WorldWideScience

Sample records for copi coatomer complex

  1. Structural characterization of coatomer in its cytosolic state

    Directory of Open Access Journals (Sweden)

    Shengliu Wang

    2016-07-01

    Full Text Available Abstract Studies on coat protein I (COPI have contributed to a basic understanding of how coat proteins generate vesicles to initiate intracellular transport. The core component of the COPI complex is coatomer, which is a multimeric complex that needs to be recruited from the cytosol to membrane in order to function in membrane bending and cargo sorting. Previous structural studies on the clathrin adaptors have found that membrane recruitment induces a large conformational change in promoting their role in cargo sorting. Here, pursuing negative-stain electron microscopy coupled with single-particle analyses, and also performing CXMS (chemical cross-linking coupled with mass spectrometry for validation, we have reconstructed the structure of coatomer in its soluble form. When compared to the previously elucidated structure of coatomer in its membrane-bound form we do not observe a large conformational change. Thus, the result uncovers a key difference between how COPI versus clathrin coats are regulated by membrane recruitment.

  2. Dominant Red Coat Color in Holstein Cattle Is Associated with a Missense Mutation in the Coatomer Protein Complex, Subunit Alpha (COPA Gene.

    Directory of Open Access Journals (Sweden)

    Ben Dorshorst

    Full Text Available Coat color in Holstein dairy cattle is primarily controlled by the melanocortin 1 receptor (MC1R gene, a central determinant of black (eumelanin vs. red/brown pheomelanin synthesis across animal species. The major MC1R alleles in Holsteins are Dominant Black (MC1RD and Recessive Red (MC1Re. A novel form of dominant red coat color was first observed in an animal born in 1980. The mutation underlying this phenotype was named Dominant Red and is epistatic to the constitutively activated MC1RD. Here we show that a missense mutation in the coatomer protein complex, subunit alpha (COPA, a gene with previously no known role in pigmentation synthesis, is completely associated with Dominant Red in Holstein dairy cattle. The mutation results in an arginine to cysteine substitution at an amino acid residue completely conserved across eukaryotes. Despite this high level of conservation we show that both heterozygotes and homozygotes are healthy and viable. Analysis of hair pigment composition shows that the Dominant Red phenotype is similar to the MC1R Recessive Red phenotype, although less effective at reducing eumelanin synthesis. RNA-seq data similarly show that Dominant Red animals achieve predominantly pheomelanin synthesis by downregulating genes normally required for eumelanin synthesis. COPA is a component of the coat protein I seven subunit complex that is involved with retrograde and cis-Golgi intracellular coated vesicle transport of both protein and RNA cargo. This suggests that Dominant Red may be caused by aberrant MC1R protein or mRNA trafficking within the highly compartmentalized melanocyte, mimicking the effect of the Recessive Red loss of function MC1R allele.

  3. Induction of cortical endoplasmic reticulum by dimerization of a coatomer-binding peptide anchored to endoplasmic reticulum membranes

    OpenAIRE

    Lavieu, Grégory; Orci, Lelio; Shi, Lei; Geiling, Michael; Ravazzola, Mariella; Wieland, Felix; Cosson, Pierre; Rothman, James E.

    2010-01-01

    Cortical endoplasmic reticulum (cER) is a permanent feature of yeast cells but occurs transiently in most animal cell types. Ist2p is a transmembrane protein that permanently localizes to the cER in yeast. When Ist2 is expressed in mammalian cells, it induces abundant cER containing Ist2. Ist2 cytoplasmic C-terminal peptide is necessary and sufficient to induce cER. This peptide sequence resembles classic coat protein complex I (COPI) coatomer protein-binding KKXX signals, and indeed the dime...

  4. 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.

  5. COPI-mediated retrograde trafficking from the Golgi to the ER regulates EGFR nuclear transport

    International Nuclear Information System (INIS)

    Wang, Ying-Nai; Wang, Hongmei; Yamaguchi, Hirohito; Lee, Hong-Jen; Lee, Heng-Huan; Hung, Mien-Chie

    2010-01-01

    Research highlights: → ARF1 activation is involved in the EGFR transport to the ER and the nucleus. → Assembly of γ-COP coatomer mediates EGFR transport to the ER and the nucleus. → Golgi-to-ER retrograde trafficking regulates nuclear transport of EGFR. -- Abstract: Emerging evidence indicates that cell surface receptors, such as the entire epidermal growth factor receptor (EGFR) family, have been shown to localize in the nucleus. A retrograde route from the Golgi to the endoplasmic reticulum (ER) is postulated to be involved in the EGFR trafficking to the nucleus; however, the molecular mechanism in this proposed model remains unexplored. Here, we demonstrate that membrane-embedded vesicular trafficking is involved in the nuclear transport of EGFR. Confocal immunofluorescence reveals that in response to EGF, a portion of EGFR redistributes to the Golgi and the ER, where its NH 2 -terminus resides within the lumen of Golgi/ER and COOH-terminus is exposed to the cytoplasm. Blockage of the Golgi-to-ER retrograde trafficking by brefeldin A or dominant mutants of the small GTPase ADP-ribosylation factor, which both resulted in the disassembly of the coat protein complex I (COPI) coat to the Golgi, inhibit EGFR transport to the ER and the nucleus. We further find that EGF-dependent nuclear transport of EGFR is regulated by retrograde trafficking from the Golgi to the ER involving an association of EGFR with γ-COP, one of the subunits of the COPI coatomer. Our findings experimentally provide a comprehensive pathway that nuclear transport of EGFR is regulated by COPI-mediated vesicular trafficking from the Golgi to the ER, and may serve as a general mechanism in regulating the nuclear transport of other cell surface receptors.

  6. 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.

  7. 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.

  8. Research on Copy-Move Image Forgery Detection Using Features of Discrete Polar Complex Exponential Transform

    Science.gov (United States)

    Gan, Yanfen; Zhong, Junliu

    2015-12-01

    With the aid of sophisticated photo-editing software, such as Photoshop, copy-move image forgery operation has been widely applied and has become a major concern in the field of information security in the modern society. A lot of work on detecting this kind of forgery has gained great achievements, but the detection results of geometrical transformations of copy-move regions are not so satisfactory. In this paper, a new method based on the Polar Complex Exponential Transform is proposed. This method addresses issues in image geometric moment, focusing on constructing rotation invariant moment and extracting features of the rotation invariant moment. In order to reduce rounding errors of the transform from the Polar coordinate system to the Cartesian coordinate system, a new transformation method is presented and discussed in detail at the same time. The new method constructs a 9 × 9 shrunk template to transform the Cartesian coordinate system back to the Polar coordinate system. It can reduce transform errors to a much greater degree. Forgery detection, such as copy-move image forgery detection, is a difficult procedure, but experiments prove our method is a great improvement in detecting and identifying forgery images affected by the rotated transform.

  9. 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.

  10. Complex Copy Number Variation of AMY1 does not Associate with Obesity in two East Asian Cohorts.

    Science.gov (United States)

    Yong, Rita Y Y; Mustaffa, Su'Aidah B; Wasan, Pavandip S; Sheng, Liang; Marshall, Christian R; Scherer, Stephen W; Teo, Yik-Ying; Yap, Eric P H

    2016-07-01

    The human amylase gene locus at chromosome 1p21.1 is structurally complex. This region contains two pancreatic amylase genes, AMY2B, AMY2A, and a salivary gene AMY1. The AMY1 gene harbors extensive copy number variation (CNV), and recent studies have implicated this variation in adaptation to starch-rich diets and in association to obesity for European and Asian populations. In this study, we showed that by combining quantitative PCR and digital PCR, coupled with careful experimental design and calibration, we can improve the resolution of genotyping CNV with high copy numbers (CNs). In two East Asian populations of Chinese and Malay ethnicity studied, we observed a unique non-normal distribution of AMY1 diploid CN genotypes with even:odd CNs ratio of 4.5 (3.3-4.7), and an association between the common AMY2A CN = 2 genotype and odd CNs of AMY1, that could be explained by the underlying haplotypic structure. In two further case-control cohorts (n = 932 and 145, for Chinese and Malays, respectively), we did not observe the previously reported association between AMY1 and obesity or body mass index. Improved methods for accurately genotyping multiallelic CNV loci and understanding the haplotype complexity at the AMY1 locus are necessary for population genetics and association studies. © 2016 WILEY PERIODICALS, INC.

  11. Rey-Osterrieth Complex Figure - copy and immediate recall: Normative data for the Latin American Spanish speaking adult population.

    Science.gov (United States)

    Rivera, D; Perrin, P B; Morlett-Paredes, A; Galarza-Del-Angel, J; Martínez, C; Garza, M T; Saracho, C P; Rodríguez, W; Rodríguez-Agudelo, Y; Rábago, B; Aliaga, A; Schebela, S; Luna, M; Longoni, M; Ocampo-Barba, N; Fernández, E; Esenarro, L; García-Egan, P; Arango-Lasprilla, J C

    2015-01-01

    To generate normative data on the Rey-Osterrieth Complex Figure Test (ROCF) across 11 countries in Latin America, with country-specific adjustments for gender, age, and education, where appropriate. The sample consisted of 3,977 healthy adults who were recruited from Argentina, Bolivia, Chile, Cuba, El Salvador, Guatemala, Honduras, Mexico, Paraguay, Peru, and, Puerto Rico. Each subject was administered the ROCF as part of a larger neuropsychological battery. A standardized five-step statistical procedure was used to generate the norms. The final multiple linear regression models explained 7-34% of the variance in ROCF copy scores and 21-41% of the variance in immediate recall scores. Although t-tests showed significant differences between men and women on ROCF copy and immediate recall scores, none of the countries had an effect size larger than 0.3. As a result, gender-adjusted norms were not generated. The present study is the first to create norms for the ROCF in Latin America. As a result, this study will have important implications for the formation and practice of neuropsychology in this region.

  12. 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.

  13. 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...

  14. 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)

  15. Detecting single DNA copy number variations in complex genomes using one nanogram of starting DNA and BAC-array CGH.

    Science.gov (United States)

    Guillaud-Bataille, Marine; Valent, Alexander; Soularue, Pascal; Perot, Christine; Inda, Maria Mar; Receveur, Aline; Smaïli, Sadek; Roest Crollius, Hugues; Bénard, Jean; Bernheim, Alain; Gidrol, Xavier; Danglot, Gisèle

    2004-07-29

    Comparative genomic hybridization to bacterial artificial chromosome (BAC)-arrays (array-CGH) is a highly efficient technique, allowing the simultaneous measurement of genomic DNA copy number at hundreds or thousands of loci, and the reliable detection of local one-copy-level variations. We report a genome-wide amplification method allowing the same measurement sensitivity, using 1 ng of starting genomic DNA, instead of the classical 1 microg usually necessary. Using a discrete series of DNA fragments, we defined the parameters adapted to the most faithful ligation-mediated PCR amplification and the limits of the technique. The optimized protocol allows a 3000-fold DNA amplification, retaining the quantitative characteristics of the initial genome. Validation of the amplification procedure, using DNA from 10 tumour cell lines hybridized to BAC-arrays of 1500 spots, showed almost perfectly superimposed ratios for the non-amplified and amplified DNAs. Correlation coefficients of 0.96 and 0.99 were observed for regions of low-copy-level variations and all regions, respectively (including in vivo amplified oncogenes). Finally, labelling DNA using two nucleotides bearing the same fluorophore led to a significant increase in reproducibility and to the correct detection of one-copy gain or loss in >90% of the analysed data, even for pseudotriploid tumour genomes.

  16. Clinical array-based karyotyping of breast cancer with equivocal HER2 status resolves gene copy number and reveals chromosome 17 complexity

    International Nuclear Information System (INIS)

    Gunn, Shelly; Gorre, Mercedes; Mohammed, Mansoor; Yeh, I-Tien; Lytvak, Irina; Tirtorahardjo, Budi; Dzidic, Natasha; Zadeh, Soheila; Kim, Jaeweon; McCaskill, Chris; Lim, Lony

    2010-01-01

    HER2 gene copy status, and concomitant administration of trastuzumab (Herceptin), remains one of the best examples of targeted cancer therapy based on understanding the genomic etiology of disease. However, newly diagnosed breast cancer cases with equivocal HER2 results present a challenge for the oncologist who must make treatment decisions despite the patient's unresolved HER2 status. In some cases both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are reported as equivocal, whereas in other cases IHC results and FISH are discordant for positive versus negative results. The recent validation of array-based, molecular karyotyping for clinical oncology testing provides an alternative method for determination of HER2 gene copy number status in cases remaining unresolved by traditional methods. In the current study, DNA extracted from 20 formalin fixed paraffin embedded (FFPE) tissue samples from newly diagnosed cases of invasive ductal carcinoma referred to our laboratory with unresolved HER2 status, were analyzed using a clinically validated genomic array containing 127 probes covering the HER2 amplicon, the pericentromeric regions, and both chromosome 17 arms. Array-based comparative genomic hybridization (array CGH) analysis of chromosome 17 resolved HER2 gene status in [20/20] (100%) of cases and revealed additional chromosome 17 copy number changes in [18/20] (90%) of cases. Array CGH analysis also revealed two false positives and one false negative by FISH due to 'ratio skewing' caused by chromosomal gains and losses in the centromeric region. All cases with complex rearrangements of chromosome 17 showed genome-wide chromosomal instability. These results illustrate the analytical power of array-based genomic analysis as a clinical laboratory technique for resolution of HER2 status in breast cancer cases with equivocal results. The frequency of complex chromosome 17 abnormalities in these cases suggests that the two

  17. Copy number neutral loss of heterozygosity at 17p and homozygous mutations of TP53 are associated with complex chromosomal aberrations in patients newly diagnosed with myelodysplastic syndromes.

    Science.gov (United States)

    Svobodova, Karla; Zemanova, Zuzana; Lhotska, Halka; Novakova, Milena; Podskalska, Lucie; Belickova, Monika; Brezinova, Jana; Sarova, Iveta; Izakova, Silvia; Lizcova, Libuse; Berkova, Adela; Siskova, Magda; Jonasova, Anna; Cermak, Jaroslav; Michalova, Kyra

    2016-03-01

    Complex karyotypes are seen in approximately 20% of patients with myelodysplastic syndromes (MDS) and are associated with a high risk of transformation to acute myeloid leukemia and poor outcomes in patients. Copy number neutral loss of heterozygosity (CN-LOH, i.e., both copies of a chromosomal pair or their parts originate from one parent) might contribute to increased genomic instability in the bone-marrow cells of patients with MDS. The pathological potential of CN-LOH, which arises as a clonal aberration in a proportion of somatic cells, consists of tumor suppressor gene and oncogene homozygous mutations. The aim of our study was to evaluate the frequency of CN-LOH at 17p in bone-marrow cells of newly diagnosed MDS patients with complex chromosomal aberrations and to assess its correlation with mutations in the TP53 gene (17p13.1). CN-LOH was detected in 40 chromosomal regions in 21 (29%) of 72 patients analyzed. The changes in 27 of the 40 regions identified were sporadic. The most common finding was CN-LOH of the short arm of chromosome 17, which was detected in 13 (18%) of 72 patients. A mutational analysis confirmed the homozygous mutation of TP53 in all CN-LOH 17p patients, among which two frameshift mutations are not registered in the International Agency for Research on Cancer TP53 Database. CN-LOH 17p correlated with aggressive disease (median overall survival 4 months) and was strongly associated with a complex karyotype in the cohort studied, which might cause rapid disease progression in high-risk MDS. No other CN-LOH region previously recorded in MDS or AML patients (1p, 4q, 7q, 11q, 13q, 19q, 21q) was detected in our cohort of patients with complex karyotype examined at the diagnosis of MDS. The LOH region appeared to be balanced (i.e., with no DNA copy number change) when examined with conventional and molecular cytogenetic methods. Therefore, a microarray that detects single-nucleotide polymorphisms is an ideal method with which to identify and

  18. 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

  19. 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.

  20. Spanish normative studies in young adults (NEURONORMA young adults project): norms for the Rey-Osterrieth Complex Figure (copy and memory) and Free and Cued Selective Reminding Test.

    Science.gov (United States)

    Palomo, R; Casals-Coll, M; Sánchez-Benavides, G; Quintana, M; Manero, R M; Rognoni, T; Calvo, L; Aranciva, F; Tamayo, F; Peña-Casanova, J

    2013-05-01

    The Rey-Osterrieth Complex Figure (ROCF) and the Free and Cued Selective Reminding Test (FCSRT) are widely used in clinical practice. The ROCF assesses visual perception, constructional praxis, and visuo-spatial memory. The FCSRT assesses verbal learning and memory. In this study, as part of the Spanish normative studies project in young adults (NEURONORMA young adults), we present age- and education-adjusted normative data for both tests obtained by using linear regression techniques. The sample consisted of 179 healthy participants ranging in age from 18 to 49 years. We provide tables for converting raw scores to scaled scores in addition to tables with scores adjusted by socio-demographic factors. The results showed that education affects scores for some of the memory tests and the figure-copying task. Age was only found to have an effect on the performance of visuo-spatial memory tests, and the effect of sex was negligible. The normative data obtained will be extremely useful in the clinical neuropsychological evaluation of young Spanish adults. Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  1. 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...

  2. 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.

  3. Global repeat discovery and estimation of genomic copy number in a large, complex genome using a high-throughput 454 sequence survey

    Directory of Open Access Journals (Sweden)

    Varala Kranthi

    2007-05-01

    Full Text Available Abstract Background Extensive computational and database tools are available to mine genomic and genetic databases for model organisms, but little genomic data is available for many species of ecological or agricultural significance, especially those with large genomes. Genome surveys using conventional sequencing techniques are powerful, particularly for detecting sequences present in many copies per genome. However these methods are time-consuming and have potential drawbacks. High throughput 454 sequencing provides an alternative method by which much information can be gained quickly and cheaply from high-coverage surveys of genomic DNA. Results We sequenced 78 million base-pairs of randomly sheared soybean DNA which passed our quality criteria. Computational analysis of the survey sequences provided global information on the abundant repetitive sequences in soybean. The sequence was used to determine the copy number across regions of large genomic clones or contigs and discover higher-order structures within satellite repeats. We have created an annotated, online database of sequences present in multiple copies in the soybean genome. The low bias of pyrosequencing against repeat sequences is demonstrated by the overall composition of the survey data, which matches well with past estimates of repetitive DNA content obtained by DNA re-association kinetics (Cot analysis. Conclusion This approach provides a potential aid to conventional or shotgun genome assembly, by allowing rapid assessment of copy number in any clone or clone-end sequence. In addition, we show that partial sequencing can provide access to partial protein-coding sequences.

  4. 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...

  5. Recurrence, submicroscopic complexity, and potential clinical relevance of copy gains detected by array CGH that are shown to be unbalanced insertions by FISH.

    Science.gov (United States)

    Neill, Nicholas J; Ballif, Blake C; Lamb, Allen N; Parikh, Sumit; Ravnan, J Britt; Schultz, Roger A; Torchia, Beth S; Rosenfeld, Jill A; Shaffer, Lisa G

    2011-04-01

    Insertions occur when a segment of one chromosome is translocated and inserted into a new region of the same chromosome or a non-homologous chromosome. We report 71 cases with unbalanced insertions identified using array CGH and FISH in 4909 cases referred to our laboratory for array CGH and found to have copy-number abnormalities. Although the majority of insertions were non-recurrent, several recurrent unbalanced insertions were detected, including three der(Y)ins(Y;18)(q?11.2;p11.32p11.32)pat inherited from parents carrying an unbalanced insertion. The clinical significance of these recurrent rearrangements is unclear, although the small size, limited gene content, and inheritance pattern of each suggests that the phenotypic consequences may be benign. Cryptic, submicroscopic duplications were observed at or near the insertion sites in two patients, further confounding the clinical interpretation of these insertions. Using FISH, linear amplification, and array CGH, we identified a 126-kb duplicated region from 19p13.3 inserted into MECP2 at Xq28 in a patient with symptoms of Rett syndrome. Our results demonstrate that although the interpretation of most non-recurrent insertions is unclear without high-resolution insertion site characterization, the potential for an otherwise benign duplication to result in a clinically relevant outcome through the disruption of a gene necessitates the use of FISH to determine whether copy-number gains detected by array CGH represent tandem duplications or unbalanced insertions. Further follow-up testing using techniques such as linear amplification or sequencing should be used to determine gene involvement at the insertion site after FISH has identified the presence of an insertion.

  6. "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)

  7. 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

  8. 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...

  9. 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

  10. 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...

  11. 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.

  12. 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...

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. Probabilistic programmable quantum processors with multiple copies of program states

    International Nuclear Information System (INIS)

    Brazier, Adam; Buzek, Vladimir; Knight, Peter L.

    2005-01-01

    We examine the execution of general U(1) transformations on programmable quantum processors. We show that, with only the minimal assumption of availability of copies of the 1-qubit program state, the apparent advantage of existing schemes proposed by G. Vidal et al. [Phys. Rev. Lett. 88, 047905 (2002)] and M. Hillery et al. [Phys. Rev. A 65, 022301 (2003)] to execute a general U(1) transformation with greater probability using complex program states appears not to hold

  18. 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.

  19. 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.

  20. 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…

  1. 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.

  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. 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.

  4. 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

  5. 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)

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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...

  11. 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.

  12. CoNVaQ: a web tool for copy number variation-based association studies

    DEFF Research Database (Denmark)

    Larsen, Simon Jonas; do Canto, Luisa Matos; Rogatto, Silvia Regina

    2018-01-01

    Copy number variations (CNVs) are large segments of the genome that are duplicated or deleted. Structural variations in the genome have been linked to many complex diseases. Similar to how genome-wide association studies (GWAS) have helped discover single-nucleotide polymorphisms linked to diseas...

  13. 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.

  14. 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)

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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)

  20. Prevalence and pathogen load estimates for the fungus Batrachochytrium dendrobatidis are impacted by ITS DNA copy number variation

    DEFF Research Database (Denmark)

    Rebollar, Eria A.; Woodhams, Douglas C.; LaBumbard, Brandon

    2017-01-01

    The ribosomal gene complex is a multi-copy region that is widely used for phylogenetic analyses of organisms from all 3 domains of life. In fungi, the copy number of the internal transcribed spacer (ITS) is used to detect abundance of pathogens causing diseases such as chytridiomycosis in amphibi...

  1. 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

  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. 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....

  4. 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.

  5. 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

  6. 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.

  7. Copy number variation in the bovine genome

    DEFF Research Database (Denmark)

    Fadista, João; Thomsen, Bo; Holm, Lars-Erik

    2010-01-01

    to genetic variation in cattle. Results We designed and used a set of NimbleGen CGH arrays that tile across the assayable portion of the cattle genome with approximately 6.3 million probes, at a median probe spacing of 301 bp. This study reports the highest resolution map of copy number variation...... in the cattle genome, with 304 CNV regions (CNVRs) being identified among the genomes of 20 bovine samples from 4 dairy and beef breeds. The CNVRs identified covered 0.68% (22 Mb) of the genome, and ranged in size from 1.7 to 2,031 kb (median size 16.7 kb). About 20% of the CNVs co-localized with segmental...... duplications, while 30% encompass genes, of which the majority is involved in environmental response. About 10% of the human orthologous of these genes are associated with human disease susceptibility and, hence, may have important phenotypic consequences. Conclusions Together, this analysis provides a useful...

  8. 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.

  9. 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.

  10. 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

  11. 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...

  12. 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.

  13. 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.

  14. 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.

  15. Copy Number Variations in Tilapia Genomes.

    Science.gov (United States)

    Li, Bi Jun; Li, Hong Lian; Meng, Zining; Zhang, Yong; Lin, Haoran; Yue, Gen Hua; Xia, Jun Hong

    2017-02-01

    Discovering the nature and pattern of genome variation is fundamental in understanding phenotypic diversity among populations. Although several millions of single nucleotide polymorphisms (SNPs) have been discovered in tilapia, the genome-wide characterization of larger structural variants, such as copy number variation (CNV) regions has not been carried out yet. We conducted a genome-wide scan for CNVs in 47 individuals from three tilapia populations. Based on 254 Gb of high-quality paired-end sequencing reads, we identified 4642 distinct high-confidence CNVs. These CNVs account for 1.9% (12.411 Mb) of the used Nile tilapia reference genome. A total of 1100 predicted CNVs were found overlapping with exon regions of protein genes. Further association analysis based on linear model regression found 85 CNVs ranging between 300 and 27,000 base pairs significantly associated to population types (R 2  > 0.9 and P > 0.001). Our study sheds first insights on genome-wide CNVs in tilapia. These CNVs among and within tilapia populations may have functional effects on phenotypes and specific adaptation to particular environments.

  16. 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...

  17. 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...

  18. 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...

  19. 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

  20. 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

  1. 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...

  2. 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...

  3. 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

  4. 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.

  5. 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...

  6. Converting hard copy documents for electronic dissemination

    Energy Technology Data Exchange (ETDEWEB)

    Hoffman, F.

    1994-12-31

    Since the advent of computer systems, the goal of a paperless office, and even a paperless society, has been pursued. While the normal paper flow in an organization is far from totally automated, particularly for items requiring signatures or authorizations, electronic information dissemination is becoming an almost simple task. The reasons for providing on-line documents are many and include faster and easier access for everyone, elimination of printing costs, reduction of wasted shelf and desk space, and the security of having a centrally-located, always up-to-date document. New computer software even provides the user with the ability to annotate documents and to have bookmarks so that the old scribbled-in and dog-eared manual can be replaced without loosing this `customizability`. Moreover, new hypermedia capabilities mean that documents can be read in a non-linear fashion and can include color figures and photographs, audio, and even animation sequences, capabilities which exceed those of paper. The proliferation of network-based information servers, coupled with the growth of the Internet, has enticed academic, governmental, and even commercial organizations to provide increasing numbers of documents and data bases in electronic form via the network, not just to internal staff, but to the public as well. Much of this information, which includes everything from mundane company procedures to spiffy marketing brochures, was previously published only in hard copy. Converting existing documents to electronic form and producing only electronic versions of new documents poses some interesting challenges to the maintainer or author.

  7. Copy Number Variation in the Horse Genome

    Science.gov (United States)

    Ghosh, Sharmila; Qu, Zhipeng; Das, Pranab J.; Fang, Erica; Juras, Rytis; Cothran, E. Gus; McDonell, Sue; Kenney, Daniel G.; Lear, Teri L.; Adelson, David L.; Chowdhary, Bhanu P.; Raudsepp, Terje

    2014-01-01

    We constructed a 400K WG tiling oligoarray for the horse and applied it for the discovery of copy number variations (CNVs) in 38 normal horses of 16 diverse breeds, and the Przewalski horse. Probes on the array represented 18,763 autosomal and X-linked genes, and intergenic, sub-telomeric and chrY sequences. We identified 258 CNV regions (CNVRs) across all autosomes, chrX and chrUn, but not in chrY. CNVs comprised 1.3% of the horse genome with chr12 being most enriched. American Miniature horses had the highest and American Quarter Horses the lowest number of CNVs in relation to Thoroughbred reference. The Przewalski horse was similar to native ponies and draft breeds. The majority of CNVRs involved genes, while 20% were located in intergenic regions. Similar to previous studies in horses and other mammals, molecular functions of CNV-associated genes were predominantly in sensory perception, immunity and reproduction. The findings were integrated with previous studies to generate a composite genome-wide dataset of 1476 CNVRs. Of these, 301 CNVRs were shared between studies, while 1174 were novel and require further validation. Integrated data revealed that to date, 41 out of over 400 breeds of the domestic horse have been analyzed for CNVs, of which 11 new breeds were added in this study. Finally, the composite CNV dataset was applied in a pilot study for the discovery of CNVs in 6 horses with XY disorders of sexual development. A homozygous deletion involving AKR1C gene cluster in chr29 in two affected horses was considered possibly causative because of the known role of AKR1C genes in testicular androgen synthesis and sexual development. While the findings improve and integrate the knowledge of CNVs in horses, they also show that for effective discovery of variants of biomedical importance, more breeds and individuals need to be analyzed using comparable methodological approaches. PMID:25340504

  8. Copy number variation in the horse genome.

    Directory of Open Access Journals (Sweden)

    Sharmila Ghosh

    2014-10-01

    Full Text Available We constructed a 400K WG tiling oligoarray for the horse and applied it for the discovery of copy number variations (CNVs in 38 normal horses of 16 diverse breeds, and the Przewalski horse. Probes on the array represented 18,763 autosomal and X-linked genes, and intergenic, sub-telomeric and chrY sequences. We identified 258 CNV regions (CNVRs across all autosomes, chrX and chrUn, but not in chrY. CNVs comprised 1.3% of the horse genome with chr12 being most enriched. American Miniature horses had the highest and American Quarter Horses the lowest number of CNVs in relation to Thoroughbred reference. The Przewalski horse was similar to native ponies and draft breeds. The majority of CNVRs involved genes, while 20% were located in intergenic regions. Similar to previous studies in horses and other mammals, molecular functions of CNV-associated genes were predominantly in sensory perception, immunity and reproduction. The findings were integrated with previous studies to generate a composite genome-wide dataset of 1476 CNVRs. Of these, 301 CNVRs were shared between studies, while 1174 were novel and require further validation. Integrated data revealed that to date, 41 out of over 400 breeds of the domestic horse have been analyzed for CNVs, of which 11 new breeds were added in this study. Finally, the composite CNV dataset was applied in a pilot study for the discovery of CNVs in 6 horses with XY disorders of sexual development. A homozygous deletion involving AKR1C gene cluster in chr29 in two affected horses was considered possibly causative because of the known role of AKR1C genes in testicular androgen synthesis and sexual development. While the findings improve and integrate the knowledge of CNVs in horses, they also show that for effective discovery of variants of biomedical importance, more breeds and individuals need to be analyzed using comparable methodological approaches.

