WorldWideScience

Sample records for two-point linkage analysis

  1. A Formalization of Linkage Analysis

    DEFF Research Database (Denmark)

    Ingolfsdottir, Anna; Christensen, A.I.; Hansen, Jens A.

    In this report a formalization of genetic linkage analysis is introduced. Linkage analysis is a computationally hard biomathematical method, which purpose is to locate genes on the human genome. It is rooted in the new area of bioinformatics and no formalization of the method has previously been ...

  2. A Formalization of Linkage Analysis

    DEFF Research Database (Denmark)

    Ingolfsdottir, Anna; Christensen, A.I.; Hansen, Jens A.

    In this report a formalization of genetic linkage analysis is introduced. Linkage analysis is a computationally hard biomathematical method, which purpose is to locate genes on the human genome. It is rooted in the new area of bioinformatics and no formalization of the method has previously been...

  3. A NEW TWO-POINT ADAPTIVENONLINEAR APPROXIMATION METHOD FOR RELIABILITY ANALYSIS

    Institute of Scientific and Technical Information of China (English)

    LiuShutian

    2004-01-01

    A two-point adaptive nonlinear approximation (referred to as TANA4) suitable for reliability analysis is proposed. Transformed and normalized random variables in probabilistic analysis could become negative and pose a challenge to the earlier developed two-point approximations; thus a suitable method that can address this issue is needed. In the method proposed, the nonlinearity indices of intervening variables are limited to integers. Then, on the basis of the present method, an improved sequential approximation of the limit state surface for reliability analysis is presented. With the gradient projection method, the data points for the limit state surface approximation are selected on the original limit state surface, which effectively represents the nature of the original response function. On the basis of this new approximation, the reliability is estimated using a first-order second-moment method. Various examples, including both structural and non-structural ones, are presented to show the effectiveness of the method proposed.

  4. Analysis of errors in the measurement of energy dissipation with two-point LDA

    Energy Technology Data Exchange (ETDEWEB)

    Ducci, A.; Yianneskis, M. [Department of Mechanical Engineering, King' s College London, Experimental and Computational Laboratory for the Analysis of Turbulence (ECLAT), London (United Kingdom)

    2005-04-01

    In the present study, an attempt has been made to identify and quantify, with a rigorous analytical approach, all possible sources of error involved in the estimation of the fluctuating velocity gradients ({partial_derivative}u{sub i}/{partial_derivative}x{sub j}){sup 2} when a two-point laser Doppler velocimetry (LDV) technique is employed. Measurements were carried out in a grid-generated turbulence flow where the local dissipation rate can be calculated from the decay of kinetic energy. An assessment of the cumulative error determined through the analysis has been made by comparing the values of the spatial gradients directly measured with the gradient estimated from the decay of kinetic energy. The main sources of error were found to be related to the length of the two control volumes and to the fitting range, as well as the function used to interpolate the correlation coefficient when the Taylor length scale (or({partial_derivative}u{sub i}/{partial_derivative}x{sub j}){sup 2}) are estimated. (orig.)

  5. Linkage analysis in alcohol dependence.

    Science.gov (United States)

    Windemuth, C; Hahn, A; Strauch, K; Baur, M P; Wienker, T F

    1999-01-01

    Alcohol dependence often is a familial disorder and has a genetic component. Research in causative factors of alcoholism is coordinated by a multi-center program, COGA [The Collaborative Study on the Genetics of Alcoholism, Begleiter et al., 1995]. We analyzed a subset of the COGA family sample, 84 pedigrees of Caucasian ancestry comprising 745 persons, 339 of whom are affected according to DSM-III-R and Feighner criteria. Using parametric and nonparametric methods, evidence for linkage was found on chromosome 1 (near markers D1S532, D1S1588, and D1S534), as well as on chromosome 15 (near marker D15S642). Other regions of the genome showed suggestive evidence for contributing loci. Related findings are discussed in recent publications investigating linkage in humans [Reich et al., 1998] and mice [Melo et al., 1996].

  6. A COMPARISON BETWEEN SINGLE LINKAGE AND COMPLETE LINKAGE IN AGGLOMERATIVE HIERARCHICAL CLUSTER ANALYSIS FOR IDENTIFYING TOURISTS SEGMENTS

    OpenAIRE

    Noor Rashidah Rashid

    2012-01-01

    Cluster Analysis is a multivariate method in statistics. Agglomerative Hierarchical Cluster Analysis is one of approaches in Cluster Analysis. There are two linkage methods in Agglomerative Hierarchical Cluster Analysis which are Single Linkage and Complete Linkage. The purpose of this study is to compare between Single Linkage and Complete Linkage in Agglomerative Hierarchical Cluster Analysis. The comparison of performances between these linkage methods was shown by using Kruskal-Wallis tes...

  7. Methods for genetic linkage analysis using trisomies

    Energy Technology Data Exchange (ETDEWEB)

    Feingold, E. [Emory Univ. School of Public Health, Atlanta, GA (United States); Lamb, N.E.; Sherman, S.L. [Emory Univ., Atlanta, GA (United States)

    1995-02-01

    Certain genetic disorders are rare in the general population, but more common in individuals with specific trisomies. Examples of this include leukemia and duodenal atresia in trisomy 21. This paper presents a linkage analysis method for using trisomic individuals to map genes for such traits. It is based on a very general gene-specific dosage model that posits that the trait is caused by specific effects of different alleles at one or a few loci and that duplicate copies of {open_quotes}susceptibility{close_quotes} alleles inherited from the nondisjoining parent give increased likelihood of having the trait. Our mapping method is similar to identity-by-descent-based mapping methods using affected relative pairs and also to methods for mapping recessive traits using inbred individuals by looking for markers with greater than expected homozygosity by descent. In the trisomy case, one would take trisomic individuals and look for markers with greater than expected homozygosity in the chromosomes inherited from the nondisjoining parent. We present statistical methods for performing such a linkage analysis, including a test for linkage to a marker, a method for estimating the distance from the marker to the trait gene, a confidence interval for that distance, and methods for computing power and sample sizes. We also resolve some practical issues involved in implementing the methods, including how to use partially informative markers and how to test candidate genes. 20 refs., 5 figs., 1 tab.

  8. Model-based methods for linkage analysis.

    Science.gov (United States)

    Rice, John P; Saccone, Nancy L; Corbett, Jonathan

    2008-01-01

    The logarithm of an odds ratio (LOD) score method originated in a seminal article by Newton Morton in 1955. The method is broadly concerned with issues of power and the posterior probability of linkage, ensuring that a reported linkage has a high probability of being a true linkage. In addition, the method is sequential so that pedigrees or LOD curves may be combined from published reports to pool data for analysis. This approach has been remarkably successful for 50 years in identifying disease genes for Mendelian disorders. After discussing these issues, we consider the situation for complex disorders where the maximum LOD score statistic shares some of the advantages of the traditional LOD score approach, but is limited by unknown power and the lack of sharing of the primary data needed to optimally combine analytic results. We may still learn from the LOD score method as we explore new methods in molecular biology and genetic analysis to utilize the complete human DNA sequence and the cataloging of all human genes.

  9. Intrinsic alignments of galaxies in the MassiveBlack-II simulation: analysis of two-point statistics

    CERN Document Server

    Tenneti, Ananth; Mandelbaum, Rachel; Di Matteo, Tiziana; Feng, Yu; Khandai, Nishikanta

    2014-01-01

    The intrinsic alignment of galaxies with the large-scale density field is an important astrophysical contaminant in upcoming weak lensing surveys whilst offering insights into galaxy formation and evolution. We present detailed measurements of the galaxy intrinsic alignments and associated ellipticity-direction (ED) and projected shape ($w_{g+}$) correlation functions for galaxies in the cosmological hydrodynamic MassiveBlack-II (MB-II) simulation. We carefully assess the effects on galaxy shapes, misalignments and two-point statistics of iterative weighted (by mass, luminosity, and color) definitions of the (reduced and unreduced) inertia tensor. We find that iterative procedures must be adopted for a reliable measurement of reduced tensor but that luminosity versus mass weighting has only negligible effects. Blue galaxies exhibit stronger misalignments and suppressed $w_{g+}$ amplitude. Both ED and $w_{g+}$ correlations increase in amplitude with subhalo mass (in the range of $10^{10} - 6.0\\times 10^{14}h^{...

  10. Methods for genetic linkage analysis using trisomies

    Energy Technology Data Exchange (ETDEWEB)

    Feingold, E.; Lamb, N.E.; Sherman, S.L. [Emory Univ., Atlanta, GA (United States)

    1994-09-01

    Certain genetic disorders (e.g. congenital cataracts, duodenal atresia) are rare in the general population, but more common in people with Down`s syndrome. We present a method for using individuals with trisomy 21 to map genes for such traits. Our methods are analogous to methods for mapping autosomal dominant traits using affected relative pairs by looking for markers with greater than expected identity-by-descent. In the trisomy case, one would take trisomic individuals and look for markers with greater than expected reduction to homozygosity in the chromosomes inherited form the non-disjoining parent. We present statistical methods for performing such a linkage analysis, including a test for linkage to a marker, a method for estimating the distance from the marker to the gene, a confidence interval for that distance, and methods for computing power and sample sizes. The methods are described in the context of gene-dosage model for the etiology of the disorder, but can be extended to other models. We also resolve some practical issues involved in implementing the methods, including how to use partially informative markers, how to test candidate genes, and how to handle the effect of reduced recombination associated with maternal meiosis I non-disjunction.

  11. Model-free linkage analysis of a binary trait.

    Science.gov (United States)

    Xu, Wei; Bull, Shelley B; Mirea, Lucia; Greenwood, Celia M T

    2012-01-01

    Genetic linkage analysis aims to detect chromosomal regions containing genes that influence risk of specific inherited diseases. The presence of linkage is indicated when a disease or trait cosegregates through the families with genetic markers at a particular region of the genome. Two main types of genetic linkage analysis are in common use, namely model-based linkage analysis and model-free linkage analysis. In this chapter, we focus solely on the latter type and specifically on binary traits or phenotypes, such as the presence or absence of a specific disease. Model-free linkage analysis is based on allele-sharing, where patterns of genetic similarity among affected relatives are compared to chance expectations. Because the model-free methods do not require the specification of the inheritance parameters of a genetic model, they are preferred by many researchers at early stages in the study of a complex disease. We introduce the history of model-free linkage analysis in Subheading 1. Table 1 describes a standard model-free linkage analysis workflow. We describe three popular model-free linkage analysis methods, the nonparametric linkage (NPL) statistic, the affected sib-pair (ASP) likelihood ratio test, and a likelihood approach for pedigrees. The theory behind each linkage test is described in this section, together with a simple example of the relevant calculations. Table 4 provides a summary of popular genetic analysis software packages that implement model-free linkage models. In Subheading 2, we work through the methods on a rich example providing sample software code and output. Subheading 3 contains notes with additional details on various topics that may need further consideration during analysis.

  12. Linkage analysis of chromosome 14 and essential hypertension in Chinese population

    Institute of Scientific and Technical Information of China (English)

    ZHAO Wei-yan; HUANG Jian-feng; GE Dong-liang; SU Shao-yong; LI Biao; GU Dong-feng

    2005-01-01

    Background Hypertension is a complex biological trait that influenced by multiple factors. The encouraging results for hypertension research showed that the linkage analysis can be used to replicate other studies and discover new genetic risk factors. Previous studies linked human chromosome 14 to essential hypertension or blood pressure traits. With a Chinese population, we tried to replicate these findings. Methods A linkage scan was performed on chromosome 14 with 14-microsatellite markers with a density of about 10 centi Morgen (cM) in 147 Chinese hypertensive nuclear families. Multipoint non-parametric linkage analysis and exclusion mapping were performed with the GENEHUNTER software, whereas quantitative analysis was performed with the variance component method integrated in the SOLAR package. Results In the qualitative analysis, the highest non-parametric linkage score is 1.0 (P=0.14) at D14S261 in the single point analysis, and no loci achieved non-parametric linkage score more than 1.0 in the multipoint analysis. Maximum-likelihood mapping showed no significant results, either. Subsequently the traditional exclusion criteria of the log-of-the-odds score-2 were adopted, and the chromosome 14 with λs≥2.4 was excluded. In the quantitative analysis of blood pressure with the SOLAR software, two-point analysis and multipoint analysis suggested no evidence for linkage occurred on chromosome 14 for systolic and diastolic blood pressure. Conclusion There was no substantial evidence to support the linkage of chromosome 14 and essential hypertension or blood pressure trait in Chinese hypertensive subjects in this study.

  13. Autosomal dominant familial spastic paraplegia; Linkage analysis and evidence for linkage to chromosome 2p

    Energy Technology Data Exchange (ETDEWEB)

    Figlewicz, D.A. [Univ. of Rochester, NY (United States); Dube, M.P.; Rouleau, G.A. [McGill Univ., Montreal (Canada)] [and others

    1994-09-01

    Familial spastic paraplegia (FSP) is a degenerative disorder of the motor system characterized by progressive weakness and spasticity of the lower limbs. Little is known about the pathophysiology of this disorder. FSP can be inherited as an autosomal dominant (AD), autosomal recessive, or X-linked trait. We have undertaken linkage analysis for a group of 36 AD FSP families from which we have collected blood samples from 427 individuals, including 148 affected individuals. Typing of polymorphic markers has allowed us to exclude more than 50% of the genome. Recently, linkage for AD FSP to a locus on chromosome 14q was reported. Our AD FSP kindreds were tested for linkage to markers spanning the 20 cM region between D14S69 and D14S66; however, we were not able to establish linkage for any of our families to chromosome 14. Lod scores suggestive of linkage for some AD FSP kindreds have been obtained for markers on chromosome 2p. We have tested seven polymorphic markers spanning the region between D2S405 and D2S177. Our highest aggregate lod score, including all families tested, was obtained at the locus D2S352: 2.4 at 20 cM. Results from HOMOG analysis for linkage heterogeneity will be reported.

  14. Characterizing the relative role of low-frequency and turbulent processes in the nocturnal boundary layer through the analysis of two-point correlations of the wind components

    Science.gov (United States)

    Teichrieb, Claudio A.; Acevedo, Otávio C.; Degrazia, Gervásio A.; Moraes, Osvaldo L. L.; Roberti, Débora R.; Zimermann, Hans R.; Santos, Daniel M.; Alves, Rita C. M.

    2013-03-01

    The study presents an analysis of two-point correlations between time series of nocturnal atmospheric wind, obtained from two micrometeorological towers, 45 m horizontally apart, each equipped with two sonic anemometers, 2.5 m vertically apart. It focuses on the scale dependence of the two-point correlations obtained from sensors vertically and horizontally separated. In particular, the role of low-frequency non-turbulent processes in the correlations is assessed, and compared to that of the turbulent scales of motion. The vertical correlations of the streamwise and vertical wind components show little dependence on the turbulence intensity, but those of the spanwise component decrease appreciably as it gets more turbulent. Multiresolution decomposition shows that the two-point correlations become increasingly dominated by low-frequency scales as it gets less turbulent, and that such large-scale processes are largely reduced in fully turbulent conditions. It is also shown that the vertical correlations of the spanwise wind component is negative for very small time scales. Horizontal two-point correlations obtained at the 45 m separation distance between the towers are almost entirely dominated by low-frequency motions, regardless of the turbulence intensity, but the magnitude of such correlations decreases with increasing turbulence intensity for any wind components. A comparison between the horizontal two-point correlations and autocorrelations taken with a time lag given by the ratio of the horizontal separation to the mean wind component in the direction that connects the two towers leads to the conclusion that the statistical properties of turbulence are often preserved over the horizontal distance, despite the lack of turbulence correlations for that separation.

  15. Identifying marker typing incompatibilities in linkage analysis

    Energy Technology Data Exchange (ETDEWEB)

    Stringham, H.M.; Boehnke, M. [Univ. of Michigan, Ann Arbor, MI (United States)

    1996-10-01

    A common problem encountered in linkage analyses is that execution of the computer program is halted because of genotypes in the data that are inconsistent with Mendelian inheritance. Such inconsistencies may arise because of pedigree errors or errors in typing. In some cases, the source of the inconsistencies is easily identified by examining the pedigree. In others, the error is not obvious, and substantial time and effort are required to identify the responsible genotypes. We have developed two methods for automatically identifying those individuals whose genotypes are most likely the cause of the inconsistencies. First, we calculate the posterior probability of genotyping error for each member of the pedigree, given the marker data on all pedigree members and allowing anyone in the pedigree to have an error. Second, we identify those individuals whose genotypes could be solely responsible for the inconsistency in the pedigree. We illustrate these methods with two examples: one a pedigree error, the second a genotyping error. These methods have been implemented as a module of the pedigree analysis program package MENDEL. 9 refs., 2 figs., 2 tabs.

  16. Linkage analysis suggests a locus of ichthyosis vulgaris on 1q22.

    Science.gov (United States)

    Zhong, Wei; Cui, Bin; Zhang, Yizhi; Jiang, Haisong; Wei, Shengcai; Bu, Lei; Zhao, Guoping; Hu, Landian; Kong, Xiangyin

    2003-01-01

    Ichthyosis vulgaris (IV) is an inherited scaling skin disorder with a prevalence estimated at 2.29% in China. The gene responsible for this disorder has not been elucidated. To find the disease gene, we ascertained two Chinese IV families. Linkage analysis identified an IV locus on chromosome 1q22 with a maximum two-point Lod score of 2.47 at D1S1653 (theta=0.00). Haplotype analysis placed the critical region in a 7-cM interval defined by D1S1653 and D1S2675. These results provide the basis for further identifying the gene responsible for IV disorder.

  17. Genome-wide family-based linkage analysis of exome chip variants and cardiometabolic risk.

    Science.gov (United States)

    Hellwege, Jacklyn N; Palmer, Nicholette D; Raffield, Laura M; Ng, Maggie C Y; Hawkins, Gregory A; Long, Jirong; Lorenzo, Carlos; Norris, Jill M; Ida Chen, Y-D; Speliotes, Elizabeth K; Rotter, Jerome I; Langefeld, Carl D; Wagenknecht, Lynne E; Bowden, Donald W

    2014-05-01

    Linkage analysis of complex traits has had limited success in identifying trait-influencing loci. Recently, coding variants have been implicated as the basis for some biomedical associations. We tested whether coding variants are the basis for linkage peaks of complex traits in 42 African-American (n = 596) and 90 Hispanic (n = 1,414) families in the Insulin Resistance Atherosclerosis Family Study (IRASFS) using Illumina HumanExome Beadchips. A total of 92,157 variants in African Americans (34%) and 81,559 (31%) in Hispanics were polymorphic and tested using two-point linkage and association analyses with 37 cardiometabolic phenotypes. In African Americans 77 LOD scores greater than 3 were observed. The highest LOD score was 4.91 with the APOE SNP rs7412 (MAF = 0.13) with plasma apolipoprotein B (ApoB). This SNP was associated with ApoB (P-value = 4 × 10(-19)) and accounted for 16.2% of the variance in African Americans. In Hispanic families, 104 LOD scores were greater than 3. The strongest evidence of linkage (LOD = 4.29) was with rs5882 (MAF = 0.46) in CETP with HDL. CETP variants were strongly associated with HDL (0.00049 evidence of strong linkage in this genome wide survey of primarily coding variants was uncommon. Loci with strong evidence of linkage was characterized by large contributions to the variance, and, in these cases, are common variants. Less compelling evidence of linkage and association was observed with additional loci that may require larger family sets to confirm. © 2014 WILEY PERIODICALS, INC.

  18. Software for analysis and manipulation of genetic linkage data.

    Science.gov (United States)

    Weaver, R; Helms, C; Mishra, S K; Donis-Keller, H

    1992-06-01

    We present eight computer programs written in the C programming language that are designed to analyze genotypic data and to support existing software used to construct genetic linkage maps. Although each program has a unique purpose, they all share the common goals of affording a greater understanding of genetic linkage data and of automating tasks to make computers more effective tools for map building. The PIC/HET and FAMINFO programs automate calculation of relevant quantities such as heterozygosity, PIC, allele frequencies, and informativeness of markers and pedigrees. PREINPUT simplifies data submissions to the Centre d'Etude du Polymorphisme Humain (CEPH) data base by creating a file with genotype assignments that CEPH's INPUT program would otherwise require to be input manually. INHERIT is a program written specifically for mapping the X chromosome: by assigning a dummy allele to males, in the nonpseudoautosomal region, it eliminates falsely perceived noninheritances in the data set. The remaining four programs complement the previously published genetic linkage mapping software CRI-MAP and LINKAGE. TWOTABLE produces a more readable format for the output of CRI-MAP two-point calculations; UNMERGE is the converse to CRI-MAP's merge option; and GENLINK and LINKGEN automatically convert between the genotypic data file formats required by these packages. All eight applications read input from the same types of data files that are used by CRI-MAP and LINKAGE. Their use has simplified the management of data, has increased knowledge of the content of information in pedigrees, and has reduced the amount of time needed to construct genetic linkage maps of chromosomes.

  19. ANALYSIS OF INTER SECTORAL LINKAGES IN SEMARANG REGENCY

    Directory of Open Access Journals (Sweden)

    Fafurida

    2014-03-01

    Full Text Available This research aims to analyze inter economic sectoral linkages and to arrange the Klassen typology of economic sectors in Semarang Regency. The Klassen typology is composed from the result of the linkage analysis. To construct the analysis, this paper also utulizes the input-output analysis. It finds that service sector has the highest backward linkage while farming sector has the highest forward linkage. Based on the Klassen typology analysis, sectors with the highest backward and forward linkages and potential to be the leading sector are farming sector, dan trade, hotel and restaurant sector.Keywords: Backward linkage,forward linkage, Klassen typologyJEL classification number: R15, O21AbstrakPenelitian ini bertujuan untuk mengkaji seberapa besar keterkaitan antar sektor ekonomi di Kabupaten Semarang dan memetakan tipologi Klassennya. Tipologi Klasen disusun berdasarkan hasil perhitungan analisis keterkaitannya. Untuk menyusun analisis tersebut, paper ini juga menggunakan analisis input-output. Hasil penelitian menunjukkan bahwa sektor jasa memiliki keterkaitan ke belakang tertinggi dibandingkan dengan sektor lainnya. Sementara itu, sektor pertanian merupakan sektor yang memiliki keterkaitan ke depan tertinggi. Berdasarkan hasil analisis tipologi Klassen, sektor yang memiliki keterkaitan ke depan dan ke belakang yang tinggi dan dapat menjadi sektor unggulan adalah sektor perdagangan, hotel dan sektor restoran.Kata kunci: Keterkaitan ke belakang, keterkaitan ke depan, tipologi KlassenJEL classification numbers: R15, O21

  20. Kinematic and Dynamic Characteristics Analysis of Bennett’ s Linkage

    Institute of Scientific and Technical Information of China (English)

    Jianfeng Li

    2015-01-01

    Bennett’ s linkage is a spatial fourlink linkage, and has an extensive application prospect in the deployable linkages.Its kinematic and dynamic characteristics analysis has a great significance in its synthesis and application. According to the geometrical conditions of Bennett ’ s linkage, the motion equations are established,and the expressions of angular displacement, angular velocity and angular acceleration of the followers and the displacement, velocity and acceleration of mass center of link are shown. Based on Lagrange’ s equation, the multi⁃rigid⁃body dynamic model of Bennett’ s linkage is established. In order to solve the reaction forces and moments of joint, screw theory and reciprocal screw method are combined to establish the computing method.The number of equations and unknown reaction forces and moments of joint are equal through adding link deformation equations. The influence of the included angle of adjacent axes on Bennett ’ s linkage ’ s kinematic characteristics, the dynamic characteristics and the reaction forces and moments of joint are analyzed. Results show that the included angle of adjacent axes has a great effect on velocity, acceleration, the reaction forces and moments of Bennett’ s linkage. The change of reaction forces and moments of joint are apparent near the singularity configuration.

  1. Typology of Empirical Attributes: Dissimilarity Linkage Analysis (DLA).

    Science.gov (United States)

    Dubin, Robert; Champoux, Joseph E.

    Dissimilarity Linkage Analysis (DLA) is an extremely simple procedure for developing a typology from empirical attributes that permits the clustering of entities. First the procedure develops a taxonomy of types from empirical attributes possessed by entities in the sample. Second, the procedure assigns entities to one, and only one, type in the…

  2. Bayesian linkage analysis of categorical traits for arbitrary pedigree designs.

    Directory of Open Access Journals (Sweden)

    Abra Brisbin

    Full Text Available BACKGROUND: Pedigree studies of complex heritable diseases often feature nominal or ordinal phenotypic measurements and missing genetic marker or phenotype data. METHODOLOGY: We have developed a Bayesian method for Linkage analysis of Ordinal and Categorical traits (LOCate that can analyze complex genealogical structure for family groups and incorporate missing data. LOCate uses a Gibbs sampling approach to assess linkage, incorporating a simulated tempering algorithm for fast mixing. While our treatment is Bayesian, we develop a LOD (log of odds score estimator for assessing linkage from Gibbs sampling that is highly accurate for simulated data. LOCate is applicable to linkage analysis for ordinal or nominal traits, a versatility which we demonstrate by analyzing simulated data with a nominal trait, on which LOCate outperforms LOT, an existing method which is designed for ordinal traits. We additionally demonstrate our method's versatility by analyzing a candidate locus (D2S1788 for panic disorder in humans, in a dataset with a large amount of missing data, which LOT was unable to handle. CONCLUSION: LOCate's accuracy and applicability to both ordinal and nominal traits will prove useful to researchers interested in mapping loci for categorical traits.

  3. Broad scan linkage analysis in a large Tourette family pedigree

    Energy Technology Data Exchange (ETDEWEB)

    Peiffer, A.; Leppert, M. [Univ. of Utah Health Sciences Center, Salt Lake City, UT (United States); Wetering, B.J.M. van der [Univ. Hospital Rotterdam (Netherlands)

    1994-09-01

    Attempts to find a gene causing Tourette syndrome (TS) using linkage analysis have been unsuccessful even though as much as 65% of the autosomal genetic map has been excluded by the pooled results from several laboratories collaborating worldwide. One reason for this failure may be the misclassification of affection status of marry-in spouses. Specifically, we have found that six unrelated spouses in our Utah TS pedigree suffer from TS, obsessive-compulsive disorder or chronic motor tics. In light of these findings we decided to conduct a complete genomic scan from this Utah kindred with polymorphic markers in three related sibships in which there was no assortative mating. A linkage study assuming autosomal dominant inheritance was done using tetranucleotide repeat markers developed at the University of Utah. We selected markers that were less than 300 bp in size and that gave a heterozygosity of over 70% upon analysis in 4 CEPH families. Results to date with 95 markers run at an interval of 30 cM (covering 61% of the genome) show no evidence of linkage. We intend to extend the coverage to 100% of the genome. Pending completion of this scan, failure to provide evidence of linkage in our TS pedigree might then be attributed to phenotypic misclassification or erroneous assumptions regarding the genetic model of transmission.

  4. LINKAGE ANALYSIS BY 2-DIMENSIONAL DNA TYPING

    NARCIS (Netherlands)

    MEERMAN, GJT; MULLAART, E; VANDERMEULEN, MA; DENDAAS, JHG; MOROLLI, B; UITTERLINDEN, AG; VIJG, J

    1993-01-01

    In two-dimensional (2-D) DNA typing, genomic DNA fragments are separated, first according to size by electrophoresis in a neutral polyacrylamide gel and second according to sequence by denaturing gradient gel electrophoresis, followed by hybridization analysis using micro- and minisatellite core pro

  5. Identification of quantitative trait loci underlying milk traits in Spanish dairy sheep using linkage plus combined linkage disequilibrium and linkage analysis approaches.

    Science.gov (United States)

    Garcia-Gámez, E; Gutiérrez-Gil, B; Suarez-Vega, A; de la Fuente, L F; Arranz, J J

    2013-09-01

    In this study, 2 procedures were used to analyze a data set from a whole-genome scan, one based on linkage analysis information and the other combing linkage disequilibrium and linkage analysis (LDLA), to determine the quantitative trait loci (QTL) influencing milk production traits in sheep. A total of 1,696 animals from 16 half-sib families were genotyped using the OvineSNP50 BeadChip (Illumina Inc., San Diego, CA) and analysis was performed using a daughter design. Moreover, the same data set has been previously investigated through a genome-wide association (GWA) analysis and a comparison of results from the 3 methods has been possible. The linkage analysis and LDLA methodologies yielded different results, although some significantly associated regions were common to both procedures. The linkage analysis detected 3 overlapping genome-wise significant QTL on sheep chromosome (OAR) 2 influencing milk yield, protein yield, and fat yield, whereas 34 genome-wise significant QTL regions were detected using the LDLA approach. The most significant QTL for protein and fat percentages was detected on OAR3, which was reported in a previous GWA analysis. Both the linkage analysis and LDLA identified many other chromosome-wise significant associations across different sheep autosomes. Additional analyses were performed on OAR2 and OAR3 to determine the possible causality of the most significant polymorphisms identified for these genetic effects by the previously reported GWA analysis. For OAR3, the analyses demonstrated additional genetic proof of the causality previously suggested by our group for a single nucleotide polymorphism located in the α-lactalbumin gene (LALBA). In summary, although the results shown here suggest that in commercial dairy populations, the LDLA method exhibits a higher efficiency to map QTL than the simple linkage analysis or linkage disequilibrium methods, we believe that comparing the 3 analysis methods is the best approach to obtain a global

  6. Linkage analysis on chromosome 2 in essential hypotension pedigrees

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    It is a new approach to study the important genes related to the control of blood pressure by probing into hypotension and hypertension at the same time. Genome scanning on whole chromosome 2 in 8 hypotension pedigrees has been done and parameter (LOD score) and non-pa- rameter (NPL score) were used in the linkage analysis by GENEHUNTER software. The results show the evidence of linkage between D2S112 and D2S117, indicating a number of critical genes may lie in thisregion and contribute to the mechanism of blood pressure regulation. Also this region has been found in the previous study in hypertension pedigrees. These genes may play an important role in the regulation of blood pressure and can also be the important candidate genes in hypertension studies.

  7. Nickel-catalyzed proton-deuterium exchange (HDX) procedures for glycosidic linkage analysis of complex carbohydrates

    Science.gov (United States)

    The structural analysis of complex carbohydrates typically requires the assignment of three parameters: monosaccharide composition, the position of glycosidic linkages between monosaccharides, and the position and nature of non-carbohydrate substituents. The glycosidic linkage positions are often de...

  8. Genome-wide linkage analysis of severe, early-onset chronic obstructive pulmonary disease: airflow obstruction and chronic bronchitis phenotypes.

    Science.gov (United States)

    Silverman, Edwin K; Mosley, Jonathan D; Palmer, Lyle J; Barth, Matthew; Senter, Jody M; Brown, Alison; Drazen, Jeffrey M; Kwiatkowski, David J; Chapman, Harold A; Campbell, Edward J; Province, Michael A; Rao, D C; Reilly, John J; Ginns, Leo C; Speizer, Frank E; Weiss, Scott T

    2002-03-15

    Familial aggregation of chronic obstructive pulmonary disease (COPD) has been demonstrated, but linkage analysis of COPD-related phenotypes has not been reported previously. An autosomal 10 cM genome-wide scan of short tandem repeat (STR) polymorphic markers was analyzed for linkage to COPD-related phenotypes in 585 members of 72 pedigrees ascertained through severe, early-onset COPD probands without severe alpha1-antitrypsin deficiency. Multipoint non-parametric linkage analysis (using the ALLEGRO program) was performed for qualitative phenotypes including moderate airflow obstruction [forced expiratory volume at one second (FEV(1)) < 60% predicted, FEV(1)/FVC < 90% predicted], mild airflow obstruction (FEV(1) < 80% predicted, FEV(1)/FVC < 90% predicted) and chronic bronchitis. The strongest evidence for linkage in all subjects was observed at chromosomes 12 (LOD = 1.70) and 19 (LOD = 1.54) for moderate airflow obstruction, chromosomes 8 (LOD = 1.36) and 19 (LOD = 1.09) for mild airflow obstruction and chromosomes 19 (LOD = 1.21) and 22 (LOD = 1.37) for chronic bronchitis. Restricting analysis to cigarette smokers only provided increased evidence for linkage of mild airflow obstruction and chronic bronchitis to several genomic regions; for mild airflow obstruction in smokers only, the maximum LOD was 1.64 at chromosome 19, whereas for chronic bronchitis in smokers only, the maximum LOD was 2.08 at chromosome 22. On chromosome 12p, 12 additional STR markers were genotyped, which provided additional support for an airflow obstruction locus in that region with a non-parametric multipoint approach for moderate airflow obstruction (LOD = 2.13) and mild airflow obstruction (LOD = 1.43). Using a dominant model with the STR markers on 12p, two point parametric linkage analysis of all subjects demonstrated a maximum LOD score of 2.09 for moderate airflow obstruction and 2.61 for mild airflow obstruction. In smokers only, the maximum two point LOD score for mild airflow

  9. Two-Point Fuzzy Ostrowski Type Inequalities

    Directory of Open Access Journals (Sweden)

    Muhammad Amer Latif

    2013-08-01

    Full Text Available Two-point fuzzy Ostrowski type inequalities are proved for fuzzy Hölder and fuzzy differentiable functions. The two-point fuzzy Ostrowski type inequality for M-lipshitzian mappings is also obtained. It is proved that only the two-point fuzzy Ostrowski type inequality for M-lipshitzian mappings is sharp and as a consequence generalize the two-point fuzzy Ostrowski type inequalities obtained for fuzzy differentiable functions.

  10. Detection of tandam duplications and implications for linkage analysis

    Energy Technology Data Exchange (ETDEWEB)

    Matise, T.C.; Weeks, D.E. (Univ. of Pittsburgh, PA (United States)); Chakravarti, A. (Case Western Reserve Univ., Cleveland, OH (United States)); Patel, P.I.; Lupski, J.R. (Baylor College of Medicine, Houston, TX (United States)); Nelis, E.; Timmerman, V.; Van Broeckhoven, C. (Univ. of Antwerp (Belgium))

    1994-06-01

    The first demonstration of an autosomal dominant human disease caused by segmental trisomy came in 1991 for Charcot-Marie-Tooth disease type 1A (CMT1A). For this disorder, the segmental trisomy is due to a large tandem duplication of 1.5 Mb of DNA located on chromosome 17p11.2-p12. The search for the CMT1A disease gene was misdirected and impeded because some chromosome 17 genetic markers that are linked to CMT1A lie within this duplication. To better understand how such a duplication might affect genetic analyses in the context of disease gene mapping, the authors studied the effects of marker duplication on transmission probabilities of marker alleles, on linkage analysis of an autosomal dominant disease, and on tests of linkage homogeneity. They demonstrate that the undetected presence of a duplication distorts transmission ratios, hampers fine localization of the disease gene, and increases false evidence of linkage heterogeneity. In addition, they devised a likelihood-based method for detecting the presence of a tandemly duplicated marker when one is suspected. They tested their methods through computer simulations and on CMT1A pedigrees genotyped at several chromosome 17 markers. On the simulated data, the method detected 96% of duplicated markers (with a false-positive rate of 5%). On the CMT1A data the method successfully identified two of three loci that are duplicated (with no false positives). This method could be used to identify duplicated markers in other regions of the genome and could be used to delineate the extent of duplications similar to that involved in CMT1A. 18 refs., 5 figs., 6 tabs.

  11. A Conservative Meta-Analysis of Linkage and Linkage-Association Studies of Developmental Dyslexia

    Science.gov (United States)

    Grigorenko, Elena L.

    2005-01-01

    Linkage studies of complex phenotypes such as reading ability/disability (developmental dyslexia or reading disorder) and related componential processes, where the effects attributable to individual genes appear to be modest, are critically dependent on the nature and composition of the samples and the phenotypes analyzed. Thus, it might be…

  12. Genomewide linkage analysis of stature in multiple populations reveals several regions with evidence of linkage to adult height.

    Science.gov (United States)

    Hirschhorn, J N; Lindgren, C M; Daly, M J; Kirby, A; Schaffner, S F; Burtt, N P; Altshuler, D; Parker, A; Rioux, J D; Platko, J; Gaudet, D; Hudson, T J; Groop, L C; Lander, E S

    2001-07-01

    Genomewide linkage analysis has been extremely successful at identification of the genetic variation underlying single-gene disorders. However, linkage analysis has been less successful for common human diseases and other complex traits in which multiple genetic and environmental factors interact to influence disease risk. We hypothesized that a highly heritable complex trait, in which the contribution of environmental factors was relatively limited, might be more amenable to linkage analysis. We therefore chose to study stature (adult height), for which heritability is approximately 75%-90% (Phillips and Matheny 1990; Carmichael and McGue 1995; Preece 1996; Silventoinen et al. 2000). We reanalyzed genomewide scans from four populations for which genotype and height data were available, using a variance-components method implemented in GENEHUNTER 2.0 (Pratt et al. 2000). The populations consisted of 408 individuals in 58 families from the Botnia region of Finland, 753 individuals in 183 families from other parts of Finland, 746 individuals in 179 families from Southern Sweden, and 420 individuals in 63 families from the Saguenay-Lac-St.-Jean region of Quebec. Four regions showed evidence of linkage to stature: 6q24-25, multipoint LOD score 3.85 at marker D6S1007 in Botnia (genomewide Pgenetically tractable and provide insight into the genetic architecture of complex traits.

  13. Association and linkage analysis of aluminum tolerance genes in maize.

    Directory of Open Access Journals (Sweden)

    Allison M Krill

    Full Text Available BACKGROUND: Aluminum (Al toxicity is a major worldwide constraint to crop productivity on acidic soils. Al becomes soluble at low pH, inhibiting root growth and severely reducing yields. Maize is an important staple food and commodity crop in acidic soil regions, especially in South America and Africa where these soils are very common. Al exclusion and intracellular tolerance have been suggested as two important mechanisms for Al tolerance in maize, but little is known about the underlying genetics. METHODOLOGY: An association panel of 282 diverse maize inbred lines and three F2 linkage populations with approximately 200 individuals each were used to study genetic variation in this complex trait. Al tolerance was measured as net root growth in nutrient solution under Al stress, which exhibited a wide range of variation between lines. Comparative and physiological genomics-based approaches were used to select 21 candidate genes for evaluation by association analysis. CONCLUSIONS: Six candidate genes had significant results from association analysis, but only four were confirmed by linkage analysis as putatively contributing to Al tolerance: Zea mays AltSB like (ZmASL, Zea mays aluminum-activated malate transporter2 (ALMT2, S-adenosyl-L-homocysteinase (SAHH, and Malic Enzyme (ME. These four candidate genes are high priority subjects for follow-up biochemical and physiological studies on the mechanisms of Al tolerance in maize. Immediately, elite haplotype-specific molecular markers can be developed for these four genes and used for efficient marker-assisted selection of superior alleles in Al tolerance maize breeding programs.

  14. Hierarchical Cluster Analysis: Comparison of Three Linkage Measures and Application to Psychological Data

    Directory of Open Access Journals (Sweden)

    Odilia Yim

    2015-02-01

    Full Text Available Cluster analysis refers to a class of data reduction methods used for sorting cases, observations, or variables of a given dataset into homogeneous groups that differ from each other. The present paper focuses on hierarchical agglomerative cluster analysis, a statistical technique where groups are sequentially created by systematically merging similar clusters together, as dictated by the distance and linkage measures chosen by the researcher. Specific distance and linkage measures are reviewed, including a discussion of how these choices can influence the clustering process by comparing three common linkage measures (single linkage, complete linkage, average linkage. The tutorial guides researchers in performing a hierarchical cluster analysis using the SPSS statistical software. Through an example, we demonstrate how cluster analysis can be used to detect meaningful subgroups in a sample of bilinguals by examining various language variables.

  15. Importance sampling. I. Computing multimodel p values in linkage analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kong, A.; Frigge, M.; Irwin, M.; Cox, N. (Univ. of Chicago, IL (United States))

    1992-12-01

    In linkage analysis, when the lod score is maximized over multiple genetic models, standard asymptotic approximation of the significance level does not apply. Monte Carlo methods can be used to estimate the p value, but procedures currently used are extremely inefficient. The authors propose a Monte Carlo procedure based on the concept of importance sampling, which can be thousands of times more efficient than current procedures. With a reasonable amount of computing time, extremely accurate estimates of the p values can be obtained. Both theoretical results and an example of maturity-onset diabetes of the young (MODY) are presented to illustrate the efficiency performance of their method. Relations between single-model and multimodel p values are explored. The new procedure is also used to investigate the performance of asymptotic approximations in a single model situation. 22 refs., 6 figs., 1 tab.

  16. Genotype transposer: automated genotype manipulation for linkage disequilibrium analysis.

    Science.gov (United States)

    Cox, D G; Canzian, F

    2001-08-01

    The purpose of this work is to provide the modern molecular geneticist with tools to perform more efficient and more accurate analysis of the genotype data they produce. By using Microsoft Excel macros written in Visual Basic, we can translate genotype data into a form readable by the versatile software 'Arlequin', read the Arlequin output, calculate statistics of linkage disequilibrium, and put the results in a format for viewing with the software 'GOLD'. The software is available by FTP at: ftp://xcsg.iarc.fr/cox/Genotype_Transposer/. Detailed instruction and examples are available at: ftp://xcsg.iarc.fr/cox/Genotype&_Transposer/. Arlequin is available at: http://lgb.unige.ch/arlequin/. GOLD is available at: http://www.well.ox.ac.uk/asthma/GOLD/.

  17. Genome-wide linkage analysis for human longevity

    DEFF Research Database (Denmark)

    Beekman, Marian; Blanché, Hélène; Perola, Markus

    2013-01-01

    sibling pairs that have been enrolled in 15 study centers of 11 European countries as part of the Genetics of Healthy Aging (GEHA) project. In the joint linkage analyses, we observed four regions that show linkage with longevity; chromosome 14q11.2 (LOD = 3.47), chromosome 17q12-q22 (LOD = 2...

  18. Mapping multiple QTL using linkage disequilibrium and linkage analysis information and multitrait data

    Directory of Open Access Journals (Sweden)

    Goddard Mike E

    2004-05-01

    Full Text Available Abstract A multi-locus QTL mapping method is presented, which combines linkage and linkage disequilibrium (LD information and uses multitrait data. The method assumed a putative QTL at the midpoint of each marker bracket. Whether the putative QTL had an effect or not was sampled using Markov chain Monte Carlo (MCMC methods. The method was tested in dairy cattle data on chromosome 14 where the DGAT1 gene was known to be segregating. The DGAT1 gene was mapped to a region of 0.04 cM, and the effects of the gene were accurately estimated. The fitting of multiple QTL gave a much sharper indication of the QTL position than a single QTL model using multitrait data, probably because the multi-locus QTL mapping reduced the carry over effect of the large DGAT1 gene to adjacent putative QTL positions. This suggests that the method could detect secondary QTL that would, in single point analyses, remain hidden under the broad peak of the dominant QTL. However, no indications for a second QTL affecting dairy traits were found on chromosome 14.

  19. A statistical design for testing apomictic diversification through linkage analysis.

    Science.gov (United States)

    Zeng, Yanru; Hou, Wei; Song, Shuang; Feng, Sisi; Shen, Lin; Xia, Guohua; Wu, Rongling

    2014-03-01

    The capacity of apomixis to generate maternal clones through seed reproduction has made it a useful characteristic for the fixation of heterosis in plant breeding. It has been observed that apomixis displays pronounced intra- and interspecific diversification, but the genetic mechanisms underlying this diversification remains elusive, obstructing the exploitation of this phenomenon in practical breeding programs. By capitalizing on molecular information in mapping populations, we describe and assess a statistical design that deploys linkage analysis to estimate and test the pattern and extent of apomictic differences at various levels from genotypes to species. The design is based on two reciprocal crosses between two individuals each chosen from a hermaphrodite or monoecious species. A multinomial distribution likelihood is constructed by combining marker information from two crosses. The EM algorithm is implemented to estimate the rate of apomixis and test its difference between two plant populations or species as the parents. The design is validated by computer simulation. A real data analysis of two reciprocal crosses between hickory (Carya cathayensis) and pecan (C. illinoensis) demonstrates the utilization and usefulness of the design in practice. The design provides a tool to address fundamental and applied questions related to the evolution and breeding of apomixis.

  20. Further analysis of previously implicated linkage regions for Alzheimer's disease in affected relative pairs

    Directory of Open Access Journals (Sweden)

    Lannfelt Lars

    2009-12-01

    Full Text Available Abstract Background Genome-wide linkage studies for Alzheimer's disease have implicated several chromosomal regions as potential loci for susceptibility genes. Methods In the present study, we have combined a selection of affected relative pairs (ARPs from the UK and the USA included in a previous linkage study by Myers et al. (Am J Med Genet, 2002, with ARPs from Sweden and Washington University. In this total sample collection of 397 ARPs, we have analyzed linkage to chromosomes 1, 9, 10, 12, 19 and 21, implicated in the previous scan. Results The analysis revealed that linkage to chromosome 19q13 close to the APOE locus increased considerably as compared to the earlier scan. However, linkage to chromosome 10q21, which provided the strongest linkage in the previous scan could not be detected. Conclusion The present investigation provides yet further evidence that 19q13 is the only chromosomal region consistently linked to Alzheimer's disease.

  1. Nickel-catalyzed proton-deuterium exchange (HDX) for linkage analysis of complex carbohydrates

    Science.gov (United States)

    The structural assignment of complex carbohydrates typically requires the analysis of at least three parameters: 1. composition; 2. linkage; and 3. substituents. These are often assigned on a small scale by gas chromatography/mass spectrometry (GC/MS). Linkage positions are determined by permethylat...

  2. Genome-Wide Linkage Analysis for Loci Affecting Pulse Pressure: The Family Blood Pressure Program

    National Research Council Canada - National Science Library

    Bielinski, Suzette J; Lynch, Amy I; Miller, Michael B; Weder, Alan; Cooper, Richard; Oberman, Albert; Chen, Yii-Der Ida; Turner, Stephen T; Fornage, Myriam; Province, Michael; Arnett, Donna K

    2005-01-01

    ... in sequential oligogenic linkage analysis routines. The analysis sample included 10 798 participants in 3320 families who were recruited as part of the Family Blood Pressure Program and were phenotyped with an oscillometric blood pressure measurement...

  3. Comparative linkage analysis and visualization of high-density oligonucleotide SNP array data

    Directory of Open Access Journals (Sweden)

    Smith Richard JH

    2005-02-01

    Full Text Available Abstract Background The identification of disease-associated genes using single nucleotide polymorphisms (SNPs has been increasingly reported. In particular, the Affymetrix Mapping 10 K SNP microarray platform uses one PCR primer to amplify the DNA samples and determine the genotype of more than 10,000 SNPs in the human genome. This provides the opportunity for large scale, rapid and cost-effective genotyping assays for linkage analysis. However, the analysis of such datasets is nontrivial because of the large number of markers, and visualizing the linkage scores in the context of genome maps remains less automated using the current linkage analysis software packages. For example, the haplotyping results are commonly represented in the text format. Results Here we report the development of a novel software tool called CompareLinkage for automated formatting of the Affymetrix Mapping 10 K genotype data into the "Linkage" format and the subsequent analysis with multi-point linkage software programs such as Merlin and Allegro. The new software has the ability to visualize the results for all these programs in dChip in the context of genome annotations and cytoband information. In addition we implemented a variant of the Lander-Green algorithm in the dChipLinkage module of dChip software (V1.3 to perform parametric linkage analysis and haplotyping of SNP array data. These functions are integrated with the existing modules of dChip to visualize SNP genotype data together with LOD score curves. We have analyzed three families with recessive and dominant diseases using the new software programs and the comparison results are presented and discussed. Conclusions The CompareLinkage and dChipLinkage software packages are freely available. They provide the visualization tools for high-density oligonucleotide SNP array data, as well as the automated functions for formatting SNP array data for the linkage analysis programs Merlin and Allegro and calling

  4. The optimal design for hypothesis test and its application in genetic linkage analysis

    Institute of Scientific and Technical Information of China (English)

    XIE; Minyu(谢民育); LI; Zhaohai(李照海)

    2003-01-01

    This paper proposes a class of linear models with inequable variance, based on background in genetic linkage analysis, and considers the optimal design problem for the hypothesis test of the parameters in such models. To assess a design for the test, a frame of decision theory is established. Under this frame, an admissible minimax design is obtained. It is shown to be not only admissible and minimax in genetic linkage analysis, but best among a reasonable subclass of designs. The power of the test in genetic linkage analysis is substantially improved by using this optimal design.

  5. Analysis of Linkage Effects among Currency Networks Using REER Data

    Directory of Open Access Journals (Sweden)

    Haishu Qiao

    2015-01-01

    Full Text Available We modeled the currency networks through the use of REER (real effective exchange rate instead of a bilateral exchange rate in order to overcome the confusion in selecting base currencies. Based on the MST (minimum spanning tree approach and the rolling-window method, we constructed time-varying and correlation-based networks with which we investigate the linkage effects among different currencies. In particular, and as the source of empirical data, we chose the monthly REER data for a set of 61 major currencies during the period from 1994 to 2014. The study demonstrated that obvious linkage effects existed among currency networks and the euro (EUR was confirmed as the predominant world currency. Additionally, we used the rolling-window method to investigate the stability of linkage effects, doing so by calculating the mean correlations and mean distances as well as the normalized tree length and degrees of those currencies. The results showed that financial crises during the study period had a great effect on the currency network’s topology structure and led to more clustered currency networks. Our results suggested that it is more appropriate to estimate the linkage effects among currency networks through the use of REER data.

  6. Two Point Pade Approximants and Duality

    CERN Document Server

    Banks, Tom

    2013-01-01

    We propose the use of two point Pade approximants to find expressions valid uniformly in coupling constant for theories with both weak and strong coupling expansions. In particular, one can use these approximants in models with a strong/weak duality, when the symmetries do not determine exact expressions for some quantity.

