasses occurred before or immediately after the establishment of the tribe Triticeae.

  13. High-resolution copy number variation analysis of schizophrenia in Japan.

    Science.gov (United States)

    Kushima, I; Aleksic, B; Nakatochi, M; Shimamura, T; Shiino, T; Yoshimi, A; Kimura, H; Takasaki, Y; Wang, C; Xing, J; Ishizuka, K; Oya-Ito, T; Nakamura, Y; Arioka, Y; Maeda, T; Yamamoto, M; Yoshida, M; Noma, H; Hamada, S; Morikawa, M; Uno, Y; Okada, T; Iidaka, T; Iritani, S; Yamamoto, T; Miyashita, M; Kobori, A; Arai, M; Itokawa, M; Cheng, M-C; Chuang, Y-A; Chen, C-H; Suzuki, M; Takahashi, T; Hashimoto, R; Yamamori, H; Yasuda, Y; Watanabe, Y; Nunokawa, A; Someya, T; Ikeda, M; Toyota, T; Yoshikawa, T; Numata, S; Ohmori, T; Kunimoto, S; Mori, D; Iwata, N; Ozaki, N

    2017-03-01

    Recent schizophrenia (SCZ) studies have reported an increased burden of de novo copy number variants (CNVs) and identified specific high-risk CNVs, although with variable phenotype expressivity. However, the pathogenesis of SCZ has not been fully elucidated. Using array comparative genomic hybridization, we performed a high-resolution genome-wide CNV analysis on a mainly (92%) Japanese population (1699 SCZ cases and 824 controls) and identified 7066 rare CNVs, 70.0% of which were small (history of congenital/developmental phenotypes, and the rate of treatment resistance was significantly higher (odds ratio=2.79, P=0.0036). We found more severe clinical manifestations in patients with two clinically significant CNVs. Gene set analysis replicated previous findings (e.g., synapse, calcium signaling) and identified novel biological pathways including oxidative stress response, genomic integrity, kinase and small GTPase signaling. Furthermore, involvement of multiple SCZ candidate genes and biological pathways in the pathogenesis of SCZ was suggested in established SCZ-associated CNV loci. Our study shows the high genetic heterogeneity of SCZ and its clinical features and raises the possibility that genomic instability is involved in its pathogenesis, which may be related to the increased burden of de novo CNVs and variable expressivity of CNVs.

  14. Alteration of rRNA gene copy number and expression in patients ...

    African Journals Online (AJOL)

    Irina S. Kolesnikova

    2017-09-01

    Sep 1, 2017 ... Asia R. Shorina d, Alexander S. Graphodatsky a, Ekaterina M. Galanina b, Dmitry V. Yudkin a,b,* ... rRNA gene copy numbers on affected acrocentric chromosomes in .... estimated using MS Excel software (Microsoft, USA).

  15. Integrative Genomics Reveals Mechanisms of Copy Number Alterations Responsible for Transcriptional Deregulation in Colorectal Cancer

    Science.gov (United States)

    Camps, Jordi; Nguyen, Quang Tri; Padilla-Nash, Hesed M.; Knutsen, Turid; McNeil, Nicole E.; Wangsa, Danny; Hummon, Amanda B.; Grade, Marian; Ried, Thomas; Difilippantonio, Michael J.

    2016-01-01

    To evaluate the mechanisms and consequences of chromosomal aberrations in colorectal cancer (CRC), we used a combination of spectral karyotyping, array comparative genomic hybridization (aCGH), and array-based global gene expression profiling on 31 primary carcinomas and 15 established cell lines. Importantly, aCGH showed that the genomic profiles of primary tumors are recapitulated in the cell lines. We revealed a preponderance of chromosome breakpoints at sites of copy number variants (CNVs) in the CRC cell lines, a novel mechanism of DNA breakage in cancer. The integration of gene expression and aCGH led to the identification of 157 genes localized within high-level copy number changes whose transcriptional deregulation was significantly affected across all of the samples, thereby suggesting that these genes play a functional role in CRC. Genomic amplification at 8q24 was the most recurrent event and led to the overexpression of MYC and FAM84B. Copy number dependent gene expression resulted in deregulation of known cancer genes such as APC, FGFR2, and ERBB2. The identification of only 36 genes whose localization near a breakpoint could account for their observed deregulated expression demonstrates that the major mechanism for transcriptional deregulation in CRC is genomic copy number changes resulting from chromosomal aberrations. PMID:19691111

  16. Copy number variation of KIR genes influences HIV-1 control

    DEFF Research Database (Denmark)

    Pelak, Kimberly; Need, Anna C; Fellay, Jacques

    2011-01-01

    A genome-wide screen for large structural variants showed that a copy number variant (CNV) in the region encoding killer cell immunoglobulin-like receptors (KIR) associates with HIV-1 control as measured by plasma viral load at set point in individuals of European ancestry. This CNV encompasses t...

  17. DUF1220 copy number is linearly associated with increased cognitive function as measured by total IQ and mathematical aptitude scores

    Science.gov (United States)

    Davis, Jonathon M.; Searles, Veronica B.; Anderson, Nathan; Keeney, Jonathon; Raznahan, Armin; Horwood, L. John; Fergusson, David M.; Kennedy, Martin A.; Giedd, Jay

    2014-01-01

    DUF1220 protein domains exhibit the greatest human lineage-specific copy number expansion of any protein-coding sequence in the genome, and variation in DUF1220 copy number has been linked to both brain size in humans and brain evolution among primates. Given these findings, we examined associations between DUF1220 subtypes CON1 and CON2 and cognitive aptitude. We identified a linear association between CON2 copy number and cognitive function in two independent populations of European descent. In North American males, an increase in CON2 copy number corresponded with an increase in WISC IQ (R2 = 0.13, p = 0.02), which may be driven by males aged 6–11 (R2 = 0.42, p = 0.003). We utilized ddPCR in a subset as a confirmatory measurement. This group had 26–33 copies of CON2 with a mean of 29, and each copy increase of CON2 was associated with a 3.3-point increase in WISC IQ (R2 = 0.22, p = 0.045). In individuals from New Zealand, an increase in CON2 copy number was associated with an increase in math aptitude ability (R2 = 0.10 p = 0.018). These were not confounded by brain size. To our knowledge, this is the first study to report a replicated association between copy number of a gene coding sequence and cognitive aptitude. Remarkably, dosage variations involving DUF1220 sequences have now been linked to human brain expansion, autism severity and cognitive aptitude, suggesting that such processes may be genetically and mechanistically inter-related. The findings presented here warrant expanded investigations in larger, well-characterized cohorts. PMID:25287832

  18. Copy number variation plays an important role in clinical epilepsy

    Science.gov (United States)

    Olson, Heather; Shen, Yiping; Avallone, Jennifer; Sheidley, Beth R.; Pinsky, Rebecca; Bergin, Ann M.; Berry, Gerard T.; Duffy, Frank H.; Eksioglu, Yaman; Harris, David J.; Hisama, Fuki M.; Ho, Eugenia; Irons, Mira; Jacobsen, Christina M.; James, Philip; Kothare, Sanjeev; Khwaja, Omar; Lipton, Jonathan; Loddenkemper, Tobias; Markowitz, Jennifer; Maski, Kiran; Megerian, J. Thomas; Neilan, Edward; Raffalli, Peter C.; Robbins, Michael; Roberts, Amy; Roe, Eugene; Rollins, Caitlin; Sahin, Mustafa; Sarco, Dean; Schonwald, Alison; Smith, Sharon E.; Soul, Janet; Stoler, Joan M.; Takeoka, Masanori; Tan, Wen-Han; Torres, Alcy R.; Tsai, Peter; Urion, David K.; Weissman, Laura; Wolff, Robert; Wu, Bai-Lin; Miller, David T.; Poduri, Annapurna

    2015-01-01

    Objective To evaluate the role of copy number abnormalities detectable by chromosomal microarray (CMA) testing in patients with epilepsy at a tertiary care center. Methods We identified patients with ICD-9 codes for epilepsy or seizures and clinical CMA testing performed between October 2006 and February 2011 at Boston Children’s Hospital. We reviewed medical records and included patients meeting criteria for epilepsy. We phenotypically characterized patients with epilepsy-associated abnormalities on CMA. Results Of 973 patients who had CMA and ICD-9 codes for epilepsy or seizures, 805 patients satisfied criteria for epilepsy. We observed 437 copy number variants (CNVs) in 323 patients (1–4 per patient), including 185 (42%) deletions and 252 (58%) duplications. Forty (9%) were confirmed de novo, 186 (43%) were inherited, and parental data were unavailable for 211 (48%). Excluding full chromosome trisomies, CNV size ranged from 18 kb to 142 Mb, and 34% were over 500 kb. In at least 40 cases (5%), the epilepsy phenotype was explained by a CNV, including 29 patients with epilepsy-associated syndromes and 11 with likely disease-associated CNVs involving epilepsy genes or “hotspots.” We observed numerous recurrent CNVs including 10 involving loss or gain of Xp22.31, a region described in patients with and without epilepsy. Interpretation Copy number abnormalities play an important role in patients with epilepsy. Given that the diagnostic yield of CMA for epilepsy patients is similar to the yield in autism spectrum disorders and in prenatal diagnosis, for which published guidelines recommend testing with CMA, we recommend the implementation of CMA in the evaluation of unexplained epilepsy. PMID:24811917

  19. Computerized micrographics in processing hard-copy records for an epidemiologic study

    International Nuclear Information System (INIS)

    Robie, D.M.; Fry, S.A.

    1983-01-01

    The availability of computers with increasing capabilities has made feasibile epidemiologic studies involving large populations such as those utilized to evaluate the health effects of occupational exposure to radiation. However, the storage and retrieval of data from the large numbers of hard-copy personnel, health physics, employment medical, historical or anecdotal documents that are the bases of such studies pose major logistics problems to investigators. The potential value of such records to epidemiologic studies depends, not only on their accuracy and completeness, but also on ease of accessibility. To address the latter problem, we are using a stand-alone user-oriented electronic filing system that records, stores, and secures hard-copy documents micrographically. This system is controlled by a computer that provides retrieval of a document image and printed copy (if desired) in less than 30 seconds from a maximum of eight fields. One thousand documents are randomly filmed and indexed on computer storage diskettes in two hours. Manual sorting and filing of the same number of documents takes over a day. At present two thousand documents can be recorded on each microfilm roll and 85,000 documents indexed on each diskette. Simultaneous searching for documents can be done using up to ten terminals while indexing is being done at the main terminal. The micrographics system provides the space-saving and security advantages of microfilm with the speed of computerized data retrieval

  20. submitter Metabolomic Profile of Low–Copy Number Carriers at the Salivary α-Amylase Gene Suggests a Metabolic Shift Toward Lipid-Based Energy Production

    CERN Document Server

    Arredouani, Abdelilah; Culeddu, Nicola; Moustafa, Julia El-Sayed; Tichet, Jean; Balkau, Beverley; Brousseau, Thierry; Manca, Marco; Falchi, Mario

    2016-01-01

    Low serum salivary amylase levels have been associated with a range of metabolic abnormalities, including obesity and insulin resistance. We recently suggested that a low copy number at the AMY1 gene, associated with lower enzyme levels, also increases susceptibility to obesity. To advance our understanding of the effect of AMY1 copy number variation on metabolism, we compared the metabolomic signatures of high– and low–copy number carriers. We analyzed, using mass spectrometry and nuclear magnetic resonance (NMR), the sera of healthy normal-weight women carrying either low–AMY1 copies (LAs: four or fewer copies; n = 50) or high–AMY1 copies (HAs: eight or more copies; n = 50). Best-fitting multivariate models (empirical P < 1 × $10^{−3})$ of mass spectrometry and NMR data were concordant in showing differences in lipid metabolism between the two groups. In particular, LA carriers showed lower levels of long- and medium-chain fatty acids, and higher levels of dicarboxylic fatty acids and 2-hydrox...

  1. 30 CFR 90.301 - Respirable dust control plan; approval by District Manager; copy to part 90 miner.

    Science.gov (United States)

    2010-07-01

    ... District Manager; copy to part 90 miner. 90.301 Section 90.301 Mineral Resources MINE SAFETY AND HEALTH... control plan; approval by District Manager; copy to part 90 miner. (a) The District Manager will approve... District Manager shall consider whether: (1) The respirable dust control measures would be likely to...

  2. Evaluation of potential mechanisms of atrazine-induced reproductive impairment in fathead minnow (Pimephales promelas) and Japanese medaka (Oryzias latipes)

    Science.gov (United States)

    Richter, Cathy; Papoulias, Diana M.; Whyte, Jeffrey J.; Tillitt, Donald E.