  9. 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.

  10. 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

  11. Genomic Diversity Using Copy Number Variations in Worldwide Chicken Populations

    Directory of Open Access Journals (Sweden)

    Erica Gorla

    2018-06-01

    Full Text Available Recently, many studies in livestock have focused on the identification of Copy Number Variants (CNVs using high-density Single Nucleotide Polymorphism (SNP arrays, but few have focused on studying chicken ecotypes coming from many locations. CNVs are polymorphisms, which may influence phenotype and are an important source of genetic variation in populations. The aim of this study was to explore the genetic difference and structure, using a high density SNP chip in 936 individuals from seven different countries (Brazil, Italy, Egypt, Mexico, Rwanda, Sri Lanka and Uganda. The DNA was genotyped with the Affymetrix Axiom®600k Chicken Genotyping Array and processed with stringent quality controls to obtain 559,201 SNPs in 915 individuals. The Log R Ratio (LRR and the B Allele Frequency of SNPs were used to perform the CNV calling with PennCNV software based on a Hidden Markov Model analysis and the LRR was used to perform CNV detection with SVS Golden Helix software.After filtering, a total of 19,027 CNVs were detected with the SVS software, while 9,065 CNVs were identified with the Penn CNV software. The CNVs were summarized in 7,001 Copy Number Variant Regions (CNVRs and 4,414 CNVRs, using the software BedTool.The consensus analysis across the CNVRs allowed the identification of 2,820 consensus CNVR, of which 1,721 were gain, 637 loss and 462 complex, for a total length of 53 Mb corresponding to the 5 % of the GalGal5 chicken autosomes. Only the consensus CNV regions obtained from both detections were considered for further analysis.The intersection analysis performed between the chicken gene database (Gallus_gallus-5.0 and the 1,927 consensus CNVRs allowed the identification (within or partial overlap of a total of 2,354 unique genes with an official gene ID.  The CNVRs identified here represent the first comprehensive mapping in several worldwide populations, using a high-density SNP chip.

  12. 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

  13. 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.

  14. Complexity of formation in holography

    International Nuclear Information System (INIS)

    Chapman, Shira; Marrochio, Hugo; Myers, Robert C.

    2017-01-01

    It was recently conjectured that the quantum complexity of a holographic boundary state can be computed by evaluating the gravitational action on a bulk region known as the Wheeler-DeWitt patch. We apply this complexity=action duality to evaluate the ‘complexity of formation’ (DOI: 10.1103/PhysRevLett.116.191301; 10.1103/PhysRevD.93.086006), i.e. the additional complexity arising in preparing the entangled thermofield double state with two copies of the boundary CFT compared to preparing the individual vacuum states of the two copies. We find that for boundary dimensions d>2, the difference in the complexities grows linearly with the thermal entropy at high temperatures. For the special case d=2, the complexity of formation is a fixed constant, independent of the temperature. We compare these results to those found using the complexity=volume duality.

  15. Complexity of formation in holography

    Energy Technology Data Exchange (ETDEWEB)

    Chapman, Shira [Perimeter Institute for Theoretical Physics,Waterloo, ON N2L 2Y5 (Canada); Marrochio, Hugo [Perimeter Institute for Theoretical Physics,Waterloo, ON N2L 2Y5 (Canada); Department of Physics & Astronomy and Guelph-Waterloo Physics Institute,University of Waterloo, Waterloo, ON N2L 3G1 (Canada); Myers, Robert C. [Perimeter Institute for Theoretical Physics,Waterloo, ON N2L 2Y5 (Canada)

    2017-01-16

    It was recently conjectured that the quantum complexity of a holographic boundary state can be computed by evaluating the gravitational action on a bulk region known as the Wheeler-DeWitt patch. We apply this complexity=action duality to evaluate the ‘complexity of formation’ (DOI: 10.1103/PhysRevLett.116.191301; 10.1103/PhysRevD.93.086006), i.e. the additional complexity arising in preparing the entangled thermofield double state with two copies of the boundary CFT compared to preparing the individual vacuum states of the two copies. We find that for boundary dimensions d>2, the difference in the complexities grows linearly with the thermal entropy at high temperatures. For the special case d=2, the complexity of formation is a fixed constant, independent of the temperature. We compare these results to those found using the complexity=volume duality.

  16. 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.

  17. 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...

  18. 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.

  19. 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.).

  20. 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

  1. 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.

  2. 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.

  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. 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.

  5. 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.

  6. Potential Value of Genomic Copy Number Variations in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Chuanjun Zhuo

    2017-06-01

    Full Text Available Schizophrenia is a devastating neuropsychiatric disorder affecting approximately 1% of the global population, and the disease has imposed a considerable burden on families and society. Although, the exact cause of schizophrenia remains unknown, several lines of scientific evidence have revealed that genetic variants are strongly correlated with the development and early onset of the disease. In fact, the heritability among patients suffering from schizophrenia is as high as 80%. Genomic copy number variations (CNVs are one of the main forms of genomic variations, ubiquitously occurring in the human genome. An increasing number of studies have shown that CNVs account for population diversity and genetically related diseases, including schizophrenia. The last decade has witnessed rapid advances in the development of novel genomic technologies, which have led to the identification of schizophrenia-associated CNVs, insight into the roles of the affected genes in their intervals in schizophrenia, and successful manipulation of the target CNVs. In this review, we focus on the recent discoveries of important CNVs that are associated with schizophrenia and outline the potential values that the study of CNVs will bring to the areas of schizophrenia research, diagnosis, and therapy. Furthermore, with the help of the novel genetic tool known as the Clustered Regularly Interspaced Short Palindromic Repeats-associated nuclease 9 (CRISPR/Cas9 system, the pathogenic CNVs as genomic defects could be corrected. In conclusion, the recent novel findings of schizophrenia-associated CNVs offer an exciting opportunity for schizophrenia research to decipher the pathological mechanisms underlying the onset and development of schizophrenia as well as to provide potential clinical applications in genetic counseling, diagnosis, and therapy for this complex mental disease.

  7. Integrative analysis of copy number and gene expression data suggests novel pathogenetic mechanisms in primary myelofibrosis.

    Science.gov (United States)

    Salati, Simona; Zini, Roberta; Nuzzo, Simona; Guglielmelli, Paola; Pennucci, Valentina; Prudente, Zelia; Ruberti, Samantha; Rontauroli, Sebastiano; Norfo, Ruggiero; Bianchi, Elisa; Bogani, Costanza; Rotunno, Giada; Fanelli, Tiziana; Mannarelli, Carmela; Rosti, Vittorio; Salmoiraghi, Silvia; Pietra, Daniela; Ferrari, Sergio; Barosi, Giovanni; Rambaldi, Alessandro; Cazzola, Mario; Bicciato, Silvio; Tagliafico, Enrico; Vannucchi, Alessandro M; Manfredini, Rossella

    2016-04-01

    Primary myelofibrosis (PMF) is a Myeloproliferative Neoplasm (MPN) characterized by megakaryocyte hyperplasia, progressive bone marrow fibrosis, extramedullary hematopoiesis and transformation to Acute Myeloid Leukemia (AML). A number of phenotypic driver (JAK2, CALR, MPL) and additional subclonal mutations have been described in PMF, pointing to a complex genomic landscape. To discover novel genomic lesions that can contribute to disease phenotype and/or development, gene expression and copy number signals were integrated and several genomic abnormalities leading to a concordant alteration in gene expression levels were identified. In particular, copy number gain in the polyamine oxidase (PAOX) gene locus was accompanied by a coordinated transcriptional up-regulation in PMF patients. PAOX inhibition resulted in rapid cell death of PMF progenitor cells, while sparing normal cells, suggesting that PAOX inhibition could represent a therapeutic strategy to selectively target PMF cells without affecting normal hematopoietic cells' survival. Moreover, copy number loss in the chromatin modifier HMGXB4 gene correlates with a concomitant transcriptional down-regulation in PMF patients. Interestingly, silencing of HMGXB4 induces megakaryocyte differentiation, while inhibiting erythroid development, in human hematopoietic stem/progenitor cells. These results highlight a previously un-reported, yet potentially interesting role of HMGXB4 in the hematopoietic system and suggest that genomic and transcriptional imbalances of HMGXB4 could contribute to the aberrant expansion of the megakaryocytic lineage that characterizes PMF patients. © 2015 UICC.

  8. 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.

  9. Copy-number variations involving the IHH locus are associated with syndactyly and craniosynostosis.

    Science.gov (United States)

    Klopocki, Eva; Lohan, Silke; Brancati, Francesco; Koll, Randi; Brehm, Anja; Seemann, Petra; Dathe, Katarina; Stricker, Sigmar; Hecht, Jochen; Bosse, Kristin; Betz, Regina C; Garaci, Francesco Giuseppe; Dallapiccola, Bruno; Jain, Mahim; Muenke, Maximilian; Ng, Vivian C W; Chan, Wilson; Chan, Danny; Mundlos, Stefan

    2011-01-07

    Indian hedgehog (IHH) is a secreted signaling molecule of the hedgehog family known to play important roles in the regulation of chondrocyte differentiation, cortical bone formation, and the development of joints. Here, we describe that copy-number variations of the IHH locus involving conserved noncoding elements (CNEs) are associated with syndactyly and craniosynostosis. These CNEs are able to drive reporter gene expression in a pattern highly similar to wild-type Ihh expression. We postulate that the observed duplications lead to a misexpression and/or overexpression of IHH and by this affect the complex regulatory signaling network during digit and skull development.

  10. 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.

  11. 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.

  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. 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.

  14. 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...

  15. 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...

  16. 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.

  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. 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. 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.

  20. 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...

  1. 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.

  2. 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...

  3. 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. ...

  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. 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)

  6. 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 ...

  7. 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.

  8. 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

  9. 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...

  10. 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...

  11. 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...

  12. 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.

  13. A Jigsaw Lesson for Operations of Complex Numbers.

    Science.gov (United States)

    Lucas, Carol A.

    2000-01-01

    Explains the cooperative learning technique of jigsaw. Details the use of a jigsaw lesson for explaining complex numbers to intermediate algebra students. Includes copies of the handouts given to the expert groups. (Author/ASK)

  14. 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.

  15. 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....

  16. 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.

  17. 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....

  18. 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

  19. 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.

  20. 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)

  1. 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...

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  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. Reafferent copies of imitated actions in the right superior temporal cortex

    Science.gov (United States)

    Iacoboni, Marco; Koski, Lisa M.; Brass, Marcel; Bekkering, Harold; Woods, Roger P.; Dubeau, Marie-Charlotte; Mazziotta, John C.; Rizzolatti, Giacomo

    2001-01-01

    Imitation is a complex phenomenon, the neural mechanisms of which are still largely unknown. When individuals imitate an action that already is present in their motor repertoire, a mechanism matching the observed action onto an internal motor representation of that action should suffice for the purpose. When one has to copy a new action, however, or to adjust an action present in one's motor repertoire to a different observed action, an additional mechanism is needed that allows the observer to compare the action made by another individual with the sensory consequences of the same action made by himself. Previous experiments have shown that a mechanism that directly matches observed actions on their motor counterparts exists in the premotor cortex of monkeys and humans. Here we report the results of functional magnetic resonance experiments, suggesting that in the superior temporal sulcus, a higher order visual region, there is a sector that becomes active both during hand action observation and during imitation even in the absence of direct vision of the imitator's hand. The motor-related activity is greater during imitation than during control motor tasks. This newly identified region has all the requisites for being the region at which the observed actions, and the reafferent motor-related copies of actions made by the imitator, interact. PMID:11717457

  8. Diversity and population-genetic properties of copy number variations and multicopy genes in cattle

    Science.gov (United States)

    Bickhart, Derek M.; Xu, Lingyang; Hutchison, Jana L.; Cole, John B.; Null, Daniel J.; Schroeder, Steven G.; Song, Jiuzhou; Garcia, Jose Fernando; Sonstegard, Tad S.; Van Tassell, Curtis P.; Schnabel, Robert D.; Taylor, Jeremy F.; Lewin, Harris A.; Liu, George E.

    2016-01-01

    The diversity and population genetics of copy number variation (CNV) in domesticated animals are not well understood. In this study, we analysed 75 genomes of major taurine and indicine cattle breeds (including Angus, Brahman, Gir, Holstein, Jersey, Limousin, Nelore, and Romagnola), sequenced to 11-fold coverage to identify 1,853 non-redundant CNV regions. Supported by high validation rates in array comparative genomic hybridization (CGH) and qPCR experiments, these CNV regions accounted for 3.1% (87.5 Mb) of the cattle reference genome, representing a significant increase over previous estimates of the area of the genome that is copy number variable (∼2%). Further population genetics and evolutionary genomics analyses based on these CNVs revealed the population structures of the cattle taurine and indicine breeds and uncovered potential diversely selected CNVs near important functional genes, including AOX1, ASZ1, GAT, GLYAT, and KRTAP9-1. Additionally, 121 CNV gene regions were found to be either breed specific or differentially variable across breeds, such as RICTOR in dairy breeds and PNPLA3 in beef breeds. In contrast, clusters of the PRP and PAG genes were found to be duplicated in all sequenced animals, suggesting that subfunctionalization, neofunctionalization, or overdominance play roles in diversifying those fertility-related genes. These CNV results provide a new glimpse into the diverse selection histories of cattle breeds and a basis for correlating structural variation with complex traits in the future. PMID:27085184

  9. 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.

  10. Bayesian model to detect phenotype-specific genes for copy number data

    Directory of Open Access Journals (Sweden)

    González Juan R

    2012-06-01

    Full Text Available Abstract Background An important question in genetic studies is to determine those genetic variants, in particular CNVs, that are specific to different groups of individuals. This could help in elucidating differences in disease predisposition and response to pharmaceutical treatments. We propose a Bayesian model designed to analyze thousands of copy number variants (CNVs where only few of them are expected to be associated with a specific phenotype. Results The model is illustrated by analyzing three major human groups belonging to HapMap data. We also show how the model can be used to determine specific CNVs related to response to treatment in patients diagnosed with ovarian cancer. The model is also extended to address the problem of how to adjust for confounding covariates (e.g., population stratification. Through a simulation study, we show that the proposed model outperforms other approaches that are typically used to analyze this data when analyzing common copy-number polymorphisms (CNPs or complex CNVs. We have developed an R package, called bayesGen, that implements the model and estimating algorithms. Conclusions Our proposed model is useful to discover specific genetic variants when different subgroups of individuals are analyzed. The model can address studies with or without control group. By integrating all data in a unique model we can obtain a list of genes that are associated with a given phenotype as well as a different list of genes that are shared among the different subtypes of cases.

  11. On-chip real-time single-copy polymerase chain reaction in picoliter droplets

    Energy Technology Data Exchange (ETDEWEB)

    Beer, N R; Hindson, B; Wheeler, E; Hall, S B; Rose, K A; Kennedy, I; Colston, B

    2007-04-20

    The first lab-on-chip system for picoliter droplet generation and PCR amplification with real-time fluorescence detection has performed PCR in isolated droplets at volumes 10{sup 6} smaller than commercial real-time PCR systems. The system utilized a shearing T-junction in a silicon device to generate a stream of monodisperse picoliter droplets that were isolated from the microfluidic channel walls and each other by the oil phase carrier. An off-chip valving system stopped the droplets on-chip, allowing them to be thermal cycled through the PCR protocol without droplet motion. With this system a 10-pL droplet, encapsulating less than one copy of viral genomic DNA through Poisson statistics, showed real-time PCR amplification curves with a cycle threshold of {approx}18, twenty cycles earlier than commercial instruments. This combination of the established real-time PCR assay with digital microfluidics is ideal for isolating single-copy nucleic acids in a complex environment.

  12. 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.

  13. 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...

  14. 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…

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. Copying you copying me: interpersonal motor co-ordination influences automatic imitation.

    Directory of Open Access Journals (Sweden)

    Daniel Joel Shaw

    Full Text Available Moving in a co-ordinated fashion with another individual changes our behaviour towards them; we tend to like them more, find them more attractive, and are more willing to co-operate with them. It is generally assumed that this effect on behaviour results from alterations in representations of self and others. Specifically, through neurophysiological perception-action matching mechanisms, interpersonal motor co-ordination (IMC is believed to forge a neural coupling between actor and observer, which serves to blur boundaries in conceptual self-other representations and causes positive views of the self to be projected onto others. An investigation into this potential neural mechanism is lacking, however. Moreover, the specific components of IMC that might influence this mechanism have not yet been specified. In the present study we exploited a robust behavioural phenomenon--automatic imitation--to assess the degree to which IMC influences neural action observation-execution matching mechanisms. This revealed that automatic imitation is reduced when the actions of another individual are perceived to be synchronised in time, but are spatially incongruent, with our own. We interpret our findings as evidence that IMC does indeed exert an effect on neural perception-action matching mechanisms, but this serves to promote better self-other distinction. Our findings demonstrate that further investigation is required to understand the complex relationship between neural perception-action coupling, conceptual self-other representations, and social behaviour.

  20. Characterization of Copy Number Variation’s Potential Role in Marek’s Disease

    Directory of Open Access Journals (Sweden)

    Lingyang Xu

    2017-05-01

    Full Text Available Marek’s Disease (MD is a highly contagious pathogenic and oncogenic disease primarily affecting chickens. Chicken Lines 63 and 72, as well as their recombinant congenic strains (RCS with varied susceptibility to MD, are ideal models to study the complex mechanisms of genetic resistance to MD. In this study, we investigated copy number variation (CNV in these inbred chicken lines using the Affymetrix Axiom HD 600 K SNP genotyping array. We detected 393 CNV segments across all ten chicken lines, of which 12 CNVs were specifically identified in Line 72. We then assessed genetic structure based on CNV and observed markedly different patterns. Finally, we validated two deletion events in Line 72 and correlated them with genes expression using qPCR and RNA-seq, respectively. Our combined results indicated that these two CNV deletions were likely to contribute to MD susceptibility.

  1. VCS: Tool for Visualizing Copy Number Variation and Single Nucleotide Polymorphism

    Directory of Open Access Journals (Sweden)

    HyoYoung Kim

    2014-12-01

    Full Text Available Copy number variation (CNV or single nucleotide phlyorphism (SNP is useful genetic resource to aid in understanding complex phenotypes or deseases susceptibility. Although thousands of CNVs and SNPs are currently avaliable in the public databases, they are somewhat difficult to use for analyses without visualization tools. We developed a web-based tool called the VCS (visualization of CNV or SNP to visualize the CNV or SNP detected. The VCS tool can assist to easily interpret a biological meaning from the numerical value of CNV and SNP. The VCS provides six visualization tools: i the enrichment of genome contents in CNV; ii the physical distribution of CNV or SNP on chromosomes; iii the distribution of log2 ratio of CNVs with criteria of interested; iv the number of CNV or SNP per binning unit; v the distribution of homozygosity of SNP genotype; and vi cytomap of genes within CNV or SNP region.

  2. 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

  3. 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

  4. Mapping copy number variation by population-scale genome sequencing

    DEFF Research Database (Denmark)

    Mills, Ryan E.; Walter, Klaudia; Stewart, Chip

    2011-01-01

    Genomic structural variants (SVs) are abundant in humans, differing from other forms of variation in extent, origin and functional impact. Despite progress in SV characterization, the nucleotide resolution architecture of most SVs remains unknown. We constructed a map of unbalanced SVs (that is......, copy number variants) based on whole genome DNA sequencing data from 185 human genomes, integrating evidence from complementary SV discovery approaches with extensive experimental validations. Our map encompassed 22,025 deletions and 6,000 additional SVs, including insertions and tandem duplications...

  5. 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....

  6. 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.

  7. Impact of constitutional copy number variants on biological pathway evolution.

    Science.gov (United States)

    Poptsova, Maria; Banerjee, Samprit; Gokcumen, Omer; Rubin, Mark A; Demichelis, Francesca

    2013-01-23

    Inherited Copy Number Variants (CNVs) can modulate the expression levels of individual genes. However, little is known about how CNVs alter biological pathways and how this varies across different populations. To trace potential evolutionary changes of well-described biological pathways, we jointly queried the genomes and the transcriptomes of a collection of individuals with Caucasian, Asian or Yoruban descent combining high-resolution array and sequencing data. We implemented an enrichment analysis of pathways accounting for CNVs and genes sizes and detected significant enrichment not only in signal transduction and extracellular biological processes, but also in metabolism pathways. Upon the estimation of CNV population differentiation (CNVs with different polymorphism frequencies across populations), we evaluated that 22% of the pathways contain at least one gene that is proximal to a CNV (CNV-gene pair) that shows significant population differentiation. The majority of these CNV-gene pairs belong to signal transduction pathways and 6% of the CNV-gene pairs show statistical association between the copy number states and the transcript levels. The analysis suggested possible examples of positive selection within individual populations including NF-kB, MAPK signaling pathways, and Alu/L1 retrotransposition factors. Altogether, our results suggest that constitutional CNVs may modulate subtle pathway changes through specific pathway enzymes, which may become fixed in some populations.

  8. Exploratory analysis of the copy number alterations in glioblastoma multiforme.

    Science.gov (United States)

    Freire, Pablo; Vilela, Marco; Deus, Helena; Kim, Yong-Wan; Koul, Dimpy; Colman, Howard; Aldape, Kenneth D; Bogler, Oliver; Yung, W K Alfred; Coombes, Kevin; Mills, Gordon B; Vasconcelos, Ana T; Almeida, Jonas S

    2008-01-01

    The Cancer Genome Atlas project (TCGA) has initiated the analysis of multiple samples of a variety of tumor types, starting with glioblastoma multiforme. The analytical methods encompass genomic and transcriptomic information, as well as demographic and clinical data about the sample donors. The data create the opportunity for a systematic screening of the components of the molecular machinery for features that may be associated with tumor formation. The wealth of existing mechanistic information about cancer cell biology provides a natural reference for the exploratory exercise. Glioblastoma multiforme DNA copy number data was generated by The Cancer Genome Atlas project for 167 patients using 227 aCGH experiments, and was analyzed to build a catalog of aberrant regions. Genome screening was performed using an information theory approach in order to quantify aberration as a deviation from a centrality without the bias of untested assumptions about its parametric nature. A novel Cancer Genome Browser software application was developed and is made public to provide a user-friendly graphical interface in which the reported results can be reproduced. The application source code and stand alone executable are available at (http://code.google.com/p/cancergenome) and (http://bioinformaticstation.org), respectively. The most important known copy number alterations for glioblastoma were correctly recovered using entropy as a measure of aberration. Additional alterations were identified in different pathways, such as cell proliferation, cell junctions and neural development. Moreover, novel candidates for oncogenes and tumor suppressors were also detected. A detailed map of aberrant regions is provided.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. Efference copy failure during smooth pursuit eye movements in schizophrenia.

    Science.gov (United States)

    Spering, Miriam; Dias, Elisa C; Sanchez, Jamie L; Schütz, Alexander C; Javitt, Daniel C

    2013-07-17

    Abnormal smooth pursuit eye movements in patients with schizophrenia are often considered a consequence of impaired motion perception. Here we used a novel motion prediction task to assess the effects of abnormal pursuit on perception in human patients. Schizophrenia patients (n = 15) and healthy controls (n = 16) judged whether a briefly presented moving target ("ball") would hit/miss a stationary vertical line segment ("goal"). To relate prediction performance and pursuit directly, we manipulated eye movements: in half of the trials, observers smoothly tracked the ball; in the other half, they fixated on the goal. Strict quality criteria ensured that pursuit was initiated and that fixation was maintained. Controls were significantly better in trajectory prediction during pursuit than during fixation, their performance increased with presentation duration, and their pursuit gain and perceptual judgments were correlated. Such perceptual benefits during pursuit may be due to the use of extraretinal motion information estimated from an efference copy signal. With an overall lower performance in pursuit and perception, patients showed no such pursuit advantage and no correlation between pursuit gain and perception. Although patients' pursuit showed normal improvement with longer duration, their prediction performance failed to benefit from duration increases. This dissociation indicates relatively intact early visual motion processing, but a failure to use efference copy information. Impaired efference function in the sensory system may represent a general deficit in schizophrenia and thus contribute to symptoms and functional outcome impairments associated with the disorder.

  14. Chromosomal Copy Number Variation in Saccharomyces pastorianus Is Evidence for Extensive Genome Dynamics in Industrial Lager Brewing Strains.

    Science.gov (United States)

    van den Broek, M; Bolat, I; Nijkamp, J F; Ramos, E; Luttik, M A H; Koopman, F; Geertman, J M; de Ridder, D; Pronk, J T; Daran, J-M

    2015-09-01

    Lager brewing strains of Saccharomyces pastorianus are natural interspecific hybrids originating from the spontaneous hybridization of Saccharomyces cerevisiae and Saccharomyces eubayanus. Over the past 500 years, S. pastorianus has been domesticated to become one of the most important industrial microorganisms. Production of lager-type beers requires a set of essential phenotypes, including the ability to ferment maltose and maltotriose at low temperature, the production of flavors and aromas, and the ability to flocculate. Understanding of the molecular basis of complex brewing-related phenotypic traits is a prerequisite for rational strain improvement. While genome sequences have been reported, the variability and dynamics of S. pastorianus genomes have not been investigated in detail. Here, using deep sequencing and chromosome copy number analysis, we showed that S. pastorianus strain CBS1483 exhibited extensive aneuploidy. This was confirmed by quantitative PCR and by flow cytometry. As a direct consequence of this aneuploidy, a massive number of sequence variants was identified, leading to at least 1,800 additional protein variants in S. pastorianus CBS1483. Analysis of eight additional S. pastorianus strains revealed that the previously defined group I strains showed comparable karyotypes, while group II strains showed large interstrain karyotypic variability. Comparison of three strains with nearly identical genome sequences revealed substantial chromosome copy number variation, which may contribute to strain-specific phenotypic traits. The observed variability of lager yeast genomes demonstrates that systematic linking of genotype to phenotype requires a three-dimensional genome analysis encompassing physical chromosomal structures, the copy number of individual chromosomes or chromosomal regions, and the allelic variation of copies of individual genes. Copyright © 2015, van den Broek et al.

  15. 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

  16. 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

  17. 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.

  18. Single-copy entanglement in critical quantum spin chains

    International Nuclear Information System (INIS)

    Eisert, J.; Cramer, M.

    2005-01-01

    We consider the single-copy entanglement as a quantity to assess quantum correlations in the ground state in quantum many-body systems. We show for a large class of models that already on the level of single specimens of spin chains, criticality is accompanied with the possibility of distilling a maximally entangled state of arbitrary dimension from a sufficiently large block deterministically, with local operations and classical communication. These analytical results--which refine previous results on the divergence of block entropy as the rate at which maximally entangled pairs can be distilled from many identically prepared chains--are made quantitative for general isotropic translationally invariant spin chains that can be mapped onto a quasifree fermionic system, and for the anisotropic XY model. For the XX model, we provide the asymptotic scaling of ∼(1/6)log 2 (L), and contrast it with the block entropy

  19. Copy number variation and autism: New insights and clinical implications

    Directory of Open Access Journals (Sweden)

    Brian Hon-Yin Chung

    2014-07-01

    Full Text Available Genomic research can lead to discoveries of copy number variations (CNVs which can be a susceptibility factor for autism spectrum disorder (ASD. The clinical translation is that this can improve the care of children with ASD. Chromosome microarray is now the first-tiered genetic investigation for ASD, with a detection rate exceeding conventional cytogenetics and any single gene testing. However, interpretation of the results is challenging and there is no consensus on “what” and “how much” to disclose. In this article, we will review how CNV studies have improved our understanding of ASD, the clinical applications, and related counseling issues. Future direction of autism genetic research is also discussed.

  20. 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...