  7. ACCURACY ANALYSIS FOR PLANAR LINKAGE WITH MULTIPLE CLEAR-ANCES AT TURNING PAIRS

    Institute of Scientific and Technical Information of China (English)

    ZHANG Guojun; CHENG Qiang; SHAO Xinyu; LI Peigen

    2008-01-01

    Clearance at turning pair has a strong impact on the kinetic accuracy of linkage, but there is short of a generic model to analyze it so far. Clearance error, input error, and manufacturing tolerance of links are taken into consideration as the random variables synthetically. The kinematics and dynamics accuracy analysis models for planar linkages with multiple clearances at joints are built up as well. At last a typical planar linkage is selected for numerical illustration. These models stated in matrix resolve the relativity of output parameter errors of mechanism and therefore are of vital significance for the reliability analysis and synthesis of mechanism with clearances.

  8. Multivariate Stable Isotope Analysis to Determine Linkages between Benzocaine Seizures

    Science.gov (United States)

    Kemp, H. F.; Meier-Augenstein, W.; Collins, M.; Salouros, H.; Cunningham, A.; Harrison, M.

    2012-04-01

    In July 2010, a woman was jailed for nine years in the UK after the prosecution successfully argued that attempting to import a cutting agent was proof of involvement in a conspiracy to supply Cocaine. That landmark ruling provided law enforcement agencies with much greater scope to tackle those involved in this aspect of the drug trade, specifically targeting those importing the likes of benzocaine or lidocaine. Huge quantities of these compounds are imported into the UK and between May and August 2010, four shipments of Benzocaine amounting to more then 4 tons had been seized as part of Operation Kitley, a joint initiative between the UK Border Agency and the Serious Organised Crime Agency (SOCA). By diluting cocaine, traffickers can make it go a lot further for very little cost, leading to huge profits. In recent years, dealers have moved away from inert substances, like sugar and baby milk powder, in favour of active pharmaceutical ingredients (APIs), including anaesthetics like Benzocaine and Lidocaine. Both these mimic the numbing effect of cocaine, and resemble it closely in colour, texture and some chemical behaviours, making it easier to conceal the fact that the drug has been diluted. API cutting agents have helped traffickers to maintain steady supplies in the face of successful interdiction and even expand the market in the UK, particularly to young people aged from their mid teens to early twenties. From importation to street-level, the purity of the drug can be reduced up to a factor of 80 and street level cocaine can have a cocaine content as low as 1%. In view of the increasing use of Benzocaine as cutting agent for Cocaine, a study was carried out to investigate if 2H, 13C, 15N and 18O stable isotope signatures could be used in conjunction with multivariate chemometric data analysis to determine potential linkage between benzocaine exhibits seized from different locations or individuals to assist with investigation and prosecution of drug

  9. Linkage analysis of quantitative refraction and refractive errors in the Beaver Dam Eye Study.

    Science.gov (United States)

    Klein, Alison P; Duggal, Priya; Lee, Kristine E; Cheng, Ching-Yu; Klein, Ronald; Bailey-Wilson, Joan E; Klein, Barbara E K

    2011-07-13

    Refraction, as measured by spherical equivalent, is the need for an external lens to focus images on the retina. While genetic factors play an important role in the development of refractive errors, few susceptibility genes have been identified. However, several regions of linkage have been reported for myopia (2q, 4q, 7q, 12q, 17q, 18p, 22q, and Xq) and for quantitative refraction (1p, 3q, 4q, 7p, 8p, and 11p). To replicate previously identified linkage peaks and to identify novel loci that influence quantitative refraction and refractive errors, linkage analysis of spherical equivalent, myopia, and hyperopia in the Beaver Dam Eye Study was performed. Nonparametric, sibling-pair, genome-wide linkage analyses of refraction (spherical equivalent adjusted for age, education, and nuclear sclerosis), myopia and hyperopia in 834 sibling pairs within 486 extended pedigrees were performed. Suggestive evidence of linkage was found for hyperopia on chromosome 3, region q26 (empiric P = 5.34 × 10(-4)), a region that had shown significant genome-wide evidence of linkage to refraction and some evidence of linkage to hyperopia. In addition, the analysis replicated previously reported genome-wide significant linkages to 22q11 of adjusted refraction and myopia (empiric P = 4.43 × 10(-3) and 1.48 × 10(-3), respectively) and to 7p15 of refraction (empiric P = 9.43 × 10(-4)). Evidence was also found of linkage to refraction on 7q36 (empiric P = 2.32 × 10(-3)), a region previously linked to high myopia. The findings provide further evidence that genes controlling refractive errors are located on 3q26, 7p15, 7p36, and 22q11.

  10. Meta-analysis of genome-wide linkage studies across autoimmune diseases

    Science.gov (United States)

    Forabosco, Paola; Bouzigon, Emmanuelle; Ng, Mandy Y; Hermanowski, Jane; Fisher, Sheila A; Criswell, Lindsey A; Lewis, Cathryn M

    2009-01-01

    Autoimmune diseases are chronic disorders initiated by a loss of immunologic tolerance to self-antigens. They cluster within families, and patients may be diagnosed with more than one disease, suggesting pleiotropic genes are involved in the aetiology of different diseases. To identify potential loci, which confer susceptibility to autoimmunity independent of disease phenotype, we pooled results from genome-wide linkage studies, using the genome scan meta-analysis method (GSMA). The meta-analysis included 42 independent studies for 11 autoimmune diseases, using 7350 families with 18 291 affected individuals. In addition to the HLA region, which showed highly significant genome-wide evidence for linkage, we obtained suggestive evidence for linkage on chromosome 16, with peak evidence at 10.0–19.8 Mb. This region may harbour a pleiotropic gene (or genes) conferring risk for several diseases, although no such gene has been identified through association studies. We did not identify evidence for linkage at several genes known to confer increased risk to different autoimmune diseases (PTPN22, CTLA4), even in subgroups of diseases consistently found to be associated with these genes. The relative risks conferred by variants in these genes are modest (<1.5 in most cases), and even a large study like this meta-analysis lacks power to detect linkage. This study illustrates the concept that linkage and association studies have power to identify very different types of disease-predisposing variants. PMID:18781189

  11. The effects of selection on linkage analysis for quantitative traits.

    Science.gov (United States)

    Mackinnon, M J; Georges, M A

    1992-12-01

    The effects of within-sample selection on the outcome of analyses detecting linkage between genetic markers and quantitative traits were studied. It was found that selection by truncation for the trait of interest significantly reduces the differences between marker genotype means thus reducing the power to detect linked quantitative trait loci (QTL). The size of this reduction is a function of proportion selected, the magnitude of the QTL effect, recombination rate between the marker locus and the QTL, and the allele frequency of the QTL. Proportion selected was the most influential of these factors on bias, e.g., for an allele substitution effect of one standard deviation unit, selecting the top 80%, 50% or 20% of the population required 2, 6 or 24 times the number of progeny, respectively, to offset the loss of power caused by this selection. The effect on power was approximately linear with respect to the size of gene effect, almost invariant to recombination rate, and a complex function of QTL allele frequency. It was concluded that experimental samples from animal populations which have been subjected to even minor amounts of selection will be inefficient in yielding information on linkage between markers and loci influencing the quantitative trait under selection.

  12. Two-point optical coherency matrix tomography.

    Science.gov (United States)

    Abouraddy, Ayman F; Kagalwala, Kumel H; Saleh, Bahaa E A

    2014-04-15

    The two-point coherence of an electromagnetic field is represented completely by a 4×4 coherency matrix G that encodes the joint polarization-spatial-field correlations. Here, we describe a systematic sequence of cascaded spatial and polarization projective measurements that are sufficient to tomographically reconstruct G--a task that, to the best of our knowledge, has not yet been realized. Our approach benefits from the correspondence between this reconstruction problem in classical optics and that of quantum state tomography for two-photon states in quantum optics. Identifying G uniquely determines all the measurable correlation characteristics of the field and, thus, lifts ambiguities that arise from reliance on traditional scalar descriptors, especially when the field's degrees of freedom are correlated or classically entangled.

  13. Viral Genetic Linkage Analysis in the Presence of Missing Data.

    Directory of Open Access Journals (Sweden)

    Shelley H Liu

    Full Text Available Analyses of viral genetic linkage can provide insight into HIV transmission dynamics and the impact of prevention interventions. For example, such analyses have the potential to determine whether recently-infected individuals have acquired viruses circulating within or outside a given community. In addition, they have the potential to identify characteristics of chronically infected individuals that make their viruses likely to cluster with others circulating within a community. Such clustering can be related to the potential of such individuals to contribute to the spread of the virus, either directly through transmission to their partners or indirectly through further spread of HIV from those partners. Assessment of the extent to which individual (incident or prevalent viruses are clustered within a community will be biased if only a subset of subjects are observed, especially if that subset is not representative of the entire HIV infected population. To address this concern, we develop a multiple imputation framework in which missing sequences are imputed based on a model for the diversification of viral genomes. The imputation method decreases the bias in clustering that arises from informative missingness. Data from a household survey conducted in a village in Botswana are used to illustrate these methods. We demonstrate that the multiple imputation approach reduces bias in the overall proportion of clustering due to the presence of missing observations.

  14. Linkage analysis of quantitative trait loci in the presence of heterogeneity.

    Science.gov (United States)

    Ekstrøm, Claus Thorn; Dalgaard, Peter

    2003-01-01

    Variance component modeling for linkage analysis of quantitative traits is a powerful tool for detecting and locating genes affecting a trait of interest, but the presence of genetic heterogeneity will decrease the power of a linkage study and may even give biased estimates of the location of the quantitative trait loci. Many complex diseases are believed to be influenced by multiple genes and therefore genetic heterogeneity is likely to be present for many real applications of linkage analysis. We consider a mixture of multivariate normals to model locus heterogeneity by allowing only a proportion of the sampled pedigrees to segregate trait-influencing allele(s) at a specific locus. However, for mixtures of normals the classical asymptotic distribution theory of the maximum likelihood estimates does not hold, so tests of linkage and/or heterogeneity are evaluated using resampling methods. It is shown that allowing for genetic heterogeneity leads to an increase in power to detect linkage. This increase is more prominent when the genetic effect of the locus is small or when the percentage of pedigrees not segregating trait-influencing allele(s) at the locus is high.

  15. Prospective linkages between peer victimization and externalizing problems in children: a meta-analysis.

    Science.gov (United States)

    Reijntjes, Albert; Kamphuis, Jan H; Prinzie, Peter; Boelen, Paul A; van der Schoot, Menno; Telch, Michael J

    2011-01-01

    Previous meta-analytic research has shown both concurrent and prospective linkages between peer victimization and internalizing problems in youth. However, the linkages between peer victimization and externalizing problems over time have not been systematically examined, and it is therefore unknown if externalizing problems are antecedents of victimization, consequences of victimization, both, or neither. This study provides a meta-analysis of 14 longitudinal studies examining prospective linkages between peer victimization and externalizing problems (n = 7,821). Two prospective paths were examined: the extent to which peer victimization at baseline predicts future residualized changes in externalizing problems, as well as the extent to which externalizing problems at baseline predict future residualized changes in peer victimization. Results revealed significant associations between peer victimization and subsequent residualized changes in externalizing problems, as well as significant associations between externalizing problems and subsequent residualized changes in peer victimization. Hence, externalizing problems function as both antecedents and consequences of peer victimization. © 2010 Wiley-Liss, Inc.

  16. Meta-analysis of genome-wide linkage studies in BMI and obesity

    NARCIS (Netherlands)

    Saunders, Catherine L.; Chiodini, Benedetta D.; Sham, Pak; Lewis, Cathryn M.; Abkevich, Victor; Adeyemo, Adebowale A.; de Andrade, Mariza; Arya, Rector; Berenson, Gerald S.; Blangero, John; Boehnke, Michael; Borecki, Ingrid B.; Chagnon, Yvon C.; Chen, Wei; Comuzzie, Anthony G.; Deng, Hong-Wen; Duggirala, Ravindranath; Feitosa, Mary F.; Froguel, Philippe; Hanson, Robert L.; Hebebrand, Johannes; Huezo-Dias, Patricia; Kissebah, Ahmed H.; Li, Weidong; Luke, Amy; Martin, Lisa J.; Nash, Matthew; Ohman, Muena; Palmer, Lyle J.; Peltonen, Leena; Perola, Markus; Price, R. Arlen; Redline, Susan; Srinivasan, Sathanur R.; Stern, Michael P.; Stone, Steven; Stringham, Heather; Turner, Stephen; Wijmenga, Cisca; Collier, David A.

    Objective: The objective was to provide an overall assessment of genetic linkage data of BMI and BMI-defined obesity using a nonparametric genome scan meta-analysis. Research Methods and Procedures: We identified 37 published studies containing data on over 31,000 individuals from more than >10,000

  17. Linkage and association analysis of CACNG3 in childhood absence epilepsy

    DEFF Research Database (Denmark)

    Everett, Kate V; Chioza, Barry; Aicardi, Jean

    2007-01-01

    and association analysis. Assuming locus heterogeneity, a significant HLOD score (HLOD = 3.54, alpha = 0.62) was obtained for markers encompassing CACNG3 in 65 nuclear families with a proband with CAE. The maximum non-parametric linkage score was 2.87 (P ... and the 65 nuclear pedigrees. Evidence for transmission disequilibrium (P

  18. Genome-Wide Association Study and Linkage Analysis of the Healthy Aging Index

    DEFF Research Database (Denmark)

    Minster, Ryan L; Sanders, Jason L; Singh, Jatinder;

    2015-01-01

    BACKGROUND: The Healthy Aging Index (HAI) is a tool for measuring the extent of health and disease across multiple systems. METHODS: We conducted a genome-wide association study and a genome-wide linkage analysis to map quantitative trait loci associated with the HAI and a modified HAI weighted...

  19. Meta-analysis of genome-wide linkage studies in BMI and obesity

    NARCIS (Netherlands)

    Saunders, Catherine L.; Chiodini, Benedetta D.; Sham, Pak; Lewis, Cathryn M.; Abkevich, Victor; Adeyemo, Adebowale A.; de Andrade, Mariza; Arya, Rector; Berenson, Gerald S.; Blangero, John; Boehnke, Michael; Borecki, Ingrid B.; Chagnon, Yvon C.; Chen, Wei; Comuzzie, Anthony G.; Deng, Hong-Wen; Duggirala, Ravindranath; Feitosa, Mary F.; Froguel, Philippe; Hanson, Robert L.; Hebebrand, Johannes; Huezo-Dias, Patricia; Kissebah, Ahmed H.; Li, Weidong; Luke, Amy; Martin, Lisa J.; Nash, Matthew; Ohman, Muena; Palmer, Lyle J.; Peltonen, Leena; Perola, Markus; Price, R. Arlen; Redline, Susan; Srinivasan, Sathanur R.; Stern, Michael P.; Stone, Steven; Stringham, Heather; Turner, Stephen; Wijmenga, Cisca; Collier, David A.

    2007-01-01

    Objective: The objective was to provide an overall assessment of genetic linkage data of BMI and BMI-defined obesity using a nonparametric genome scan meta-analysis. Research Methods and Procedures: We identified 37 published studies containing data on over 31,000 individuals from more than >10,000

  20. VT Wildlife Linkage Habitat

    Data.gov (United States)

    Vermont Center for Geographic Information — (Link to Metadata) The Wildlife Linkage Habitat Analysis uses landscape scale data to identify or predict the location of potentially significant wildlife linkage...

  1. Genome-wide Linkage Disequilibrium Linkage Analysis (LDLA) of Body Fat Traits in an F2 Porcine Model for Human Obesity

    DEFF Research Database (Denmark)

    Pant, Sameer Dinkar; Karlskov-Mortensen, Peter; Cirera Salicio, Susanna;

    , body composition was determined at about two months of age (64 ± 11 days) via dual-energy xray absorptiometry (DXA) scanning. All pigs were genotyped using Illumina Porcine 60k SNP Beadchip and a combined LDLA approach was used to perform genomewide linkage and association analysis for body fat traits...

  2. SwiftLink: parallel MCMC linkage analysis using multicore CPU and GPU.

    Science.gov (United States)

    Medlar, Alan; Głowacka, Dorota; Stanescu, Horia; Bryson, Kevin; Kleta, Robert

    2013-02-15

    Linkage analysis remains an important tool in elucidating the genetic component of disease and has become even more important with the advent of whole exome sequencing, enabling the user to focus on only those genomic regions co-segregating with Mendelian traits. Unfortunately, methods to perform multipoint linkage analysis scale poorly with either the number of markers or with the size of the pedigree. Large pedigrees with many markers can only be evaluated with Markov chain Monte Carlo (MCMC) methods that are slow to converge and, as no attempts have been made to exploit parallelism, massively underuse available processing power. Here, we describe SWIFTLINK, a novel application that performs MCMC linkage analysis by spreading the computational burden between multiple processor cores and a graphics processing unit (GPU) simultaneously. SWIFTLINK was designed around the concept of explicitly matching the characteristics of an algorithm with the underlying computer architecture to maximize performance. We implement our approach using existing Gibbs samplers redesigned for parallel hardware. We applied SWIFTLINK to a real-world dataset, performing parametric multipoint linkage analysis on a highly consanguineous pedigree with EAST syndrome, containing 28 members, where a subset of individuals were genotyped with single nucleotide polymorphisms (SNPs). In our experiments with a four core CPU and GPU, SWIFTLINK achieves a 8.5× speed-up over the single-threaded version and a 109× speed-up over the popular linkage analysis program SIMWALK. SWIFTLINK is available at https://github.com/ajm/swiftlink. All source code is licensed under GPLv3.

  3. Genomewide linkage analysis of quantitative spirometric phenotypes in severe early-onset chronic obstructive pulmonary disease.

    Science.gov (United States)

    Silverman, Edwin K; Palmer, Lyle J; Mosley, Jonathan D; Barth, Matthew; Senter, Jody M; Brown, Alison; Drazen, Jeffrey M; Kwiatkowski, David J; Chapman, Harold A; Campbell, Edward J; Province, Michael A; Rao, D C; Reilly, John J; Ginns, Leo C; Speizer, Frank E; Weiss, Scott T

    2002-05-01

    Chronic obstructive pulmonary disease (COPD) is a common, complex disease associated with substantial morbidity and mortality. COPD is defined by irreversible airflow obstruction; airflow obstruction is typically determined by reductions in quantitative spirometric indices, including forced expiratory volume at 1 s (FEV(1)) and the ratio of FEV(1) to forced vital capacity (FVC). To identify genetic determinants of quantitative spirometric phenotypes, an autosomal 10-cM genomewide scan of short tandem repeat (STR) polymorphic markers was performed in 72 pedigrees (585 individuals) ascertained through probands with severe early-onset COPD. Multipoint variance-component linkage analysis (using SOLAR) was performed for quantitative phenotypes, including FEV(1), FVC, and FEV(1)/FVC. In the initial genomewide scan, significant evidence for linkage to FEV(1)/FVC was demonstrated on chromosome 2q (LOD score 4.12 at 222 cM). Suggestive evidence was found for linkage to FEV(1)/FVC on chromosomes 1 (LOD score 1.92 at 120 cM) and 17 (LOD score 2.03 at 67 cM) and to FVC on chromosome 1 (LOD score 2.05 at 13 cM). The highest LOD score for FEV(1) in the initial genomewide scan was 1.53, on chromosome 12, at 36 cM. After inclusion of 12 additional STR markers on chromosome 12p, which had been previously genotyped in this population, suggestive evidence for linkage of FEV(1) (LOD score 2.43 at 37 cM) to this region was demonstrated. These observations provide both significant evidence for an early-onset COPD-susceptibility locus on chromosome 2 and suggestive evidence for linkage of spirometry-related phenotypes to several other genomic regions. The significant linkage of FEV(1)/FVC to chromosome 2q could reflect one or more genes influencing the development of airflow obstruction or dysanapsis.

  4. Linkage analysis by two-dimensional DNA typing

    NARCIS (Netherlands)

    te Meerman, G J; Mullaart, E; van der Meulen, M A; den Daas, J H; Morolli, B; Uitterlinden, A G; Vijg, J

    1993-01-01

    In two-dimensional (2-D) DNA typing, genomic DNA fragments are separated, first according to size by electrophoresis in a neutral polyacrylamide gel and second according to sequence by denaturing gradient gel electrophoresis, followed by hybridization analysis using micro- and minisatellite core pro

  5. Multipoint linkage analysis in X-linked Alport syndrome

    DEFF Research Database (Denmark)

    Hertz, Jens Michael; Kruse, T A; Thomsen, A

    1991-01-01

    In order to localize the gene for the X-linked form of Alport syndrome (ATS) more precisely, we performed restriction fragment length polymorphism analysis with nine different X-chromosomal DNA markers in 107 members of twelve Danish families segregating for classic ATS or progressive hereditary ...

  6. Meta analysis of whole-genome linkage scans with data uncertainty: an application to Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Gasser Thomas

    2007-07-01

    Full Text Available Abstract Background Genome wide linkage scans have often been successful in the identification of genetic regions containing susceptibility genes for a disease. Meta analysis is used to synthesize information and can even deliver evidence for findings missed by original studies. If researchers are not contributing their data, extracting valid information from publications is technically challenging, but worth the effort. We propose an approach to include data extracted from published figures of genome wide linkage scans. The validity of the extraction was examined on the basis of those 25 markers, for which sufficient information was reported. Monte Carlo simulations were used to take into account the uncertainty in marker position and in linkage test statistic. For the final meta analysis we compared the Genome Search Meta Analysis method (GSMA and the Corrected p-value Meta analysis Method (CPMM. An application to Parkinson's disease is given. Because we had to use secondary data a meta analysis based on original summary values would be desirable. Results Data uncertainty by replicated extraction of marker position is shown to be much smaller than 30 cM, a distance up to which a maximum LOD score may usually be found away from the true locus. The main findings are not impaired by data uncertainty. Conclusion Applying the proposed method a novel linked region for Parkinson's disease was identified on chromosome 14 (p = 0.036. Comparing the two meta analysis methods we found in this analysis more regions of interest being identified by GSMA, whereas CPMM provides stronger evidence for linkage. For further validation of the extraction method comparisons with raw data would be required.

  7. Meta analysis of whole-genome linkage scans with data uncertainty: an application to Parkinson's disease

    Science.gov (United States)

    Rosenberger, Albert; Sharma, Manu; Müller-Myhsok, Bertram; Gasser, Thomas; Bickeböller, Heike

    2007-01-01

    Background Genome wide linkage scans have often been successful in the identification of genetic regions containing susceptibility genes for a disease. Meta analysis is used to synthesize information and can even deliver evidence for findings missed by original studies. If researchers are not contributing their data, extracting valid information from publications is technically challenging, but worth the effort. We propose an approach to include data extracted from published figures of genome wide linkage scans. The validity of the extraction was examined on the basis of those 25 markers, for which sufficient information was reported. Monte Carlo simulations were used to take into account the uncertainty in marker position and in linkage test statistic. For the final meta analysis we compared the Genome Search Meta Analysis method (GSMA) and the Corrected p-value Meta analysis Method (CPMM). An application to Parkinson's disease is given. Because we had to use secondary data a meta analysis based on original summary values would be desirable. Results Data uncertainty by replicated extraction of marker position is shown to be much smaller than 30 cM, a distance up to which a maximum LOD score may usually be found away from the true locus. The main findings are not impaired by data uncertainty. Conclusion Applying the proposed method a novel linked region for Parkinson's disease was identified on chromosome 14 (p = 0.036). Comparing the two meta analysis methods we found in this analysis more regions of interest being identified by GSMA, whereas CPMM provides stronger evidence for linkage. For further validation of the extraction method comparisons with raw data would be required. PMID:17605797

  8. Bivariate linkage analysis of the insulin resistance syndrome phenotypes on chromosome 7q.

    Science.gov (United States)

    Lehman, Donna M; Arya, Rector; Blangero, John; Almasy, Laura; Puppala, Sobha; Dyer, Thomas D; Leach, Robin J; O'Connell, Peter; Stern, Michael P; Duggirala, Ravindranath

    2005-04-01

    Metabolic abnormalities of the insulin resistance syndrome (IRS) have been shown to aggregate in families and to exhibit trait-pair correlations, suggesting a common genetic component. A broad region on chromosome 7q has been implicated in several studies to contain loci that cosegregate with IRS-related traits. However, it is not clear whether such loci have any common genetic (pleiotropic) influences on the correlated traits. Also, it is not clear whether the chromosomal regions contain more than one locus influencing the IRS-related phenotypes. In this study we present evidence for linkage of five IRS-related traits [body mass index (BMI), waist circumference (WC), In split proinsulin (LSPI), In triglycerides (LTG), and high-density lipoprotein cholesterol (HDLC)] to a region at 7q11.23. Subsequently, to gain further insight into the genetic component(s) mapping to this region, we explored whether linkage of these traits is due to pleiotropic effects using a bivariate linkage analytical technique, which has been shown to localize susceptibility regions with precision. Four hundred forty individuals from 27 Mexican American families living in Texas were genotyped for 19 highly polymorphic markers on chromosome 7. Multipoint variance component linkage analysis was used to identify genetic location(s) influencing IRS-related traits of obesity (BMI and WC), dyslipidemia (LTG and HDLC), and insulin levels (LSPI); the analysis identified a broad chromosomal region spanning approximately 24 cM. To gain more precision in localization, we used a bivariate linkage approach for each trait pair. These analyses suggest localization of most of these bivariate traits to an approximately 6-cM region near marker D7S653 [7q11.23, 103-109 cM; a maximum bivariate LOD of 4.51 was found for the trait pair HDLC and LSPI (the LODeq score is 3.94)]. We observed evidence of pleiotropic effects in this region on obesity and insulin-related trait pairs.

  9. Linkages and Interactions Analysis of Major Effect Drought Grain Yield QTLs in Rice.

    Directory of Open Access Journals (Sweden)

    Prashant Vikram

    Full Text Available Quantitative trait loci conferring high grain yield under drought in rice are important genomic resources for climate resilient breeding. Major and consistent drought grain yield QTLs usually co-locate with flowering and/or plant height QTLs, which could be due to either linkage or pleiotropy. Five mapping populations used for the identification of major and consistent drought grain yield QTLs underwent multiple-trait, multiple-interval mapping test (MT-MIM to estimate the significance of pleiotropy effects. Results indicated towards possible linkages between the drought grain yield QTLs with co-locating flowering and/or plant height QTLs. Linkages of days to flowering and plant height were eliminated through a marker-assisted breeding approach. Drought grain yield QTLs also showed interaction effects with flowering QTLs. Drought responsiveness of the flowering locus on chromosome 3 (qDTY3.2 has been revealed through allelic analysis. Considering linkage and interaction effects associated with drought QTLs, a comprehensive marker-assisted breeding strategy was followed to develop rice genotypes with improved grain yield under drought stress.

  10. Genetic mapping of X-linked ocular albinism: Linkage analysis in a large Newfoundland kindred

    Energy Technology Data Exchange (ETDEWEB)

    Charles, S.J.; Moore, A.T.; Barton, D.E.; Yates, J.R.W. (Addenbrooke' s Hospital, Cambridge (United Kingdom)); Green, J.S. (Memorial Univ. of Newfoundland, St. John' s (Canada))

    1993-04-01

    Genetic linkage studies in a large Newfoundland family affected by X-linked ocular albinism (OA1) showed linkage to markers from Xp22.3. One recombinant mapped the disease proximal to DXS143 (dic56) and two recombinants mapped the disease distal to DXS85 (782). Combining the data with that from 16 British families previously published confirmed close linkage between OA1 and DXS143 (dic56; Z[sub max] = 21.96 at [theta] = 0.01, confidence interval (CI) 0.0005--0.05) and linkage to DXS85 (782; Z[sub max] = 17.60 at [theta] = 0.07, CI = 0.03--0.13) and DXS237 (GMGX9; Z[sub max] = 15.20 at [theta] = 0.08, CI = 0.03--0.15). Multipoint analysis (LINKMAP) gave the most likely order as Xpter-XG-DXS237-DXS143-OA1-DXS85, with odds of 48:1 over the order Xpter-XG-DXS237-OA1-DXS143-DXS85, and odds exceeding 10[sup 10]:1 over other locations for the disease locus. 11 refs., 1 fig., 1 tab.

  11. QTL linkage analysis of connected populations using ancestral marker and pedigree information.

    Science.gov (United States)

    Bink, Marco C A M; Totir, L Radu; ter Braak, Cajo J F; Winkler, Christopher R; Boer, Martin P; Smith, Oscar S

    2012-04-01

    The common assumption in quantitative trait locus (QTL) linkage mapping studies that parents of multiple connected populations are unrelated is unrealistic for many plant breeding programs. We remove this assumption and propose a Bayesian approach that clusters the alleles of the parents of the current mapping populations from locus-specific identity by descent (IBD) matrices that capture ancestral marker and pedigree information. Moreover, we demonstrate how the parental IBD data can be incorporated into a QTL linkage analysis framework by using two approaches: a Threshold IBD model (TIBD) and a Latent Ancestral Allele Model (LAAM). The TIBD and LAAM models are empirically tested via numerical simulation based on the structure of a commercial maize breeding program. The simulations included a pilot dataset with closely linked QTL on a single linkage group and 100 replicated datasets with five linkage groups harboring four unlinked QTL. The simulation results show that including parental IBD data (similarly for TIBD and LAAM) significantly improves the power and particularly accuracy of QTL mapping, e.g., position, effect size and individuals' genotype probability without significantly increasing computational demand.

  12. Saturation of an intra-gene pool linkage map: towards a unified consensus linkage map for fine mapping and synteny analysis in common bean.

    Science.gov (United States)

    Galeano, Carlos H; Fernandez, Andrea C; Franco-Herrera, Natalia; Cichy, Karen A; McClean, Phillip E; Vanderleyden, Jos; Blair, Matthew W

    2011-01-01

    Map-based cloning and fine mapping to find genes of interest and marker assisted selection (MAS) requires good genetic maps with reproducible markers. In this study, we saturated the linkage map of the intra-gene pool population of common bean DOR364 × BAT477 (DB) by evaluating 2,706 molecular markers including SSR, SNP, and gene-based markers. On average the polymorphism rate was 7.7% due to the narrow genetic base between the parents. The DB linkage map consisted of 291 markers with a total map length of 1,788 cM. A consensus map was built using the core mapping populations derived from inter-gene pool crosses: DOR364 × G19833 (DG) and BAT93 × JALO EEP558 (BJ). The consensus map consisted of a total of 1,010 markers mapped, with a total map length of 2,041 cM across 11 linkage groups. On average, each linkage group on the consensus map contained 91 markers of which 83% were single copy markers. Finally, a synteny analysis was carried out using our highly saturated consensus maps compared with the soybean pseudo-chromosome assembly. A total of 772 marker sequences were compared with the soybean genome. A total of 44 syntenic blocks were identified. The linkage group Pv6 presented the most diverse pattern of synteny with seven syntenic blocks, and Pv9 showed the most consistent relations with soybean with just two syntenic blocks. Additionally, a co-linear analysis using common bean transcript map information against soybean coding sequences (CDS) revealed the relationship with 787 soybean genes. The common bean consensus map has allowed us to map a larger number of markers, to obtain a more complete coverage of the common bean genome. Our results, combined with synteny relationships provide tools to increase marker density in selected genomic regions to identify closely linked polymorphic markers for indirect selection, fine mapping or for positional cloning.

  13. Linkage analysis of five Chinese families with arrhythmogenic right ventricular cardiomyopathy using microsatellite genetic markers

    Institute of Scientific and Technical Information of China (English)

    黄峻; 杨春梅; 马立隽; 单其俊; 许迪; 华子春; 曹克将

    2003-01-01

    Objective To explore the linkage relationship between specific genetic markers and arrhythmogenic right ventricular cardiomyopathy (ARVC) in Chinese pedigrees.Methods The microsatellite genetic markers D2S152, D14S252, and D10S1664 were studied for their linkages to ARVC in five Chinese ARVC pedigrees and a normal population of 121 Chinese individuals. Genomic DNA of the pedigrees and normal population was amplified using PCR techniques. Denaturing polyacrylamide sequencing gel (4%) electrophoresis was used to detect microsatellite repeat polymorphisms. Gels were silver-stained. A classical linkage analysis program was used assuming models of autosomal dominance and recession. Results The logarithm of the odds (LOD) scores of D2S152 with ARVC in LW, WD, DS, LC and TY pedigrees were 2.174, -0.589, -∞, - (indicating that linkage is not supported in this mode), and -∞ respectively in autosomal dominant model (recombination fraction=0.000 respectively)and were -∞, -∞, -∞, -∞, and 0.182 respectively in the autosomal recessive model. The LOD scores of D14S252 with ARVC in LW, WD, DS, LC and TY pedigrees were -, -, -∞, -, and 0 respectively in autosomal dominant model, and were -∞, -0.812, -∞, -∞, and 0.087 respectively in autosomal recessive model. The LOD scores of D2S152 with ARVC in LW, WD, DS, LC and TY pedigrees were -, -0.539, -, and 0.602 respectively in autosomal dominant model and were -, -∞, -∞, -∞, and -∞ respectively in autosomal recessive model. Conclusions The LOD score for D2S152 in the LW pedigree was 2.174, indicating that the chance of linkage is about 150∶ 1. This suggests that there is a possible ARVC-related gene near this marker. There were no clear linkage relationships between ARVC and D10S1664 and D14S252 in this family, and no linkages between ARVC and any of the three genetic markers in the other four families. These results also suggest that there is genetic heterogeneity in LW and in the other pedigrees.

  14. A Novel Linkage to Generalized Vitiligo on 4q13-q21 Identified in a Genomewide Linkage Analysis of Chinese Families

    OpenAIRE

    Chen, Jian-Jun; Huang, Wei; Gui, Jin-Ping; Yang, Sen; Zhou, Fu-Sheng; Xiong, Quan-Geng; Wu, Hong-Bo; Cui, Yong; Gao, Min; Li, Wei; Li, Jin-Xian; Yan, Kai-Lin; Yuan, Wen-tao; Xu, Shi-Jie; Liu, Jian-Jun

    2005-01-01

    Generalized vitiligo is a common, autoimmune, familial-clustering depigmentary disorder of the skin and hair that results from selective destruction of melanocytes. Generalized vitiligo is likely a heterogeneous disease, with five susceptibility loci reported so far—on chromosomes 1p31, 6p21, 7q, 8p, and 17p13—in white populations. To investigate vitiligo susceptibility loci in the Chinese population, we performed a genomewide linkage analysis in 57 multiplex Chinese families, each with at le...

  15. High-resolution mapping of the gene for cystinosis, using combined biochemical and linkage analysis.

    Science.gov (United States)

    Jean, G; Fuchshuber, A; Town, M M; Gribouval, O; Schneider, J A; Broyer, M; van't Hoff, W; Niaudet, P; Antignac, C

    1996-03-01

    Infantile nephropathic cystinosis is an autosomal recessive disorder characterized biochemically by an abnormally high intracellular content of free cystine in different organs and tissues due to a transport defect of cystine through the lysosomal membrane. Affected children present with the Fanconi syndrome and usually develop progressive renal failure within the 1st decade of life. Measurement of free cystine in purified polymorphonuclear leukocytes provides an accurate method for diagnosis and detection of heterozygous carriers. In order to localize the gene locus for cystinosis we performed linkage analysis in 18 cystinosis families. However, since 17 of these were simplex families, we decided to include the phenotypes of the heterozygous carriers previously determined by their leukocyte cystine content in the linkage analysis. This approach allowed us to obtain highly significant results, confirming the localization of the cystinosis gene locus recently mapped to the short arm of chromosome 17 by the Cystinosis Collaborative Research Group. Crucial recombination events allowed us to refine the interval of the cystinosis gene to a genetic distance of 1 cM. No evidence of genetic heterogeneity was found. Our results demonstrate that the use of the previously determined phenotypes of heterozygous carriers in linkage analysis provides a reliable method for the investigation of simplex families in autosomal recessive traits.

  16. Clinical features and linkage analysis for a Chinese family with autosomal dominant central areolar choroidal dystrophy

    Institute of Scientific and Technical Information of China (English)

    MA Kai; LIU Ning-pu; YANG Xiu-fen; HAN Cui; ZHANG Ning; XU Jun; LIU Shou-bin; LU Hal; Torkel Snellingen; WANG Ning-li

    2009-01-01

    Background A Chinese family with autosomal dominant central areolar choroidal dystrophy (CACD) was identified.The purpose of this study was to collect the clinical findings from the family and to identify the genetic entity by linkage nalysis.Methods Forty-three individuals from 3 generations of the family underwent ophthalmologic examinations, including best-corrected visual acuity, examination of the anterior segments, and inspection of the ocular fundus after pharmacologic mydriasis. Affected family members further underwent color vision test, color fundus photography,fluorescein angiography, automated perimetry, and electroretinography. The family was followed up for 30 months.Peripheral venous blood or buccal swabs were collected from each family member and genomic DNA was extracted.Linkage analysis was performed for candidate genes or loci using microsatellite markers.Results Seven family members in 3 continuous generations were diagnosed as having autosomal dominant CACD.The family showed progressive development of the disease, affecting both male and female. Age of onset of visual disturbances varied between 11 and 50 years. Phenotypic variability among affected individuals was apparent and ranged from relatively normal-appearing fundus with mild parafoveal pigment mottling to geographic atrophy of the macula. Fluorescein angiography showed hyperfluorescent parafoveal changes in early stage or well-demarcated area of chorioretinal atrophy with enhanced visibility of the residual underlying choroidal vessels in the late stage. Peripheral retina and visual fields were normal in affected individuals. Electroretinogram showed normal or mild reduction in the photopic amplitude. Eight candidate genes (STGD4, RCD1, peripherin/RDS, GUCA1A, RIMS1, UNC119, GUC Y2D, and AIPL1) and two genetic loci (4p15.2-16.3, and 17p13) were excluded to be responsible for the disease by linkage analysis.Conclusions The clinical findings of this Chinese family with CACD shared

  17. Linkage Analysis in Autoimmune Addison's Disease: NFATC1 as a Potential Novel Susceptibility Locus.

    Science.gov (United States)

    Mitchell, Anna L; Bøe Wolff, Anette; MacArthur, Katie; Weaver, Jolanta U; Vaidya, Bijay; Erichsen, Martina M; Darlay, Rebecca; Husebye, Eystein S; Cordell, Heather J; Pearce, Simon H S

    2015-01-01

    Autoimmune Addison's disease (AAD) is a rare, highly heritable autoimmune endocrinopathy. It is possible that there may be some highly penetrant variants which confer disease susceptibility that have yet to be discovered. DNA samples from 23 multiplex AAD pedigrees from the UK and Norway (50 cases, 67 controls) were genotyped on the Affymetrix SNP 6.0 array. Linkage analysis was performed using Merlin. EMMAX was used to carry out a genome-wide association analysis comparing the familial AAD cases to 2706 UK WTCCC controls. To explore some of the linkage findings further, a replication study was performed by genotyping 64 SNPs in two of the four linked regions (chromosomes 7 and 18), on the Sequenom iPlex platform in three European AAD case-control cohorts (1097 cases, 1117 controls). The data were analysed using a meta-analysis approach. In a parametric analysis, applying a rare dominant model, loci on chromosomes 7, 9 and 18 had LOD scores >2.8. In a non-parametric analysis, a locus corresponding to the HLA region on chromosome 6, known to be associated with AAD, had a LOD score >3.0. In the genome-wide association analysis, a SNP cluster on chromosome 2 and a pair of SNPs on chromosome 6 were associated with AAD (P <5x10-7). A meta-analysis of the replication study data demonstrated that three chromosome 18 SNPs were associated with AAD, including a non-synonymous variant in the NFATC1 gene. This linkage study has implicated a number of novel chromosomal regions in the pathogenesis of AAD in multiplex AAD families and adds further support to the role of HLA in AAD. The genome-wide association analysis has also identified a region of interest on chromosome 2. A replication study has demonstrated that the NFATC1 gene is worthy of future investigation, however each of the regions identified require further, systematic analysis.

  18. Linkage Analysis in Autoimmune Addison's Disease: NFATC1 as a Potential Novel Susceptibility Locus.

    Directory of Open Access Journals (Sweden)

    Anna L Mitchell

    Full Text Available Autoimmune Addison's disease (AAD is a rare, highly heritable autoimmune endocrinopathy. It is possible that there may be some highly penetrant variants which confer disease susceptibility that have yet to be discovered.DNA samples from 23 multiplex AAD pedigrees from the UK and Norway (50 cases, 67 controls were genotyped on the Affymetrix SNP 6.0 array. Linkage analysis was performed using Merlin. EMMAX was used to carry out a genome-wide association analysis comparing the familial AAD cases to 2706 UK WTCCC controls. To explore some of the linkage findings further, a replication study was performed by genotyping 64 SNPs in two of the four linked regions (chromosomes 7 and 18, on the Sequenom iPlex platform in three European AAD case-control cohorts (1097 cases, 1117 controls. The data were analysed using a meta-analysis approach.In a parametric analysis, applying a rare dominant model, loci on chromosomes 7, 9 and 18 had LOD scores >2.8. In a non-parametric analysis, a locus corresponding to the HLA region on chromosome 6, known to be associated with AAD, had a LOD score >3.0. In the genome-wide association analysis, a SNP cluster on chromosome 2 and a pair of SNPs on chromosome 6 were associated with AAD (P <5x10-7. A meta-analysis of the replication study data demonstrated that three chromosome 18 SNPs were associated with AAD, including a non-synonymous variant in the NFATC1 gene.This linkage study has implicated a number of novel chromosomal regions in the pathogenesis of AAD in multiplex AAD families and adds further support to the role of HLA in AAD. The genome-wide association analysis has also identified a region of interest on chromosome 2. A replication study has demonstrated that the NFATC1 gene is worthy of future investigation, however each of the regions identified require further, systematic analysis.

  19. Whole-genome linkage analysis in mapping alcoholism genes using single-nucleotide polymorphisms and microsatellites.

    Science.gov (United States)

    Wang, Shuang; Huang, Song; Liu, Nianjun; Chen, Liang; Oh, Cheongeun; Zhao, Hongyu

    2005-12-30

    There is currently a great interest in using single-nucleotide polymorphisms (SNPs) in genetic linkage and association studies because of the abundance of SNPs as well as the availability of high-throughput genotyping technologies. In this study, we compared the performance of whole-genome scans using SNPs with microsatellites on 143 pedigrees from the Collaborative Studies on Genetics of Alcoholism provided by Genetic Analysis Workshop 14. A total of 315 microsatellites and 10,081 SNPs from Affymetrix on 22 autosomal chromosomes were used in our analyses. We found that the results from the two scans had good overall concordance. One region on chromosome 2 and two regions on chromosome 7 showed significant linkage signals (i.e., NPL >or= 2) for alcoholism from both the SNP and microsatellite scans. The different results observed between the two scans may be explained by the difference observed in information content between the SNPs and the microsatellites.

  20. Ascertainment correction for Markov chain Monte Carlo segregation and linkage analysis of a quantitative trait.

    Science.gov (United States)

    Ma, Jianzhong; Amos, Christopher I; Warwick Daw, E

    2007-09-01

    Although extended pedigrees are often sampled through probands with extreme levels of a quantitative trait, Markov chain Monte Carlo (MCMC) methods for segregation and linkage analysis have not been able to perform ascertainment corrections. Further, the extent to which ascertainment of pedigrees leads to biases in the estimation of segregation and linkage parameters has not been previously studied for MCMC procedures. In this paper, we studied these issues with a Bayesian MCMC approach for joint segregation and linkage analysis, as implemented in the package Loki. We first simulated pedigrees ascertained through individuals with extreme values of a quantitative trait in spirit of the sequential sampling theory of Cannings and Thompson [Cannings and Thompson [1977] Clin. Genet. 12:208-212]. Using our simulated data, we detected no bias in estimates of the trait locus location. However, in addition to allele frequencies, when the ascertainment threshold was higher than or close to the true value of the highest genotypic mean, bias was also found in the estimation of this parameter. When there were multiple trait loci, this bias destroyed the additivity of the effects of the trait loci, and caused biases in the estimation all genotypic means when a purely additive model was used for analyzing the data. To account for pedigree ascertainment with sequential sampling, we developed a Bayesian ascertainment approach and implemented Metropolis-Hastings updates in the MCMC samplers used in Loki. Ascertainment correction greatly reduced biases in parameter estimates. Our method is designed for multiple, but a fixed number of trait loci.

  1. Genetic mapping of the gene for Usher syndrome: Linkage analysis in a large Samaritan kindred

    Energy Technology Data Exchange (ETDEWEB)

    Bonne-Tamir, B.; Korostishevsky, M.; Kalinsky, H.; Seroussi, E.; Beker, R.; Weiss, S. (Sackler Faculty of Medicine, Ramat-Aviv (Israel)); Godel, V. (Ichilov Hospital, Tel-Aviv (Israel))

    1994-03-01

    Usher syndrome is a group of autosomal recessive disorders associated with congenital sensorineural deafness and progressive visual loss due to retinitis pigmentosa. Sixteen members of the small inbred Samaritan isolate with autosomal recessive deafness from 59 individuals including parents and affected and nonaffected sibs were typed for markers on chromosomes 1q and 11q for which linkage has recently been established for Usher syndrome types II and I. Statistically significant linkage was observed with four markers on 11q (D11S533, D11S527, OMP, and INT2) with a maximum six-point location score of 11.61 at the D11S533 locus. Analysis of haplotypes supports the notion that the mutation arose only once in an ancestral chromosome carrying a specific haplotype. The availability of markers closely linked to the disease locus allows indirect genotype analysis and identifies all carriers of the gene within the community. Furthermore, the detection of complete linkage disequilibrium between the D11S533 marker and the Usher gene suggests that these loci are either identical or adjacent and narrows the critical region to which physical mapping efforts are currently directed. 35 refs., 2 figs., 6 tabs.

  2. A variable age of onset segregation model for linkage analysis, with correction for ascertainment, applied to glioma

    DEFF Research Database (Denmark)

    Sun, Xiangqing; Vengoechea, Jaime; Elston, Robert

    2012-01-01

    We propose a 2-step model-based approach, with correction for ascertainment, to linkage analysis of a binary trait with variable age of onset and apply it to a set of multiplex pedigrees segregating for adult glioma.......We propose a 2-step model-based approach, with correction for ascertainment, to linkage analysis of a binary trait with variable age of onset and apply it to a set of multiplex pedigrees segregating for adult glioma....

  3. Genome-wide linkage analysis of malaria infection intensity and mild disease.

    Directory of Open Access Journals (Sweden)

    Christian Timmann

    2007-03-01

    Full Text Available Although balancing selection with the sickle-cell trait and other red blood cell disorders has emphasized the interaction between malaria and human genetics, no systematic approach has so far been undertaken towards a comprehensive search for human genome variants influencing malaria. By screening 2,551 families in rural Ghana, West Africa, 108 nuclear families were identified who were exposed to hyperendemic malaria transmission and were homozygous wild-type for the established malaria resistance factors of hemoglobin (HbS, HbC, alpha(+ thalassemia, and glucose-6-phosphate-dehydrogenase deficiency. Of these families, 392 siblings aged 0.5-11 y were characterized for malaria susceptibility by closely monitoring parasite counts, malaria fever episodes, and anemia over 8 mo. An autosome-wide linkage analysis based on 10,000 single-nucleotide polymorphisms was conducted in 68 selected families including 241 siblings forming 330 sib pairs. Several regions were identified which showed evidence for linkage to the parasitological and clinical phenotypes studied, among them a prominent signal on Chromosome 10p15 obtained with malaria fever episodes (asymptotic z score = 4.37, empirical p-value = 4.0 x 10(-5, locus-specific heritability of 37.7%; 95% confidence interval, 15.7%-59.7%. The identification of genetic variants underlying the linkage signals may reveal as yet unrecognized pathways influencing human resistance to malaria.

  4. Inflammatory bowel disease gene hunting by linkage analysis: rationale, methodology, and present status of the field.

    Science.gov (United States)

    Brant, Steven R; Shugart, Yin Yao

    2004-05-01

    Observed inflammatory bowel disease (IBD) familial clustering and increased monozygotic twin concordance has led to the hypothesis that genetic loci containing IBD susceptibility genes can be identified by whole genome linkage mapping approaches. Methodology including collecting carefully phenotyped multiplex pedigrees, genotyping using highly informative microsatellite markers and linkage analysis by non-parametric allele sharing methods has been established. Eleven published genome wide screens (GWS) have studied more than 1,200 multiplex IBD pedigrees. Two-thirds of affected relative pairs were Crohn's disease (CD), 20% ulcerative colitis (UC) and the remaining were mixed. Seven loci (IBDI-7) on chromosomes 16q, 12, 6p, 14q, 5q, 19, and 1p have been identified with genome wide significant and independently replicated linkage. Risk alleles/haplotypes have been defined for the IBD1 (CARD15/NOD2), IBD3 (HLA) and IBD5 (5q cytokine cluster) loci. There has been evidence for a second chromosome 16 locus (IBD8) independent of NOD2 that overlaps IBD1 on the pericentromeric p-arm. Several other regions show great promise for containing additional IBD loci, particularly chromosome 3p with genome wide evidence in one study at 3p26 and more centromeric evidence in several other studies, and chromosomes 2q, 3q, 4q, 7, 11p, and Xp each with suggestive evidence of linkage in one and additional evidence in two or more studies. Single GWSs and fine mapping studies containing very large sets of pedigrees and in particular, more UC pedigrees, and the use of creative analytic and disease stratification schemes are required to identify, establish and refine weaker IBD loci.