    2016-01-01

    Atrazine has been implicated in reproductive dysfunction of exposed organisms, and previous studies documented decreased egg production in Japanese medaka (Oryzias latipes) and fathead minnows (Pimephales promelas) during 30-d to 38-d exposures to 0.5 µg/L, 5 µg/L, and 50 µg/L atrazine. The authors evaluated possible mechanisms underlying the reduction in egg production. Gene expression in steroidogenesis pathways and the hypothalamus–pituitary–gonad axis of male and female fish was measured. Atrazine did not significantly induce gonad aromatase (cyp19a1a) expression. An atrazine-induced shift in the number of females in an active reproductive state was observed. Expression of the egg maturation genes vitellogenin 1 (vtg1) and zona pellucida glycoprotein 3.1 (zp3.1) in medaka females was correlated and had a bimodal distribution. In both species, females with low vtg1 or zp3.1 expression also had low expression of steroidogenesis genes in the gonad, estrogen receptor in the liver, and gonadotropins in the brain. In the medaka, the number of females per tank that had high expression of zp3.1 was significantly correlated with egg production per tank. The number of medaka females with low expression of zp3.1 increased significantly with atrazine exposure. Thus, the decline in egg production observed in response to atrazine exposure may be the result of a coordinated downregulation of genes required for reproduction in a subset of females.

  3. Variability of rRNA Operon Copy Number and Growth Rate Dynamics of Bacillus Isolated from an Extremely Oligotrophic Aquatic Ecosystem

    Science.gov (United States)

    Valdivia-Anistro, Jorge A.; Eguiarte-Fruns, Luis E.; Delgado-Sapién, Gabriela; Márquez-Zacarías, Pedro; Gasca-Pineda, Jaime; Learned, Jennifer; Elser, James J.; Olmedo-Alvarez, Gabriela; Souza, Valeria

    2016-01-01

    The ribosomal RNA (rrn) operon is a key suite of genes related to the production of protein synthesis machinery and thus to bacterial growth physiology. Experimental evidence has suggested an intrinsic relationship between the number of copies of this operon and environmental resource availability, especially the availability of phosphorus (P), because bacteria that live in oligotrophic ecosystems usually have few rrn operons and a slow growth rate. The Cuatro Ciénegas Basin (CCB) is a complex aquatic ecosystem that contains an unusually high microbial diversity that is able to persist under highly oligotrophic conditions. These environmental conditions impose a variety of strong selective pressures that shape the genome dynamics of their inhabitants. The genus Bacillus is one of the most abundant cultivable bacterial groups in the CCB and usually possesses a relatively large number of rrn operon copies (6–15 copies). The main goal of this study was to analyze the variation in the number of rrn operon copies of Bacillus in the CCB and to assess their growth-related properties as well as their stoichiometric balance (N and P content). We defined 18 phylogenetic groups within the Bacilli clade and documented a range of from six to 14 copies of the rrn operon. The growth dynamic of these Bacilli was heterogeneous and did not show a direct relation to the number of operon copies. Physiologically, our results were not consistent with the Growth Rate Hypothesis, since the copies of the rrn operon were decoupled from growth rate. However, we speculate that the diversity of the growth properties of these Bacilli as well as the low P content of their cells in an ample range of rrn copy number is an adaptive response to oligotrophy of the CCB and could represent an ecological mechanism that allows these taxa to coexist. These findings increase the knowledge of the variability in the number of copies of the rrn operon in the genus Bacillus and give insights about the

  4. Using Copy Change with Trade Books to Teach Earth Science

    Science.gov (United States)

    Bintz, William P.; Wright, Pam; Sheffer, Julie

    2010-01-01

    Developing and implementing relevant, challenging, integrative, and exploratory curriculum is critical at all levels of schooling. This article describes one attempt to develop and implement an instance of interdisciplinary curriculum by using copy change with trade books to teach earth science. Specifically, it introduces trade books as a way to…

  5. Juvenile Galápagos pelicans increase their foraging success by copying adult behaviour.

    Directory of Open Access Journals (Sweden)

    Henrik Brumm

    Full Text Available Social learning is the building block of culture and traditions in humans and nonhuman animals, and its study has a long history. Most investigations have addressed either the causation or the function of social learning. Though much is known about the underlying mechanisms of social learning, demonstrations of its adaptive value in a natural setting are lacking. Here we show that juvenile brown pelicans (Pelecanus occidentalis can increase their foraging efficiency by copying adult diving behaviour, suggesting that social learning helps juveniles to find profitable food patches. Our findings demonstrate the potential fitness consequences of behavioural copying and thus highlight the possible adaptive importance of social learning.

  6. Stoichiometric balance of protein copy numbers is measurable and functionally significant in a protein-protein interaction network for yeast endocytosis.

    Science.gov (United States)

    Holland, David O; Johnson, Margaret E

    2018-03-01

    Stoichiometric balance, or dosage balance, implies that proteins that are subunits of obligate complexes (e.g. the ribosome) should have copy numbers expressed to match their stoichiometry in that complex. Establishing balance (or imbalance) is an important tool for inferring subunit function and assembly bottlenecks. We show here that these correlations in protein copy numbers can extend beyond complex subunits to larger protein-protein interactions networks (PPIN) involving a range of reversible binding interactions. We develop a simple method for quantifying balance in any interface-resolved PPINs based on network structure and experimentally observed protein copy numbers. By analyzing such a network for the clathrin-mediated endocytosis (CME) system in yeast, we found that the real protein copy numbers were significantly more balanced in relation to their binding partners compared to randomly sampled sets of yeast copy numbers. The observed balance is not perfect, highlighting both under and overexpressed proteins. We evaluate the potential cost and benefits of imbalance using two criteria. First, a potential cost to imbalance is that 'leftover' proteins without remaining functional partners are free to misinteract. We systematically quantify how this misinteraction cost is most dangerous for strong-binding protein interactions and for network topologies observed in biological PPINs. Second, a more direct consequence of imbalance is that the formation of specific functional complexes depends on relative copy numbers. We therefore construct simple kinetic models of two sub-networks in the CME network to assess multi-protein assembly of the ARP2/3 complex and a minimal, nine-protein clathrin-coated vesicle forming module. We find that the observed, imperfectly balanced copy numbers are less effective than balanced copy numbers in producing fast and complete multi-protein assemblies. However, we speculate that strategic imbalance in the vesicle forming module

  7. Sequencing Chromosomal Abnormalities Reveals Neurodevelopmental Loci that Confer Risk across Diagnostic Boundaries

    DEFF Research Database (Denmark)

    Talkowski, Michael E.; Rosenfeld, Jill A.; Blumenthal, Ian

    2012-01-01

    Sequencing of balanced chromosomal abnormalities, combined with convergent genomic studies of gene expression, copy-number variation, and genome-wide association, identifies 22 new loci that contribute to autism and related neurodevelopmental disorders. These data support a polygenic risk model...

  8. Selective regain of egfr gene copies in CD44+/CD24-/low breast cancer cellular model MDA-MB-468

    International Nuclear Information System (INIS)

    Agelopoulos, Konstantin; Buerger, Horst; Brandt, Burkhard; Greve, Burkhard; Schmidt, Hartmut; Pospisil, Heike; Kurtz, Stefan; Bartkowiak, Kai; Andreas, Antje; Wieczorek, Marek; Korsching, Eberhard

    2010-01-01

    Increased transcription of oncogenes like the epidermal growth factor receptor (EGFR) is frequently caused by amplification of the whole gene or at least of regulatory sequences. Aim of this study was to pinpoint mechanistic parameters occurring during egfr copy number gains leading to a stable EGFR overexpression and high sensitivity to extracellular signalling. A deeper understanding of those marker events might improve early diagnosis of cancer in suspect lesions, early detection of cancer progression and the prediction of egfr targeted therapies. The basal-like/stemness type breast cancer cell line subpopulation MDA-MB-468 CD44 high /CD24 -/low , carrying high egfr amplifications, was chosen as a model system in this study. Subclones of the heterogeneous cell line expressing low and high EGF receptor densities were isolated by cell sorting. Genomic profiling was carried out for these by means of SNP array profiling, qPCR and FISH. Cell cycle analysis was performed using the BrdU quenching technique. Low and high EGFR expressing MDA-MB-468 CD44 + /CD24 -/low subpopulations separated by cell sorting showed intermediate and high copy numbers of egfr, respectively. However, during cell culture an increase solely for egfr gene copy numbers in the intermediate subpopulation occurred. This shift was based on the formation of new cells which regained egfr gene copies. By two parametric cell cycle analysis clonal effects mediated through growth advantage of cells bearing higher egfr gene copy numbers could most likely be excluded for being the driving force. Subsequently, the detection of a fragile site distal to the egfr gene, sustaining uncapped telomere-less chromosomal ends, the ladder-like structure of the intrachromosomal egfr amplification and a broader range of egfr copy numbers support the assumption that dynamic chromosomal rearrangements, like breakage-fusion-bridge-cycles other than proliferation drive the gain of egfr copies. Progressive genome modulation

  9. Genome-wide gene copy number and expression analysis of primary gastric tumors and gastric cancer cell lines

    International Nuclear Information System (INIS)

    Junnila, Siina; Kokkola, Arto; Karjalainen-Lindsberg, Marja-Liisa; Puolakkainen, Pauli; Monni, Outi

    2010-01-01

    Gastric cancer is one of the most common malignancies worldwide and the second most common cause of cancer related death. Gene copy number alterations play an important role in the development of gastric cancer and a change in gene copy number is one of the main mechanisms for a cancer cell to control the expression of potential oncogenes and tumor suppressor genes. To highlight genes of potential biological and clinical relevance in gastric cancer, we carried out a systematic array-based survey of gene expression and copy number levels in primary gastric tumors and gastric cancer cell lines and validated the results using an affinity capture based transcript analysis (TRAC assay) and real-time qRT-PCR. Integrated microarray analysis revealed altogether 256 genes that were located in recurrent regions of gains or losses and had at least a 2-fold copy number- associated change in their gene expression. The expression levels of 13 of these genes, ALPK2, ASAP1, CEACAM5, CYP3A4, ENAH, ERBB2, HHIPL2, LTB4R, MMP9, PERLD1, PNMT, PTPRA, and OSMR, were validated in a total of 118 gastric samples using either the qRT-PCR or TRAC assay. All of these 13 genes were differentially expressed between cancerous samples and nonmalignant tissues (p < 0.05) and the association between copy number and gene expression changes was validated for nine (69.2%) of these genes (p < 0.05). In conclusion, integrated gene expression and copy number microarray analysis highlighted genes that may be critically important for gastric carcinogenesis. TRAC and qRT-PCR analyses validated the microarray results and therefore the role of these genes as potential biomarkers for gastric cancer

  10. Soft-copy sonography: cost reduction sensitivity analysis in a pediatric hospital.

    Science.gov (United States)

    Don, S; Albertina, M J; Ammann, D

    1998-03-01

    Our objective was to determine whether interpreting sonograms of pediatric patients using soft-copy (computer workstation) instead of laser-printed film could reduce costs for a pediatric radiology department. We used theoretic models of growth to analyze costs. The costs of a sonographic picture archiving and communication system (three interface devices, two workstations, a network server, maintenance expenses, and storage media costs) were compared with the potential savings of eliminating film and increasing technologist efficiency or reducing the number of technologists. The model was based on historic trends and future capitation estimates that will reduce fee-for-service reimbursement. The effects of varying the study volume and reducing technologists' work hours were analyzed. By converting to soft-copy interpretation, we saved 6 min 32 sec per examination by eliminating film processing waiting time, thus reducing examination time from 30 min to 24 min. During an average day of 27 examinations, 176 min were saved. However, 33 min a day were spent retrieving prior studies from long-term storage; thus, 143 extra minutes a day were available for scanning. This improved efficiency could result in five more sonograms a day obtained by converting to soft-copy interpretation, using existing staff and equipment. Alternatively, five examinations a day would equate to one half of a full-time equivalent technologists position. Our analysis of costs considered that the hospital's anticipated growth of sonography and the depreciation of equipment during 5 years resulted in a savings of more than $606,000. Increasing the examinations by just 200 sonograms in the first year and no further growth resulted in a savings of more than $96,000. If the number of sonograms stayed constant, elimination of film printing alone resulted in a loss of approximately $157,000; reduction of one half of a full-time equivalent technologist's position would recuperate approximately $134

  11. Integrative analysis of copy number alteration and gene expression profiling in ovarian clear cell adenocarcinoma.

    Science.gov (United States)

    Sung, Chang Ohk; Choi, Chel Hun; Ko, Young-Hyeh; Ju, Hyunjeong; Choi, Yoon-La; Kim, Nyunsu; Kang, So Young; Ha, Sang Yun; Choi, Kyusam; Bae, Duk-Soo; Lee, Jeong-Won; Kim, Tae-Joong; Song, Sang Yong; Kim, Byoung-Gie

    2013-05-01

    Ovarian clear cell adenocarcinoma (Ov-CCA) is a distinctive subtype of ovarian epithelial carcinoma. In this study, we performed array comparative genomic hybridization (aCGH) and paired gene expression microarray of 19 fresh-frozen samples and conducted integrative analysis. For the copy number alterations, significantly amplified regions (false discovery rate [FDR] q genes demonstrating frequent copy number alterations (>25% of samples) that correlated with gene expression (FDR genes were mainly located on 8p11.21, 8p21.2-p21.3, 8q22.1, 8q24.3, 17q23.2-q23.3, 19p13.3, and 19p13.11. Among the regions, 8q24.3 was found to contain the most genes (30 of 94 genes) including PTK2. The 8q24.3 region was indicated as the most significant region, as supported by copy number, GISTIC, and integrative analysis. Pathway analysis using differentially expressed genes on 8q24.3 revealed several major nodes, including PTK2. In conclusion, we identified a set of 94 candidate genes with frequent copy number alterations that correlated with gene expression. Specific chromosomal alterations, such as the 8q24.3 gain containing PTK2, could be a therapeutic target in a subset of Ov-CCAs. Copyright © 2013. Published by Elsevier Inc.