  1. Type II dehydroquinase: molecular replacement with many copies

    International Nuclear Information System (INIS)

    Stewart, Kirsty Anne; Robinson, David Alexander; Lapthorn, Adrian Jonathan

    2007-01-01

    The type II dehydroquinase enzyme is a symmetrical dodecameric protein which crystallizes in either high-symmetry cubic space groups or low-symmetry crystal systems with multiple copies in the asymmetric unit. Both systems have provided challenging examples for molecular replacement; for example, a triclinic crystal form has 16 dodecamers (192 monomers) in the unit cell. Three difficult examples are discussed and two are used as test cases to compare the performance of four commonly used molecular-replacement packages. Type II dehydroquinase is a small (150-amino-acid) protein which in solution packs together to form a dodecamer with 23 cubic symmetry. In crystals of this protein the symmetry of the biological unit can be coincident with the crystallographic symmetry, giving rise to cubic crystal forms with a single monomer in the asymmetric unit. In crystals where this is not the case, multiple copies of the monomer are present, giving rise to significant and often confusing noncrystallographic symmetry in low-symmetry crystal systems. These different crystal forms pose a variety of challenges for solution by molecular replacement. Three examples of structure solutions, including a highly unusual triclinic crystal form with 16 dodecamers (192 monomers) in the unit cell, are described. Four commonly used molecular-replacement packages are assessed against two of these examples, one of high symmetry and the other of low symmetry; this study highlights how program performance can vary significantly depending on the given problem. In addition, the final refined structure of the 16-dodecamer triclinic crystal form is analysed and shown not to be a superlattice structure, but rather an F-centred cubic crystal with frustrated crystallographic symmetry

  2. Exploratory analysis of the copy number alterations in glioblastoma multiforme.

    Directory of Open Access Journals (Sweden)

    Pablo Freire

    Full Text Available The Cancer Genome Atlas project (TCGA has initiated the analysis of multiple samples of a variety of tumor types, starting with glioblastoma multiforme. The analytical methods encompass genomic and transcriptomic information, as well as demographic and clinical data about the sample donors. The data create the opportunity for a systematic screening of the components of the molecular machinery for features that may be associated with tumor formation. The wealth of existing mechanistic information about cancer cell biology provides a natural reference for the exploratory exercise.Glioblastoma multiforme DNA copy number data was generated by The Cancer Genome Atlas project for 167 patients using 227 aCGH experiments, and was analyzed to build a catalog of aberrant regions. Genome screening was performed using an information theory approach in order to quantify aberration as a deviation from a centrality without the bias of untested assumptions about its parametric nature. A novel Cancer Genome Browser software application was developed and is made public to provide a user-friendly graphical interface in which the reported results can be reproduced. The application source code and stand alone executable are available at (http://code.google.com/p/cancergenome and (http://bioinformaticstation.org, respectively.The most important known copy number alterations for glioblastoma were correctly recovered using entropy as a measure of aberration. Additional alterations were identified in different pathways, such as cell proliferation, cell junctions and neural development. Moreover, novel candidates for oncogenes and tumor suppressors were also detected. A detailed map of aberrant regions is provided.

  3. 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.

  4. Exploiting a Reference Genome in Terms of Duplications: The Network of Paralogs and Single Copy Genes in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Mara Sangiovanni

    2013-12-01

    Full Text Available Arabidopsis thaliana became the model organism for plant studies because of its small diploid genome, rapid lifecycle and short adult size. Its genome was the first among plants to be sequenced, becoming the reference in plant genomics. However, the Arabidopsis genome is characterized by an inherently complex organization, since it has undergone ancient whole genome duplications, followed by gene reduction, diploidization events and extended rearrangements, which relocated and split up the retained portions. These events, together with probable chromosome reductions, dramatically increased the genome complexity, limiting its role as a reference. The identification of paralogs and single copy genes within a highly duplicated genome is a prerequisite to understand its organization and evolution and to improve its exploitation in comparative genomics. This is still controversial, even in the widely studied Arabidopsis genome. This is also due to the lack of a reference bioinformatics pipeline that could exhaustively identify paralogs and singleton genes. We describe here a complete computational strategy to detect both duplicated and single copy genes in a genome, discussing all the methodological issues that may strongly affect the results, their quality and their reliability. This approach was used to analyze the organization of Arabidopsis nuclear protein coding genes, and besides classifying computationally defined paralogs into networks and single copy genes into different classes, it unraveled further intriguing aspects concerning the genome annotation and the gene relationships in this reference plant species. Since our results may be useful for comparative genomics and genome functional analyses, we organized a dedicated web interface to make them accessible to the scientific community.

  5. 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

  6. 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

  7. A microhomology-mediated break-induced replication model for the origin of human copy number variation.

    Directory of Open Access Journals (Sweden)

    P J Hastings

    2009-01-01

    Full Text Available Chromosome structural changes with nonrecurrent endpoints associated with genomic disorders offer windows into the mechanism of origin of copy number variation (CNV. A recent report of nonrecurrent duplications associated with Pelizaeus-Merzbacher disease identified three distinctive characteristics. First, the majority of events can be seen to be complex, showing discontinuous duplications mixed with deletions, inverted duplications, and triplications. Second, junctions at endpoints show microhomology of 2-5 base pairs (bp. Third, endpoints occur near pre-existing low copy repeats (LCRs. Using these observations and evidence from DNA repair in other organisms, we derive a model of microhomology-mediated break-induced replication (MMBIR for the origin of CNV and, ultimately, of LCRs. We propose that breakage of replication forks in stressed cells that are deficient in homologous recombination induces an aberrant repair process with features of break-induced replication (BIR. Under these circumstances, single-strand 3' tails from broken replication forks will anneal with microhomology on any single-stranded DNA nearby, priming low-processivity polymerization with multiple template switches generating complex rearrangements, and eventual re-establishment of processive replication.

  8. 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

  9. 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.

  10. Association of coatomer proteins with the beta-receptor for platelet-derived growth factor

    DEFF Research Database (Denmark)

    Hansen, Klaus; Rönnstrand, L; Rorsman, C

    1997-01-01

    The nonreceptor tyrosine kinase Src binds to and is activated by the beta-receptor for platelet-derived growth factor (PDGF). The interaction leads to Src phosphorylation of Tyr934 in the kinase domain of the receptor. In the course of the functional characterization of this phosphorylation, we...... of intracellular vesicle transport. In order to explore the functional significance of the interaction between alpha- and beta'-COP and the PDGF receptor, a receptor mutant was made in which the conserved histidine residue 928 was mutated to an alanine residue. The mutant receptor, which was unable to bind alpha...

  11. Automotive advertising copy test. Final report. [Mileage estimates

    Energy Technology Data Exchange (ETDEWEB)

    1984-10-01

    The purpose of this research project was to explore the following issues: (1) mileage recall/recognition of miles per gallon/highway mileage estimates in print ads by advertisement readers; (2) determine consumer expectations and believability of advertised mileage guidelines; (3) measure recall/comprehension of mileage disclaimers; and (4) determine how consumers utilize published mileage estimates. The evidence from this study points to a public which is quite familiar with the EPA mileage estimates, in terms of using them as guidelines and in finding them to be helpful. Most adults also appear to be knowledgeable about factors which can affect car performance and, therefore, anticipate that, within certain tolerances, their actual mileage will differ from the EPA estimates. Although the consumer has been educated regarding fuel estimates, there is a very strong suggestion from this research that typical automobile print advertising does a less than an effective job in generating awareness of specific EPA estimates as well as their attendant disclaimer. Copy strategy and execution have a critical impact on recall of the EPA mileage estimates. 18 tables.

  12. Copy Number Variation in Hereditary Non-Polyposis Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Garry N. Hannan

    2013-09-01

    Full Text Available Hereditary non-polyposis colorectal cancer (HNPCC is the commonest form of inherited colorectal cancer (CRC predisposition and by definition describes families which conform to the Amsterdam Criteria or reiterations thereof. In ~50% of patients adhering to the Amsterdam criteria germline variants are identified in one of four DNA Mismatch repair (MMR genes MLH1, MSH2, MSH6 and PMS2. Loss of function of any one of these genes results in a failure to repair DNA errors occurring during replication which can be most easily observed as DNA microsatellite instability (MSI—a hallmark feature of this disease. The remaining 50% of patients without a genetic diagnosis of disease may harbour more cryptic changes within or adjacent to MLH1, MSH2, MSH6 or PMS2 or elsewhere in the genome. We used a high density cytogenetic array to screen for deletions or duplications in a series of patients, all of whom adhered to the Amsterdam/Bethesda criteria, to determine if genomic re-arrangements could account for a proportion of patients that had been shown not to harbour causative mutations as assessed by standard diagnostic techniques. The study has revealed some associations between copy number variants (CNVs and HNPCC mutation negative cases and further highlights difficulties associated with CNV analysis.

  13. A comprehensive Software Copy Protection and Digital Rights Management platform

    Directory of Open Access Journals (Sweden)

    Ayman Mohammad Bahaa-Eldin

    2014-09-01

    Full Text Available This article proposes a Powerful and Flexible System for Software Copy Protection (SCP and Digital Rights Management (DRM based on Public Key Infrastructure (PKI standards. Software protection is achieved through a multi-phase methodology with both static and dynamic processing of the executable file. The system defeats most of the attacks and cracking techniques and makes sure that the protected software is never in a flat form, with a suitable portion of it always being encrypted during execution. A novel performance-tuning algorithm is proposed to lower the overhead of the protection process to its minimum depending on the software dynamic execution behavior. All system calls to access resources and objects such as files, and input/output devices are intercepted and encapsulated with secure rights management code to enforce the required license model. The system can be integrated with hardware authentication techniques (like dongles, and to Internet based activation and DRM servers over the cloud. The system is flexible to apply any model of licensing including state-based license such as expiration dates and number of trials. The usage of a standard markup language (XrML to describe the license makes it easier to apply new licensing operations like re-sale and content rental.

  14. 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.

  15. ON COPIES OF THE MANUSCRIPT OF THE GLAGOLITIC QUARESIMALE

    Directory of Open Access Journals (Sweden)

    Andrea Radošević

    2014-01-01

    Full Text Available Studies about the linguistic characteristics of a few Glagolitic manuscript versions of Quaresimale, as well as studies about other texts (The Treatise on the Seven Deadly Sins; Greblo's Commentary on the Passion of Christ that were included in the same manuscripts as the Lenten sermons, have already been published. After the structure of the Glagolitic Quaresimale, that has been preserved in the form of five Glagolitic manuscripts (Kolunić Quaresimale, Quaresimale III a 19, Greblo Quaresimale, Oport Quaresimale, Fatević Miscellany, had been studied, the next step in the research of the Glagolitic Quaresimale was to study the relationship between the written sermons and their performance, because the performance, or orality, is one of the main characteristics of sermons as a genre. The results of this study show that the different places in which the copies of the manuscript were kept, the thematic similarity between the sermons and other texts in manuscripts, as well as the attitude of the scribes towards the graphic design of the text, had influenced the performance of the Lenten sermons. The performances of these Glagolitic sermons reflect a great deal more variety than would be expected on the basis of the content of sermons in all five manuscripts which is very similar.

  16. 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

  17. Association tests and software for copy number variant data

    Directory of Open Access Journals (Sweden)

    Plagnol Vincent

    2009-01-01

    Full Text Available Abstract Recent studies have suggested that copy number variation (CNV significantly contributes to genetic predisposition to several common disorders. These findings, combined with the imperfect tagging of CNVs by single nucleotide polymorphisms (SNPs, have motivated the development of association studies directly targeting CNVs. Several assays, including comparative genomic hybridisation arrays, SNP genotyping arrays, or DNA quantification through real-time polymerase chain reaction analysis, allow direct assessment of CNV status in cohorts sufficiently large to provide adequate statistical power for association studies. When analysing data provided by these assays, association tests for CNV data are not fundamentally different from SNP-based association tests. The main difference arises when the quality of the CNV assay is not sufficient to convert unequivocally the raw measurement into discrete calls -- a common issue, given the technological limitations of current CNV assays. When this is the case, association tests are more appropriately based on the raw continuous measurement provided by the CNV assay, instead of potentially inaccurate discrete calls, thus motivating the development of new statistical methods. Here, the programs available for CNV association testing for case control or family data are reviewed, using either discrete calls or raw continuous data.

  18. Gene copy number variation throughout the Plasmodium falciparum genome

    Directory of Open Access Journals (Sweden)

    Stewart Lindsay B

    2009-08-01

    Full Text Available Abstract Background Gene copy number variation (CNV is responsible for several important phenotypes of the malaria parasite Plasmodium falciparum, including drug resistance, loss of infected erythrocyte cytoadherence and alteration of receptor usage for erythrocyte invasion. Despite the known effects of CNV, little is known about its extent throughout the genome. Results We performed a whole-genome survey of CNV genes in P. falciparum using comparative genome hybridisation of a diverse set of 16 laboratory culture-adapted isolates to a custom designed high density Affymetrix GeneChip array. Overall, 186 genes showed hybridisation signals consistent with deletion or amplification in one or more isolate. There is a strong association of CNV with gene length, genomic location, and low orthology to genes in other Plasmodium species. Sub-telomeric regions of all chromosomes are strongly associated with CNV genes independent from members of previously described multigene families. However, ~40% of CNV genes were located in more central regions of the chromosomes. Among the previously undescribed CNV genes, several that are of potential phenotypic relevance are identified. Conclusion CNV represents a major form of genetic variation within the P. falciparum genome; the distribution of gene features indicates the involvement of highly non-random mutational and selective processes. Additional studies should be directed at examining CNV in natural parasite populations to extend conclusions to clinical settings.

  19. Supervised classification of combined copy number and gene expression data

    Directory of Open Access Journals (Sweden)

    Riccadonna S.

    2007-12-01

    Full Text Available In this paper we apply a predictive profiling method to genome copy number aberrations (CNA in combination with gene expression and clinical data to identify molecular patterns of cancer pathophysiology. Predictive models and optimal feature lists for the platforms are developed by a complete validation SVM-based machine learning system. Ranked list of genome CNA sites (assessed by comparative genomic hybridization arrays – aCGH and of differentially expressed genes (assessed by microarray profiling with Affy HG-U133A chips are computed and combined on a breast cancer dataset for the discrimination of Luminal/ ER+ (Lum/ER+ and Basal-like/ER- classes. Different encodings are developed and applied to the CNA data, and predictive variable selection is discussed. We analyze the combination of profiling information between the platforms, also considering the pathophysiological data. A specific subset of patients is identified that has a different response to classification by chromosomal gains and losses and by differentially expressed genes, corroborating the idea that genomic CNA can represent an independent source for tumor classification.

  20. 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.

  1. The importance of copy number variation in congenital heart disease

    Science.gov (United States)

    Costain, Gregory; Silversides, Candice K; Bassett, Anne S

    2016-01-01

    Congenital heart disease (CHD) is the most common class of major malformations in humans. The historical association with large chromosomal abnormalities foreshadowed the role of submicroscopic rare copy number variations (CNVs) as important genetic causes of CHD. Recent studies have provided robust evidence for these structural variants as genome-wide contributors to all forms of CHD, including CHD that appears isolated without extra-cardiac features. Overall, a CNV-related molecular diagnosis can be made in up to one in eight patients with CHD. These include de novo and inherited variants at established (chromosome 22q11.2), emerging (chromosome 1q21.1), and novel loci across the genome. Variable expression of rare CNVs provides support for the notion of a genetic spectrum of CHD that crosses traditional anatomic classification boundaries. Clinical genetic testing using genome-wide technologies (e.g., chromosomal microarray analysis) is increasingly employed in prenatal, paediatric and adult settings. CNV discoveries in CHD have translated to changes to clinical management, prognostication and genetic counselling. The convergence of findings at individual gene and at pathway levels is shedding light on the mechanisms that govern human cardiac morphogenesis. These clinical and research advances are helping to inform whole-genome sequencing, the next logical step in delineating the genetic architecture of CHD. PMID:28706735

  2. ATLAS copies its first PetaByte out of CERN

    CERN Multimedia

    M. Branco; P. Salgado; L. Goossens; A. Nairz

    2006-01-01

    On 6th August ATLAS reached a major milestone for its Distributed Data Management project - copying its first PetaByte (1015 Bytes) of data out from CERN to computing centers around the world. This achievement is part of the so-called 'Tier-0 exercise' running since 19th June, where simulated fake data is used to exercise the expected data flow within the CERN computing centre and out over the Grid to the Tier-1 computing centers as would happen during the real data taking. The expected rate of data output from CERN when the detector is running at full trigger rate is 780 MB/s shared among 10 external Tier-1 sites(*), amounting to around 8 PetaBytes per year. The idea of the exercise was to try to reach this data rate and sustain it for as long as possible. The exercise was run as part of the LCG's Service Challenges and allowed ATLAS to test successfully the integration of ATLAS software with the LCG middleware services that are used for low level cataloging and the actual data movement. When ATLAS is produ...

  3. 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

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  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. 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…

  10. 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.).

  11. 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...

  12. 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…

  13. 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.

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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…

  19. 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

  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. 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.

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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.” ...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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.

  12. 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.

  13. Optimization of Critical Hairpin Features Allows miRNA-based Gene Knockdown Upon Single-copy Transduction

    Directory of Open Access Journals (Sweden)

    Renier Myburgh

    2014-01-01

    Full Text Available Gene knockdown using micro RNA (miRNA-based vector constructs is likely to become a prominent gene therapy approach. It was the aim of this study to improve the efficiency of gene knockdown through optimizing the structure of miRNA mimics. Knockdown of two target genes was analyzed: CCR5 and green fluorescent protein. We describe here a novel and optimized miRNA mimic design called mirGE comprising a lower stem length of 13 base pairs (bp, positioning of the targeting strand on the 5′ side of the miRNA, together with nucleotide mismatches in upper stem positions 1 and 12 placed on the passenger strand. Our mirGE proved superior to miR-30 in four aspects: yield of targeting strand incorporation into RNA-induced silencing complex (RISC; incorporation into RISC of correct targeting strand; precision of cleavage by Drosha; and ratio of targeting strand over passenger strand. A triple mirGE hairpin cassette targeting CCR5 was constructed. It allowed CCR5 knockdown with an efficiency of over 90% upon single-copy transduction. Importantly, single-copy expression of this construct rendered transduced target cells, including primary human macrophages, resistant to infection with a CCR5-tropic strain of HIV. Our results provide new insights for a better knockdown efficiency of constructs containing miRNA. Our results also provide the proof-of-principle that cells can be rendered HIV resistant through single-copy vector transduction, rendering this approach more compatible with clinical applications.

  14. A map of copy number variations in Chinese populations.

    Directory of Open Access Journals (Sweden)

    Haiyi Lou

    Full Text Available It has been shown that the human genome contains extensive copy number variations (CNVs. Investigating the medical and evolutionary impacts of CNVs requires the knowledge of locations, sizes and frequency distribution of them within and between populations. However, CNV study of Chinese minorities, which harbor the majority of genetic diversity of Chinese populations, has been underrepresented considering the same efforts in other populations. Here we constructed, to our knowledge, a first CNV map in seven Chinese populations representing the major linguistic groups in China with 1,440 CNV regions identified using Affymetrix SNP 6.0 Array. Considerable differences in distributions of CNV regions between populations and substantial population structures were observed. We showed that ∼35% of CNV regions identified in minority ethnic groups are not shared by Han Chinese population, indicating that the contribution of the minorities to genetic architecture of Chinese population could not be ignored. We further identified highly differentiated CNV regions between populations. For example, a common deletion in Dong and Zhuang (44.4% and 50%, which overlaps two keratin-associated protein genes contributing to the structure of hair fibers, was not observed in Han Chinese. Interestingly, the most differentiated CNV deletion between HapMap CEU and YRI containing CCL3L1 gene reported in previous studies was also the highest differentiated regions between Tibetan and other populations. Besides, by jointly analyzing CNVs and SNPs, we found a CNV region containing gene CTDSPL were in almost perfect linkage disequilibrium between flanking SNPs in Tibetan while not in other populations except HapMap CHD. Furthermore, we found the SNP taggability of CNVs in Chinese populations was much lower than that in European populations. Our results suggest the necessity of a full characterization of CNVs in Chinese populations, and the CNV map we constructed serves as a

  15. A Map of Copy Number Variations in Chinese Populations

    Science.gov (United States)

    Yang, Yajun; Kang, Longli; Zhang, Xin; Jin, Wenfei; Wu, Bailin; Jin, Li; Xu, Shuhua

    2011-01-01

    It has been shown that the human genome contains extensive copy number variations (CNVs). Investigating the medical and evolutionary impacts of CNVs requires the knowledge of locations, sizes and frequency distribution of them within and between populations. However, CNV study of Chinese minorities, which harbor the majority of genetic diversity of Chinese populations, has been underrepresented considering the same efforts in other populations. Here we constructed, to our knowledge, a first CNV map in seven Chinese populations representing the major linguistic groups in China with 1,440 CNV regions identified using Affymetrix SNP 6.0 Array. Considerable differences in distributions of CNV regions between populations and substantial population structures were observed. We showed that ∼35% of CNV regions identified in minority ethnic groups are not shared by Han Chinese population, indicating that the contribution of the minorities to genetic architecture of Chinese population could not be ignored. We further identified highly differentiated CNV regions between populations. For example, a common deletion in Dong and Zhuang (44.4% and 50%), which overlaps two keratin-associated protein genes contributing to the structure of hair fibers, was not observed in Han Chinese. Interestingly, the most differentiated CNV deletion between HapMap CEU and YRI containing CCL3L1 gene reported in previous studies was also the highest differentiated regions between Tibetan and other populations. Besides, by jointly analyzing CNVs and SNPs, we found a CNV region containing gene CTDSPL were in almost perfect linkage disequilibrium between flanking SNPs in Tibetan while not in other populations except HapMap CHD. Furthermore, we found the SNP taggability of CNVs in Chinese populations was much lower than that in European populations. Our results suggest the necessity of a full characterization of CNVs in Chinese populations, and the CNV map we constructed serves as a useful resource in

  16. Contribution of Rare Copy Number Variants to Isolated Human Malformations

    Science.gov (United States)

    Serra-Juhé, Clara; Rodríguez-Santiago, Benjamín; Cuscó, Ivon; Vendrell, Teresa; Camats, Núria; Torán, Núria; Pérez-Jurado, Luis A.

    2012-01-01

    Background Congenital malformations are present in approximately 2–3% of liveborn babies and 20% of stillborn fetuses. The mechanisms underlying the majority of sporadic and isolated congenital malformations are poorly understood, although it is hypothesized that the accumulation of rare genetic, genomic and epigenetic variants converge to deregulate developmental networks. Methodology/Principal Findings We selected samples from 95 fetuses with congenital malformations not ascribed to a specific syndrome (68 with isolated malformations, 27 with multiple malformations). Karyotyping and Multiplex Ligation-dependent Probe Amplification (MLPA) discarded recurrent genomic and cytogenetic rearrangements. DNA extracted from the affected tissue (46%) or from lung or liver (54%) was analyzed by molecular karyotyping. Validations and inheritance were obtained by MLPA. We identified 22 rare copy number variants (CNV) [>100 kb, either absent (n = 7) or very uncommon (n = 15, malformations (21%), including 11 deletions and 11 duplications. One of the 9 tested rearrangements was de novo while the remaining were inherited from a healthy parent. The highest frequency was observed in fetuses with heart hypoplasia (8/17, 62.5%), with two events previously related with the phenotype. Double events hitting candidate genes were detected in two samples with brain malformations. Globally, the burden of deletions was significantly higher in fetuses with malformations compared to controls. Conclusions/Significance Our data reveal a significant contribution of rare deletion-type CNV, mostly inherited but also de novo, to human congenital malformations, especially heart hypoplasia, and reinforce the hypothesis of a multifactorial etiology in most cases. PMID:23056206

  17. Rare copy number variants identified in prune belly syndrome.

    Science.gov (United States)

    Boghossian, Nansi S; Sicko, Robert J; Giannakou, Andreas; Dimopoulos, Aggeliki; Caggana, Michele; Tsai, Michael Y; Yeung, Edwina H; Pankratz, Nathan; Cole, Benjamin R; Romitti, Paul A; Browne, Marilyn L; Fan, Ruzong; Liu, Aiyi; Kay, Denise M; Mills, James L

    2018-03-01

    Prune belly syndrome (PBS), also known as Eagle-Barrett syndrome, is a rare congenital disorder characterized by absence or hypoplasia of the abdominal wall musculature, urinary tract anomalies, and cryptorchidism in males. The etiology of PBS is largely unresolved, but genetic factors are implicated given its recurrence in families. We examined cases of PBS to identify novel pathogenic copy number variants (CNVs). A total of 34 cases (30 males and 4 females) with PBS identified from all live births in New York State (1998-2005) were genotyped using Illumina HumanOmni2.5 microarrays. CNVs were prioritized if they were absent from in-house controls, encompassed ≥10 consecutive probes, were ≥20 Kb in size, had ≤20% overlap with common variants in population reference controls, and had ≤20% overlap with any variant previously detected in other birth defect phenotypes screened in our laboratory. We identified 17 candidate autosomal CNVs; 10 cases each had one CNV and four cases each had two CNVs. The CNVs included a 158 Kb duplication at 4q22 that overlaps the BMPR1B gene; duplications of different sizes carried by two cases in the intron of STIM1 gene; a 67 Kb duplication 202 Kb downstream of the NOG gene, and a 1.34 Mb deletion including the MYOCD gene. The identified rare CNVs spanned genes involved in mesodermal, muscle, and urinary tract development and differentiation, which might help in elucidating the genetic contribution to PBS. We did not have parental DNA and cannot identify whether these CNVs were de novo or inherited. Further research on these CNVs, particularly BMP signaling is warranted to elucidate the pathogenesis of PBS. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  18. Rare copy number variants implicated in posterior urethral valves.

    Science.gov (United States)

    Boghossian, Nansi S; Sicko, Robert J; Kay, Denise M; Rigler, Shannon L; Caggana, Michele; Tsai, Michael Y; Yeung, Edwina H; Pankratz, Nathan; Cole, Benjamin R; Druschel, Charlotte M; Romitti, Paul A; Browne, Marilyn L; Fan, Ruzong; Liu, Aiyi; Brody, Lawrence C; Mills, James L

    2016-03-01

    The cause of posterior urethral valves (PUV) is unknown, but genetic factors are suspected given their familial occurrence. We examined cases of isolated PUV to identify novel copy number variants (CNVs). We identified 56 cases of isolated PUV from all live-births in New York State (1998-2005). Samples were genotyped using Illumina HumanOmni2.5 microarrays. Autosomal and sex-linked CNVs were identified using PennCNV and cnvPartition software. CNVs were prioritized for follow-up if they were absent from in-house controls, contained ≥ 10 consecutive probes, were ≥ 20 Kb in size, had ≤ 20% overlap with variants detected in other birth defect phenotypes screened in our lab, and were rare in population reference controls. We identified 47 rare candidate PUV-associated CNVs in 32 cases; one case had a 3.9 Mb deletion encompassing BMP7. Mutations in BMP7 have been associated with severe anomalies in the mouse urethra. Other interesting CNVs, each detected in a single PUV case included: a deletion of PIK3R3 and TSPAN1, duplication/triplication in FGF12, duplication of FAT1--a gene essential for normal growth and development, a large deletion (>2 Mb) on chromosome 17q that involves TBX2 and TBX4, and large duplications (>1 Mb) on chromosomes 3q and 6q. Our finding of previously unreported novel CNVs in PUV suggests that genetic factors may play a larger role than previously understood. Our data show a potential role of CNVs in up to 57% of cases examined. Investigation of genes in these CNVs may provide further insights into genetic variants that contribute to PUV. © 2015 Wiley Periodicals, Inc.

  19. Rare copy number deletions predict individual variation in intelligence.

    Directory of Open Access Journals (Sweden)

    Ronald A Yeo

    2011-01-01

    Full Text Available Phenotypic variation in human intellectual functioning shows substantial heritability, as demonstrated by a long history of behavior genetic studies. Many recent molecular genetic studies have attempted to uncover specific genetic variations responsible for this heritability, but identified effects capture little variance and have proven difficult to replicate. The present study, motivated an interest in "mutation load" emerging from evolutionary perspectives, examined the importance of the number of rare (or infrequent copy number variations (CNVs, and the total number of base pairs included in such deletions, for psychometric intelligence. Genetic data was collected using the Illumina 1MDuoBeadChip Array from a sample of 202 adult individuals with alcohol dependence, and a subset of these (N = 77 had been administered the Wechsler Abbreviated Scale of Intelligence (WASI. After removing CNV outliers, the impact of rare genetic deletions on psychometric intelligence was investigated in 74 individuals. The total length of the rare deletions significantly and negatively predicted intelligence (r = -.30, p = .01. As prior studies have indicated greater heritability in individuals with relatively higher parental socioeconomic status (SES, we also examined the impact of ethnicity (Anglo/White vs. Other, as a proxy measure of SES; these groups did not differ on any genetic variable. This categorical variable significantly moderated the effect of length of deletions on intelligence, with larger effects being noted in the Anglo/White group. Overall, these results suggest that rare deletions (between 5% and 1% population frequency or less adversely affect intellectual functioning, and that pleotropic effects might partly account for the association of intelligence with health and mental health status. Significant limitations of this research, including issues of generalizability and CNV measurement, are discussed.