  5. Genetic linkage analysis of familial amyotrophic lateral sclerosis using human chromosome 21 microsatellite DNA markers

    Energy Technology Data Exchange (ETDEWEB)

    Rosen, D.R.; Sapp, P.; O`Regan, J.; McKenna-Yasek, D.; Schlumpf, K.S.; Haines, J.L.; Gusella, J.F.; Horvitz, H.R.; Brown, R.H. Jr. [Massachusetts Institute of Technology, Cambridge, MA (United States)

    1994-05-15

    Amyotrophic lateral sclerosis (ALS; Lou Gehrig`s Disease) is a lethal neurodegenerative disease of upper and lower motorneurons in the brain and spinal cord. We previously reported linkage of a gene for familial ALS (FALS) to human chromosome 21 using 4 restriction fragment length polymorphism DNA markers and identified disease-associated mutations in the superoxide dismutase (SOD)-1 gene in some ALS families. We report here the genetic linkage data that led us to examine the SOD-1 gene for mutations. We also report a new microsatellite DNA marker for D21S63, derived from the cosmid PW517. Ten microsatellite DNA markers, including the new marker D21S63, were used to reinvestigate linkage of FALS to chromosome 21. Genetic linkage analysis performed with 13 ALS familes for these 10 DNA markers confirmed the presence of a FALS gene on chromosome 21. The highest total 2-point LOD score for all families was 4.33, obtained at a distance of 10 cM from the marker D21S223. For 5 ALS families linked to chromosome 21, a peak 2-point LOD score of 5.94 was obtained at the DNA marker D21S223. A multipoint score of 6.50 was obtained with the markers D21S213, D21S223, D21S167, and FALS for 5 chromosome 21-linked ALS families. The haplotypes of these families for the 10 DNA markers reveal recombination events that further refined the location of the FALS gene to a segment of approximately 5 megabases (Mb) between D21S213 and D21S219. The only characterized gene within this segment was SOD-1, the structural gene for Cu, Zn SOD. 30 refs., 4 figs., 4 tabs.

  6. Importance sampling method of correction for multiple testing in affected sib-pair linkage analysis

    OpenAIRE

    Klein, Alison P.; Kovac, Ilija; Sorant, Alexa JM; Baffoe-Bonnie, Agnes; Doan, Betty Q; Ibay, Grace; Lockwood, Erica; Mandal, Diptasri; Santhosh, Lekshmi; Weissbecker, Karen; Woo, Jessica; Zambelli-Weiner, April; Zhang, Jie; Naiman, Daniel Q.; Malley, James

    2003-01-01

    Using the Genetic Analysis Workshop 13 simulated data set, we compared the technique of importance sampling to several other methods designed to adjust p-values for multiple testing: the Bonferroni correction, the method proposed by Feingold et al., and naïve Monte Carlo simulation. We performed affected sib-pair linkage analysis for each of the 100 replicates for each of five binary traits and adjusted the derived p-values using each of the correction methods. The type I error rates for each...

  7. Linkage analysis and the study of Mendelian disease in the era of whole exome and genome sequencing.

    Science.gov (United States)

    Teare, M Dawn; Santibañez Koref, Mauro F

    2014-09-01

    Whole exome and whole genome sequencing are now routinely used in the study of inherited disease, and some of their major successes have been the identification of genes involved in disease predisposition in pedigrees where disease seems to follow Mendelian inheritance patterns. These successes include scenarios where only a single individual was sequenced and raise the question whether linkage analysis has become superfluous. Linkage analysis requires genome-wide genotyping on family-based data, and traditionally the linkage analysis was performed before the targeting sequencing stage. However, methods are emerging that seek to exploit the capability of linkage analysis to integrate data both across individuals and across pedigrees. This ability has been exploited to select samples used for sequencing studies and to identify among the variants uncovered by sequencing those mapping to regions likely to contain the gene of interest and, more generally, to improve variant detection. So, although the formal isolated linkage analysis stage is less commonly seen, when uncovering the genetic basis of Mendelian disease, methods relying heavily on genetic linkage analysis principles are being integrated directly into the whole mapping process ranging from sample selection to variant calling and filtering. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  8. Two-point orientation discrimination versus the traditional two-point test for tactile spatial acuity assessment.

    Science.gov (United States)

    Tong, Jonathan; Mao, Oliver; Goldreich, Daniel

    2013-01-01

    Two-point discrimination is widely used to measure tactile spatial acuity. The validity of the two-point threshold as a spatial acuity measure rests on the assumption that two points can be distinguished from one only when the two points are sufficiently separated to evoke spatially distinguishable foci of neural activity. However, some previous research has challenged this view, suggesting instead that two-point task performance benefits from an unintended non-spatial cue, allowing spuriously good performance at small tip separations. We compared the traditional two-point task to an equally convenient alternative task in which participants attempt to discern the orientation (vertical or horizontal) of two points of contact. We used precision digital readout calipers to administer two-interval forced-choice versions of both tasks to 24 neurologically healthy adults, on the fingertip, finger base, palm, and forearm. We used Bayesian adaptive testing to estimate the participants' psychometric functions on the two tasks. Traditional two-point performance remained significantly above chance levels even at zero point separation. In contrast, two-point orientation discrimination approached chance as point separation approached zero, as expected for a valid measure of tactile spatial acuity. Traditional two-point performance was so inflated at small point separations that 75%-correct thresholds could be determined on all tested sites for fewer than half of participants. The 95%-correct thresholds on the two tasks were similar, and correlated with receptive field spacing. In keeping with previous critiques, we conclude that the traditional two-point task provides an unintended non-spatial cue, resulting in spuriously good performance at small spatial separations. Unlike two-point discrimination, two-point orientation discrimination rigorously measures tactile spatial acuity. We recommend the use of two-point orientation discrimination for neurological assessment.

  9. Two-point orientation discrimination versus the traditional two-point test for tactile spatial acuity assessment

    Directory of Open Access Journals (Sweden)

    Jonathan eTong

    2013-09-01

    Full Text Available Two-point discrimination is widely used to measure tactile spatial acuity. The validity of the two-point threshold as a spatial acuity measure rests on the assumption that two points can be distinguished from one only when the two points are sufficiently separated to evoke spatially distinguishable foci of neural activity. However, some previous research has challenged this view, suggesting instead that two-point task performance benefits from an unintended non-spatial cue, allowing spuriously good performance at small tip separations. We compared the traditional two-point task to an equally convenient alternative task in which participants attempt to discern the orientation (vertical or horizontal of two points of contact. We used precision digital readout calipers to administer two-interval forced-choice versions of both tasks to 24 neurologically healthy adults, on the fingertip, finger base, palm, and forearm. We used Bayesian adaptive testing to estimate the participants’ psychometric functions on the two tasks. Traditional two-point performance remained significantly above chance levels even at zero point separation. In contrast, two-point orientation discrimination approached chance as point separation approached zero, as expected for a valid measure of tactile spatial acuity. Traditional two-point performance was so inflated at small point separations that 75%-correct thresholds could be determined on all tested sites for fewer than half of participants. The 95%-correct thresholds on the two tasks were similar, and correlated with receptive field spacing. In keeping with previous critiques, we conclude that the traditional two-point task provides an unintended non-spatial cue, resulting in spuriously good performance at small spatial separations. Unlike two-point discrimination, two-point orientation discrimination rigorously measures tactile spatial acuity. We recommend the use of two-point orientation discrimination for neurological

  10. Strategies for assessing proton linkage to bimolecular interactions by global analysis of isothermal titration calorimetry data.

    Science.gov (United States)

    Coussens, Nathan P; Schuck, Peter; Zhao, Huaying

    2012-09-01

    Isothermal titration calorimetry (ITC) is a traditional and powerful method for studying the linkage of ligand binding to proton uptake or release. The theoretical framework has been developed for more than two decades and numerous applications have appeared. In the current work, we explored strategic aspects of experimental design. To this end, we simulated families of ITC data sets that embed different strategies with regard to the number of experiments, range of experimental pH, buffer ionization enthalpy, and temperature. We then re-analyzed the families of data sets in the context of global analysis, employing a proton linkage binding model implemented in the global data analysis platform SEDPHAT, and examined the information content of all data sets by a detailed statistical error analysis of the parameter estimates. In particular, we studied the impact of different assumptions about the knowledge of the exact concentrations of the components, which in practice presents an experimental limitation for many systems. For example, the uncertainty in concentration may reflect imperfectly known extinction coefficients and stock concentrations or may account for different extents of partial inactivation when working with proteins at different pH values. Our results show that the global analysis can yield reliable estimates of the thermodynamic parameters for intrinsic binding and protonation, and that in the context of the global analysis the exact molecular component concentrations may not be required. Additionally, a comparison of data from different experimental strategies illustrates the benefit of conducting experiments at a range of temperatures.

  11. A combined linkage and exome sequencing analysis for electrocardiogram parameters in the Erasmus Rucphen Family study

    Directory of Open Access Journals (Sweden)

    Claudia Tamar Silva

    2016-11-01

    Full Text Available Electrocardiogram (ECG measurements play a key role in the diagnosis and prediction of cardiac arrhythmias and sudden cardiac death. ECG parameters, such as the PR, QRS, and QT intervals, are known to be heritable and genome-wide association studies (GWAS of these phenotypes have been successful in identifying common variants; however, a large proportion of the genetic variability of these traits remains to be elucidated. The aim of this study was to discover loci potentially harboring rare variants utilizing variance component linkage analysis in 1547 individuals from a large family-based study, the Erasmus Rucphen Family Study (ERF. Linked regions were further explored using exome sequencing. Five suggestive linkage peaks were identified: two for QT interval (1q24, LOD = 2.63; 2q34, LOD = 2.05, one for QRS interval (1p35, LOD = 2.52 and two for PR interval (9p22, LOD = 2.20; 14q11, LOD = 2.29. Fine-mapping using exome sequence data identified a C > G missense variant (c.713C>G, p.Ser238Cys in the FCRL2 gene associated with QT (rs74608430; P = 2.8 ×10-4, minor allele frequency = 0.019. Heritability analysis demonstrated that the SNP explained 2.42% of the trait’s genetic variability in ERF (P = 0.02. Pathway analysis suggested that the gene is involved in cytosolic Ca2+ levels (P = 3.3 × 10-3 and AMPK stimulated fatty acid oxidation in muscle (P = 4.1 ×10-3. Look-ups in bioinformatics resources showed that expression of FCRL2 is associated with ARHGAP24 and SETBP1 expression. This finding was not replicated in the Rotterdam study. Combining the bioinformatics information with the association and linkage analyses, FCRL2 emerges as a strong candidate gene for QT interval.

  12. The sumLINK statistic for genetic linkage analysis in the presence of heterogeneity.

    Science.gov (United States)

    Christensen, G B; Knight, S; Camp, N J

    2009-11-01

    We present the "sumLINK" statistic--the sum of multipoint LOD scores for the subset of pedigrees with nominally significant linkage evidence at a given locus--as an alternative to common methods to identify susceptibility loci in the presence of heterogeneity. We also suggest the "sumLOD" statistic (the sum of positive multipoint LOD scores) as a companion to the sumLINK. sumLINK analysis identifies genetic regions of extreme consistency across pedigrees without regard to negative evidence from unlinked or uninformative pedigrees. Significance is determined by an innovative permutation procedure based on genome shuffling that randomizes linkage information across pedigrees. This procedure for generating the empirical null distribution may be useful for other linkage-based statistics as well. Using 500 genome-wide analyses of simulated null data, we show that the genome shuffling procedure results in the correct type 1 error rates for both the sumLINK and sumLOD. The power of the statistics was tested using 100 sets of simulated genome-wide data from the alternative hypothesis from GAW13. Finally, we illustrate the statistics in an analysis of 190 aggressive prostate cancer pedigrees from the International Consortium for Prostate Cancer Genetics, where we identified a new susceptibility locus. We propose that the sumLINK and sumLOD are ideal for collaborative projects and meta-analyses, as they do not require any sharing of identifiable data between contributing institutions. Further, loci identified with the sumLINK have good potential for gene localization via statistical recombinant mapping, as, by definition, several linked pedigrees contribute to each peak.

  13. Preimplantation genetic diagnosis of X-linked Charcot-Marie-Tooth disease by indirect linkage analysis.

    Science.gov (United States)

    Borgulová, Irena; Putzová, Martina; Soldatova, Inna; Stejskal, David

    2017-08-07

    To present methodical approach of preimplantation genetic diagnosis (PGD) as an option for an unaffected pregnancy in reproductive-age couples who have a genetic risk of the X-linked dominant peripheral neuropathy Charcot-Marie-Tooth type 1 disease. We performed PGD of X-linked Charcot-Marie-Tooth type 1 disease using haplotyping/indirect linkage analysis, when during analysis we reach to exclude embryos that carry a high-risk haplotype linked to the causal mutation p.Leu9Phe in the GJB1 gene. Within the PGD cycle, we examined 4 blastomeres biopsied from cleavage-stage embryos and recommended 3 embryos for transfer. Two embryos were implanted into the uterus; however, it resulted in a singleton pregnancy with a male descendant. Three years later, the couple returned again with spontaneous gravidity. A chorionic biopsy examination of this gravidity ascertained the female sex and a pericentric inversion of chromosome 5 in 70% of the cultivated foetal cells. Using indirect linkage analysis, PGD may help to identify genetic X-linked defects within embryos during screening, thereby circumventing the potential problems with abortion. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  14. Neurofibromatosis type I (NFI) in Israeli families: Linkage analysis as a diagnostic tool

    Energy Technology Data Exchange (ETDEWEB)

    Elyakim, S.; Lerer, I.; Zlotogora, J.; Sagi, M.; Merin, S.; Abeliovich, D. [Hadassah Univ. Hospital, Jerusalem (Israel); Gelman-Kohan, Z. [Hebrew Univ. Hadassah Medical School, Rehovot (Israel)

    1994-12-01

    Linkage analysis of 18 neurofibromatosis type I (NFI) families was performed using intragenic and flanking polymorphic markers. The aims of the analysis were prenatal diagnosis of at-risk fetuses, and of asymptomatic individuals who were relatives of NFI patients. Prenatal diagnosis was performed in 9 pregnancies of 7 families; 5 fetuses were diagnosed as affected. In 6 families with an affected spouse, the request was to identify informative polymorphisms to be used in future pregnancies. Presymptomatic diagnosis was performed in 4 families. One individual, a brother of an NFI patient, was found to have Lisch nodules as the only NFI symptom. Linkage analysis indicated that if this person is a carrier of the NFI gene, he must be a product of intragenic crossover. In 2 individuals with a new NFI mutation, the origin of the NFI-bearing chromosomes was paternal. The same observation was noted by others. A summary of published cases shows that some 90% of the NFI-bearing chromosomes of patients with new mutations were of paternal origin. We therefore suggest that for the purpose of prenatal diagnosis in carriers of NFI new (and unidentified) mutations, the paternal chromosome will be considered as the NFI-bearing chromosome. 49 refs., 4 figs., 3 tabs.

  15. Nonlinear Analysis of Time Series in Genome-Wide Linkage Disequilibrium Data

    Science.gov (United States)

    Hernández-Lemus, Enrique; Estrada-Gil, Jesús K.; Silva-Zolezzi, Irma; Fernández-López, J. Carlos; Hidalgo-Miranda, Alfredo; Jiménez-Sánchez, Gerardo

    2008-02-01

    The statistical study of large scale genomic data has turned out to be a very important tool in population genetics. Quantitative methods are essential to understand and implement association studies in the biomedical and health sciences. Nevertheless, the characterization of recently admixed populations has been an elusive problem due to the presence of a number of complex phenomena. For example, linkage disequilibrium structures are thought to be more complex than their non-recently admixed population counterparts, presenting the so-called ancestry blocks, admixed regions that are not yet smoothed by the effect of genetic recombination. In order to distinguish characteristic features for various populations we have implemented several methods, some of them borrowed or adapted from the analysis of nonlinear time series in statistical physics and quantitative physiology. We calculate the main fractal dimensions (Kolmogorov's capacity, information dimension and correlation dimension, usually named, D0, D1 and D2). We also have made detrended fluctuation analysis and information based similarity index calculations for the probability distribution of correlations of linkage disequilibrium coefficient of six recently admixed (mestizo) populations within the Mexican Genome Diversity Project [1] and for the non-recently admixed populations in the International HapMap Project [2]. Nonlinear correlations showed up as a consequence of internal structure within the haplotype distributions. The analysis of these correlations as well as the scope and limitations of these procedures within the biomedical sciences are discussed.

  16. An approach to incorporate linkage disequilibrium structure into genomic association analysis

    Institute of Scientific and Technical Information of China (English)

    Fengyu Zhang; Diane Wagener

    2008-01-01

    In this study, we propose to use the principal component analysis (PCA) and regression model to incorporate linkage disequilibrium (LD) in genomic association data analysis. To accommodate LD in genomic data and reduce multiple testing, we suggest performing PCA and extracting the PCA score to capture the variation of genomic data, after which regression analysis is used to assess the association of the disease with the principal component score. An empirical analysis result shows that both genotype-basod correlation matrix and haplotype-based LD matrix can produce similar results for PCA. Principal component score seems to be more powerful in detecting genetic association because the principal component score is quantitatively measured and may be able to capture the effect of multiple loci.

  17. 基于两点式步行吸引盆计算的稳定性分析%Stability analysis of attraction basin in two-point-foot walking pattern

    Institute of Scientific and Technical Information of China (English)

    钟林枫; 罗翔; 郭晨光

    2011-01-01

    A new walking pattern denoted as two-point-foot walking pattern is proposed according to the foot structure of human being. The equations of a planar straight leg-inverted pendulum based on this pattern are derived to study the stability of gait and the energy consumption in biped walking. A new kind of numerical algorithm is put forward according to Poincare mapping. The fixed points and the basin of attraction of this model are obtained by the numerical method. The effects of λ and step variation on the basin of attraction and energy consumption are discussed for the biped walking. The area of basin of attraction decreases with the increase of coefficient λ; meanwhile, the speed converging to the fixed point accelerates; the ratio of initial conditions which can converge to the fixed point quickly increases. On the other hand, the area of basin of attraction increases with the step length;so that more energy would be consumed for unit distance of the model's walk. A parameters combination that λ is 0. 55 and step is 0. 50 is of advantage for the control of robot.%为了研究两足步行过程中步态稳定性及步行能耗的问题,通过对人脚结构的分析提出了一种新型的步行模式--两点式步行模式,并建立了基于此模式的直腿无膝-倒立摆动力学模型.运用Poincare映射法,提出了一种数值算法,计算了该直腿无膝模型的不动点及吸引盆;研究了模型特性参数λ、步长对吸引盆特性及步行能耗的影响.系数λ增大会使吸引盆面积减小,收敛到不动点的速度变快,快速收敛到不动点的初始条件比例变大.步长增大会使吸引盆面积增大,模型在步行过程中单位距离消耗的能量增加.结果表明,λ为0.55和步长为0.50的参数组合更有利于对机器人系统的控制.

  18. Combined genome-wide linkage and targeted association analysis of head circumference in autism spectrum disorder families.

    Science.gov (United States)

    Woodbury-Smith, M; Bilder, D A; Morgan, J; Jerominski, L; Darlington, T; Dyer, T; Paterson, A D; Coon, H

    2017-01-01

    It has long been recognized that there is an association between enlarged head circumference (HC) and autism spectrum disorder (ASD), but the genetics of HC in ASD is not well understood. In order to investigate the genetic underpinning of HC in ASD, we undertook a genome-wide linkage study of HC followed by linkage signal targeted association among a sample of 67 extended pedigrees with ASD. HC measurements on members of 67 multiplex ASD extended pedigrees were used as a quantitative trait in a genome-wide linkage analysis. The Illumina 6K SNP linkage panel was used, and analyses were carried out using the SOLAR implemented variance components model. Loci identified in this way formed the target for subsequent association analysis using the Illumina OmniExpress chip and imputed genotypes. A modification of the qTDT was used as implemented in SOLAR. We identified a linkage signal spanning 6p21.31 to 6p22.2 (maximum LOD = 3.4). Although targeted association did not find evidence of association with any SNP overall, in one family with the strongest evidence of linkage, there was evidence for association (rs17586672, p = 1.72E-07). Although this region does not overlap with ASD linkage signals in these same samples, it has been associated with other psychiatric risk, including ADHD, developmental dyslexia, schizophrenia, specific language impairment, and juvenile bipolar disorder. The genome-wide significant linkage signal represents the first reported observation of a potential quantitative trait locus for HC in ASD and may be relevant in the context of complex multivariate risk likely leading to ASD.

  19. Linkage Map Construction and Quantitative Trait Locus Analysis of Agronomic and Fiber Quality Traits in Cotton

    Directory of Open Access Journals (Sweden)

    Michael A. Gore

    2014-03-01

    Full Text Available The superior fiber properties of L. serve as a source of novel variation for improving fiber quality in Upland cotton ( L., but introgression from has been largely unsuccessful due to hybrid breakdown and a lack of genetic and genomic resources. In an effort to overcome these limitations, we constructed a linkage map and conducted a quantitative trait locus (QTL analysis of 10 agronomic and fiber quality traits in a recombinant inbred mapping population derived from a cross between TM-1, an Upland cotton line, and NM24016, an elite line with stabilized introgression from . The linkage map consisted of 429 simple-sequence repeat (SSR and 412 genotyping-by-sequencing (GBS-based single-nucleotide polymorphism (SNP marker loci that covered half of the tetraploid cotton genome. Notably, the 841 marker loci were unevenly distributed among the 26 chromosomes of tetraploid cotton. The 10 traits evaluated on the TM-1 × NM24016 population in a multienvironment trial were highly heritable, and most of the fiber traits showed considerable transgressive variation. Through the QTL analysis, we identified a total of 28 QTLs associated with the 10 traits. Our study provides a novel resource that can be used by breeders and geneticists for the genetic improvement of agronomic and fiber quality traits in Upland cotton.

  20. Creative Activities in Music – A Genome-Wide Linkage Analysis

    Science.gov (United States)

    Oikkonen, Jaana; Kuusi, Tuire; Peltonen, Petri; Raijas, Pirre; Ukkola-Vuoti, Liisa; Karma, Kai; Onkamo, Päivi; Järvelä, Irma

    2016-01-01

    Creative activities in music represent a complex cognitive function of the human brain, whose biological basis is largely unknown. In order to elucidate the biological background of creative activities in music we performed genome-wide linkage and linkage disequilibrium (LD) scans in musically experienced individuals characterised for self-reported composing, arranging and non-music related creativity. The participants consisted of 474 individuals from 79 families, and 103 sporadic individuals. We found promising evidence for linkage at 16p12.1-q12.1 for arranging (LOD 2.75, 120 cases), 4q22.1 for composing (LOD 2.15, 103 cases) and Xp11.23 for non-music related creativity (LOD 2.50, 259 cases). Surprisingly, statistically significant evidence for linkage was found for the opposite phenotype of creative activity in music (neither composing nor arranging; NCNA) at 18q21 (LOD 3.09, 149 cases), which contains cadherin genes like CDH7 and CDH19. The locus at 4q22.1 overlaps the previously identified region of musical aptitude, music perception and performance giving further support for this region as a candidate region for broad range of music-related traits. The other regions at 18q21 and 16p12.1-q12.1 are also adjacent to the previously identified loci with musical aptitude. Pathway analysis of the genes suggestively associated with composing suggested an overrepresentation of the cerebellar long-term depression pathway (LTD), which is a cellular model for synaptic plasticity. The LTD also includes cadherins and AMPA receptors, whose component GSG1L was linked to arranging. These results suggest that molecular pathways linked to memory and learning via LTD affect music-related creative behaviour. Musical creativity is a complex phenotype where a common background with musicality and intelligence has been proposed. Here, we implicate genetic regions affecting music-related creative behaviour, which also include genes with neuropsychiatric associations. We also propose

  1. Creative Activities in Music--A Genome-Wide Linkage Analysis.

    Directory of Open Access Journals (Sweden)

    Jaana Oikkonen

    Full Text Available Creative activities in music represent a complex cognitive function of the human brain, whose biological basis is largely unknown. In order to elucidate the biological background of creative activities in music we performed genome-wide linkage and linkage disequilibrium (LD scans in musically experienced individuals characterised for self-reported composing, arranging and non-music related creativity. The participants consisted of 474 individuals from 79 families, and 103 sporadic individuals. We found promising evidence for linkage at 16p12.1-q12.1 for arranging (LOD 2.75, 120 cases, 4q22.1 for composing (LOD 2.15, 103 cases and Xp11.23 for non-music related creativity (LOD 2.50, 259 cases. Surprisingly, statistically significant evidence for linkage was found for the opposite phenotype of creative activity in music (neither composing nor arranging; NCNA at 18q21 (LOD 3.09, 149 cases, which contains cadherin genes like CDH7 and CDH19. The locus at 4q22.1 overlaps the previously identified region of musical aptitude, music perception and performance giving further support for this region as a candidate region for broad range of music-related traits. The other regions at 18q21 and 16p12.1-q12.1 are also adjacent to the previously identified loci with musical aptitude. Pathway analysis of the genes suggestively associated with composing suggested an overrepresentation of the cerebellar long-term depression pathway (LTD, which is a cellular model for synaptic plasticity. The LTD also includes cadherins and AMPA receptors, whose component GSG1L was linked to arranging. These results suggest that molecular pathways linked to memory and learning via LTD affect music-related creative behaviour. Musical creativity is a complex phenotype where a common background with musicality and intelligence has been proposed. Here, we implicate genetic regions affecting music-related creative behaviour, which also include genes with neuropsychiatric associations. We

  2. Creative Activities in Music--A Genome-Wide Linkage Analysis.

    Science.gov (United States)

    Oikkonen, Jaana; Kuusi, Tuire; Peltonen, Petri; Raijas, Pirre; Ukkola-Vuoti, Liisa; Karma, Kai; Onkamo, Päivi; Järvelä, Irma

    2016-01-01

    Creative activities in music represent a complex cognitive function of the human brain, whose biological basis is largely unknown. In order to elucidate the biological background of creative activities in music we performed genome-wide linkage and linkage disequilibrium (LD) scans in musically experienced individuals characterised for self-reported composing, arranging and non-music related creativity. The participants consisted of 474 individuals from 79 families, and 103 sporadic individuals. We found promising evidence for linkage at 16p12.1-q12.1 for arranging (LOD 2.75, 120 cases), 4q22.1 for composing (LOD 2.15, 103 cases) and Xp11.23 for non-music related creativity (LOD 2.50, 259 cases). Surprisingly, statistically significant evidence for linkage was found for the opposite phenotype of creative activity in music (neither composing nor arranging; NCNA) at 18q21 (LOD 3.09, 149 cases), which contains cadherin genes like CDH7 and CDH19. The locus at 4q22.1 overlaps the previously identified region of musical aptitude, music perception and performance giving further support for this region as a candidate region for broad range of music-related traits. The other regions at 18q21 and 16p12.1-q12.1 are also adjacent to the previously identified loci with musical aptitude. Pathway analysis of the genes suggestively associated with composing suggested an overrepresentation of the cerebellar long-term depression pathway (LTD), which is a cellular model for synaptic plasticity. The LTD also includes cadherins and AMPA receptors, whose component GSG1L was linked to arranging. These results suggest that molecular pathways linked to memory and learning via LTD affect music-related creative behaviour. Musical creativity is a complex phenotype where a common background with musicality and intelligence has been proposed. Here, we implicate genetic regions affecting music-related creative behaviour, which also include genes with neuropsychiatric associations. We also propose

  3. Genetic Linkage Map Construction and QTL Analysis of Two Interspecific Reproductive Isolation Traits in Sponge Gourd

    Science.gov (United States)

    Wu, Haibin; He, Xiaoli; Gong, Hao; Luo, Shaobo; Li, Mingzhu; Chen, Junqiu; Zhang, Changyuan; Yu, Ting; Huang, Wangping; Luo, Jianning

    2016-01-01

    The hybrids between Luffa acutangula (L.) Roxb. and L.cylindrica (L.) Roem. have strong heterosis effects. However, some reproductive isolation traits hindered their normal hybridization and fructification, which was mainly caused by the flowering time and hybrid pollen sterility. In order to study the genetic basis of two interspecific reproductive isolation traits, we constructed a genetic linkage map using an F2 population derived from a cross between S1174 [L. acutangula (L.) Roxb.] and 93075 [L. cylindrica (L.) Roem.]. The map spans 1436.12 CentiMorgans (cM), with an average of 8.11 cM among markers, and consists of 177 EST-SSR markers distributed in 14 linkage groups (LG) with an average of 102.58 cM per LG. Meanwhile, we conducted colinearity analysis between the sequences of EST-SSR markers and the genomic sequences of cucumber, melon and watermelon. On the basis of genetic linkage map, we conducted QTL mapping of two reproductive isolation traits in sponge gourd, which were the flowering time and hybrid male sterility. Two putative QTLs associated with flowering time (FT) were both detected on LG 1. The accumulated contribution of these two QTLs explained 38.07% of the total phenotypic variance (PV), and each QTL explained 15.36 and 22.71% of the PV respectively. Four QTLs for pollen fertility (PF) were identified on LG 1 (qPF1.1 and qPF1.2), LG 3 (qPF3) and LG 7 (qPF7), respectively. The percentage of PF explained by these QTLs varied from 2.91 to 16.79%, and all together the four QTLs accounted for 39.98% of the total PV. Our newly developed EST-SSR markers and linkage map are very useful for gene mapping, comparative genomics and molecular marker-assisted breeding. These QTLs for interspecific reproductive isolation will also contribute to the cloning of genes relating to interspecific reproductive isolation and the utilization of interspecific heterosis in sponge gourd in further studies. PMID:27458467

  4. Setting up Multiplex Panels for Genetic Testing of Familial Hy¬pertrophic Cardiomyopathy Based on Linkage Analysis

    Directory of Open Access Journals (Sweden)

    Hoorieh SAGHAFI

    2016-03-01

    Full Text Available Background: Familial hypertrophic cardiomyopathy (HCM is caused by mutations in genes encoding cardiac sarcomere proteins. Nowadays genetic testing of HCM plays an important role in clinical practice by contributing to the diagnosis, prognosis, and screening of high-risk individuals. The aim of this study was developing a reliable testing strategy for HCM based on linkage analysis and appropriate for Iranian population.Methods: Six panels of four microsatellite markers surrounding MYH7, MYBPC3, TNNT2, TNNI3, TPM1, and MYL2 genes (24 markers in total were selected for multiplex PCR and fragment length analysis. Characteristics of markers and informativeness of the panels were evaluated in 50 unrelated Iranians. The efficacy of the strategy was verified in a family with HCM.Results: All markers were highly polymorphic. The panels were informative in 96-100% of samples. Multipoint linkage analysis excluded the linkage between the disease and all six genes by obtaining maximum LOD score ≤-2.Conclusion: This study suggests a reliable genetic testing method based on linkage analysis between 6 sarcomere genes and familial HCM. It could be applied for diagnostic, predictive, or screening testing in clinical setting. Keywords: Cardiomyopathy, Hypertrophic, Genetic linkage, Diagnosis 

  5. Fluorescent multiplex linkage analysis and carrier detection for Duchenne/Becker muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, L.S.; Hoffman, E.P. (Univ. of Pittsburgh Schoool of Medicine, Pittsburgh, PA (United States)); Tarleton, J. (Self Memorial Hospital, Greenwood, SC (United States)); Popovich, B. (Children' s Hosptial and Health Center, San Diego, CA (United States)); Seltzer, W.K. (Univ. of Colorado Health Sciences Center, Denver, CO (United States))

    1992-10-01

    The authors have developed a fast and accurate PCR-based linkage and carrier detection protocol for families of Duchenne muscular dystrophy (DMD)/Becker muscular dystrophy (BMD) patients with or without detectable deletions of the dystrophin gene, using fluorescent PCR products analyzed on an automated sequencer. When a deletion is found in the affected male DMD/BMD patient by standard multiplex PCR, fluorescently labeled primers specific for the deleted and nondeleted exon(s) are used to amplify the DNA of at-risk female relatives by using multiplex PCR at low cycle number (20 cycles). The products are then quantitatively analyzed on an automatic sequencer to determine whether they are heterozygous for the deletion and thus are carriers. As a confirmation of the deletion data, and in cases in which a deletion is not found in the proband, fluorescent multiplex PCR linkage is done by using four previously described polymorphic dinucleotide sequences. The four (CA)[sub n] repeats are located throughout the dystrophin gene, making the analysis highly informative and accurate. The authors present the successful application of this protocol in families who proved refractory to more traditional analyses. 22 refs., 3 figs.

  6. Holographic Two-Point Functions in Conformal Gravity

    CERN Document Server

    Ghodsi, Ahmad; Naseh, Ali

    2014-01-01

    In this paper we compute the holographic two-point functions of four dimensional conformal gravity. Precisely we calculate the two-point functions for Energy-Momentum (EM) and Partially Massless Response (PMR) operators that have been identified as two response functions for two independent sources in the dual CFT. The correlation function of EM with PMR tensors turns out to be zero which is expected according to the conformal symmetry. The two-point function of EM is that of a transverse and traceless tensor, and the two-point function of PMR which is a traceless operator contains two distinct parts, one for a transverse-traceless tensor operator and another one for a vector field, both of which fulfill criteria of a CFT. We also discuss about the unitarity of the theory.

  7. Linkage analysis of 19 French breast cancer families, with five chromosome 17q markers.

    OpenAIRE

    Mazoyer, S; Lalle, P.; Narod, S. A.; Bignon, Y J; Courjal, F; Jamot, B.; Dutrillaux, B.; Stoppa-Lyonnett, D; Sobol, H

    1993-01-01

    Nineteen French breast and breast-ovarian cancer families were tested for linkage with five chromosome 17q markers. The five breast-ovarian cancer families as a group give positive evidence for linkage, whereas the 14 breast cancer-only families do not. Heterogeneity of linkage of breast and breast-ovarian cancers is significant in France and supports the existence of more than one susceptibility gene.

  8. Genome-Wide Linkage Analysis Identifies Loci for Physical Appearance Traits in Chickens.

    Science.gov (United States)

    Sun, Yanfa; Liu, Ranran; Zhao, Guiping; Zheng, Maiqing; Sun, Yan; Yu, Xiaoqiong; Li, Peng; Wen, Jie

    2015-08-06

    Physical appearance traits, such as feather-crested head, comb size and type, beard, wattles size, and feathered feet, are used to distinguish between breeds of chicken and also may be associated with economic traits. In this study, a genome-wide linkage analysis was used to identify candidate regions and genes for physical appearance traits and to potentially provide further knowledge of the molecular mechanisms that underlie these traits. The linkage analysis was conducted with an F2 population derived from Beijing-You chickens and a commercial broiler line. Single-nucleotide polymorphisms were analyzed using the Illumina 60K Chicken SNP Beadchip. The data were used to map quantitative trait loci and genes for six physical appearance traits. A 10-cM/0.51-Mb region (0.0-10.0 cM/0.00-0.51 Mb) with 1% genome-wide significant level on LGE22C19W28_E50C23 linkage group (LGE22) for crest trait was identified, which is likely very closely linked to the HOXC8. A QTL with 5% chromosome-wide significant level for comb weight, which partly overlaps with a region identified in a previous study, was identified at 74 cM/25.55 Mb on chicken (Gallus gallus; GG) chromosome 3 (i.e., GGA3). For beard and wattles traits, an identical region 11 cM/2.23 Mb (0.0-11.0 cM/0.00-2.23 Mb) including WNT3 and GH genes on GGA27 was identified. Two QTL with 1% genome-wide significant level for feathered feet trait, one 9-cM/2.80-Mb (48.0-57.0/13.40-16.20 Mb) region on GGA13, and another 12-cM/1.45-Mb (41.0-53.0 cM/11.37-12.82 Mb) region on GGA15 were identified. These candidate regions and genes provide important genetic information for the physical appearance traits in chicken. Copyright © 2015 Sun et al.

  9. A unified test of linkage analysis and rare-variant association for analysis of pedigree sequence data.

    Science.gov (United States)

    Hu, Hao; Roach, Jared C; Coon, Hilary; Guthery, Stephen L; Voelkerding, Karl V; Margraf, Rebecca L; Durtschi, Jacob D; Tavtigian, Sean V; Shankaracharya; Wu, Wilfred; Scheet, Paul; Wang, Shuoguo; Xing, Jinchuan; Glusman, Gustavo; Hubley, Robert; Li, Hong; Garg, Vidu; Moore, Barry; Hood, Leroy; Galas, David J; Srivastava, Deepak; Reese, Martin G; Jorde, Lynn B; Yandell, Mark; Huff, Chad D

    2014-07-01

    High-throughput sequencing of related individuals has become an important tool for studying human disease. However, owing to technical complexity and lack of available tools, most pedigree-based sequencing studies rely on an ad hoc combination of suboptimal analyses. Here we present pedigree-VAAST (pVAAST), a disease-gene identification tool designed for high-throughput sequence data in pedigrees. pVAAST uses a sequence-based model to perform variant and gene-based linkage analysis. Linkage information is then combined with functional prediction and rare variant case-control association information in a unified statistical framework. pVAAST outperformed linkage and rare-variant association tests in simulations and identified disease-causing genes from whole-genome sequence data in three human pedigrees with dominant, recessive and de novo inheritance patterns. The approach is robust to incomplete penetrance and locus heterogeneity and is applicable to a wide variety of genetic traits. pVAAST maintains high power across studies of monogenic, high-penetrance phenotypes in a single pedigree to highly polygenic, common phenotypes involving hundreds of pedigrees.

  10. Genetic linkage map and comparative genome analysis for the estuarine Atlantic killifish (Fundulus heteroclitus)

    Data.gov (United States)

    U.S. Environmental Protection Agency — Genetic linkage maps are valuable tools in evolutionary biology; however, their availability for wild populations is extremely limited. Fundulus heteroclitus...

  11. Late onset autosomal dominant cerebellar ataxia a family description and linkage analysis with the hla system

    Directory of Open Access Journals (Sweden)

    Walter O. Arruda

    1991-09-01

    Full Text Available A family suffering an autosomal dominant form of late onset hereditary cerebellar ataxia is described. Eight affected family members were personally studied, and data from another four were obtained through anamnesis. The mean age of onset was 37.1±5.4 years (27-47 years. The clinical picture consisted basically of a pure ataxic cerebellar syndrome. CT-scan disclosed diffuse cerebellar atrophy with relative sparing of the brainstem (and no involvement of supratentorial structures. Neurophysiological studies (nerve conduction, VEP and BAEP were normal. Twenty-six individuals were typed for HLA histocompatibility antigens. Lod scores were calculated with the computer program LINKMAP. Close linkage of the ataxia gene with the HLA system in this family could be excluded - 0==0,02, z=(-2,17 - and the overall analysis of the lod scores suggest another chromossomal location than chromosome 6.

  12. Linkage Analysis of Genomic Regions Contributing to the Expression of Type 1 Diabetes Microvascular Complications and Interaction with HLA

    Directory of Open Access Journals (Sweden)

    Ettie M. Lipner

    2015-01-01

    Full Text Available We conducted linkage analysis to follow up earlier work on microvascular complications of type 1 diabetes (T1D. We analyzed 415 families (2,008 individuals previously genotyped for 402 SNP markers spanning chromosome 6. We did linkage analysis for the phenotypes of retinopathy and nephropathy. For retinopathy, two linkage peaks were mapped: one located at the HLA region and another novel locus telomeric to HLA. For nephropathy, a linkage peak centromeric to HLA was mapped, but the linkage peak telomeric to HLA seen in retinopathy was absent. Because of the strong association of T1D with DRB1*03:01 and DRB1*04:01, we stratified our analyses based on families whose probands were positive for DRB1*03:01 or DRB1*04:01. When analyzing the DRB1*03:01-positive retinopathy families, in addition to the novel telomeric locus, one centromeric to HLA was identified at the same location as the nephropathy peak. When we stratified on DRB1*04:01-positive families, the HLA telomeric peak strengthened but the centromeric peak disappeared. Our findings showed that HLA and non-HLA loci on chromosome 6 are involved in T1D complications’ expression. While the HLA region is a major contributor to the expression of T1D, our results suggest an interaction between specific HLA alleles and other loci that influence complications’ expression.

  13. Computational complexity for the two-point block method

    Science.gov (United States)

    See, Phang Pei; Majid, Zanariah Abdul

    2014-12-01

    In this paper, we discussed and compared the computational complexity for two-point block method and one-point method of Adams type. The computational complexity for both methods is determined based on the number of arithmetic operations performed and expressed in O(n). These two methods will be used to solve two-point second order boundary value problem directly and implemented using variable step size strategy adapted with the multiple shooting technique via three-step iterative method. Two numerical examples will be tested. The results show that the computational complexity of these methods is reliable to estimate the cost of these methods in term of the execution time. We conclude that the two-point block method has better computational performance compare to the one-point method as the total number of steps is larger.

  14. Polymorphism analysis of microsatellites and construction of linkage map in part regions of four chromosomes in chicken

    Institute of Scientific and Technical Information of China (English)

    WANG Shouzhi; LI Hui; LI Ning; GAO Yu; DU Zhiqiang; GU Zhiliang; WANG Qigui; LI Zhihui; WANG Ying

    2007-01-01

    Based on chicken' consensus map issued in 2000, 17 microsatellites near 4 candidate genes such as IGF2, OBR, GDFS and APOA1 in 4 chromosomes (chromosome 5, 7, 8 and 24) were chosen for polymorphism analysis and construction of linkage map. Combining the technique of PCR and the fluorescent semi-automated detection, genome scanning was performed for 440 chickens, which was derived from China Agricultural University chicken resource families within three generations. The individuals of this resource families were genotyped. The results showed that the number of alleles ranged from 4 to 14; heterozygosity (H) of markers was between 0.3116 and 0.9148. Polymorphic information content (PIC) varied from 0.2672 to 0.8679. Microsatellites along with above-mentioned 4 candidate genes doing as general markers were used to construct linkage map. The spans of 4 linkage maps constructed in the part region of chromosome 5, 7, 8 and 24 were 263.5, 79.9, 206.2 and 104.2 cM, respectively. The order of markers was consistent with that of counterpart of reported consensus map. However, The spans of linkage map were larger than that of consensus map. The constructed linkage maps laid the foundation for mapping quantitative trait loci (QTL) responsible for economically important traits in chicken.

  15. Meta-analysis of genome-wide linkage scans of attention deficit hyperactivity disorder

    NARCIS (Netherlands)

    Zhou, Kaixin; Dempfle, Astrid; Arcos-Burgos, Mauricio; Bakker, Steven C; Banaschewski, Tobias; Biederman, Joseph; Buitelaar, Jan; Castellanos, F Xavier; Doyle, Alysa; Ebstein, Richard P; Ekholm, Jenny; Forabosco, Paola; Franke, Barbara; Freitag, Christine; Friedel, Susann; Gill, Michael; Hebebrand, Johannes; Hinney, Anke; Jacob, Christian; Lesch, Klaus Peter; Loo, Sandra K; Lopera, Francisco; McCracken, James T; McGough, James J; Meyer, Jobst; Mick, Eric; Miranda, Ana; Muenke, Maximilian; Mulas, Fernando; Nelson, Stanley F; Nguyen, T Trang; Oades, Robert D; Ogdie, Matthew N; Palacio, Juan David; Pineda, David; Reif, Andreas; Renner, Tobias J; Roeyers, Herbert; Romanos, Marcel; Rothenberger, Aribert; Schäfer, Helmut; Sergeant, Joseph; Sinke, Richard J; Smalley, Susan L; Sonuga-Barke, Edmund; Steinhausen, Hans-Christoph; van der Meulen, Emma; Walitza, Susanne; Warnke, Andreas; Lewis, Cathryn M; Faraone, Stephen V; Asherson, Philip

    2008-01-01

    Genetic contribution to the development of attention deficit hyperactivity disorder (ADHD) is well established. Seven independent genome-wide linkage scans have been performed to map loci that increase the risk for ADHD. Although significant linkage signals were identified in some of the studies, th

  16. Joint linkage and association analysis with exome sequence data implicates SLC25A40 in hypertriglyceridemia.

    Science.gov (United States)

    Rosenthal, Elisabeth A; Ranchalis, Jane; Crosslin, David R; Burt, Amber; Brunzell, John D; Motulsky, Arno G; Nickerson, Deborah A; Wijsman, Ellen M; Jarvik, Gail P

    2013-12-01

    Hypertriglyceridemia (HTG) is a heritable risk factor for cardiovascular disease. Investigating the genetics of HTG may identify new drug targets. There are ~35 known single-nucleotide variants (SNVs) that explain only ~10% of variation in triglyceride (TG) level. Because of the genetic heterogeneity of HTG, a family study design is optimal for identification of rare genetic variants with large effect size because the same mutation can be observed in many relatives and cosegregation with TG can be tested. We considered HTG in a five-generation family of European American descent (n = 121), ascertained for familial combined hyperlipidemia. By using Bayesian Markov chain Monte Carlo joint oligogenic linkage and association analysis, we detected linkage to chromosomes 7 and 17. Whole-exome sequence data revealed shared, highly conserved, private missense SNVs in both SLC25A40 on chr7 and PLD2 on chr17. Jointly, these SNVs explained 49% of the genetic variance in TG; however, only the SLC25A40 SNV was significantly associated with TG (p = 0.0001). This SNV, c.374A>G, causes a highly disruptive p.Tyr125Cys substitution just outside the second helical transmembrane region of the SLC25A40 inner mitochondrial membrane transport protein. Whole-gene testing in subjects from the Exome Sequencing Project confirmed the association between TG and SLC25A40 rare, highly conserved, coding variants (p = 0.03). These results suggest a previously undescribed pathway for HTG and illustrate the power of large pedigrees in the search for rare, causal variants.

  17. Detection of Duchenne/Becker Muscular Dystrophy Carriers in a Group of Iranian Families by Linkage Analysis

    Directory of Open Access Journals (Sweden)

    Fardeen Ali Malayeri

    2011-03-01

    Full Text Available This study determines the value of linkage analysis using six RFLP markers for carrier detection and prenatal diagnosis in familial DMD/BMD cases and their family members for the first time in the Iranian population. We studied the dystrophin gene in 33 unrelated patients with clinical diagnosis of DMD or BMD. Subsequently, we determined the rate of heterozygosity for six intragenic RFLP markers in the mothers of patients with dystrophin gene deletions. Finally, we studied the efficiency of linkage analysis by using RFLP markers for carrier status detection of DMD/BMD. In 63.6% of the patients we found one or more deletions. The most common heterozygous RFLP marker with 57.1% heterozygosity was pERT87.15Taq1. More than 80% of mothers in two groups of familial or non-familial cases had at least two heterozygous markers. Family linkage analysis was informative in more than 80% of the cases, allowing for accurate carrier detection. We found that linkage analysis using these six RFLP markers for carrier detection and prenatal diagnosis is a rapid, easy, reliable, and inexpensive method, suitable for most routine diagnostic services. The heterozygosity frequency of these markers is high enough in the Iranian population to allow carrier detection and prenatal diagnosis of DMD/BMD in more than 80% of familial cases in Iran.

  18. Construction of high-quality recombination maps with low-coverage genomic sequencing for joint linkage analysis in maize

    Science.gov (United States)

    A genome-wide association study (GWAS) is the foremost strategy used for finding genes that control human diseases and agriculturally important traits, but it often reports false positives. In contrast, its complementary method, linkage analysis, provides direct genetic confirmation, but with limite...

  19. Two-point functions on deformed space-time

    CERN Document Server

    Trampetic, Josip

    2014-01-01

    We present a review of one-loop photon (\\Pi) and neutrino (\\Sigma) two-point functions in a covariant and deformed U(1) gauge-theory on d-dimensional noncommutative spaces, determined by a constant antisymmetric tensor \\theta, and by a parameter-space (\\kappa_f,\\kappa_g), respectively. For the general fermion-photon S_f(\\kappa_f) and photon self-interaction S_g(\\kappa_g) the closed form results reveal two-point functions with all kind of pathological terms: the UV divergence, the quadratic UV/IR mixing terms as well as a logarithmic IR divergent term of the type ln(\\mu^2(\\theta p)^2). In addition, the photon-loop produces new tensor structures satisfying transversality condition by themselves. We show that the photon two-point function in four-dimensional Euclidean spacetime can be reduced to two finite terms by imposing a specific full rank of \\theta and setting deformation parameters (\\kappa_f,\\kappa_g)=(0,3). In this case the neutrino two-point function vanishes. Thus for a specific point (0,3) in the para...

  20. Similarity of solution branches for two-point semilinear problems

    Directory of Open Access Journals (Sweden)

    Philip Korman

    2003-02-01

    Full Text Available For semilinear autonomous two-point problems, we show that all Neumann branches and all Dirichlet branches with odd number of interior roots have the same shape. On the other hand, Dirichlet branches with even number of roots may look differently. While this result has been proved previously by Schaaf cite{S}, our approach appears to be simpler.

  1. Localization, by linkage analysis, of the cystinuria type III gene to chromosome 19q13.1

    Energy Technology Data Exchange (ETDEWEB)

    Bisceglia, L.; Totaro, A.; Melchionda, S. [and others

    1997-03-01

    Cystinuria is an autosomal recessive aminoaciduria in which three urinary phenotypes (I, II, and III) have been described. An amino acid transporter gene, SLC3A1 (formerly rBAT), was found to be responsible for this disorder. Mutational and linkage analysis demonstrated the presence of genetic heterogeneity in which the SLC3A1 gene is responsible for type I cystinuria but not for type II or type III. In this study, we report the identification of the cystinuria type III locus on the long arm of chromosome 19 (19q13.1), obtained after a genomewide search. Pairwise linkage analysis in a series of type III or type II families previously excluded from linkage to the cystinuria type I locus (SLC3A1 gene) revealed a significant maximum LOD score (Z{sub max}) of 13.11 at a maximum recombination fraction ({theta}{sub max}) of .00, with marker D19S225. Multipoint linkage analysis performed with the use of additional markers from the region placed the cystinuria type III locus between D19S414 and D19S220. Preliminary data on type II families also seem to place the disease locus for this rare type of cystinuria at 19q13.1 (significant Z{sub max} = 3.11 at {theta}{sub max} of .00, with marker D19S225). 33 refs., 2 figs., 1 tab.