  12. Simple and versatile molecular method of copy-number measurement using cloned competitors.

    Directory of Open Access Journals (Sweden)

    Hyun-Kyoung Kim

    Full Text Available Variations and alterations of copy numbers (CNVs and CNAs carry disease susceptibility and drug responsiveness implications. Although there are many molecular methods to measure copy numbers, sensitivity, reproducibility, cost, and time issues remain. In the present study, we were able to solve those problems utilizing our modified real competitive PCR method with cloned competitors (mrcPCR. First, the mrcPCR for ERBB2 copy number was established, and the results were comparable to current standard methods but with a shorter assay time and a lower cost. Second, the mrcPCR assays for 24 drug-target genes were established, and the results in a panel of NCI-60 cells were comparable to those from real-time PCR and microarray. Third, the mrcPCR results for FCGR3A and the FCGR3B CNVs were comparable to those by the paralog ratio test (PRT, but without PRT's limitations. These results suggest that mrcPCR is comparable to the currently available standard or the most sensitive methods. In addition, mrcPCR would be invaluable for measurement of CNVs in genes with variants of similar structures, because combination of the other methods is not necessary, along with its other advantages such as short assay time, small sample amount requirement, and applicability to all sequences and genes.

  13. Simultaneous Binding of Multiple EF-Tu Copies to Translating Ribosomes in Live Escherichia coli.

    Science.gov (United States)

    Mustafi, Mainak; Weisshaar, James C

    2018-01-16

    In bacteria, elongation factor Tu is a translational cofactor that forms ternary complexes with aminoacyl-tRNA (aa-tRNA) and GTP. Binding of a ternary complex to one of four flexible L7/L12 units on the ribosome tethers a charged tRNA in close proximity to the ribosomal A site. Two sequential tests for a match between the aa-tRNA anticodon and the current mRNA codon then follow. Because one elongation cycle can occur in as little as 50 ms and the vast majority of aa-tRNA copies are not cognate with the current mRNA codon, this testing must occur rapidly. We present a single-molecule localization and tracking study of fluorescently labeled EF-Tu in live Escherichia coli Imaging at 2 ms/frame distinguishes 60% slowly diffusing EF-Tu copies (assigned as transiently bound to translating ribosome) from 40% rapidly diffusing copies (assigned as a mixture of free ternary complexes and free EF-Tu). Combining these percentages with copy number estimates, we infer that the four L7/L12 sites are essentially saturated with ternary complexes in vivo. The results corroborate an earlier inference that all four sites can simultaneously tether ternary complexes near the A site, creating a high local concentration that may greatly enhance the rate of testing of aa-tRNAs. Our data and a combinatorial argument both suggest that the initial recognition test for a codon-anticodon match occurs in less than 1 to 2 ms per aa-tRNA copy. The results refute a recent study (A. Plochowietz, I. Farrell, Z. Smilansky, B. S. Cooperman, and A. N. Kapanidis, Nucleic Acids Res 45:926-937, 2016, https://doi.org/10.1093/nar/gkw787) of tRNA diffusion in E. coli that inferred that aa-tRNAs arrive at the ribosomal A site as bare monomers, not as ternary complexes. IMPORTANCE Ribosomes catalyze translation of the mRNA codon sequence into the corresponding sequence of amino acids within the nascent polypeptide chain. Polypeptide elongation can be as fast as 50 ms per added amino acid. Each amino acid

  14. 75 FR 74007 - Federal Aquatic Nuisance Species Research Risk Analysis Protocol

    Science.gov (United States)

    2010-11-30

    ... site, http://anstaskforce.gov/documents.php . To obtain a hard copy of the Protocol, see Document... aquatic species that are the target of this risk analysis. Language used in the NANPCA differentiates...: http://anstaskforce.gov/documents.php Write: Susan Pasko, National Oceanic and Atmospheric...

  15. 18 CFR 34.7 - Number of copies to be filed.

    Science.gov (United States)

    2010-04-01

    ..., § 34.7 was revised, effective at the time of the next e-filing release during the Commission's next fiscal year. For the convenience of the user, the revised text follows: § 34.7 Filing requirements. Each...) and (2) of this chapter. As a qualified document, no paper copy version of the filing is required...

  16. 9Å structure of the COPI coat reveals that the Arf1 GTPase occupies two contrasting molecular environments.

    Science.gov (United States)

    Dodonova, Svetlana O; Aderhold, Patrick; Kopp, Juergen; Ganeva, Iva; Röhling, Simone; Hagen, Wim J H; Sinning, Irmgard; Wieland, Felix; Briggs, John A G

    2017-06-16

    COPI coated vesicles mediate trafficking within the Golgi apparatus and between the Golgi and the endoplasmic reticulum. Assembly of a COPI coated vesicle is initiated by the small GTPase Arf1 that recruits the coatomer complex to the membrane, triggering polymerization and budding. The vesicle uncoats before fusion with a target membrane. Coat components are structurally conserved between COPI and clathrin/adaptor proteins. Using cryo-electron tomography and subtomogram averaging, we determined the structure of the COPI coat assembled on membranes in vitro at 9 Å resolution. We also obtained a 2.57 Å resolution crystal structure of βδ-COP. By combining these structures we built a molecular model of the coat. We additionally determined the coat structure in the presence of ArfGAP proteins that regulate coat dissociation. We found that Arf1 occupies contrasting molecular environments within the coat, leading us to hypothesize that some Arf1 molecules may regulate vesicle assembly while others regulate coat disassembly.

  17. Industrial Relevance of Chromosomal Copy Number Variation in Saccharomyces Yeasts.

    Science.gov (United States)

    Gorter de Vries, Arthur R; Pronk, Jack T; Daran, Jean-Marc G

    2017-06-01

    Chromosomal copy number variation (CCNV) plays a key role in evolution and health of eukaryotes. The unicellular yeast Saccharomyces cerevisiae is an important model for studying the generation, physiological impact, and evolutionary significance of CCNV. Fundamental studies of this yeast have contributed to an extensive set of methods for analyzing and introducing CCNV. Moreover, these studies provided insight into the balance between negative and positive impacts of CCNV in evolutionary contexts. A growing body of evidence indicates that CCNV not only frequently occurs in industrial strains of Saccharomyces yeasts but also is a key contributor to the diversity of industrially relevant traits. This notion is further supported by the frequent involvement of CCNV in industrially relevant traits acquired during evolutionary engineering. This review describes recent developments in genome sequencing and genome editing techniques and discusses how these offer opportunities to unravel contributions of CCNV in industrial Saccharomyce s strains as well as to rationally engineer yeast chromosomal copy numbers and karyotypes. Copyright © 2017 Gorter de Vries et al.

  18. High-Performance, Multi-Node File Copies and Checksums for Clustered File Systems

    Science.gov (United States)

    Kolano, Paul Z.; Ciotti, Robert B.

    2012-01-01

    Modern parallel file systems achieve high performance using a variety of techniques, such as striping files across multiple disks to increase aggregate I/O bandwidth and spreading disks across multiple servers to increase aggregate interconnect bandwidth. To achieve peak performance from such systems, it is typically necessary to utilize multiple concurrent readers/writers from multiple systems to overcome various singlesystem limitations, such as number of processors and network bandwidth. The standard cp and md5sum tools of GNU coreutils found on every modern Unix/Linux system, however, utilize a single execution thread on a single CPU core of a single system, and hence cannot take full advantage of the increased performance of clustered file systems. Mcp and msum are drop-in replacements for the standard cp and md5sum programs that utilize multiple types of parallelism and other optimizations to achieve maximum copy and checksum performance on clustered file systems. Multi-threading is used to ensure that nodes are kept as busy as possible. Read/write parallelism allows individual operations of a single copy to be overlapped using asynchronous I/O. Multinode cooperation allows different nodes to take part in the same copy/checksum. Split-file processing allows multiple threads to operate concurrently on the same file. Finally, hash trees allow inherently serial checksums to be performed in parallel. Mcp and msum provide significant performance improvements over standard cp and md5sum using multiple types of parallelism and other optimizations. The total speed-ups from all improvements are significant. Mcp improves cp performance over 27x, msum improves md5sum performance almost 19x, and the combination of mcp and msum improves verified copies via cp and md5sum by almost 22x. These improvements come in the form of drop-in replacements for cp and md5sum, so are easily used and are available for download as open source software at http://mutil.sourceforge.net.

  19. CARAT: A novel method for allelic detection of DNA copy number changes using high density oligonucleotide arrays

    Directory of Open Access Journals (Sweden)

    Ishikawa Shumpei

    2006-02-01

    Full Text Available Abstract Background DNA copy number alterations are one of the main characteristics of the cancer cell karyotype and can contribute to the complex phenotype of these cells. These alterations can lead to gains in cellular oncogenes as well as losses in tumor suppressor genes and can span small intervals as well as involve entire chromosomes. The ability to accurately detect these changes is central to understanding how they impact the biology of the cell. Results We describe a novel algorithm called CARAT (Copy Number Analysis with Regression And Tree that uses probe intensity information to infer copy number in an allele-specific manner from high density DNA oligonuceotide arrays designed to genotype over 100, 000 SNPs. Total and allele-specific copy number estimations using CARAT are independently evaluated for a subset of SNPs using quantitative PCR and allelic TaqMan reactions with several human breast cancer cell lines. The sensitivity and specificity of the algorithm are characterized using DNA samples containing differing numbers of X chromosomes as well as a test set of normal individuals. Results from the algorithm show a high degree of agreement with results from independent verification methods. Conclusion Overall, CARAT automatically detects regions with copy number variations and assigns a significance score to each alteration as well as generating allele-specific output. When coupled with SNP genotype calls from the same array, CARAT provides additional detail into the structure of genome wide alterations that can contribute to allelic imbalance.

  20. Analysis of Intellectual Disability Copy Number Variants for Association With Schizophrenia.

    Science.gov (United States)

    Rees, Elliott; Kendall, Kimberley; Pardiñas, Antonio F; Legge, Sophie E; Pocklington, Andrew; Escott-Price, Valentina; MacCabe, James H; Collier, David A; Holmans, Peter; O'Donovan, Michael C; Owen, Michael J; Walters, James T R; Kirov, George

    2016-09-01

    At least 11 rare copy number variants (CNVs) have been shown to be major risk factors for schizophrenia (SZ). These CNVs also increase the risk for other neurodevelopmental disorders, such as intellectual disability. It is possible that additional intellectual disability-associated CNVs increase the risk for SZ but have not yet been implicated in SZ because of previous studies being underpowered. To examine whether additional CNVs implicated in intellectual disability represent novel SZ risk loci. We used single-nucleotide polymorphism (SNP) array data to evaluate a set of 51 CNVs implicated in intellectual disability (excluding the known SZ loci) in a large data set of patients with SZ and healthy persons serving as controls recruited in a variety of settings. We analyzed a new sample of 6934 individuals with SZ and 8751 controls and combined those data with previously published large data sets for a total of 20 403 cases of SZ and 26 628 controls. Burden analysis of CNVs implicated in intellectual disability (excluding known SZ CNVs) for association with SZ. Association of individual intellectual disability CNV loci with SZ. Of data on the 20 403 cases (6151 [30.15%] female) and 26 628 controls (14 252 [53.52%] female), 51 intellectual disability CNVs were analyzed. Collectively, intellectual disability CNVs were significantly enriched for SZ (P = 1.0 × 10-6; odds ratio [OR], 1.9 [95% CI, 1.46-2.49]). Of the 51 CNVs tested, 19 (37%) were more common in SZ cases; only 4 (8%) were more common in controls (no observations were made for the remaining 28 [55%] loci). One novel locus, deletion at 16p12.1, was significantly associated with SZ after correction for multiple testing (rate in SZ, 33 [0.16%]; rate in controls, 12 [0.05%]; corrected P = .017; OR, 3.3; 95% CI, 1.61-7.05), and 2 loci reached nominal levels of significance (deletions at 2q11.2: 6 [0.03%] vs 1 [0.004%]; OR, 9.3; 95% CI, 1.03-447.76; corrected P > .99; and duplications

  1. Cognitive predictors of copying and drawing from memory of the Rey-Osterrieth complex figure in 7- to 10-year-old children.

    Science.gov (United States)

    Senese, Vincenzo Paolo; De Lucia, Natascia; Conson, Massimiliano

    2015-01-01

    Cognitive models of drawing are mainly based on assessment of copying performance of adults, whereas only a few studies have verified these models in young children. Moreover, developmental investigations have only rarely performed a systematic examination of the contribution of perceptual and representational visuo-spatial processes to copying and drawing from memory. In this study we investigated the role of visual perception and mental representation in both copying and drawing from memory skills in a sample of 227 typically developing children (53% females) aged 7-10 years. Participants underwent a neuropsychological assessment and the Rey-Osterrieth Complex Figure (ROCF). The fit and invariance of the predictive model considering visuo-spatial abilities, working memory, and executive functions were tested by means of hierarchical regressions and path analysis. Results showed that, in a gender invariant way, visual perception abilities and spatial mental representation had a direct effect on copying performance, whereas copying performance was the only specific predictor for drawing from memory. These effects were independent from age and socioeconomic status, and showed that cognitive models of drawing built up for adults could be considered for predicting copying and drawing from memory in children.