  20. Rare Copy Number Deletions Predict Individual Variation in Intelligence

    Science.gov (United States)

    Yeo, Ronald A.; Gangestad, Steven W.; Liu, Jingyu; Calhoun, Vince D.; Hutchison, Kent E.

    2011-01-01

    Phenotypic variation in human intellectual functioning shows substantial heritability, as demonstrated by a long history of behavior genetic studies. Many recent molecular genetic studies have attempted to uncover specific genetic variations responsible for this heritability, but identified effects capture little variance and have proven difficult to replicate. The present study, motivated an interest in “mutation load” emerging from evolutionary perspectives, examined the importance of the number of rare (or infrequent) copy number variations (CNVs), and the total number of base pairs included in such deletions, for psychometric intelligence. Genetic data was collected using the Illumina 1MDuoBeadChip Array from a sample of 202 adult individuals with alcohol dependence, and a subset of these (N = 77) had been administered the Wechsler Abbreviated Scale of Intelligence (WASI). After removing CNV outliers, the impact of rare genetic deletions on psychometric intelligence was investigated in 74 individuals. The total length of the rare deletions significantly and negatively predicted intelligence (r = −.30, p = .01). As prior studies have indicated greater heritability in individuals with relatively higher parental socioeconomic status (SES), we also examined the impact of ethnicity (Anglo/White vs. Other), as a proxy measure of SES; these groups did not differ on any genetic variable. This categorical variable significantly moderated the effect of length of deletions on intelligence, with larger effects being noted in the Anglo/White group. Overall, these results suggest that rare deletions (between 5% and 1% population frequency or less) adversely affect intellectual functioning, and that pleotropic effects might partly account for the association of intelligence with health and mental health status. Significant limitations of this research, including issues of generalizability and CNV measurement, are discussed. PMID:21298096

  1. Family-Based Benchmarking of Copy Number Variation Detection Software.

    Science.gov (United States)

    Nutsua, Marcel Elie; Fischer, Annegret; Nebel, Almut; Hofmann, Sylvia; Schreiber, Stefan; Krawczak, Michael; Nothnagel, Michael

    2015-01-01

    The analysis of structural variants, in particular of copy-number variations (CNVs), has proven valuable in unraveling the genetic basis of human diseases. Hence, a large number of algorithms have been developed for the detection of CNVs in SNP array signal intensity data. Using the European and African HapMap trio data, we undertook a comparative evaluation of six commonly used CNV detection software tools, namely Affymetrix Power Tools (APT), QuantiSNP, PennCNV, GLAD, R-gada and VEGA, and assessed their level of pair-wise prediction concordance. The tool-specific CNV prediction accuracy was assessed in silico by way of intra-familial validation. Software tools differed greatly in terms of the number and length of the CNVs predicted as well as the number of markers included in a CNV. All software tools predicted substantially more deletions than duplications. Intra-familial validation revealed consistently low levels of prediction accuracy as measured by the proportion of validated CNVs (34-60%). Moreover, up to 20% of apparent family-based validations were found to be due to chance alone. Software using Hidden Markov models (HMM) showed a trend to predict fewer CNVs than segmentation-based algorithms albeit with greater validity. PennCNV yielded the highest prediction accuracy (60.9%). Finally, the pairwise concordance of CNV prediction was found to vary widely with the software tools involved. We recommend HMM-based software, in particular PennCNV, rather than segmentation-based algorithms when validity is the primary concern of CNV detection. QuantiSNP may be used as an additional tool to detect sets of CNVs not detectable by the other tools. Our study also reemphasizes the need for laboratory-based validation, such as qPCR, of CNVs predicted in silico.

  2. A genome-wide copy number variant study of suicidal behavior.

    Directory of Open Access Journals (Sweden)

    Jeffrey A Gross

    Full Text Available Suicide and suicide attempts are complex behaviors that result from the interaction of different factors, including genetic variants that increase the predisposition to suicidal behaviors. Copy number variations (CNVs are deletions or duplications of a segment of DNA usually larger than one kilobase. These structural genetic changes, although quite rare, have been associated with genetic liability to mental disorders, such as autism, schizophrenia, and bipolar disorder. No genome-wide level studies have been published investigating the potential role of CNVs in suicidal behaviors. Based on single-nucleotide polymorphism array data, we followed the Penn-CNV standards to detect CNVs in 1,608 subjects, comprising 475 suicide and suicide attempt cases and 1,133 controls. Although the initial algorithms determined the presence of CNVs on chromosomes 6 and 12 in seven and eight cases, respectively, compared with none of the controls, visual inspection of the raw data did not support this finding. Furthermore we were unable to validate these findings by CNV-specific real-time polymerase chain reaction. Additionally, rare CNV burden analysis did not find an association between the frequency or length of rare CNVs and suicidal behavior in our sample population. Although our findings suggest CNVs do not play an important role in the etiology of suicidal behaviors, they are not inconsistent with the strong evidence from the literature suggesting that other genetic variants account for a portion of the total phenotypic variability in suicidal behavior.

  3. ParseCNV integrative copy number variation association software with quality tracking.

    Science.gov (United States)

    Glessner, Joseph T; Li, Jin; Hakonarson, Hakon

    2013-03-01

    A number of copy number variation (CNV) calling algorithms exist; however, comprehensive software tools for CNV association studies are lacking. We describe ParseCNV, unique software that takes CNV calls and creates probe-based statistics for CNV occurrence in both case-control design and in family based studies addressing both de novo and inheritance events, which are then summarized based on CNV regions (CNVRs). CNVRs are defined in a dynamic manner to allow for a complex CNV overlap while maintaining precise association region. Using this approach, we avoid failure to converge and non-monotonic curve fitting weaknesses of programs, such as CNVtools and CNVassoc, and although Plink is easy to use, it only provides combined CNV state probe-based statistics, not state-specific CNVRs. Existing CNV association methods do not provide any quality tracking information to filter confident associations, a key issue which is fully addressed by ParseCNV. In addition, uncertainty in CNV calls underlying CNV associations is evaluated to verify significant results, including CNV overlap profiles, genomic context, number of probes supporting the CNV and single-probe intensities. When optimal quality control parameters are followed using ParseCNV, 90% of CNVs validate by polymerase chain reaction, an often problematic stage because of inadequate significant association review. ParseCNV is freely available at http://parsecnv.sourceforge.net.

  4. A genome-wide association study of copy number variations with umbilical hernia in swine.

    Science.gov (United States)

    Long, Yi; Su, Ying; Ai, Huashui; Zhang, Zhiyan; Yang, Bin; Ruan, Guorong; Xiao, Shijun; Liao, Xinjun; Ren, Jun; Huang, Lusheng; Ding, Nengshui

    2016-06-01

    Umbilical hernia (UH) is one of the most common congenital defects in pigs, leading to considerable economic loss and serious animal welfare problems. To test whether copy number variations (CNVs) contribute to pig UH, we performed a case-control genome-wide CNV association study on 905 pigs from the Duroc, Landrace and Yorkshire breeds using the Porcine SNP60 BeadChip and penncnv algorithm. We first constructed a genomic map comprising 6193 CNVs that pertain to 737 CNV regions. Then, we identified eight CNVs significantly associated with the risk for UH in the three pig breeds. Six of seven significantly associated CNVs were validated using quantitative real-time PCR. Notably, a rare CNV (CNV14:13030843-13059455) encompassing the NUGGC gene was strongly associated with UH (permutation-corrected P = 0.0015) in Duroc pigs. This CNV occurred exclusively in seven Duroc UH-affected individuals. SNPs surrounding the CNV did not show association signals, indicating that rare CNVs may play an important role in complex pig diseases such as UH. The NUGGC gene has been implicated in human omphalocele and inguinal hernia. Our finding supports that CNVs, including the NUGGC CNV, contribute to the pathogenesis of pig UH. © 2016 Stichting International Foundation for Animal Genetics.

  5. Copy Protection in Jet Set Willy: developing methodology for retrogame archaeology

    Directory of Open Access Journals (Sweden)

    John Aycock

    2017-04-01

    Full Text Available Video games, and more generally computer games, are unquestionably technological artefacts that have cultural significance. Old computer games in particular had to function under technical constraints that would be alien to many modern programmers, while at the same time providing something novel and at first foreign to consumers. How did their creators accomplish their technical feats, and what impact did that have for the player-consumer? The study of 'retro' computer games' implementation is one topic within the nascent area of archaeogaming. Digital rights management (DRM continues to be a major issue in the protection and distribution of content in electronic form. In this article, we study an early example of the implementation of copy protection in the 1984 game Jet Set Willy, something that comprises both physical and digital artefacts. It acts as a vehicle to illustrate a number of methods that we used to understand game implementation, culminating in a full reconstruction of the technique. The methods we cover include: 'traditional' research, along with its limitations in this context; code and data analysis; hypothesis testing; reconstruction. Through this positivist experimental approach, our results are both independently verifiable and repeatable. We also approach the complex context of early DRM, its hacks and workarounds by the player community, and what precipitated the design choices made for this particular game.

  6. Complexity explained

    CERN Document Server

    Erdi, Peter

    2008-01-01

    This book explains why complex systems research is important in understanding the structure, function and dynamics of complex natural and social phenomena. Readers will learn the basic concepts and methods of complex system research.

  7. Copy number variations in Saudi family with intellectual disability and epilepsy

    Directory of Open Access Journals (Sweden)

    Muhammad I. Naseer

    2016-10-01

    Full Text Available Abstract Background Epilepsy is genetically complex but common brain disorder of the world affecting millions of people with almost of all age groups. Novel Copy number variations (CNVs are considered as important reason for the numerous neurodevelopmental disorders along with intellectual disability and epilepsy. DNA array based studies contribute to explain a more severe clinical presentation of the disease but interoperation of many detected CNVs are still challenging. Results In order to study novel CNVs with epilepsy related genes in Saudi family with six affected and two normal individuals with several forms of epileptic seizures, intellectual disability (ID, and minor dysmorphism, we performed the high density whole genome Agilent sure print G3 Hmn CGH 2x 400 K array-CGH chips analysis. Our results showed de novo deletions, duplications and deletion plus duplication on differential chromosomal regions in the affected individuals that were not shown in the normal fathe and normal kids by using Agilent CytoGenomics 3.0.6.6 softwear. Copy number gain were observed in the chromosome 1, 16 and 22 with LCE3C, HPR, GSTT2, GSTTP2, DDT and DDTL genes respectively whereas the deletions observed in the chromosomal regions 8p23-p21 (4303127–4337759 and the potential gene in this region is CSMD1 (OMIM: 612279. Moreover, the array CGH results deletions and duplication were also validated by using primer design of deleted regions utilizing the flanked SNPs using simple PCR and also by using quantitative real time PCR. Conclusions We found some of the de novo deletions and duplication in our study in Saudi family with intellectual disability and epilepsy. Our results suggest that array-CGH should be used as a first line of genetic test for epilepsy except there is a strong indication for a monogenic syndrome. The advanced high through put array-CGH technique used in this study aim to collect the data base and to identify new mechanisms describing

  8. Copy number variations in Saudi family with intellectual disability and epilepsy.

    Science.gov (United States)

    Naseer, Muhammad I; Chaudhary, Adeel G; Rasool, Mahmood; Kalamegam, Gauthaman; Ashgan, Fai T; Assidi, Mourad; Ahmed, Farid; Ansari, Shakeel A; Zaidi, Syed Kashif; Jan, Mohammed M; Al-Qahtani, Mohammad H

    2016-10-17

    Epilepsy is genetically complex but common brain disorder of the world affecting millions of people with almost of all age groups. Novel Copy number variations (CNVs) are considered as important reason for the numerous neurodevelopmental disorders along with intellectual disability and epilepsy. DNA array based studies contribute to explain a more severe clinical presentation of the disease but interoperation of many detected CNVs are still challenging. In order to study novel CNVs with epilepsy related genes in Saudi family with six affected and two normal individuals with several forms of epileptic seizures, intellectual disability (ID), and minor dysmorphism, we performed the high density whole genome Agilent sure print G3 Hmn CGH 2x 400 K array-CGH chips analysis. Our results showed de novo deletions, duplications and deletion plus duplication on differential chromosomal regions in the affected individuals that were not shown in the normal fathe and normal kids by using Agilent CytoGenomics 3.0.6.6 softwear. Copy number gain were observed in the chromosome 1, 16 and 22 with LCE3C, HPR, GSTT2, GSTTP2, DDT and DDTL genes respectively whereas the deletions observed in the chromosomal regions 8p23-p21 (4303127-4337759) and the potential gene in this region is CSMD1 (OMIM: 612279). Moreover, the array CGH results deletions and duplication were also validated by using primer design of deleted regions utilizing the flanked SNPs using simple PCR and also by using quantitative real time PCR. We found some of the de novo deletions and duplication in our study in Saudi family with intellectual disability and epilepsy. Our results suggest that array-CGH should be used as a first line of genetic test for epilepsy except there is a strong indication for a monogenic syndrome. The advanced high through put array-CGH technique used in this study aim to collect the data base and to identify new mechanisms describing epileptic disorder, may help to improve the clinical

  9. Complex chemistry

    International Nuclear Information System (INIS)

    Kim, Bong Gon; Kim, Jae Sang; Kim, Jin Eun; Lee, Boo Yeon

    2006-06-01

    This book introduces complex chemistry with ten chapters, which include development of complex chemistry on history coordination theory and Warner's coordination theory and new development of complex chemistry, nomenclature on complex with conception and define, chemical formula on coordination compound, symbol of stereochemistry, stereo structure and isomerism, electron structure and bond theory on complex, structure of complex like NMR and XAFS, balance and reaction on solution, an organo-metallic chemistry, biology inorganic chemistry, material chemistry of complex, design of complex and calculation chemistry.

  10. 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).

  11. 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.

  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. 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.

  14. 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.

  15. 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.

  16. Genetic mechanisms and age-related macular degeneration: common variants, rare variants, copy number variations, epigenetics, and mitochondrial genetics

    Directory of Open Access Journals (Sweden)

    Liu Melissa M

    2012-08-01

    Full Text Available Abstract Age-related macular degeneration (AMD is a complex and multifaceted disease involving contributions from both genetic and environmental influences. Previous work exploring the genetic contributions of AMD has implicated numerous genomic regions and a variety of candidate genes as modulators of AMD susceptibility. Nevertheless, much of this work has revolved around single-nucleotide polymorphisms (SNPs, and it is apparent that a significant portion of the heritability of AMD cannot be explained through these mechanisms. In this review, we consider the role of common variants, rare variants, copy number variations, epigenetics, microRNAs, and mitochondrial genetics in AMD. Copy number variations in regulators of complement activation genes (CFHR1 and CFHR3 and glutathione S transferase genes (GSTM1 and GSTT1 have been associated with AMD, and several additional loci have been identified as regions of potential interest but require further evaluation. MicroRNA dysregulation has been linked to the retinal pigment epithelium degeneration in geographic atrophy, ocular neovascularization, and oxidative stress, all of which are hallmarks in the pathogenesis of AMD. Certain mitochondrial DNA haplogroups and SNPs in mitochondrially encoded NADH dehydrogenase genes have also been associated with AMD. The role of these additional mechanisms remains only partly understood, but the importance of their further investigation is clear to elucidate more completely the genetic basis of AMD.

  17. 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.

  18. Understanding the impact of 1q21.1 copy number variant

    Directory of Open Access Journals (Sweden)

    Harvard Chansonette

    2011-08-01

    Full Text Available Abstract Background 1q21.1 Copy Number Variant (CNV is associated with a highly variable phenotype ranging from congenital anomalies, learning deficits/intellectual disability (ID, to a normal phenotype. Hence, the clinical significance of this CNV can be difficult to evaluate. Here we described the consequences of the 1q21.1 CNV on genome-wide gene expression and function of selected candidate genes within 1q21.1 using cell lines from clinically well described subjects. Methods and Results Eight subjects from 3 families were included in the study: six with a 1q21.1 deletion and two with a 1q21.1 duplication. High resolution Affymetrix 2.7M array was used to refine the 1q21.1 CNV breakpoints and exclude the presence of secondary CNVs of pathogenic relevance. Whole genome expression profiling, studied in lymphoblast cell lines (LBCs from 5 subjects, showed enrichment of genes from 1q21.1 in the top 100 genes ranked based on correlation of expression with 1q21.1 copy number. The function of two top genes from 1q21.1, CHD1L/ALC1 and PRKAB2, was studied in detail in LBCs from a deletion and a duplication carrier. CHD1L/ALC1 is an enzyme with a role in chromatin modification and DNA damage response while PRKAB2 is a member of the AMP kinase complex, which senses and maintains systemic and cellular energy balance. The protein levels for CHD1L/ALC1 and PRKAB2 were changed in concordance with their copy number in both LBCs. A defect in chromatin remodeling was documented based on impaired decatenation (chromatid untangling checkpoint (DCC in both LBCs. This defect, reproduced by CHD1L/ALC1 siRNA, identifies a new role of CHD1L/ALC1 in DCC. Both LBCs also showed elevated levels of micronuclei following treatment with a Topoisomerase II inhibitor suggesting increased DNA breaks. AMP kinase function, specifically in the deletion containing LBCs, was attenuated. Conclusion Our studies are unique as they show for the first time that the 1q21.1 CNV not only

  19. 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....

  20. 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.

  1. 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.

  2. Construction of a restriction map and gene map of the lettuce chloroplast small single-copy region using Southern cross-hybridization.

    Science.gov (United States)

    Mitchelson, K R

    1996-01-01

    The small single-copy region (SSCR) of the chloroplast genome of many higher plants typically contain ndh genes encoding proteins that share homology with subunits of the respiratory-chain reduced nicotinamide adenine dinucleotide (NADH) dehydrogenase complex of mitochondria. A map of the lettuce chloroplast SSCR has been determined by Southern cross-hybridization, taking advantage of the high degree of homology between a tobacco small single-copy fragment and a corresponding lettuce chloroplast fragment. The gene order of the SSCR of lettuce and tobacco chloroplasts is similar. The cross-hybridization method can rapidly create a primary gene map of unknown chloroplast fragments, thus providing detailed information of the localization and arrangement of genes and conserved open reading frame regions.

  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. 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...

  5. 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...

  6. 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).

  7. 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).

  8. 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.

  9. 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.

  10. 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.

  11. Left ventricular hypertrabeculation/noncompaction with epilepsy, other heart defects, minor facial anomalies and new copy number variants

    Directory of Open Access Journals (Sweden)

    Nagel Bert

    2012-07-01

    Full Text Available Abstract Background Left ventricular hypertrabeculation/noncompaction (LVHT is a cardiac abnormality of unknown etiology which has been described in children as well as in adults with and without chromosomal aberrations. LVHT has been reported in association with various cardiac and extracardiac abnormalities like epilepsy and facial dysmorphism. Case presentation A unique combination of LVHT, atrial septal defect, pulmonary valve stenosis, aortic stenosis, epilepsy and minor facial anomalies is presented in a 5.5 years old girl. Microarray-based genomic hybridization (array-CGH detected six previously not described copy number variants (CNVs inherited from a clinically unaffected father and minimally affected mother, thus, most likely, not clinically significant but rare benign variants. Conclusions Despite this complex phenotype de novo microdeletions or microduplications were not detected by array CGH. Further investigations, such as whole exome sequencing, could reveal point mutations and small indels as the possible cause.

  12. 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...

  13. 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.

  14. Single-nucleotide variant in multiple copies of a deleted in azoospermia (DAZ) sequence - a human Y chromosome quantitative polymorphism.

    Science.gov (United States)

    Szmulewicz, Martin N; Ruiz, Luis M; Reategui, Erika P; Hussini, Saeed; Herrera, Rene J

    2002-01-01

    The evolution of the deleted in azoospermia (DAZ) gene family supports prevalent theories on the origin and development of sex chromosomes and sexual dimorphism. The ancestral DAZL gene in human chromosome 3 is known to be involved in germline development of both males and females. The available phylogenetic data suggest that some time after the divergence of the New World and Old World monkey lineages, the DAZL gene, which is found in all mammals, was copied to the Y chromosome of an ancestor to the Old World monkeys, but not New World monkeys. In modern man, the Y-linked DAZ gene complex is located on the distal part of the q arm. It is thought that after being copied to the Y chromosome, and after the divergence of the human and great ape lineages, the DAZ gene in the former underwent internal rearrangements. This included tandem duplications as well as a T > C transition altering an MboI restriction enzyme site in a duplicated sequence. In this study, we report on the ratios of MboI-/MboI+ variant sequences in individuals from seven worldwide human populations (Basque, Benin, Egypt, Formosa, Kungurtug, Oman and Rwanda) in the DAZ complex. The ratio of PCR MboI- and MboI+ amplicons can be used to characterize individuals and populations. Our results show a nonrandom distribution of MboI-/MboI+ sequence ratios in all populations examined, as well as significant differences in ratios between populations when compared pairwise. The multiple ratios imply that there have been more than one recent reorganization events at this locus. Considering the dynamic nature of this locus and its involvement in male fertility, we investigated the extent and distribution of this polymorphism. Copyright 2002 S. Karger AG, Basel

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. Autism genome-wide copy number variation reveals ubiquitin and neuronal genes.

    Science.gov (United States)

    Glessner, Joseph T; Wang, Kai; Cai, Guiqing; Korvatska, Olena; Kim, Cecilia E; Wood, Shawn; Zhang, Haitao; Estes, Annette; Brune, Camille W; Bradfield, Jonathan P; Imielinski, Marcin; Frackelton, Edward C; Reichert, Jennifer; Crawford, Emily L; Munson, Jeffrey; Sleiman, Patrick M A; Chiavacci, Rosetta; Annaiah, Kiran; Thomas, Kelly; Hou, Cuiping; Glaberson, Wendy; Flory, James; Otieno, Frederick; Garris, Maria; Soorya, Latha; Klei, Lambertus; Piven, Joseph; Meyer, Kacie J; Anagnostou, Evdokia; Sakurai, Takeshi; Game, Rachel M; Rudd, Danielle S; Zurawiecki, Danielle; McDougle, Christopher J; Davis, Lea K; Miller, Judith; Posey, David J; Michaels, Shana; Kolevzon, Alexander; Silverman, Jeremy M; Bernier, Raphael; Levy, Susan E; Schultz, Robert T; Dawson, Geraldine; Owley, Thomas; McMahon, William M; Wassink, Thomas H; Sweeney, John A; Nurnberger, John I; Coon, Hilary; Sutcliffe, James S; Minshew, Nancy J; Grant, Struan F A; Bucan, Maja; Cook, Edwin H; Buxbaum, Joseph D; Devlin, Bernie; Schellenberg, Gerard D; Hakonarson, Hakon

    2009-05-28

    Autism spectrum disorders (ASDs) are childhood neurodevelopmental disorders with complex genetic origins. Previous studies focusing on candidate genes or genomic regions have identified several copy number variations (CNVs) that are associated with an increased risk of ASDs. Here we present the results from a whole-genome CNV study on a cohort of 859 ASD cases and 1,409 healthy children of European ancestry who were genotyped with approximately 550,000 single nucleotide polymorphism markers, in an attempt to comprehensively identify CNVs conferring susceptibility to ASDs. Positive findings were evaluated in an independent cohort of 1,336 ASD cases and 1,110 controls of European ancestry. Besides previously reported ASD candidate genes, such as NRXN1 (ref. 10) and CNTN4 (refs 11, 12), several new susceptibility genes encoding neuronal cell-adhesion molecules, including NLGN1 and ASTN2, were enriched with CNVs in ASD cases compared to controls (P = 9.5 x 10(-3)). Furthermore, CNVs within or surrounding genes involved in the ubiquitin pathways, including UBE3A, PARK2, RFWD2 and FBXO40, were affected by CNVs not observed in controls (P = 3.3 x 10(-3)). We also identified duplications 55 kilobases upstream of complementary DNA AK123120 (P = 3.6 x 10(-6)). Although these variants may be individually rare, they target genes involved in neuronal cell-adhesion or ubiquitin degradation, indicating that these two important gene networks expressed within the central nervous system may contribute to the genetic susceptibility of ASD.

  2. 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

  3. (II) complexes

    African Journals Online (AJOL)

    activities of Schiff base tin (II) complexes. Neelofar1 ... Conclusion: All synthesized Schiff bases and their Tin (II) complexes showed high antimicrobial and ...... Singh HL. Synthesis and characterization of tin (II) complexes of fluorinated Schiff bases derived from amino acids. Spectrochim Acta Part A: Molec Biomolec.

  4. 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.

  5. Communication complexity and information complexity

    Science.gov (United States)

    Pankratov, Denis

    Information complexity enables the use of information-theoretic tools in communication complexity theory. Prior to the results presented in this thesis, information complexity was mainly used for proving lower bounds and direct-sum theorems in the setting of communication complexity. We present three results that demonstrate new connections between information complexity and communication complexity. In the first contribution we thoroughly study the information complexity of the smallest nontrivial two-party function: the AND function. While computing the communication complexity of AND is trivial, computing its exact information complexity presents a major technical challenge. In overcoming this challenge, we reveal that information complexity gives rise to rich geometrical structures. Our analysis of information complexity relies on new analytic techniques and new characterizations of communication protocols. We also uncover a connection of information complexity to the theory of elliptic partial differential equations. Once we compute the exact information complexity of AND, we can compute exact communication complexity of several related functions on n-bit inputs with some additional technical work. Previous combinatorial and algebraic techniques could only prove bounds of the form theta( n). Interestingly, this level of precision is typical in the area of information theory, so our result demonstrates that this meta-property of precise bounds carries over to information complexity and in certain cases even to communication complexity. Our result does not only strengthen the lower bound on communication complexity of disjointness by making it more exact, but it also shows that information complexity provides the exact upper bound on communication complexity. In fact, this result is more general and applies to a whole class of communication problems. In the second contribution, we use self-reduction methods to prove strong lower bounds on the information

  6. [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.

  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. Complexity and Entropy Analysis of DNMT1 Gene

    Science.gov (United States)

    Background: The application of complexity information on DNA sequence and protein in biological processes are well established in this study. Available sequences for DNMT1 gene, which is a maintenance methyltransferase is responsible for copying DNA methylation patterns to the daughter strands durin...

  9. Possible gene dosage effect of glutathione-S-transferases on atopic asthma: using real-time PCR for quantification of GSTM1 and GSTT1 gene copy numbers

    DEFF Research Database (Denmark)

    Brasch-Andersen, Charlotte; Christiansen, L; Tan, Q

    2004-01-01

    -S-transferase (GST) involved in the antioxidant defense were tested for association to asthma using 246 Danish atopic families in a family-based transmission disequilibrium test (TDT) design. A real-time PCR assay for relative quantification of gene copy number of GSTM1 and GSTT1 was developed. The assay made......Asthma is a complex genetic disorder characterized by chronic inflammation in the airways. As oxidative stress is a key component of inflammation, variations in genes involved in antioxidant defense could therefore be likely candidates for asthma. Three enzymes from the superfamily glutathione...

  10. 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

  11. 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 .

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. [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.

  17. Complexity Plots

    KAUST Repository

    Thiyagalingam, Jeyarajan

    2013-06-01

    In this paper, we present a novel visualization technique for assisting the observation and analysis of algorithmic complexity. In comparison with conventional line graphs, this new technique is not sensitive to the units of measurement, allowing multivariate data series of different physical qualities (e.g., time, space and energy) to be juxtaposed together conveniently and consistently. It supports multivariate visualization as well as uncertainty visualization. It enables users to focus on algorithm categorization by complexity classes, while reducing visual impact caused by constants and algorithmic components that are insignificant to complexity analysis. It provides an effective means for observing the algorithmic complexity of programs with a mixture of algorithms and black-box software through visualization. Through two case studies, we demonstrate the effectiveness of complexity plots in complexity analysis in research, education and application. © 2013 The Author(s) Computer Graphics Forum © 2013 The Eurographics Association and Blackwell Publishing Ltd.

  18. Subunit stoichiometry of the chloroplast photosystem I complex

    International Nuclear Information System (INIS)

    Bruce, B.D.; Malkin, R.

    1988-01-01

    A native photosystem I (PS I) complex and a PS I core complex depleted of antenna subunits has been isolated from the uniformly 14 C-labeled aquatic higher plant, Lemna. These complexes have been analyzed for their subunit stoichiometry by quantitative sodium dodecyl sulfate-polyacrylamide gel electrophoresis methods. The results for both preparations indicate that one copy of each high molecular mass subunit is present per PS I complex and that a single copy of most low molecular mass subunits is also present. These results suggest that iron-sulfur center X, an early PS I electron acceptor proposed to bind to the high molecular mass subunits, contains a single [4Fe-4S] cluster which is bound to a dimeric structure of high molecular mass subunits, each providing 2 cysteine residues to coordinate this cluster

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. Complexity Theory

    Science.gov (United States)

    Lee, William H K.