  2. Analysis of stock market linkages: evidence from the selected CEE markets

    Directory of Open Access Journals (Sweden)

    Michaela Chocholatá

    2013-04-01

    Full Text Available This paper analyses the stock market linkages of the selected Central and Eastern European (CEE markets (Czech Republic – PX, Hungary – BUX and Poland – WIG20 with the Western European stock market represented by the German DAX and studies also the co-movement between the individual CEE countries’ stock markets. The dynamic conditional correlation (DCC models were used to model the co-movements and thereafter in some cases the smooth transition analysis was carried out in order to capture how these correla-tions evolve over time. The analysis was based on weekly data over the sample period Jan-uary 3rd, 1997 – November 29th, 2013 (883 observations. In the first step the asymmetric univariate autoregressive conditional heteroscedasticity model of Glosten, Jagannathan and Runkle (GJR was estimated for individual stock return series. The results of the DCC-GJR models estimated in the next step show almost in all analysed cases the increasing lev-el of conditional correlations. In four cases (BUX_DAX, WIG20_DAX, BUX_PX and PX_WIG20 the DCC series were identified to be nonstationary – I(1 and nonlinear lo-gistic smooth transition regression (LSTR model was used to capture the gradual transi-tion towards greater co-movements and to find out if the increasing level of DCC could be attributed to the accession of these countries into the European Union (EU in May 2004.

  3. Subsidiary Linkage Patterns

    DEFF Research Database (Denmark)

    Perri, Alessandra; Andersson, Ulf; Nell, Phillip C.;

    This paper investigates local vertical linkages of foreign subsidiaries and the dual role of such linkages as conduits for learning as well as potential channels for spillovers to competitors. On the basis of data from 97 subsidiaries, we analyze the quality of such linkages under varying levels...... of competition and subsidiary capabilities. Our theoretical development and the results from the analysis document a far more complex and dynamic relationship between levels of competition and MNCs’ local participation in knowledge intensive activities, i.e. learning and spillovers, than previous studies do. We...

  4. Within-family outliers: segregating alleles or environmental effects? A linkage analysis of height from 5815 sibling pairs.

    Science.gov (United States)

    Benyamin, Beben; Perola, Markus; Cornes, Belinda K; Madden, Pamela Af; Palotie, Aarno; Nyholt, Dale R; Montgomery, Grant W; Peltonen, Leena; Martin, Nicholas G; Visscher, Peter M

    2008-04-01

    Most information in linkage analysis for quantitative traits comes from pairs of relatives that are phenotypically most discordant or concordant. Confounding this, within-family outliers from non-genetic causes may create false positives and negatives. We investigated the influence of within-family outliers empirically, using one of the largest genome-wide linkage scans for height. The subjects were drawn from Australian twin cohorts consisting of 8447 individuals in 2861 families, providing a total of 5815 possible pairs of siblings in sibships. A variance component linkage analysis was performed, either including or excluding the within-family outliers. Using the entire dataset, the largest LOD scores were on chromosome 15q (LOD 2.3) and 11q (1.5). Excluding within-family outliers increased the LOD score for most regions, but the LOD score on chromosome 15 decreased from 2.3 to 1.2, suggesting that the outliers may create false negatives and false positives, although rare alleles of large effect may also be an explanation. Several regions suggestive of linkage to height were found after removing the outliers, including 1q23.1 (2.0), 3q22.1 (1.9) and 5q32 (2.3). We conclude that the investigation of the effect of within-family outliers, which is usually neglected, should be a standard quality control measure in linkage analysis for complex traits and may reduce the noise for the search of common variants of modest effect size as well as help identify rare variants of large effect and clinical significance. We suggest that the effect of within-family outliers deserves further investigation via theoretical and simulation studies.

  5. Linkage analysis and physical mapping near the gene for x-linked agammaglobulinemia at Xq22

    Energy Technology Data Exchange (ETDEWEB)

    Parolini, O.; Lassiter, G.L.; Henry, M.J.; Conley, M.E. (Univ. of Tennessee College of Medicine, Memphis (United States) St. Jude Children' s Research Hospital, Memphis, TN (United States)); Hejtmancik, J.F. (National Inst. of Health, Bethesda, MD (United States)); Allen, R.C.; Belmont, J.W. (Baylor College of Medicine, Houston, TX (United States)); Barker, D.F. (Univ. of Utah, Salt Lake City (United States))

    1993-02-01

    The gene for x-linked agammaglobulinemia (XLA) has been mapped to Xq22. No recombinations have been reported between the gene and the prob p212 at DXS178; however, this probe is informative in only 30-40% of women and the reported flanking markers, DXS3 and DXS94, and 10-15 cM apart. To identify additional probes that might be useful in genetic counseling, we examined 11 polymorphisms that have been mapped to the Xq21.3-q22 region in 13 families with XLA. In addition, pulsed-field gel electrophoresis and yeast artificial chromosomes (YACs) were used to further characterize the segman of DNA within which the gene for SLA must lie. The results demonstrated that DXS366 and DXS442, which share a 430-kb pulsed-field fragment, could replace DXS3 as proximal flanking markers. Probes at DXS178 and DXS265 identified the same 145-kb pulsed-field fragment, and both loci were contained within a 200-kb YAC identified with the probe p212. A highly polymorphic CA repeat (DCS178CA) was isolated from one end of this YAC and used in linkage analysis. Probes at DXS101 and DXS328 shared several pulsed-field fragments, the smallest of which was 250 kb. No recombinations were seen between XLA and the DXS178-DXS265-DXS178CA complex, DXS101, DXS328, DXS87, or the gene for proteolipid protein (PLP). Key crossovers, when combined with the linkage data from families with Alport syndrome, suggested the following order of loci: cen-DXS3-DXS366-DXS442-(PLP, DXS101, DXS328, DXS178-DXS265-DXS178CA complex, XL)-(DXS87, DXS94)-DXS327-(DXS350, DXS362)-tel. Our studies also limit the segment of DNA within which the XLA gene must lie to the 3- to 4-cM distance between DCS442 and DXS94 and they identify and orient polymorphisms that can be used in genetic counseling not only for XLA but also for Pelizaeus-Merzbacher disease (PLP deficiency), Alport syndrome (COL4A5 deficiency), and Fabry disease ([alpha]-galactosidase A difficiency). 31 refs., 5 figs., 2 tabs.

  6. Mistakes and Pitfalls Associated with Two-Point Compression Ultrasound for Deep Vein Thrombosis

    Directory of Open Access Journals (Sweden)

    Tony Zitek, MD

    2016-03-01

    Full Text Available Introduction: Two-point compression ultrasound is purportedly a simple and accurate means to diagnose proximal lower extremity deep vein thrombosis (DVT, but the pitfalls of this technique have not been fully elucidated. The objective of this study is to determine the accuracy of emergency medicine resident-performed two-point compression ultrasound, and to determine what technical errors are commonly made by novice ultrasonographers using this technique. Methods: This was a prospective diagnostic test assessment of a convenience sample of adult emergency department (ED patients suspected of having a lower extremity DVT. After brief training on the technique, residents performed two-point compression ultrasounds on enrolled patients. Subsequently a radiology department ultrasound was performed and used as the gold standard. Residents were instructed to save videos of their ultrasounds for technical analysis. Results: Overall, 288 two-point compression ultrasound studies were performed. There were 28 cases that were deemed to be positive for DVT by radiology ultrasound. Among these 28, 16 were identified by the residents with two-point compression. Among the 260 cases deemed to be negative for DVT by radiology ultrasound, 10 were thought to be positive by the residents using two-point compression. This led to a sensitivity of 57.1% (95% CI [38.8-75.5] and a specificity of 96.1% (95% CI [93.8-98.5] for resident-performed two-point compression ultrasound. This corresponds to a positive predictive value of 61.5% (95% CI [42.8-80.2] and a negative predictive value of 95.4% (95% CI [92.9-98.0]. The positive likelihood ratio is 14.9 (95% CI [7.5-29.5] and the negative likelihood ratio is 0.45 (95% CI [0.29-0.68]. Video analysis revealed that in four cases the resident did not identify a DVT because the thrombus was isolated to the superior femoral vein (SFV, which is not evaluated by two-point compression. Moreover, the video analysis revealed that the

  7. Molecular investigation of mental retardation locus gene PRSS12 by linkage analysis

    Directory of Open Access Journals (Sweden)

    Zafar Ali

    2011-01-01

    Full Text Available The present study was carried out to determine the prevalence of families having mental retardation in Pakistani population. We enrolled seven mentally retarded (MR families with two or more affected individuals. Family history was taken to minimize the chances of other abnormalities. Pedigrees were drawn using the Cyrillic software (version 2.1. The structure of pedigrees shows that all the marriages are consanguineous and the families have recessive mode of inheritance. All the families were studied by linkage analysis to mental retardation locus (MRT1/gene PRSS12. Three STR markers (D4S191, D4S2392, and D4S3024 in vicinity of mental retardation (MR locus (MRT1/gene PRSS12 were amplified on all the sample of each family by PCR. The PCR products were then genotyped on non denaturing polyacrylamide gel electrophoresis (PAGE. The Haplotype were constructed to determine the pattern of inheritance and also to determine that a family was linked or unlinked to gene PRSS12. One out of the seven families was potentially linked to gene PRSS12, while the other six families remain unlinked.

  8. Haplotype and linkage disequilibrium analysis of the CRMP1 and EVC genes.

    Science.gov (United States)

    Sivakumaran, Theru A; Lesperance, Marci M

    2004-11-01

    In this report, we present the haplotype and linkage disequilibrium (LD) pattern in the Collapsin Response Mediator Protein 1 (CRMP1) and Ellis-van Creveld syndrome (EVC) gene region. We genotyped eight different single nucleotide polymorphisms (SNPs) in the CRMP1 and EVC genes in 90 control individuals of diverse ethnicity. The minor allele frequencies ranged from 3.3-49.4%, with most having a frequency >25%. A total of 37 haplotypes were derived from these eight polymorphisms, with only one haplotype having a frequency >10%. Pairwise LD analysis showed a weak but significant LD between markers located about 243 kb apart in this region. The LD was significant between markers spaced about 208 kb apart in EVC, whereas no LD was found between a pair of markers located about 5 kb apart in CRMP1. However, in general, LD correlated with the distance between loci. The CRMP1 and EVC genes are located near WFS1, the Wolfram syndrome type 1 gene, in which mutations also cause low frequency sensorineural hearing loss (LFSNHL). The haplotypes obtained from these polymorphisms will be useful to track the segregation of phenotypes in families with Ellis-van Creveld syndrome, Weyers acrodental dysostosis, LFSNHL and Wolfram syndrome type 1.

  9. Cross border hospital use: analysis using data linkage across four Australian states.

    Science.gov (United States)

    Spilsbury, Katrina; Rosman, Diana; Alan, Janine; Boyd, James H; Ferrante, Anna M; Semmens, James B

    2015-06-15

    To determine the quality and effectiveness of national data linkage capacity by performing a proof-of-concept project investigating cross-border hospital use and hospital-related deaths. Analysis of person-level linked hospital separation and death registration data of all public and private hospital patients in New South Wales, Queensland and Western Australia and of public hospital patients in South Australia, totalling 7.7 million hospital patients from 1 July 2004 to 30 June 2009. Counts and proportions of hospital stays and patient movement patterns. 223 262 patients (3.0%) travelled across a state border to attend hospitals, in particular, far northern and western NSW patients travelling to Queensland and SA hospitals, respectively. A further 48 575 patients (0.6%) moved their place of residence interstate between hospital visits, particularly to and from areas associated with major mining and tourism industries. Over 11 000 cross-border hospital transfers were also identified. Of patients who travelled across a state border to hospital, 2800 (1.3%) died in that hospital. An additional 496 deaths recorded in one jurisdiction occurred within 30 days of hospital separation from another jurisdiction. Access to person-level data linked across jurisdictions identified geographical hot spots of cross-border hospital use and hospital-related deaths in Australia. This has implications for planning of health service delivery and for longitudinal follow-up studies, particularly those involving mobile populations.

  10. Genome-wide linkage analysis of inguinal hernia in pigs using affected sib pairs

    Directory of Open Access Journals (Sweden)

    Taubert Helge

    2006-05-01

    Full Text Available Abstract Background Inguinal and scrotal hernias are of great concern to pig producers, and lead to poor animal welfare and severe economic loss. Selection against these conditions is highly preferable, but at this time no gene, Quantitative Trait Loci (QTL, or mode of inheritance has been identified in pigs or in any other species. Therefore, a complete genome scan was performed in order to identify genomic regions affecting inguinal and scrotal hernias in pigs. Records from seedstock breeding farms were collected. No clinical examinations were executed on the pigs and there was therefore no distinction between inguinal and scrotal hernias. The genome scan utilised affected sib pairs (ASP, and the data was analysed using both an ASP test based on Non-parametric Linkage (NPL analysis, and a Transmission Disequilibrium Test (TDT. Results Significant QTLs (p Conclusion For the first time in any species, a genome scan has revealed suggestive QTLs for inguinal and scrotal hernias. While this study permitted the detection of chromosomal regions only, it is interesting to note that several promising candidate genes, including INSL3, MIS, and CGRP, are located within the highly significant QTL regions. Further studies are required in order to narrow down the suggestive QTL regions, investigate the candidate genes, and to confirm the suggestive QTLs in other populations. The haplotype associated with inguinal and scrotal hernias may help in achieving selection against the disorder.

  11. Polymorphisms and linkage analysis for ICAM-1 and the selectin gene cluster

    Energy Technology Data Exchange (ETDEWEB)

    Vora, D.K.; Rosenbloom, C.L.; Cottingham, R.W. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1994-06-01

    Genetic polymorphisms in leukocyte and endothelial cell adhesion molecules may be important variables with regard to susceptibility to multifactorial disease processes that include an inflammatory component. For this reason, polymorphisms were sought for intercellular adhesion molecule-1 (ICAM-1; gene symbol ICAM1) and for the three genes in the selectin cluster, P-selectin, L-selectin, and E-selectin (gene symbols SELP, SELL, and SELE, respectively). Two amino acid polymorphisms were identified for ICAM-1; Gly or Arg at codon 241 and Lys or Glu at codon 469. Dinucleotide repeat polymorphisms were identified in the 3{prime}-untranslated region for ICAM-1 and in intron 9 for P-selectin. Restriction fragment length polymorphisms were found using cDNAs for each of the three selectin genes as probes; E-selectin with BglII, P-selectin with ScaI, and L-selectin with HincII. Linkage analysis was performed for the selectin gene cluster and for ICAM-1 using the CEPH families; ICAM-1 is very tightly linked to the LDL receptor on chromosome 19, and the selectin cluster is linked to markers at chromosome 1q23. 41 refs., 2 tabs.

  12. Total Ossiculoplasty: Advantages of Two-Point Stabilization Technique

    Directory of Open Access Journals (Sweden)

    Leonard Berenholz

    2012-01-01

    Full Text Available Objective. Evaluate a porous polyethylene prosthesis with two-point stabilization in total ossiculoplasty. This approach utilizes a lateral as well as a medial graft to stabilize a total ossicular prosthesis (TOP. Study Design. Retrospective cohort review of total ossiculoplasty. Methods. All patients who underwent total ossiculoplasty during the years 2004–2007 were included in the study group. Only five patients (10% had primary surgery whereas 45 (90% underwent revision surgery. Cartilage grafts covering the prosthesis (Sheehy, Xomed laterally were used in all patients with areolar tissue being used for medial stabilization at the stapes footplate. Follow-up examination and audiometrics were performed a mean of 8.1 months following surgery. Results. The percentage of patients closing their ABG to within 10 dB was 44% with 66% closing their ABG to within 20 dB. The mean four-frequency hearing gain was 15.7 dB. The mean postoperative ABG was 15.7 dB. Conclusion. Audiometric results following total ossiculoplasty surgery using two-point stabilization exceeded results from the otologic literature. Proper two-point fixation with areolar tissue and stabilization utilizing cartilage were the keys to achieving a relatively high percentage of success in chronic ear disease in this sample.

  13. Linkage between stature and a region on chromosome 20 and analysis of a candidate gene, bone morphogenetic protein 2

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, D.B.; Ossowski, V.; Janssen, R.C.; Knowler, W.C.; Bogardus, C. [National Inst. of Health, Phoenix, AZ (United States)

    1995-12-04

    Sib-pair linkage analysis of the quantitative trait, stature, in over 500 Pima Indians indicates that a genetic determinant of governing stature is located on chromosome 20. Analysis of 10 short tandem repeat polymorphisms localized this linkage to a 3. cM region that includes D20S98 and D20S66. Using all possible sib-pair combinations, linkage was detected to both stature (P = 0.0001) and to leg length (P = 0.001), but not to sitting height. Single-strand conformational polymorphism analysis of exon 3 of the bone morphogenetic protein 2 (BMP2) gene, a candidate gene in this region, in genomic DNA of 20 of the tallest and 20 of the shortest individuals did not show any consistent differences associated with leg length or height. Sequence analysis of the region encoding the mature protein revealed a single nucleotide substitution, a T to G transversion, not detected by single-strand conformational polymorphism (SSCP) analysis. This transversion results in a conservative amino acid substitution of glycine for valine at codon 80 of BMP2. The frequency of this allele was 0.23 in the sample. No significant differences in height were noted in persons carrying either allele. This indicates that this structural alteration in the mature BMP2 protein does not contribute to the differences in stature observed in the Pima Indians, nor is this structural change in the mature protein likely to be responsible for the linkage observed with stature on chromosome 20. 33 refs., 2 figs., 2 tabs.

  14. A Computationally Efficient Approach for Calculating Galaxy Two-Point Correlations

    CERN Document Server

    Demina, Regina; BenZvi, Segev; Hindrichs, Otto

    2016-01-01

    We develop a modification to the calculation of the two-point correlation function commonly used in the analysis of large scale structure in cosmology. An estimator of the two-point correlation function is constructed by contrasting the observed distribution of galaxies with that of a uniformly populated random catalog. Using the assumption that the distribution of random galaxies in redshift is independent of angular position allows us to replace pairwise combinatorics with fast integration over probability maps. The new method significantly reduces the computation time while simultaneously increasing the precision of the calculation.

  15. Genome-wide linkage meta-analysis identifies susceptibility loci at 2q34 and 13q31.3 for genetic generalized epilepsies

    DEFF Research Database (Denmark)

    Leu, Costin; de Kovel, Carolien G F; Zara, Federico

    2012-01-01

    Purpose: Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3% with heritability estimates of 80%. A considerable proportion of families with siblings affected by GGEs presumably display an oligogenic inheritance. The present genome-wide linkage meta-analysis aimed to map: (1...... ancestry including 982 relatives with GGEs. To dissect out seizure type-related susceptibility genes, two family subgroups were stratified comprising 235 families with predominantly genetic absence epilepsies (GAEs) and 118 families with an aggregation of juvenile myoclonic epilepsy (JME). To map shared...... Findings: For the entire set of 379 GGE-multiplex families, linkage analysis revealed six loci achieving suggestive evidence for linkage at 1p36.22, 3p14.2, 5q34, 13q12.12, 13q31.3, and 19q13.42. The linkage finding at 5q34 was consistently supported by both NPL and parametric linkage results across all...

  16. Molecular analysis and test of linkage between the FMR-I gene and infantile autism in multiplex families

    Energy Technology Data Exchange (ETDEWEB)

    Hallmayer, J.; Pintado, E.; Lotspeich, L.; Spiker, D.; Kraemer, H.C.; Lee Wong, D.; Lin, A.; Herbert, J.; Cavalli-Sforza, L.L.; Ciaranello, R.D. [Stanford Univ., CA (United States)] [and others

    1994-11-01

    Approximately 2%-5% of autistic children show cytogenetic evidence of the fragile X syndrome. This report tests whether infantile autism in multiplex autism families arises from an unusual manifestion of the fragile X syndrome. This could arise either by expansion of the (CGG)n trinucleotide repeat in FMR-1 or from a mutation elsewhere in the gene. We studied 35 families that met stringent criteria for multiplex autism. Amplification of the trinucleotide repeat and analysis of methylation status were performed in 79 autistic children and in 31 of their unaffected siblings by Southern blot analysis. No examples of amplified repeats were seen in the autistic or control children or in their parents or grandparents. We next examined the hypothesis that there was a mutation elsewhere in the FMR-1 gene, by linkage analysis in 32 of these families. We tested four different dominant models and a recessive model. Linkage to FMR-1 could be excluded (lod score between -24 and -62) in all models by using probes DXS548, FRAXAC1, and FRAXAC2 and the CGG repeat itself. Tests for heterogeneity in this sample were negative, and the occurrence of positive lod scores in this data set could be attributed to chance. Analysis of the data by the affected-sib method also did not show evidence for linkage of any marker to autism. These results enable us to reject the hypothesis that multiplex autism arises from expansion of the (CGG)n trinucleotide repeat in FMR-1. Further, because the overall lod scores for all probes in all models tested were highly negative, linkage to FMR-1 can also be ruled out in multiplex autistic families. 35 refs., 2 figs., 5 tabs.

  17. Theory of resistor networks: the two-point resistance

    Energy Technology Data Exchange (ETDEWEB)

    Wu, F Y [Department of Physics, Northeastern University Boston, MA 02115 (United States)

    2004-07-02

    The resistance between two arbitrary nodes in a resistor network is obtained in terms of the eigenvalues and eigenfunctions of the Laplacian matrix associated with the network. Explicit formulae for two-point resistances are deduced for regular lattices in one, two and three dimensions under various boundary conditions including that of a Moebius strip and a Klein bottle. The emphasis is on lattices of finite sizes. We also deduce summation and product identities which can be used to analyse large-size expansions in two and higher dimensions.

  18. Candidate region linkage analysis in twins discordant or concordant for depression symptomatology

    DEFF Research Database (Denmark)

    Christiansen, Lene; Tan, Q; Kruse, T A

    2009-01-01

    Genetic risk factors contribute considerably to both clinical affective disorders and subsyndromal mood level. There is moreover evidence to suggest that the genetic basis of bipolar disorder and unipolar depression overlap to some extent, and several linkage analyses have suggested evidence...... for a common susceptibility locus in affective disorders on chromosome 12q24. In this study we investigated the chromosome 12 candidate region for linkage to the mean level of depression symptomatology, over a 10-year follow-up, using a highly informative sample of concordant and discordant twin pairs selected...

  19. Linkage analyses in type I diabetes mellitus using CASPAR, a software and statistical program for conditional analysis of polygenic diseases.

    Science.gov (United States)

    Buhler, J; Owerbach, D; Schäffer, A A; Kimmel, M; Gabbay, K H

    1997-01-01

    We have developed software and statistical tools for linkage analysis of polygenic diseases. We use type I diabetes mellitus (insulin-dependent diabetes mellitus, IDDM) as our model system. Two susceptibility loci (IDDM1 on 6p21 and IDDM2 on 11p15) are well established, and recent genome searches suggest the existence of other susceptibility loci. We have implemented CASPAR, a software tool that makes it possible to test for linkage quickly and efficiently using multiple polymorphic DNA markers simultaneously in nuclear families consisting of two unaffected parents and a pair of affected siblings (ASP). We use a simulation-based method to determine whether lod scores from a collection of ASP tests are significant. We test our new software and statistical tools to assess linkage of IDDM5 and IDDM7 conditioned on analyses with 1 or 2 other unlinked type I diabetes susceptibility loci. The results from the CASPAR analysis suggest that conditioning of IDDM5 on IDDM1 and IDDM4, and of IDDM7 on IDDM1 and IDDM2 provides significant benefits for the genetic analysis of polygenic loci.

  20. Two-point correlation functions in inhomogeneous and anisotropic cosmologies

    Science.gov (United States)

    Marcori, Oton H.; Pereira, Thiago S.

    2017-02-01

    Two-point correlation functions are ubiquitous tools of modern cosmology, appearing in disparate topics ranging from cosmological inflation to late-time astrophysics. When the background spacetime is maximally symmetric, invariance arguments can be used to fix the functional dependence of this function as the invariant distance between any two points. In this paper we introduce a novel formalism which fixes this functional dependence directly from the isometries of the background metric, thus allowing one to quickly assess the overall features of Gaussian correlators without resorting to the full machinery of perturbation theory. As an application we construct the CMB temperature correlation function in one inhomogeneous (namely, an off-center LTB model) and two spatially flat and anisotropic (Bianchi) universes, and derive their covariance matrices in the limit of almost Friedmannian symmetry. We show how the method can be extended to arbitrary N-point correlation functions and illustrate its use by constructing three-point correlation functions in some simple geometries.

  1. Genetic Linkage Analysis of the Natural Colored Fiber and Fuzzless Traits in Cotton

    Institute of Scientific and Technical Information of China (English)

    LI Fu-zhen; QIU Xin-mian; WANG Ju-qin; LU Yan-tin; BAO Li-sheng

    2008-01-01

    @@ Genetic linkage relationship of the natural colored fiber and six fuzzless seed germplasms in obsolete backgrounds of Gossypium hirsutum (AD genome) and G.barbadense were analyzed in the past two years.Three lines of natural brown fiber that were controlled by single dominant genes and two lines of green fiber controlled by another single dominant gene.

  2. QTL linkage analysis of connected populations using ancestral marker and pedigree information

    NARCIS (Netherlands)

    Bink, M.C.A.M.; Radu Totir, L.; Braak, ter C.J.F.; Winkler, C.R.; Boer, M.P.; Smith, O.S.

    2012-01-01

    The common assumption in quantitative trait locus (QTL) linkage mapping studies that parents of multiple connected populations are unrelated is unrealistic for many plant breeding programs. We remove this assumption and propose a Bayesian approach that clusters the alleles of the parents of the

  3. A Linkage Map and QTL Analysis for Pyrethroid Resistance in the Bed Bug Cimex lectularius.

    Science.gov (United States)

    Fountain, Toby; Ravinet, Mark; Naylor, Richard; Reinhardt, Klaus; Butlin, Roger K

    2016-12-07

    The rapid evolution of insecticide resistance remains one of the biggest challenges in the control of medically and economically important pests. Insects have evolved a diverse range of mechanisms to reduce the efficacy of the commonly used classes of insecticides, and finding the genetic basis of resistance is a major aid to management. In a previously unstudied population, we performed an F2 resistance mapping cross for the common bed bug, Cimex lectularius, for which insecticide resistance is increasingly widespread. Using 334 SNP markers obtained through RAD-sequencing, we constructed the first linkage map for the species, consisting of 14 putative linkage groups (LG), with a length of 407 cM and an average marker spacing of 1.3 cM. The linkage map was used to reassemble the recently published reference genome, facilitating refinement and validation of the current genome assembly. We detected a major QTL on LG12 associated with insecticide resistance, occurring in close proximity (1.2 Mb) to a carboxylesterase encoding candidate gene for pyrethroid resistance. This provides another example of this candidate gene playing a major role in determining survival in a bed bug population following pesticide resistance evolution. The recent availability of the bed bug genome, complete with a full list of potential candidate genes related to insecticide resistance, in addition to the linkage map generated here, provides an excellent resource for future research on the development and spread of insecticide resistance in this resurging pest species. Copyright © 2016 Fountain et al.

  4. A Linkage Map and QTL Analysis for Pyrethroid Resistance in the Bed Bug Cimex lectularius

    Directory of Open Access Journals (Sweden)

    Toby Fountain

    2016-12-01

    Full Text Available The rapid evolution of insecticide resistance remains one of the biggest challenges in the control of medically and economically important pests. Insects have evolved a diverse range of mechanisms to reduce the efficacy of the commonly used classes of insecticides, and finding the genetic basis of resistance is a major aid to management. In a previously unstudied population, we performed an F2 resistance mapping cross for the common bed bug, Cimex lectularius, for which insecticide resistance is increasingly widespread. Using 334 SNP markers obtained through RAD-sequencing, we constructed the first linkage map for the species, consisting of 14 putative linkage groups (LG, with a length of 407 cM and an average marker spacing of 1.3 cM. The linkage map was used to reassemble the recently published reference genome, facilitating refinement and validation of the current genome assembly. We detected a major QTL on LG12 associated with insecticide resistance, occurring in close proximity (1.2 Mb to a carboxylesterase encoding candidate gene for pyrethroid resistance. This provides another example of this candidate gene playing a major role in determining survival in a bed bug population following pesticide resistance evolution. The recent availability of the bed bug genome, complete with a full list of potential candidate genes related to insecticide resistance, in addition to the linkage map generated here, provides an excellent resource for future research on the development and spread of insecticide resistance in this resurging pest species.

  5. A Linkage Map and QTL Analysis for Pyrethroid Resistance in the Bed Bug Cimex lectularius

    Science.gov (United States)

    Fountain, Toby; Ravinet, Mark; Naylor, Richard; Reinhardt, Klaus; Butlin, Roger K.

    2016-01-01

    The rapid evolution of insecticide resistance remains one of the biggest challenges in the control of medically and economically important pests. Insects have evolved a diverse range of mechanisms to reduce the efficacy of the commonly used classes of insecticides, and finding the genetic basis of resistance is a major aid to management. In a previously unstudied population, we performed an F2 resistance mapping cross for the common bed bug, Cimex lectularius, for which insecticide resistance is increasingly widespread. Using 334 SNP markers obtained through RAD-sequencing, we constructed the first linkage map for the species, consisting of 14 putative linkage groups (LG), with a length of 407 cM and an average marker spacing of 1.3 cM. The linkage map was used to reassemble the recently published reference genome, facilitating refinement and validation of the current genome assembly. We detected a major QTL on LG12 associated with insecticide resistance, occurring in close proximity (1.2 Mb) to a carboxylesterase encoding candidate gene for pyrethroid resistance. This provides another example of this candidate gene playing a major role in determining survival in a bed bug population following pesticide resistance evolution. The recent availability of the bed bug genome, complete with a full list of potential candidate genes related to insecticide resistance, in addition to the linkage map generated here, provides an excellent resource for future research on the development and spread of insecticide resistance in this resurging pest species. PMID:27733453

  6. QTL linkage analysis of connected populations using ancestral marker and pedigree information

    NARCIS (Netherlands)

    Bink, M.C.A.M.; Radu Totir, L.; Braak, ter C.J.F.; Winkler, C.R.; Boer, M.P.; Smith, O.S.

    2012-01-01

    The common assumption in quantitative trait locus (QTL) linkage mapping studies that parents of multiple connected populations are unrelated is unrealistic for many plant breeding programs. We remove this assumption and propose a Bayesian approach that clusters the alleles of the parents of the curr

  7. A Longitudinal Analysis of the Linkage between Suicide, Unemployment, and Marital Dissolution.

    Science.gov (United States)

    Wasserman, Ira M.

    1984-01-01

    Explores the linkage of divorce and suicide from 1964 to 1977, controlling for variations in unemployment. Findings demonstrated that, even with controls, the divorce rate explains variations in the suicide rate, suggesting that the kinship system is being greatly altered, which increases the propensity toward suicide. (JAC)

  8. FBN1 mutation in Chinese patients with Marfan syndrome and its gene diagnosis using haplotype linkage analysis

    Institute of Scientific and Technical Information of China (English)

    王冰; 胡冬煦; 夏家辉; 李崎; 杨进福; 吕国华

    2003-01-01

    Objectives To analyze the FBN1 mutations in Chinese patients with Marfan syndrome (MFS) and to make a genetic diagnosis based on haplotype linkage analysis for MFS. Methods Nine MFS families (17 patients) were analyzed with single strand conformation polymorphism (SSCP) and sequencing. Four primers were designed for the flanking sequences of FBN1 gene and used for haplotype-segregation analysis of MFS (B).Conclusion The combination of mutation detection and chromosome haplotype analysis can provide better evidence for a genetic diagnosis of MFS.

  9. Whole exome sequencing combined with linkage analysis identifies a novel 3 bp deletion in NR5A1.

    Science.gov (United States)

    Eggers, Stefanie; Smith, Katherine R; Bahlo, Melanie; Looijenga, Leendert H J; Drop, Stenvert L S; Juniarto, Zulfa A; Harley, Vincent R; Koopman, Peter; Faradz, Sultana M H; Sinclair, Andrew H

    2015-04-01

    Disorders of sex development (DSDs) encompass a broad spectrum of conditions affecting the development of the gonads and genitalia. The underlying causes for DSDs include gain or loss of function variants in genes responsible for gonad development or steroidogenesis. Most patients with DSD have an unknown genetic etiology and cannot be given an accurate diagnosis. We used whole exome capture and massively parallel sequencing to analyse a large family with 46,XY DSD and 46,XX premature ovarian insufficiency. In addition, we used a recently developed method for linkage analysis using genotypes extracted from the MPS data. This approach identified a unique linkage peak on chromosome 9 and a novel, 3 bp, in-frame deletion in exon six of NR5A1 (steroidogenic factor-1 or SF1) in all affected individuals. We confirmed that the variant disrupts the SF1 protein and its ability to bind and regulate downstream genes. NR5A1 has key roles at multiple points in gonad development and steroidogenic pathways. The variant described here affects the function of SF1 in early testis development and later ovarian function, ultimately leading to the 46,XY DSD and 46,XX premature ovarian insufficiency phenotypes, respectively. This study shows that even at low coverage, whole exome sequencing, when combined with linkage analysis, can be a powerful tool to identify rapidly the disease-causing variant in large pedigrees.

  10. A Hierarchical Generalized Linear Model in Combination with Dispersion Modeling to Improve Sib-Pair Linkage Analysis.

    Science.gov (United States)

    Lee, Woojoo; Kim, Jeonghwan; Lee, Youngjo; Park, Taesung; Suh, Young Ju

    2015-01-01

    We explored a hierarchical generalized linear model (HGLM) in combination with dispersion modeling to improve the sib-pair linkage analysis based on the revised Haseman-Elston regression model for a quantitative trait. A dispersion modeling technique was investigated for sib-pair linkage analysis using simulation studies and real data applications. We considered 4 heterogeneous dispersion settings according to a signal-to-noise ratio (SNR) in the various statistical models based on the Haseman-Elston regression model. Our numerical studies demonstrated that susceptibility loci could be detected well by modeling the dispersion parameter appropriately. In particular, the HGLM had better performance than the linear regression model and the ordinary linear mixed model when the SNR is low, i.e., when substantial noise was present in the data. The study shows that the HGLM in combination with dispersion modeling can be utilized to identify multiple markers showing linkage to familial complex traits accurately. Appropriate dispersion modeling might be more powerful to identify markers closest to the major genes which determine a quantitative trait. © 2015 S. Karger AG, Basel.

  11. Comparative linkage meta-analysis reveals regionally-distinct, disparate genetic architectures: application to bipolar disorder and schizophrenia.

    Directory of Open Access Journals (Sweden)

    Brady Tang

    Full Text Available New high-throughput, population-based methods and next-generation sequencing capabilities hold great promise in the quest for common and rare variant discovery and in the search for "missing heritability." However, the optimal analytic strategies for approaching such data are still actively debated, representing the latest rate-limiting step in genetic progress. Since it is likely a majority of common variants of modest effect have been identified through the application of tagSNP-based microarray platforms (i.e., GWAS, alternative approaches robust to detection of low-frequency (1-5% MAF and rare (<1% variants are of great importance. Of direct relevance, we have available an accumulated wealth of linkage data collected through traditional genetic methods over several decades, the full value of which has not been exhausted. To that end, we compare results from two different linkage meta-analysis methods--GSMA and MSP--applied to the same set of 13 bipolar disorder and 16 schizophrenia GWLS datasets. Interestingly, we find that the two methods implicate distinct, largely non-overlapping, genomic regions. Furthermore, based on the statistical methods themselves and our contextualization of these results within the larger genetic literatures, our findings suggest, for each disorder, distinct genetic architectures may reside within disparate genomic regions. Thus, comparative linkage meta-analysis (CLMA may be used to optimize low-frequency and rare variant discovery in the modern genomic era.

  12. DNA Marker Transmission and Linkage Analysis in Populations Derived from a Sugarcane (Saccharum spp. x Erianthus arundinaceus Hybrid.

    Directory of Open Access Journals (Sweden)

    Jian-wen Chen

    Full Text Available Introgression of Erianthus arundinaceus has been the focus of several sugarcane breeding programs in the world, because the species has desirable traits such as high biomass production, vigour, ratooning ability and good resistance to environmental stresses and disease. In this study four genetic maps were constructed for two intergeneric populations. The first population (BC1 was generated from a cross between an Erianthus/Saccharum hybrid YC96-40 and a commercial sugarcane variety CP84-1198. The second population (BC2 was generated from a cross between YCE01-116, a progeny of the BC1 cross and NJ57-416, a commercial sugarcane cultivar. Markers across both populations were generated using 35 AFLP and 23 SSR primer pairs. A total of 756 and 728 polymorphic markers were scored in the BC1 and BC2 populations, respectively. In the BC1 population, a higher proportion of markers was derived from the Erianthus ancestor than those from the Saccharum ancestor Badila. In the BC2 population, both the number and proportion of markers derived from Erianthus were approximately half of those in the BC1 population. Linkage analysis led to the construction of 38, 57, 36 and 47 linkage groups (LGs for YC96-40, CP84-1198, YCE01-116, and NJ57-416, encompassing 116, 174, 97 and 159 markers (including single dose, double dose and bi-parental markers, respectively. These LGs could be further placed into four, five, five and six homology groups (HGs, respectively, based on information from multi-allelic SSR markers and repulsion phase linkages detected between LGs. Analysis of repulsion phase linkage indicated that Erianthus behaved like a true autopolyploid.

  13. Two-point functions in (loop) quantum cosmology

    Energy Technology Data Exchange (ETDEWEB)

    Calcagni, Gianluca; Gielen, Steffen; Oriti, Daniele, E-mail: calcagni@aei.mpg.de, E-mail: gielen@aei.mpg.de, E-mail: doriti@aei.mpg.de [Max Planck Institute for Gravitational Physics (Albert Einstein Institute), Am Muehlenberg 1, D-14476 Golm (Germany)

    2011-06-21

    The path-integral formulation of quantum cosmology with a massless scalar field as a sum-over-histories of volume transitions is discussed, with particular but non-exclusive reference to loop quantum cosmology. Exploiting the analogy with the relativistic particle, we give a complete overview of the possible two-point functions, pointing out the choices involved in their definitions, deriving their vertex expansions and the composition laws they satisfy. We clarify the origin and relations of different quantities previously defined in the literature, in particular the tie between definitions using a group averaging procedure and those in a deparametrized framework. Finally, we draw some conclusions about the physics of a single quantum universe (where there exist superselection rules on positive- and negative-frequency sectors and different choices of inner product are physically equivalent) and multiverse field theories where the role of these sectors and the inner product are reinterpreted.

  14. Two-point functions in (loop) quantum cosmology

    Energy Technology Data Exchange (ETDEWEB)

    Calcagni, Gianluca; Oriti, Daniele [Max-Planck-Institute for Gravitational Physics (Albert Einstein Institute), Am Muehlenberg 1, D-14476 Golm (Germany); Gielen, Steffen [Max-Planck-Institute for Gravitational Physics (Albert Einstein Institute), Am Muehlenberg 1, D-14476 Golm (Germany); DAMTP, Centre for Mathematical Sciences, Wilberforce Road, Cambridge CB3 0WA (United Kingdom)

    2011-07-01

    We discuss the path-integral formulation of quantum cosmology with a massless scalar field as a sum-over-histories of volume transitions, with particular but non-exclusive reference to loop quantum cosmology (LQC). Exploiting the analogy with the relativistic particle, we give a complete overview of the possible two-point functions, pointing out the choices involved in their definitions, deriving their vertex expansions and the composition laws they satisfy. We clarify the origin and relations of different quantities previously defined in the literature, in particular the tie between definitions using a group averaging procedure and those in a deparametrized framework. Finally, we draw some conclusions about the physics of a single quantum universe (where there exist superselection rules on positive- and negative-frequency sectors and different choices of inner product are physically equivalent) and multiverse field theories where the role of these sectors and the inner product are reinterpreted.

  15. Two-point Correlator Fits on HISQ Ensembles

    CERN Document Server

    Bazavov, A; Bouchard, C; DeTar, C; Du, D; El-Khadra, A X; Foley, J; Freeland, E D; Gamiz, E; Gottlieb, Steven; Heller, U M; Hetrick, J E; Kim, J; Kronfeld, A S; Laiho, J; Levkova, L; Lightman, M; Mackenzie, P B; Neil, E T; Oktay, M; Simone, J N; Sugar, R L; Toussaint, D; Van de Water, R S; Zhou, R

    2012-01-01

    We present our methods to fit the two point correlators for light, strange, and charmed pseudoscalar meson physics with the highly improved staggered quark (HISQ) action. We make use of the least-squares fit including the full covariance matrix of the correlators and including Gaussian constraints on some parameters. We fit the correlators on a variety of the HISQ ensembles. The lattice spacing ranges from 0.15 fm down to 0.06 fm. The light sea quark mass ranges from 0.2 times the strange quark mass down to the physical light quark mass. The HISQ ensembles also include lattices with different volumes and with unphysical values of the strange quark mass. We use the results from this work to obtain our preliminary results of $f_D$, $f_{D_s}$, $f_{D_s}/f_{D}$, and ratios of quark masses presented in another talk [1].

  16. Exploring a Nonmodel Teleost Genome Through RAD Sequencing-Linkage Mapping in Common Pandora, Pagellus erythrinus and Comparative Genomic Analysis.

    Science.gov (United States)

    Manousaki, Tereza; Tsakogiannis, Alexandros; Taggart, John B; Palaiokostas, Christos; Tsaparis, Dimitris; Lagnel, Jacques; Chatziplis, Dimitrios; Magoulas, Antonios; Papandroulakis, Nikos; Mylonas, Constantinos C; Tsigenopoulos, Costas S

    2015-12-29

    Common pandora (Pagellus erythrinus) is a benthopelagic marine fish belonging to the teleost family Sparidae, and a newly recruited species in Mediterranean aquaculture. The paucity of genetic information relating to sparids, despite their growing economic value for aquaculture, provides the impetus for exploring the genomics of this fish group. Genomic tool development, such as genetic linkage maps provision, lays the groundwork for linking genotype to phenotype, allowing fine-mapping of loci responsible for beneficial traits. In this study, we applied ddRAD methodology to identify polymorphic markers in a full-sib family of common pandora. Employing the Illumina MiSeq platform, we sampled and sequenced a size-selected genomic fraction of 99 individuals, which led to the identification of 920 polymorphic loci. Downstream mapping analysis resulted in the construction of 24 robust linkage groups, corresponding to the karyotype of the species. The common pandora linkage map showed varying degrees of conserved synteny with four other teleost genomes, namely the European seabass (Dicentrarchus labrax), Nile tilapia (Oreochromis niloticus), stickleback (Gasterosteus aculeatus), and medaka (Oryzias latipes), suggesting a conserved genomic evolution in Sparidae. Our work exploits the possibilities of genotyping by sequencing to gain novel insights into genome structure and evolution. Such information will boost the study of cultured species and will set the foundation for a deeper understanding of the complex evolutionary history of teleosts.

  17. Exploring a Nonmodel Teleost Genome Through RAD Sequencing—Linkage Mapping in Common Pandora, Pagellus erythrinus and Comparative Genomic Analysis

    Directory of Open Access Journals (Sweden)

    Tereza Manousaki

    2016-03-01

    Full Text Available Common pandora (Pagellus erythrinus is a benthopelagic marine fish belonging to the teleost family Sparidae, and a newly recruited species in Mediterranean aquaculture. The paucity of genetic information relating to sparids, despite their growing economic value for aquaculture, provides the impetus for exploring the genomics of this fish group. Genomic tool development, such as genetic linkage maps provision, lays the groundwork for linking genotype to phenotype, allowing fine-mapping of loci responsible for beneficial traits. In this study, we applied ddRAD methodology to identify polymorphic markers in a full-sib family of common pandora. Employing the Illumina MiSeq platform, we sampled and sequenced a size-selected genomic fraction of 99 individuals, which led to the identification of 920 polymorphic loci. Downstream mapping analysis resulted in the construction of 24 robust linkage groups, corresponding to the karyotype of the species. The common pandora linkage map showed varying degrees of conserved synteny with four other teleost genomes, namely the European seabass (Dicentrarchus labrax, Nile tilapia (Oreochromis niloticus, stickleback (Gasterosteus aculeatus, and medaka (Oryzias latipes, suggesting a conserved genomic evolution in Sparidae. Our work exploits the possibilities of genotyping by sequencing to gain novel insights into genome structure and evolution. Such information will boost the study of cultured species and will set the foundation for a deeper understanding of the complex evolutionary history of teleosts.

  18. Exploring a Nonmodel Teleost Genome Through RAD Sequencing—Linkage Mapping in Common Pandora, Pagellus erythrinus and Comparative Genomic Analysis

    Science.gov (United States)

    Manousaki, Tereza; Tsakogiannis, Alexandros; Taggart, John B.; Palaiokostas, Christos; Tsaparis, Dimitris; Lagnel, Jacques; Chatziplis, Dimitrios; Magoulas, Antonios; Papandroulakis, Nikos; Mylonas, Constantinos C.; Tsigenopoulos, Costas S.

    2015-01-01

    Common pandora (Pagellus erythrinus) is a benthopelagic marine fish belonging to the teleost family Sparidae, and a newly recruited species in Mediterranean aquaculture. The paucity of genetic information relating to sparids, despite their growing economic value for aquaculture, provides the impetus for exploring the genomics of this fish group. Genomic tool development, such as genetic linkage maps provision, lays the groundwork for linking genotype to phenotype, allowing fine-mapping of loci responsible for beneficial traits. In this study, we applied ddRAD methodology to identify polymorphic markers in a full-sib family of common pandora. Employing the Illumina MiSeq platform, we sampled and sequenced a size-selected genomic fraction of 99 individuals, which led to the identification of 920 polymorphic loci. Downstream mapping analysis resulted in the construction of 24 robust linkage groups, corresponding to the karyotype of the species. The common pandora linkage map showed varying degrees of conserved synteny with four other teleost genomes, namely the European seabass (Dicentrarchus labrax), Nile tilapia (Oreochromis niloticus), stickleback (Gasterosteus aculeatus), and medaka (Oryzias latipes), suggesting a conserved genomic evolution in Sparidae. Our work exploits the possibilities of genotyping by sequencing to gain novel insights into genome structure and evolution. Such information will boost the study of cultured species and will set the foundation for a deeper understanding of the complex evolutionary history of teleosts. PMID:26715088

  19. A potential novel spontaneous preterm birth gene, AR, identified by linkage and association analysis of X chromosomal markers.

    Directory of Open Access Journals (Sweden)

    Minna K Karjalainen

    Full Text Available Preterm birth is the major cause of neonatal mortality and morbidity. In many cases, it has severe life-long consequences for the health and neurological development of the newborn child. More than 50% of all preterm births are spontaneous, and currently there is no effective prevention. Several studies suggest that genetic factors play a role in spontaneous preterm birth (SPTB. However, its genetic background is insufficiently characterized. The aim of the present study was to perform a linkage analysis of X chromosomal markers in SPTB in large northern Finnish families with recurrent SPTBs. We found a significant linkage signal (HLOD = 3.72 on chromosome locus Xq13.1 when the studied phenotype was being born preterm. There were no significant linkage signals when the studied phenotype was giving preterm deliveries. Two functional candidate genes, those encoding the androgen receptor (AR and the interleukin-2 receptor gamma subunit (IL2RG, located near this locus were analyzed as candidates for SPTB in subsequent case-control association analyses. Nine single-nucleotide polymorphisms (SNPs within these genes and an AR exon-1 CAG repeat, which was previously demonstrated to be functionally significant, were analyzed in mothers with preterm delivery (n = 272 and their offspring (n = 269, and in mothers with exclusively term deliveries (n = 201 and their offspring (n = 199, all originating from northern Finland. A replication study population consisting of individuals born preterm (n = 111 and term (n = 197 from southern Finland was also analyzed. Long AR CAG repeats (≥ 26 were overrepresented and short repeats (≤ 19 underrepresented in individuals born preterm compared to those born at term. Thus, our linkage and association results emphasize the role of the fetal genome in genetic predisposition to SPTB and implicate AR as a potential novel fetal susceptibility gene for SPTB.

  20. A potential novel spontaneous preterm birth gene, AR, identified by linkage and association analysis of X chromosomal markers.

    Science.gov (United States)

    Karjalainen, Minna K; Huusko, Johanna M; Ulvila, Johanna; Sotkasiira, Jenni; Luukkonen, Aino; Teramo, Kari; Plunkett, Jevon; Anttila, Verneri; Palotie, Aarno; Haataja, Ritva; Muglia, Louis J; Hallman, Mikko

    2012-01-01

    Preterm birth is the major cause of neonatal mortality and morbidity. In many cases, it has severe life-long consequences for the health and neurological development of the newborn child. More than 50% of all preterm births are spontaneous, and currently there is no effective prevention. Several studies suggest that genetic factors play a role in spontaneous preterm birth (SPTB). However, its genetic background is insufficiently characterized. The aim of the present study was to perform a linkage analysis of X chromosomal markers in SPTB in large northern Finnish families with recurrent SPTBs. We found a significant linkage signal (HLOD = 3.72) on chromosome locus Xq13.1 when the studied phenotype was being born preterm. There were no significant linkage signals when the studied phenotype was giving preterm deliveries. Two functional candidate genes, those encoding the androgen receptor (AR) and the interleukin-2 receptor gamma subunit (IL2RG), located near this locus were analyzed as candidates for SPTB in subsequent case-control association analyses. Nine single-nucleotide polymorphisms (SNPs) within these genes and an AR exon-1 CAG repeat, which was previously demonstrated to be functionally significant, were analyzed in mothers with preterm delivery (n = 272) and their offspring (n = 269), and in mothers with exclusively term deliveries (n = 201) and their offspring (n = 199), all originating from northern Finland. A replication study population consisting of individuals born preterm (n = 111) and term (n = 197) from southern Finland was also analyzed. Long AR CAG repeats (≥ 26) were overrepresented and short repeats (≤ 19) underrepresented in individuals born preterm compared to those born at term. Thus, our linkage and association results emphasize the role of the fetal genome in genetic predisposition to SPTB and implicate AR as a potential novel fetal susceptibility gene for SPTB.

  1. Linkage analysis of genes for resistance to downy mildew (Bremia lactucae) in lettuce (Lactuca sativa).

    Science.gov (United States)

    Hulbert, S H; Michelmore, R W

    1985-08-01

    The genetics of specific resistance was studied in F2 populations which segregated for either one or two resistance genes. The resistance factors 1, 11 and 14 which had not previously been characterized genetically segregated as single dominant genes (Dm). Resistance was determined by three linkage groups; R 1/14, 2, 3, and 6 in the first, R 5/8, and 10 in the second and R 4, 7 and 11 in the third. Cultivars of lettuce commonly used in the differential series to detect virulence to R3 and R10, were demonstrated to carry two tightly linked resistance genes. Implications of this linkage arrangement to the manipulation and characterization of these resistance genes are discussed.