  2. Transcriptional analysis of bla NDM-1 and copy number alteration under carbapenem stress

    Directory of Open Access Journals (Sweden)

    Deepjyoti Paul

    2017-02-01

    Full Text Available Abstract Background New Delhi metallo beta-lactamase is known to compromise carbapenem therapy and leading to treatment failure. However, their response to carbapenem stress is not clearly known. Here, we have investigated the transcriptional response of bla NDM-1 and plasmid copy number alteration under carbapenem exposure. Methods Three bla NDM-1 harboring plasmids representing three incompatibility types (IncFIC, IncA/C and IncK were inoculated in LB broth with and without imipenem, meropenem and ertapenem. After each 1 h total RNA was isolated, immediately reverse transcribed into cDNA and quantitative real time PCR was used for transcriptional expression of bla NDM-1. Horizontal transferability and stability of the plasmids encoding bla NDM-1 were also determined. Changes in copy number of bla NDM-1 harboring plasmids under the exposure of different carbapenems were determined by real time PCR. Clonal relatedness among the isolates was determined by pulsed field gel electrophoresis. Results Under carbapenem stress over an interval of time there was a sharp variation in the transcriptional expression of bla NDM-1 although it did not follow a specific pattern. All bla NDM-1 carrying plasmids were transferable by conjugation. These plasmids were highly stable and complete loss was observed between 92nd to 96th serial passages when antibiotic pressure was withdrawn. High copy number of bla NDM-1 was found for IncF type plasmids compared to the other replicon types. Conclusion This study suggests that the single dose of carbapenem pressure does not significantly influence the expression of bla NDM-1 and also focus on the stability of this gene as well as the change in copy number with respect to the incompatible type of plasmid harboring resistance determinant.

  3. RUBIC identifies driver genes by detecting recurrent DNA copy number breaks

    NARCIS (Netherlands)

    van Dyk, H.O.; Hoogstraat, M; ten Hoeve, J; Reinders, M.J.T.; Wessels, L.F.A.

    2016-01-01

    The frequent recurrence of copy number aberrations across tumour samples is a reliable hallmark of certain cancer driver genes. However, state-of-the-art algorithms for detecting recurrent aberrations fail to detect several known drivers. In this study, we propose RUBIC, an approach that detects

  4. Advertisement for the position of “Copy Editor cum Proof Reader ...

    Indian Academy of Sciences (India)

    user

    Advertisement for the position of “Copy Editor cum. Proof Reader”. Indian Academy of Sciences (IASc), an institution under the. Department of Science & Technology, Government of India publishes scholarly journals, thematic books and other publications. The. Academy currently publishes 10 journals in various disciplines ...

  5. Effective Normalization for Copy Number Variation Detection from Whole Genome Sequencing

    NARCIS (Netherlands)

    Janevski, A.; Varadan, V.; Kamalakaran, S.; Banerjee, N.; Dimitrova, D.

    2012-01-01

    Background Whole genome sequencing enables a high resolution view ofthe human genome and provides unique insights into genome structureat an unprecedented scale. There have been a number of tools to infer copy number variation in the genome. These tools while validatedalso include a number of

  6. Role of Mitochondrial DNA Copy Number Alteration in Human Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Chen-Sung Lin

    2016-05-01

    Full Text Available We investigated the role of mitochondrial DNA (mtDNA copy number alteration in human renal cell carcinoma (RCC. The mtDNA copy numbers of paired cancer and non-cancer parts from five resected RCC kidneys after radical nephrectomy were determined by quantitative polymerase chain reaction (Q-PCR. An RCC cell line, 786-O, was infected by lentiviral particles to knock down mitochondrial transcriptional factor A (TFAM. Null target (NT and TFAM-knockdown (TFAM-KD represented the control and knockdown 786-O clones, respectively. Protein or mRNA expression levels of TFAM; mtDNA-encoded NADH dehydrogenase subunit 1 (ND1, ND6 and cytochrome c oxidase subunit 2 (COX-2; nuclear DNA (nDNA-encoded succinate dehydrogenase subunit A (SDHA; v-akt murine thymoma viral oncogene homolog 1 gene (AKT-encoded AKT and v-myc myelocytomatosis viral oncogene homolog gene (c-MYC-encoded MYC; glycolytic enzymes including hexokinase II (HK-II, glucose 6-phosphate isomerase (GPI, phosphofructokinase (PFK, and lactate dehydrogenase subunit A (LDHA; and hypoxia-inducible factors the HIF-1α and HIF-2α, pyruvate dehydrogenase kinase 1 (PDK1, and pyruvate dehydrogenase E1 component α subunit (PDHA1 were analyzed by Western blot or Q-PCR. Bioenergetic parameters of cellular metabolism, basal mitochondrial oxygen consumption rate (mOCRB and basal extracellular acidification rate (ECARB, were measured by a Seahorse XFe-24 analyzer. Cell invasiveness was evaluated by a trans-well migration assay and vimentin expression. Doxorubicin was used as a chemotherapeutic agent. The results showed a decrease of mtDNA copy numbers in resected RCC tissues (p = 0.043. The TFAM-KD clone expressed lower mtDNA copy number (p = 0.034, lower mRNA levels of TFAM (p = 0.008, ND1 (p = 0.007, and ND6 (p = 0.017, and lower protein levels of TFAM and COX-2 than did the NT clone. By contrast, the protein levels of HIF-2α, HK-II, PFK, LDHA, AKT, MYC and vimentin; trans-well migration activity (p = 0

  7. Copy number variants in extended autism spectrum disorder families reveal candidates potentially involved in autism risk.

    Directory of Open Access Journals (Sweden)

    Daria Salyakina

    Full Text Available Copy number variations (CNVs are a major cause of genetic disruption in the human genome with far more nucleotides being altered by duplications and deletions than by single nucleotide polymorphisms (SNPs. In the multifaceted etiology of autism spectrum disorders (ASDs, CNVs appear to contribute significantly to our understanding of the pathogenesis of this complex disease. A unique resource of 42 extended ASD families was genotyped for over 1 million SNPs to detect CNVs that may contribute to ASD susceptibility. Each family has at least one avuncular or cousin pair with ASD. Families were then evaluated for co-segregation of CNVs in ASD patients. We identified a total of five deletions and seven duplications in eleven families that co-segregated with ASD. Two of the CNVs overlap with regions on 7p21.3 and 15q24.1 that have been previously reported in ASD individuals and two additional CNVs on 3p26.3 and 12q24.32 occur near regions associated with schizophrenia. These findings provide further evidence for the involvement of ICA1 and NXPH1 on 7p21.3 in ASD susceptibility and highlight novel ASD candidates, including CHL1, FGFBP3 and POUF41. These studies highlight the power of using extended families for gene discovery in traits with a complex etiology.

  8. Lviv Copy of Missing Painting by Iacomo Negretti Called Palma II Vechio

    Directory of Open Access Journals (Sweden)

    Marta Giżyńska-Matecka

    2004-12-01

    Full Text Available For over a hundred years in a private collection in Cracow there has been a distemper painting on parchment with an image of the Holy Family. Dark letters show through the faded front as the back was originally a document written in the Roman type. When the document expired, the other side of the parchment was used for a painting and the format was moved by 90 degrees. The document is a decorated copy of a church fair privilege given by pope Pius VI to the Bemardine Nuns in Lviv in 1777. At the bottom there is an authentication issued in the Obroszyn castle by a Lviv archbishop Waclaw Hieronim Sierakowski. Thus, both the copy and the authentication were issued jointly in Lviv Archbishop Curia in Lviv.

  9. Dynamic Copy Number Evolution of X- and Y-Linked Ampliconic Genes in Human Populations

    DEFF Research Database (Denmark)

    Lucotte, Elise A; Skov, Laurits; Jensen, Jacob Malte

    2018-01-01

    we explore the evolution of human X- and Y-linked ampliconic genes by investigating copy number variation (CNV) and coding variation between populations using the Simons Genome Diversity Project. We develop a method to assess CNVs using the read-depth on modified X and Y chromosome targets containing...... related Y haplogroups, that diversified less than 50,000 years ago. Moreover, X and Y-linked ampliconic genes seem to have a faster amplification dynamic than autosomal multicopy genes. Looking at expression data from another study, we also find that XY-linked ampliconic genes with extensive copy number...

  10. [Progress in transgenic fish techniques and application].

    Science.gov (United States)

    Ye, Xing; Tian, Yuan-Yuan; Gao, Feng-Ying

    2011-05-01

    Transgenic technique provides a new way for fish breeding. Stable lines of growth hormone gene transfer carps, salmon and tilapia, as well as fluorescence protein gene transfer zebra fish and white cloud mountain minnow have been produced. The fast growth characteristic of GH gene transgenic fish will be of great importance to promote aquaculture production and economic efficiency. This paper summarized the progress in transgenic fish research and ecological assessments. Microinjection is still the most common used method, but often resulted in multi-site and multi-copies integration. Co-injection of transposon or meganuclease will greatly improve the efficiency of gene transfer and integration. "All fish" gene or "auto gene" should be considered to produce transgenic fish in order to eliminate misgiving on food safety and to benefit expression of the transferred gene. Environmental risk is the biggest obstacle for transgenic fish to be commercially applied. Data indicates that transgenic fish have inferior fitness compared with the traditional domestic fish. However, be-cause of the genotype-by-environment effects, it is difficult to extrapolate simple phenotypes to the complex ecological interactions that occur in nature based on the ecological consequences of the transgenic fish determined in the laboratory. It is critical to establish highly naturalized environments for acquiring reliable data that can be used to evaluate the environ-mental risk. Efficacious physical and biological containment strategies remain to be crucial approaches to ensure the safe application of transgenic fish technology.

  11. Integrative analysis of genome-wide gene copy number changes and gene expression in non-small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Verena Jabs

    Full Text Available Non-small cell lung cancer (NSCLC represents a genomically unstable cancer type with extensive copy number aberrations. The relationship of gene copy number alterations and subsequent mRNA levels has only fragmentarily been described. The aim of this study was to conduct a genome-wide analysis of gene copy number gains and corresponding gene expression levels in a clinically well annotated NSCLC patient cohort (n = 190 and their association with survival. While more than half of all analyzed gene copy number-gene expression pairs showed statistically significant correlations (10,296 of 18,756 genes, high correlations, with a correlation coefficient >0.7, were obtained only in a subset of 301 genes (1.6%, including KRAS, EGFR and MDM2. Higher correlation coefficients were associated with higher copy number and expression levels. Strong correlations were frequently based on few tumors with high copy number gains and correspondingly increased mRNA expression. Among the highly correlating genes, GO groups associated with posttranslational protein modifications were particularly frequent, including ubiquitination and neddylation. In a meta-analysis including 1,779 patients we found that survival associated genes were overrepresented among highly correlating genes (61 of the 301 highly correlating genes, FDR adjusted p<0.05. Among them are the chaperone CCT2, the core complex protein NUP107 and the ubiquitination and neddylation associated protein CAND1. In conclusion, in a comprehensive analysis we described a distinct set of highly correlating genes. These genes were found to be overrepresented among survival-associated genes based on gene expression in a large collection of publicly available datasets.

  12. Penicillin production in industrial strain Penicillium chrysogenum P2niaD18 is not dependent on the copy number of biosynthesis genes.

    Science.gov (United States)

    Ziemons, Sandra; Koutsantas, Katerina; Becker, Kordula; Dahlmann, Tim; Kück, Ulrich

    2017-02-16

    Multi-copy gene integration into microbial genomes is a conventional tool for obtaining improved gene expression. For Penicillium chrysogenum, the fungal producer of the beta-lactam antibiotic penicillin, many production strains carry multiple copies of the penicillin biosynthesis gene cluster. This discovery led to the generally accepted view that high penicillin titers are the result of multiple copies of penicillin genes. Here we investigated strain P2niaD18, a production line that carries only two copies of the penicillin gene cluster. We performed pulsed-field gel electrophoresis (PFGE), quantitative qRT-PCR, and penicillin bioassays to investigate production, deletion and overexpression strains generated in the P. chrysogenum P2niaD18 background, in order to determine the copy number of the penicillin biosynthesis gene cluster, and study the expression of one penicillin biosynthesis gene, and the penicillin titer. Analysis of production and recombinant strain showed that the enhanced penicillin titer did not depend on the copy number of the penicillin gene cluster. Our assumption was strengthened by results with a penicillin null strain lacking pcbC encoding isopenicillin N synthase. Reintroduction of one or two copies of the cluster into the pcbC deletion strain restored transcriptional high expression of the pcbC gene, but recombinant strains showed no significantly different penicillin titer compared to parental strains. Here we present a molecular genetic analysis of production and recombinant strains in the P2niaD18 background carrying different copy numbers of the penicillin biosynthesis gene cluster. Our analysis shows that the enhanced penicillin titer does not strictly depend on the copy number of the cluster. Based on these overall findings, we hypothesize that instead, complex regulatory mechanisms are prominently implicated in increased penicillin biosynthesis in production strains.