    2016-01-01

    A complex system consists of many interacting parts, generates new collective behavior through self organization, and adaptively evolves through time. Many theories have been developed to study complex systems, including chaos, fractals, cellular automata, self organization, stochastic processes, turbulence, and genetic algorithms.

  13. 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...

  14. 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...

  15. 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.

  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. 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.

  18. 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...

  19. Managing Complexity

    DEFF Research Database (Denmark)

    Maylath, Bruce; Vandepitte, Sonia; Minacori, Patricia

    2013-01-01

    and into French. The complexity of the undertaking proved to be a central element in the students' learning, as the collaboration closely resembles the complexity of international documentation workplaces of language service providers. © Association of Teachers of Technical Writing.......This article discusses the largest and most complex international learning-by-doing project to date- a project involving translation from Danish and Dutch into English and editing into American English alongside a project involving writing, usability testing, and translation from English into Dutch...

  20. Complex variables

    CERN Document Server

    Fisher, Stephen D

    1999-01-01

    The most important topics in the theory and application of complex variables receive a thorough, coherent treatment in this introductory text. Intended for undergraduates or graduate students in science, mathematics, and engineering, this volume features hundreds of solved examples, exercises, and applications designed to foster a complete understanding of complex variables as well as an appreciation of their mathematical beauty and elegance. Prerequisites are minimal; a three-semester course in calculus will suffice to prepare students for discussions of these topics: the complex plane, basic

  1. Interaction of complexes I, III, and IV within the bovine respirasome by single particle cryoelectron tomography

    NARCIS (Netherlands)

    Dudkina, Natalya V.; Kudryashev, Mikhail; Stahlberg, Henning; Boekema, Egbert J.

    2011-01-01

    The respirasome is a multisubunit supercomplex of the respiratory chain in mitochondria. Here we report the 3D reconstruction of the bovine heart respirasome, composed of dimeric complex III and single copies of complex I and IV, at about 2.2-nm resolution, determined by cryoelectron tomography and

  2. Softball Complex

    Science.gov (United States)

    Ellis, Jim

    1977-01-01

    The Parks and Recreation Department of Montgomery, Alabama, has developed a five-field softball complex as part of a growing community park with facilities for camping, golf, aquatics, tennis, and picnicking. (MJB)

  3. Lecithin Complex

    African Journals Online (AJOL)

    1Department of Food Science and Engineering, Xinyang College of Agriculture and ... Results: The UV and IR spectra of the complex showed an additive effect of polydatin-lecithin, in which .... Monochromatic Cu Ka radiation (wavelength =.

  4. A double copy for N=2 supergravity: a linearised tale told on-shell

    International Nuclear Information System (INIS)

    Cardoso, G.L.; Nagy, S.; Nampuri, S.

    2016-01-01

    We construct the on-shell double copy dictionary for linearised four-dimensional N=2 supergravity coupled to one vector multiplet with a quadratic prepotential. We apply this dictionary to the weak-field approximation of dyonic BPS black holes in this theory.

  5. 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.

  6. Effect of copy number and spacing of the ACGT and GT cis elements ...

    Indian Academy of Sciences (India)

    Unknown

    cognized by transcription factors of the bZIP family. The core ACGT element occurs at different relative positions in one or more copies upstream of the minimal promoter region. Protein-DNA interaction studies have shown that sequences flanking the ACGT core affect bZIP protein binding specificity. The bZIP transcription ...

  7. Association of beta-Defensin Copy Number and Psoriasis in Three Cohorts of European Origin

    NARCIS (Netherlands)

    Stuart, P.E.; Huffmeier, U.; Nair, R.P.; Palla, R.; Tejasvi, T.; Schalkwijk, J.; Elder, J.T.; Reis, A.; Armour, J.A.

    2012-01-01

    A single previous study has demonstrated significant association of psoriasis with copy number of beta-defensin genes, using DNA from psoriasis cases and controls from Nijmegen and Erlangen. In this study, we attempted to replicate that finding in larger new cohorts from Erlangen (N=2,017) and

  8. Effects of Color Stimulation and Information on the Copying Performance of Attention-Problem Adolescents.

    Science.gov (United States)

    Zentall, Sydney S.; And Others

    The optimal stimulaton theory (which proposes that hyperactive children are more readily underaroused than nonhyperactive children and should thus derive greater gains from stimulation added to repetitive copying tasks than comparisons) was tested with 16 adolescents, rating high on attention and behavior problems, and 16 controls. Matched pairs…

  9. 17 CFR 230.497 - Filing of investment company prospectuses-number of copies.

    Science.gov (United States)

    2010-04-01

    ... of a radio or television broadcast shall be reduced in writing. Five copies of every such prospectus... 1934 (15 U.S.C. 78o) that has adopted rules providing standards for the investment company advertising practices of its members and has established and implemented procedures to review that advertising. (j) In...

  10. Diversity and population-genetic properties of copy number variations and multicopy genes in cattle

    Science.gov (United States)

    The diversity and population-genetics of copy number variation (CNV) in domesticated animals are not well understood. In this study, we analyzed 75 genomes of major taurine and indicine cattle breeds (including Angus, Brahman, Gir, Holstein, Jersey, Limousin, Nelore, Romagnola), sequenced to 11-fold...

  11. 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

  12. Identification of a low copy number plasmid in Xylella fastidiosa Strain Stag’s Leap

    Science.gov (United States)

    Xylella fastidiosa (Xf) causes Pierce’s Disease (PD) in grapevine. The Stag’s Leap strain is known for its high virulence level and is a model for PD research. Research on Xf has been difficult due to its nutritional fastidiousness. One difficult research issue is the low copy number plasmid. Plasmi...

  13. 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.

  14. 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...

  15. Persuading on Paper: The Complete Guide to Writing Copy That Pulls in Business.

    Science.gov (United States)

    Yudkin, Marcia

    Noting that entrepreneurs know that marketing can make or break a business and that outreach requires effective written materials, this guide argues that anyone can learn to write effective copy. The guide demonstrates how to write effective sales letters and advertisements and persuasive press releases. It takes readers step-by-step through the…

  16. 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

  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. Copy number variation in obsessive-compulsive disorder and tourette syndrome : a cross-disorder study

    NARCIS (Netherlands)

    McGrath, Lauren M; Yu, Dongmei; Marshall, Christian; Davis, Lea K; Thiruvahindrapuram, Bhooma; Li, Bingbin; Cappi, Carolina; Gerber, Gloria; Wolf, Aaron; Schroeder, Frederick A; Osiecki, Lisa; O'Dushlaine, Colm; Kirby, Andrew; Illmann, Cornelia; Haddad, Stephen; Gallagher, Patience; Fagerness, Jesen A; Barr, Cathy L; Bellodi, Laura; Benarroch, Fortu; Bienvenu, O Joseph; Black, Donald W; Bloch, Michael H; Bruun, Ruth D; Budman, Cathy L; Camarena, Beatriz; Cath, Danielle C; Cavallini, Maria C; Chouinard, Sylvain; Coric, Vladimir; Cullen, Bernadette; Delorme, Richard; Denys, D.; Derks, Eske M; Dion, Yves; Rosário, Maria C; Eapen, Valsama; Evans, Patrick; Falkai, Peter; Fernandez, Thomas V; Garrido, Helena; Geller, Daniel; Grabe, Hans J; Grados, Marco A; Greenberg, Benjamin D; Gross-Tsur, Varda; Grünblatt, Edna; Heiman, Gary A; Hemmings, Sian M J; Herrera, Luis D; Hounie, Ana G; Jankovic, Joseph; Kennedy, James L; King, Robert A; Kurlan, Roger; Lanzagorta, Nuria; Leboyer, Marion; Leckman, James F; Lennertz, Leonhard; Lochner, Christine; Lowe, Thomas L; Lyon, Gholson J; Macciardi, Fabio; Maier, Wolfgang; McCracken, James T; McMahon, William; Murphy, Dennis L; Naarden, Allan L; Neale, Benjamin M; Nurmi, Erika; Pakstis, Andrew J; Pato, Michele T; Pato, Carlos N; Piacentini, John; Pittenger, Christopher; Pollak, Yehuda; Reus, Victor I; Richter, Margaret A; Riddle, Mark; Robertson, Mary M; Rosenberg, David; Rouleau, Guy A; Ruhrmann, Stephan; Sampaio, Aline S; Samuels, Jack; Sandor, Paul; Sheppard, Brooke; Singer, Harvey S; Smit, Jan H; Stein, Dan J; Tischfield, Jay A; Vallada, Homero; Veenstra-VanderWeele, Jeremy; Walitza, Susanne; Wang, Ying; Wendland, Jens R; Shugart, Yin Yao; Miguel, Euripedes C; Nicolini, Humberto; Oostra, Ben A; Moessner, Rainald; Wagner, Michael; Ruiz-Linares, Andres; Heutink, Peter; Nestadt, Gerald; Freimer, Nelson; Petryshen, Tracey; Posthuma, Danielle; Jenike, Michael A; Cox, Nancy J; Hanna, Gregory L; Brentani, Helena; Scherer, Stephen W; Arnold, Paul D; Stewart, S Evelyn; Mathews, Carol A; Knowles, James A; Cook, Edwin H; Pauls, David L; Wang, Kai; Scharf, Jeremiah M

    OBJECTIVE: Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (<1%) copy number variants (CNVs) in OCD and the largest

  19. Copy number variation in obsessive-compulsive disorder and tourette syndrome: a cross-disorder study

    NARCIS (Netherlands)

    McGrath, Lauren M.; Yu, Dongmei; Marshall, Christian; Davis, Lea K.; Thiruvahindrapuram, Bhooma; Li, Bingbin; Cappi, Carolina; Gerber, Gloria; Wolf, Aaron; Schroeder, Frederick A.; Osiecki, Lisa; O'Dushlaine, Colm; Kirby, Andrew; Illmann, Cornelia; Haddad, Stephen; Gallagher, Patience; Fagerness, Jesen A.; Barr, Cathy L.; Bellodi, Laura; Benarroch, Fortu; Bienvenu, O. Joseph; Black, Donald W.; Bloch, Michael H.; Bruun, Ruth D.; Budman, Cathy L.; Camarena, Beatriz; Cath, Danielle C.; Cavallini, Maria C.; Chouinard, Sylvain; Coric, Vladimir; Cullen, Bernadette; Delorme, Richard; Denys, Damiaan; Derks, Eske M.; Dion, Yves; Rosário, Maria C.; Eapen, Valsama; Evans, Patrick; Falkai, Peter; Fernandez, Thomas V.; Garrido, Helena; Geller, Daniel; Grabe, Hans J.; Grados, Marco A.; Greenberg, Benjamin D.; Gross-Tsur, Varda; Grünblatt, Edna; Heiman, Gary A.; Hemmings, Sian M. J.; Herrera, Luis D.; Hounie, Ana G.; Jankovic, Joseph; Kennedy, James L.; King, Robert A.; Kurlan, Roger; Lanzagorta, Nuria; Leboyer, Marion; Leckman, James F.; Lennertz, Leonhard; Lochner, Christine; Lowe, Thomas L.; Lyon, Gholson J.; Macciardi, Fabio; Maier, Wolfgang; McCracken, James T.; McMahon, William; Murphy, Dennis L.; Naarden, Allan L.; Neale, Benjamin M.; Nurmi, Erika; Pakstis, Andrew J.; Pato, Michele T.; Pato, Carlos N.; Piacentini, John; Pittenger, Christopher; Pollak, Yehuda; Reus, Victor I.; Richter, Margaret A.; Riddle, Mark; Robertson, Mary M.; Rosenberg, David; Rouleau, Guy A.; Ruhrmann, Stephan; Sampaio, Aline S.; Samuels, Jack; Sandor, Paul; Sheppard, Brooke; Singer, Harvey S.; Smit, Jan H.; Stein, Dan J.; Tischfield, Jay A.; Vallada, Homero; Veenstra-Vanderweele, Jeremy; Walitza, Susanne; Wang, Ying; Wendland, Jens R.; Shugart, Yin Yao; Miguel, Euripedes C.; Nicolini, Humberto; Oostra, Ben A.; Moessner, Rainald; Wagner, Michael; Ruiz-Linares, Andres; Heutink, Peter; Nestadt, Gerald; Freimer, Nelson; Petryshen, Tracey; Posthuma, Danielle; Jenike, Michael A.; Cox, Nancy J.; Hanna, Gregory L.; Brentani, Helena; Scherer, Stephen W.; Arnold, Paul D.; Stewart, S. Evelyn; Mathews, Carol A.; Knowles, James A.; Cook, Edwin H.; Pauls, David L.; Wang, Kai; Scharf, Jeremiah M.

    2014-01-01

    Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare ( <1%) copy number variants (CNVs) in OCD and the largest genome-wide

  20. Copy number variation in obsessive-compulsive disorder and tourette syndrome: A cross-disorder study

    NARCIS (Netherlands)

    L.M. McGrath; D. Yu (D.); C.R. Marshall (Christian); L.K. Davis (Lea); B. Thiruvahindrapuram (Bhooma); B. Li (Bingbin); C. Cappi (Carolina); G. Gerber (Gloria); A. de Wolf (Anneke); F.A. Schroeder (Frederick); L. Osiecki (Lisa); C. O'Dushlaine (Colm); A. Kirby (Andrew); C. Illmann (Cornelia); S. Haddad (Stephen); P. Gallagher (Patience); J. Fagerness (Jesen); C.L. Barr (Cathy); L. Bellodi (Laura); F. Benarroch (Fortu); O.J. Bienvenu (Oscar); D.W. Black (Donald); J. Bloch (Jocelyne); R.D. Bruun (Ruth); C.L. Budman (Cathy); B. Camarena (Beatriz); D. Cath (Daniëlle); M.C. Cavallini (Maria); S. Chouinard; V. Coric (Vladimir); C. Cullen; R. Delorme (Richard); D.A.J.P. Denys (Damiaan); E.M. Derks (Eske); Y. Dion (Yves); M.C. Rosário (Maria); C.E. Eapen (Chundamannil Eapen); P. Evans; P. Falkai (Peter); T.V. Fernandez (Thomas); H. Garrido (Helena); D. Geller (Daniel); H.J. Grabe (Hans Jörgen); M. Grados (Marco); B.D. Greenberg (Benjamin); V. Gross-Tsur (Varda); E. Grünblatt (Edna); M.L. Heiman (Mark); S.M.J. Hemmings (Sian); L.D. Herrera (Luis); A.G. Hounie (Ana); J. Jankovic (Joseph); J.L. Kennedy; R.A. King; R. Kurlan; N. Lanzagorta (Nuria); M. Leboyer (Marion); J.F. Leckman; L. Lennertz (Leonhard); C. Lochner (Christine); T.L. Lowe (Thomas); H.N. Lyon (Helen); F. MacCiardi (Fabio); W. Maier (Wolfgang); J.T. McCracken (James); W.M. McMahon (William); D.L. Murphy (Dennis); A.L. Naarden (Allan); E. Nurmi (Erika); A.J. Pakstis; C. Pato (Carlos); C. Pato (Carlos); J. Piacentini (John); C. Pittenger (Christopher); M.N. Pollak (Michael); V.I. Reus (Victor); M.A. Richter (Margaret); M. Riddle (Mark); M.M. Robertson; D. Rosenberg (David); G.A. Rouleau; S. Ruhrmann (Stephan); A.S. Sampaio (Aline); J. Samuels (Jonathan); P. Sandor (Paul); B. Sheppard (Brooke); H.S. Singer (Harvey); J.H. Smit (Jan); D.J. Stein (Dan); J.A. Tischfield (Jay); H. Vallada (Homero); J. Veenstra-Vanderweele (Jeremy); S. Walitza (Susanne); Y. Wang (Ying); A. Wendland (Annika); Y.Y. Shugart; E.C. Miguel (Euripedes); H. Nicolini (Humberto); B.A. Oostra (Ben); R. Moessner (Rainald); M. Wagner (Michael); A. Ruiz-Linares (Andres); P. Heutink (Peter); G. Nestadt (Gerald); N.B. Freimer (Nelson); T.L. Petryshen (Tracey); D. Posthuma (Danielle); M.A. Jenike (Michael); N.J. Cox (Nancy); G.L. Hanna (Gregory); H. Brentani (Helena); S.W. Scherer (Stephen); P.D. Arnold (Paul); S.E. Stewart; C. Mathews; J.A. Knowles (James A); E.H. Cook (Edwin); D.L. Pauls (David); K. Wang (Kai); J.M. Scharf; B.M. Neale (Benjamin)

    2014-01-01

    textabstractObjective Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (<1%) copy number variants (CNVs) in OCD and

  1. Copy number variation in obsessive-compulsive disorder and tourette syndrome: a cross-disorder study.

    NARCIS (Netherlands)

    McGrath, L.M.; Yu, D.; Marshall, C.; Davis, L.K.; Thiruvahindrapuram, B.; Li, B.; Cappi, C.; Gerber, G.; Wolf, A.; Schroeder, F.A.; Osiecki, L.; O'Dushlaine, C.; Kirby, A.; Illmann, C.; Haddad, S.; Gallagher, P.; Fagerness, J.A.; Barr, C.L.; Bellodi, L.; Benarroch, F.; Bienvenu, O.J.; Black, D. W.; Bloch, M.H.; Bruun, R.D.; Budman, C.L.; Camarena, B.; Cath, D.C.; Cavallini, M.C.; Chouinard, S.; Coric, V.; Cullen, B.; Delorme, R.; Denys, D.; Derks, E.M.; Dion, Y.; Rosário, M.C.; Eapen, V.; Evans, P.; Falkai, P.; Fernandez, T.V.; Garrido, H.; Geller, D.; Grabe, H.J.; Grados, M.A.; Greenberg, B.D.; Gross-Tsur, V.; Grünblatt, E.; Heiman, G.A.; Hemmings, S.M.; Herrera, L.D.; Hounie, A.G.; Jankovic, J.; Kennedy, J.L.; King, R.A.; Kurlan, R.; Lanzagorta, N.; Leboyer, M.; Leckman, J.F.; Lennertz, L.; Lochner, C.; Lowe, T.L.; Lyon, G.J.; Macciardi, F.; Maier, W.; McCracken, J.T.; McMahon, W.; Murphy, D.L.; Naarden, A.L.; Neale, B. M.; Nurmi, E.; Pakstis, A.J.; Pato, M. T.; Piacentini, J.; Pittenger, C.; Pollak, Y.; Reus, V.I.; Richter, M.A.; Riddle, M.; Robertson, M.M.; Rosenberg, D.; Rouleau, G.A.; Ruhrmann, S.; Sampaio, A.S.; Samuels, J.; Sandor, P.; Sheppard, B.; Singer, H.S.; Smit, J.H.; Stein, D.J.; Tischfield, J.A.; Vallada, H.; Veenstra-Vanderweele, J.; Walitza, S.; Wang, Y.; Wendland, J.R.; Shugart, Y.Y.; Miguel, E.C.; Nicolini, H.; Oostra, B.A.; Moessner, R.; Wagner, M.; Ruiz-Linares, A.; Heutink, P.; Nestadt, G.; Freimer, N.; Petryshen, T.; Posthuma, D.; Jenike, M.A.; Cox, N.J.; Hanna, G.L.; Brentani, H.; Scherer, S.W.; Arnold, P.D.; Stewart, S.E.; Mathews, C.A.; Knowles, J.A.; Cook, E.H.; Pauls, D.L.; Wang, K.; Scharf, J.M.

    2014-01-01

    Objective Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (<1%) copy number variants (CNVs) in OCD and the largest

  2. 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

  3. 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.

  4. 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...

  5. 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

  6. A double copy for N=2 supergravity: a linearised tale told on-shell

    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, 1049-001 Lisboa (Portugal)

    2016-10-24

    We construct the on-shell double copy dictionary for linearised four-dimensional N=2 supergravity coupled to one vector multiplet with a quadratic prepotential. We apply this dictionary to the weak-field approximation of dyonic BPS black holes in this theory.

  7. The line copy task for kinesthesia and internal movement representation: application in children.

    NARCIS (Netherlands)

    Smits-Engelsman, B.C.M.; Duysens, J.E.J.

    2008-01-01

    In the present study a new test is proposed and tested, which requires ability to use information both from kinesthesia and from mental rotation of previously produced cyclic movements over a distinct trajectory. This Line Copy Test (LICT) was performed by 58 children aged 7-11 years. For the

  8. 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.

  9. Distribution of Disease-Associated Copy Number Variants across Distinct Disorders of Cognitive Development

    Science.gov (United States)

    Pescosolido, Matthew F.; Gamsiz, Ece D.; Nagpal, Shailender; Morrow, Eric M.

    2013-01-01

    Objective: The purpose of the present study was to discover the extent to which distinct "DSM" disorders share large, highly recurrent copy number variants (CNVs) as susceptibility factors. We also sought to identify gene mechanisms common to groups of diagnoses and/or specific to a given diagnosis based on associations with CNVs. Method:…

  10. 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...

  11. 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...

  12. 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

  13. 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.

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

    NARCIS (Netherlands)

    Armour, J.A.; Palla, R.; Zeeuwen, P.L.J.M.; Heijer, M. den; Schalkwijk, J.; Hollox, E.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

  15. Copying and Coping Conceptualizations of Language: Counseling and the Ethic of Appreciation for Human Differences

    Science.gov (United States)

    Hansen, James T.

    2008-01-01

    The author takes the position that the foundational value of the counseling profession is an ethic of appreciation for human differences. The professional tool that is used to actualize this value is language. In this regard, the philosophical distinction between copying and coping conceptualizations of language is overviewed. The author argues…

  16. Design and Validation of a Straight-Copy Typewriting Prognostic Test Using Kinesthetic Sensitivity.

    Science.gov (United States)

    Olson, Norma Jean

    1979-01-01

    Describes the development and application of a kinesthetic sensitivity test to determine whether it is a valid and reliable measure of straight-copy typing speed and accuracy. The author states that this kinesthetic sensitivity instrument may be used as a prognostic aptitude test and recommends administration methods. (MF)

  17. 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

  18. 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.

  19. Detection of Answer Copying Based on the Structure of a High-Stakes Test

    Science.gov (United States)

    Belov, Dmitry I.

    2011-01-01

    This article presents the Variable Match Index (VM-Index), a new statistic for detecting answer copying. The power of the VM-Index relies on two-dimensional conditioning as well as the structure of the test. The asymptotic distribution of the VM-Index is analyzed by reduction to Poisson trials. A computational study comparing the VM-Index with the…

  20. 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 ...

  1. 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

  2. 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

  3. Does receiving a copy of correspondence improve patients' satisfaction with their out-patient consultation?

    NARCIS (Netherlands)

    Saunders, N. C.; Georgalas, C.; Blaney, S. P. A.; Dixon, H.; Topham, J. H.

    2003-01-01

    It is standard practice to write to a patient's general practitioner (GP) following an out-patients consultation. This study set out to assess whether sending a copy of this letter to the patient improves their satisfaction with the consultation. Two hundred patients were randomly assigned to

  4. 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

  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. 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

  7. 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...

  8. 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)

  9. 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

  10. 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.

  11. TOP1 gene copy numbers are increased in cancers of the bile duct and pancreas

    DEFF Research Database (Denmark)

    Grunnet, Mie; Calatayud, Dan; Schultz, Nicolai Aa.

    2015-01-01

    ) poison. Top1 protein, TOP1 gene copy number and mRNA expression, respectively, have been proposed as predictive biomarkers of response to irinotecan in other cancers. Here we investigate the occurrence of TOP1 gene aberrations in cancers of the bile ducts and pancreas. Material and methods. TOP1...

  12. 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.

  13. The Orphan Gene dauerless Regulates Dauer Development and Intraspecific Competition in Nematodes by Copy Number Variation.

    Directory of Open Access Journals (Sweden)

    Melanie G Mayer

    2015-06-01

    Full Text Available Many nematodes form dauer larvae when exposed to unfavorable conditions, representing an example of phenotypic plasticity and a major survival and dispersal strategy. In Caenorhabditis elegans, the regulation of dauer induction is a model for pheromone, insulin, and steroid-hormone signaling. Recent studies in Pristionchus pacificus revealed substantial natural variation in various aspects of dauer development, i.e. pheromone production and sensing and dauer longevity and fitness. One intriguing example is a strain from Ohio, having extremely long-lived dauers associated with very high fitness and often forming the most dauers in response to other strains' pheromones, including the reference strain from California. While such examples have been suggested to represent intraspecific competition among strains, the molecular mechanisms underlying these dauer-associated patterns are currently unknown. We generated recombinant-inbred-lines between the Californian and Ohioan strains and used quantitative-trait-loci analysis to investigate the molecular mechanism determining natural variation in dauer development. Surprisingly, we discovered that the orphan gene dauerless controls dauer formation by copy number variation. The Ohioan strain has one dauerless copy causing high dauer formation, whereas the Californian strain has two copies, resulting in strongly reduced dauer formation. Transgenic animals expressing multiple copies do not form dauers. dauerless is exclusively expressed in CAN neurons, and both CAN ablation and dauerless mutations increase dauer formation. Strikingly, dauerless underwent several duplications and acts in parallel or downstream of steroid-hormone signaling but upstream of the nuclear-hormone-receptor daf-12. We identified the novel or fast-evolving gene dauerless as inhibitor of dauer development. Our findings reveal the importance of gene duplications and copy number variations for orphan gene function and suggest daf-12 as

  14. 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.

  15. Does strategy instruction on the Rey-Osterrieth Complex Figure task lead to transferred performance improvement on the Modified Taylor Complex Figure task? A randomized controlled trial in school-aged children.

    Science.gov (United States)

    Resch, Christine; Keulers, Esther; Martens, Rosa; van Heugten, Caroline; Hurks, Petra

    2018-04-05

    Providing children with organizational strategy instruction on the Rey Osterrieth Complex Figure (ROCF) has previously been found to improve organizational and accuracy performance on this task. It is unknown whether strategy instruction on the ROCF would also transfer to performance improvement on copying and the recall of another complex figure. Participants were 98 typically developing children (aged 9.5-12.6 years, M = 10.6). Children completed the ROCF (copy and recall) as a pretest. Approximately a month later, they were randomized to complete the ROCF with strategy instruction in the form of a stepwise administration of the ROCF or again in the standard format. All children then copied and recalled the Modified Taylor Complex Figure (MTCF). All productions were assessed in terms of organization, accuracy and completion time. Organization scores for the MTCF did not differ for the two groups for the copy production, but did differ for the recall production, indicating transfer. Accuracy and completion times did not differ between groups. Performance on all measures, except copy accuracy, improved between pretest ROCF and posttest MTCF production for both groups, suggesting practice effects. Findings indicate that transfer of strategy instruction from one complex figure to another is only present for organization of recalled information. The increase in RCF-OSS scores did not lead to a higher accuracy or a faster copy or recall.

  16. The F1 -ATPase from Trypanosoma brucei is elaborated by three copies of an additional p18-subunit.

    Science.gov (United States)

    Gahura, Ondřej; Šubrtová, Karolína; Váchová, Hana; Panicucci, Brian; Fearnley, Ian M; Harbour, Michael E; Walker, John E; Zíková, Alena

    2018-02-01

    The F-ATPases (also called the F 1 F o -ATPases or ATP synthases) are multi-subunit membrane-bound molecular machines that produce ATP in bacteria and in eukaryotic mitochondria and chloroplasts. The structures and enzymic mechanisms of their F 1 -catalytic domains are highly conserved in all species investigated hitherto. However, there is evidence that the F-ATPases from the group of protozoa known as Euglenozoa have novel features. Therefore, we have isolated pure and active F 1 -ATPase from the euglenozoan parasite, Trypanosoma brucei, and characterized it. All of the usual eukaryotic subunits (α, β, γ, δ, and ε) were present in the enzyme, and, in addition, two unique features were detected. First, each of the three α-subunits in the F 1 -domain has been cleaved by proteolysis in vivo at two sites eight residues apart, producing two assembled fragments. Second, the T. brucei F 1 -ATPase has an additional subunit, called p18, present in three copies per complex. Suppression of expression of p18 affected in vitro growth of both the insect and infectious mammalian forms of T. brucei. It also reduced the levels of monomeric and multimeric F-ATPase complexes and diminished the in vivo hydrolytic activity of the enzyme significantly. These observations imply that p18 plays a role in the assembly of the F 1 domain. These unique features of the F 1 -ATPase extend the list of special characteristics of the F-ATPase from T. brucei, and also, demonstrate that the architecture of the F 1 -ATPase complex is not strictly conserved in eukaryotes. © 2017 Federation of European Biochemical Societies.