  2. Asymptotic estimation theory of multipoint linkage analysis under perfect marker information

    OpenAIRE

    Hössjer, Ola

    2003-01-01

    We consider estimation of a disease susceptibility locus $\\tau$ at a chromosome. With perfect marker data available, the estimator $\\htau_N$ of $\\tau$ based on $N$-pedigrees has a rate of convergence $N^{-1}$ under mild regularity conditions. The limiting distribution is the arg max of a certain compound Poisson process. Our approach is conditional on observed phenotypes, and therefore treats parametric and nonparametric linkage, as well as quantitative trait loci methods within a unified fra...

  3. Genotyping of PCR-based polymorphisms and linkage-disequilibrium analysis at the NF1 locus

    Energy Technology Data Exchange (ETDEWEB)

    Purandare, S.M.; Viskochil, D.H.; Cawthon, R. [Univ. of Utah, Salt Lake City, UT (United States)] [and others

    1996-07-01

    Six polymorphism across the NF1 gene have been adapted for genotyping through application of PCR-based assays. Three exon-based polymorphisms - at positions 702, 2034, and 10647 in the NF1 cDNA - were genotyped by mutagenically separated PCR (MS-PCR). A fourth polymorphism, DV1.9, is an L1 insertion element in intron 30, and the other two polymorphisms, GXAlu and EVI-20, are short tandem repeats in intron 27b. All the polymorphisms were evaluated in a cohort of 110 CEPH individuals who previously had been analyzed by use of eight RFLPs at the NF1 locus. Pairwise linkage-disequilibrium analyses with the six PCR-based polymorphisms and their flanking markers demonstrated disequilibrium between all tested loci. Genotypes of the four diallelic polymorphisms (702, 2034, 10647, and DV1.9) were also evaluated in cohorts from the CEPH, African, and Japanese populations. The CEPH and Japanese cohorts showed similar heterozygosities and linkage-disequilibrium coefficients. The African cohort showed a higher degree of heterozygosity and lower linkage-disequilibrium values, compared with the CEPH and Japanese cohorts. 36 refs., 2 figs., 3 tabs.

  4. Construction of Commercial Sweet Cherry Linkage Maps and QTL Analysis for Trunk Diameter.

    Science.gov (United States)

    Wang, Jing; Zhang, Kaichun; Zhang, Xiaoming; Yan, Guohua; Zhou, Yu; Feng, Laibao; Ni, Yang; Duan, Xuwei

    2015-01-01

    A cross between the sweet cherry (Prunus avium) cultivars 'Wanhongzhu' and 'Lapins' was performed to create a mapping population suitable for the construction of a linkage map. The specific-locus amplified fragment (SLAF) sequencing technique used as a single nucleotide polymorphism (SNP) discovery platform and generated 701 informative genotypic assays; these, along with 16 microsatellites (SSRs) and the incompatibility (S) gene, were used to build a map which comprised 8 linkage groups (LGs) and covered a genetic distance of 849.0 cM. The mean inter-marker distance was 1.18 cM and there were few gaps > 5 cM in length. Marker collinearity was maintained with the established peach genomic sequence. The map was used to show that trunk diameter (TD) is under the control of 4 loci, mapping to 3 different LGs. Different locus influenced TD at a varying stage of the tree's development. The high density 'W×L' genetic linkage map has the potential to enable high-resolution identification of QTLs of agronomically relevant traits, and accelerate sweet cherry breeding.

  5. Construction of Commercial Sweet Cherry Linkage Maps and QTL Analysis for Trunk Diameter.

    Directory of Open Access Journals (Sweden)

    Jing Wang

    Full Text Available A cross between the sweet cherry (Prunus avium cultivars 'Wanhongzhu' and 'Lapins' was performed to create a mapping population suitable for the construction of a linkage map. The specific-locus amplified fragment (SLAF sequencing technique used as a single nucleotide polymorphism (SNP discovery platform and generated 701 informative genotypic assays; these, along with 16 microsatellites (SSRs and the incompatibility (S gene, were used to build a map which comprised 8 linkage groups (LGs and covered a genetic distance of 849.0 cM. The mean inter-marker distance was 1.18 cM and there were few gaps > 5 cM in length. Marker collinearity was maintained with the established peach genomic sequence. The map was used to show that trunk diameter (TD is under the control of 4 loci, mapping to 3 different LGs. Different locus influenced TD at a varying stage of the tree's development. The high density 'W×L' genetic linkage map has the potential to enable high-resolution identification of QTLs of agronomically relevant traits, and accelerate sweet cherry breeding.

  6. A generalization of Kempe's linkages

    Institute of Scientific and Technical Information of China (English)

    MAO De-can; LUO Yao-zhi; YOU Zhong

    2007-01-01

    A new, general type of planar linkages is presented, which extends the classical linkages developed by Kempe consisting of two single-looped kinematic chains of linkages, interconnected by revolute hinges. Together with a locking device, these new linkages have only one degree of freedom (DOF), which makes them ideal for serving as deployable structures for different purposes. Here, we start with a fresh matrix method of analysis for double-loop planar linkages, using 2D transformation matrices and a new symbolic notation. Further inspection for one case of Kempe's linkages is provided. Basing on the inspection, by means of some novel algebraic and geometric techniques, one particularly fascinating solution was found. Physical models were built to show that the derivation in this paper is valid and the new mechanisms are correct.

  7. A multiscale two-point flux-approximation method

    Science.gov (United States)

    Møyner, Olav; Lie, Knut-Andreas

    2014-10-01

    A large number of multiscale finite-volume methods have been developed over the past decade to compute conservative approximations to multiphase flow problems in heterogeneous porous media. In particular, several iterative and algebraic multiscale frameworks that seek to reduce the fine-scale residual towards machine precision have been presented. Common for all such methods is that they rely on a compatible primal-dual coarse partition, which makes it challenging to extend them to stratigraphic and unstructured grids. Herein, we propose a general idea for how one can formulate multiscale finite-volume methods using only a primal coarse partition. To this end, we use two key ingredients that are computed numerically: (i) elementary functions that correspond to flow solutions used in transmissibility upscaling, and (ii) partition-of-unity functions used to combine elementary functions into basis functions. We exemplify the idea by deriving a multiscale two-point flux-approximation (MsTPFA) method, which is robust with regards to strong heterogeneities in the permeability field and can easily handle general grids with unstructured fine- and coarse-scale connections. The method can easily be adapted to arbitrary levels of coarsening, and can be used both as a standalone solver and as a preconditioner. Several numerical experiments are presented to demonstrate that the MsTPFA method can be used to solve elliptic pressure problems on a wide variety of geological models in a robust and efficient manner.

  8. Flow speed measurement using two-point collective light scattering

    Energy Technology Data Exchange (ETDEWEB)

    Heinemeier, N.P

    1998-09-01

    Measurements of turbulence in plasmas and fluids using the technique of collective light scattering have always been plagued by very poor spatial resolution. In 1994, a novel two-point collective light scattering system for the measurement of transport in a fusion plasma was proposed. This diagnostic method was design for a great improvement of the spatial resolution, without sacrificing accuracy in the velocity measurement. The system was installed at the W7-AS steallartor in Garching, Germany, in 1996, and has been operating since. This master thesis is an investigation of the possible application of this new method to the measurement of flow speeds in normal fluids, in particular air, although the results presented in this work have significance for the plasma measurements as well. The main goal of the project was the experimental verification of previous theoretical predictions. However, the theoretical considerations presented in the thesis show that the method can only be hoped to work for flows that are almost laminar and shearless, which makes it of very small practical interest. Furthermore, this result also implies that the diagnostic at W7-AS cannot be expected to give the results originally hoped for. (au) 1 tab., 51 ills., 29 refs.

  9. Joint multi-population analysis for genetic linkage of bipolar disorder or "wellness" to chromosome 4p.

    Science.gov (United States)

    Visscher, P M; Haley, C S; Ewald, H; Mors, O; Egeland, J; Thiel, B; Ginns, E; Muir, W; Blackwood, D H

    2005-02-05

    To test the hypothesis that the same genetic loci confer susceptibility to, or protection from, disease in different populations, and that a combined analysis would improve the map resolution of a common susceptibility locus, we analyzed data from three studies that had reported linkage to bipolar disorder in a small region on chromosome 4p. Data sets comprised phenotypic information and genetic marker data on Scottish, Danish, and USA extended pedigrees. Across the three data sets, 913 individuals appeared in the pedigrees, 462 were classified, either as unaffected (323) or affected (139) with unipolar or bipolar disorder. A consensus linkage map was created from 14 microsatellite markers in a 33 cM region. Phenotypic and genetic data were analyzed using a variance component (VC) and allele sharing method. All previously reported elevated test statistics in the region were confirmed with one or both analysis methods, indicating the presence of one or more susceptibility genes to bipolar disorder in the three populations in the studied chromosome segment. When the results from both the VC and allele sharing method were considered, there was strong evidence for a susceptibility locus in the data from Scotland, some evidence in the data from Denmark and relatively less evidence in the data from the USA. The test statistics from the Scottish data set dominated the test statistics from the other studies, and no improved map resolution for a putative genetic locus underlying susceptibility in all three studies was obtained. Studies reporting linkage to the same region require careful scrutiny and preferably joint or meta analysis on the same basis in order to ensure that the results are truly comparable. (c) 2004 Wiley-Liss, Inc.

  10. Considerations in using linkage analysis as a presymptomatic test for Huntington's disease.

    Science.gov (United States)

    Farrer, L A; Myers, R H; Cupples, L A; Conneally, P M

    1988-09-01

    The polymorphic locus D4S10 that is genetically linked to the locus for Huntington's disease (HD) has made possible a presymptomatic test for those at risk. Because the symptoms of this progressively debilitating and fatal illness are not usually manifest until adulthood, the outcome of the test will influence major decisions about career, marriage, and procreation. Several differential diagnoses must be considered before using the test if HD is not confirmed in at least one family member. Review of a large number of pedigrees has shown that 40% of persons at risk do not have appropriate family structure for a linkage test. Furthermore, uncooperative or inaccessible relatives may make this test infeasible for many others who wish to be tested. Linkage phase, which must be known in the affected parent for an informative test, can be determined using one or more of 12 probe-enzyme combinations for D4S10. Although the polymorphism information content (PIC) value for any one RFLP is less than 40%, the PIC value for the haplotype of the two G8 HindIII, pK083 EcoRI, and R7 BglII RFLPs is greater than 88%. We have developed a scheme to incorporate linkage data and age at onset information adjusted for censored observations, sex of affected parent, and familial correlation for age at onset, using the computer program MLINK for calculation of risk of having HD. Simulated experiments showed that proper age at onset adjustment is crucial to the calculation of the probability of risk. A formal presymptomatic testing protocol, including pre- and post-test counselling, psychological testing, and paternity testing is recommended. Many of these considerations are illustrated in several actual test cases.

  11. Analysis in a large hyperkalemic periodic paralysis pedigree supports tight linkage to a sodium channel locus.

    Science.gov (United States)

    Ptacek, L J; Tyler, F; Trimmer, J S; Agnew, W S; Leppert, M

    1991-01-01

    Hyperkalemic periodic paralysis (HYPP) is an autosomal dominant muscle disease with electrophysiological abnormalities suggesting a defect in a voltage-gated sodium channel (NaCh) gene. A human NaCh gene was recently shown to cosegregate with the disease allele in a family with HYPP. Using an independent clone, we have demonstrated close genetic linkage between an NaCh gene and the HYPP locus in another family. With physiological data demonstrating abnormal NaCh function in HYPP patients, the absence of any obligate recombinations in the two families strengthens the argument that this NaCh gene is the site of the defect in this disorder. PMID:1651050

  12. Linkage Map Construction and Quantitative Trait Loci Analysis for Bolting Based on a Double Haploid Population of Brassica rapa

    Institute of Scientific and Technical Information of China (English)

    Xu Yang; Yang-Jun Yu; Feng-Lan Zhang; Zhi-Rong Zou; Xiu-Yun Zhao; De-Shuang Zhang; Jia-Bing Xu

    2007-01-01

    Early bolting of Chinese cabbage (Brassica rapa L.) during spring cultivation often has detrimental effects on the yield and quality of the harvested products. Breeding late bolting varieties is a major objective of Chinese cabbage breeding programs. in order to analyze the genetic basis of bolting traits, a genetic map of B. rapa was constructed based on amplified fragment-length polymorphism (AFLP), sequence-related amplified polymorphism (SRAP), simple sequence repeat (SSR), random amplification of polymorphic DNA (RAPD), and isozyme markers. Marker analysis was carried out on 81 double haploid (DH) lines obtained by mlcrospore culture from F1 progeny of two homozygous parents: B. rapa L. ssp. pekinensis (BY) (an extra-early bolting Chinese cabbage line) and B. rapa L. ssp. rapifera (MM) (an extra-late bolting European turnip line). A total of 326 markers including 130 AFLPs, 123 SRAPs, 16 SSRs, 43RAPDs and 14 isozymes were used to construct a linkage map with 10 linkage groups covering 882 cM with an average distance of 2.71 cM between loci. The bolting trait of each DH line was evaluated by the bolting index under controlled conditions. Quantitative trait loci (QTL) analysis was conducted using multiple QTL model mapping with MapQTL5.0 software. Eight QTLs controlling bolting resistance were identified. These QTLs, accounting for 14.1% to 25.2% of the phenotyplc variation with positive additive effects, were distributed into three linkage groups. These results provide useful information for molecular marker-assisted selection of late bolting traits in Chinese cabbage breeding programs.

  13. Multicolor in situ hybridization and linkage analysis order Charcot-Marie-Tooth type I (CMTIA) gene-region markers

    Energy Technology Data Exchange (ETDEWEB)

    Lebo, R.V.; Lynch, E.D.; Golbus, M.S. (Univ. of California, San Francisco (United States)); Bird, T.D. (Univ. of Washington, Seattle (United States)); Barker, D.F.; O' Connell, P.; Chance, P.F. (Univ. of Utah, Salt Lake City (United States))

    1992-01-01

    This study demonstrates a clear and current role for multicolor in situ hybridization in expediting positional cloning studies of unknown disease genes. Nine polymorphic DNA cosmids have been mapped to eight ordered locations spanning the Charcot-Marie-Tooth type 1 (CMT1A) disease gene region in distal band 17p11.2, by multicolor in situ hybridization. When used with linkage analysis, these methods have generated a fine physical map and have firmly assigned the CMT1A gene to distal band 17p11.2. Linkage analysis with four CMT1A pedigrees mapped the CMT1A gene with respect to two flanking markers. Additional loci were physically mapped and ordered by in situ hybridization and analysis of phase-known recombinants in CMT1A pedigrees. These data demonstrate the ability of in situ hybridization to resolve loci within 0.5 Mb on early-metaphase chromosomes. Multicolor in situ hybridization also excluded the possibility of pericentric inversions in two unrelated patients with CMT1 and neurofibromatosis type 1. When used with pulsed-field gel electrophoresis, multicolor in situ hybridization can establish physical location, order, and distance in closely spaced chromosome loci.

  14. Examination of X chromosome markers in Rett syndrome: Exclusion mapping with a novel variation on multilocus linkage analysis

    Energy Technology Data Exchange (ETDEWEB)

    Ellison, K.A.; Fill, C.P. (Baylor College of Medicine, Houston, TX (United States)); Terwililger, J.; Percy, A.K.; Zobhbi, H. (Columbia University, NY (United States)); DeGennaro, L.J.; Ott, J. (University of Massachusetts Medical School, Worcester (United States)); Anvret, M.; Martin-Gallardo, A. (National Institutes of Health, Bethesda, MD (United States))

    1992-02-01

    Rett syndrome is a neurologic disorder characterized by early normal development followed by regression, acquired deceleration of head growth, autism, ataxia, and sterotypic hand movements. The exclusive occurrence of the syndrome in females and the occurrence of a few familial cases with inheritance through maternal lines suggest that this disorder is most likely secondary to a mutation on the X chromosome. To address this hypothesis and to identify candidate regions for the Rett syndrome gene locus, genotypic analysis was performed in two families with maternally related affected half-sisters by using 63 DNA markers from the X chromosome. Nineteen of the loci studied were chosen for multipoint linkage analysis because they have been previously genetically mapped using a large number of meioses from reference families. Using the exclusion criterion of a lod score less than [minus]2, the authors were able to exclude the region between the Duchenne muscular dystrophy locus and the DXS456 locus. This region extends from Xp21.2 to Xq21-q23. The use of the multipoint linkage analysis approach outlined in this study should allow the exclusion of additional regions of the X chromosome as new markers are analyzed.

  15. Linkage analysis of congenital nuclear cataract and DLAD locus%先天性核性白内障家系DLAD基因的连锁分析

    Institute of Scientific and Technical Information of China (English)

    陈琳琳; 唐爱兰; 张学; 张劲松

    2005-01-01

    目的:为进一步确定DLAD基因缺陷与人类白内障发生的关系.方法:对6个先天性白内障家系进行临床遗传学分析,然后进行连锁分析.结果:D1 S551和D1 S3471(GATA65B07)引物两点LOD值均为负值.结论:该6个家系的先天性白内障的发生与DLAD基因缺陷无关.%· AIM: DLAD (DnaseII-like acid Dnase) is an acid DNase that is highly expressed in human and murine lens fibre cells. Recently, the DLAD-/- mice with a deficience in DLAD gene were reported to develop nuclear cataract.To elucidate whether a deficient DLAD gene can cause some human cataract, we studied autosomal dominant nuclear catarat in 6 families and analysed linkage between cataract and DLAD locus.·METHODS: Two-point Lod score values were obtained for markers D1S551 and GATA65B07.· RESULTS: The results show negative Lod scores (z=-∞ at θ =0), so linkage was excluded between the defect and DLAD locus in these families.·CONCLUSION: no evidence for cataracts in these families linkage to chromosome 1p22.3, the DLAD locus.

  16. Genomewide Linkage Analysis of Bipolar Disorder by Use of a High-Density Single-Nucleotide–Polymorphism (SNP) Genotyping Assay: A Comparison with Microsatellite Marker Assays and Finding of Significant Linkage to Chromosome 6q22

    Science.gov (United States)

    Middleton, F. A.; Pato, M. T.; Gentile, K. L.; Morley, C. P.; Zhao, X.; Eisener, A. F.; Brown, A.; Petryshen, T. L.; Kirby, A. N.; Medeiros, H.; Carvalho, C.; Macedo, A.; Dourado, A.; Coelho, I.; Valente, J.; Soares, M. J.; Ferreira, C. P.; Lei, M.; Azevedo, M. H.; Kennedy, J. L.; Daly, M. J.; Sklar, P.; Pato, C. N.

    2004-01-01

    We performed a linkage analysis on 25 extended multiplex Portuguese families segregating for bipolar disorder, by use of a high-density single-nucleotide–polymorphism (SNP) genotyping assay, the GeneChip Human Mapping 10K Array (HMA10K). Of these families, 12 were used for a direct comparison of the HMA10K with the traditional 10-cM microsatellite marker set and the more dense 4-cM marker set. This comparative analysis indicated the presence of significant linkage peaks in the SNP assay in chromosomal regions characterized by poor coverage and low information content on the microsatellite assays. The HMA10K provided consistently high information and enhanced coverage throughout these regions. Across the entire genome, the HMA10K had an average information content of 0.842 with 0.21-Mb intermarker spacing. In the 12-family set, the HMA10K-based analysis detected two chromosomal regions with genomewide significant linkage on chromosomes 6q22 and 11p11; both regions had failed to meet this strict threshold with the microsatellite assays. The full 25-family collection further strengthened the findings on chromosome 6q22, achieving genomewide significance with a maximum nonparametric linkage (NPL) score of 4.20 and a maximum LOD score of 3.56 at position 125.8 Mb. In addition to this highly significant finding, several other regions of suggestive linkage have also been identified in the 25-family data set, including two regions on chromosome 2 (57 Mb, NPL = 2.98; 145 Mb, NPL = 3.09), as well as regions on chromosomes 4 (91 Mb, NPL = 2.97), 16 (20 Mb, NPL = 2.89), and 20 (60 Mb, NPL = 2.99). We conclude that at least some of the linkage peaks we have identified may have been largely undetected in previous whole-genome scans for bipolar disorder because of insufficient coverage or information content, particularly on chromosomes 6q22 and 11p11. PMID:15060841

  17. Improving linkage analysis in outcrossed forest trees - an example from Acacia mangium.

    Science.gov (United States)

    Butcher, A.; Williams, R.; Whitaker, D.; Ling, S.; Speed, P.; Moran, F.

    2002-05-01

    Mapping in forest trees generally relies on outbred pedigrees in which genetic segregation is the result of meiotic recombination from both parents. The currently available mapping packages are not optimal for outcrossed pedigrees as they either cannot order phase-ambiguous data or only use pairwise information when ordering loci within linkage groups. A new package, OUTMAP, has been developed for mapping codominant loci in outcrossed trees. A comparison of maps produced using linkage data from two pedigrees of Acacia mangium Willd demonstrated that the marker orders produced using OUTMAP were consistently of higher likelihood than those produced by JOINMAP. In addition, the maps were produced more efficiently, without the need for recoding data or the detailed investigation of pairwise recombination fractions which was necessary to select the optimal marker order using JOINMAP. Distances between markers often varied from those calculated by JOINMAP, resulting in an increase in the estimated genome length. OUTMAP can be used with all segregation types to determine phase and to calculate the likelihood of alternative marker orders, with a choice of three optimisation methods.

  18. Effective Linkages of Continuum of Care for Improving Neonatal, Perinatal, and Maternal Mortality: A Systematic Review and Meta-Analysis.

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    Kimiyo Kikuchi

    Full Text Available Continuum of care has the potential to improve maternal, newborn, and child health (MNCH by ensuring care for mothers and children. Continuum of care in MNCH is widely accepted as comprising sequential time (from pre-pregnancy to motherhood and childhood and space dimensions (from community-family care to clinical care. However, it is unclear which linkages of care could have a greater effect on MNCH outcomes. The objective of the present study is to assess the effectiveness of different continuum of care linkages for reducing neonatal, perinatal, and maternal mortality in low- and middle-income countries.We searched for randomized and quasi-randomized controlled trials that addressed two or more linkages of continuum of care and attempted to increase mothers' uptake of antenatal care, skilled birth attendance, and postnatal care. The outcome variables were neonatal, perinatal, and maternal mortality.Out of the 7,142 retrieved articles, we selected 19 as eligible for the final analysis. Of these studies, 13 used packages of intervention that linked antenatal care, skilled birth attendance, and postnatal care. One study each used packages that linked antenatal care and skilled birth attendance or skilled birth attendance and postnatal care. Four studies used an intervention package that linked antenatal care and postnatal care. Among the packages that linked antenatal care, skilled birth attendance, and postnatal care, a significant reduction was observed in combined neonatal, perinatal, and maternal mortality risks (RR 0.83; 95% CI 0.77 to 0.89, I2 79%. Furthermore, this linkage reduced combined neonatal, perinatal, and maternal mortality when integrating the continuum of care space dimension (RR 0.85; 95% CI 0.77 to 0.93, I2 81%.Our review suggests that continuous uptake of antenatal care, skilled birth attendance, and postnatal care is necessary to improve MNCH outcomes in low- and middle-income countries. The review was conclusive for the

  19. Cointegration and causality analysis of dynamic linkage between stock market and equity mutual funds in Australia

    Directory of Open Access Journals (Sweden)

    Sasipa Pojanavatee

    2014-12-01

    Full Text Available The existing literature finds conflicting results on the magnitude of price linkages between equity mutual funds and the stock market. The study contends that in an optimal lagged model, the expectations of future prices using knowledge of past price behaviour in a particular equity mutual fund category will improve forecasts of prices of other equity mutual fund categories and the stock market index. The evidence shows that the long-run pricing of equity mutual funds is cointegrated with the stock market index. In the short run, the results indicate that some equity mutual fund categories possess both long-run and short-run exogeneity with the stock market. Therefore, the short-run dynamic indicates short-run Granger causal links running between different equity mutual fund categories.

  20. A genome-wide linkage analysis for the personality trait neuroticism in the Irish affected sib-pair study of alcohol dependence.

    Science.gov (United States)

    Kuo, Po-Hsiu; Neale, Michael C; Riley, Brien P; Patterson, Diana G; Walsh, Dermot; Prescott, Carol A; Kendler, Kenneth S

    2007-06-05

    Neuroticism is a personality trait which reflects individual differences in emotional stability and vulnerability to stress and anxiety. Consistent evidence shows substantial genetic influences on variation in this trait. The present study seeks to identify regions containing susceptibility loci for neuroticism using a selected sib-pair sample from Ireland. Using Merlin regress, we conducted a 4 cM whole-genome linkage analysis on 714 sib-pairs. Evidence for linkage to neuroticism was found on chromosomes 11p, 12q, and 15q. The highest linkage peak was on 12q at marker D12S1638 with a Lod score of 2.13 (-log p = 2.76, empirical P-value neuroticism, with male specific linkage regions on chromosomes 1, 4, 11, 12, 15, 16, and 22, and female specific linkage regions on chromosomes 2, 4, 9, 12, 13, and 18. Some genome regions reported in the present study replicate findings from previous linkage studies of neuroticism. These results, together with prior studies, indicate several potential regions for quantitative trait loci for neuroticism that warrant further study.

  1. State feedback control of surge oscillations of two-point mooring system

    Science.gov (United States)

    Mitra, R. K.; Banik, A. K.; Chatterjee, S.

    2017-01-01

    Stability analysis of surge oscillations of two-point mooring system under state feedback control with time-delay is investigated. The two-point mooring system is harmonically excited and essentially represents a strongly nonlinear Duffing oscillator. In this paper, a frequency domain based method viz. incremental harmonic balance method along with arc-length continuation technique (IHBC) is first employed to identify the primary and higher order subharmonic responses which may be present in such system. The IHBC is then reformulated in a manner to treat two-point mooring system under state feedback control with time-delay and is applied to obtain control of responses in an efficient and systematic way. The stability of uncontrolled responses for primary and higher order subharmonic oscillations is obtained by Floquet's theory using Hsu' scheme; whereas the stability of controlled responses is obtained by applying semi-discretization method for delay differential equation. The study focussed on the controlling primary, higher order subharmonics and chaotic responses by considering appropriate feedback gains and delay by way of (i) appreciable reduction of primary, subharmonic responses, (ii) exclusion of all higher order subharmonics 2T, 3T, 5T and 9T (1/n subharmonics or period-n solutions), and (iii) reduction of the extent of domain of all instability phenomena represented by various type of bifurcation of solutions, jump phenomena, chaotic responses etc. In the study, negative velocity feedback is observed to be much effective than state feedback for better controlling of surge oscillation of two-point mooring system. Also, the effect of larger gain values is investigated by an extensive parametric study for vibration control with different delay values.

  2. Identification of a candidate gene for panicle length in rice (Oryza sativa L. via association and linkage analysis

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    Erbao eLiu

    2016-05-01

    Full Text Available Panicle length (PL is an important trait for improving panicle architecture and grain yield in rice (Oryza sativa L.. Three populations were used to identify QTLs and candidate genes associated with PL. Four QTLs for PL were detected on chromosomes 4, 6 and 9 through linkage mapping in the recombinant inbred line population derived from a cross between the cultivars Xiushui79 (short panicle and C-bao (long panicle. Ten SSR markers associated with PL were detected on chromosomes 2, 3, 5, 6, 8, 9 and 10 in the natural population consisting of 540 accessions collected from East and Southeast Asia. A major locus on chromosome 9 with the largest effect was identified via both linkage and association mapping. LONG PANICLE 1 (LP1 locus was delimited to a 90-kb region of the long arm of chromosome 9 through fine mapping using a single segment segregating F2 population. Two single nucleotide polymorphisms (SNPs leading to amino acid changes were detected in the third and fifth exons of LP1. LP1encodes a Remorin_C-containing protein of unknown function with homologs in a variety of species. Sequencing analysis of LP1 in two parents and 103 rice accessions indicated that SNP1 is associated with panicle length. The LP1 allele of Xiushui79 leads to reduced panicle length, whereas the allele of C-bao relieves the suppression of panicle length. LP1 and the elite alleles can be used to improve panicle length in rice.

  3. Construction of a linkage map and QTL analysis of horticultural traits for watermelon [Citrullus lanatus (THUNB.) MATSUM & NAKAI] using RAPD, RFLP and ISSR markers.

    Science.gov (United States)

    Hashizume, T; Shimamoto, I; Hirai, M

    2003-03-01

    We have been constructing linkage maps for watermelon ( Citrullus lanatus) on the basis of random amplified polymorphic DNA (RAPD), restriction fragment length polymorphism (RFLP), inter-simple sequence repeats (ISSRs) and isozymes using an F(2) population derived from a crossing between a cultivated inbred line (H-7; C. lanatus) and an African wild form (SA-1; C. lanatus). A total of 120 F(2) plants was used for construction of a linkage map using 477 RAPDs, 53 RFLPs, 23 ISSRs and one isozyme markers. Linkage analysis revealed that 554 loci could be mapped to 11 linkage groups that extended for 2,384 centimorgans (cM). While a BC(1) population [(H-7 x SA-1) x H-7] consisting of 60 individuals was grown and scored for quantitative traits. Another linkage map with a total length of 1,729 cM was constructed in the BC(1) using genetic markers found to segregate in the F(2) population. A QTL analysis was applied by means of interval mapping for locating such agronomic traits as hardness of rind, Brix of flesh juice, flesh color (red and yellow) and rind color. The relative order of markers in the BC(1) map was essentially the same as that on the linkage map in the F(2). A total of five QTLs for four agronomic traits was detected. The QTL for hardness of rind was mapped on group 4. The linkage group 8 contained the QTL for sugar content of the flesh as expressed in Brix of the juice. The QTL for red flesh color was detected on groups 2 and 8. The QTL for rind color mapped on the group 3. The present map and QTL analysis may provide a useful tool for breeders by introducing valuable wild watermelon genes to cultivars.

  4. Genomewide High-Density SNP Linkage Analysis of 236 Japanese Families Supports the Existence of Schizophrenia Susceptibility Loci on Chromosomes 1p, 14q, and 20p

    Science.gov (United States)

    Arinami, Tadao; Ohtsuki, Tsuyuka; Ishiguro, Hiroki; Ujike, Hiroshi; Tanaka, Yuji; Morita, Yukitaka; Mineta, Mari; Takeichi, Masashi; Yamada, Shigeto; Imamura, Akira; Ohara, Koichi; Shibuya, Haruo; Ohara, Kenshiro; Suzuki, Yasuo; Muratake, Tatsuyuki; Kaneko, Naoshi; Someya, Toshiyuki; Inada, Toshiya; Yoshikawa, Takeo; Toyota, Tomoko; Yamada, Kazuo; Kojima, Takuya; Takahashi, Sakae; Osamu, Ohmori; Shinkai, Takahiro; Nakamura, Michiko; Fukuzako, Hiroshi; Hashiguchi, Tomo; Niwa, Shin-ich; Ueno, Takuya; Tachikawa, Hirokazu; Hori, Takafumi; Asada, Takashi; Nanko, Shinichiro; Kunugi, Hiroshi; Hashimoto, Ryota; Ozaki, Norio; Iwata, Nakao; Harano, Mutsuo; Arai, Heii; Ohnuma, Tohru; Kusumi, Ichiro; Koyama, Tsukasa; Yoneda, Hiroshi; Fukumaki, Yasuyuki; Shibata, Hiroki; Kaneko, Sunao; Higuchi, Hisashi; Yasui-Furukori, Norio; Numachi, Yohtaro; Itokawa, Masanari; Okazaki, Yuji

    2005-01-01

    The Japanese Schizophrenia Sib-Pair Linkage Group (JSSLG) is a multisite collaborative study group that was organized to create a national resource for affected sib pair (ASP) studies of schizophrenia in Japan. We used a high-density single-nucleotide–polymorphism (SNP) genotyping assay, the Illumina BeadArray linkage mapping panel (version 4) comprising 5,861 SNPs, to perform a genomewide linkage analysis of JSSLG samples comprising 236 Japanese families with 268 nonindependent ASPs with schizophrenia. All subjects were Japanese. Among these families, 122 families comprised the same subjects analyzed with short tandem repeat markers. All the probands and their siblings, with the exception of seven siblings with schizoaffective disorder, had schizophrenia. After excluding SNPs with high linkage disequilibrium, we found significant evidence of linkage of schizophrenia to chromosome 1p21.2-1p13.2 (LOD=3.39) and suggestive evidence of linkage to 14q11.2 (LOD=2.87), 14q11.2-q13.2 (LOD=2.33), and 20p12.1-p11.2 (LOD=2.33). Although linkage to these regions has received little attention, these regions are included in or partially overlap the 10 regions reported by Lewis et al. that passed the two aggregate criteria of a meta-analysis. Results of the present study—which, to our knowledge, is the first genomewide analysis of schizophrenia in ASPs of a single Asian ethnicity that is comparable to the analyses done of ASPs of European descent—indicate the existence of schizophrenia susceptibility loci that are common to different ethnic groups but that likely have different ethnicity-specific effects. PMID:16380906

  5. SNP linkage analysis and whole exome sequencing identify a novel POU4F3 mutation in autosomal dominant late-onset nonsyndromic hearing loss (DFNA15.

    Directory of Open Access Journals (Sweden)

    Hee-Jin Kim

    Full Text Available Autosomal dominant non-syndromic hearing loss (AD-NSHL is one of the most common genetic diseases in human and is well-known for the considerable genetic heterogeneity. In this study, we utilized whole exome sequencing (WES and linkage analysis for direct genetic diagnosis in AD-NSHL. The Korean family had typical AD-NSHL running over 6 generations. Linkage analysis was performed by using genome-wide single nucleotide polymorphism (SNP chip and pinpointed a genomic region on 5q31 with a significant linkage signal. Sequential filtering of variants obtained from WES, application of the linkage region, bioinformatic analyses, and Sanger sequencing validation identified a novel missense mutation Arg326Lys (c.977G>A in the POU homeodomain of the POU4F3 gene as the candidate disease-causing mutation in the family. POU4F3 is a known disease gene causing AD-HSLH (DFNA15 described in 5 unrelated families until now each with a unique mutation. Arg326Lys was the first missense mutation affecting the 3(rd alpha helix of the POU homeodomain harboring a bipartite nuclear localization signal sequence. The phenotype findings in our family further supported previously noted intrafamilial and interfamilial variability of DFNA15. This study demonstrated that WES in combination with linkage analysis utilizing bi-allelic SNP markers successfully identified the disease locus and causative mutation in AD-NSHL.

  6. Linkage analysis and map construction in genetic populations of clonal F1 and double cross.

    Science.gov (United States)

    Zhang, Luyan; Li, Huihui; Wang, Jiankang

    2015-01-15

    In this study, we considered four categories of molecular markers based on the number of distinguishable alleles at the marker locus and the number of distinguishable genotypes in clonal F1 progenies. For two marker loci, there are nine scenarios that allow the estimation of female, male, and/or combined recombination frequencies. In a double cross population derived from four inbred lines, five categories of markers are classified and another five scenarios are present for recombination frequency estimation. Theoretical frequencies of identifiable genotypes were given for each scenario, from which the maximum likelihood estimates of one or more of the three recombination frequencies could be estimated. If there was no analytic solution, then Newton-Raphson method was used to acquire a numerical solution. We then proposed to use an algorithm in Traveling Salesman Problem to determine the marker order. Finally, we proposed a procedure to build the two haploids of the female parent and the two haploids of the male parent in clonal F1. Once the four haploids were built, clonal F1 hybrids could be exactly regarded as a double cross population. Efficiency of the proposed methods was demonstrated in simulated clonal F1 populations and one actual maize double cross. Extensive comparisons with software JoinMap4.1, OneMap, and R/qtl show that the methodology proposed in this article can build more accurate linkage maps in less time.

  7. Major factors influencing linkage disequilibrium by analysis of different chromosome regions in distinct populations: demography, chromosome recombination frequency and selection.

    Science.gov (United States)

    Zavattari, P; Deidda, E; Whalen, M; Lampis, R; Mulargia, A; Loddo, M; Eaves, I; Mastio, G; Todd, J A; Cucca, F

    2000-12-12

    Linkage disequilibrium (LD) mapping of disease genes is complicated by population- and chromosome-region-specific factors. We have analysed demographic factors by contrasting intermarker LD results obtained in a large cosmopolitan population (UK), a large genetic isolate (Sardinia) and a subisolate (village of Gavoi) for two regions of the X chromosome. A dramatic increase of LD was found in the subisolate. Demographic history of populations therefore influences LD. Chromosome-region-specific effects, namely the pattern and frequency of homologous recombination, were next delineated by the analysis of chromosome 6p21, including the HLA region. Patterns of global LD in this region were very similar in the UK and Sardinian populations despite their entirely distinct demographies, and correlate well with the pattern of recombinations. Nevertheless, haplotypes extend across recombination hot spots indicative of selection of certain haplotypes. Subisolate aside, chromosome-region-specific differences in LD patterns appear to be more important than the differences in intermarker LD between distinct populations.

  8. A Novel Method to Magnetic Flux Linkage Optimization of Direct-Driven Surface-Mounted Permanent Magnet Synchronous Generator Based on Nonlinear Dynamic Analysis

    Directory of Open Access Journals (Sweden)

    Qian Xie

    2016-07-01

    Full Text Available This paper pays attention to magnetic flux linkage optimization of a direct-driven surface-mounted permanent magnet synchronous generator (D-SPMSG. A new compact representation of the D-SPMSG nonlinear dynamic differential equations to reduce system parameters is established. Furthermore, the nonlinear dynamic characteristics of new D-SPMSG equations in the process of varying magnetic flux linkage are considered, which are illustrated by Lyapunov exponent spectrums, phase orbits, Poincaré maps, time waveforms and bifurcation diagrams, and the magnetic flux linkage stable region of D-SPMSG is acquired concurrently. Based on the above modeling and analyses, a novel method of magnetic flux linkage optimization is presented. In addition, a 2 MW D-SPMSG 2D/3D model is designed by ANSYS software according to the practical design requirements. Finally, five cases of D-SPMSG models with different magnetic flux linkages are simulated by using the finite element analysis (FEA method. The nephograms of magnetic flux density are agreement with theoretical analysis, which both confirm the correctness and effectiveness of the proposed approach.

  9. THE CHERNOBYL ACCIDENT AND HEALTH (TWO POINTS OF VIEW

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    V. M. Shubik

    2011-01-01

    Full Text Available The article presents two alternative points of view on the relationship of health malfunctions after the Chernobyl accident with radiation effect or with the factors of non-radiation nature (social, stress, nutrition peculiarities, etc.. An analysis of literature data and results of author’s own research of radiosensitive indicators of immunity condition, having essential value for the immediate and long term consequences of radiation effect was done. Possible correlation between health malfunctions of the population living in the regions, contaminated by the radionuclides, and combined effect of radiation and factors of non-radiation nature is shown.

  10. Analysis of biomarkers for the cross-linkage of formaldehyde with bovine serum albumin peptides

    Institute of Scientific and Technical Information of China (English)

    AHMAD Waqar; DENG YuLin; LI Bo; LI LiLi; AHAMD Manzoor; IQBAL Zafar; PARVEEN Zahida

    2008-01-01

    Formaldehyde, a well-known environmental toxic hazard, has been found to produce endogenously via semicarbazide-sensitive amine oxidase-catalyzed oxidative deamination of methylamine. In diabetes,the activity of SSAO has been found to increase with a subsequent increase in endogenous formalde-hyde production. It has been postulated that SSAO-induced production of formaldehyde may be in-volved in the alteration of protein structure, which may subsequently cause protein deposition associ-ated with chronic pathological disorders. Formaldehyde has also been found to react (cross-link) withamino group of the N-terminal amino acid residue and with the side-chains of arginine, cysteine, his-tidine and lysine residues. Therefore, formaldehyde may be responsible, at least in part, for protein cross-linkage, oxidative stress and cytotoxicity. The cross-linking of formaldehyde with bovine serum albumin was studied using LC-MS and Mascot database. The peptides sequence for control BSA (un-treated) digested with trypsin was matched in the online database search query by exporting the MS/MS data to online MASCOT database. In this way, a total of twenty-seven peptides were matched in the database search query. These twenty-seven peptides were then searched manually in all of the tryptic BSA samples treated with different concentrations of FA that were incubated in different time intervals.Six formaldehyde-treated BSA peptides (FKDLGEEHFK, HLVDEPQNLIK, KVPQVSTPTLVEVSR,RPCFSALTPDETYVPK, LVNELTEFAK, DAFLGSFLYEYSR) were found to be the possible markers for formaldehyde-protein/peptides adducts.

  11. Linkage disequilibrium and population-structure analysis among Capsicum annuum L. cultivars for use in association mapping.

    Science.gov (United States)

    Nimmakayala, Padma; Abburi, Venkata L; Abburi, Lavanya; Alaparthi, Suresh Babu; Cantrell, Robert; Park, Minkyu; Choi, Doil; Hankins, Gerald; Malkaram, Sridhar; Reddy, Umesh K

    2014-08-01

    Knowledge of population structure and linkage disequilibrium among the worldwide collections of peppers currently classified as hot, mild, sweet and ornamental types is indispensable for applying association mapping and genomic selection to improve pepper. The current study aimed to resolve the genetic diversity and relatedness of Capsicum annuum germplasm by use of simple sequence repeat (SSR) loci across all chromosomes in samples collected in 2011 and 2012. The physical distance covered by the entire set of SSRs used was 2,265.9 Mb from the 3.48-Gb hot-pepper genome size. The model-based program STRUCTURE was used to infer five clusters, which was further confirmed by classical molecular-genetic diversity analysis. Mean heterozygosity of various loci was estimated to be 0.15. Linkage disequilibrium (LD) was used to identify 17 LD blocks across various chromosomes with sizes from 0.154 Kb to 126.28 Mb. CAMS-142 of chromosome 1 was significantly associated with both capsaicin (CA) and dihydrocapsaicin (DCA) levels. Further, CAMS-142 was located in an LD block of 98.18 Mb. CAMS-142 amplified bands of 244, 268, 283 and 326 bp. Alleles 268 and 283 bp had positive effects on both CA and DCA levels, with an average R(2) of 12.15 % (CA) and 12.3 % (DCA). Eight markers from seven different chromosomes were significantly associated with fruit weight, contributing an average effect of 15 %. CAMS-199, HpmsE082 and CAMS-190 are the three major quantitative trait loci located on chromosomes 8, 9, and 10, respectively, and were associated with fruit weight in samples from both years of the study. This research demonstrates the effectiveness of using genome-wide SSR-based markers to assess features of LD and genetic diversity within C. annuum.

  12. Linkage Maps of a Mediterranean × Continental Tall Fescue Population and their Comparative Analysis with Other Poaceae Species

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    Ryan Dierking

    2015-03-01

    Full Text Available Temperate grasses belonging to the complex are important throughout the world in pasture and grassland agriculture. Tall fescue ( Schreb. is the predominant species in the United States, covering approximately 15 million ha. Tall fescue has distinctive morphotypes, two of which are Continental (summer active and Mediterranean (summer semidormant. This is the first report of a linkage map created for Mediterranean tall fescue, while updating the Continental map with additional simple sequence repeat and sequence-tagged site markers. Additionally, this is the first time that diversity arrays technology (DArT markers were used in the construction of a tall fescue map. The male parent (Continental, R43-64, map consisted of 594 markers arranged in 22 linkage groups (LGs and covered a total of 1577 cM. The female parent (Mediterranean, 103-2, map was shorter (1258 cM and consisted of only 208 markers arranged in 29 LGs. Marker densities for R43-64 and 103-2 were 2.65 and 6.08 cM per marker, respectively. When compared with the other Poaceae species, meadow fescue ( Huds., annual ryegrass ( Lam., perennial ryegrass ( L., (L. Beauv., and barley ( L., a total of 171 and 98 orthologous or homologous sequences, identified by DArT analysis, were identified in R43-64 and 103-2, respectively. By using genomic in situ hybridization, we aimed to identify potential progenitors of both morphotypes. However, no clear conclusion on genomic constitution was reached. These maps will aid in the search for quantitative trait loci of various traits as well as help define and distinguish genetic differences between the two morphotypes.

  13. Analysing H(z) data using two-point diagnostics

    Science.gov (United States)

    Leaf, Kyle; Melia, Fulvio

    2017-09-01

    Measurements of the Hubble constant H(z) are increasingly being used to test the expansion rate predicted by various cosmological models. But the recent application of 2-point diagnostics, such as Om(z_i,z_j) and Omh^2(z_i,z_j), has produced considerable tension between LCDM's predictions and several observations, with other models faring even worse. Part of this problem is attributable to the continued mixing of truly model-independent measurements using the cosmic-chronomter approach, and model-dependent data extracted from BAOs. In this paper, we advance the use of 2-point diagnostics beyond their current status, and introduce new variations, which we call Delta h(z_i,z_j), that are more useful for model comparisons. But we restrict our analysis exclusively to cosmic-chronometer data, which are truly model independent. Even for these measurements, however, we confirm the conclusions drawn by earlier workers that the data have strongly non-Gaussian uncertainties, requiring the use of both "median" and "mean" statistical approaches. Our results reveal that previous analyses using 2-point diagnostics greatly underestimated the errors, thereby misinterpreting the level of tension between theoretical predictions and H(z) data. Instead, we demonstrate that as of today, only Einstein-de Sitter is ruled out by the 2-point diagnostics at a level of significance exceeding ~ 3 sigma. The R_h=ct universe is slightly favoured over the remaining models, including LCDM and Chevalier-Polarski-Linder, though all of them (other than Einstein-de Sitter) are consistent to within 1 sigma with the measured mean of the Delta h(z_i,z_j) diagnostics.

  14. Power of non-parametric linkage analysis in mapping genes contributing to human longevity in long-lived sib-pairs

    DEFF Research Database (Denmark)

    Tan, Qihua; Zhao, J H; Iachine, I

    2004-01-01

    This report investigates the power issue in applying the non-parametric linkage analysis of affected sib-pairs (ASP) [Kruglyak and Lander, 1995: Am J Hum Genet 57:439-454] to localize genes that contribute to human longevity using long-lived sib-pairs. Data were simulated by introducing a recently...... developed statistical model for measuring marker-longevity associations [Yashin et al., 1999: Am J Hum Genet 65:1178-1193], enabling direct power comparison between linkage and association approaches. The non-parametric linkage (NPL) scores estimated in the region harboring the causal allele are evaluated...... in case of a dominant effect. Although the power issue may depend heavily on the true genetic nature in maintaining survival, our study suggests that results from small-scale sib-pair investigations should be referred with caution, given the complexity of human longevity....

  15. Metallomic profiling and linkage map analysis of early Parkinson's disease: a new insight to aluminum marker for the possible diagnosis.

    Directory of Open Access Journals (Sweden)

    Shiek S S J Ahmed

    Full Text Available BACKGROUND: Parkinson's disease (PD is the most common neurodegenerative disorder. The diagnosis of PD is challenging and currently none of the biochemical tests have proven to help in diagnosis. Serum metallomic analysis may suggest the possibility of diagnosis of PD. METHODOLOGY/RESULTS: The metallomic analysis was targeted on 31 elements obtained from 42 healthy controls and 45 drug naive PD patients using ICP-AES and ICP-MS to determine the concentration variations of elements between PD and normal. The targeted metallomic analysis showed the significant variations in 19 elements of patients compared to healthy control (p<0.04. The partial least squares discriminant analysis (PLS-DA showed aluminium, copper, iron, manganese and zinc are the key elements, contributes the separation of PD patients from control samples. The correlation coefficient analysis and element-element ratio confirm the imbalance of inter-elements relationship in PD patients' serum. Furthermore, elements linkage map analysis showed aluminium is a key element involved in triggering of phosphorus, which subsequently lead to imbalance of homeostatic in PD serum. The execution of neural network using elements concentrations provides 95% accuracy in detection of disease. CONCLUSIONS/SIGNIFICANCE: These results suggest that there is a disturbance in the elements homeostasis and inter-elements relationship in PD patients' serum. The analysis of serum elements helps in linking the underlying cellular processes such as oxidative stress, neuronal dysfunction and apoptosis, which are the dominating factors in PD. Also, these results increase the prospect of detection of early PD from serum through neural network algorithm.