  13. Copy Number Variations in Candidate Genes and Intergenic Regions Affect Body Mass Index and Abdominal Obesity in Mexican Children

    Science.gov (United States)

    Burguete-García, Ana Isabel; Bonnefond, Amélie; Peralta-Romero, Jesús; Froguel, Philippe

    2017-01-01

    Introduction. Increase in body weight is a gradual process that usually begins in childhood and in adolescence as a result of multiple interactions among environmental and genetic factors. This study aimed to analyze the relationship between copy number variants (CNVs) in five genes and four intergenic regions with obesity in Mexican children. Methods. We studied 1423 children aged 6–12 years. Anthropometric measurements and blood levels of biochemical parameters were obtained. Identification of CNVs was performed by real-time PCR. The effect of CNVs on obesity or body composition was assessed using regression models adjusted for age, gender, and family history of obesity. Results. Gains in copy numbers of LEPR and NEGR1 were associated with decreased body mass index (BMI), waist circumference (WC), and risk of abdominal obesity, whereas gain in ARHGEF4 and CPXCR1 and the intergenic regions 12q15c, 15q21.1a, and 22q11.21d and losses in INS were associated with increased BMI and WC. Conclusion. Our results indicate a possible contribution of CNVs in LEPR, NEGR1, ARHGEF4, and CPXCR1 and the intergenic regions 12q15c, 15q21.1a, and 22q11.21d to the development of obesity, particularly abdominal obesity in Mexican children. PMID:28428959

  14. A Comparison of Math Cover, Copy, Compare Intervention Procedures for Children with Autism Spectrum Disorder.

    Science.gov (United States)

    Morton, Reeva C; Gadke, Daniel L

    2018-03-01

    Cover, Copy, Compare (CCC) and Copy, Cover, Compare (MCCC) procedures are effective interventions for improving math fluency. However, there is a gap in literature exploring the use of these interventions for children with autism spectrum disorders (ASD). The purpose of the current study was to compare the use of CCC and MCCC for children with ASD using a multi-component single-case experimental design. The results showed no notable difference between the interventions. Implications and limitations, particularly surrounding experimental control, are discussed in detail.

  15. Copy Chic: Status Representation and Intellectual Property Rights in Contemporary Fashion

    DEFF Research Database (Denmark)

    Mackinney-Valentin, Maria; Teilmann-Lock, Stina

    2014-01-01

    . And the luxury fashion industry has historically benefited from mass-market as a way of stimulating consumers’ appetite for innovation. The article explores the presence of “copy chic” in luxury fashion as an ambiguous celebration of the conspicuously inauthentic through a study of luxury version...

  16. Detection and localization of copy-paste forgeries in digital videos.

    Science.gov (United States)

    Singh, Raahat Devender; Aggarwal, Naveen

    2017-12-01

    Amidst the continual march of technology, we find ourselves relying on digital videos to proffer visual evidence in several highly sensitive areas such as journalism, politics, civil and criminal litigation, and military and intelligence operations. However, despite being an indispensable source of information with high evidentiary value, digital videos are also extremely vulnerable to conscious manipulations. Therefore, in a situation where dependence on video evidence is unavoidable, it becomes crucial to authenticate the contents of this evidence before accepting them as an accurate depiction of reality. Digital videos can suffer from several kinds of manipulations, but perhaps, one of the most consequential forgeries is copy-paste forgery, which involves insertion/removal of objects into/from video frames. Copy-paste forgeries alter the information presented by the video scene, which has a direct effect on our basic understanding of what that scene represents, and so, from a forensic standpoint, the challenge of detecting such forgeries is especially significant. In this paper, we propose a sensor pattern noise based copy-paste detection scheme, which is an improved and forensically stronger version of an existing noise-residue based technique. We also study a demosaicing artifact based image forensic scheme to estimate the extent of its viability in the domain of video forensics. Furthermore, we suggest a simplistic clustering technique for the detection of copy-paste forgeries, and determine if it possess the capabilities desired of a viable and efficacious video forensic scheme. Finally, we validate these schemes on a set of realistically tampered MJPEG, MPEG-2, MPEG-4, and H.264/AVC encoded videos in a diverse experimental set-up by varying the strength of post-production re-compressions and transcodings, bitrates, and sizes of the tampered regions. Such an experimental set-up is representative of a neutral testing platform and simulates a real

  17. COPI: transgressão e escrita transformista

    OpenAIRE

    Teixeira, Renata Pimentel

    2007-01-01

    Copi é o pseudônimo sob o qual foi assinada a obra de Raul Damonte Botana, nascido em Buenos Aires, em 1939, e morto em Paris (de Aids), em 1987. Egresso de uma família vinculada à cultura e à política (neto de Natálio Botana, fundador do diário Crítica), que se opôs à ditadura peronista, por isso acabou por exilar-se no Uruguai e, depois, em Paris; onde se instalou definitivamente, em 1962. Toda sua obra é marcada por humor e grande violência transgressora, além de uma crítica...

  18. Copy number variation is a fundamental aspect of the placental genome.

    Directory of Open Access Journals (Sweden)

    Roberta L Hannibal

    2014-05-01

    Full Text Available Discovery of lineage-specific somatic copy number variation (CNV in mammals has led to debate over whether CNVs are mutations that propagate disease or whether they are a normal, and even essential, aspect of cell biology. We show that 1,000 N polyploid trophoblast giant cells (TGCs of the mouse placenta contain 47 regions, totaling 138 Megabases, where genomic copies are underrepresented (UR. UR domains originate from a subset of late-replicating heterochromatic regions containing gene deserts and genes involved in cell adhesion and neurogenesis. While lineage-specific CNVs have been identified in mammalian cells, classically in the immune system where V(DJ recombination occurs, we demonstrate that CNVs form during gestation in the placenta by an underreplication mechanism, not by recombination nor deletion. Our results reveal that large scale CNVs are a normal feature of the mammalian placental genome, which are regulated systematically during embryogenesis and are propagated by a mechanism of underreplication.

  19. RNA-sequencing and pathway analysis reveal alteration of hepatic steroid biosynthesis and retinol metabolism by tributyltin exposure in male rare minnow (Gobiocypris rarus).

    Science.gov (United States)

    Zhang, Jiliang; Zhang, Chunnuan; Sun, Ping; Huang, Maoxian; Fan, Mingzhen; Liu, Min

    2017-07-01

    Tributyltin (TBT) is widely spread in aquatic ecosystems. Although adverse effects of TBT on reproduction and lipogenesis are observed in fishes, the underlying mechanisms, especially in livers, are still scarce and inconclusive. Thus, RNA-sequencing runs were performed on the hepatic libraries of adult male rare minnow (Gobiocypris rarus) after TBT exposure for 60d. After differentially expressed genes were identified, enrichment analysis and validation by quantitative real-time PCR were conducted. The results showed that TBT up-regulated the profile of hepatic genes in the steroid biosynthesis pathway and down-regulated the profile of hepatic genes in the retinol metabolism pathway. In the hepatic steroid biosynthesis pathway, TBT might induce biosynthesis of cholesterol, which could affect the bioavailability of steroid hormones. More important, 3beta-hydroxysteroid 3-dehydrogenase, a key enzyme in the biosynthesis of all active steroid hormones, was up-regulated by TBT exposure. In the hepatic retinol metabolism pathway, TBT impaired retinoic acid homeostasis which plays essential roles in both reproduction and lipogenesis. The results of two pathways offered new mechanisms underlying the toxicology of TBT and represented a starting point from which detailed mechanistic links should be explored. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Specific functions of the Rep and Rep' proteins of porcine circovirus during copy-release and rolling-circle DNA replication

    Science.gov (United States)

    The roles of two porcine circovirus replication initiator proteins, Rep and Rep', in generating copy-release and rolling-circle DNA replication intermediates were determined. Rep uses the supercoiled closed-circular genome (ccc) to initiate leading-strand synthesis (identical to copy-release replica...

  1. The potential role for use of mitochondrial DNA copy number as predictive biomarker in presbycusis

    Directory of Open Access Journals (Sweden)

    Falah M

    2016-10-01

    Full Text Available Masoumeh Falah,1,2 Massoud Houshmand,3 Mohammad Najafi,2 Maryam Balali,1 Saeid Mahmoudian,1 Alimohamad Asghari,4 Hessamaldin Emamdjomeh,1 Mohammad Farhadi1 1ENT and Head & Neck Research Center and Department, Iran University of Medical Sciences, Tehran, Iran; 2Cellular and Molecular Research Center, Biochemistry Department, Iran University of Medical Sciences, Tehran, Iran; 3Department of Medical Genetics, National Institute for Genetic Engineering and Biotechnology, Tehran, Iran; 4Skull base research center, Iran University of Medical Sciences, Tehran, Iran Objectives: Age-related hearing impairment, or presbycusis, is the most common communication disorder and neurodegenerative disease in the elderly. Its prevalence is expected to increase, due to the trend of growth of the elderly population. The current diagnostic test for detection of presbycusis is implemented after there has been a change in hearing sensitivity. Identification of a pre-diagnostic biomarker would raise the possibility of preserving hearing sensitivity before damage occurs. Mitochondrial dysfunction, including the production of reactive oxygen species and induction of expression of apoptotic genes, participates in the progression of presbycusis. Mitochondrial DNA sequence variation has a critical role in presbycusis. However, the nature of the relationship between mitochondrial DNA copy number, an important biomarker in many other diseases, and presbycusis is undetermined.Methods: Fifty-four subjects with presbycusis and 29 healthy controls were selected after ear, nose, throat examination and pure-tone audiometry. DNA was extracted from peripheral blood samples. The copy number of mitochondrial DNA relative to the nuclear genome was measured by quantitative real-time polymerase chain reaction.Results: Subjects with presbycusis had a lower median mitochondrial DNA copy number than healthy subjects and the difference was statistically significant (P=0.007. Mitochondrial DNA

  2. 14 CFR 221.550 - Copies of tariffs made from filer's printer(s) located in Department's public reference room.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Copies of tariffs made from filer's printer... Electronically Filed Tariffs § 221.550 Copies of tariffs made from filer's printer(s) located in Department's... obtained by any user at Departmental Headquarters from the printer or printers placed in Tariff Public...

  3. A large-scale survey of genetic copy number variations among Han Chinese residing in Taiwan

    Directory of Open Access Journals (Sweden)

    Wu Jer-Yuarn

    2008-12-01

    Full Text Available Abstract Background Copy number variations (CNVs have recently been recognized as important structural variations in the human genome. CNVs can affect gene expression and thus may contribute to phenotypic differences. The copy number inferring tool (CNIT is an effective hidden Markov model-based algorithm for estimating allele-specific copy number and predicting chromosomal alterations from single nucleotide polymorphism microarrays. The CNIT algorithm, which was constructed using data from 270 HapMap multi-ethnic individuals, was applied to identify CNVs from 300 unrelated Han Chinese individuals in Taiwan. Results Using stringent selection criteria, 230 regions with variable copy numbers were identified in the Han Chinese population; 133 (57.83% had been reported previously, 64 displayed greater than 1% CNV allele frequency. The average size of the CNV regions was 322 kb (ranging from 1.48 kb to 5.68 Mb and covered a total of 2.47% of the human genome. A total of 196 of the CNV regions were simple deletions and 27 were simple amplifications. There were 449 genes and 5 microRNAs within these CNV regions; some of these genes are known to be associated with diseases. Conclusion The identified CNVs are characteristic of the Han Chinese population and should be considered when genetic studies are conducted. The CNV distribution in the human genome is still poorly characterized, and there is much diversity among different ethnic populations.

  4. Probabilistic deletion of copies of linearly independent quantum states

    International Nuclear Information System (INIS)

    Feng Jian; Gao Yunfeng; Wang Jisuo; Zhan Mingsheng

    2002-01-01

    We show that each of two copies of the nonorthogonal states randomly selected from a certain set S can be probabilistically deleted by a general unitary-reduction operation if and only if the states are linearly independent. We derive a tight bound on the best possible deleting efficiencies. These results for 2→1 probabilistic deleting are also generalized into the case of N→M deleting (N,M positive integers and N>M)

  5. Comparing Android Applications to Find Copying

    Directory of Open Access Journals (Sweden)

    Larry Melling

    2012-03-01

    Full Text Available The Android smartphone operating system includes a Java mobile development platform that provides for rapid development and deployment of a wide variety of applications. The open nature of the platform means that reverse engineering of applications is relatively easy, and many developers are concerned as applications similar to their own show up in the Android marketplace and want to know if these applications are pirated. Fortunately, the same characteristics that make an Android application easy to reverse engineer and copy also provide opportunities for Android developers to compare downloaded applications to their own. This paper describes the process for comparing a developer’s application with a downloaded application and defines an identifiability metric to quantify the degree to which an application can be identified by its bytecode.