  17. Identification of copy number variations and translocations in cancer cells from Hi-C data.

    Science.gov (United States)

    Chakraborty, Abhijit; Ay, Ferhat

    2017-10-18

    Eukaryotic chromosomes adapt a complex and highly dynamic three-dimensional (3D) structure, which profoundly affects different cellular functions and outcomes including changes in epigenetic landscape and in gene expression. Making the scenario even more complex, cancer cells harbor chromosomal abnormalities (e.g., copy number variations (CNVs) and translocations) altering their genomes both at the sequence level and at the level of 3D organization. High-throughput chromosome conformation capture techniques (e.g., Hi-C), which are originally developed for decoding the 3D structure of the chromatin, provide a great opportunity to simultaneously identify the locations of genomic rearrangements and to investigate the 3D genome organization in cancer cells. Even though Hi-C data has been used for validating known rearrangements, computational methods that can distinguish rearrangement signals from the inherent biases of Hi-C data and from the actual 3D conformation of chromatin, and can precisely detect rearrangement locations de novo have been missing. In this work, we characterize how intra and inter-chromosomal Hi-C contacts are distributed for normal and rearranged chromosomes to devise a new set of algorithms (i) to identify genomic segments that correspond to CNV regions such as amplifications and deletions (HiCnv), (Nurtdinov et al.) to call inter-chromosomal translocations and their boundaries (HiCtrans) from Hi-C experiments, and (iii) to simulate Hi-C data from genomes with desired rearrangements and abnormalities (AveSim) in order to select optimal parameters for and to benchmark the accuracy of our methods. Our results on 10 different cancer cell lines with Hi-C data show that we identify a total number of 105 amplifications and 45 deletions together with 90 translocations, whereas we identify virtually no such events for two karyotypically normal cell lines. Our CNV predictions correlate very well with whole genome sequencing (WGS) data among chromosomes

  18. 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,

  19. 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...

  20. 33 CFR 148.115 - How many copies of the application must I send and where must I send them?

    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 application must I send and where must I send them? 148.115 Section 148.115 Navigation and Navigable Waters... Application for a License § 148.115 How many copies of the application must I send and where must I send them...

  1. 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.

  2. 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.

  3. 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....

  4. 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...

  5. 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...

  6. 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...

  7. Complex analysis

    CERN Document Server

    Freitag, Eberhard

    2005-01-01

    The guiding principle of this presentation of ``Classical Complex Analysis'' is to proceed as quickly as possible to the central results while using a small number of notions and concepts from other fields. Thus the prerequisites for understanding this book are minimal; only elementary facts of calculus and algebra are required. The first four chapters cover the essential core of complex analysis: - differentiation in C (including elementary facts about conformal mappings) - integration in C (including complex line integrals, Cauchy's Integral Theorem, and the Integral Formulas) - sequences and series of analytic functions, (isolated) singularities, Laurent series, calculus of residues - construction of analytic functions: the gamma function, Weierstrass' Factorization Theorem, Mittag-Leffler Partial Fraction Decomposition, and -as a particular highlight- the Riemann Mapping Theorem, which characterizes the simply connected domains in C. Further topics included are: - the theory of elliptic functions based on...

  8. Subgroup complexes

    CERN Document Server

    Smith, Stephen D

    2011-01-01

    This book is intended as an overview of a research area that combines geometries for groups (such as Tits buildings and generalizations), topological aspects of simplicial complexes from p-subgroups of a group (in the spirit of Brown, Quillen, and Webb), and combinatorics of partially ordered sets. The material is intended to serve as an advanced graduate-level text and partly as a general reference on the research area. The treatment offers optional tracks for the reader interested in buildings, geometries for sporadic simple groups, and G-equivariant equivalences and homology for subgroup complexes.

  9. Complex manifolds

    CERN Document Server

    Morrow, James

    2006-01-01

    This book, a revision and organization of lectures given by Kodaira at Stanford University in 1965-66, is an excellent, well-written introduction to the study of abstract complex (analytic) manifolds-a subject that began in the late 1940's and early 1950's. It is largely self-contained, except for some standard results about elliptic partial differential equations, for which complete references are given. -D. C. Spencer, MathSciNet The book under review is the faithful reprint of the original edition of one of the most influential textbooks in modern complex analysis and geometry. The classic

  10. 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.

  11. Copy Masters.

    Science.gov (United States)

    Humane Education, 1984

    1984-01-01

    Three activities related to pets are presented. The first focuses on caring for a pet. The second focuses on who is responsible for the actions of a pet. The third is a mathematics activity on pet overpopulation. The activities are designed to be duplicated for class use. (JN)

  12. 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

  13. 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

  14. 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

  15. Complex Networks

    CERN Document Server

    Evsukoff, Alexandre; González, Marta

    2013-01-01

    In the last decade we have seen the emergence of a new inter-disciplinary field focusing on the understanding of networks which are dynamic, large, open, and have a structure sometimes called random-biased. The field of Complex Networks is helping us better understand many complex phenomena such as the spread of  deseases, protein interactions, social relationships, to name but a few. Studies in Complex Networks are gaining attention due to some major scientific breakthroughs proposed by network scientists helping us understand and model interactions contained in large datasets. In fact, if we could point to one event leading to the widespread use of complex network analysis is the availability of online databases. Theories of Random Graphs from Erdös and Rényi from the late 1950s led us to believe that most networks had random characteristics. The work on large online datasets told us otherwise. Starting with the work of Barabási and Albert as well as Watts and Strogatz in the late 1990s, we now know th...

  16. Assessment of Tumor Heterogeneity, as Evidenced by Gene Expression Profiles, Pathway Activation, and Gene Copy Number, in Patients with Multifocal Invasive Lobular Breast Tumors

    Science.gov (United States)

    Norton, Nadine; Advani, Pooja P.; Serie, Daniel J.; Geiger, Xochiquetzal J.; Necela, Brian M.; Axenfeld, Bianca C.; Kachergus, Jennifer M.; Feathers, Ryan W.; Carr, Jennifer M.; Crook, Julia E.; Moreno-Aspitia, Alvaro; Anastasiadis, Panos Z.; Perez, Edith A.; Thompson, E. Aubrey

    2016-01-01

    Background Invasive lobular carcinoma (ILC) comprises approximately ~10–20% of breast cancers. In general, multifocal/multicentric (MF/MC) breast cancer has been associated with an increased rate of regional lymph node metastases. Tumor heterogeneity between foci represents a largely unstudied source of genomic variation in those rare patients with MF/MC ILC. Methods We characterized gene expression and copy number in 2 or more foci from 11 patients with MF/MC ILC (all ER+, HER2-) and adjacent normal tissue. RNA and DNA were extracted from 3x1.5mm cores from all foci. Gene expression (730 genes) and copy number (80 genes) were measured using Nanostring PanCancer and Cancer CNV panels. Linear mixed models were employed to compare expression in tumor versus normal samples from the same patient, and to assess heterogeneity (variability) in expression among multiple ILC within an individual. Results 35 and 34 genes were upregulated (FC>2) and down-regulated (FC<0.5) respectively in ILC tumor relative to adjacent normal tissue, q<0.05. 9/34 down-regulated genes (FIGF, RELN, PROM1, SFRP1, MMP7, NTRK2, LAMB3, SPRY2, KIT) had changes larger than CDH1, a hallmark of ILC. Copy number changes in these patients were relatively few but consistent across foci within each patient. Amplification of three genes (CCND1, FADD, ORAOV1) at 11q13.3 was present in 2/11 patients in both foci. We observed significant evidence of within-patient between-foci variability (heterogeneity) in gene expression for 466 genes (p<0.05 with FDR 8%), including CDH1, FIGF, RELN, SFRP1, MMP7, NTRK2, LAMB3, SPRY2 and KIT. Conclusions There was substantial variation in gene expression between ILC foci within patients, including known markers of ILC, suggesting an additional level of complexity that should be addressed. PMID:27078887

  17. Copy number variations of genes involved in stress responses reflect the redox state and DNA damage in brewing yeasts.

    Science.gov (United States)

    Adamczyk, Jagoda; Deregowska, Anna; Skoneczny, Marek; Skoneczna, Adrianna; Natkanska, Urszula; Kwiatkowska, Aleksandra; Rawska, Ewa; Potocki, Leszek; Kuna, Ewelina; Panek, Anita; Lewinska, Anna; Wnuk, Maciej

    2016-09-01

    The yeast strains of the Saccharomyces sensu stricto complex involved in beer production are a heterogeneous group whose genetic and genomic features are not adequately determined. Thus, the aim of the present study was to provide a genetic characterization of selected group of commercially available brewing yeasts both ale top-fermenting and lager bottom-fermenting strains. Molecular karyotyping revealed that the diversity of chromosome patterns and four strains with the most accented genetic variabilities were selected and subjected to genome-wide array-based comparative genomic hybridization (array-CGH) analysis. The differences in the gene copy number were found in five functional gene categories: (1) maltose metabolism and transport, (2) response to toxin, (3) siderophore transport, (4) cellular aldehyde metabolic process, and (5) L-iditol 2-dehydrogenase activity (p < 0.05). In the Saflager W-34/70 strain (Fermentis) with the most affected array-CGH profile, loss of aryl-alcohol dehydrogenase (AAD) gene dosage correlated with an imbalanced redox state, oxidative DNA damage and breaks, lower levels of nucleolar proteins Nop1 and Fob1, and diminished tolerance to fermentation-associated stress stimuli compared to other strains. We suggest that compromised stress response may not only promote oxidant-based changes in the nucleolus state that may affect fermentation performance but also provide novel directions for future strain improvement.

  18. Absence of Substantial Copy Number Differences in a Pair of Monozygotic Twins Discordant for Features of Autism Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Marina Laplana

    2014-01-01

    Full Text Available Autism spectrum disorder (ASD is a highly heritable disease (~0.9 with a complex genetic etiology. It is initially characterized by altered cognitive ability which commonly includes impaired language and communication skills as well as fundamental deficits in social interaction. Despite the large amount of studies described so far, the high clinical diversity affecting the autism phenotype remains poorly explained. Recent studies suggest that rare genomic variations, in particular copy number variation (CNV, may account for a significant proportion of the genetic basis of ASD. The use of disease-discordant monozygotic twins represents a powerful strategy to identify de novo and inherited CNV in the disorder. Here we present the results of a comparative genome hybridization (CGH analysis with a pair of monozygotic twins affected of ASD with significant differences in their clinical manifestations that specially affect speech language impairment and communication skills. Array CGH was performed in three different tissues: blood, saliva, and hair follicle, in an attempt to identify germinal and somatic CNV regions that may explain these differences. Our results argue against a role of large CNV rearrangements as a molecular etiology of the observed differences. This forwards future research to explore de novo point mutation and epigenomic alterations as potential explanations of the observed clinical differences.

  19. 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.

  20. 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.

  1. 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.

  2. Lepton number violation in theories with a large number of standard model copies

    International Nuclear Information System (INIS)

    Kovalenko, Sergey; Schmidt, Ivan; Paes, Heinrich

    2011-01-01

    We examine lepton number violation (LNV) in theories with a saturated black hole bound on a large number of species. Such theories have been advocated recently as a possible solution to the hierarchy problem and an explanation of the smallness of neutrino masses. On the other hand, the violation of the lepton number can be a potential phenomenological problem of this N-copy extension of the standard model as due to the low quantum gravity scale black holes may induce TeV scale LNV operators generating unacceptably large rates of LNV processes. We show, however, that this issue can be avoided by introducing a spontaneously broken U 1(B-L) . Then, due to the existence of a specific compensation mechanism between contributions of different Majorana neutrino states, LNV processes in the standard model copy become extremely suppressed with rates far beyond experimental reach.

  3. 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.

  4. 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.

  5. 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.

  6. Genome Wide Distributions and Functional Characterization of Copy Number Variations between Chinese and Western Pigs.

    Directory of Open Access Journals (Sweden)

    Hongyang Wang

    Full Text Available Copy number variations (CNVs refer to large insertions, deletions and duplications in the genomic structure ranging from one thousand to several million bases in size. Since the development of next generation sequencing technology, several methods have been well built for detection of copy number variations with high credibility and accuracy. Evidence has shown that CNV occurring in gene region could lead to phenotypic changes due to the alteration in gene structure and dosage. However, it still remains unexplored whether CNVs underlie the phenotypic differences between Chinese and Western domestic pigs. Based on the read-depth methods, we investigated copy number variations using 49 individuals derived from both Chinese and Western pig breeds. A total of 3,131 copy number variation regions (CNVRs were identified with an average size of 13.4 Kb in all individuals during domestication, harboring 1,363 genes. Among them, 129 and 147 CNVRs were Chinese and Western pig specific, respectively. Gene functional enrichments revealed that these CNVRs contribute to strong disease resistance and high prolificacy in Chinese domestic pigs, but strong muscle tissue development in Western domestic pigs. This finding is strongly consistent with the morphologic characteristics of Chinese and Western pigs, indicating that these group-specific CNVRs might have been preserved by artificial selection for the favored phenotypes during independent domestication of Chinese and Western pigs. In this study, we built high-resolution CNV maps in several domestic pig breeds and discovered the group specific CNVs by comparing Chinese and Western pigs, which could provide new insight into genomic variations during pigs' independent domestication, and facilitate further functional studies of CNV-associated genes.

  7. 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.

  8. Generation of single-copy transgenic mouse embryos directly from ES cells by tetraploid embryo complementation

    Directory of Open Access Journals (Sweden)

    Zhao Roong

    2001-12-01

    Full Text Available Abstract Background Transgenic mice have been used extensively to analyze gene function. Unfortunately, traditional transgenic procedures have only limited use in analyzing alleles that cause lethality because lines of founder mice cannot be established. This is frustrating given that such alleles often reveal crucial aspects of gene function. For this reason techniques that facilitate the generation of embryos expressing such alleles would be of enormous benefit. Although the transient generation of transgenic embryos has allowed limited analysis of lethal alleles, it is expensive, time consuming and technically challenging. Moreover a fundamental limitation with this approach is that each embryo generated is unique and transgene expression is highly variable due to the integration of different transgene copy numbers at random genomic sites. Results Here we describe an alternative method that allows the generation of clonal mouse embryos harboring a single-copy transgene at a defined genomic location. This was facilitated through the production of Hprt negative embryonic stem cells that allow the derivation of embryos by tetraploid embryo complementation. We show that targeting transgenes to the hprt locus in these ES cells by homologous recombination can be efficiently selected by growth in HAT medium. Moreover, embryos derived solely from targeted ES cells containing a single copy LacZ transgene under the control of the α-myosin heavy chain promoter exhibited the expected cardiac specific expression pattern. Conclusion Our results demonstrate that tetraploid embryo complementation by F3 hprt negative ES cells facilitates the generation of transgenic mouse embryos containing a single copy gene at a defined genomic locus. This approach is simple, extremely efficient and bypasses any requirement to generate chimeric mice. Moreover embryos generated by this procedure are clonal in that they are all derived from a single ES cell lines. This

  9. Applying pause analysis to explore cognitive processes in the copying of sentences by second language users

    OpenAIRE

    Zulkifli, Putri Afzan Maria Binti

    2013-01-01

    Pause analysis is a method that investigates processes of writing by measuring the amount of time between pen strokes. It provides the field of second language studies with a means to explore the cognitive processes underpinning the nature of writing. This study examined the potential of using free handwritten copying of sentences as a means of investigating components of the cognitive processes of adults who have English as their Second Language (ESL).\\ud \\ud A series of one pilot and three ...

  10. 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.

  11. 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.

  12. Stack Overflow Considered Harmful? The Impact of Copy&Paste on Android Application Security

    OpenAIRE

    Fischer, Felix; Böttinger, Konstantin; Xiao, Huang; Stransky, Christian; Acar, Yasemin; Backes, Michael; Fahl, Sascha

    2017-01-01

    Online programming discussion platforms such as Stack Overflow serve as a rich source of information for software developers. Available information include vibrant discussions and oftentimes ready-to-use code snippets. Anecdotes report that software developers copy and paste code snippets from those information sources for convenience reasons. Such behavior results in a constant flow of community-provided code snippets into production software. To date, the impact of this behaviour on code se...

  13. 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

  14. A Poisson hierarchical modelling approach to detecting copy number variation in sequence coverage data

    OpenAIRE

    Sep?lveda, Nuno; Campino, Susana G; Assefa, Samuel A; Sutherland, Colin J; Pain5, Arnab; Clark, Taane G

    2013-01-01

    BACKGROUND: The advent of next generation sequencing technology has accelerated efforts to map and catalogue copy number variation (CNV) in genomes of important micro-organisms for public health. A typical analysis of the sequence data involves mapping reads onto a reference genome, calculating the respective coverage, and detecting regions with too-low or too-high coverage (deletions and amplifications, respectively). Current CNV detection methods rely on statistical assumptions (e.g., a Poi...

  15. Duplication and relocation of the functional DPY19L2 gene within low copy repeats

    Directory of Open Access Journals (Sweden)

    Cheung Joseph

    2006-03-01

    Full Text Available Abstract Background Low copy repeats (LCRs are thought to play an important role in recent gene evolution, especially when they facilitate gene duplications. Duplicate genes are fundamental to adaptive evolution, providing substrates for the development of new or shared gene functions. Moreover, silencing of duplicate genes can have an indirect effect on adaptive evolution by causing genomic relocation of functional genes. These changes are theorized to have been a major factor in speciation. Results Here we present a novel example showing functional gene relocation within a LCR. We characterize the genomic structure and gene content of eight related LCRs on human Chromosomes 7 and 12. Two members of a novel transmembrane gene family, DPY19L, were identified in these regions, along with six transcribed pseudogenes. One of these genes, DPY19L2, is found on Chromosome 12 and is not syntenic with its mouse orthologue. Instead, the human locus syntenic to mouse Dpy19l2 contains a pseudogene, DPY19L2P1. This indicates that the ancestral copy of this gene has been silenced, while the descendant copy has remained active. Thus, the functional copy of this gene has been relocated to a new genomic locus. We then describe the expansion and evolution of the DPY19L gene family from a single gene found in invertebrate animals. Ancient duplications have led to multiple homologues in different lineages, with three in fish, frogs and birds and four in mammals. Conclusion Our results show that the DPY19L family has expanded throughout the vertebrate lineage and has undergone recent primate-specific evolution within LCRs.

  16. Managing Complexity

    Energy Technology Data Exchange (ETDEWEB)

    Chassin, David P.; Posse, Christian; Malard, Joel M.

    2004-08-01

    Physical analogs have shown considerable promise for understanding the behavior of complex adaptive systems, including macroeconomics, biological systems, social networks, and electric power markets. Many of today’s most challenging technical and policy questions can be reduced to a distributed economic control problem. Indeed, economically-based control of large-scale systems is founded on the conjecture that the price-based regulation (e.g., auctions, markets) results in an optimal allocation of resources and emergent optimal system control. This paper explores the state of the art in the use physical analogs for understanding the behavior of some econophysical systems and to deriving stable and robust control strategies for them. In particular we review and discussion applications of some analytic methods based on the thermodynamic metaphor according to which the interplay between system entropy and conservation laws gives rise to intuitive and governing global properties of complex systems that cannot be otherwise understood.

  17. 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.

  18. 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.

  19. 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

  20. CCL3L1 copy number, CCR5 genotype and susceptibility to tuberculosis.

    Science.gov (United States)

    Carpenter, Danielle; Taype, Carmen; Goulding, Jon; Levin, Mike; Eley, Brian; Anderson, Suzanne; Shaw, Marie-Anne; Armour, John A L

    2014-01-09

    Tuberculosis is a major infectious disease and functional studies have provided evidence that both the chemokine MIP-1α and its receptor CCR5 play a role in susceptibility to TB. Thus by measuring copy number variation of CCL3L1, one of the genes that encode MIP-1α, and genotyping a functional promoter polymorphism -2459A > G in CCR5 (rs1799987) we investigate the influence of MIP-1α and CCR5, independently and combined, in susceptibility to clinically active TB in three populations, a Peruvian population (n = 1132), a !Xhosa population (n = 605) and a South African Coloured population (n = 221). The three populations include patients with clinically diagnosed pulmonary TB, as well as other, less prevalent forms of extrapulmonary TB. Copy number of CCL3L1 was measured using the paralogue ratio test and exhibited ranges between 0-6 copies per diploid genome (pdg) in Peru, between 0-12 pdg in !Xhosa samples and between 0-10 pdg in South African Coloured samples. The CCR5 promoter polymorphism was observed to differ significantly in allele frequency between populations (*A; Peru f = 0.67, !Xhosa f = 0.38, Coloured f = 0.48). The case-control association studies performed however find, surprisingly, no evidence for an influence of variation in genes coding for MIP-1α or CCR5 individually or together in susceptibility to clinically active TB in these populations.

  1. 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.

  2. 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.

  3. 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.

  4. Clinical relevance of copy number profiling in oral and oropharyngeal squamous cell carcinoma

    Science.gov (United States)

    van Kempen, Pauline M W; Noorlag, Rob; Braunius, Weibel W; Moelans, Cathy B; Rifi, Widad; Savola, Suvi; Koole, Ronald; Grolman, Wilko; van Es, Robert J J; Willems, Stefan M

    2015-01-01

    Current conventional treatment modalities in head and neck squamous cell carcinoma (HNSCC) are nonselective and have shown to cause serious side effects. Unraveling the molecular profiles of head and neck cancer may enable promising clinical applications that pave the road for personalized cancer treatment. We examined copy number status in 36 common oncogenes and tumor suppressor genes in a cohort of 191 oropharyngeal squamous cell carcinomas (OPSCC) and 164 oral cavity squamous cell carcinomas (OSCC) using multiplex ligation probe amplification. Copy number status was correlated with human papillomavirus (HPV) status in OPSCC, with occult lymph node status in OSCC and with patient survival. The 11q13 region showed gain or amplifications in 59% of HPV-negative OPSCC, whereas this amplification was almost absent in HPV-positive OPSCC. Additionally, in clinically lymph node-negative OSCC (Stage I–II), gain of the 11q13 region was significantly correlated with occult lymph node metastases with a negative predictive value of 81%. Multivariate survival analysis revealed a significantly decreased disease-free survival in both HPV-negative and HPV-positive OPSCC with a gain of Wnt-induced secreted protein-1. Gain of CCND1 showed to be an independent predictor for worse survival in OSCC. These results show that copy number aberrations, mainly of the 11q13 region, may be important predictors and prognosticators which allow for stratifying patients for personalized treatment of HNSCC. PMID:26194878

  5. Clinical relevance of copy number profiling in oral and oropharyngeal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Kempen, Pauline M W van; Noorlag, Rob; Braunius, Weibel W; Moelans, Cathy B; Rifi, Widad; Savola, Suvi; Koole, Ronald; Grolman, Wilko; Es, Robert J J van; Willems, Stefan M

    2015-01-01

    Current conventional treatment modalities in head and neck squamous cell carcinoma (HNSCC) are nonselective and have shown to cause serious side effects. Unraveling the molecular profiles of head and neck cancer may enable promising clinical applications that pave the road for personalized cancer treatment. We examined copy number status in 36 common oncogenes and tumor suppressor genes in a cohort of 191 oropharyngeal squamous cell carcinomas (OPSCC) and 164 oral cavity squamous cell carcinomas (OSCC) using multiplex ligation probe amplification. Copy number status was correlated with human papillomavirus (HPV) status in OPSCC, with occult lymph node status in OSCC and with patient survival. The 11q13 region showed gain or amplifications in 59% of HPV-negative OPSCC, whereas this amplification was almost absent in HPV-positive OPSCC. Additionally, in clinically lymph node-negative OSCC (Stage I–II), gain of the 11q13 region was significantly correlated with occult lymph node metastases with a negative predictive value of 81%. Multivariate survival analysis revealed a significantly decreased disease-free survival in both HPV-negative and HPV-positive OPSCC with a gain of Wnt-induced secreted protein-1. Gain of CCND1 showed to be an independent predictor for worse survival in OSCC. These results show that copy number aberrations, mainly of the 11q13 region, may be important predictors and prognosticators which allow for stratifying patients for personalized treatment of HNSCC

  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. 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.

  8. 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

  9. 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.

  10. 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

  11. ReadDepth: a parallel R package for detecting copy number alterations from short sequencing reads.

    Directory of Open Access Journals (Sweden)

    Christopher A Miller

    2011-01-01

    Full Text Available Copy number alterations are important contributors to many genetic diseases, including cancer. We present the readDepth package for R, which can detect these aberrations by measuring the depth of coverage obtained by massively parallel sequencing of the genome. In addition to achieving higher accuracy than existing packages, our tool runs much faster by utilizing multi-core architectures to parallelize the processing of these large data sets. In contrast to other published methods, readDepth does not require the sequencing of a reference sample, and uses a robust statistical model that accounts for overdispersed data. It includes a method for effectively increasing the resolution obtained from low-coverage experiments by utilizing breakpoint information from paired end sequencing to do positional refinement. We also demonstrate a method for inferring copy number using reads generated by whole-genome bisulfite sequencing, thus enabling integrative study of epigenomic and copy number alterations. Finally, we apply this tool to two genomes, showing that it performs well on genomes sequenced to both low and high coverage. The readDepth package runs on Linux and MacOSX, is released under the Apache 2.0 license, and is available at http://code.google.com/p/readdepth/.

  12. 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.

  13. 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.

  14. Rare copy of "Life of Saint Volo-dymyr" (Kyiv, 1670 from the manuscript Corpus of Lives of the Saints as a source for the 17th century Kyiv hagiography study

    Directory of Open Access Journals (Sweden)

    Bondar N. P.

    2017-01-01

    Full Text Available In the article a rare copy of an old-printed edition of “Life of Saint Volodymyr”, published circa 1670 in the Kyiv-Pechersk Lavra printing-house is characterized. The copy was included to Corpus of Lives of the Saints of the17th-18th centuries from the collection of Church and Archeological museum of Kyiv Ecclesiastical Academy (Fond 301, Unit 416L. According to the modern advances of codicology, archeology, filigranology it became possible to critically review the data of descriptions, which brought new results. The approximate dating of the old-printed edition, which has no title and imprint, is confirmed. The publishing history of “Life of Saint Volodymyr” is analyzed. The research of the copy is accompanied by the complex description of overall manuscript hagiography codex, the analysis of its content, specifics, ownership notes and paper filigrees. Archeographic analysis of Corpus of Lives of the Saints was combined with study of formation of Ukrainian hagiography complex of the second half of the 17th - the early 18th centuries.

  15. Autism-specific copy number variants further implicate the phosphatidylinositol signaling pathway and the glutamatergic synapse in the etiology of the disorder.

    Science.gov (United States)

    Cuscó, Ivon; Medrano, Andrés; Gener, Blanca; Vilardell, Mireia; Gallastegui, Fátima; Villa, Olaya; González, Eva; Rodríguez-Santiago, Benjamín; Vilella, Elisabet; Del Campo, Miguel; Pérez-Jurado, Luis A

    2009-05-15

    Autism spectrum disorders (ASDs) constitute a group of severe neurodevelopmental conditions with complex multifactorial etiology. In order to explore the hypothesis that submicroscopic genomic rearrangements underlie some ASD cases, we have analyzed 96 Spanish patients with idiopathic ASD after extensive clinical and laboratory screening, by array comparative genomic hybridization (aCGH) using a homemade bacterial artificial chromosome (BAC) array. Only 13 of the 238 detected copy number alterations, ranging in size from 89 kb to 2.4 Mb, were present specifically in the autistic population (12 out of 96 individuals, 12.5%). Following validation by additional molecular techniques, we have characterized these novel candidate regions containing 24 different genes including alterations in two previously reported regions of chromosome 7 associated with the ASD phenotype. Some of the genes located in ASD-specific copy number variants act in common pathways, most notably the phosphatidylinositol signaling and the glutamatergic synapse, both known to be affected in several genetic syndromes related with autism and previously associated with ASD. Our work supports the idea that the functional alteration of genes in related neuronal networks is involved in the etiology of the ASD phenotype and confirms a significant diagnostic yield for aCGH, which should probably be included in the diagnostic workup of idiopathic ASD.

  16. Two-color fluorescence analysis of individual virions determines the distribution of the copy number of proteins in herpes simplex virus particles.

    Science.gov (United States)

    Clarke, Richard W; Monnier, Nilah; Li, Haitao; Zhou, Dejian; Browne, Helena; Klenerman, David

    2007-08-15

    We present a single virion method to determine absolute distributions of copy number in the protein composition of viruses and apply it to herpes simplex virus type 1. Using two-color coincidence fluorescence spectroscopy, we determine the virion-to-virion variability in copy numbers of fluorescently labeled tegument and envelope proteins relative to a capsid protein by analyzing fluorescence intensity ratios for ensembles of individual dual-labeled virions and fitting the resulting histogram of ratios. Using EYFP-tagged capsid protein VP26 as a reference for fluorescence intensity, we are able to calculate the mean and also, for the first time to our knowledge, the variation in numbers of gD, VP16, and VP22 tegument. The measurement of the number of glycoprotein D molecules was in good agreement with independent measurements of average numbers of these glycoproteins in bulk virus preparations, validating the method. The accuracy, straightforward data processing, and high throughput of this technique make it widely applicable to the analysis of the molecular composition of large complexes in general, and it is particularly suited to providing insights into virus structure, assembly, and infectivity.