  16. Stability analysis of glutamic acid linked peptides coupled to NOTA through different chemical linkages.

    Science.gov (United States)

    Lang, Lixin; Ma, Ying; Kiesewetter, Dale O; Chen, Xiaoyuan

    2014-11-03

    Glutamic acid is a commonly used linker to form dimeric peptides with enhanced binding affinity than their corresponding monomeric counterparts. We have previously labeled NOTA-Bn-NCS-PEG3-E[c(RGDyK)]2 (NOTA-PRGD2) [1] with [(18)F]AlF and (68)Ga for imaging tumor angiogenesis. The p-SCN-Bn-NOTA was attached to E[c(RGDyK)]2 [2] through a mini-PEG with a thiourea linkage, and the product [1] was stable at radiolabeling condition of 100 °C and pH 4.0 acetate buffer. However, when the same p-SCN-Bn-NOTA was directly attached to the α-amine of E[c(RGDfK)]2 [3], the product NOTA-Bn-NCS-E[c(RGDfK)]2 [4] became unstable under similar conditions and the release of monomeric c(RGDfK) [5] was observed. The purpose of this work was to use HPLC and LC-MS to monitor the decomposition of glutamic acid linked dimeric peptides and their NOTA derivatives. A c(RGDyK) [6] and bombesin (BBN) [7] heterodimer c(RGDyK)-E-BBN [8], and a dimeric bombesin E(BBN)2 [9], both with a glutamic acid as the linker, along with a model compound PhSCN-E[c(RGDfK)] [10] were also studied. All the compounds were dissolved in 0.5 M pH 4.0 acetate buffer at the concentration of 1 mg/mL, and 0.1 mL of each sample was heated at 100 °C for 10 min and the more stable compounds were heated for another 30 min. The samples at both time points were analyzed with analytical HPLC to monitor the decomposition of the heated samples. The samples with decomposition were further analyzed by LC-MS to determine the mass of products from the decomposition for possible structure elucidation. After 10 min heating, the obvious release of c(RGDfK) [5] was observed for NOTA-Bn-NCS-E[c(RGDfK)]2 [4] and Ph-SCN-E[c(RGDfK)] [10]. Little or no release of monomers was observed for the remaining samples at this time point. After further heating, the release of monomers was clearly observed for E[c(RGDyK)]2 [2], E[c(RGDfK)]2 [3], c(RGDyK)-E-BBN [8], and E(BBN)2 [9]. No decomposition or little decomposition was observed for NOTA

  17. Genome scan for linkage to Gilles de la Tourette syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Barr, C.L.; Livingston, J.; Williamson, R. [and others

    1994-09-01

    Gilles de la Tourette Syndrome (TS) is a familial, neuropsychiatric disorder characterized by chronic, intermittent motor and vocal tics. In addition to tics, affected individuals frequently display symptoms such as attention-deficit hyperactivity disorder and/or obsessive compulsive disorder. Genetic analyses of family data have suggested that susceptibility to the disorder is most likely due to a single genetic locus with a dominant mode of transmission and reduced penetrance. In the search for genetic linkage for TS, we have collected well-characterized pedigrees with multiple affected individuals on whom extensive diagnostic evaluations have been done. The first stage of our study is to scan the genome systematically using a panel of uniformly spaced (10 to 20 cM), highly polymorphic, microsatellite markers on 5 families segregating TS. To date, 290 markers have been typed and 3,660 non-overlapping cM of the genome have been excluded for possible linkage under the assumption of genetic homogeneity. Because of the possibility of locus heterogeneity overall summed exclusion is not considered tantamount to absolute exclusion of a disease locus in that region. The results from each family are carefully evaluated and a positive lod score in a single family is followed up by typing closely linked markers. Linkage to TS was examined by two-point analysis using the following genetic model: single autosomal dominant gene with gene frequency .003 and maximum penetrance of .99. An age-of-onset correction is included using a linear function increasing from age 2 years to 21 years. A small rate of phenocopies is also incorporated into the model. Only individuals with TS or CMT according to DSM III-R criteria were regarded as affected for the purposes of this summary. Additional markers are being tested to provide coverage at 5 cM intervals. Moreover, we are currently analyzing the data non-parametrically using the Affected-Pedigree-Member Method of linkage analysis.

  18. Statistics of the two-point cross-covariance function of solar oscillations

    Science.gov (United States)

    Nagashima, Kaori; Sekii, Takashi; Gizon, Laurent; Birch, Aaron C.

    2016-09-01

    Context. The cross-covariance of solar oscillations observed at pairs of points on the solar surface is a fundamental ingredient in time-distance helioseismology. Wave travel times are extracted from the cross-covariance function and are used to infer the physical conditions in the solar interior. Aims: Understanding the statistics of the two-point cross-covariance function is a necessary step towards optimizing the measurement of travel times. Methods: By modeling stochastic solar oscillations, we evaluate the variance of the cross-covariance function as function of time-lag and distance between the two points. Results: We show that the variance of the cross-covariance is independent of both time-lag and distance in the far field, that is, when they are large compared to the coherence scales of the solar oscillations. Conclusions: The constant noise level for the cross-covariance means that the signal-to-noise ratio for the cross-covariance is proportional to the amplitude of the expectation value of the cross-covariance. This observation is important for planning data analysis efforts.

  19. Towards finding the linkage between metabolic and age-related disorders using semantic gene data network analysis

    Science.gov (United States)

    Uzzal Hossain, Mohammad; Zaffar Shibly, Abu; Md. Omar, Taimur; Tous Zohora, Fatama; Sara Santona, Umme; Hossain, Md. Jakir; Hosen Khoka, Md. Sadek; Ara Keya, Chaman; Salimullah, Md.

    2016-01-01

    A metabolic disorder (MD) occurs when the metabolic process is disturbed. This process is carried out by thousands of enzymes participating in numerous inter-dependent metabolic pathways. Critical biochemical reactions that involve the processing and transportation of carbohydrates, proteins and lipids are affected in metabolic diseases. Therefore, it is of interest to identify the common pathways of metabolic disorders by building protein-protein interactions (PPI) for network analysis. The molecular network linkages between MD and age related diseases (ARD) are intriguing. Hence, we created networks of protein-protein interactions that are related with MD and ARD using relevant known data in the public domain. The network analysis identified known MD associated proteins and predicted genes and or its products of ARD in common pathways. The genes in the common pathways were isolated from the network and further analyzed for their co-localization and shared domains. Thus, a model hypothesis is proposed using interaction networks that are linked between MD and ARD. This data even if less conclusive finds application in understanding the molecular mechanism of known diseases in relation to observed molecular events PMID:27212841

  20. Directed Graphs, Decompositions, and Spatial Linkages

    CERN Document Server

    Shai, Offer; Whiteley, Walter

    2010-01-01

    The decomposition of a system of constraints into small basic components is an important tool of design and analysis. Specifically, the decomposition of a linkage into minimal components is a central tool of analysis and synthesis of linkages. In this paper we prove that every pinned 3-isostatic (minimally rigid) graph (grounded linkage) has a unique decomposition into minimal strongly connected components (in the sense of directed graphs) which we call 3-Assur graphs. This analysis extends the Assur decompositions of plane linkages previously studied in the mathematical and the mechanical engineering literature. These 3-Assur graphs are the central building blocks for all kinematic linkages in 3-space. They share a number of key combinatorial and geometric properties with the 2-Assur graphs, including an associated lower block-triangular decomposition of the pinned rigidity matrix which provides a format for extending the motion induced by inserting one driver in a bottom Assur linkage to the joints of the e...

  1. Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG families

    Directory of Open Access Journals (Sweden)

    Bailey-Wilson Joan E

    2012-06-01

    Full Text Available Abstract Background Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive. Methods Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG. Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed. Results Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD of 1.28, and an allele-sharing lod score (LOD of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2–3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM. For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM when families used in the original published report of linkage to Xq27-28 were excluded. Conclusions Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2–3 affected individuals and with some evidence of male to male disease transmission

  2. CONSIDERATIONS OVER THE METHODOLOGY OF FINANCIAL ANALYSIS AND ITS LINKAGE WITH BANKABILITY OF EUROPEAN FUNDED INVESTMENT PROJECTS

    OpenAIRE

    Ioan TRENCA; Petria, Nicolae; Laurentiu DROJ

    2012-01-01

    European funding is considered to be one of the hot topics in Romania and all over Eastern Europe since its novelty and its expected capacity to improve the life of the newly integrated European citizens. The linkages between the European Financial Support Programmes, the private financing performed by the banking sector and the private companies which are intending to use the structural funds to finance their investments is obvious. The present paper analyzed these linkages, creates a case s...

  3. An analysis of the organizational linkages in the cotton industry in Benin

    NARCIS (Netherlands)

    Sinzogan, A.A.C.; Jiggins, J.; Vodouhè, S.; Kossou, D.; Totin, G.G.E.; Huis, van A.

    2007-01-01

    A study of the institutional context of the cotton industry in Benin was conducted in 2004, based on an analysis of stakeholders' interests and influence. The impacts on innovation processes and production systems are analysed with respect to farmers' organizations, the research and extension system

  4. Linkages between biodiversity loss and human health: a global indicator analysis

    NARCIS (Netherlands)

    Huynen, M.M.T.E.; Martens, P.; Groot, de R.S.

    2004-01-01

    The association between health and biodiversity loss was explored by means of regression analysis on a global scale, with control for confounding by socio-economic developments. For this we selected indicators of human health (life expectancy, disability adjusted life expectancy, infant mortality

  5. Automatic spike sorting for extracellular electrophysiological recording using unsupervised single linkage clustering based on grey relational analysis

    Science.gov (United States)

    Lai, Hsin-Yi; Chen, You-Yin; Lin, Sheng-Huang; Lo, Yu-Chun; Tsang, Siny; Chen, Shin-Yuan; Zhao, Wan-Ting; Chao, Wen-Hung; Chang, Yao-Chuan; Wu, Robby; Shih, Yen-Yu I.; Tsai, Sheng-Tsung; Jaw, Fu-Shan

    2011-06-01

    Automatic spike sorting is a prerequisite for neuroscience research on multichannel extracellular recordings of neuronal activity. A novel spike sorting framework, combining efficient feature extraction and an unsupervised clustering method, is described here. Wavelet transform (WT) is adopted to extract features from each detected spike, and the Kolmogorov-Smirnov test (KS test) is utilized to select discriminative wavelet coefficients from the extracted features. Next, an unsupervised single linkage clustering method based on grey relational analysis (GSLC) is applied for spike clustering. The GSLC uses the grey relational grade as the similarity measure, instead of the Euclidean distance for distance calculation; the number of clusters is automatically determined by the elbow criterion in the threshold-cumulative distribution. Four simulated data sets with four noise levels and electrophysiological data recorded from the subthalamic nucleus of eight patients with Parkinson's disease during deep brain stimulation surgery are used to evaluate the performance of GSLC. Feature extraction results from the use of WT with the KS test indicate a reduced number of feature coefficients, as well as good noise rejection, despite similar spike waveforms. Accordingly, the use of GSLC for spike sorting achieves high classification accuracy in all simulated data sets. Moreover, J-measure results in the electrophysiological data indicating that the quality of spike sorting is adequate with the use of GSLC.

  6. Linkage disequilibrium analysis in young populations: Pseudo-vitamin D-deficiency rickets and the founder effect in French Canadians

    Energy Technology Data Exchange (ETDEWEB)

    Labuda, M.; Glorieux, F.H. [McGill Univ., Montreal (Canada); Labuda, D.; Korab-Laskowska, M. [Universite de Montreal (Canada)] [and others

    1996-09-01

    Pseudo-vitamin D-deficiency rickets (PDDR) was mapped close to D12S90 and between proximal D12S312 and distal (D12S305, D12S104) microsatellites that were subsequently found on a single YAC clone. Analysis of a complex haplotype in linkage disequilibrium (LD) with the disease discriminated among distinct founder effects in French Canadian populations in Acadia and in Charlevoix-Saguenay-Lac-Saint-Jean (Ch-SLSJ), as well as an earlier one in precolonial Europe. A simple demographic model suggested the historical age of the founder effect in Ch-SLSJ to be {approximately}12 generations. The corresponding LD data are consistent with this figure when they are analyzed within the framework of Luria-Delbruck model, which takes into account the population growth. Population sampling due to a limited number of first settlers and the rapid demographic expansion appear to have played a major role in the founding of PDDR in Ch-SLSJ and, presumably, other genetic disorders endemic to French Canada. Similarly, the founder effect in Ashkenazim, coinciding with their early settlement in medieval Poland and subsequent expansion eastward, could explain the origin of frequent genetic diseases in this population. 48 refs., 5 figs., 2 tabs.

  7. Eco-Health linkages: assessing the role of ecosystem goods and services on human health using causal criteria analysis.

    Science.gov (United States)

    de Jesus Crespo, Rebeca; Fulford, Richard

    2017-08-01

    In the last decade, we saw an upsurge of studies evaluating the role of ecosystem goods and services (EGS) on human health (Eco-Health). Most of this work consists of observational research of intermediate processes and few address the full pathways from ecosystem to EGS to human health, limiting our ability to assess causality. We conducted a causal criteria analysis of Eco-Health literature using Eco-Evidence, a software tool that helps evaluate evidence of cause-effect relationships. We focus on the context of green spaces providing "buffering" EGS that may influence disease. We found support for a causal linkage between green spaces and all of the EGS tested, and sufficient evidence linking EGS to gastro intestinal disease and heat morbidities. Inconsistencies were found when assessing the link between EGS to cardiovascular and respiratory diseases. Few studies directly link green spaces to health. Those that do, support a connection to cardiovascular disease, and heat morbidities, but provide inconsistent evidence regarding respiratory illness. Our results help establish an agenda to shape future Eco-Health research and define priorities for managing green spaces to provide human health benefits.

  8. Investigating fault propagation and segment linkage using throw distribution analysis within the Agbada formation of Ewan and Oloye fields, northwestern Niger delta

    Science.gov (United States)

    Durogbitan, Abimbola Adewole

    2016-08-01

    Throw distribution analysis of the key stratigraphic surfaces (sequence boundaries and maximum flooding surfaces) across faults has allowed detailed investigation of the tectonic history within the Ewan and Oloye fields, northwestern Niger delta. The structure in the studied area is dominated by growth fault systems which are listric in cross section and concave to the basin in plan-view. Generally, the faults are active down to 2000 m depth before they die out or sole into the underlying shale. The hanging-wall blocks of growth faults are deformed into broad rollover anticlines, with some synthetic and antithetic faults initiated from the anticline crests, and fault splays off major faults, further complicating these structures. Stratigraphic key surfaces within the syn-faulting succession range in age from 16.7 to 10.35 Ma. Periods of maximum and minimum throw are established from 2-Dimensional throw distribution on the growth fault plane. Throw distribution allows analysis of growth fault nucleation, propagation and linkage. Each fault nucleated at different and a distinct interval within the stratigraphic section, as a result of the paleo-stress distribution between the interacting faults. Nucleation and linkage positions can be identified at points of maximum and minimum throw respectively. Following nucleation, faults propagated radially and linked to form the present geometry. Within the study area, fault propagation and segment linkage (lateral and vertical) are important features of the fault system. Understanding of growth fault evolution and linkage has greatly improved prediction of seal potential, trap geometry and migration. The accurate timing of the segment linkage has helped to evaluate the seal risk.

  9. Asymptotic behaviour of two-point functions in multi-species models

    Directory of Open Access Journals (Sweden)

    Karol K. Kozlowski

    2016-05-01

    Full Text Available We extract the long-distance asymptotic behaviour of two-point correlation functions in massless quantum integrable models containing multi-species excitations. For such a purpose, we extend to these models the method of a large-distance regime re-summation of the form factor expansion of correlation functions. The key feature of our analysis is a technical hypothesis on the large-volume behaviour of the form factors of local operators in such models. We check the validity of this hypothesis on the example of the SU(3-invariant XXX magnet by means of the determinant representations for the form factors of local operators in this model. Our approach confirms the structure of the critical exponents obtained previously for numerous models solvable by the nested Bethe Ansatz.

  10. Asymptotic behaviour of two-point functions in multi-species models

    Science.gov (United States)

    Kozlowski, Karol K.; Ragoucy, Eric

    2016-05-01

    We extract the long-distance asymptotic behaviour of two-point correlation functions in massless quantum integrable models containing multi-species excitations. For such a purpose, we extend to these models the method of a large-distance regime re-summation of the form factor expansion of correlation functions. The key feature of our analysis is a technical hypothesis on the large-volume behaviour of the form factors of local operators in such models. We check the validity of this hypothesis on the example of the SU (3)-invariant XXX magnet by means of the determinant representations for the form factors of local operators in this model. Our approach confirms the structure of the critical exponents obtained previously for numerous models solvable by the nested Bethe Ansatz.

  11. Two-point resistance of a resistor network embedded on a globe.

    Science.gov (United States)

    Tan, Zhi-Zhong; Essam, J W; Wu, F Y

    2014-07-01

    We consider the problem of two-point resistance in an (m-1) × n resistor network embedded on a globe, a geometry topologically equivalent to an m × n cobweb with its boundary collapsed into one single point. We deduce a concise formula for the resistance between any two nodes on the globe using a method of direct summation pioneered by one of us [Z.-Z. Tan, L. Zhou, and J. H. Yang, J. Phys. A: Math. Theor. 46, 195202 (2013)]. This method is contrasted with the Laplacian matrix approach formulated also by one of us [F. Y. Wu, J. Phys. A: Math. Gen. 37, 6653 (2004)], which is difficult to apply to the geometry of a globe. Our analysis gives the result in the form of a single summation.

  12. Enhanced understanding of ectoparasite–host trophic linkages on coral reefs through stable isotope analysis

    Directory of Open Access Journals (Sweden)

    Amanda W.J. Demopoulos

    2015-04-01

    Full Text Available Parasitism, although the most common type of ecological interaction, is usually ignored in food web models and studies of trophic connectivity. Stable isotope analysis is widely used in assessing the flow of energy in ecological communities and thus is a potentially valuable tool in understanding the cryptic trophic relationships mediated by parasites. In an effort to assess the utility of stable isotope analysis in understanding the role of parasites in complex coral-reef trophic systems, we performed stable isotope analysis on three common Caribbean reef fish hosts and two kinds of ectoparasitic isopods: temporarily parasitic gnathiids (Gnathia marleyi and permanently parasitic cymothoids (Anilocra. To further track the transfer of fish-derived carbon (energy from parasites to parasite consumers, gnathiids from host fish were also fed to captive Pederson shrimp (Ancylomenes pedersoni for at least 1 month. Parasitic isopods had δ13C and δ15N values similar to their host, comparable with results from the small number of other host–parasite studies that have employed stable isotopes. Adult gnathiids were enriched in 15N and depleted in 13C relative to juvenile gnathiids, providing insights into the potential isotopic fractionation associated with blood-meal assimilation and subsequent metamorphosis. Gnathiid-fed Pedersen shrimp also had δ13C values consistent with their food source and enriched in 15N as predicted due to trophic fractionation. These results further indicate that stable isotopes can be an effective tool in deciphering cryptic feeding relationships involving parasites and their consumers, and the role of parasites and cleaners in carbon transfer in coral-reef ecosystems specifically.

  13. Enhanced understanding of ectoparasite: host trophic linkages on coral reefs through stable isotope analysis

    Science.gov (United States)

    Demopoulos, Amanda W. J.; Sikkel, Paul C.

    2015-01-01

    Parasitism, although the most common type of ecological interaction, is usually ignored in food web models and studies of trophic connectivity. Stable isotope analysis is widely used in assessing the flow of energy in ecological communities and thus is a potentially valuable tool in understanding the cryptic trophic relationships mediated by parasites. In an effort to assess the utility of stable isotope analysis in understanding the role of parasites in complex coral-reef trophic systems, we performed stable isotope analysis on three common Caribbean reef fish hosts and two kinds of ectoparasitic isopods: temporarily parasitic gnathiids (Gnathia marleyi) and permanently parasitic cymothoids (Anilocra). To further track the transfer of fish-derived carbon (energy) from parasites to parasite consumers, gnathiids from host fish were also fed to captive Pederson shrimp (Ancylomenes pedersoni) for at least 1 month. Parasitic isopods had δ13C and δ15N values similar to their host, comparable with results from the small number of other host–parasite studies that have employed stable isotopes. Adult gnathiids were enriched in 15N and depleted in13C relative to juvenile gnathiids, providing insights into the potential isotopic fractionation associated with blood-meal assimilation and subsequent metamorphosis. Gnathiid-fed Pedersen shrimp also had δ13C values consistent with their food source and enriched in 15N as predicted due to trophic fractionation. These results further indicate that stable isotopes can be an effective tool in deciphering cryptic feeding relationships involving parasites and their consumers, and the role of parasites and cleaners in carbon transfer in coral-reef ecosystems specifically.

  14. A Genome-Wide SNP Linkage Analysis Suggests a Susceptibility Locus on 6p21 for Ankylosing Spondylitis and Inflammatory Back Pain Trait

    Science.gov (United States)

    Zhang, Yanli; Liao, Zetao; Wei, Qiujing; Pan, Yunfeng; Wang, Xinwei; Cao, Shuangyan; Guo, Zishi; Wu, Yuqiong; Rong, Ju; Jin, Ou; Xu, Manlong; Gu, Jieruo

    2016-01-01

    Objectives To screen susceptibility loci for ankylosing spondylitis (AS) using an affected-only linkage analysis based on high-density single nucleotide polymorphisms (SNPs) in a genome-wide manner. Patients and Methods AS patients from ten families with Cantonese origin of China were enrolled in the study. Blood samples were genotyped using genomic DNA derived from peripheral blood leukocytes by Illumina HumanHap 610-Quad SNP Chip. Genotype data were generated using the Illumina BeadStudio 3.2 software. PLINK package was used to remove non-autosomal SNPs and to further eliminate markers of typing errors. An affected-only linkage analysis was carried out using both non-parametric and parametric linkage analyses, as implemented in MERLIN. Result Seventy-eight AS patients (48 males and 30 females, mean age: 39±16 years) were enrolled in the study. The mean age of onset was 23±10 years and mean duration of disease was 16.7±12.2 years. Iritis (2/76, 2.86%), dactylitis (5/78, 6.41%), hip joint involvement (9/78, 11.54%), peripheral arthritis (22/78, 28.21%), inflammatory back pain (IBP) (69/78, 88.46%) and HLA-B27 positivity (70/78, 89.74%) were observed in these patients. Using non-parameter linkage analysis, we found one susceptibility locus for AS, IBP and HLA-B27 in 6p21 respectively, spanning about 13.5Mb, 20.9Mb and 21.2Mb, respectively No significant results were found in the other clinical trait groups including dactylitis, hip involved and arthritis. The identical susceptibility locus region spanning above 9.44Mb was detected in AS IBP and HLA-B27 by the parametric linkage analysis. Conclusion Our genome-wide SNP linkage analysis in ten families with ankylosing spondylitis suggests a susceptibility locus on 6p21 in AS, which is a risk locus for IBP in AS patients. PMID:27973620

  15. Molecular characterization of Blau syndrome: Genetic linkage to chromosome 16

    Energy Technology Data Exchange (ETDEWEB)

    Tromp, G.; Duivaniemi, H.; Christiano, A. [Thomas Jefferson Univ., Philadelphia, PA (United States)] [and others

    1994-09-01

    The Blau syndrome is an autosomal, dominantly-inherited disease characterized by multi-organ, tissue-specific inflammation. Its clinical phenotype includes granulomatous uveitis, arthritis and skin rash. The syndrome is unique in that it is the sole human model for a variety of multi-system inflammatory diseases that afflict a significant percentage of the population. Karyotypic analysis of the large, three generation kindred whose disease originally characterized the syndrome was unremarkable. Following exclusion of a number of extracellular matrix candidates genes, a genome-wide search was undertaken of the Blau susceptibility locus. Fifty-seven members of the family were genotyped for about 200 highly polymorphic dinucleotide repeat markers. Linkage analysis was performed using the LINKAGE package of programs under a model of dominant inheritance with reduced penetrance. Five liability classes were used to specify penetrances and phenocopy rates for those affected the arthritis, uveitis, skin rash and combinations thererof. In addition, five age-dependent penetrance classes were used for unaffected individuals. The marker D16S298 gave a maximum lod score of 3.6 at {theta} = 0.05 with two-point analysis. Lod scores for flanking markers were consistent. These data provide convincing evidence that the Blau susceptibility locus is situated within the 16p12-q21 interval. Fine mapping of the candidate interval with additional families exhibiting the Blau phenotype, as well as with more polymorphic markers, is underway.

  16. Dubin's Minimal Linkage Construct Revisited.

    Science.gov (United States)

    Rogers, Donald P.

    This paper contains a theoretical analysis and empirical study that support the major premise of Robert Dubin's minimal-linkage construct-that restricting communication links increases organizational stability. The theoretical analysis shows that fewer communication links are associated with less uncertainty, more redundancy, and greater…

  17. Linkage analysis of quantitative traits for obesity, diabetes, hypertension, and dyslipidemia on the island of Kosrae, Federated States of Micronesia.

    Science.gov (United States)

    Shmulewitz, Dvora; Heath, Simon C; Blundell, Maude L; Han, Zhihua; Sharma, Ratnendra; Salit, Jacqueline; Auerbach, Steven B; Signorini, Stefano; Breslow, Jan L; Stoffel, Markus; Friedman, Jeffrey M

    2006-03-07

    Obesity, diabetes, hypertension, and heart disease are highly heritable conditions that in aggregate are the major causes of morbidity and mortality in the developed world and are growing problems in developing countries. To map the causal genes, we conducted a population screen for these conditions on the Pacific Island of Kosrae. Family history and genetic data were used to construct a pedigree for the island. Analysis of the pedigree showed highly significant heritability for the metabolic traits under study. DNA samples from 2,188 participants were genotyped with 405 microsatellite markers with an average intermarker distance of 11 cM. A protocol using loki, a Markov chain Monte Carlo sampling method, was developed to analyze the Kosraen pedigree for height, a model quantitative trait. Robust quantitative trait loci for height were found on 10q21 and 1p31. This protocol was used to map a set of metabolic traits, including plasma leptin to chromosome region 5q35; systolic blood pressure to 20p12; total cholesterol to 19p13, 12q24, and 16qter; hip circumference to 10q25 and 4q23; body mass index to 18p11 and 20q13; apolipoprotein B to 2p24-25; weight to 18q21; and fasting blood sugar to 1q31-1q43. Several of these same chromosomal regions have been identified in previous studies validating the use of loki. These studies add information about the genetics of the metabolic syndrome and establish an analytical approach for linkage analysis of complex pedigrees. These results also lay the foundation for whole genome scans with dense sets of SNPs aimed to identifying causal genes.

  18. Glycomic analysis of sialic acid linkages in glycans derived from blood serum glycoproteins.

    Science.gov (United States)

    Alley, William R; Novotny, Milos V

    2010-06-04

    A number of alterations to the normal glycomic profile have been previously described for a number of diseases and disorders, thus underscoring the medical importance of studying the glycans associated with proteins present in biological samples. An important alteration in cancer progression is an increased level of alpha2,6-sialylation, which aids in increasing the metastatic potential of tumor cells. Here we report a glycomic method that selectively amidates alpha2,6-linked sialic acids, while those that are alpha2,3-linked undergo spontaneous lactonization. Following subsequent permethylation, MALDI-TOF MS analysis revealed that many sialylated glycans present on glycoproteins found in blood serum featured increased levels of alpha2,6-sialylation in breast cancer samples. On the basis of the altered ratios of alpha2,3-linked to alpha2,6-linked sialic acids, many of these glycans became diagnostically relevant when they did not act as such indicators when based on traditional glycomic profiling alone.

  19. Sequence analysis of 21 genes located in the Kartagener syndrome linkage region on chromosome 15q.

    Science.gov (United States)

    Geremek, Maciej; Schoenmaker, Frederieke; Zietkiewicz, Ewa; Pogorzelski, Andrzej; Diehl, Scott; Wijmenga, Cisca; Witt, Michal

    2008-06-01

    Primary ciliary dyskinesia (PCD) is a rare genetic disorder, which shows extensive genetic heterogeneity and is mostly inherited in an autosomal recessive fashion. There are four genes with a proven pathogenetic role in PCD. DNAH5 and DNAI1 are involved in 28 and 10% of PCD cases, respectively, while two other genes, DNAH11 and TXNDC3, have been identified as causal in one PCD family each. We have previously identified a 3.5 cM (2.82 Mb) region on chromosome 15q linked to Kartagener syndrome (KS), a subtype of PCD characterized by the randomization of body organ positioning. We have now refined the KS candidate region to a 1.8 Mb segment containing 18 known genes. The coding regions of these genes and three neighboring genes were subjected to sequence analysis in seven KS probands, and we were able to identify 60 single nucleotide sequence variants, 35 of which resided in mRNA coding sequences. However, none of the variations alone could explain the occurrence of the disease in these patients.

  20. Construction of a genetic linkage map and genetic analysis of domestication related traits in mungbean (Vigna radiata.

    Directory of Open Access Journals (Sweden)

    Takehisa Isemura

    Full Text Available The genetic differences between mungbean and its presumed wild ancestor were analyzed for domestication related traits by QTL mapping. A genetic linkage map of mungbean was constructed using 430 SSR and EST-SSR markers from mungbean and its related species, and all these markers were mapped onto 11 linkage groups spanning a total of 727.6 cM. The present mungbean map is the first map where the number of linkage groups coincided with the haploid chromosome number of mungbean. In total 105 QTLs and genes for 38 domestication related traits were identified. Compared with the situation in other Vigna crops, many linkage groups have played an important role in the domestication of mungbean. In particular the QTLs with high contribution were distributed on seven out of 11 linkage groups. In addition, a large number of QTLs with small contribution were found. The accumulation of many mutations with large and/or small contribution has contributed to the differentiation between wild and cultivated mungbean. The useful QTLs for seed size, pod dehiscence and pod maturity that have not been found in other Asian Vigna species were identified in mungbean, and these QTLs may play the important role as new gene resources for other Asian Vigna species. The results provide the foundation that will be useful for improvement of mungbean and related legumes.

  1. A sugar beet (Beta vulgaris L.) reference FISH karyotype for chromosome and chromosome-arm identification, integration of genetic linkage groups and analysis of major repeat family distribution.

    Science.gov (United States)

    Paesold, Susanne; Borchardt, Dietrich; Schmidt, Thomas; Dechyeva, Daryna

    2012-11-01

    We developed a reference karyotype for B. vulgaris which is applicable to all beet cultivars and provides a consistent numbering of chromosomes and genetic linkage groups. Linkage groups of sugar beet were assigned to physical chromosome arms by FISH (fluorescent in situ hybridization) using a set of 18 genetically anchored BAC (bacterial artificial chromosome) markers. Genetic maps of sugar beet were correlated to chromosome arms, and North-South orientation of linkage groups was established. The FISH karyotype provides a technical platform for genome studies and can be applied for numbering and identification of chromosomes in related wild beet species. The discrimination of all nine chromosomes by BAC probes enabled the study of chromosome-specific distribution of the major repetitive components of sugar beet genome comprising pericentromeric, intercalary and subtelomeric satellites and 18S-5.8S-25S and 5S rRNA gene arrays. We developed a multicolor FISH procedure allowing the identification of all nine sugar beet chromosome pairs in a single hybridization using a pool of satellite DNA probes. Fiber-FISH was applied to analyse five chromosome arms in which the furthermost genetic marker of the linkage group was mapped adjacently to terminal repetitive sequences on pachytene chromosomes. Only on two arms telomere arrays and the markers are physically linked, hence these linkage groups can be considered as terminally closed making the further identification of distal informative markers difficult. The results support genetic mapping by marker localization, the anchoring of contigs and scaffolds for the annotation of the sugar beet genome sequence and the analysis of the chromosomal distribution patterns of major families of repetitive DNA.

  2. Autosomal dominant familial spastic paraplegia: Tight linkage to chromosome 15q

    Energy Technology Data Exchange (ETDEWEB)

    Fink, J.K.; Wu, C.B.; Jones, S.M.; Lesicki, A.; Reinglass, T. [Univ. of Michigan, Ann Arbor, MI (United States); Sharp, G.B.; Lange, B.M. [Arkansas Children`s Hospital, Little Rock, AR (United States); Varvil, T.; Otterud, B.; Leppert, M. [Univ. of Utah, Salt Lake City, UT (United States)

    1995-01-01

    Autosomal dominant, uncomplicated familial spastic paraplegia (FSP) is a genetically heterogeneous disorder characterized by insidiously progressive lower-extremity spasticity. Recently, a locus on chromosome 14q was shown to be tightly linked with the disorder in one of three families. We performed linkage analysis in a kindred with autosomal dominant uncomplicated FSP. After excluding the chromosome 14q locus, we observed tight linkage of the disorder to a group of markers on chromosome 15q (maximum two-point lod score 9.70; {theta} = .05). Our results clearly establish the existence of a locus for autosomal dominant FSP in the centromeric region of chromosome 15q. Comparing clinical and genetic features in FSP families linked to chromosome 14q with those linked to chromosome 15q may provide insight into the pathophysiology of this disorder. 34 refs., 1 fig., 1 tab.

  3. Identification of Single Nucleotide Polymorphisms and analysis of Linkage Disequilibrium in sunflower elite inbred lines using the candidate gene approach

    Directory of Open Access Journals (Sweden)

    Heinz Ruth A

    2008-01-01

    Full Text Available Abstract Background Association analysis is a powerful tool to identify gene loci that may contribute to phenotypic variation. This includes the estimation of nucleotide diversity, the assessment of linkage disequilibrium structure (LD and the evaluation of selection processes. Trait mapping by allele association requires a high-density map, which could be obtained by the addition of Single Nucleotide Polymorphisms (SNPs and short insertion and/or deletions (indels to SSR and AFLP genetic maps. Nucleotide diversity analysis of randomly selected candidate regions is a promising approach for the success of association analysis and fine mapping in the sunflower genome. Moreover, knowledge of the distance over which LD persists, in agronomically meaningful sunflower accessions, is important to establish the density of markers and the experimental design for association analysis. Results A set of 28 candidate genes related to biotic and abiotic stresses were studied in 19 sunflower inbred lines. A total of 14,348 bp of sequence alignment was analyzed per individual. In average, 1 SNP was found per 69 nucleotides and 38 indels were identified in the complete data set. The mean nucleotide polymorphism was moderate (θ = 0.0056, as expected for inbred materials. The number of haplotypes per region ranged from 1 to 9 (mean = 3.54 ± 1.88. Model-based population structure analysis allowed detection of admixed individuals within the set of accessions examined. Two putative gene pools were identified (G1 and G2, with a large proportion of the inbred lines being assigned to one of them (G1. Consistent with the absence of population sub-structuring, LD for G1 decayed more rapidly (r2 = 0.48 at 643 bp; trend line, pooled data than the LD trend line for the entire set of 19 individuals (r2 = 0.64 for the same distance. Conclusion Knowledge about the patterns of diversity and the genetic relationships between breeding materials could be an invaluable aid in crop

  4. Genetic correlates of brain aging on MRI and cognitive test measures: a genome-wide association and linkage analysis in the Framingham study

    OpenAIRE

    2007-01-01

    Abstract Background Brain magnetic resonance imaging (MRI) and cognitive tests can identify heritable endophenotypes associated with an increased risk of developing stroke, dementia and Alzheimer's disease (AD). We conducted a genome-wide association (GWA) and linkage analysis exploring the genetic basis of these endophenotypes in a community-based sample. Methods A total of 705 stroke- and dementia-free Framingham participants (age 62 +9 yrs, 50% male) who underwent volumetric brain MRI and ...

  5. Identification of a glutamic acid repeat polymorphism of ALMS1 as a novel genetic risk marker for early-onset myocardial infarction by genome-wide linkage analysis.

    Science.gov (United States)

    Ichihara, Sahoko; Yamamoto, Ken; Asano, Hiroyuki; Nakatochi, Masahiro; Sukegawa, Mayo; Ichihara, Gaku; Izawa, Hideo; Hirashiki, Akihiro; Takatsu, Fumimaro; Umeda, Hisashi; Iwase, Mitsunori; Inagaki, Haruo; Hirayama, Haruo; Sone, Takahito; Nishigaki, Kazuhiko; Minatoguchi, Shinya; Cho, Myeong-Chan; Jang, Yangsoo; Kim, Hyo-Soo; Park, Jeong E; Tada-Oikawa, Saeko; Kitajima, Hidetoshi; Matsubara, Tatsuaki; Sunagawa, Kenji; Shimokawa, Hiroaki; Kimura, Akinori; Lee, Jong-Young; Murohara, Toyoaki; Inoue, Ituro; Yokota, Mitsuhiro

    2013-12-01

    Myocardial infarction (MI) is a leading cause of death worldwide. Given that a family history is an independent risk factor for coronary artery disease, genetic variants are thought to contribute directly to the development of this condition. The identification of susceptibility genes for coronary artery disease or MI may thus help to identify high-risk individuals and offer the opportunity for disease prevention. We designed a 5-step protocol, consisting of a genome-wide linkage study followed by association analysis, to identify novel genetic variants that confer susceptibility to coronary artery disease or MI. A genome-wide affected sib-pair linkage study with 221 Japanese families with coronary artery disease yielded a statistically significant logarithm of the odds score of 3.44 for chromosome 2p13 and MI. Further association analysis implicated Alström syndrome 1 gene (ALMS1) as a candidate gene within the linkage region. Validation association analysis revealed that representative single-nucleotide polymorphisms of the ALMS1 promoter region were significantly associated with early-onset MI in both Japanese and Korean populations. Moreover, direct sequencing of the ALMS1 coding region identified a glutamic acid repeat polymorphism in exon 1, which was subsequently found to be associated with early-onset MI. The glutamic acid repeat polymorphism of ALMS1 identified in the present study may provide insight into the pathogenesis of early-onset MI.

  6. BATTEN-DISEASE GENE, CLN3 - LINKAGE DISEQUILIBRIUM MAPPING IN THE FINNISH POPULATION, AND ANALYSIS OF EUROPEAN HAPLOTYPES

    NARCIS (Netherlands)

    MITCHISON, HM; ORAWE, AM; TASCHNER, PEM; SANDKUIJL, LA; SANTAVUORI, P; DEVOS, N; BREUNING, MH; MOLE, SE; GARDINER, RM; JARVELA, IE

    The gene for Batten disease (juvenile-onset neuronal ceroid lipofuscinosis, or Spielmeyer-Sjogren disease), CLN3, maps to 16p11.2-12.1. Four microsatellite markers-D16S288, D16S299, D16S298, and SPN-are in strong linkage disequilibrium with CLN3 in 142 families from 16 different countries. These

  7. Cost-Utility Analysis of Three U.S. HIV Linkage and Re-engagement in Care Programs from Positive Charge.

    Science.gov (United States)

    Jain, Kriti M; Zulliger, Rose; Maulsby, Cathy; Kim, Jeeyon Janet; Charles, Vignetta; Riordan, Maura; Holtgrave, David

    2016-05-01

    Linking and retaining people living with HIV in ongoing, HIV medical care is vital for ending the U.S. HIV epidemic. Yet, 41-44 % of HIV+ individuals are out of care. In response, AIDS United initiated Positive Charge, a series of five HIV linkage and re-engagement projects around the U.S. This paper investigates whether three Positive Charge programs were cost effective and calculates a return on investment for each program. It uses standard methods of cost utility analysis and WHO-CHOICE thresholds. All three projects were found to be cost effective, and two were highly cost effective. Cost utility ratios ranged from $4439 to $137,271. These results suggest that HIV linkage to care programs are a productive and efficient use of public health funds.

  8. Refining the localization of the PKD2 locus on chromosome 4q by linkage analysis in Spanish families with autosomal dominant polycystic kidney disease type 2

    Energy Technology Data Exchange (ETDEWEB)

    San Millan, J.L.; Viribay, M.; Peral, B.; Moreno, F. [Unidad de Genetica Molecular, Madrid (Spain); Martinez, I. [Hospital de Galdacano (Spain); Weissenbach, J. [Genethon, Evry (France)

    1995-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disorder. At least two distinct forms of ADPKD are now well defined. In {approximately}86% of affected European families, a gene defect localized to 16p13.3 was responsible for ADPKD, while a second locus has been recently localized to 4q13-q23 as candidate for the disease in the remaining families. We present confirmation of linkage to microsatellite markers on chromosome 4q in eight Spanish families with ADPKD, in which the disease was not linked to 16p13.3. By linkage analysis with marker D4S423, a maximum lod score of 9.03 at a recombination fraction of .00 was obtained. Multipoint linkage analysis, as well as a study of recombinant haplotypes, placed the PKD2 locus between D4S1542 and D4S1563, thereby defining a genetic interval of {approximately}1 cM. The refined map will serve as a genetic framework for additional genetic and physical mapping of the region and will improve the accuracy of presymptomatic diagnosis of PKD2. 25 refs., 4 figs., 1 tab.

  9. Parent-of-origin effects in autism identified through genome-wide linkage analysis of 16,000 SNPs.

    Directory of Open Access Journals (Sweden)

    Delphine Fradin

    Full Text Available BACKGROUND: Autism is a common heritable neurodevelopmental disorder with complex etiology. Several genome-wide linkage and association scans have been carried out to identify regions harboring genes related to autism or autism spectrum disorders, with mixed results. Given the overlap in autism features with genetic abnormalities known to be associated with imprinting, one possible reason for lack of consistency would be the influence of parent-of-origin effects that may mask the ability to detect linkage and association. METHODS AND FINDINGS: We have performed a genome-wide linkage scan that accounts for potential parent-of-origin effects using 16,311 SNPs among families from the Autism Genetic Resource Exchange (AGRE and the National Institute of Mental Health (NIMH autism repository. We report parametric (GH, Genehunter and allele-sharing linkage (Aspex results using a broad spectrum disorder case definition. Paternal-origin genome-wide statistically significant linkage was observed on chromosomes 4 (LOD(GH = 3.79, empirical p<0.005 and LOD(Aspex = 2.96, p = 0.008, 15 (LOD(GH = 3.09, empirical p<0.005 and LOD(Aspex = 3.62, empirical p = 0.003 and 20 (LOD(GH = 3.36, empirical p<0.005 and LOD(Aspex = 3.38, empirical p = 0.006. CONCLUSIONS: These regions may harbor imprinted sites associated with the development of autism and offer fruitful domains for molecular investigation into the role of epigenetic mechanisms in autism.

  10. Finite-size scaling of two-point statistics and the turbulent energy cascade generators.

    Science.gov (United States)

    Cleve, Jochen; Dziekan, Thomas; Schmiegel, Jürgen; Barndorff-Nielsen, Ole E; Pearson, Bruce R; Sreenivasan, Katepalli R; Greiner, Martin

    2005-02-01

    Within the framework of random multiplicative energy cascade models of fully developed turbulence, finite-size-scaling expressions for two-point correlators and cumulants are derived, taking into account the observationally unavoidable conversion from an ultrametric to an Euclidean two-point distance. The comparison with two-point statistics of the surrogate energy dissipation, extracted from various wind tunnel and atmospheric boundary layer records, allows an accurate deduction of multiscaling exponents and cumulants, even at moderate Reynolds numbers for which simple power-law fits are not feasible. The extracted exponents serve as input for parametric estimates of the probabilistic cascade generator. Various cascade generators are evaluated.

  11. Five blood pressure loci identified by an updated genome-wide linkage scan: meta-analysis of the Family Blood Pressure Program.

    Science.gov (United States)

    Simino, Jeannette; Shi, Gang; Kume, Rezart; Schwander, Karen; Province, Michael A; Gu, C Charles; Kardia, Sharon; Chakravarti, Aravinda; Ehret, Georg; Olshen, Richard A; Turner, Stephen T; Ho, Low-Tone; Zhu, Xiaofeng; Jaquish, Cashell; Paltoo, Dina; Cooper, Richard S; Weder, Alan; Curb, J David; Boerwinkle, Eric; Hunt, Steven C; Rao, Dabeeru C

    2011-03-01

    A preliminary genome-wide linkage analysis of blood pressure in the Family Blood Pressure Program (FBPP) was reported previously. We harnessed the power and ethnic diversity of the final pooled FBPP dataset to identify novel loci for blood pressure thereby enhancing localization of genes containing less common variants with large effects on blood pressure levels and hypertension. We performed one overall and 4 race-specific meta-analyses of genome-wide blood pressure linkage scans using data on 4,226 African-American, 2,154 Asian, 4,229 Caucasian, and 2,435 Mexican-American participants (total N = 13,044). Variance components models were fit to measured (raw) blood pressure levels and two types of antihypertensive medication adjusted blood pressure phenotypes within each of 10 subgroups defined by race and network. A modified Fisher's method was used to combine the P values for each linkage marker across the 10 subgroups. Five quantitative trait loci (QTLs) were detected on chromosomes 6p22.3, 8q23.1, 20q13.12, 21q21.1, and 21q21.3 based on significant linkage evidence (defined by logarithm of odds (lod) score ≥3) in at least one meta-analysis and lod scores ≥1 in at least 2 subgroups defined by network and race. The chromosome 8q23.1 locus was supported by Asian-, Caucasian-, and Mexican-American-specific meta-analyses. The new QTLs reported justify new candidate gene studies. They may help support results from genome-wide association studies (GWAS) that fall in these QTL regions but fail to achieve the genome-wide significance.

  12. Approach to the origin of turbulence on the basis of two-point kinetic theory

    Science.gov (United States)

    Tsuge, S.

    1974-01-01

    Equations for the fluctuation correlation in an incompressible shear flow are derived on the basis of kinetic theory, utilizing the two-point distribution function which obeys the BBGKY hierarchy equation truncated with the hypothesis of 'ternary' molecular chaos. The step from the molecular to the hydrodynamic description is accomplished by a moment expansion which is a two-point version of the thirteen-moment method, and which leads to a series of correlation equations, viz., the two-point counterparts of the continuity equation, the Navier-Stokes equation, etc. For almost parallel shearing flows the two-point equation is separable and reduces to two Orr-Sommerfeld equations with different physical implications.

  13. New two-point scleral-fixation technique for foldable intraocular lenses with four hollow haptics.

    Science.gov (United States)

    Liu, He-Ting; Jiang, Zheng-Xuan; Tao, Li-Ming

    2016-01-01

    The study was to report a new two-point scleral-fixation technique for foldable intraocular lenses with four haptics. Lenses were slid into the anterior chamber from a 2.8 mm corneal incision and fixed under two sclera flaps at two opposite points. The postoperative best-corrected visual acuities (BCVAs) of all patients were significantly better than their preoperative BCVA. The results demonstrate that two-point, scleral fixations of foldable, intraocular lenses might be practicable and effective.

  14. Using Linkage Analysis to Detect Gene-Gene Interactions. 2. Improved Reliability and Extension to More-Complex Models.

    Directory of Open Access Journals (Sweden)

    Susan E Hodge

    Full Text Available Detecting gene-gene interaction in complex diseases has become an important priority for common disease genetics, but most current approaches to detecting interaction start with disease-marker associations. These approaches are based on population allele frequency correlations, not genetic inheritance, and therefore cannot exploit the rich information about inheritance contained within families. They are also hampered by issues of rigorous phenotype definition, multiple test correction, and allelic and locus heterogeneity. We recently developed, tested, and published a powerful gene-gene interaction detection strategy based on conditioning family data on a known disease-causing allele or a disease-associated marker allele4. We successfully applied the method to disease data and used computer simulation to exhaustively test the method for some epistatic models. We knew that the statistic we developed to indicate interaction was less reliable when applied to more-complex interaction models. Here, we improve the statistic and expand the testing procedure. We computer-simulated multipoint linkage data for a disease caused by two interacting loci. We examined epistatic as well as additive models and compared them with heterogeneity models. In all our models, the at-risk genotypes are "major" in the sense that among affected individuals, a substantial proportion has a disease-related genotype. One of the loci (A has a known disease-related allele (as would have been determined from a previous analysis. We removed (pruned family members who did not carry this allele; the resultant dataset is referred to as "stratified." This elimination step has the effect of raising the "penetrance" and detectability at the second locus (B. We used the lod scores for the stratified and unstratified data sets to calculate a statistic that either indicated the presence of interaction or indicated that no interaction was detectable. We show that the new method is robust

  15. Structure-Function Analysis of a Mixed-linkage β-Glucanase/Xyloglucanase from the Key Ruminal Bacteroidetes Prevotella bryantii B(1)4.

    Science.gov (United States)

    McGregor, Nicholas; Morar, Mariya; Fenger, Thomas Hauch; Stogios, Peter; Lenfant, Nicolas; Yin, Victor; Xu, Xiaohui; Evdokimova, Elena; Cui, Hong; Henrissat, Bernard; Savchenko, Alexei; Brumer, Harry

    2016-01-15

    The recent classification of glycoside hydrolase family 5 (GH5) members into subfamilies enhances the prediction of substrate specificity by phylogenetic analysis. However, the small number of well characterized members is a current limitation to understanding the molecular basis of the diverse specificity observed across individual GH5 subfamilies. GH5 subfamily 4 (GH5_4) is one of the largest, with known activities comprising (carboxymethyl)cellulases, mixed-linkage endo-glucanases, and endo-xyloglucanases. Through detailed structure-function analysis, we have revisited the characterization of a classic GH5_4 carboxymethylcellulase, PbGH5A (also known as Orf4, carboxymethylcellulase, and Cel5A), from the symbiotic rumen Bacteroidetes Prevotella bryantii B14. We demonstrate that carboxymethylcellulose and phosphoric acid-swollen cellulose are in fact relatively poor substrates for PbGH5A, which instead exhibits clear primary specificity for the plant storage and cell wall polysaccharide, mixed-linkage β-glucan. Significant activity toward the plant cell wall polysaccharide xyloglucan was also observed. Determination of PbGH5A crystal structures in the apo-form and in complex with (xylo)glucan oligosaccharides and an active-site affinity label, together with detailed kinetic analysis using a variety of well defined oligosaccharide substrates, revealed the structural determinants of polysaccharide substrate specificity. In particular, this analysis highlighted the PbGH5A active-site motifs that engender predominant mixed-linkage endo-glucanase activity vis à vis predominant endo-xyloglucanases in GH5_4. However the detailed phylogenetic analysis of GH5_4 members did not delineate particular clades of enzymes sharing these sequence motifs; the phylogeny was instead dominated by bacterial taxonomy. Nonetheless, our results provide key enzyme functional and structural reference data for future bioinformatics analyses of (meta)genomes to elucidate the biology of

  16. Genetic linkage map and expression analysis of genes expressed in the lamellae of the edible basidiomycete Pleurotus ostreatus.

    Science.gov (United States)

    Park, Sang-Kyu; Peñas, María M; Ramírez, Lucía; Pisabarro, Antonio G

    2006-05-01

    Pleurotus ostreatus is an industrially cultivated basidiomycete with nutritional and environmental applications. Its genome contains 35 Mbp organized in 11 chromosomes. There is currently available a genetic linkage map based predominantly on anonymous molecular markers complemented with the mapping of QTLs controlling growth rate and industrial productivity. To increase the saturation of the existing linkage maps, we have identified and mapped 82 genes expressed in the lamellae. Their manual annotation revealed that 34.1% of the lamellae-expressed and 71.5% of the lamellae-specific genes correspond to previously unknown sequences or to hypothetical proteins without a clearly established function. Furthermore, the expression pattern of some genes provides an experimental basis for studying gene regulation during the change from vegetative to reproductive growth. Finally, the identification of various differentially regulated genes involved in protein metabolism suggests the relevance of these processes in fruit body formation and maturation.