  6. Tumor transcriptome sequencing reveals allelic expression imbalances associated with copy number alterations.

    Directory of Open Access Journals (Sweden)

    Brian B Tuch

    Full Text Available Due to growing throughput and shrinking cost, massively parallel sequencing is rapidly becoming an attractive alternative to microarrays for the genome-wide study of gene expression and copy number alterations in primary tumors. The sequencing of transcripts (RNA-Seq should offer several advantages over microarray-based methods, including the ability to detect somatic mutations and accurately measure allele-specific expression. To investigate these advantages we have applied a novel, strand-specific RNA-Seq method to tumors and matched normal tissue from three patients with oral squamous cell carcinomas. Additionally, to better understand the genomic determinants of the gene expression changes observed, we have sequenced the tumor and normal genomes of one of these patients. We demonstrate here that our RNA-Seq method accurately measures allelic imbalance and that measurement on the genome-wide scale yields novel insights into cancer etiology. As expected, the set of genes differentially expressed in the tumors is enriched for cell adhesion and differentiation functions, but, unexpectedly, the set of allelically imbalanced genes is also enriched for these same cancer-related functions. By comparing the transcriptomic perturbations observed in one patient to his underlying normal and tumor genomes, we find that allelic imbalance in the tumor is associated with copy number mutations and that copy number mutations are, in turn, strongly associated with changes in transcript abundance. These results support a model in which allele-specific deletions and duplications drive allele-specific changes in gene expression in the developing tumor.

  7. A study of the bending resistance of implant-supported reinforced alumina and machined zirconia abutments and copies.

    Science.gov (United States)

    Sundh, Anders; Sjögren, Göran

    2008-05-01

    The purpose of the present study was to evaluate the bending resistance of implant-supported CAD/CAM-processed restorations made out of zirconia or manually shaped made out of reinforced alumina. Units of abutments and copies made of (i) a prefabricated hot isostatic pressed (HIPed) yttrium oxide partially-stabilized zirconia (Y-TZP) (Denzir), (ii) a prefabricated densely-sintered magnesia partially stabilized zirconia (Mg-PSZ) (Denzir-M) or, copies made of (iii) a prefabricated partially-sintered, porous reinforced alumina ceramic (RN synOcta-In-Ceram) were subjected to static loading perpendicularly at the long axis. The abutments were attached to either stainless steel analogs or titanium implant fixtures. The Y-TZP and Mg-PSZ copies were bonded onto the ceramic abutments with a dual-cured resin composite (Rely-X Unicem). Units of titanium abutment attached to a titanium implant fixtures were used as reference. The units comprising Denzir abutments as delivered (pstainless steel analogs exhibited significantly higher bending resistance than the control. The heat-treated Denzir copies bonded to the heat-treated Denzir M abutments attached to titanium implant fixtures and the In-Ceram specimens attached to stainless steel analogs showed significantly (pstainless steel analogs. No statistically significant (p>0.05) differences were seen among the other groups studied. All the ceramic abutments and copies exhibited values that were equal or superior to that of the control and exceeded the reported value, up to 300 N, for maximum incisal bite forces. To assess the clinical behavior long-term clinical studies should be conducted.

  8. New cytogenetically visible copy number variant in region 8q21.2

    Directory of Open Access Journals (Sweden)

    Ewers Elisabeth

    2011-01-01

    Full Text Available Abstract Background Cytogenetically visible unbalanced chromosomal abnormalities (UBCA, reported for >50 euchromatic regions of almost all human autosomes, are comprised of a few megabases of DNA, and carriers are in many cases clinically healthy. It may be speculated, that some of the UBCA may be similar or identical to copy number variants (CNV of the human genome. Results Here we report on a yet unreported cytogenetically visible copy number variant (CNV in the long arm of chromosome 8, region 8q21.2, detected in three unrelated clinically healthy carriers. Conclusion The first description of a cytogenetically visible CNV/UBCA in 8q21.2 shows that banding cytogenetics is far from being outdated. It is a cost efficient, up-to-date method for a single cell specific overview on the whole genome, still prepared to deliver unexpected findings.

  9. Detection of copy number variations and their effects in Chinese bulls

    KAUST Repository

    Zhang, Liangzhi

    2014-06-17

    Background: Copy number variations (CNVs) are a main source of genomic structural variations underlying animal evolution and production traits. Here, with one pure-blooded Angus bull as reference, we describe a genome-wide analysis of CNVs based on comparative genomic hybridization arrays in 29 Chinese domesticated bulls and examined their effects on gene expression and cattle growth traits.Results: We identified 486 copy number variable regions (CNVRs), covering 2.45% of the bovine genome, in 24 taurine (Bos taurus), together with 161 ones in 2 yaks (Bos grunniens) and 163 ones in 3 buffaloes (Bubalus bubalis). Totally, we discovered 605 integrated CNVRs, with more " loss" events than both " gain" and " both" ones, and clearly clustered them into three cattle groups. Interestingly, we confirmed their uneven distributions across chromosomes, and the differences of mitochondrion DNA copy number (gain: taurine, loss: yak & buffalo). Furthermore, we confirmed approximately 41.8% (253/605) and 70.6% (427/605) CNVRs span cattle genes and quantitative trait loci (QTLs), respectively. Finally, we confirmed 6 CNVRs in 9 chosen ones by using quantitative PCR, and further demonstrated that CNVR22 had significantly negative effects on expression of PLA2G2D gene, and both CNVR22 and CNVR310 were associated with body measurements in Chinese cattle, suggesting their key effects on gene expression and cattle traits.Conclusions: The results advanced our understanding of CNV as an important genomic structural variation in taurine, yak and buffalo. This study provides a highly valuable resource for Chinese cattle\\'s evolution and breeding researches. 2014 Zhang et al.; licensee BioMed Central Ltd.

  10. Dynamic changes in functional gene copy numbers and microbial communities during degradation of pyrene in soils

    International Nuclear Information System (INIS)

    Peng Jingjing; Cai Chao; Qiao Min; Li Hong; Zhu Yongguan

    2010-01-01

    This study investigates the dynamics of pyrene degradation rates, microbial communities, and functional gene copy numbers during the incubation of pyrene-spiked soils. Spiking pyrene to the soil was found to have negligible effects on the bacterial community present. Our results demonstrated that there was a significant difference in nidA gene copy numbers between sampling dates in QZ soil. Mycobacterium 16S rDNA clone libraries showed that more than 90% mycobacteria detected were closely related to fast-growing PAH-degrading Mycobacterium in pyrene-spiked soil, while other sequences related to slow-growing Mycobacterium were only detected in the control soil. It is suggested that nidA gene copy number and fast-growing PAH-degrading Mycobacterium could be used as indicators to predict pyrene contamination and its degradation activity in soils. - nidA gene and fast-growing PAH-degrading Mycobacterium can serve as indicators for pyrene contamination.

  11. Towards a Video Passive Content Fingerprinting Method for Partial-Copy Detection Robust against Non-Simulated Attacks.

    Directory of Open Access Journals (Sweden)

    Zobeida Jezabel Guzman-Zavaleta

    Full Text Available Passive content fingerprinting is widely used for video content identification and monitoring. However, many challenges remain unsolved especially for partial-copies detection. The main challenge is to find the right balance between the computational cost of fingerprint extraction and fingerprint dimension, without compromising detection performance against various attacks (robustness. Fast video detection performance is desirable in several modern applications, for instance, in those where video detection involves the use of large video databases or in applications requiring real-time video detection of partial copies, a process whose difficulty increases when videos suffer severe transformations. In this context, conventional fingerprinting methods are not fully suitable to cope with the attacks and transformations mentioned before, either because the robustness of these methods is not enough or because their execution time is very high, where the time bottleneck is commonly found in the fingerprint extraction and matching operations. Motivated by these issues, in this work we propose a content fingerprinting method based on the extraction of a set of independent binary global and local fingerprints. Although these features are robust against common video transformations, their combination is more discriminant against severe video transformations such as signal processing attacks, geometric transformations and temporal and spatial desynchronization. Additionally, we use an efficient multilevel filtering system accelerating the processes of fingerprint extraction and matching. This multilevel filtering system helps to rapidly identify potential similar video copies upon which the fingerprint process is carried out only, thus saving computational time. We tested with datasets of real copied videos, and the results show how our method outperforms state-of-the-art methods regarding detection scores. Furthermore, the granularity of our method makes

  12. Analysis of copy number loss of the ErbB4 receptor tyrosine kinase in glioblastoma.

    Directory of Open Access Journals (Sweden)

    DeAnalisa C Jones

    Full Text Available Current treatments for glioblastoma multiforme (GBM-an aggressive form of brain cancer-are minimally effective and yield a median survival of 14.6 months and a two-year survival rate of 30%. Given the severity of GBM and the limitations of its treatment, there is a need for the discovery of novel drug targets for GBM and more personalized treatment approaches based on the characteristics of an individual's tumor. Most receptor tyrosine kinases-such as EGFR-act as oncogenes, but publicly available data from the Cancer Cell Line Encyclopedia (CCLE indicates copy number loss in the ERBB4 RTK gene across dozens of GBM cell lines, suggesting a potential tumor suppressor role. This loss is mutually exclusive with loss of its cognate ligand NRG1 in CCLE as well, more strongly suggesting a functional role. The availability of higher resolution copy number data from clinical GBM patients in The Cancer Genome Atlas (TCGA revealed that a region in Intron 1 of the ERBB4 gene was deleted in 69.1% of tumor samples harboring ERBB4 copy number loss; however, it was also found to be deleted in the matched normal tissue samples from these GBM patients (n = 81. Using the DECIPHER Genome Browser, we also discovered that this mutation occurs at approximately the same frequency in the general population as it does in the disease population. We conclude from these results that this loss in Intron 1 of the ERBB4 gene is neither a de novo driver mutation nor a predisposing factor to GBM, despite the indications from CCLE. A biological role of this significantly occurring genetic alteration is still unknown. While this is a negative result, the broader conclusion is that while copy number data from large cell line-based data repositories may yield compelling hypotheses, careful follow up with higher resolution copy number assays, patient data, and general population analyses are essential to codify initial hypotheses prior to investing experimental resources.

  13. 47 CFR 25.110 - Filing of applications, fees, and number of copies.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Filing of applications, fees, and number of copies. 25.110 Section 25.110 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES SATELLITE COMMUNICATIONS Applications and Licenses General Application Filing...

  14. The interactive effects of multiple stressors on physiological stress responses and club cell investment in fathead minnows

    International Nuclear Information System (INIS)

    Manek, Aditya K.; Ferrari, Maud C.O.; Niyogi, Som; Chivers, Douglas P.

    2014-01-01

    Anthropogenic activities have dramatically increased over the past decades, with the consequence that many organisms are simultaneously exposed to multiple stressors. Understanding how organisms respond to these stressors is a key focus for scientists from many disciplines. Here we investigated the interactive effects of two stressors, UV radiation (UVR) and cadmium (Cd) exposure on a common freshwater fish, fathead minnow (Pimephales promelas). UVR is known to influence the density of epidermal club cells (ECCs), which are not only a key component of the innate immune system of fishes, but are also the source of chemical alarm cues that serve to warn other fishes of nearby predators. In contrast, Cd impairs the physiological stress response and ability of fish to respond to alarm cues. We used an integrative approach to examine physiological stress response as well as investment in ECCs. Fish exposed to UVR had higher levels of cortisol than non-exposed controls, but Cd reduced cortisol levels substantially for fish exposed to UVR. Fish exposed to UVR, either in the presence or absence of Cd, showed consistent decreases in ECC investment compared to non-exposed controls. Despite differences in ECC number, there was no difference in the potency of alarm cues prepared from the skin of UVR and Cd exposed or non-exposed fish indicating that UVR and Cd exposure combined may have little influence on chemically-mediated predator–prey interactions. - Highlights: • UV radiation caused a physiological stress response (cortisol release) in fish. • Cd reduced cortisol levels substantially for fish exposed to UV. • Fish exposed to UV, with or without Cd, showed decreases in club cell investment. • There was no difference in alarm cues potency from UV and Cd exposed fish. • Our work highlights the difficulty of untangling effects of multiple stressors

  15. The interactive effects of multiple stressors on physiological stress responses and club cell investment in fathead minnows

    Energy Technology Data Exchange (ETDEWEB)

    Manek, Aditya K., E-mail: aditya.manek@usask.ca [Department of Biology, University of Saskatchewan, Saskatoon, S7N 5E2 SK (Canada); Ferrari, Maud C.O. [Department of Biomedical Sciences, WCVM, University of Saskatchewan, Saskatoon, SK S7N 5B4 (Canada); Niyogi, Som; Chivers, Douglas P. [Department of Biology, University of Saskatchewan, Saskatoon, S7N 5E2 SK (Canada)

    2014-04-01

    Anthropogenic activities have dramatically increased over the past decades, with the consequence that many organisms are simultaneously exposed to multiple stressors. Understanding how organisms respond to these stressors is a key focus for scientists from many disciplines. Here we investigated the interactive effects of two stressors, UV radiation (UVR) and cadmium (Cd) exposure on a common freshwater fish, fathead minnow (Pimephales promelas). UVR is known to influence the density of epidermal club cells (ECCs), which are not only a key component of the innate immune system of fishes, but are also the source of chemical alarm cues that serve to warn other fishes of nearby predators. In contrast, Cd impairs the physiological stress response and ability of fish to respond to alarm cues. We used an integrative approach to examine physiological stress response as well as investment in ECCs. Fish exposed to UVR had higher levels of cortisol than non-exposed controls, but Cd reduced cortisol levels substantially for fish exposed to UVR. Fish exposed to UVR, either in the presence or absence of Cd, showed consistent decreases in ECC investment compared to non-exposed controls. Despite differences in ECC number, there was no difference in the potency of alarm cues prepared from the skin of UVR and Cd exposed or non-exposed fish indicating that UVR and Cd exposure combined may have little influence on chemically-mediated predator–prey interactions. - Highlights: • UV radiation caused a physiological stress response (cortisol release) in fish. • Cd reduced cortisol levels substantially for fish exposed to UV. • Fish exposed to UV, with or without Cd, showed decreases in club cell investment. • There was no difference in alarm cues potency from UV and Cd exposed fish. • Our work highlights the difficulty of untangling effects of multiple stressors.