  17. 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.

  18. Rare copy number alterations and copy-neutral loss of heterozygosity revealed in ameloblastomas by high-density whole-genome microarray analysis.

    Science.gov (United States)

    Diniz, Marina Gonçalves; Duarte, Alessandra Pires; Villacis, Rolando A; Guimarães, Bruna V A; Duarte, Luiz Cláudio Pires; Rogatto, Sílvia R; Gomez, Ricardo Santiago; Gomes, Carolina Cavaliéri

    2017-05-01

    Ameloblastoma (unicystic, UA, or multicystic, MA) is a rare tumor associated with bone destruction and facial deformity. Its malignant counterpart is the ameloblastic carcinoma (AC). The BRAFV600E mutation is highly prevalent in all these tumors subtypes and cannot account for their different clinical behaviors. We assessed copy number alterations (CNAs) and copy-neutral loss of heterozygosity (cnLOH) in UA (n = 2), MA (n = 3), and AC (n = 1) using the CytoScan HD Array (Affymetrix) and the BRAFV600E status. RT-qPCR was applied in four selected genes (B4GALT1, BAG1, PKD1L2, and PPP2R5A) covered by rare alterations, also including three MA and four normal oral tissues. Fifty-seven CNAs and cnLOH were observed in the ameloblastomas and six CNAs in the AC. Seven of the CNAs were rare (six in UA and one in MA), four of them encompassing genes (gains of 7q11.21, 1q32.3, and 9p21.1 and loss of 16q23.2). We found positive correlation between rare CNA gene dosage and the expression of B4GALT1, BAG1, PKD1L2, and PPP2R5A. The AC and 1 UA were BRAF wild-type; however, this UA showed rare genomic alterations encompassing genes associated with RAF/MAPK activation. Ameloblastomas show rare CNAs and cnLOH, presenting a specific genomic profile with no overlapping of the rare alterations among UA, MA, and AC. These genomic changes might play a role in tumor evolution and in BRAFV600E-negative tumors. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. 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

  20. Fidelity analysis of mechanically aided copying/enlarging of Jan van Eyck's Portrait of Niccolo Albergati

    Science.gov (United States)

    Stork, David G.; Duarte, Marco

    2007-01-01

    The contemporary artist David Hockney has hypothesized that some early Renaissance painters secretly projected optical images onto their supports (canvas, paper, oak panel, ...), directly traced these projections, and then filled in the tracings with paint[1]. Hockney has presented somewhat impressionistic image evidence for this claim, but he and thin-film physicist Charles Falco also point to perspective anomalies, to the fidelity of passages in certain paintings, and to historical documents in search of support for this direct tracing claim[2]. Key visual evidence adduced in support of this tracing claim is a pair of portraits by Jan van Eyck of Cardinal Niccolo Albergati - a small informal silverpoint study of 1431 and a slightly larger formal work in oil on panel of 1432. The contours in these two works bear striking resemblance in shape (after being appropriately scaled) and there are at least two "relative shifts" - passages that co-align well after a spatial shift of one of the images [2]. This evidence has led the theory's proponents to claim that van Eyck copied the silverpoint by means of an optical projector, or epidiascope, the relative shifts due to him accidentally bumping the setup during the copying. Previous tests of the tracing theory for these works considered four candidate methods van Eyck might have used to copied and enlarged the image in the silverpoint study: unaided ("by eye"), mechanical, grid, and the optical projection method itself [3]. Based on the full evidence, including the recent discovery of tiny pinprick holes in the silverpoint, reenactments, material culture and optical knowledge in the early 15th century, the mechanical method was judged most plausible and optical method the least plausible[3]. However, this earlier work did not adequately test whether a trained artist could "re-enact" the copying by mechanical methods: "Although we have not explicitly verified that high fidelities can be achieved through the use of a

  1. Integration of transcript expression, copy number and LOH analysis of infiltrating ductal carcinoma of the breast

    Directory of Open Access Journals (Sweden)

    Hawthorn Lesleyann

    2010-08-01

    Full Text Available Abstract Background A major challenge in the interpretation of genomic profiling data generated from breast cancer samples is the identification of driver genes as distinct from bystander genes which do not impact tumorigenesis. One way to assess the relative importance of alterations in the transcriptome profile is to combine parallel analyses that assess changes in the copy number alterations (CNAs. This integrated analysis permits the identification of genes with altered expression that map within specific chromosomal regions which demonstrate copy number alterations, providing a mechanistic approach to identify the 'driver genes'. Methods We have performed whole genome analysis of CNAs using the Affymetrix 250K Mapping array on 22 infiltrating ductal carcinoma samples (IDCs. Analysis of transcript expression alterations was performed using the Affymetrix U133 Plus2.0 array on 16 IDC samples. Fourteen IDC samples were analyzed using both platforms and the data integrated. We also incorporated data from loss of heterozygosity (LOH analysis to identify genes showing altered expression in LOH regions. Results Common chromosome gains and amplifications were identified at 1q21.3, 6p21.3, 7p11.2-p12.1, 8q21.11 and 8q24.3. A novel amplicon was identified at 5p15.33. Frequent losses were found at 1p36.22, 8q23.3, 11p13, 11q23, and 22q13. Over 130 genes were identified with concurrent increases or decreases in expression that mapped to these regions of copy number alterations. LOH analysis revealed three tumors with whole chromosome or p arm allelic loss of chromosome 17. Genes were identified that mapped to copy neutral LOH regions. LOH with accompanying copy loss was detected on Xp24 and Xp25 and genes mapping to these regions with decreased expression were identified. Gene expression data highlighted the PPARα/RXRα Activation Pathway as down-regulated in the tumor samples. Conclusion We have demonstrated the utility of the application of

  2. 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.

  3. Characterization of α-isopropylmalate synthases containing different copy numbers of tandem repeats in Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Palittapongarnpim Prasit

    2009-06-01

    Full Text Available Abstract Background Alpha-isopropylmalate synthase (α-IPMS is the key enzyme that catalyzes the first committed step in the leucine biosynthetic pathway. The gene encoding α-IPMS in Mycobacterium tuberculosis, leuA, is polymorphic due to the insertion of 57-bp repeat units referred to as Variable Number of Tandem Repeats (VNTR. The role of the VNTR found within the M. tuberculosis genome is unclear. To investigate the role of the VNTR in leuA, we compared two α-IPMS proteins with different numbers of amino acid repeats, one with two copies and the other with 14 copies. We have cloned leuA with 14 copies of the repeat units into the pET15b expression vector with a His6-tag at the N-terminus, as was previously done for the leuA gene with two copies of the repeat units. Results The recombinant His6-α-IPMS proteins with two and 14 copies (α-IPMS-2CR and α-IPMS-14CR, respectively of the repeat units were purified by immobilized metal ion affinity chromatography and gel filtration. Both enzymes were found to be dimers by gel filtration. Both enzymes work well at pH values of 7–8.5 and temperatures of 37–42°C. However, α-IPMS-14CR tolerates pH values and temperatures outside of this range better than α-IPMS-2CR does. α-IPMS-14CR has higher affinity than α-IPMS-2CR for the two substrates, α-ketoisovalerate and acetyl CoA. Furthermore, α-IPMS-2CR was feedback inhibited by the end product l-leucine, whereas α-IPMS-14CR was not. Conclusion The differences in the kinetic properties and the l-leucine feedback inhibition between the two M. tuberculosis α-IPMS proteins containing low and high numbers of VNTR indicate that a large VNTR insertion affects protein structure and function. Demonstration of l-leucine binding to α-IPMS-14CR would confirm whether or not α-IPMS-14CR responds to end-product feedback inhibition.

  4. 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

  5. Comprehensive analysis of copy number aberrations in microsatellite stable colon cancer in view of stromal component.

    Science.gov (United States)

    Alonso, M Henar; Aussó, Susanna; Lopez-Doriga, Adriana; Cordero, David; Guinó, Elisabet; Solé, Xavier; Barenys, Mercè; de Oca, Javier; Capella, Gabriel; Salazar, Ramón; Sanz-Pamplona, Rebeca; Moreno, Victor

    2017-07-25

    Somatic copy number aberrations (CNAs) are common acquired changes in cancer cells having an important role in the progression of colon cancer (colorectal cancer, CRC). This study aimed to perform a characterisation of CNA and their impact in gene expression. Copy number aberrations were inferred from SNP array data in a series of 99 CRC. Copy number aberration events were calculated and used to assess the association between copy number dosage, clinical and molecular characteristics of the tumours, and gene expression changes. All analyses were adjusted for the quantity of stroma in each sample, which was inferred from gene expression data. High heterogeneity among samples was observed; the proportion of altered genome ranged between 0.04 and 26.6%. Recurrent CNA regions with gains were frequent in chromosomes 7p, 8q, 13q, and 20, whereas 8p, 17p, and 18 cumulated losses. A significant positive correlation was observed between the number of somatic mutations and total CNA (Spearman's r=0.42, P=0.006). Approximately 37% of genes located in CNA regions changed their level of expression and the average partial correlation (adjusted for stromal content) with copy number was 0.54 (interquartile range 0.20 to 0.81). Altered genes showed enrichment in pathways relevant for CRC. Tumours classified as CMS2 and CMS4 by the consensus molecular subtyping showed higher frequency of CNA. Losses of one small region in 1p36.33, with gene CDK11B, were associated with poor prognosis. More than 66% of the recurrent CNA were validated in the The Cancer Genome Atlas (TCGA) data when analysed with the same procedure. Furthermore, 79% of the genes with altered expression in our data were validated in the TCGA. Although CNA are frequent events in microsatellite stable CRC, few focal recurrent regions were found. These aberrations have strong effects on gene expression and contribute to deregulate relevant cancer pathways. Owing to the diploid nature of stromal cells, it is important to

  6. Complex variables

    CERN Document Server

    Flanigan, Francis J

    2010-01-01

    A caution to mathematics professors: Complex Variables does not follow conventional outlines of course material. One reviewer noting its originality wrote: ""A standard text is often preferred [to a superior text like this] because the professor knows the order of topics and the problems, and doesn't really have to pay attention to the text. He can go to class without preparation."" Not so here-Dr. Flanigan treats this most important field of contemporary mathematics in a most unusual way. While all the material for an advanced undergraduate or first-year graduate course is covered, discussion

  7. 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

  8. Complex dynamics

    CERN Document Server

    Carleson, Lennart

    1993-01-01

    Complex dynamics is today very much a focus of interest. Though several fine expository articles were available, by P. Blanchard and by M. Yu. Lyubich in particular, until recently there was no single source where students could find the material with proofs. For anyone in our position, gathering and organizing the material required a great deal of work going through preprints and papers and in some cases even finding a proof. We hope that the results of our efforts will be of help to others who plan to learn about complex dynamics and perhaps even lecture. Meanwhile books in the field a. re beginning to appear. The Stony Brook course notes of J. Milnor were particularly welcome and useful. Still we hope that our special emphasis on the analytic side will satisfy a need. This book is a revised and expanded version of notes based on lectures of the first author at UCLA over several \\Vinter Quarters, particularly 1986 and 1990. We owe Chris Bishop a great deal of gratitude for supervising the production of cour...

  9. Cosmic Complexity

    Science.gov (United States)

    Mather, John C.

    2012-01-01

    What explains the extraordinary complexity of the observed universe, on all scales from quarks to the accelerating universe? My favorite explanation (which I certainty did not invent) ls that the fundamental laws of physics produce natural instability, energy flows, and chaos. Some call the result the Life Force, some note that the Earth is a living system itself (Gaia, a "tough bitch" according to Margulis), and some conclude that the observed complexity requires a supernatural explanation (of which we have many). But my dad was a statistician (of dairy cows) and he told me about cells and genes and evolution and chance when I was very small. So a scientist must look for me explanation of how nature's laws and statistics brought us into conscious existence. And how is that seemll"!gly Improbable events are actually happening a!1 the time? Well, the physicists have countless examples of natural instability, in which energy is released to power change from simplicity to complexity. One of the most common to see is that cooling water vapor below the freezing point produces snowflakes, no two alike, and all complex and beautiful. We see it often so we are not amazed. But physlc!sts have observed so many kinds of these changes from one structure to another (we call them phase transitions) that the Nobel Prize in 1992 could be awarded for understanding the mathematics of their common features. Now for a few examples of how the laws of nature produce the instabilities that lead to our own existence. First, the Big Bang (what an insufficient name!) apparently came from an instability, in which the "false vacuum" eventually decayed into the ordinary vacuum we have today, plus the most fundamental particles we know, the quarks and leptons. So the universe as a whole started with an instability. Then, a great expansion and cooling happened, and the loose quarks, finding themselves unstable too, bound themselves together into today's less elementary particles like protons and

  10. The Lincoln Repository presentation: ten reasons why you should put a copy of your work in the Repository

    OpenAIRE

    Stainthorp, Paul

    2010-01-01

    Slideshow presentation created to promote the Lincoln Repository to staff at the University of Lincoln. Consists of ten reasons why academic authors should consider depositing copies of their work in the Repository.

  11. 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.

  12. Susceptibility for Lupus Nephritis by Low Copy Number of the FCGR3B Gene Is Linked to Increased Levels of Pathogenic Autoantibodies

    Directory of Open Access Journals (Sweden)

    Johannes C. Nossent

    2013-01-01

    Full Text Available Low copy number (CN of the FCGR3B gene reduces FCGR3B membrane expression on neutrophils and results in clearance of a smaller amount of immune complex. We investigated FCGR3B CN in relation to the clinical phenotype in a Caucasian SLE cohort (. FCGR3B CN was determined by three different qPCR parameter estimations (Ct−, Cy0, and cpD1 and confirmed by the FCGR2C/FCGR2A paralog ratio test. Clinical and serological data were then analyzed for their association with FCGR3B CN. Low FCGR3B CN (2. In multivariate analyses, LN was independently associated with anti-C1q-Ab levels ( and low FCGR3B CN (. We conclude that the susceptibility for LN in patients with low FCGR3B CN is linked to increased levels of pathogenic autoantibodies.

  13. A continental-wide perspective: the genepool of nuclear encoded ribosomal DNA and single-copy gene sequences in North American Boechera (Brassicaceae.

    Directory of Open Access Journals (Sweden)

    Christiane Kiefer

    Full Text Available 74 of the currently accepted 111 taxa of the North American genus Boechera (Brassicaceae were subject to pyhlogenetic reconstruction and network analysis. The dataset comprised 911 accessions for which ITS sequences were analyzed. Phylogenetic analyses yielded largely unresolved trees. Together with the network analysis confirming this result this can be interpreted as an indication for multiple, independent, and rapid diversification events. Network analyses were superimposed with datasets describing i geographical distribution, ii taxonomy, iii reproductive mode, and iv distribution history based on phylogeographic evidence. Our results provide first direct evidence for enormous reticulate evolution in the entire genus and give further insights into the evolutionary history of this complex genus on a continental scale. In addition two novel single-copy gene markers, orthologues of the Arabidopsis thaliana genes At2g25920 and At3g18900, were analyzed for subsets of taxa and confirmed the findings obtained through the ITS data.

  14. An analysis of initial acquisition and maintenance of sight words following picture matching and copy cover, and compare teaching methods.

    OpenAIRE

    Conley, Colleen M; Derby, K Mark; Roberts-Gwinn, Michelle; Weber, Kimberly P; McLaughlin, T E

    2004-01-01

    This study compared the copy, cover, and compare method to a picture-word matching method for teaching sight word recognition. Participants were 5 kindergarten students with less than preprimer sight word vocabularies who were enrolled in a public school in the Pacific Northwest. A multielement design was used to evaluate the effects of the two interventions. Outcomes suggested that sight words taught using the copy, cover, and compare method resulted in better maintenance of word recognition...

  15. 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.

  16. 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

  17. Clinical Omics Analysis of Colorectal Cancer Incorporating Copy Number Aberrations and Gene Expression Data

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Yoshida

    2010-07-01

    Full Text Available Background: Colorectal cancer (CRC is one of the most frequently occurring cancers in Japan, and thus a wide range of methods have been deployed to study the molecular mechanisms of CRC. In this study, we performed a comprehensive analysis of CRC, incorporating copy number aberration (CRC and gene expression data. For the last four years, we have been collecting data from CRC cases and organizing the information as an “omics” study by integrating many kinds of analysis into a single comprehensive investigation. In our previous studies, we had experienced difficulty in finding genes related to CRC, as we observed higher noise levels in the expression data than in the data for other cancers. Because chromosomal aberrations are often observed in CRC, here, we have performed a combination of CNA analysis and expression analysis in order to identify some new genes responsible for CRC. This study was performed as part of the Clinical Omics Database Project at Tokyo Medical and Dental University. The purpose of this study was to investigate the mechanism of genetic instability in CRC by this combination of expression analysis and CNA, and to establish a new method for the diagnosis and treatment of CRC. Materials and methods: Comprehensive gene expression analysis was performed on 79 CRC cases using an Affymetrix Gene Chip, and comprehensive CNA analysis was performed using an Affymetrix DNA Sty array. To avoid the contamination of cancer tissue with normal cells, laser micro-dissection was performed before DNA/RNA extraction. Data analysis was performed using original software written in the R language. Result: We observed a high percentage of CNA in colorectal cancer, including copy number gains at 7, 8q, 13 and 20q, and copy number losses at 8p, 17p and 18. Gene expression analysis provided many candidates for CRC-related genes, but their association with CRC did not reach the level of statistical significance. The combination of CNA and gene

  18. Multi-platform whole-genome microarray analyses refine the epigenetic signature of breast cancer metastasis with gene expression and copy number.

    Directory of Open Access Journals (Sweden)

    Joseph Andrews

    2010-01-01

    Full Text Available We have previously identified genome-wide DNA methylation changes in a cell line model of breast cancer metastasis. These complex epigenetic changes that we observed, along with concurrent karyotype analyses, have led us to hypothesize that complex genomic alterations in cancer cells (deletions, translocations and ploidy are superimposed over promoter-specific methylation events that are responsible for gene-specific expression changes observed in breast cancer metastasis.We undertook simultaneous high-resolution, whole-genome analyses of MDA-MB-468GFP and MDA-MB-468GFP-LN human breast cancer cell lines (an isogenic, paired lymphatic metastasis cell line model using Affymetrix gene expression (U133, promoter (1.0R, and SNP/CNV (SNP 6.0 microarray platforms to correlate data from gene expression, epigenetic (DNA methylation, and combination copy number variant/single nucleotide polymorphism microarrays. Using Partek Software and Ingenuity Pathway Analysis we integrated datasets from these three platforms and detected multiple hypomethylation and hypermethylation events. Many of these epigenetic alterations correlated with gene expression changes. In addition, gene dosage events correlated with the karyotypic differences observed between the cell lines and were reflected in specific promoter methylation patterns. Gene subsets were identified that correlated hyper (and hypo methylation with the loss (or gain of gene expression and in parallel, with gene dosage losses and gains, respectively. Individual gene targets from these subsets were also validated for their methylation, expression and copy number status, and susceptible gene pathways were identified that may indicate how selective advantage drives the processes of tumourigenesis and metastasis.Our approach allows more precisely profiling of functionally relevant epigenetic signatures that are associated with cancer progression and metastasis.

  19. Efficient Detection of Copy Number Mutations in PMS2 Exons with a Close Homolog.

    Science.gov (United States)

    Herman, Daniel S; Smith, Christina; Liu, Chang; Vaughn, Cecily P; Palaniappan, Selvi; Pritchard, Colin C; Shirts, Brian H

    2018-07-01

    Detection of 3' PMS2 copy-number mutations that cause Lynch syndrome is difficult because of highly homologous pseudogenes. To improve the accuracy and efficiency of clinical screening for these mutations, we developed a new method to analyze standard capture-based, next-generation sequencing data to identify deletions and duplications in PMS2 exons 9 to 15. The approach captures sequences using PMS2 targets, maps sequences randomly among regions with equal mapping quality, counts reads aligned to homologous exons and introns, and flags read count ratios outside of empirically derived reference ranges. The method was trained on 1352 samples, including 8 known positives, and tested on 719 samples, including 17 known positives. Clinical implementation of the first version of this method detected new mutations in the training (N = 7) and test (N = 2) sets that had not been identified by our initial clinical testing pipeline. The described final method showed complete sensitivity in both sample sets and false-positive rates of 5% (training) and 7% (test), dramatically decreasing the number of cases needing additional mutation evaluation. This approach leveraged the differences between gene and pseudogene to distinguish between PMS2 and PMS2CL copy-number mutations. These methods enable efficient and sensitive Lynch syndrome screening for 3' PMS2 copy-number mutations and may be applied similarly to other genomic regions with highly homologous pseudogenes. Copyright © 2018 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  20. 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.

  1. 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.

  2. 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

  3. K13 mutations and pfmdr1 copy number variation in Plasmodium falciparum malaria in Myanmar.

    Science.gov (United States)

    Win, Aye A; Imwong, Mallika; Kyaw, Myat P; Woodrow, Charles J; Chotivanich, Kesinee; Hanboonkunupakarn, Borimas; Pukrittayakamee, Sasithon

    2016-02-24

    Artemisinin-based combination therapy has been first-line treatment for falciparum malaria in Myanmar since 2005. The wide extent of artemisinin resistance in the Greater Mekong sub-region and the presence of mefloquine resistance at the Myanmar-Thailand border raise concerns over resistance patterns in Myanmar. The availability of molecular markers for resistance to both drugs enables assessment even in remote malaria-endemic areas. A total of 250 dried blood spot samples collected from patients with Plasmodium falciparum malarial infection in five malaria-endemic areas across Myanmar were analysed for kelch 13 sequence (k13) and pfmdr1 copy number variation. K13 mutations in the region corresponding to amino acids 210-726 (including the propeller region of the protein) were detected by nested PCR amplification and sequencing, and pfmdr1 copy number variation by real-time PCR. In two sites, a sub-set of patients were prospectively followed up for assessment of day-3 parasite clearance rates after a standard course of artemether-lumefantrine. K13 mutations and pfmdr1 amplification were successfully analysed in 206 and 218 samples, respectively. Sixty-nine isolates (33.5 %) had mutations within the k13 propeller region with 53 of these (76.8 %) having mutations already known to be associated with artemisinin resistance. F446I (32 isolates) and P574L (15 isolates) were the most common examples. K13 mutation was less common in sites in western border regions (29 of 155 isolates) compared to samples from the east and north (40 of 51 isolates; p Myanmar. There is a low prevalence of parasites with multiple pfmdr1 copies across the country. The efficacy of artemisinin-based combination therapy containing mefloquine and lumefantrine is, therefore, expected to be high, although regular monitoring of efficacy will be important.

  4. 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.

  5. Sex bias in copy number variation of olfactory receptor gene family depends on ethnicity

    Directory of Open Access Journals (Sweden)

    Farideh eShadravan

    2013-03-01

    Full Text Available Gender plays a pivotal role in the human genetic identity and is also manifested in many genetic disorders particularly mental retardation. In this study its effect on copy number variation (CNV, known to cause genetic disorders was explored. As the olfactory receptor (OR repertoire comprises the largest human gene family, it was selected for this study, which was carried out within and between three populations, derived from 150 individuals from the 1000 Genome Project. Analysis of 3872 CNVs detected among 791 OR loci, in which 307 loci showed CNV, revealed the following novel findings: Sex bias in CNV was significantly more prevalent in uncommon than common CNV variants of OR pseudogenes, in which the male genome showed more CNVs; and in one-copy number loss compared to complete deletion of OR pseudogenes; both findings implying a more recent evolutionary role for gender. Sex bias in copy number gain was also detected. Another novel finding was that the observed six bias was largely dependent on ethnicity and was in general absent in East Asians. Using a CNV public database for sick children (ISCA the application of these findings for improving clinical molecular diagnostics is discussed by showing an example of sex bias in CNV among kids with autism. Additional clinical relevance is discussed, as the most polymorphic CNV-enriched OR cluster in the human genome, located on chr 15q11.2, is found near the PWS/AS bi-directionally imprinted region associated with two well-known mental retardation syndromes. As olfaction represents the primitive cognition in most mammals, arguably in competition with the development of a larger brain, the extensive retention of OR pseudogenes in females of this study, might point to a parent-of-origin indirect regulatory role for OR pseudogenes in the embryonic development of human brain. Thus any perturbation in the temporal regulation of olfactory system could lead to developmental delay disorders including

  6. Genome-wide detection of copy number variations among diverse horse breeds by array CGH.

    Directory of Open Access Journals (Sweden)

    Wei Wang

    Full Text Available Recent studies have found that copy number variations (CNVs are widespread in human and animal genomes. CNVs are a significant source of genetic variation, and have been shown to be associated with phenotypic diversity. However, the effect of CNVs on genetic variation in horses is not well understood. In the present study, CNVs in 6 different breeds of mare horses, Mongolia horse, Abaga horse, Hequ horse and Kazakh horse (all plateau breeds and Debao pony and Thoroughbred, were determined using aCGH. In total, seven hundred CNVs were identified ranging in size from 6.1 Kb to 0.57 Mb across all autosomes, with an average size of 43.08 Kb and a median size of 15.11 Kb. By merging overlapping CNVs, we found a total of three hundred and fifty-three CNV regions (CNVRs. The length of the CNVRs ranged from 6.1 Kb to 1.45 Mb with average and median sizes of 38.49 Kb and 13.1 Kb. Collectively, 13.59 Mb of copy number variation was identified among the horses investigated and accounted for approximately 0.61% of the horse genome sequence. Five hundred and eighteen annotated genes were affected by CNVs, which corresponded to about 2.26% of all horse genes. Through the gene ontology (GO, genetic pathway analysis and comparison of CNV genes among different breeds, we found evidence that CNVs involving 7 genes may be related to the adaptation to severe environment of these plateau horses. This study is the first report of copy number variations in Chinese horses, which indicates that CNVs are ubiquitous in the horse genome and influence many biological processes of the horse. These results will be helpful not only in mapping the horse whole-genome CNVs, but also to further research for the adaption to the high altitude severe environment for plateau horses.

  7. Copy number variations of chromosome 16p13.1 region associated with schizophrenia

    DEFF Research Database (Denmark)

    Ingason, A; Rujescu, D; Cichon, S

    2011-01-01

    .007) and deletions in 0.12 % of cases and 0.04% of controls (P>0.05). The region can be divided into three intervals defined by flanking low copy repeats. Duplications spanning intervals I and II showed the most significant (P = 0.00010) association with schizophrenia. The age of onset in duplication and deletion...... carriers among cases ranged from 12 to 35 years, and the majority were males with a family history of psychiatric disorders. In a single Icelandic family, a duplication spanning intervals I and II was present in two cases of schizophrenia, and individual cases of alcoholism, attention deficit hyperactivity...

  8. Insights into the genome structure and copy-number variation of Eimeria tenella

    Directory of Open Access Journals (Sweden)

    Lim Lik-Sin

    2012-08-01

    Full Text Available Abstract Background Eimeria is a genus of parasites in the same phylum (Apicomplexa as human parasites such as Toxoplasma, Cryptosporidium and the malaria parasite Plasmodium. As an apicomplexan whose life-cycle involves a single host, Eimeria is a convenient model for understanding this group of organisms. Although the genomes of the Apicomplexa are diverse, that of Eimeria is unique in being composed of large alternating blocks of sequence with very different characteristics - an arrangement seen in no other organism. This arrangement has impeded efforts to fully sequence the genome of Eimeria, which remains the last of the major apicomplexans to be fully analyzed. In order to increase the value of the genome sequence data and aid in the effort to gain a better understanding of the Eimeria tenella genome, we constructed a whole genome map for the parasite. Results A total of 1245 contigs representing 70.0% of the whole genome assembly sequences (Wellcome Trust Sanger Institute were selected and subjected to marker selection. Subsequently, 2482 HAPPY markers were developed and typed. Of these, 795 were considered as usable markers, and utilized in the construction of a HAPPY map. Markers developed from chromosomally-assigned genes were then integrated into the HAPPY map and this aided the assignment of a number of linkage groups to their respective chromosomes. BAC-end sequences and contigs from whole genome sequencing were also integrated to improve and validate the HAPPY map. This resulted in an integrated HAPPY map consisting of 60 linkage groups that covers approximately half of the estimated 60 Mb genome. Further analysis suggests that the segmental organization first seen in Chromosome 1 is present throughout the genome, with repeat-poor (P regions alternating with repeat-rich (R regions. Evidence of copy-number variation between strains was also uncovered. Conclusions This paper describes the application of a whole genome mapping

  9. Using cover, copy, and compare spelling with and without timing for elementary students with behavior disorders

    Directory of Open Access Journals (Sweden)

    Danette Darrow

    2012-04-01

    Full Text Available The purpose of this study was to determine the effectiveness of cover, copy, and compare (CCC procedures on spelling performance with two students. The participants were two elementary students enrolled in a self-contained behavior intervention classroom. A multiple baseline design across participants was employed to evaluate the effects of CCC on time to completion and words spelled correctly. Improvements in all measures were found when CCC was in effect. The participants enjoyed the procedures and each improved their spelling over baseline performance. The applicability of CCC across academic contexts and for students with behavior disorders was discussed.