  17. Parent-Of-Origin Effects in Autism Identified through Genome-Wide Linkage Analysis of 16,000 SNPs

    OpenAIRE

    Delphine Fradin; Keely Cheslack-Postava; Christine Ladd-Acosta; Craig Newschaffer; Aravinda Chakravarti; Arking, Dan E.; Andrew Feinberg; M Daniele Fallin

    2010-01-01

    BACKGROUND: Autism is a common heritable neurodevelopmental disorder with complex etiology. Several genome-wide linkage and association scans have been carried out to identify regions harboring genes related to autism or autism spectrum disorders, with mixed results. Given the overlap in autism features with genetic abnormalities known to be associated with imprinting, one possible reason for lack of consistency would be the influence of parent-of-origin effects that may mask the ability to d...

  18. Comparative analysis of premature mortality among urban immigrants in Bremen, Germany: a retrospective register-based linkage study

    OpenAIRE

    Makarova, Nataliya; Brand, Tilman; Brünings-Kuppe, Claudia; Pohlabeln, Hermann; Luttmann, Sabine

    2016-01-01

    Objectives The main objective of this study was to explore differences in mortality patterns among two large immigrant groups in Germany: one from Turkey and the other from the former Soviet Union (FSU). To this end, we investigated indicators of premature mortality. Design This study was conducted as a retrospective population-based study based on mortality register linkage. Using mortality data for the period 2004–2010, we calculated age-standardised death rates (SDR) and standardised morta...

  19. Exploring a Nonmodel Teleost Genome Through RAD Sequencing—Linkage Mapping in Common Pandora, Pagellus erythrinus and Comparative Genomic Analysis

    OpenAIRE

    Tereza Manousaki; Alexandros Tsakogiannis; Taggart, John B.; Christos Palaiokostas; Dimitris Tsaparis; Jacques Lagnel; Dimitrios Chatziplis; Antonios Magoulas; Nikos Papandroulakis; Mylonas, Constantinos C.; Tsigenopoulos, Costas S

    2016-01-01

    Common pandora (Pagellus erythrinus) is a benthopelagic marine fish belonging to the teleost family Sparidae, and a newly recruited species in Mediterranean aquaculture. The paucity of genetic information relating to sparids, despite their growing economic value for aquaculture, provides the impetus for exploring the genomics of this fish group. Genomic tool development, such as genetic linkage maps provision, lays the groundwork for linking the genotype to phenotype allowing fine-mapping of ...

  20. High density linkage mapping of genomic and transcriptomic SNPs for synteny analysis and anchoring the genome sequence of chickpea

    Science.gov (United States)

    Gaur, Rashmi; Jeena, Ganga; Shah, Niraj; Gupta, Shefali; Pradhan, Seema; Tyagi, Akhilesh K; Jain, Mukesh; Chattopadhyay, Debasis; Bhatia, Sabhyata

    2015-01-01

    This study presents genome-wide discovery of SNPs through next generation sequencing of the genome of Cicer reticulatum. Mapping of the C. reticulatum sequenced reads onto the draft genome assembly of C. arietinum (desi chickpea) resulted in identification of 842,104 genomic SNPs which were utilized along with an additional 36,446 genic SNPs identified from transcriptome sequences of the aforementioned varieties. Two new chickpea Oligo Pool All (OPAs) each having 3,072 SNPs were designed and utilized for SNP genotyping of 129 Recombinant Inbred Lines (RILs). Using Illumina GoldenGate Technology genotyping data of 5,041 SNPs were generated and combined with the 1,673 marker data from previously published studies, to generate a high resolution linkage map. The map comprised of 6698 markers distributed on eight linkage groups spanning 1083.93 cM with an average inter-marker distance of 0.16 cM. Utility of the present map was demonstrated for improving the anchoring of the earlier reported draft genome sequence of desi chickpea by ~30% and that of kabuli chickpea by 18%. The genetic map reported in this study represents the most dense linkage map of chickpea , with the potential to facilitate efficient anchoring of the draft genome sequences of desi as well as kabuli chickpea varieties. PMID:26303721

  1. Genome-wide linkage and copy number variation analysis reveals 710 kb duplication on chromosome 1p31.3 responsible for autosomal dominant omphalocele

    Science.gov (United States)

    Radhakrishna, Uppala; Nath, Swapan K; McElreavey, Ken; Ratnamala, Uppala; Sun, Celi; Maiti, Amit K; Gagnebin, Maryline; Béna, Frédérique; Newkirk, Heather L; Sharp, Andrew J; Everman, David B; Murray, Jeffrey C; Schwartz, Charles E; Antonarakis, Stylianos E; Butler, Merlin G

    2017-01-01

    Background Omphalocele is a congenital birth defect characterised by the presence of internal organs located outside of the ventral abdominal wall. The purpose of this study was to identify the underlying genetic mechanisms of a large autosomal dominant Caucasian family with omphalocele. Methods and findings A genetic linkage study was conducted in a large family with an autosomal dominant transmission of an omphalocele using a genome-wide single nucleotide polymorphism (SNP) array. The analysis revealed significant evidence of linkage (non-parametric NPL = 6.93, p=0.0001; parametric logarithm of odds (LOD) = 2.70 under a fully penetrant dominant model) at chromosome band 1p31.3. Haplotype analysis narrowed the locus to a 2.74 Mb region between markers rs2886770 (63014807 bp) and rs1343981 (65757349 bp). Molecular characterisation of this interval using array comparative genomic hybridisation followed by quantitative microsphere hybridisation analysis revealed a 710 kb duplication located at 63.5–64.2 Mb. All affected individuals who had an omphalocele and shared the haplotype were positive for this duplicated region, while the duplication was absent from all normal individuals of this family. Multipoint linkage analysis using the duplication as a marker yielded a maximum LOD score of 3.2 at 1p31.3 under a dominant model. The 710 kb duplication at 1p31.3 band contains seven known genes including FOXD3, ALG6, ITGB3BP, KIAA1799, DLEU2L, PGM1, and the proximal portion of ROR1. Importantly, this duplication is absent from the database of genomic variants. Conclusions The present study suggests that development of an omphalocele in this family is controlled by overexpression of one or more genes in the duplicated region. To the authors’ knowledge, this is the first reported association of an inherited omphalocele condition with a chromosomal rearrangement. PMID:22499347

  2. Genetic linkage analysis supports the presence of two susceptibility loci for alcoholism and heavy drinking on chromosome 1p22.1-11.2 and 1q21.3-24.2

    Directory of Open Access Journals (Sweden)

    Curtis David

    2005-03-01

    Full Text Available Abstract Background In order to confirm a previous finding of linkage to alcoholism on chromosome 1 we have carried out a genetic linkage study. Methods DNA from eighteen families, densely affected by alcoholism, was used to genotype a set of polymorphic microsatellite markers at loci approximately 10 centimorgans apart spanning the short arm and part of the long arm of chromosome 1. Linkage analyses were performed using the classical lod score and a model-free method. Three different definitions of affection status were defined, these were 1. Heavy Drinking (HD where affected subjects drank more than the Royal College of Psychiatrists recommended weekly amount. 2. The Research Diagnostic Criteria for alcoholism (RDCA 3. Alcohol Dependence Syndrome (ADS as defined by Edwards and Gross (1976 and now incorporated into ICD10 and DSMIV. Results Linkage analyses with the markers D1S1588, D1S2134, D1S1675 covering the cytogenetic region 1p22.1-11.2 all gave positive two point and multipoint lods with a maximum lod of 1.8 at D1S1588 (1p22.1 for the RDCA definition of alcoholism. Another lod of 1.8 was found with D1S1653 in the region 1q21.3-24.2 using the HD affection model. Conclusion These results both support the presence of linkage in the 1p22.1-11.2 region which was previously implicated by the USA Collaborative Study of the Genetics of Alcoholism (COGA study and also suggest the presence of another susceptibility locus at 1q21.3-24.2.

  3. Aspects of record linkage

    NARCIS (Netherlands)

    Schraagen, Marijn Paul

    2014-01-01

    This thesis is an exploration of the subject of historical record linkage. The general goal of historical record linkage is to discover relations between historical entities in a database, for any specific definition of relation, entity and database. Although this task originates from historical

  4. Subsidiary Linkage Patterns

    DEFF Research Database (Denmark)

    Andersson, Ulf; Perri, Alessandra; Nell, Phillip C.

    2012-01-01

    This paper investigates the pattern of subsidiaries' local vertical linkages under varying levels of competition and subsidiary capabilities. Contrary to most previous literature, we explicitly account for the double role of such linkages as conduits of learning prospects as well as potential...

  5. Analysis of four studies in a comparative framework reveals: health linkage consent rates on British cohort studies higher than on UK household panel surveys.

    Science.gov (United States)

    Knies, Gundi; Burton, Jonathan

    2014-11-27

    A number of cohort studies and longitudinal household panel studies in Great Britain have asked for consent to link survey data to administrative health data. We explore commonalities and differences in the process of collecting consent, achieved consent rates and biases in consent with respect to socio-demographic, socio-economic and health characteristics. We hypothesise that British cohort studies which are rooted within the health sciences achieve higher consent rates than the UK household longitudinal studies which are rooted within the social sciences. By contrast, the lack of a specific health focus in household panel studies means there may be less selectivity in consent, in particular, with respect to health characteristics. Survey designs and protocols for collecting informed consent to health record linkage on two British cohort studies and two UK household panel studies are systematically compared. Multivariate statistical analysis is then performed on information from one cohort and two household panel studies that share a great deal of the data linkage protocol but vary according to study branding, survey design and study population. We find that consent is higher in the British cohort studies than in the UK household panel studies, and is higher the more health-focused the study is. There are no systematic patterns of consent bias across the studies and where effects exist within a study or study type they tend to be small. Minority ethnic groups will be underrepresented in record linkage studies on the basis of all three studies. Systematic analysis of three studies in a comparative framework suggests that the factors associated with consent are idiosyncratic to the study. Analysis of linked health data is needed to establish whether selectivity in consent means the resulting research databases suffer from any biases that ought to be considered.

  6. Of River Linkage and Issue Linkage

    NARCIS (Netherlands)

    Warner, Jeroen Frank

    2016-01-01

    It is a truism in mainstream International Relations that issue linkage promotes regime formation and integration. The present article applies this idea to the transboundary lower river Meuse and finds its history of integration to be a tortuous one. Contextual political factors have at times

  7. Gauge-fixing parameter dependence of two-point gauge variant correlation functions

    CERN Document Server

    Zhai, C

    1996-01-01

    The gauge-fixing parameter \\xi dependence of two-point gauge variant correlation functions is studied for QED and QCD. We show that, in three Euclidean dimensions, or for four-dimensional thermal gauge theories, the usual procedure of getting a general covariant gauge-fixing term by averaging over a class of covariant gauge-fixing conditions leads to a nontrivial gauge-fixing parameter dependence in gauge variant two-point correlation functions (e.g. fermion propagators). This nontrivial gauge-fixing parameter dependence modifies the large distance behavior of the two-point correlation functions by introducing additional exponentially decaying factors. These factors are the origin of the gauge dependence encountered in some perturbative evaluations of the damping rates and the static chromoelectric screening length in a general covariant gauge. To avoid this modification of the long distance behavior introduced by performing the average over a class of covariant gauge-fixing conditions, one can either choose ...

  8. Inheritance of 15 microsatellites in the Pacific oyster Crassostrea gigas: segregation and null allele identification for linkage analysis

    Institute of Scientific and Technical Information of China (English)

    LI Li; GUO Ximing; ZHANG Guofan

    2009-01-01

    Microsatellites were screened in a backcross family of the Pacific oyster, Crassostrea gigas. Fifteen microsatellite loci were distinguishable and polymorphic with 6 types of allele-combinations. Null alleles were detected in 46.7% of loci, accounting for 11.7% of the total alleles. Four loci did not segregate in Mendelian Ratios. Three linkage groups were identified among 7 of the 15 segregating loci. Fluorescence-based automated capillary electrophoresis (ABI 310 Genetic Analyzer) that used to detect the microsatellite loci, has been proved a fast, precise, and reliable method in microsatellite genotyping.

  9. Holographic two-point functions for 4d log-gravity

    CERN Document Server

    Johansson, Niklas; Zojer, Thomas

    2012-01-01

    We compute holographic one- and two-point functions of critical higher curvature gravity in four dimensions. The two most important operators are the stress tensor and its logarithmic partner, sourced by ordinary massless and by logarithmic non-normalisable gravitons, respectively. In addition, the logarithmic gravitons source two ordinary operators, one with spin-one and one with spin-zero. The one-point function of the stress tensor vanishes for all Einstein solutions, but has a non-zero contribution from logarithmic gravitons. The two-point functions of all operators match the expectations from a three-dimensional logarithmic conformal field theory.

  10. Numerical methods for stiff systems of two-point boundary value problems

    Science.gov (United States)

    Flaherty, J. E.; Omalley, R. E., Jr.

    1983-01-01

    Numerical procedures are developed for constructing asymptotic solutions of certain nonlinear singularly perturbed vector two-point boundary value problems having boundary layers at one or both endpoints. The asymptotic approximations are generated numerically and can either be used as is or to furnish a general purpose two-point boundary value code with an initial approximation and the nonuniform computational mesh needed for such problems. The procedures are applied to a model problem that has multiple solutions and to problems describing the deformation of thin nonlinear elastic beam that is resting on an elastic foundation.

  11. Verified solutions of two-point boundary value problems for nonlinear oscillators

    Science.gov (United States)

    Bünger, Florian

    Using techniques introduced by Nakao [4], Oishi [5, 6] and applied by Takayasu, Oishi, Kubo [11, 12] to certain nonlinear two-point boundary value problems (see also Rump [7], Chapter 15), we provide a numerical method for verifying the existence of weak solutions of two-point boundary value problems of the form -u″ = a(x, u) + b(x, u)u‧, 0 b are functions that fulfill some regularity properties. The numerical approximation is done by cubic spline interpolation. Finally, the method is applied to the Duffing, the van der Pol and the Toda oscillator. The rigorous numerical computations were done with INTLAB [8].

  12. Adaptation of a two-point boundary value problem solver to a vector-multiprocessor environment

    Energy Technology Data Exchange (ETDEWEB)

    Wright, S.J. (Mathematics Dept., North Carolina State Univ., Raleigh, NC (US)); Pereyra, V. (Weidlinger Associates, Los Angeles, CA (US))

    1990-05-01

    Systems of linear equations arising from finite-difference discretization of two-point boundary value problems have coefficient matrices that are sparse, with most or all of the nonzeros clustered in blocks near the main diagonal. Some efficiently vectorizable algorithms for factorizing these types of matrices and solving the corresponding linear systems are described. The relative effectiveness of the different algorithms varies according to the distribution of initial, final, and coupled end conditions. The techniques described can be extended to handle linear systems arising from other methods for two-point boundary value problems, such as multiple shooting and collocation. An application to seismic ray tracing is discussed.

  13. Construction of a genetic linkage map and QTL analysis for some leaf traits in pear (Pyrus L .)

    Institute of Scientific and Technical Information of China (English)

    Wenying SUN; Yuxing ZHANG; Wenquan LE; Hai'e ZHANG

    2009-01-01

    The major incompatibility barriers to specific inbred lines and the long generation duration in Pyrus L. May hinder the Pyrus breeding process. A genetic linkage map provides the foundation for quantitative trait loci (QTL) mapping and molecular marker-assisted breeding. In this study, we constructed a genetic map with 145 F1 populations from a cross of two cultivars, Yali and Jingbaili, using AFLP and SSR markers. The map consisted of 18 linkage groups which included 402 genetic markers and covered 1395.9 cM, with an average genetic distance of 3.8 cM. The interval mapping was used to identify quantitative trait loci associated with four leaf agronomic traits in the F1 population. The results indicated that four QTLs were associated with leaf length, two QTLs with leaf width, two with leaf length/leaf width, and three with petiole length. The eleven QTLs were associated with 9.9%-48.5% of the phenotypic variation in different traits. It is considered that the map covers almost the whole genome, and molecular markers will be greatly helpful to the related breeding.

  14. Linkage analysis between dominant and co-dominant makers in full-sib families of out-breeding species

    Directory of Open Access Journals (Sweden)

    Alexandre Alonso Alves

    2010-01-01

    Full Text Available As high-throughput genomic tools, such as the DNA microarray platform, have lead to the development of novel genotyping procedures, such as Diversity Arrays Technology (DArT and Single Nucleotide Polymorphisms (SNPs, it is likely that, in the future, high density linkage maps will be constructed from both dominant and co-dominant markers. Recently, a strictly genetic approach was described for estimating recombination frequency (r between co-dominant markers in full-sib families. The complete set of maximum likelihood estimators for r in full-sib families was almost obtained, but unfortunately, one particular configuration involving dominant markers, segregating in a 3:1 ratio and co-dominant markers, was not considered. Here we add nine further estimators to the previously published set, thereby making it possible to cover all combinations of molecular markers with two to four alleles (without epistasis in a full-sib family. This includes segregation in one or both parents, dominance and all linkage phase configurations.

  15. Linkage analysis between dominant and co-dominant makers in full-sib families of out-breeding species.

    Science.gov (United States)

    Alves, Alexandre Alonso; Bhering, Leonardo Lopes; Cruz, Cosme Damião; Alfenas, Acelino Couto

    2010-07-01

    As high-throughput genomic tools, such as the DNA microarray platform, have lead to the development of novel genotyping procedures, such as Diversity Arrays Technology (DArT) and Single Nucleotide Polymorphisms (SNPs), it is likely that, in the future, high density linkage maps will be constructed from both dominant and co-dominant markers. Recently, a strictly genetic approach was described for estimating recombination frequency (r) between co-dominant markers in full-sib families. The complete set of maximum likelihood estimators for r in full-sib families was almost obtained, but unfortunately, one particular configuration involving dominant markers, segregating in a 3:1 ratio and co-dominant markers, was not considered. Here we add nine further estimators to the previously published set, thereby making it possible to cover all combinations of molecular markers with two to four alleles (without epistasis) in a full-sib family. This includes segregation in one or both parents, dominance and all linkage phase configurations.

  16. Development of a molecular genetic linkage map for Colletotrichum lindemuthianum and segregation analysis of two avirulence genes.

    Science.gov (United States)

    Luna-Martínez, Francisco; Rodríguez-Guerra, Raúl; Victoria-Campos, Mayra; Simpson, June

    2007-02-01

    A framework genetic map was developed for the fungal pathogen Colletotrichum lindemuthianum, the causal agent of anthracnose of common bean (Phaseolus vulgaris L.). This is the first genetic map for any species within the family Melanconiaceae and the genus Colletotrichum and provides the first estimate of genome length for C. lindemuthianum. The map was generated using 106 haploid F1 progeny derived from crossing two Mexican C. lindemuthianum isolates differing in two avirulence genes (AvrclMex and AvrclTO). The map comprises 165 AFLP markers covering 1,897 cM with an average spacing of 11.49 cM. The markers are distributed over 19 major linkage groups containing between 5 and 25 markers each and the genome length was estimated to be approximately 3,241 cM. The avirulence genes AvrclMex and AvrclTO segregate in a 1:1 ratio supporting the gene for gene hypothesis for the incompatible reaction between C. lindemuthianum and P. vulgaris, but could not be incorporated into the genetic map. This initial outline map forms the basis for the development of a more detailed C. lindemuthianum linkage map, which would include other types of molecular markers and allow the location of genes previously isolated and characterized in this species.

  17. Review on the Application of Web Linkage-analysis%网络链接分析应用研究综述

    Institute of Scientific and Technical Information of China (English)

    文庭孝; 王尧; 杨雅惟; 刘璇

    2011-01-01

    Web linkage-analysis is an important method in Webometrics research,and it has extensive application.Now Web linkage-analysis was used in following fields: web information resourse assessment,website impact evaluation,university evaluation,discovery of co%网络链接分析法是网络信息计量学研究的重要研究方法,具有广泛的应用。目前国内外主要将网络链接分析方法用于网络信息资源评价、网站网络影响力评价、大学评价、核心网络与核心作者发现、竞争情报与竞争对手分析、网站关联分析、期刊评价以及搜索引擎优化等方面。

  18. Genome-wide linkage and sequence analysis challenge CCDC66 as a human retinal dystrophy candidate gene and support a distinct NMNAT1-related fundus phenotype.

    Science.gov (United States)

    Khan, A O; Budde, B S; Nürnberg, P; Kawalia, A; Lenzner, S; Bolz, H J

    2017-03-30

    To uncover the genotype underlying early-onset cone-rod dystrophy and central nummular macular atrophic lesion in 2 siblings from an endogamous Arab family, we performed targeted next-generation sequencing (NGS) of 44 retinal dystrophy genes, whole-exome sequencing (WES) and genome-wide linkage analysis. Targeted NGS and WES in the index patient highlighted 2 homozygous variants, a CCDC66 frameshift deletion and a novel missense NMNAT1 variant, c.500G>A (p.Asn167Ser). Linkage and segregation analysis excluded the CCDC66 variant and confirmed the NMNAT1 mutation. Biallelic NMNAT1 mutations cause Leber congenital amaurosis with a central nummular macular atrophic lesion (LCA9). The NMNAT1 mutation reported here underlied cone-rod dystrophy rather than LCA but the fundus lesion was compatible with that of LCA9 patients, highlighting that such a fundus appearance should raise suspicion for biallelic mutations in NMNAT1 when in the context of any retinal dystrophy. Although Ccdc66 mutations have been proposed to cause retinal disease in dogs, our results and public databases challenge CCDC66 as a candidate gene for human retinal dystrophy. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Analysis of RUNX1 binding site and RAPTOR polymorphisms in psoriasis: no evidence for association despite adequate power and evidence for linkage

    Science.gov (United States)

    Stuart, P; Nair, R P; Abecasis, G R; Nistor, I; Hiremagalore, R; Chia, N V; Qin, Z S; Thompson, R A; Jenisch, S; Weichenthal, M; Janiga, J; Lim, H W; Christophers, E; Voorhees, J J; Elder, J T

    2006-01-01

    Background A previous study identified two peaks of allelic association between psoriasis and single nucleotide polymorphisms (SNPs) mapping to distal chromosome 17q, including a disease associated SNP that leads to loss of a RUNX1 transcription factor binding site, and additional SNPs in the third intron of the RAPTOR gene. Another study found an association with SNPs in the RAPTOR gene, but not with the RUNX1 binding site polymorphism. Methods In an effort to confirm these observations, we genotyped 579 pedigrees containing 1285 affected individuals for three SNPs immediately flanking and including the RUNX1 binding site, and for three SNPs in the RAPTOR gene. Results Here we report further evidence for linkage to distal chromosome 17q, with a linkage peak mapping 1.7 cM distal to the RUNX1 binding site (logarithm of the odds 2.26 to 2.73, depending upon statistic used). However, we found no evidence for association to individual SNPs or haplotypes in either of the previously identified peaks of association. Power analysis demonstrated 80% power to detect significant association at genotype relative risks of 1.2 (additive and multiplicative models) to 1.5 (dominant and recessive models) for the RUNX1 binding site, and 1.3 to 1.4 for the RAPTOR locus under all models except dominant. Conclusions Our data provide no support for the previously identified RUNX1 binding site or for the RAPTOR locus as genetic determinants of psoriasis, despite evidence for linkage of psoriasis to distal chromosome 17q. PMID:15923274

  20. Using linkage analysis to detect gene-gene interaction by stratifying family data on known disease, or disease-associated, alleles.

    Directory of Open Access Journals (Sweden)

    Barbara Corso

    Full Text Available Detecting gene-gene interaction in complex diseases is a major challenge for common disease genetics. Most interaction detection approaches use disease-marker associations and such methods have low power and unknown reliability in real data. We developed and tested a powerful linkage-analysis-based gene-gene interaction detection strategy based on conditioning the family data on a known disease-causing allele or disease-associated marker allele. We computer-generated multipoint linkage data for a disease caused by two epistatically interacting loci (A and B. We examined several two-locus epistatic inheritance models: dominant-dominant, dominant-recessive, recessive-dominant, recessive-recessive. At one of the loci (A, there was a known disease-related allele. We stratified the family data on the presence of this allele, eliminating family members who were without it. This elimination step has the effect of raising the "penetrance" at the second locus (B. We then calculated the lod score at the second locus (B and compared the pre- and post-stratification lod scores at B. A positive difference indicated interaction. We also examined if it was possible to detect interaction with locus B based on a disease-marker association (instead of an identified disease allele at locus A. We also tested whether the presence of genetic heterogeneity would generate false positive evidence of interaction. The power to detect interaction for a known disease allele was 60-90%. The probability of false positives, based on heterogeneity, was low. Decreasing linkage disequilibrium between the disease and marker at locus A decreased the likelihood of detecting interaction. The allele frequency of the associated marker made little difference to the power.

  1. Meta-conformal invariance and the boundedness of two-point correlation functions

    Science.gov (United States)

    Henkel, Malte; Stoimenov, Stoimen

    2016-11-01

    The covariant two-point functions, derived from Ward identities in direct space, can be affected by consistency problems and can become unbounded for large time- or space-separations. This difficulty arises for several extensions of dynamical scaling, for example Schrödinger-invariance, conformal Galilei invariance or meta-conformal invariance, but not for standard ortho-conformal invariance. For meta-conformal invariance in (1+1) dimensions, which acts as a dynamical symmetry of a simple advection equation, these difficulties can be cured by going over to a dual space and an extension of these dynamical symmetries through the construction of a new generator in the Cartan sub-algebra. This provides a canonical interpretation of meta-conformally covariant two-point functions as correlators. Galilei-conformal correlators can be obtained from meta-conformal invariance through a simple contraction. In contrast, by an analogus construction, Schrödinger-covariant two-point functions are causal response functions. All these two-point functions are bounded at large separations, for sufficiently positive values of the scaling exponents.

  2. Meta-conformal invariance and the boundedness of two-point correlation functions

    CERN Document Server

    Henkel, Malte

    2016-01-01

    The covariant two-point functions, derived from Ward identities in direct space, can be affected by consistency problems and can become unbounded for large time- or space-separations. This difficulty arises for several extensions of dynamical scaling, for example Schr\\"odinger-invariance, conformal Galilei invariance or meta-conformal invariance, but not for standard ortho-conformal invariance. For meta-conformal invariance in 1+1 dimensions, these difficulties can be cured by going over to a dual space and an extension of these dynamical symmetries through the construction of a new generator in the Cartan sub-algebra. This provides a canonical interpretation of meta-conformally covariant two-point functions as correlators. Galilei-conformal correlators can be obtained from meta-conformal invariance through a simple contraction. In contrast, by an analogus construction, Schr\\"odinger-covariant two-point functions are causal response functions. All these two-point functions are bounded at large separations, fo...

  3. Holographic two-point functions for 4d log-gravity

    NARCIS (Netherlands)

    Johansson, Niklas; Naseh, Ali; Zojer, Thomas

    2012-01-01

    We compute holographic one- and two-point functions of critical higher-curvature gravity in four dimensions. The two most important operators are the stress tensor and its logarithmic partner, sourced by ordinary massless and by logarithmic non-normalisable gravitons, respectively. In addition, the

  4. Solvability for a Class of Abstract Two-Point Boundary Value Problems Derived from Optimal Control

    Directory of Open Access Journals (Sweden)

    Wang Lianwen

    2007-01-01

    Full Text Available The solvability for a class of abstract two-point boundary value problems derived from optimal control is discussed. By homotopy technique existence and uniqueness results are established under some monotonic conditions. Several examples are given to illustrate the application of the obtained results.

  5. Solvability for a Class of Abstract Two-Point Boundary Value Problems Derived from Optimal Control

    Directory of Open Access Journals (Sweden)

    Lianwen Wang

    2008-01-01

    Full Text Available The solvability for a class of abstract two-point boundary value problems derived from optimal control is discussed. By homotopy technique existence and uniqueness results are established under some monotonic conditions. Several examples are given to illustrate the application of the obtained results.

  6. Modification of the Two-Point Touch Cane Technique: A Pilot Study.

    Science.gov (United States)

    Jacobson, William H.; Ehresman, Paul

    1983-01-01

    Four blind adults were observed to determine the extent of the natural movement of their centers of gravity in relation to arc height during the two-point touch technique for long cane travel. The Ss learned and practiced a modified technique using their center of gravity as much as possible. (Author)

  7. Two-point discrimination of the upper extremities of healthy Koreans in their 20's.

    Science.gov (United States)

    Koo, Ja-Pung; Kim, Soon-Hee; An, Ho-Jung; Moon, Ok-Gon; Choi, Jung-Hyun; Yun, Young-Dae; Park, Joo-Hyun; Min, Kyoung-Ok

    2016-03-01

    [Purpose] The present study attempted to measure two-point discrimination in the upper extremities of healthy Koreans in their 20's. [Subjects and Methods] Using a three-point esthesiometer, we conducted an experiment with a group of 256 college students (128 male and 128 female), attending N University in Chonan, Republic of Korea. [Results] Females showed two-point discrimination at a shorter distance than males at the following points: (i) 5 cm above the elbow joint, the middle part, and 5 cm below the shoulder joint of the anterior upper arm; (ii) 5 cm above the elbow joint and 5 cm below the shoulder joint of the posterior upper arm; (iii) 5 cm above the front of the wrist joint of the forearm; 5 cm below the elbow joint, the palmar part of the distal interphalangeal joint of the thumb, the dorsal part of the distal interphalangeal joint of the middle and little fingers. It was also found that females showed greater two-point discrimination than males in distal regions rather than proximal regions. [Conclusion] The findings of this study will help establish normal values for two-point discrimination of upper extremities of young Koreans in their 20's.

  8. Logarithmic two-Point Correlation Functions from a z = 2 Lifshitz Model

    NARCIS (Netherlands)

    Zingg, T.

    2013-01-01

    The Einstein-Proca action is known to have asymptotically locally Lifshitz spacetimes as classical solutions. For dynamical exponent z=2, two-point correlation functions for fluctuations around such a geometry are derived analytically. It is found that the retarded correlators are stable in the sens

  9. Problem with two-point conditions for parabolic equation of second order on time

    Directory of Open Access Journals (Sweden)

    M. M. Symotyuk

    2014-12-01

    Full Text Available The  correctness of a problem with two-point conditions ontime-variable and of  Dirichlet-type conditions  on spatialcoordinates for the linear  parabolic equations with variablecoefficients are established. The metric theorem on estimationsfrom below of small denominators of the problem (the notions of Hausdorff measure is proved.

  10. NUMERICAL SIMULATION OF TWO-POINT CONTACT BETWEEN WHEEL AND RAIL

    Institute of Scientific and Technical Information of China (English)

    Jun Zhang; Shouguang Sun; Xuesong Jin

    2009-01-01

    The elastic-plastic contact problem with rolling friction of wheel-rail is solved using the FE parametric quadratic programming method. Thus, the complex elastic-plastic contact problem can be calculated with high accuracy and efficiency, while the Hertz's hypothesis and the elastic semi-space assumption are avoided. Based on the 'one-point' contact calculation of wheel-rail, the computational model of 'two-point' contact are established and calculated when the wheel flange is close to the rail. In the case of 'two-point' contact, the changing laws of wheelrail contact are introduced and contact forces in various load cases are carefully analyzed. The main reason of wheel flange wear and rail side wear is found. Lubrication computational model of the wheel flange is constructed. Comparing with the result without lubrication, the contact force between wheel flange and rail decreases, which is beneficial for reducing the wear of wheel-rail.

  11. Equal-time two-point correlation functions in Coulomb gauge Yang-Mills theory

    CERN Document Server

    Campagnari, D; Reinhardt, H; Astorga, F; Schleifenbaum, W

    2009-01-01

    We apply a new functional perturbative approach to the calculation of the equal-time two-point correlation functions and the potential between static color charges to one-loop order in Coulomb gauge Yang-Mills theory. The functional approach proceeds through a solution of the Schroedinger equation for the vacuum wave functional to order g^2 and derives the equal-time correlation functions from a functional integral representation via new diagrammatic rules. We show that the results coincide with those obtained from the usual Lagrangian functional integral approach, extract the beta function and determine the anomalous dimensions of the equal-time gluon and ghost two-point functions and the static potential under the assumption of multiplicative renormalizability to all orders.

  12. Two-point functions of conformal primary operators in $\\mathcal{N}=1$ superconformal theories

    CERN Document Server

    Li, Daliang

    2014-01-01

    In $\\mathcal{N}=1$ superconformal theories in four dimensions the two-point function of superconformal multiplets is known up to an overall constant. A superconformal multiplet contains several conformal primary operators, whose two-point function coefficients can be determined in terms of the multiplet's quantum numbers. In this paper we work out these coefficients in full generality, i.e. for superconformal multiplets that belong to any irreducible representation of the Lorentz group with arbitrary scaling dimension and R-charge. From our results we recover the known unitarity bounds, and also find all shortening conditions, even for non-unitary theories. For the purposes of our computations we have developed a Mathematica package for the efficient handling of expansions in Grassmann variables.

  13. Beyond Kaiser bias: mildly non-linear two-point statistics of densities in distant spheres

    Science.gov (United States)

    Uhlemann, C.; Codis, S.; Kim, J.; Pichon, C.; Bernardeau, F.; Pogosyan, D.; Park, C.; L'Huillier, B.

    2017-04-01

    We present simple parameter-free analytic bias functions for the two-point correlation of densities in spheres at large separation. These bias functions generalize the so-called Kaiser bias to the mildly non-linear regime for arbitrary density contrasts and grow as b(ρ) - b(1) ∝ (1 - ρ-13/21)ρ1 + n/3 with b(1) = -4/21 - n/3 for a power-law initial spectrum with index n. We carry out the derivation in the context of large-deviation statistics while relying on the spherical collapse model. We use a logarithmic transformation that provides a saddle-point approximation that is valid for the whole range of densities and show its accuracy against the 30 Gpc cube state-of-the-art Horizon Run 4 simulation. Special configurations of two concentric spheres that allow us to identify peaks are employed to obtain the conditional bias and a proxy for the BBKS extremum correlation functions. These analytic bias functions should be used jointly with extended perturbation theory to predict two-point clustering statistics as they capture the non-linear regime of structure formation at the per cent level down to scales of about 10 Mpc h-1 at redshift 0. Conversely, the joint statistics also provide us with optimal dark matter two-point correlation estimates that can be applied either universally to all spheres or to a restricted set of biased (over- or underdense) pairs. Based on a simple fiducial survey, we show that the variance of this estimator is reduced by five times relative to the traditional sample estimator for the two-point function. Extracting more information from correlations of different types of objects should prove essential in the context of upcoming surveys like Euclid, DESI and WFIRST.

  14. Microsatellite isolation and marker development in carrot - genomic distribution, linkage mapping, genetic diversity analysis and marker transferability across Apiaceae

    Directory of Open Access Journals (Sweden)

    Yildiz Mehtap

    2011-08-01

    Full Text Available Abstract Background The Apiaceae family includes several vegetable and spice crop species among which carrot is the most economically important member, with ~21 million tons produced yearly worldwide. Despite its importance, molecular resources in this species are relatively underdeveloped. The availability of informative, polymorphic, and robust PCR-based markers, such as microsatellites (or SSRs, will facilitate genetics and breeding of carrot and other Apiaceae, including integration of linkage maps, tagging of phenotypic traits and assisting positional gene cloning. Thus, with the purpose of isolating carrot microsatellites, two different strategies were used; a hybridization-based library enrichment for SSRs, and bioinformatic mining of SSRs in BAC-end sequence and EST sequence databases. This work reports on the development of 300 carrot SSR markers and their characterization at various levels. Results Evaluation of microsatellites isolated from both DNA sources in subsets of 7 carrot F2 mapping populations revealed that SSRs from the hybridization-based method were longer, had more repeat units and were more polymorphic than SSRs isolated by sequence search. Overall, 196 SSRs (65.1% were polymorphic in at least one mapping population, and the percentage of polymophic SSRs across F2 populations ranged from 17.8 to 24.7. Polymorphic markers in one family were evaluated in the entire F2, allowing the genetic mapping of 55 SSRs (38 codominant onto the carrot reference map. The SSR loci were distributed throughout all 9 carrot linkage groups (LGs, with 2 to 9 SSRs/LG. In addition, SSR evaluations in carrot-related taxa indicated that a significant fraction of the carrot SSRs transfer successfully across Apiaceae, with heterologous amplification success rate decreasing with the target-species evolutionary distance from carrot. SSR diversity evaluated in a collection of 65 D. carota accessions revealed a high level of polymorphism for these

  15. A rapid and accurate two-point ray tracing method in horizontally layered velocity model

    Institute of Scientific and Technical Information of China (English)

    TIAN Yue; CHEN Xiao-fei

    2005-01-01

    A rapid and accurate method for two-point ray tracing in horizontally layered velocity model is presented in this paper. Numerical experiments show that this method provides stable and rapid convergence with high accuracies, regardless of various 1-D velocity structures, takeoff angles and epicentral distances. This two-point ray tracing method is compared with the pseudobending technique and the method advanced by Kim and Baag (2002). It turns out that the method in this paper is much more efficient and accurate than the pseudobending technique, but is only applicable to 1-D velocity model. Kim(s method is equivalent to ours for cases without large takeoff angles, but it fails to work when the takeoff angle is close to 90o. On the other hand, the method presented in this paper is applicable to cases with any takeoff angles with rapid and accurate convergence. Therefore, this method is a good choice for two-point ray tracing problems in horizontally layered velocity model and is efficient enough to be applied to a wide range of seismic problems.

  16. Comparison of Optimization and Two-point Methods in Estimation of Soil Water Retention Curve

    Science.gov (United States)

    Ghanbarian-Alavijeh, B.; Liaghat, A. M.; Huang, G.

    2009-04-01

    Soil water retention curve (SWRC) is one of the soil hydraulic properties in which its direct measurement is time consuming and expensive. Since, its measurement is unavoidable in study of environmental sciences i.e. investigation of unsaturated hydraulic conductivity and solute transport, in this study the attempt is to predict soil water retention curve from two measured points. By using Cresswell and Paydar (1996) method (two-point method) and an optimization method developed in this study on the basis of two points of SWRC, parameters of Tyler and Wheatcraft (1990) model (fractal dimension and air entry value) were estimated and then water content at different matric potentials were estimated and compared with their measured values (n=180). For each method, we used both 3 and 1500 kPa (case 1) and 33 and 1500 kPa (case 2) as two points of SWRC. The calculated RMSE values showed that in the Creswell and Paydar (1996) method, there exists no significant difference between case 1 and case 2. However, the calculated RMSE value in case 2 (2.35) was slightly less than case 1 (2.37). The results also showed that the developed optimization method in this study had significantly less RMSE values for cases 1 (1.63) and 2 (1.33) rather than Cresswell and Paydar (1996) method.

  17. Calculating two-point resistances in distance-regular resistor networks

    Energy Technology Data Exchange (ETDEWEB)

    Jafarizadeh, M A [Department of Theoretical Physics and Astrophysics, University of Tabriz, Tabriz 51664 (Iran, Islamic Republic of); Sufiani, R [Department of Theoretical Physics and Astrophysics, University of Tabriz, Tabriz 51664 (Iran, Islamic Republic of); Jafarizadeh, S [Department of Electrical and computer engineering, University of Tabriz, Tabriz 51664 (Iran, Islamic Republic of)

    2007-05-11

    An algorithm for the calculation of the resistance between two arbitrary nodes in an arbitrary distance-regular resistor network is provided, where the calculation is based on stratification introduced in Jafarizadeh and Salimi (2006 J. Phys. A: Math. Gen. 39 1-29) and the Stieltjes transform of the spectral distribution (Stieltjes function) associated with the network. It is shown that the resistances between a node {alpha} and all nodes {beta} belonging to the same stratum with respect to the {alpha} (R{sub {alpha}}{sub {beta}{sup (i)}}), {beta} belonging to the ith stratum with respect to the {alpha}) are the same. Also, the analytical formulae for two-point resistances R{sub {alpha}}{sub {beta}{sup (i)}}, i=1,2,3, are given in terms of the size of the network and corresponding intersection numbers. In particular, the two-point resistances in a strongly regular network are given in terms of its parameters (v, {kappa}, {lambda}, {mu}). Moreover, the lower and upper bounds for two-point resistances in strongly regular networks are discussed.

  18. An estimating function approach to linkage heterogeneity

    Indian Academy of Sciences (India)

    He Gao; Ying Zhou; Weijun Ma; Haidong Liu; Linan Zhao

    2013-12-01

    Testing linkage heterogeneity between two loci is an important issue in genetics. Currently, there are four methods (K-test, A-test, B-test and D-test) for testing linkage heterogeneity in linkage analysis, which are based on the likelihood-ratio test. Among them, the commonly used methods are the K-test and A-test. In this paper, we present a novel test method which is different from the above four tests, called G-test. The new test statistic is based on estimating function, possessing a theoretic asymptotic distribution, and therefore demonstrates its own advantages. The proposed test is applied to analyse a real pedigree dataset. Our simulation results also indicate that the G-test performs well in terms of power of testing linkage heterogeneity and outperforms the current methods to some degree.

  19. Construction of a genetic linkage map of Thlaspi caerulescens and quantitative trait loci analysis of zinc accumulation.

    Science.gov (United States)

    Assunção, Ana G L; Pieper, Bjorn; Vromans, Jaap; Lindhout, Pim; Aarts, Mark G M; Schat, Henk

    2006-01-01

    Zinc (Zn) hyperaccumulation seems to be a constitutive species-level trait in Thlaspi caerulescens. When compared under conditions of equal Zn availability, considerable variation in the degree of hyperaccumulation is observed among accessions originating from different soil types. This variation offers an excellent opportunity for further dissection of the genetics of this trait. A T. caerulescens intraspecific cross was made between a plant from a nonmetallicolous accession [Lellingen (LE)], characterized by relatively high Zn accumulation, and a plant from a calamine accession [La Calamine (LC)], characterized by relatively low Zn accumulation. Zinc accumulation in roots and shoots segregated in the F3 population. This population was used to construct an LE/LC amplified fragment length polymorphism (AFLP)-based genetic linkage map and to map quantitative trait loci (QTL) for Zn accumulation. Two QTL were identified for root Zn accumulation, with the trait-enhancing alleles being derived from each of the parents, and explaining 21.7 and 16.6% of the phenotypic variation observed in the mapping population. Future development of more markers, based on Arabidopsis orthologous genes localized in the QTL regions, will allow fine-mapping and map-based cloning of the genes underlying the QTL.

  20. A Unified Discussion on the Concept of Score Functions Used in the Context of Nonparametric Linkage Analysis

    Directory of Open Access Journals (Sweden)

    Lars Ängquist

    2008-01-01

    Full Text Available In this article we try to discuss nonparametric linkage (NPL score functions within a broad and quite general framework. The main focus of the paper is the structure, derivation principles and interpretations of the score function entity itself. We define and discuss several families of one-locus score function definitions, i.e. the implicit, explicit and optimal ones. Some generalizations and comments to the two-locus, unconditional and conditional, cases are included as well. Although this article mainly aims at serving as an overview, where the concept of score functions are put into a covering context, we generalize the noncentrality parameter (NCP optimal score functions in Ängquist et al. (2007 to facilitate—through weighting—for incorporation of several plausible distinct genetic models. Since the genetic model itself most oftenly is to some extent unknown this facilitates weaker prior assumptions with respect to plausible true disease models without loosing the property of NCP-optimality. Moreover, we discuss general assumptions and properties of score functions in the above sense. For instance, the concept of identical by descent (IBD sharing structures and score function equivalence are discussed in some detail.

  1. Automation of High-Throughput Mass Spectrometry-Based Plasma N-Glycome Analysis with Linkage-Specific Sialic Acid Esterification.

    Science.gov (United States)

    Bladergroen, Marco R; Reiding, Karli R; Hipgrave Ederveen, Agnes L; Vreeker, Gerda C M; Clerc, Florent; Holst, Stephanie; Bondt, Albert; Wuhrer, Manfred; van der Burgt, Yuri E M

    2015-09-04

    Glycosylation is a post-translational modification of key importance with heterogeneous structural characteristics. Previously, we have developed a robust, high-throughput MALDI-TOF-MS method for the comprehensive profiling of human plasma N-glycans. In this approach, sialic acid residues are derivatized with linkage-specificity, namely the ethylation of α2,6-linked sialic acid residues with parallel lactone formation of α2,3-linked sialic acids. In the current study, this procedure was used as a starting point for the automation of all steps on a liquid-handling robot system. This resulted in a time-efficient and fully standardized procedure with throughput times of 2.5 h for a first set of 96 samples and approximately 1 h extra for each additional sample plate. The mass analysis of the thus-obtained glycans was highly reproducible in terms of relative quantification, with improved interday repeatability as compared to that of manual processing.

  2. Linkage between passenger demand and surrounding land-use patterns at urban rail transit stations: A canonical correlation analysis method and case study in Chongqing

    Directory of Open Access Journals (Sweden)

    Xin Li

    2016-08-01

    Full Text Available This paper employs a canonical correlation analysis method to quantify the linkage between urban rail transit station demand and the surrounding land-use patterns. It is used to identify key land use variables by evaluating their degrees of contribution to the rail transit station demand. A full month of IC card data and detailed regulatory land use plan from Chongqing, China are collected for model development and validation. The proposed model contributes to offering the capability of targeting key land use patterns and associating them with rail transit station boarding and alighting demand simultaneously. The proposed model can reveal underlying rules between rail transit station demand and land use variables and can be used to evaluate the Transit Oriented Development (TOD plans to improve land use and transit operational efficiency.

  3. Interactive Record Linkage

    Directory of Open Access Journals (Sweden)

    2000-12-01

    Full Text Available In order to carry out demographic analyses at individual and group levels, a manual method of linking individual event records from parish registers was developed in the late 1950s. In order to save time and to work with larger areas than small parishes, systems for automatic record linkage were developed a couple of decades later. A third method, an interactive record linkage, named Demolink, has been developed even more recently. The main new feature of the method is the possibility of linking from more than two historical sources simultaneously. This improves the process of sorting out which events belong to which individual life courses. This paper discusses how Demolink was used for record linkage in a large Norwegian parish for the period 1801-1878.

  4. Ordered-subset analysis of savant skills in autism for 15q11-q13.

    Science.gov (United States)

    Ma, D Q; Jaworski, J; Menold, M M; Donnelly, S; Abramson, R K; Wright, H H; Delong, G R; Gilbert, J R; Pericak-Vance, M A; Cuccaro, Michael L

    2005-05-05

    Autism is a complex disorder characterized by genetic and phenotypic heterogeneity. Analysis of phenotypically homogeneous subtypes has been used to both confirm and narrow potential autism linkage regions such as the chromosomal region 15q11-q13. Increased evidence for linkage in this region had been found in a subgroup of 21 autism families (total families = 94) stratified based on a savant skill factor (SSF) from the Autism Diagnostic Interview, Revised (ADI-R). We examined the savant phenotypic finding in our sample of 91 multiplex autism families. Using two-point parametric analysis in stratification with a cutoff point of a savant skill score of 0.16, our families failed to demonstrate linkage to 15q11-q13. In addition, ordered subset analysis (OSA) using SSF as a covariate also failed to show evidence for linkage. Our findings do not support savant skills as an informative phenotypic subset for linkage in our sample.

  5. Optimal Constraints on Local Primordial Non-Gaussianity from the Two-Point Statistics of Large-Scale Structure

    CERN Document Server

    Hamaus, Nico; Desjacques, Vincent

    2011-01-01

    One of the main signatures of primordial non-Gaussianity of the local type is a scale-dependent correction to the bias of large-scale structure tracers such as galaxies or clusters, whose amplitude depends on the bias of the tracers itself. The dominant source of noise in the power spectrum of the tracers is caused by sampling variance on large scales (where the non-Gaussian signal is strongest) and shot noise arising from their discrete nature. Recent work has argued that one can avoid sampling variance by comparing multiple tracers of different bias, and suppress shot noise by optimally weighting halos of different mass. Here we combine these ideas and investigate how well the signatures of non-Gaussian fluctuations in the primordial potential can be extracted from the two-point correlations of halos and dark matter. On the basis of large $N$-body simulations with local non-Gaussian initial conditions and their halo catalogs we perform a Fisher matrix analysis of the two-point statistics. Compared to the st...

  6. A consensus microsatellite-based linkage map for the hermaphroditic bay scallop (Argopecten irradians and its application in size-related QTL analysis.

    Directory of Open Access Journals (Sweden)

    Hongjun Li

    Full Text Available Bay scallop (Argopecten irradians is one of the most economically important aquaculture species in China. In this study, we constructed a consensus microsatellite-based genetic linkage map with a mapping panel containing two hybrid backcross-like families involving two subspecies of bay scallop, A. i. irradians and A. i. concentricus. One hundred sixty-one microsatellite and one phenotypic (shell color markers were mapped to 16 linkage groups (LGs, which corresponds to the haploid chromosome number of bay scallop. The sex-specific map was 779.2 cM and 781.6 cM long in female and male, respectively, whereas the sex-averaged map spanned 849.3 cM. The average resolution of integrated map was 5.9 cM/locus and the estimated coverage was 81.3%. The proportion of distorted markers occurred more in the hybrid parents, suggesting that the segregation distortion was possibly resulted from heterospecific interaction between genomes of two subspecies of bay scallop. The overall female-to-male recombination rate was 1.13:1 across all linked markers in common to both parents, and considerable differences in recombination also existed among different parents in both families. Four size-related traits, including shell length (SL, shell height (SH, shell width (SW and total weight (TW were measured for quantitative trait loci (QTL analysis. Three significant and six suggestive QTL were detected on five LGs. Among the three significant QTL, two (qSW-10 and qTW-10, controlling SW and TW, respectively were mapped on the same region near marker AiAD121 on LG10 and explained 20.5% and 27.7% of the phenotypic variance, while the third (qSH-7, controlling SH was located on LG7 and accounted for 15.8% of the phenotypic variance. Six suggestive QTL were detected on four different LGs. The linkage map and size-related QTL obtained in this study may facilitate marker-assisted selection (MAS in bay scallop.