  16. Modern printers and hard copy devices for documentation in nuclear medicine

    International Nuclear Information System (INIS)

    Mahlstedt, J.

    1987-01-01

    Modern printers in nuclear medicine comprise technologies such as ink jet print, thermo transfer print or electrostatic plotting in combination with a digital processor. For clinical work these machines provide robust light weight copies within a short time thus fulfilling most of the criteria for an ideal documentation. (orig.) [de

  17. 33 CFR 150.20 - How many copies of the operations manual must be given to the Coast Guard?

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false How many copies of the operations manual must be given to the Coast Guard? 150.20 Section 150.20 Navigation and Navigable Waters COAST... § 150.20 How many copies of the operations manual must be given to the Coast Guard? The draft operations...

  18. A Coarse-Grained Biophysical Model of E. coli and Its Application to Perturbation of the rRNA Operon Copy Number

    Science.gov (United States)

    Tadmor, Arbel

    2009-03-01

    In this work a biophysical model of Escherichia coli is presented that predicts growth rate and an effective cellular composition from an effective, coarse-grained representation of its genome. We assume that E. coli is in a state of balanced exponential steady-state growth, growing in a temporally and spatially constant environment, rich in resources. We apply this model to a series of past measurements, where the growth rate and rRNA-to-protein ratio have been measured for seven E. coli strains with an rRNA operon copy number ranging from one to seven (the wild-type copy number). These experiments show that growth rate markedly decreases for strains with fewer than six copies. Using the model, we were able to reproduce these measurements. We show that the model that best fits these data suggests that the volume fraction of macromolecules inside E. coli is not fixed when the rRNA operon copy number is varied. Moreover, the model predicts that increasing the copy number beyond seven results in a cytoplasm densely packed with ribosomes and proteins. Assuming that under such overcrowded conditions prolonged diffusion times tend to weaken binding affinities, the model predicts that growth rate will not increase substantially beyond the wild-type growth rate, as indicated by other experiments. Our model therefore suggests that changing the rRNA operon copy number of wild-type E. coli cells growing in a constant rich environment does not substantially increase their growth rate. Other observations regarding strains with an altered rRNA operon copy number, such as nucleoid compaction and the rRNA operon feedback response, appear to be qualitatively consistent with this model. In addition, we discuss possible design principles suggested by the model and propose further experiments to test its validity.

  19. SVA retrotransposon insertion-associated deletion represents a novel mutational mechanism underlying large genomic copy number changes with non-recurrent breakpoints

    NARCIS (Netherlands)

    J. Vogt (Julia); K. Bengesser (Kathrin); K.B.M. Claes (Kathleen B.M.); K. Wimmer (Katharina); V.-F. Mautner (Victor-Felix); R. van Minkelen (Rick); E. Legius (Eric); H. Brems (Hilde); M. Upadhyaya (Meena); J. Högel (Josef); C. Lazaro (Conxi); T. Rosenbaum (Thorsten); S. Bammert (Simone); L. Messiaen (Ludwine); D.N. Cooper (David); H. Kehrer-Sawatzki (Hildegard)

    2014-01-01

    textabstractBackground: Genomic disorders are caused by copy number changes that may exhibit recurrent breakpoints processed by nonallelic homologous recombination. However, region-specific disease-associated copy number changes have also been observed which exhibit non-recurrent breakpoints. The

  20. The Diagnostic Agreement of Original and Faxed Copies of Electrocardiograms

    Directory of Open Access Journals (Sweden)

    Sadrihe Hajesmaeel-Gohari

    2013-02-01

    Full Text Available Background: General practitioners working in remote and rural areas sometimes need consultation with cardiologists. One practical and cost-effective way is transmission of patients’ electrocardiographic images via ordinary fax machine to the cardiologists, but there is an important question that how much agreement exists between the diagnoses made by reading an original electrocardiogram and its copy transmitted via fax.Materials and Methods: In this cross-sectional study, 60 original electrocardiographic images were given to cardiologists for diagnosis. In the next step those electrocardiographic images were faxed to the hospital through a simple cheap fax machine, one month later the same cardiologist was asked to put his diagnosis on the copied versions of electrocardiographs, and the results were compared. Results: In 59 studied cases, the two method of diagnoses were exactly the same and only in one case the diagnoses were different. Therefore, Kappa agreement coefficient was calculated as 96%.Conclusion: According to the results of this study, general practitioners working in deprived areas can be certainly recommended to send patients’ electrocardiographic images to the cardiologists via fax in the case of needing consultation.

  1. Accurate measurement of mitochondrial DNA deletion level and copy number differences in human skeletal muscle.

    Directory of Open Access Journals (Sweden)

    John P Grady

    Full Text Available Accurate and reliable quantification of the abundance of mitochondrial DNA (mtDNA molecules, both wild-type and those harbouring pathogenic mutations, is important not only for understanding the progression of mtDNA disease but also for evaluating novel therapeutic approaches. A clear understanding of the sensitivity of mtDNA measurement assays under different experimental conditions is therefore critical, however it is routinely lacking for most published mtDNA quantification assays. Here, we comprehensively assess the variability of two quantitative Taqman real-time PCR assays, a widely-applied MT-ND1/MT-ND4 multiplex mtDNA deletion assay and a recently developed MT-ND1/B2M singleplex mtDNA copy number assay, across a range of DNA concentrations and mtDNA deletion/copy number levels. Uniquely, we provide a specific guide detailing necessary numbers of sample and real-time PCR plate replicates for accurately and consistently determining a given difference in mtDNA deletion levels and copy number in homogenate skeletal muscle DNA.

  2. TumorBoost: Normalization of allele-specific tumor copy numbers from a single pair of tumor-normal genotyping microarrays

    Directory of Open Access Journals (Sweden)

    Neuvial Pierre

    2010-05-01

    Full Text Available Abstract Background High-throughput genotyping microarrays assess both total DNA copy number and allelic composition, which makes them a tool of choice for copy number studies in cancer, including total copy number and loss of heterozygosity (LOH analyses. Even after state of the art preprocessing methods, allelic signal estimates from genotyping arrays still suffer from systematic effects that make them difficult to use effectively for such downstream analyses. Results We propose a method, TumorBoost, for normalizing allelic estimates of one tumor sample based on estimates from a single matched normal. The method applies to any paired tumor-normal estimates from any microarray-based technology, combined with any preprocessing method. We demonstrate that it increases the signal-to-noise ratio of allelic signals, making it significantly easier to detect allelic imbalances. Conclusions TumorBoost increases the power to detect somatic copy-number events (including copy-neutral LOH in the tumor from allelic signals of Affymetrix or Illumina origin. We also conclude that high-precision allelic estimates can be obtained from a single pair of tumor-normal hybridizations, if TumorBoost is combined with single-array preprocessing methods such as (allele-specific CRMA v2 for Affymetrix or BeadStudio's (proprietary XY-normalization method for Illumina. A bounded-memory implementation is available in the open-source and cross-platform R package aroma.cn, which is part of the Aroma Project (http://www.aroma-project.org/.

  3. Association studies of the copy-number variable ß-defensin cluster on 8p23.1 in adenocarcinoma and chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    Taudien Stefan

    2012-11-01

    Full Text Available Abstract Background Human ß-defensins are a family of antimicrobial peptides located at the mucosal surface. Both sequence multi-site variations (MSV and copy-number variants (CNV of the defensin-encoding genes are associated with increased risk for various diseases, including cancer and inflammatory conditions such as psoriasis and acute pancreatitis. In a case–control study, we investigated the association between MSV in DEFB104 as well as defensin gene (DEF cluster copy number (CN, and pancreatic ductal adenocarcinoma (PDAC and chronic pancreatitis (CP. Results Two groups of PDAC (N=70 and CP (N=60 patients were compared to matched healthy control groups CARLA1 (N=232 and CARLA2 (N=160, respectively. Four DEFB104 MSV were haplotyped by PCR, cloning and sequencing. DEF cluster CN was determined by multiplex ligation-dependent probe amplification. Neither the PDAC nor the CP cohorts show significant differences in the DEFB104 haplotype distribution compared to the respective control groups CARLA1 and CARLA2, respectively. The diploid DEF cluster CN exhibit a significantly different distribution between PDAC and CARLA1 (Fisher’s exact test P=0.027, but not between CP and CARLA2 (P=0.867. Conclusion Different DEF cluster b CN distribution between PDAC patients and healthy controls indicate a potential protective effect of higher CNs against the disease.

  4. Detection of Copy-move Image Modification Using JPEG Compression Model

    Czech Academy of Sciences Publication Activity Database

    Novozámský, Adam; Šorel, Michal

    2018-01-01

    Roč. 283, č. 1 (2018), s. 47-57 ISSN 0379-0738 R&D Projects: GA ČR(CZ) GA16-13830S; GA ČR GA15-16928S Institutional support: RVO:67985556 Keywords : Copy-move modification * Forgery * Image tampering * Quantization constraint set Subject RIV: JD - Computer Applications, Robotics Impact factor: 1.989, year: 2016 http://library.utia.cas.cz/separaty/2017/ZOI/novozamsky-0483329.pdf

  5. Prediction of a deletion copy number variant by a dense SNP panel

    NARCIS (Netherlands)

    Kadri, N.K.; Koks, P.D.; Meuwissen, T.H.E.

    2012-01-01

    Background: A newly recognized type of genetic variation, Copy Number Variation (CNV), is detected in mammalian genomes, e.g. the cattle genome. This form of variation can potentially cause phenotypic variation. Our objective was to determine whether dense SNP (single nucleotide polymorphisms)

  6. Heritable heading time variation in wheat lines with the same number of Ppd-B1 gene copies.

    Science.gov (United States)

    Ivaničová, Zuzana; Valárik, Miroslav; Pánková, Kateřina; Trávníčková, Martina; Doležel, Jaroslav; Šafář, Jan; Milec, Zbyněk

    2017-01-01

    The ability of plants to identify an optimal flowering time is critical for ensuring the production of viable seeds. The main environmental factors that influence the flowering time include the ambient temperature and day length. In wheat, the ability to assess the day length is controlled by photoperiod (Ppd) genes. Due to its allohexaploid nature, bread wheat carries the following three Ppd-1 genes: Ppd-A1, Ppd-B1 and Ppd-D1. While photoperiod (in)sensitivity controlled by Ppd-A1 and Ppd-D1 is mainly determined by sequence changes in the promoter region, the impact of the Ppd-B1 alleles on the heading time has been linked to changes in the copy numbers (and possibly their methylation status) and sequence changes in the promoter region. Here, we report that plants with the same number of Ppd-B1 copies may have different heading times. Differences were observed among F7 lines derived from crossing two spring hexaploid wheat varieties. Several lines carrying three copies of Ppd-B1 headed 16 days later than other plants in the population with the same number of gene copies. This effect was associated with changes in the gene expression level and methylation of the Ppd-B1 gene.

  7. Heritable heading time variation in wheat lines with the same number of Ppd-B1 gene copies.

    Directory of Open Access Journals (Sweden)

    Zuzana Ivaničová

    Full Text Available The ability of plants to identify an optimal flowering time is critical for ensuring the production of viable seeds. The main environmental factors that influence the flowering time include the ambient temperature and day length. In wheat, the ability to assess the day length is controlled by photoperiod (Ppd genes. Due to its allohexaploid nature, bread wheat carries the following three Ppd-1 genes: Ppd-A1, Ppd-B1 and Ppd-D1. While photoperiod (insensitivity controlled by Ppd-A1 and Ppd-D1 is mainly determined by sequence changes in the promoter region, the impact of the Ppd-B1 alleles on the heading time has been linked to changes in the copy numbers (and possibly their methylation status and sequence changes in the promoter region. Here, we report that plants with the same number of Ppd-B1 copies may have different heading times. Differences were observed among F7 lines derived from crossing two spring hexaploid wheat varieties. Several lines carrying three copies of Ppd-B1 headed 16 days later than other plants in the population with the same number of gene copies. This effect was associated with changes in the gene expression level and methylation of the Ppd-B1 gene.