  10. CCL3L1 copy number, CCR5 genotype and susceptibility to tuberculosis

    OpenAIRE

    Carpenter, Danielle; Taype, Carmen; Goulding, Jon; Levin, Mike; Eley, Brian; Anderson, Suzanne; Shaw, Marie-Anne; Armour, John AL

    2014-01-01

    Background: Tuberculosis is a major infectious disease and functional studies have provided evidence that both the chemokine MIP-1α and its receptor CCR5 play a role in susceptibility to TB. Thus by measuring copy number variation of CCL3L1, one of the genes that encode MIP-1α, and genotyping a functional promoter polymorphism -2459A > G in CCR5 (rs1799987) we investigate the influence of MIP-1α and CCR5, independently and combined, in susceptibility to clinically active TB in three populatio...

  11. Using Efference Copy and a Forward Internal Model for Adaptive Biped Walking

    DEFF Research Database (Denmark)

    Schröder-Schetelig, Johannes; Manoonpong, Poramate; Wörgötter, Florentin

    2010-01-01

    an application of this for our dynamic walking robot RunBot. We use efference copies of the motor commands with a simple forward internal model to predict the expected self-generated acceleration during walking. The difference to the actually measured acceleration is then used to stabilize the walking...... on terrains with changing slopes through its upper body component controller. As a consequence, the controller drives the upper body component (UBC) to lean forwards/backwards as soon as an error occurs resulting in dynamical stable walking. We have evaluated the performance of the system on four different...

  12. Copy-Number Disorders Are a Common Cause of Congenital Kidney Malformations

    OpenAIRE

    Sanna-Cherchi, Simone; Kiryluk, Krzysztof; Burgess, Katelyn E.; Bodria, Monica; Sampson, Matthew G.; Hadley, Dexter; Nees, Shannon N.; Verbitsky, Miguel; Perry, Brittany J.; Sterken, Roel; Lozanovski, Vladimir J.; Materna-Kiryluk, Anna; Barlassina, Cristina; Kini, Akshata; Corbani, Valentina

    2012-01-01

    We examined the burden of large, rare, copy-number variants (CNVs) in 192 individuals with renal hypodysplasia (RHD) and replicated findings in 330 RHD cases from two independent cohorts. CNV distribution was significantly skewed toward larger gene-disrupting events in RHD cases compared to 4,733 ethnicity-matched controls (p = 4.8 × 10−11). This excess was attributable to known and novel (i.e., not present in any database or in the literature) genomic disorders. All together, 55/522 (10.5%) ...

  13. Multi-copy entanglement purification with practical spontaneous parametric down conversion sources

    International Nuclear Information System (INIS)

    Zhang Shuai-Shuai; Shu Qi; Sheng Yu-Bo; Zhou Lan

    2017-01-01

    Entanglement purification is to distill the high quality entanglement from the low quality entanglement with local operations and classical communications. It is one of the key technologies in long-distance quantum communication. We discuss an entanglement purification protocol (EPP) with spontaneous parametric down conversion (SPDC) sources, in contrast to previous EPP with multi-copy mixed states, which requires ideal entanglement sources. We show that the SPDC source is not an obstacle for purification, but can benefit the fidelity of the purified mixed state. This EPP works for linear optics and is feasible in current experiment technology. (paper)

  14. Global copy number profiling of cancer genomes | Office of Cancer Genomics

    Science.gov (United States)

    In this article, we introduce a robust and efficient strategy for deriving global and allele-specific copy number alternations (CNA) from cancer whole exome sequencing data based on Log R ratios and B-allele frequencies. Applying the approach to the analysis of over 200 skin cancer samples, we demonstrate its utility for discovering distinct CNA events and for deriving ancillary information such as tumor purity. Availability and implementation: https://github.com/xfwang/CLOSE CONTACT: xuefeng.wang@stonybrook.edu or michael.krauthammer@yale.edu. (Publication Abstract)

  15. 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

  16. [Abnormality of TOP2A expression and its gene copy number variations in neuroblastic tumors].

    Science.gov (United States)

    Chen, J M; Zhou, C J; Ma, X L; Guan, D D; Yang, L Y; Yue, P; Gong, L P

    2016-11-08

    Objective: To detect TOP2A protein expression and gene copy number alterations, and to analyze related clinical and pathological implications in pediatric neuroblastic tumors (NT). Methods: Immunohistochemistry was used to detect TOP2A protein expression. Fluorescence in situ hybridization (FISH) was used to detect numerical aberrations of TOP2A. Results: TOP2A protein was expressed in 59.1%(52/88) of cases, which was associated with differentiation ( P =0.006), Ki-67 index ( P INSS stages (Ⅲ and Ⅳ). As a target of the anthracycline-based adjuvant drugs, TOP2A test can be used to select patient with NT for the therapy.

  17. 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

  18. Diversity in Copy Number and Structure of a Silkworm Morphogenetic Gene as a Result of Domestication

    OpenAIRE

    Sakudoh, Takashi; Nakashima, Takeharu; Kuroki, Yoko; Fujiyama, Asao; Kohara, Yuji; Honda, Naoko; Fujimoto, Hirofumi; Shimada, Toru; Nakagaki, Masao; Banno, Yutaka; Tsuchida, Kozo

    2011-01-01

    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 strain...

  19. Comparisons of Copy Number, Genomic Structure, and Conserved Motifs for α-Amylase Genes from Barley, Rice, and Wheat

    Directory of Open Access Journals (Sweden)

    Qisen Zhang

    2017-10-01

    Full Text Available Barley is an important crop for the production of malt and beer. However, crops such as rice and wheat are rarely used for malting. α-amylase is the key enzyme that degrades starch during malting. In this study, we compared the genomic properties, gene copies, and conserved promoter motifs of α-amylase genes in barley, rice, and wheat. In all three crops, α-amylase consists of four subfamilies designated amy1, amy2, amy3, and amy4. In wheat and barley, members of amy1 and amy2 genes are localized on chromosomes 6 and 7, respectively. In rice, members of amy1 genes are found on chromosomes 1 and 2, and amy2 genes on chromosome 6. The barley genome has six amy1 members and three amy2 members. The wheat B genome contains four amy1 members and three amy2 members, while the rice genome has three amy1 members and one amy2 member. The B genome has mostly amy1 and amy2 members among the three wheat genomes. Amy1 promoters from all three crop genomes contain a GA-responsive complex consisting of a GA-responsive element (CAATAAA, pyrimidine box (CCTTTT and TATCCAT/C box. This study has shown that amy1 and amy2 from both wheat and barley have similar genomic properties, including exon/intron structures and GA-responsive elements on promoters, but these differ in rice. Like barley, wheat should have sufficient amy activity to degrade starch completely during malting. Other factors, such as high protein with haze issues and the lack of husk causing Lauting difficulty, may limit the use of wheat for brewing.

  20. 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

  1. Contribution of Regional White Matter Integrity to Visuospatial Construction Accuracy, Organizational Strategy, and Memory for a Complex Figure in Abstinent Alcoholics.

    Science.gov (United States)

    Rosenbloom, Margaret J; Sassoon, Stephanie A; Pfefferbaum, Adolf; Sullivan, Edith V

    2009-12-01

    Visuospatial construction ability as used in drawing complex figures is commonly impaired in chronic alcoholics, but memory for such information can be enhanced by use of a holistic drawing strategy during encoding. We administered the Rey-Osterrieth Complex Figure Test (ROCFT) to 41 alcoholic and 38 control men and women and assessed the contribution of diffusion tensor imaging (DTI) measures of integrity of selected white matter tracts to ROCFT copy accuracy, copy strategy, and recall accuracy. Although alcoholics copied the figure less accurately than controls, a more holistic strategy at copy was associated with better recall in both groups. Greater radial diffusivity, reflecting compromised myelin integrity, in occipital forceps and external capsule was associated with poorer copy accuracy in both groups. Lower FA, reflecting compromised fiber microstructure in the inferior cingulate bundle, which links frontal and medial temporal episodic memory systems, was associated with piecemeal copy strategy and poorer immediate recall in the alcoholics. The correlations were generally modest and should be considered exploratory. To the extent that the inferior cingulate was relatively spared in alcoholics, it may have provided an alternative pathway to the compromised frontal system for successful copy strategy and, by extension, aided recall.

  2. CNV analysis in 169 patients with bladder exstrophy-epispadias complex

    NARCIS (Netherlands)

    Lowtzow, C. von; Hofmann, A.; Zhang, R.; Marsch, F.; Ebert, A.K.; Rosch, W.; Stein, R.; Boemers, T.M.; Hirsch, K.; Marcelis, C.L.M.; Feitz, W.F.J.; Brusco, A.; Migone, N.; Grazia, M. Di; Moebus, S.; Nothen, M.M.; Reutter, H.; Ludwig, M.; Draaken, M.

    2016-01-01

    BACKGROUND: The bladder exstrophy-epispadias complex (BEEC) represents the severe end of the congenital uro-rectal malformation spectrum. Initial studies have implicated rare copy number variations (CNVs), including recurrent duplications of chromosomal region 22q11.21, in BEEC etiology. METHODS: To

  3. Association of β-defensin copy number and psoriasis in three cohorts of European origin.

    Science.gov (United States)

    Stuart, Philip E; Hüffmeier, Ulrike; Nair, Rajan P; Palla, Raquel; Tejasvi, Trilokraj; Schalkwijk, Joost; Elder, James T; Reis, Andre; Armour, John A L

    2012-10-01

    A single previous study has demonstrated significant association of psoriasis with copy number of β-defensin genes, using DNA from psoriasis cases and controls from Nijmegen and Erlangen. In this study, we attempted to replicate that finding in larger new cohorts from Erlangen (N=2,017) and Michigan (N=5,412), using improved methods for β-defensin copy number determination based on the paralog ratio test, and enhanced methods of analysis and association testing implemented in the CNVtools resource. We demonstrate that the association with psoriasis found in the discovery sample is maintained after applying improved typing and analysis methods (P=5.5 × 10(-4), odds ratio (OR)=1.25). We also find that the association is replicated in 2,616 cases and 2,526 controls from Michigan, although at reduced significance (P=0.014), but not in new samples from Erlangen (1,396 cases and 621 controls, P=0.38). Meta-analysis across all cohorts suggests a nominally significant association (P=6.6 × 10(-3)/2 × 10(-4)) with an effect size (OR=1.081) much lower than found in the discovery study (OR=1.32). This reduced effect size and significance on replication is consistent with a genuine but weak association.

  4. Copy Number Deletion Has Little Impact on Gene Expression Levels in Racehorses

    Directory of Open Access Journals (Sweden)

    Kyung-Do Park

    2014-09-01

    Full Text Available Copy number variations (CNVs, important genetic factors for study of human diseases, may have as large of an effect on phenotype as do single nucleotide polymorphisms. Indeed, it is widely accepted that CNVs are associated with differential disease susceptibility. However, the relationships between CNVs and gene expression have not been characterized in the horse. In this study, we investigated the effects of copy number deletion in the blood and muscle transcriptomes of Thoroughbred racing horses. We identified a total of 1,246 CNVs of deletion polymorphisms using DNA re-sequencing data from 18 Thoroughbred racing horses. To discover the tendencies between CNV status and gene expression levels, we extracted CNVs of four Thoroughbred racing horses of which RNA sequencing was available. We found that 252 pairs of CNVs and genes were associated in the four horse samples. We did not observe a clear and consistent relationship between the deletion status of CNVs and gene expression levels before and after exercise in blood and muscle. However, we found some pairs of CNVs and associated genes that indicated relationships with gene expression levels: a positive relationship with genes responsible for membrane structure or cytoskeleton and a negative relationship with genes involved in disease. This study will lead to conceptual advances in understanding the relationship between CNVs and global gene expression in the horse.

  5. 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.

  6. Genomic copy number analysis of Chernobyl papillary thyroid carcinoma in the Ukrainian–American Cohort

    Science.gov (United States)

    Selmansberger, Martin; Braselmann, Herbert; Hess, Julia; Bogdanova, Tetiana; Abend, Michael; Tronko, Mykola; Brenner, Alina; Zitzelsberger, Horst; Unger, Kristian

    2015-01-01

    One of the major consequences of the 1986 Chernobyl reactor accident was a dramatic increase in papillary thyroid carcinoma (PTC) incidence, predominantly in patients exposed to the radioiodine fallout at young age. The present study is the first on genomic copy number alterations (CNAs) of PTCs of the Ukrainian–American cohort (UkrAm) generated by array comparative genomic hybridization (aCGH). Unsupervised hierarchical clustering of CNA profiles revealed a significant enrichment of a subgroup of patients with female gender, long latency (>17 years) and negative lymph node status. Further, we identified single CNAs that were significantly associated with latency, gender, radiation dose and BRAF V600E mutation status. Multivariate analysis revealed no interactions but additive effects of parameters gender, latency and dose on CNAs. The previously identified radiation-associated gain of the chromosomal bands 7q11.22-11.23 was present in 29% of cases. Moreover, comparison of our radiation-associated PTC data set with the TCGA data set on sporadic PTCs revealed altered copy numbers of the tumor driver genes NF2 and CHEK2. Further, we integrated the CNA data with transcriptomic data that were available on a subset of the herein analyzed cohort and did not find statistically significant associations between the two molecular layers. However, applying hierarchical clustering on a ‘BRAF-like/RAS-like’ transcriptome signature split the cases into four groups, one of which containing all BRAF-positive cases validating the signature in an independent data set. PMID:26320103

  7. Using Copy Number Alterations to Identify New Therapeutic Targets for Bladder Carcinoma

    Directory of Open Access Journals (Sweden)

    Donatella Conconi

    2016-02-01

    Full Text Available Bladder cancer represents the ninth most widespread malignancy throughout the world. It is characterized by the presence of two different clinical and prognostic subtypes: non-muscle-invasive bladder cancers (NMIBCs and muscle-invasive bladder cancers (MIBCs. MIBCs have a poor outcome with a common progression to metastasis. Despite improvements in knowledge, treatment has not advanced significantly in recent years, with the absence of new therapeutic targets. Because of the limitations of current therapeutic options, the greater challenge will be to identify biomarkers for clinical application. For this reason, we compared our array comparative genomic hybridization (array-CGH results with those reported in literature for invasive bladder tumors and, in particular, we focused on the evaluation of copy number alterations (CNAs present in biopsies and retained in the corresponding cancer stem cell (CSC subpopulations that should be the main target of therapy. According to our data, CCNE1, MYC, MDM2 and PPARG genes could be interesting therapeutic targets for bladder CSC subpopulations. Surprisingly, HER2 copy number gains are not retained in bladder CSCs, making the gene-targeted therapy less interesting than the others. These results provide precious advice for further study on bladder therapy; however, the clinical importance of these results should be explored.

  8. iGC-an integrated analysis package of gene expression and copy number alteration.

    Science.gov (United States)

    Lai, Yi-Pin; Wang, Liang-Bo; Wang, Wei-An; Lai, Liang-Chuan; Tsai, Mong-Hsun; Lu, Tzu-Pin; Chuang, Eric Y

    2017-01-14

    With the advancement in high-throughput technologies, researchers can simultaneously investigate gene expression and copy number alteration (CNA) data from individual patients at a lower cost. Traditional analysis methods analyze each type of data individually and integrate their results using Venn diagrams. Challenges arise, however, when the results are irreproducible and inconsistent across multiple platforms. To address these issues, one possible approach is to concurrently analyze both gene expression profiling and CNAs in the same individual. We have developed an open-source R/Bioconductor package (iGC). Multiple input formats are supported and users can define their own criteria for identifying differentially expressed genes driven by CNAs. The analysis of two real microarray datasets demonstrated that the CNA-driven genes identified by the iGC package showed significantly higher Pearson correlation coefficients with their gene expression levels and copy numbers than those genes located in a genomic region with CNA. Compared with the Venn diagram approach, the iGC package showed better performance. The iGC package is effective and useful for identifying CNA-driven genes. By simultaneously considering both comparative genomic and transcriptomic data, it can provide better understanding of biological and medical questions. The iGC package's source code and manual are freely available at https://www.bioconductor.org/packages/release/bioc/html/iGC.html .

  9. Association of β-defensin copy number and psoriasis in three cohorts of European origin

    Science.gov (United States)

    Stuart, Philip E; Hüffmeier, Ulrike; Nair, Rajan P; Palla, Raquel; Tejasvi, Trilokraj; Schalkwijk, Joost; Elder, James T; Reis, Andre; Armour, John AL

    2012-01-01

    A single previous study has demonstrated significant association of psoriasis with copy number of beta-defensin genes, using DNA from psoriasis cases and controls from Nijmegen and Erlangen. In this study we attempted to replicate that finding in larger new cohorts from Erlangen (N = 2017) and Michigan (N = 5412), using improved methods for beta-defensin copy number determination based on the paralog ratio test (PRT), and enhanced methods of analysis and association testing implemented in the CNVtools resource. We demonstrate that the association with psoriasis found in the discovery sample is maintained after applying improved typing and analysis methods (p = 5.5 × 10−4, OR = 1.25). We also find that the association is replicated in 2616 cases and 2526 controls from Michigan, although at reduced significance (p = 0.014), but not in new samples from Erlangen (1396 cases and 621 controls, p = 0.38). Meta-analysis across all cohorts suggests a nominally significant association (p = 6.6 × 10−3/2 × 10−4) with an effect size (OR = 1.081) much lower than found in the discovery study (OR = 1.32). This reduced effect size and significance on replication is consistent with a genuine but weak association. PMID:22739795

  10. Parallel Evolution of Copy-Number Variation across Continents in Drosophila melanogaster

    Science.gov (United States)

    Schrider, Daniel R.; Hahn, Matthew W.; Begun, David J.

    2016-01-01

    Genetic differentiation across populations that is maintained in the presence of gene flow is a hallmark of spatially varying selection. In Drosophila melanogaster, the latitudinal clines across the eastern coasts of Australia and North America appear to be examples of this type of selection, with recent studies showing that a substantial portion of the D. melanogaster genome exhibits allele frequency differentiation with respect to latitude on both continents. As of yet there has been no genome-wide examination of differentiated copy-number variants (CNVs) in these geographic regions, despite their potential importance for phenotypic variation in Drosophila and other taxa. Here, we present an analysis of geographic variation in CNVs in D. melanogaster. We also present the first genomic analysis of geographic variation for copy-number variation in the sister species, D. simulans, in order to investigate patterns of parallel evolution in these close relatives. In D. melanogaster we find hundreds of CNVs, many of which show parallel patterns of geographic variation on both continents, lending support to the idea that they are influenced by spatially varying selection. These findings support the idea that polymorphic CNVs contribute to local adaptation in D. melanogaster. In contrast, we find very few CNVs in D. simulans that are geographically differentiated in parallel on both continents, consistent with earlier work suggesting that clinal patterns are weaker in this species. PMID:26809315

  11. 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

  12. ORF Sequence: NC_001141 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_001141 gi|6322114 >gi|6322114|ref|NP_012189.1| Part of a heptameric protein complex that regulates retro...grade Golgi-to-ER protein traffic in eukaryotic cells; coatomer forms the COP I ves

  13. 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.

  14. 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.

  15. Notes de lecture et édition du ''second volume'' de Bouvard et Pécuchet : configurations complexes de l'inachèvement

    OpenAIRE

    Dord-Crouslé, Stéphanie

    2012-01-01

    International audience; Examining the preparatory documents allows to establish the regular pattern of development of the second volume of Bouvard et Pécuchet despite its incompleteness: Flaubert selects textual fragments on his reading notes pages before they are copied first on summary pages and then on pages prepared for the second volume. However some in absentia fragments (designated by Flaubert for the second volume, but not actually copied) pose complex editorial problems: the text ref...

  16. Copy number of the transposon, Pokey, in rDNA is positively correlated with rDNA copy number in Daphnia obtuse [corrected].

    Directory of Open Access Journals (Sweden)

    Kaitlynn LeRiche

    Full Text Available Pokey is a class II DNA transposon that inserts into 28S ribosomal RNA (rRNA genes and other genomic regions of species in the subgenus, Daphnia. Two divergent lineages, PokeyA and PokeyB have been identified. Recombination between misaligned rRNA genes changes their number and the number of Pokey elements. We used quantitative PCR (qPCR to estimate rRNA gene and Pokey number in isolates from natural populations of Daphnia obtusa, and in clonally-propagated mutation accumulation lines (MAL initiated from a single D. obtusa female. The change in direction and magnitude of Pokey and rRNA gene number did not show a consistent pattern across ∼ 87 generations in the MAL; however, Pokey and rRNA gene number changed in concert. PokeyA and 28S gene number were positively correlated in the isolates from both natural populations and the MAL. PokeyB number was much lower than PokeyA in both MAL and natural population isolates, and showed no correlation with 28S gene number. Preliminary analysis did not detect PokeyB outside rDNA in any isolates and detected only 0 to 4 copies of PokeyA outside rDNA indicating that Pokey may be primarily an rDNA element in D. obtusa. The recombination rate in this species is high and the average size of the rDNA locus is about twice as large as that in other Daphnia species such as D. pulicaria and D. pulex, which may have facilitated expansion of PokeyA to much higher numbers in D. obtusa rDNA than these other species.

  17. Inferring species trees from incongruent multi-copy gene trees using the Robinson-Foulds distance

    Science.gov (United States)

    2013-01-01

    Background Constructing species trees from multi-copy gene trees remains a challenging problem in phylogenetics. One difficulty is that the underlying genes can be incongruent due to evolutionary processes such as gene duplication and loss, deep coalescence, or lateral gene transfer. Gene tree estimation errors may further exacerbate the difficulties of species tree estimation. Results We present a new approach for inferring species trees from incongruent multi-copy gene trees that is based on a generalization of the Robinson-Foulds (RF) distance measure to multi-labeled trees (mul-trees). We prove that it is NP-hard to compute the RF distance between two mul-trees; however, it is easy to calculate this distance between a mul-tree and a singly-labeled species tree. Motivated by this, we formulate the RF problem for mul-trees (MulRF) as follows: Given a collection of multi-copy gene trees, find a singly-labeled species tree that minimizes the total RF distance from the input mul-trees. We develop and implement a fast SPR-based heuristic algorithm for the NP-hard MulRF problem. We compare the performance of the MulRF method (available at http://genome.cs.iastate.edu/CBL/MulRF/) with several gene tree parsimony approaches using gene tree simulations that incorporate gene tree error, gene duplications and losses, and/or lateral transfer. The MulRF method produces more accurate species trees than gene tree parsimony approaches. We also demonstrate that the MulRF method infers in minutes a credible plant species tree from a collection of nearly 2,000 gene trees. Conclusions Our new phylogenetic inference method, based on a generalized RF distance, makes it possible to quickly estimate species trees from large genomic data sets. Since the MulRF method, unlike gene tree parsimony, is based on a generic tree distance measure, it is appealing for analyses of genomic data sets, in which many processes such as deep coalescence, recombination, gene duplication and losses as

  18. Saving HEBBLE Data from Oblivion: From Faded Paper Copy to Digital Files

    Science.gov (United States)

    Mishonov, A. V.; Richardson, M. J.; Gardner, W. D.

    2017-12-01

    The high-energy benthic boundary-layer experiment (HEBBLE) was designed to test the hypothesis that bed modifications can result from contemporary local erosion and deposition. We observed several 'benthic storms' that resuspended record-high concentrations of particulate matter - filtered samples up to 12,700 µg/l. High kinetic energy and near-bed flow were associated with these record-high concentrations of particulate matter at 4,9600 m off the Nova Scotian Rise in the north-west Atlantic, showing that large episodic events resuspend bottom sediments in deep ocean areas. As part of HEBBLE, CTD/Transmissometer data were collected in the late 1970's and early 1980's, including more than 40 stations on cruise KN74. Although many papers were published based on HEBBLE data, no electronic copies of the KN74 CTD/Transmissometer data were preserved. Because of the uniqueness of the record-high particulate matter concentrations, with ambient current velocities of >70 cm/sec near the seafloor, it was important to rescue these data. We had a paper printout of all of the digital CTD data. Attempts to scan and apply OCR to the data proved futile with standard copying/scanning machines. Texas A&M University Library Digital Service Center scanned our copies with a SupraScanQuartzA00-CamQuartzHD scanner and used ABBYY Fine Reader for OCR and PDF, more frequently used in the humanities for digital preservation and conservation. Their scans were markedly better, but still contained many errors because of poor quality originals. Two students were hired to QA/QC the hundreds of pages of data. While tedious, they successfully corrected the data, thus making it possible to make maps and sections shown here and submit data to publicly accessible archives for future generations to use. These data reside in the OAKTrust Digital Repository at Texas A&M University. After final QA/QC these data will be submitted to NCEI and will be merged with World Ocean Database (WOD).

  19. An integrated analysis of miRNA and gene copy numbers in xenografts of Ewing's sarcoma

    Directory of Open Access Journals (Sweden)

    Mosakhani Neda

    2012-03-01

    Full Text Available Abstract Background Xenografts have been shown to provide a suitable source of tumor tissue for molecular analysis in the absence of primary tumor material. We utilized ES xenograft series for integrated microarray analyses to identify novel biomarkers. Method Microarray technology (array comparative genomic hybridization (aCGH and micro RNA arrays was used to screen and identify copy number changes and differentially expressed miRNAs of 34 and 14 passages, respectively. Incubated cells used for xenografting (Passage 0 were considered to represent the primary tumor. Four important differentially expressed miRNAs (miR-31, miR-31*, miR-145, miR-106 were selected for further validation by real time polymerase chain reaction (RT-PCR. Integrated analysis of aCGH and miRNA data was performed on 14 xenograft passages by bioinformatic methods. Results The most frequent losses and gains of DNA copy number were detected at 9p21.3, 16q and at 8, 15, 17q21.32-qter, 1q21.1-qter, respectively. The presence of these alterations was consistent in all tumor passages. aCGH profiles of xenograft passages of each series resembled their corresponding primary tumors (passage 0. MiR-21, miR-31, miR-31*, miR-106b, miR-145, miR-150*, miR-371-5p, miR-557 and miR-598 showed recurrently altered expression. These miRNAS were predicted to regulate many ES-associated genes, such as genes of the IGF1 pathway, EWSR1, FLI1 and their fusion gene (EWS-FLI1. Twenty differentially expressed miRNAs were pinpointed in regions carrying altered copy numbers. Conclusion In the present study, ES xenografts were successfully applied for integrated microarray analyses. Our findings showed expression changes of miRNAs that were predicted to regulate many ES associated genes, such as IGF1 pathway genes, FLI1, EWSR1, and the EWS-FLI1 fusion genes.

  20. BRAF Gene Copy Number and Mutant Allele Frequency Correlate with Time to Progression in Metastatic Melanoma Patients Treated with MAPK Inhibitors.

    Science.gov (United States)

    Stagni, Camilla; Zamuner, Carolina; Elefanti, Lisa; Zanin, Tiziana; Bianco, Paola Del; Sommariva, Antonio; Fabozzi, Alessio; Pigozzo, Jacopo; Mocellin, Simone; Montesco, Maria Cristina; Chiarion-Sileni, Vanna; De Nicolo, Arcangela; Menin, Chiara

    2018-06-01

    Metastatic melanoma is characterized by complex genomic alterations, including a high rate of mutations in driver genes and widespread deletions and amplifications encompassing various chromosome regions. Among them, chromosome 7 is frequently gained in BRAF -mutant melanoma, inducing a mutant allele-specific imbalance. Although BRAF amplification is a known mechanism of acquired resistance to therapy with MAPK inhibitors, it is still unclear if BRAF copy-number variation and BRAF mutant allele imbalance at baseline can be associated with response to treatment. In this study, we used a multimodal approach to assess BRAF copy number and mutant allele frequency in pretreatment melanoma samples from 46 patients who received MAPK inhibitor-based therapy, and we analyzed the association with progression-free survival. We found that 65% patients displayed BRAF gains, often supported by chromosome 7 polysomy. In addition, we observed that 64% patients had a balanced BRAF -mutant/wild-type allele ratio, whereas 14% and 23% patients had low and high BRAF mutant allele frequency, respectively. Notably, a significantly higher risk of progression was observed in patients with a diploid BRAF status versus those with BRAF gains [HR, 2.86; 95% confidence interval (CI), 1.29-6.35; P = 0.01] and in patients with low percentage versus those with a balanced BRAF mutant allele percentage (HR, 4.54; 95% CI, 1.33-15.53; P = 0.016). Our data suggest that quantitative analysis of the BRAF gene could be useful to select the melanoma patients who are most likely to benefit from therapy with MAPK inhibitors. Mol Cancer Ther; 17(6); 1332-40. ©2018 AACR . ©2018 American Association for Cancer Research.