  8. Effect of pencil grasp on the speed and legibility of handwriting after a 10-minute copy task in Grade 4 children.

    Science.gov (United States)

    Schwellnus, Heidi; Carnahan, Heather; Kushki, Azadeh; Polatajko, Helene; Missiuna, Cheryl; Chau, Tom

    2012-06-01

    To investigate the impact of common pencil grasp patterns on the speed and legibility of handwriting after a 10-minute copy task, intended to induce muscle fatigue, in typically developing children and in those non-proficient in handwriting. A total of 120 Grade 4 students completed a standardised handwriting assessment before and after a 10-minute copy task. The students indicated the perceived difficulty of the handwriting task at baseline and after 10 minutes. The students also completed a self-report questionnaire regarding their handwriting proficiency upon completion. The majority of the students rated higher effort after the 10-minute copy task than at baseline (rank sum: P = 0.00001). The effort ratings were similar for the different grasp patterns (multiple linear regression: F = 0.37, P = 0.895). For both typically developing children and those with handwriting issues, the legibility of the writing samples decreased after the 10-minute copy task but the speed of writing increased. CONCLUSIONS AND SIGNIFICANCE OF THE STUDY: The quality of the handwriting decreased after the 10-minute copy task; however, there was no difference in the quality or speed scores among the different pencil grasps before and after the copy task. The dynamic tripod pencil grasp did not offer any advantage over the lateral tripod or the dynamic or lateral quadrupod pencil grasps in terms of quality of handwriting after a 10-minute copy task. These four pencil grasp patterns performed equivalently. Our findings question the practice of having students adopt the dynamic tripod pencil grasp. © 2012 The Authors Australian Occupational Therapy Journal © 2012 Occupational Therapy Australia.

  9. Insertion sequence typing of Mycobacterium tuberculosis: characterization of a widespread subtype with a single copy of IS6110.

    Science.gov (United States)

    Fomukong, N G; Tang, T H; al-Maamary, S; Ibrahim, W A; Ramayah, S; Yates, M; Zainuddin, Z F; Dale, J W

    1994-12-01

    DNA fingerprinting with the insertion sequence IS6110 (also known as IS986) has become established as a major tool for investigating the spread of tuberculosis. Most strains of Mycobacterium tuberculosis have multiple copies of IS6110, but a small minority carry a single copy only. We have examined selected strains from Malaysia, Tanzania and Oman, in comparison with M. bovis isolates and BCG strains carrying one or two copies of IS6110. The insertion sequence appears to be present in the same position in all these strains, which suggests that in these organisms the element is defective in transposition and that the loss of transposability may have occurred at an early stage in the evolution of the M. tuberculosis complex.

  10. Alpha-defensin DEFA1A3 gene copy number elevation in Danish Crohn's disease patients

    DEFF Research Database (Denmark)

    Jespersgaard, Cathrine; Fode, Peder; Dybdahl, Marianne

    2011-01-01

    BACKGROUND AND PURPOSE OF STUDY: Extensive copy number variation is observed for the DEFA1A3 gene encoding alpha-defensins 1-3. The objective of this study was to determine the involvement of alpha-defensins in colonic tissue from Crohn's disease (CD) patients and the possible genetic association...... of DEFA1A3 with CD. METHODS: Two-hundred and forty ethnic Danish CD patients were included in the study. Reverse transcriptase PCR assays determined DEFA1A3 expression in colonic tissue from a subset of patients. Immunohistochemical analysis identified alpha-defensin peptides in colonic tissue. Copy...

  11. Classification of human cancers based on DNA copy number amplification modeling

    Directory of Open Access Journals (Sweden)

    Knuutila Sakari

    2008-05-01

    Full Text Available Abstract Background DNA amplifications alter gene dosage in cancer genomes by multiplying the gene copy number. Amplifications are quintessential in a considerable number of advanced cancers of various anatomical locations. The aims of this study were to classify human cancers based on their amplification patterns, explore the biological and clinical fundamentals behind their amplification-pattern based classification, and understand the characteristics in human genomic architecture that associate with amplification mechanisms. Methods We applied a machine learning approach to model DNA copy number amplifications using a data set of binary amplification records at chromosome sub-band resolution from 4400 cases that represent 82 cancer types. Amplification data was fused with background data: clinical, histological and biological classifications, and cytogenetic annotations. Statistical hypothesis testing was used to mine associations between the data sets. Results Probabilistic clustering of each chromosome identified 111 amplification models and divided the cancer cases into clusters. The distribution of classification terms in the amplification-model based clustering of cancer cases revealed cancer classes that were associated with specific DNA copy number amplification models. Amplification patterns – finite or bounded descriptions of the ranges of the amplifications in the chromosome – were extracted from the clustered data and expressed according to the original cytogenetic nomenclature. This was achieved by maximal frequent itemset mining using the cluster-specific data sets. The boundaries of amplification patterns were shown to be enriched with fragile sites, telomeres, centromeres, and light chromosome bands. Conclusions Our results demonstrate that amplifications are non-random chromosomal changes and specifically selected in tumor tissue microenvironment. Furthermore, statistical evidence showed that specific chromosomal features

  12. Gene copy number reduction in the azoospermia factor c (AZFc) region and its effect on total motile sperm count

    NARCIS (Netherlands)

    Noordam, Michiel J.; Westerveld, G. Henrike; Hovingh, Suzanne E.; van Daalen, Saskia K. M.; Korver, Cindy M.; van der Veen, Fulco; van Pelt, Ans M. M.; Repping, Sjoerd

    2011-01-01

    The azoospermia factor c (AZFc) region harbors multi-copy genes that are expressed in the testis. Deletions of the AZFc region lead to reduced copy numbers of these genes. Four (partial) AZFc deletions have been described of which the b2/b4 and gr/gr deletions affect semen quality. In most studies,

  13. Distribution and functional impact of DNA copy number variation in the rat.

    NARCIS (Netherlands)

    Guryev, V.; Saar, K.; Adamovic, T.; Verheul, M.; van Heesch, S.; Cook, S.; Pravenec, M.; Aitman, T.; Jacob, H.; Shull, J.D.; Hubner, N.; Cuppen, E.

    2008-01-01

    The abundance and dynamics of copy number variants (CNVs) in mammalian genomes poses new challenges in the identification of their impact on natural and disease phenotypes. We used computational and experimental methods to catalog CNVs in rat and found that they share important functional

  14. Rare Copy Number Variations in Adults with Tetralogy of Fallot Implicate Novel Risk Gene Pathways

    Science.gov (United States)

    Costain, Gregory; Merico, Daniele; Migita, Ohsuke; Liu, Ben; Yuen, Tracy; Rickaby, Jessica; Thiruvahindrapuram, Bhooma; Marshall, Christian R.; Scherer, Stephen W.; Bassett, Anne S.

    2012-01-01

    Structural genetic changes, especially copy number variants (CNVs), represent a major source of genetic variation contributing to human disease. Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart disease, but to date little is known about the role of CNVs in the etiology of TOF. Using high-resolution genome-wide microarrays and stringent calling methods, we investigated rare CNVs in a prospectively recruited cohort of 433 unrelated adults with TOF and/or pulmonary atresia at a single centre. We excluded those with recognized syndromes, including 22q11.2 deletion syndrome. We identified candidate genes for TOF based on converging evidence between rare CNVs that overlapped the same gene in unrelated individuals and from pathway analyses comparing rare CNVs in TOF cases to those in epidemiologic controls. Even after excluding the 53 (10.7%) subjects with 22q11.2 deletions, we found that adults with TOF had a greater burden of large rare genic CNVs compared to controls (8.82% vs. 4.33%, p = 0.0117). Six loci showed evidence for recurrence in TOF or related congenital heart disease, including typical 1q21.1 duplications in four (1.18%) of 340 Caucasian probands. The rare CNVs implicated novel candidate genes of interest for TOF, including PLXNA2, a gene involved in semaphorin signaling. Independent pathway analyses highlighted developmental processes as potential contributors to the pathogenesis of TOF. These results indicate that individually rare CNVs are collectively significant contributors to the genetic burden of TOF. Further, the data provide new evidence for dosage sensitive genes in PLXNA2-semaphorin signaling and related developmental processes in human cardiovascular development, consistent with previous animal models. PMID:22912587

  15. Mate-Choice Copying in Single and Coupled Women: The Influence of Mate Acceptance and Mate Rejection Decisions of other Women

    Directory of Open Access Journals (Sweden)

    Yan Deng

    2015-01-01

    Full Text Available Studies of humans and non-human animals indicate that females tend to change the likelihood of choosing a potential mate based on the decisions of other females; this is known as mate-choice copying. In a sample of both single and coupled women, we examined the influence of other women's (model mate-choice decisions, including mate acceptance and mate rejection, on participants' attractiveness ratings of men (target and willingness of mate selection. We also examined whether different types of relationships between the target men and the model women affected mate-choice copying. We found that both the single and coupled women showed mate-choice copying, but their response patterns differed. The significant effects for single women were dependent on a decrease in attractiveness ratings when they perceived the models' mate rejection. However, the significant findings for coupled women relied on an increase in attractiveness ratings when they observed the models' mate acceptance. Furthermore, the relationship status between the target men and the model women affected the magnitude of mate-choice copying effects for the single women. Specifically, they showed less mate-choice copying when the targets and models were in a committed romantic relationship than when in a temporary relationship.

  16. Phenotypic manifestations of copy number variation in chromosome 16p13.11

    NARCIS (Netherlands)

    Nagamani, Sandesh C. Sreenath; Erez, Ayelet; Bader, Patricia; Lalani, Seema R.; Scott, Daryl A.; Scaglia, Fernando; Plon, Sharon E.; Tsai, Chun-Hui; Reimschisel, Tyler; Roeder, Elizabeth; Malphrus, Amy D.; Eng, Patricia A.; Hixson, Patricia M.; Kang, Sung-Hae L.; Stankiewicz, Pawel; Patel, Ankita; Cheung, Sau Wai

    The widespread clinical utilization of array comparative genome hybridization, has led to the unraveling of many new copy number variations (CNVs). Although some of these CNVs are clearly pathogenic, the phenotypic consequences of others, such as those in 16p13.11 remain unclear. Whereas deletions

  17. Nonparametric testing for DNA copy number induced differential mRNA gene expression

    NARCIS (Netherlands)

    van Wieringen, W.N.; van de Wiel, M.A.

    2009-01-01

    The central dogma of molecular biology relates DNA with mRNA. Array CGH measures DNA copy number and gene expression microarrays measure the amount of mRNA. Methods that integrate data from these two platforms may uncover meaningful biological relationships that further our understanding of cancer.

  18. 77 FR 5470 - Periodicals-Recognition of Distribution of Periodicals via Electronic Copies

    Science.gov (United States)

    2012-02-03

    ... Electronic Copies AGENCY: Postal Service TM . ACTION: Proposed rule. SUMMARY: The Postal Service proposes to revise the Mailing Standards of the United States Postal Service, Domestic Mail Manual (DMM[supreg]) 707.6, to allow publishers who use electronic distribution methods to report such circulation as paid or...

  19. Construction of a food-grade multiple-copy integration system for Lactococcus lactis

    NARCIS (Netherlands)

    Leenhouts, K.; Bolhuis, A.; Venema, G.; Kok, J.

    A food-grade vector system was developed that allows stable integration of multiple plasmid copies in the chromosome of Lactococcus lactis. The vector consists of the plus origin of replication (Ori(+)) of the lactococcal plasmid pWV01, the sucrose genes of the lactic acid bacterium Pediococcus

  20. Obesity, starch digestion and amylase: association between copy number variants at human salivary (AMY1) and pancreatic (AMY2) amylase genes.

    Science.gov (United States)

    Carpenter, Danielle; Dhar, Sugandha; Mitchell, Laura M; Fu, Beiyuan; Tyson, Jess; Shwan, Nzar A A; Yang, Fengtang; Thomas, Mark G; Armour, John A L

    2015-06-15

    The human salivary amylase genes display extensive copy number variation (CNV), and recent work has implicated this variation in adaptation to starch-rich diets, and in association with body mass index. In this work, we use paralogue ratio tests, microsatellite analysis, read depth and fibre-FISH to demonstrate that human amylase CNV is not a smooth continuum, but is instead partitioned into distinct haplotype classes. There is a fundamental structural distinction between haplotypes containing odd or even numbers of AMY1 gene units, in turn coupled to CNV in pancreatic amylase genes AMY2A and AMY2B. Most haplotypes have one copy each of AMY2A and AMY2B and contain an odd number of copies of AMY1; consequently, most individuals have an even total number of AMY1. In contrast, haplotypes carrying an even number of AMY1 genes have rearrangements leading to CNVs of AMY2A/AMY2B. Read-depth and experimental data show that different populations harbour different proportions of these basic haplotype classes. In Europeans, the copy numbers of AMY1 and AMY2A are correlated, so that phenotypic associations caused by variation in pancreatic amylase copy number could be detected indirectly as weak association with AMY1 copy number. We show that the quantitative polymerase chain reaction (qPCR) assay previously applied to the high-throughput measurement of AMY1 copy number is less accurate than the measures we use and that qPCR data in other studies have been further compromised by systematic miscalibration. Our results uncover new patterns in human amylase variation and imply a potential role for AMY2 CNV in functional associations. © The Author 2015. Published by Oxford University Press.

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