  7. Genetic correlates of brain aging on MRI and cognitive test measures: a genome-wide association and linkage analysis in the Framingham study

    Science.gov (United States)

    Seshadri, Sudha; DeStefano, Anita L; Au, Rhoda; Massaro, Joseph M; Beiser, Alexa S; Kelly-Hayes, Margaret; Kase, Carlos S; D'Agostino, Ralph B; DeCarli, Charles; Atwood, Larry D; Wolf, Philip A

    2007-01-01

    Background Brain magnetic resonance imaging (MRI) and cognitive tests can identify heritable endophenotypes associated with an increased risk of developing stroke, dementia and Alzheimer's disease (AD). We conducted a genome-wide association (GWA) and linkage analysis exploring the genetic basis of these endophenotypes in a community-based sample. Methods A total of 705 stroke- and dementia-free Framingham participants (age 62 +9 yrs, 50% male) who underwent volumetric brain MRI and cognitive testing (1999–2002) were genotyped. We used linear models adjusting for first degree relationships via generalized estimating equations (GEE) and family based association tests (FBAT) in additive models to relate qualifying single nucleotide polymorphisms (SNPs, 70,987 autosomal on Affymetrix 100K Human Gene Chip with minor allele frequency ≥ 0.10, genotypic call rate ≥ 0.80, and Hardy-Weinberg equilibrium p-value ≥ 0.001) to multivariable-adjusted residuals of 9 MRI measures including total cerebral brain (TCBV), lobar, ventricular and white matter hyperintensity (WMH) volumes, and 6 cognitive factors/tests assessing verbal and visuospatial memory, visual scanning and motor speed, reading, abstract reasoning and naming. We determined multipoint identity-by-descent utilizing 10,592 informative SNPs and 613 short tandem repeats and used variance component analyses to compute LOD scores. Results The strongest gene-phenotype association in FBAT analyses was between SORL1 (rs1131497; p = 3.2 × 10-6) and abstract reasoning, and in GEE analyses between CDH4 (rs1970546; p = 3.7 × 10-8) and TCBV. SORL1 plays a role in amyloid precursor protein processing and has been associated with the risk of AD. Among the 50 strongest associations (25 each by GEE and FBAT) were other biologically interesting genes. Polymorphisms within 28 of 163 candidate genes for stroke, AD and memory impairment were associated with the endophenotypes studied at p < 0.001. We confirmed our previously

  8. Covariant and infrared-free graviton two-point function in de Sitter spacetime. II.

    Science.gov (United States)

    Pejhan, Hamed; Rahbardehghan, Surena

    2016-11-01

    The solution to the linearized Einstein equation in de Sitter (dS) spacetime and the corresponding two-point function are explicitly written down in a gauge with two parameters "a " and "b ". The quantization procedure, independent of the choice of the coordinate system, is based on a rigorous group theoretical approach. Our result takes the form of a universal spin-two (transverse-traceless) sector and a gauge-dependent spin-zero (pure-trace) sector. Scalar equations are derived for the structure functions of each part. We show that the spin-two sector can be written as the resulting action of a second-order differential operator (the spin-two projector) on a massless minimally coupled scalar field (the spin-two structure function). The operator plays the role of a symmetric rank-2 polarization tensor and has a spacetime dependence. The calculated spin-two projector grows logarithmically with distance and also no dS-invariant solution for either structure functions exist. We show that the logarithmically growing part and the dS-breaking contribution to the spin-zero part can be dropped out, respectively, for suitable choices of parameters "a " and "b ". Considering the transverse-traceless graviton two-point function, however, shows that dS breaking is universal (cannot be gauged away). More exactly, if one wants to respect the covariance and positiveness conditions, the quantization of the dS graviton field (as for any gauge field) cannot be carried out directly in a Hilbert space and involves unphysical negative norm states. However, a suitable adaptation (Krein spaces) of the Gupta-Bleuler scheme for massless fields, based on the group theoretical approach, enables us to obtain the corresponding two-point function satisfying the conditions of locality, covariance, transversality, index symmetrizer, and tracelessness.

  9. Futures market efficiency diagnostics via temporal two-point correlations. Russian market case study

    OpenAIRE

    Mikhail Kopytin; Evgeniy Kazantsev

    2013-01-01

    Using a two-point correlation technique, we study emergence of market efficiency in the emergent Russian futures market by focusing on lagged correlations. The correlation strength of leader-follower effects in the lagged inter-market correlations on the hourly time frame is seen to be significant initially (2009-2011) but gradually goes down, as the erstwhile leader instruments -- crude oil, the USD/RUB exchange rate, and the Russian stock market index -- seem to lose the leader status. An i...

  10. Covalent docking using autodock: Two-point attractor and flexible side chain methods.

    Science.gov (United States)

    Bianco, Giulia; Forli, Stefano; Goodsell, David S; Olson, Arthur J

    2016-01-01

    We describe two methods of automated covalent docking using Autodock4: the two-point attractor method and the flexible side chain method. Both methods were applied to a training set of 20 diverse protein-ligand covalent complexes, evaluating their reliability in predicting the crystallographic pose of the ligands. The flexible side chain method performed best, recovering the pose in 75% of cases, with failures for the largest inhibitors tested. Both methods are freely available at the AutoDock website (http://autodock.scripps.edu). © 2015 The Protein Society.

  11. A Note on Reflection Positivity and the Kallen-Lehmann Representation of Two Point Correlation Functions

    CERN Document Server

    Usui, Kouta

    2012-01-01

    It will be proved that a model of lattice field theories which satisfies (A1) Hermiticity, (A2) translational invariance, (A3) reflection positivity, and (A4) polynomial boundedness of correlations, permits the Kallen-Lehmann representation of two point correlation functions with positive spectral density function. Then, we will also argue that positivity of spectral density functions is necessary for a lattice theory to satisfy conditions (A1) - (A4). As an example, a lattice overlap scalar boson model will be discussed. We will find that the overlap scalar boson violates the reflection positivity.

  12. Two-point Functions at Two Loops in Three Flavour Chiral Perturbation Theory

    CERN Document Server

    Amorós, G; Talavera, P; Amoros, Gabriel; Bijnens, Johan; Talavera, Pere

    2000-01-01

    The vector and axial-vector two-point functions are calculated to next-to-next-to-leading order in Chiral Perturbation Theory for three light flavours. We also obtain expressions at the same order for the masses, $m_\\pi^2$, $m_K^2$ and $m_\\eta^2$, and the decay constants, $F_\\pi$, $F_K$ and $F_\\eta$. We present some numerical results after a simple resonance estimate of some of the new ${\\cal O}(p^6)$ constants.

  13. Exact relation with two-point correlation functions and phenomenological approach for compressible magnetohydrodynamic turbulence.

    Science.gov (United States)

    Banerjee, Supratik; Galtier, Sébastien

    2013-01-01

    Compressible isothermal magnetohydrodynamic turbulence is analyzed under the assumption of statistical homogeneity and in the asymptotic limit of large kinetic and magnetic Reynolds numbers. Following Kolmogorov we derive an exact relation for some two-point correlation functions which generalizes the expression recently found for hydrodynamics. We show that the magnetic field brings new source and flux terms into the dynamics which may act on the inertial range similarly as a source or a sink for the mean energy transfer rate. The introduction of a uniform magnetic field simplifies significantly the exact relation for which a simple phenomenology may be given. A prediction for axisymmetric energy spectra is eventually proposed.

  14. Two-point correlators revisited: Fast and slow scales in multifield models of Inflation

    CERN Document Server

    Ghersi, José T Gálvez

    2016-01-01

    We study the structure of two-point correlators of the inflationary field fluctuations in order to improve the accuracy and efficiency of the existing spectral methods. We present a description motivated by the separation of the fast and slow evolving components of the spectrum. Our purpose is to rephrase all the relevant equations of motion in terms of slowly varying quantities. This is important in order to consider the contribution from high-frequency modes to the spectrum without affecting computational performance. The slow-roll approximation is not required to reproduce the main distinctive features in the power spectrum for each specific model of inflation.

  15. A Linkage Learning Genetic Algorithm with Linkage Matrix

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The goal of linkage learning, or building block identification, is the creation of a more effective Genetic Algorithm (GA). This paper proposes a new Linkage Learning Genetic Algorithms, named m-LLGA. With the linkage learning module and the linkage-based genetic operation, m-LLGA is not only able to learn and record the linkage information among genes without any prior knowledge of the function being optimized. It also can use the linkage information stored in the linkage matrix to guide the selection of crossover point. The preliminary experiments on two kinds of bounded difficulty problems and a TSP problem validated the performance of m-LLGA. The m-LLGA learns the linkage of different building blocks parallel and therefore solves these problems effectively; it can also reasonably reduce the probability of building blocks being disrupted by crossover at the same time give attention to getting away from local minimum.

  16. Genome-wide linkage analysis of QTL for growth and body composition employing the PorcineSNP60 BeadChip

    Directory of Open Access Journals (Sweden)

    Fernández Ana I

    2012-05-01

    Full Text Available Abstract Background The traditional strategy to map QTL is to use linkage analysis employing a limited number of markers. These analyses report wide QTL confidence intervals, making very difficult to identify the gene and polymorphisms underlying the QTL effects. The arrival of genome-wide panels of SNPs makes available thousands of markers increasing the information content and therefore the likelihood of detecting and fine mapping QTL regions. The aims of the current study are to confirm previous QTL regions for growth and body composition traits in different generations of an Iberian x Landrace intercross (IBMAP and especially identify new ones with narrow confidence intervals by employing the PorcineSNP60 BeadChip in linkage analyses. Results Three generations (F3, Backcross 1 and Backcross 2 of the IBMAP and their related animals were genotyped with PorcineSNP60 BeadChip. A total of 8,417 SNPs equidistantly distributed across autosomes were selected after filtering by quality, position and frequency to perform the QTL scan. The joint and separate analyses of the different IBMAP generations allowed confirming QTL regions previously identified in chromosomes 4 and 6 as well as new ones mainly for backfat thickness in chromosomes 4, 5, 11, 14 and 17 and shoulder weight in chromosomes 1, 2, 9 and 13; and many other to the chromosome-wide signification level. In addition, most of the detected QTLs displayed narrow confidence intervals, making easier the selection of positional candidate genes. Conclusions The use of higher density of markers has allowed to confirm results obtained in previous QTL scans carried out with microsatellites. Moreover several new QTL regions have been now identified in regions probably not covered by markers in previous scans, most of these QTLs displayed narrow confidence intervals. Finally, prominent putative biological and positional candidate genes underlying those QTL effects are listed based on recent porcine

  17. Cosmopolitan linkage disequilibrium maps

    Directory of Open Access Journals (Sweden)

    Gibson Jane

    2005-03-01

    Full Text Available Abstract Linkage maps have been invaluable for the positional cloning of many genes involved in severe human diseases. Standard genetic linkage maps have been constructed for this purpose from the Centre d'Etude du Polymorphisme Humain and other panels, and have been widely used. Now that attention has shifted towards identifying genes predisposing to common disorders using linkage disequilibrium (LD and maps of single nucleotide polymorphisms (SNPs, it is of interest to consider a standard LD map which is somewhat analogous to the corresponding map for linkage. We have constructed and evaluated a cosmopolitan LD map by combining samples from a small number of populations using published data from a 10-megabase region on chromosome 20. In support of a pilot study, which examined a number of small genomic regions with a lower density of markers, we have found that a cosmopolitan map, which serves all populations when appropriately scaled, recovers 91 to 95 per cent of the information within population-specific maps. Recombination hot spots appear to have a dominant role in shaping patterns of LD. The success of the cosmopolitan map might be attributed to the co-localisation of hot spots in all populations. Although there must be finer scale differences between populations due to other processes (mutation, drift, selection, the results suggest that a whole-genome standard LD map would indeed be a useful resource for disease gene mapping.

  18. Beyond Kaiser bias: mildly non-linear two-point statistics of densities in distant spheres

    CERN Document Server

    Uhlemann, C; Kim, J; Pichon, C; Bernardeau, F; Pogosyan, D; Park, C; L'Huillier, B

    2016-01-01

    Simple parameter-free analytic bias functions for the two-point correlation of densities in spheres at large separation are presented. These bias functions generalize the so-called Kaiser bias to the mildly non-linear regime for arbitrary density contrasts. The derivation is carried out in the context of large deviation statistics while relying on the spherical collapse model. A logarithmic transformation provides a saddle approximation which is valid for the whole range of densities and shown to be accurate against the 30 Gpc cube state-of-the-art Horizon Run 4 simulation. Special configurations of two concentric spheres that allow to identify peaks are employed to obtain the conditional bias and a proxy to BBKS extrema correlation functions. These analytic bias functions should be used jointly with extended perturbation theory to predict two-point clustering statistics as they capture the non-linear regime of structure formation at the percent level down to scales of about 10 Mpc/h at redshift 0. Conversely...

  19. Solving Directly Two Point Non Linear Boundary Value Problems Using Direct Adams Moulton Method

    Directory of Open Access Journals (Sweden)

    Zanariah A. Majid

    2011-01-01

    Full Text Available Problem statement: In this study, a direct method of Adams Moulton type was developed for solving non linear two point Boundary Value Problems (BVPs directly. Most of the existence researches involving BVPs will reduced the problem to a system of first order Ordinary Differential Equations (ODEs. This approach is very well established but it obviously will enlarge the systems of first order equations. However, the direct method in this research will solved the second order BVPs directly without reducing it to first order ODEs. Approach: Lagrange interpolation polynomial was applied in the derivation of the proposed method. The method was implemented using constant step size via shooting technique in order to determine the approximated solutions. The shooting technique will employ the Newton’s method for checking the convergent of the guessing values for the next iteration. Results: Numerical results confirmed that the direct method gave better accuracy and converged faster compared to the existing method. Conclusion: The proposed direct method is suitable for solving two point non linear boundary value problems.

  20. Two-point concrete resistivity measurements: interfacial phenomena at the electrode-concrete contact zone

    Science.gov (United States)

    McCarter, W. J.; Taha, H. M.; Suryanto, B.; Starrs, G.

    2015-08-01

    Ac impedance spectroscopy measurements are used to critically examine the end-to-end (two-point) testing technique employed in evaluating the bulk electrical resistivity of concrete. In particular, this paper focusses on the interfacial contact region between the electrode and specimen and the influence of contacting medium and measurement frequency on the impedance response. Two-point and four-point electrode configurations were compared and modelling of the impedance response was undertaken to identify and quantify the contribution of the electrode-specimen contact region on the measured impedance. Measurements are presented in both Bode and Nyquist formats to aid interpretation. Concretes mixes conforming to BSEN206-1 and BS8500-1 were investigated which included concretes containing the supplementary cementitious materials fly ash and ground granulated blast-furnace slag. A measurement protocol is presented for the end-to-end technique in terms of test frequency and electrode-specimen contacting medium in order to minimize electrode-specimen interfacial effect and ensure correct measurement of bulk resistivity.

  1. Statistics of the two-point cross-covariance function of solar oscillations

    CERN Document Server

    Nagashima, Kaori; Gizon, Laurent; Birch, Aaron C

    2016-01-01

    Context: The cross-covariance of solar oscillations observed at pairs of points on the solar surface is a fundamental ingredient in time-distance helioseismology. Wave travel times are extracted from the cross-covariance function and are used to infer the physical conditions in the solar interior. Aims: Understanding the statistics of the two-point cross-covariance function is a necessary step towards optimizing the measurement of travel times. Methods: By modeling stochastic solar oscillations, we evaluate the variance of the cross-covariance function as function of time-lag and distance between the two points. Results: We show that the variance of the cross-covariance is independent of both time-lag and distance in the far field, i.e., when they are large compared to the coherence scales of the solar oscillations. Conclusions: The constant noise level for the cross-covariance means that the signal-to-noise ratio for the cross-covariance is proportional to the amplitude of the expectation value of the cross-...

  2. Genetic linkage analysis of susceptible gene of congenital dislocation of the hip with chromosome 7, 22 in four Yunnan pedigrees%云南地区先天性髋关节脱位4个家系22号与7号染色体易感基因连锁分析

    Institute of Scientific and Technical Information of China (English)

    鲁宁; 张宝华; 胡侦明; 浦波; 王迎松; 虞弘; 曹有良; 王少飞; 杨庆秋; 劳汉昌

    2008-01-01

    Objective To investigate genetic linkage between the phenotype of congenital dislocation of the hip (CDH) and genes located in chromosome 22,7, and attempt initially process of the genome-wide scan for searching disease-susceptibility loci.Methods According to epidemiological data,we studied 4 kindred with CDH in yunna,which include 65 persons in 5 generations.the affected status of 17 individuals had been established on the basis of their clinical and radiological presentation of the disorder.44 blood specimens were collected from those members who could be followed trail, and their nucleus DNA was extracted from peripheral leukocytes as phenol method.35 Tetnuc or Trinuc repeat microsatellite markers exploited by CHLC were chosen.8 markers distributed on chromosome 22, and 10 markers distributed on 7chromosome with an average interval of 10 cm.Genimic DNA were amplified by PCR technique.The PCR products were subjected to vertical electrophoresis in PAGE gel with continous buffer system, followed by siliver staining.graphic analysis system was used to define each allele.Parametric linkage analysi using maximum likelihood estimation were computed by the linkage package for various recombination fraction valus, with a disease gene grequency of 0.02.Results 18 STR loci are showen to provide good discrimination power by highly polymorphism and heterozygosity.Gnotype dated were obtained and conformed to Mendel law.Linkage analysis with those markers gave minus two-point LOD score values (Z<1), which the markers in 22and 7 chromosome indicated that there no linkage between the markers and CDH gene in those pedigrees.Conclusions CDH susceptibility genes are not likely located on chromosome 22, 7.The approach to geno-wide scan using highly density STR markers would play an important role in map the gene responsible for CDH.%目的 探讨先天性髋关节脱位 (CDH) 与22、7号染色体之间的连锁关系.方法 以4个云南地区CDH家系为研究对象,提取所有

  3. Adaptive Linkage Disequilibrium Between Two Esterase Loci of a Salamander

    Science.gov (United States)

    Webster, T. Preston

    1973-01-01

    In some populations of the salamander Plethodon cinereus, two polymorphic esterase loci are in linkage disequilibrium. Short-term stability of the linkage disequilibrium is demonstrated by an age class analysis. Long, perhaps very long, term stability is suggested by its distribution. This stability and concordant geographic variation in allelic frequencies imply selective origin and maintenance. Data on the frequencies of two color morphs suggest that formation of the linkage disequilibrium is dependent on the genetic background. Images PMID:4515614

  4. From Enclave to Linkage Economies?

    DEFF Research Database (Denmark)

    Hansen, Michael W.

    and local enterprises by themselves will indeed produce linkages, the scope, depth and development impacts of linkages eventually depend on government intervention. Resource-rich African countries’ governments are aware of this and linkage promotion is increasingly becoming a key element...

  5. Logarithmic two-point correlation functions from a z=2 Lifshitz model

    Energy Technology Data Exchange (ETDEWEB)

    Zingg, T. [Institute for Theoretical Physics and Spinoza Institute, Universiteit Utrecht,Leuvenlaan 4, 3584 CE Utrecht (Netherlands)

    2014-01-21

    The Einstein-Proca action is known to have asymptotically locally Lifshitz spacetimes as classical solutions. For dynamical exponent z=2, two-point correlation functions for fluctuations around such a geometry are derived analytically. It is found that the retarded correlators are stable in the sense that all quasinormal modes are situated in the lower half-plane of complex frequencies. Correlators in the longitudinal channel exhibit features that are reminiscent of a structure usually obtained in field theories that are logarithmic, i.e. contain an indecomposable but non-diagonalizable highest weight representation. This provides further evidence for conjecturing the model at hand as a candidate for a gravity dual of a logarithmic field theory with anisotropic scaling symmetry.

  6. Inverted catenoid as a fluid membrane with two points pulled together.

    Science.gov (United States)

    Castro-Villarreal, Pavel; Guven, Jemal

    2007-07-01

    Under inversion in any (interior) point, a catenoid transforms into a deflated compact geometry which touches at two points (its poles). The catenoid is a minimal surface and, as such, is an equilibrium shape of a symmetric fluid membrane. The conformal symmetry of the Hamiltonian implies that inverted minimal surfaces are also equilibrium shapes. However, they will exhibit curvature singularities at their poles. Such singularities are the geometrical signature of the external forces required to pull the poles together. These forces will set up stresses in the inverted shapes. Tuning the force corresponds geometrically to the translation of the point of inversion. For any fixed surface area, there will be a maximum force. The associated shape is a symmetric discocyte. Lowering the external force will induce a transition from the discocyte to a cup-shaped stomatocyte.

  7. An improved iterative technique for solving nonlinear doubly singular two-point boundary value problems

    Science.gov (United States)

    Roul, Pradip

    2016-06-01

    This paper presents a new iterative technique for solving nonlinear singular two-point boundary value problems with Neumann and Robin boundary conditions. The method is based on the homotopy perturbation method and the integral equation formalism in which a recursive scheme is established for the components of the approximate series solution. This method does not involve solution of a sequence of nonlinear algebraic or transcendental equations for the unknown coefficients as in some other iterative techniques developed for singular boundary value problems. The convergence result for the proposed method is established in the paper. The method is illustrated by four numerical examples, two of which have physical significance: The first problem is an application of the reaction-diffusion process in a porous spherical catalyst and the second problem arises in the study of steady-state oxygen-diffusion in a spherical cell with Michaelis-Menten uptake kinetics.

  8. A High Performance Spread Spectrum Clock Generator Using Two-Point Modulation Scheme

    Science.gov (United States)

    Kao, Yao-Huang; Hsieh, Yi-Bin

    A new spread spectrum clock generator (SSCG) using two-point delta-sigma modulation is presented in this paper. Not only the divider is varied, but also the voltage controlled oscillator is modulated. This technique can enhance the modulation bandwidth so that the effect of EMI suppression is improved with lower order ΣΔ modulator and can simultaneously optimize the jitter and the modulation profile. In addition, the method of two-path is applied to the loop filter to reduce the capacitance value such that the total integration can be achieved. The proposed SSCG has been fabricated in a 0.35μm CMOS process. The clock of 400MHz with center spread ratios of 1.25% and 2.5% are verified. The peak EMI reduction is 19.73dB for the case of 2.5%. The size of chip area is 0.90×0.89mm2.

  9. Implementation of the Two-Point Angular Correlation Function on a High-Performance Reconfigurable Computer

    Directory of Open Access Journals (Sweden)

    Volodymyr V. Kindratenko

    2009-01-01

    Full Text Available We present a parallel implementation of an algorithm for calculating the two-point angular correlation function as applied in the field of computational cosmology. The algorithm has been specifically developed for a reconfigurable computer. Our implementation utilizes a microprocessor and two reconfigurable processors on a dual-MAP SRC-6 system. The two reconfigurable processors are used as two application-specific co-processors. Two independent computational kernels are simultaneously executed on the reconfigurable processors while data pre-fetching from disk and initial data pre-processing are executed on the microprocessor. The overall end-to-end algorithm execution speedup achieved by this implementation is over 90× as compared to a sequential implementation of the algorithm executed on a single 2.8 GHz Intel Xeon microprocessor.

  10. Two-point gauge invariant quark Green's functions with polygonal phase factor lines

    CERN Document Server

    Sazdjian, H

    2013-01-01

    Polygonal lines are used for the paths of the gluon field phase factors entering in the definition of gauge invariant quark Green's functions. This allows classification of the Green's functions according to the number of segments the polygonal lines contain. Functional relations are established between Green's functions with polygonal lines with different numbers of segments. An integrodifferential equation is obtained for the quark two-point Green's function with a path along a single straight line segment where the kernels are represented by a series of Wilson loop averages along polygonal contours. The equation is exactly and analytically solved in the case of two-dimensional QCD in the large-$N_c$ limit. The solution displays generation of an infinite number of dynamical quark masses accompanied with branch point singularities that are stronger than simple poles. An approximation scheme, based on the counting of functional derivatives of Wilson loops, is proposed for the resolution of the equation in fou...

  11. Applying inversion to construct planar, rational spirals that satisfy two-point G(2) Hermite data

    CERN Document Server

    Kurnosenko, A

    2010-01-01

    A method of two-point G(2) Hermite interpolation with spirals is proposed. To construct a sought for curve, the inversion is applied to an arc of some other spiral. To illustrate the method, inversions of parabola are considered in detail. The resulting curve is 4th degree rational. The method allows the matching of a wide range of boundary conditions, including those which require an inflection. Although not all G(2) Hermite data can be matched with a spiral generated from a parabolic arc, introducing one intermediate G(2) data solves the problem. Expanding the method by involving other spirals arcs is also discussed. (C) 2009 Elsevier B.V. All rights reserved.

  12. Expansion schemes for gravitational clustering: computing two-point and three-point functions

    CERN Document Server

    Valageas, P

    2007-01-01

    We describe various expansion schemes that can be used to study gravitational clustering. Obtained from the equations of motion or their path-integral formulation, they provide several perturbative expansions that are organized in different fashion or involve different partial resummations. We focus on the two-point and three-point correlation functions, but these methods also apply to all higher-order correlation and response functions. We present the general formalism, which holds for the gravitational dynamics as well as for similar models, such as the Zeldovich dynamics, that obey similar hydrodynamical equations of motion with a quadratic nonlinearity. We give our explicit analytical results up to one-loop order for the simpler Zeldovich dynamics. For the gravitational dynamics, we compare our one-loop numerical results with numerical simulations. We check that the standard perturbation theory is recovered from the path integral by expanding over Feynman's diagrams. However, the latter expansion is organ...

  13. Quantization of fluctuations in DSR: the two-point function and beyond

    CERN Document Server

    Gubitosi, Giulia; Magueijo, Joao

    2015-01-01

    We show that the two-point function of a quantum field theory with de Sitter momentum space (herein called DSR) can be expressed as the product of a standard delta function and an energy-dependent factor. This is a highly non-trivial technical result in any theory without a preferred frame. Applied to models exhibiting running of the dimensionality of space, this result is essential in proving that vacuum fluctuations are generally scale-invariant at high energies whenever there is running to two dimensions. This is equally true for theories with and without a preferred frame, with differences arising only as we consider higher order correlators. Specifically, the three-point function of DSR has a unique structure of "open triangles", as shown here.

  14. Measuring baryon acoustic oscillations with angular two-point correlation function

    CERN Document Server

    Alcaniz, Jailson S; Bernui, Armando; Carvalho, Joel C; Benetti, Micol

    2016-01-01

    The Baryon Acoustic Oscillations (BAO) imprinted a characteristic correlation length in the large-scale structure of the universe that can be used as a standard ruler for mapping out the cosmic expansion history. Here, we discuss the application of the angular two-point correlation function, $w(\\theta)$, to a sample of luminous red galaxies of the Sloan Digital Sky Survey (SDSS) and derive two new measurements of the BAO angular scale at $z = 0.235$ and $z = 0.365$. Since noise and systematics may hinder the identification of the BAO signature in the $w - \\theta$ plane, we also introduce a potential new method to localize the acoustic bump in a model-independent way. We use these new measurements along with previous data to constrain cosmological parameters of dark energy models and to derive a new estimate of the acoustic scale $r_s$.

  15. Two-point paraxial traveltime formula for inhomogeneous isotropic and anisotropic media: Tests of accuracy

    KAUST Repository

    Waheed, Umair bin

    2013-09-01

    On several simple models of isotropic and anisotropic media, we have studied the accuracy of the two-point paraxial traveltime formula designed for the approximate calculation of the traveltime between points S\\' and R\\' located in the vicinity of points S and R on a reference ray. The reference ray may be situated in a 3D inhomogeneous isotropic or anisotropic medium with or without smooth curved interfaces. The twopoint paraxial traveltime formula has the form of the Taylor expansion of the two-point traveltime with respect to spatial Cartesian coordinates up to quadratic terms at points S and R on the reference ray. The constant term and the coefficients of the linear and quadratic terms are determined from quantities obtained from ray tracing and linear dynamic ray tracing along the reference ray. The use of linear dynamic ray tracing allows the evaluation of the quadratic terms in arbitrarily inhomogeneous media and, as shown by examples, it extends the region of accurate results around the reference ray between S and R (and even outside this interval) obtained with the linear terms only. Although the formula may be used for very general 3D models, we concentrated on simple 2D models of smoothly inhomogeneous isotropic and anisotropic (~8% and ~20% anisotropy) media only. On tests, in which we estimated twopoint traveltimes between a shifted source and a system of shifted receivers, we found that the formula may yield more accurate results than the numerical solution of an eikonal-based differential equation. The tests also indicated that the accuracy of the formula depends primarily on the length and the curvature of the reference ray and only weakly depends on anisotropy. The greater is the curvature of the reference ray, the narrower its vicinity, in which the formula yields accurate results.

  16. A Turkish family with Ellis-van Creveld syndrome in six siblings; linkage analysis on 4p16 region (D4S3360-D4S2366).

    Science.gov (United States)

    Cağdaş, D N; Parlar, A I; Pac, A; Tutun, U; Balci, S

    2008-01-01

    We present a Turkish family and their 6 children, consecutively affected by Ellis-van Creveld (EVC) Syndrome. Four of the affected children died in the postnatal period, and 2 of them had been admitted to the pediatric cardiology department for their cardiologic evaluation. Since they had the features of the EVC Syndrome, linkage analysis was performed with the polymorphic markers, D4S3360-D4S2366, selected from 4p 16 locus. There was complete segregation between the disease and marker allels and the two affected siblings were homozygote for the polymorphic markers, as expected in autosomal recessive inheritance. The diagnosis of EVC Syndrome was confirmed by this molecular analysis. Two cases with EVC were presented in this report. Case 1 had partial abnormal pulmonary venous return and pulmonary stenosis additional to ostium primum atrial septal defect and mitral cleft. Partial abnormal pulmonary venous return and pulmonary stenosis were previously not reported with EVC Syndrome. Postaxial polydactyly phenotype of the Case 2 differs from her brother's. There is bifid 5th metacarpal and unilateral (L) bifid middle and distal phalanges resembling syndactyly.

  17. Mapping one form of autosomal dominant postaxial polydactyly type A to chromosome 7p15-q11.23 by linkage analysis

    Energy Technology Data Exchange (ETDEWEB)

    Radhakrishna, U.; Mehenni, H.; Antonarakis, S.E. [Geneva Medical School (Switzerland)] [and others

    1997-03-01

    Postaxial polydactyly type-A (PAP-A) in humans is an autosomal dominant trait characterized by an extra digit in the ulnar and/or fibular side of the upper and/or lower extremities. The extra digit is well formed and articulates with the fifth, or extra, metacarpal/metatarsal, and thus it is usually functional. In order to map the gene responsible for PAP-A, we studied a five-generation Indian family of 37 individuals (15 of whom were affected). A genomewide search with highly informative polymorphic markers on part of the pedigree showed linkage between the PAP-A phenotype and markers on chromosome 7p15-q11.23 (no crossovers were found with D7S526, D7S795, D7S528, D7S521, D7S691, D7S667, D7S478, D7S1830, D7S803, D7S801, or ELN). The highest LOD score was obtained with marker D7S801 (Z{sub max} = 4.21; {theta} = 0). Haplotype analysis enabled the mapping of the PAP-A phenotype in this family between markers D7S2848 and D7S669. Analysis of additional families with PAP-A will narrow down the critical genomic region, facilitate positional cloning of the PAP-A gene, and/or uncover potential genetic heterogeneity. 42 refs., 4 figs., 1 tab.

  18. AN ANALYSIS ON LARGE-SCALE AIR-SEA INTERACTIVE LINKAGES BETWEEN THE TROPICAL INDIAN OCEAN AND THE PACIFIC OCEAN DURING ENSO EVENTS

    Institute of Scientific and Technical Information of China (English)

    DENG Bei-sheng; LIU Hai-tao; CHOU Ji-fan

    2010-01-01

    By utilizing a 3-D atmospheric circulation resolving method, the authors studied the air-sea interactive linkages between the tropical Indian Ocean and the Pacific Ocean in 1979-2008 El Nino-Southern Oscillation (ENSO) events. Their findings showed that evident 3-D gear-coupling characteristics existed in the 1979-2008 ENSO events. Their resolving analyses also suggested that the general circulation showed stronger and wider sinking motions over the eastern Indian Ocean-western Pacific during the mature phase of 1979-2008 ENSO events, compared with the vertical velocities from the U.S. National Centers for Enviornmental Prediction (NCEP) reanalysis data. With their 3-D analysis method, the vertical velocity was resolved by two components, i.e. zonal and meridional components. It was found that the zonal component of the vertical velocities showed a strong sinking motion while the meridional components showed an upward motion during the prevailing phases of the ENSO events,In the tropics, the zonal component of the vertical velocities was found greater than the meridional component, reflecting the dominant characteristics of the vertical velocity, and the overall outcomes showed a strong sinking motion, although the two components also partially offset each other in the processes. Compared with the vertical velocities from NCEP reanalysis, the vertical motions calculated with the 3-D resolving analysis method demonstrate some advantages.

  19. CURRENCY LINKAGES AMONG ASEAN

    OpenAIRE

    CHIN LEE; M. Azali

    2010-01-01

    The purpose of this study is to examine the potential linkages among ASEAN-5 currencies, in particular the possibility of a Singapore dollar bloc during the pre- and post-crisis periods by using the Johansen multivariate cointegration test and the Granger causality test. Significant nonstationarity and the presence of unit roots were documented for each currency under both study periods. Using ASEAN-4 exchange rates against the Singapore dollar, the Johansen cointegration test showed that the...

  20. A Narrow and Highly Significant Linkage Signal for Severe Bipolar Disorder in the Chromosome 5q33 Region in Latin American Pedigrees

    Science.gov (United States)

    Jasinska, A.J.; Service, S.; Jawaheer, D.; DeYoung, J.; Levinson, M.; Zhang, Z.; Kremeyer, B.; Muller, H.; Aldana, I.; Garcia, J.; Restrepo, G.; Lopez, C.; Palacio, C.; Duque, C.; Parra, M.; Vega, J.; Ortiz, D.; Bedoya, G.; Mathews, C.; Davanzo, P.; Fournier, E.; Bejarano, J.; Ramirez, M.; Ortiz, C. Araya; Araya, X.; Molina, J.; Sabatti, C.; Reus, V.; Ospina, J.; Macaya, G.; Ruiz-Linares, A.; Freimer, N.B.

    2016-01-01

    We previously reported linkage of bipolar disorder to 5q33-q34 in families from two closely related population isolates, the Central Valley of Costa Rica (CVCR) and Antioquia, Colombia (CO). Here we present follow up results from fine-scale mapping in large CVCR and CO families segregating severe bipolar disorder, BP-I, and in 343 population trios/duos from CVCR and CO. Employing densely spaced SNPs to fine map the prior linkage peak region increases linkage evidence and clarifies the position of the putative BP-I locus. We performed two-point linkage analysis with 1134 SNPs in an approximately 9 Mb region between markers D5S410 and D5S422. Combining pedigrees from CVCR and CO yields a LOD score of 4.9 at SNP rs10035961. Two other SNPs (rs7721142 and rs1422795) within the same 94 kb region also displayed LOD scores greater than 4. This linkage peak coincides with our prior microsatellite results and suggests a narrowed BP-I susceptibility regions in these families. To investigate if the locus implicated in the familial form of BP-I also contributes to disease risk in the population, we followed up the family results with association analysis in duo and trio samples, obtaining signals within 2 Mb of the peak linkage signal in the pedigrees; rs12523547 and rs267015 (P = 0.00004 and 0.00016, respectively) in the CO sample and rs244960 in the CVCR sample and the combined sample, with P = 0.00032 and 0.00016, respectively. It remains unclear whether these association results reflect the same locus contributing to BP susceptibility within the extended pedigrees. PMID:19319892

  1. Phenotypic variability in X-linked ocular albinism: Relationship to linkage genotypes

    Energy Technology Data Exchange (ETDEWEB)

    Schnur, R.E. [Children`s Hospital of Philadelphia, PA (United States)]|[Univ. of Pennsylvania School of Medicine, Philadelphia, PA (United States); Wick, P.A. [Children`s Hospital of Philadelphia, PA (United States); Bailey, C. [Univ. of Pennsylvania School of Medicine, Philadelphia, PA (United States); Rebbeck, T. [Fox Chase Cancer Center, Philadelphia, PA (United States); Weleber, R.G. [Oregon Health Sciences Univ., Portland, OR (United States); Wagstaff, J. [Boston Children`s Hospital, MA (United States); Grix, A.W. [Univ. of California, Davis, CA (United States); Pagon, R.A. [Children`s Hospital and Medical Center, Seattle, WA (United States); Hockey, A. [Princess Margaret Hospital, Perth (Australia); Edwards, M.J. [Newcastle Western Suburbs Hospital, Waratah (Australia)

    1994-09-01

    One hundred nineteen individuals from 11 families with X-linked ocular albinism (OA1) were studied with respect to both their clinical phenotypes and their linkage genotypes. In a four-generation Australian family, two affected males and an obligatory carrier lacked cutaneous melanin macroglobules (MMGs); ocular features were identical to those of Nettleship-Falls OA1. Four other families had more unusual phenotypic features in addition to OA1. All OA1 families were genotyped at DXS16, DXS85, DXS143, STS, and DXS452 and for a CA-repeat polymorphism at the Kallmann syndrome locus (KAL). Separate two-point linkage analyses were performed for the following: group A, six families with biopsy-proved MMGs in at least one affected male; group B, four families whose biopsy status was not known; and group C, OA-9 only (16 samples), the family without MMGs. At the set of loci closest to OA1, there is no clear evidence in our data set for locus heterogeneity between groups A and C or among the four other families with complex phenotypes. Combined multipoint analysis (LINKMAP) in the 11 families and analysis of individual recombination events confirms that the major locus for OA1 resides within the DXS85-DXS143 interval. The authors suggest that more detailed clinical evaluations of OA1 individuals and families should be performed for future correlation with specific mutations in candidate OA1 genes. 29 refs., 5 figs., 4 tabs.

  2. X-linked sideroblastic anemia and ataxia: linkage to phosphoglycerate kinase at Xq13.

    Science.gov (United States)

    Raskind, W H; Wijsman, E; Pagon, R A; Cox, T C; Bawden, M J; May, B K; Bird, T D

    1991-02-01

    Molecular linkage analysis was performed on a kindred with X-linked sideroblastic anemia and ataxia. Two-point analysis with a DNA probe for phosphoglycerate kinase (PGK1), which maps to Xq13, suggested linkage to the disorder by a lod score of at least 2.60 at a recombination fraction of zero. The disease in this kindred appears to be clinically and genetically distinct from that in previously reported families with X-linked hereditary ataxia or spastic paraparesis. No mapping data are available for inherited X-linked sideroblastic anemia without neurologic abnormalities. However, structural alterations of band Xq13 may be involved in the development of idiopathic acquired sideroblastic anemia. No alterations in the restriction patterns of two X-linked genes involved in erythrocyte formation-i.e., a DNA-binding protein (GF-1) and 5-aminolevulinate synthase (ALAS)-were detected in DNA from affected males, arguing against a large deletion in either of these candidate genes.

  3. Multivariate analysis of anxiety disorders yields further evidence of linkage to chromosomes 4q21, and 7p in panic disorder families

    Science.gov (United States)

    Logue, M.W.; Bauver, S.R.; Knowles, J.A.; Gameroff, M.J.; Weissman, M.M.; Crowe, R.R.; Fyer, A.J.; Hamilton, S.P.

    2012-01-01

    Replication has been difficult to achieve in linkage studies of psychiatric disease. Linkage studies of panic disorder have indicated regions of interest on chromosomes 1q, 2p, 2q, 3, 7, 9, 11, 12q13, 12q23, and 15. Few regions have been implicated in more than one study. We examine two samples, the Iowa and the Columba panic disorder families. We use the fuzzy clustering method presented by Kaabi et al. (2006) to summarize liability to panic disorder, agoraphobia, simple phobia, and social phobia. Kaabi et al. applied this method to the Yale panic disorder linkage families and found evidence of linkage to chromosomes 4q21, 4q32, 7p, and 8. When we apply the same method to the Iowa families, we obtain overlapping evidence of linkage to chromosomes 4q21 and 7p. Additionally, we find evidence of linkage on chromosomes 1, 5, 6, 16, and 22. The Columbia data does not indicate linkage to any of the Kaabi et al. peaks, instead implicating chromosomes 2 and 22q11 (2 Mb from COMT). There is some evidence of overlapping linkage between the Iowa and Columbia datasets on chromosomes 1 and 14. While use of fuzzy clustering has not produced complete concordance across datasets, it has produced more than previously seen in analyses of panic disorder proper. We conclude that chromosomes 4q21 and 7p should be considered strong candidate regions for panic and fear-associated anxiety disorder loci. More generally, this suggests that analyses including multiple aspects of psychopathology may lead to greater consistency across datasets. PMID:22253211

  4. Genomewide high-density SNP linkage analysis of non-BRCA1/2 breast cancer families identifies various candidate regions and has greater power than microsatellite studies

    Directory of Open Access Journals (Sweden)

    Gonzalez-Neira Anna

    2007-08-01

    Full Text Available Abstract Background The recent development of new high-throughput technologies for SNP genotyping has opened the possibility of taking a genome-wide linkage approach to the search for new candidate genes involved in heredity diseases. The two major breast cancer susceptibility genes BRCA1 and BRCA2 are involved in 30% of hereditary breast cancer cases, but the discovery of additional breast cancer predisposition genes for the non-BRCA1/2 breast cancer families has so far been unsuccessful. Results In order to evaluate the power improvement provided by using SNP markers in a real situation, we have performed a whole genome screen of 19 non-BRCA1/2 breast cancer families using 4720 genomewide SNPs with Illumina technology (Illumina's Linkage III Panel, with an average distance of 615 Kb/SNP. We identified six regions on chromosomes 2, 3, 4, 7, 11 and 14 as candidates to contain genes involved in breast cancer susceptibility, and additional fine mapping genotyping using microsatellite markers around linkage peaks confirmed five of them, excluding the region on chromosome 3. These results were consistent in analyses that excluded SNPs in high linkage disequilibrium. The results were compared with those obtained previously using a 10 cM microsatellite scan (STR-GWS and we found lower or not significant linkage signals with STR-GWS data compared to SNP data in all cases. Conclusion Our results show the power increase that SNPs can supply in linkage studies.

  5. Genome-wide linkage analysis of longitudinal phenotypes using sigma(2)(A) random effects (SSARs) fitted by Gibbs sampling

    NARCIS (Netherlands)

    Palmer, LJ; Scurrah, KJ; Tobin, M; Patel, [No Value; Celedon, JC; Burton, PR; Weiss, ST

    2003-01-01

    The study of change in intermediate phenotypes over time is important in genetics. In this paper we explore a new approach to phenotype definition in the genetic analysis of longitudinal phenotypes. We utilized data from the longitudinal Framingham Heart Study Family Cohort to investigate the famili

  6. Improved linkage analysis of Quantitative Trait Loci using bulk segregants unveils a novel determinant of high ethanol tolerance in yeast

    NARCIS (Netherlands)

    Duitama, Jorge; Sánchez-Rodríguez, Aminael; Goovaerts, Annelies; Pulido-Tamayo, Sergio; Hubmann, Georg; Foulquié-Moreno, María R.; Thevelein, Johan M.; Verstrepen, Kevin J.; Marchal, Kathleen

    2014-01-01

    Background: Bulk segregant analysis (BSA) coupled to high throughput sequencing is a powerful method to map genomic regions related with phenotypes of interest. It relies on crossing two parents, one inferior and one superior for a trait of interest. Segregants displaying the trait of the superior p

  7. Linkage disequilibrium analysis reveals an albuminuria risk haplotype containing three missense mutations in the cubilin gene with striking differences among European and African ancestry populations

    Directory of Open Access Journals (Sweden)

    Tzur Shay

    2012-10-01

    Full Text Available Abstract Background A recent meta-analysis described a variant (p.Ile2984Val in the cubilin gene (CUBN that is associated with levels of albuminuria in the general population and in diabetics. Methods We implemented a Linkage Disequilibrium (LD search with data from the 1000 Genomes Project, on African and European population genomic sequences. Results We found that the p.Ile2984Val variation is part of a larger haplotype in European populations and it is almost absent in west Africans. This haplotype contains 19 single nucleotide polymorphisms (SNPs in very high LD, three of which are missense mutations (p.Leu2153Phe, p.Ile2984Val, p.Glu3002Gly, and two have not been previously reported. Notably, this European haplotype is absent in west African populations, and the frequency of each individual polymorphism differs significantly in Africans. Conclusions Genotyping of these variants in existing African origin sample sets coupled to measurements of urine albumin excretion levels should reveal which is the most likely functional candidate for albuminuria risk. The unique haplotypic structure of CUBN in different populations may leverage the effort to identify the functional variant and to shed light on evolution of the CUBN gene locus.

  8. Epithelium-off photochemical corneal collagen cross-linkage using riboflavin and ultraviolet a for keratoconus and keratectasia: a systematic review and meta-analysis.

    Science.gov (United States)

    Craig, Joyce A; Mahon, James; Yellowlees, Ann; Barata, Teresa; Glanville, Julie; Arber, Mick; Mandava, Lakshmi; Powell, John; Figueiredo, Francisco

    2014-07-01

    This report presents the results of a systematic review and meta-analyses of studies on epithelium-off photochemical corneal collagen cross-linkage for the management of keratoconus and secondary ectasia. The literature search identified 3,400 records of which 49 were considered for inclusion in the meta-analyses. Eight papers reported 4 unique randomized controlled trials, 29 studies were prospective, and 12 were retrospective studies. The majority of the studies (39/49) were graded as very low quality evidence. Twenty-six studies described adverse events and were included in the safety analysis. Meta-analyses are presented for changes in four outcomes: visual acuity, topography, refraction and astigmatism, and central corneal thickness. Statistically significant improvements were found in all efficacy outcomes at 12 months after the operation. Common side effects were pain, corneal edema, and corneal haze, which resolved usually within a few days after the procedure. The remaining uncertainty is duration of benefit to establish the procedure's potential benefit in avoiding or delaying disease progression and possibly reducing the need for corneal transplantation.

  9. Definition of the locus responsible for systemic carnitine deficiency within a 1.6-cM region of mouse chromosome 11 by detailed linkage analysis

    Energy Technology Data Exchange (ETDEWEB)

    Okita, Kohei; Tokino, Takashi; Nishimori, Hiroyuki [Univ. of Tokyo (Japan)] [and others

    1996-04-15

    Carnitine is an essential cofactor for oxidation of mitochondrial fatty acids. Carnitine deficiency results in failure of energy production by mitochondria and leads to metabolic encephalopathy, lipid-storage myopathy, and cardiomyopathy. The juvenile visceral steatosis (JVS) mouse, an animal model of systemic carnitine deficiency, inherits the JVS phenotype in autosomal recessive fashion, through a mutant allele mapped to mouse chromosome 11. As a step toward identifying the gene responsible for JVS by positional cloning, we attempted to refine the jvs locus in the mouse by detailed linkage analysis with 13 microsatellite markers, using 190 backcross progeny. Among the 13 loci tested, 5 (defined by markers D11Mit24, D11Mit111,D11Nds9, D11Mit86, and D11Mit23) showed no recombination, with a maximum lod score of 52.38. Our results implied that the jvs gene can be sought on mouse chromosome 11 within a genetic distance no greater than about 1.6 cM. 21 refs., 2 figs.

  10. Phylogenetic and Functional Analysis of Metagenome Sequence from High-Temperature Archaeal Habitats Demonstrate Linkages between Metabolic Potential and Geochemistry

    DEFF Research Database (Denmark)

    Inskeep, William P; Jay, Zackary J; Herrgard, Markus

    2013-01-01

    from the sequence data. Analysis of protein family occurrence, particularly of those involved in energy conservation, electron transport, and autotrophic metabolism, revealed significant differences in metabolic strategies across sites consistent with differences in major geochemical attributes (e.......4 and to discuss specific examples where the metabolic potential correlated with measured environmental parameters and geochemical processes occurring in situ. Random shotgun metagenome sequence (∼40-45 Mb Sanger sequencing per site) was obtained from environmental DNA extracted from high-temperature sediments and....../or microbial mats and subjected to numerous phylogenetic and functional analyses. Analysis of individual sequences (e.g., MEGAN and G + C content) and assemblies from each habitat type revealed the presence of dominant archaeal populations in all environments, 10 of whose genomes were largely reconstructed...

  11. Two-point L1 shortest path queries in the plane

    Directory of Open Access Journals (Sweden)

    Danny Z. Chen

    2016-12-01

    Full Text Available Let $P$ be a set of $h$ pairwise-disjoint polygonal obstacles with a total of $n$ vertices in the plane. We consider the problem of building a data structure that can quickly compute an $L_1$ shortest obstacle-avoiding path between any two  query points $s$ and $t$. Previously, a data structure of size $O(n^2\\log n$ was constructed in $O(n^2\\log^2 n$ time that answers each two-point query in $O(\\log^2 n+k$ time, i.e., the shortest path length is reported in $O(\\log^2 n$ time and an actual path is reported in additional $O(k$ time, where $k$ is the number of edges of the output path. In this paper, we build a new data structure of size $O(n+h^2 \\log h 4^{\\sqrt{\\log h}}$ in $O(n+h^2 \\log^{2}h 4^{\\sqrt{\\log h}}$ time that answers each query in $O(\\log n+k$ time. (In contrast, for the Euclidean version of this two-point query problem, the best known algorithm uses $O(n^{11}$ space to achieve an $O(\\log n+k$ query time. Further, we extend our techniques to the weighted rectilinear version in which the ``obstacles" of $P$ are rectilinear regions with ``weights" and allow $L_1$ paths to travel through them with weighted costs. Previously, a data structure of size $O(n^2\\log^2 n$ was built in $O(n^2\\log^2 n$ time that answers each query in $O(\\log^2 n+k$ time. Our new algorithm answers each query in $O(\\log n+k$ time with a data structure of size $O(n^2 \\log n 4^{\\sqrt{\\log n}}$ that is built in $O(n^2 \\log^2 n 4^{\\sqrt{\\log n}}$ time.

  12. An Attempt to Derive the epsilon Equation from a Two-Point Closure

    Science.gov (United States)

    Canuto, V. M.; Cheng, Y.; Howard, A. M.

    2010-01-01

    The goal of this paper is to derive the equation for the turbulence dissipation rate epsilon for a shear-driven flow. In 1961, Davydov used a one-point closure model to derive the epsilon equation from first principles but the final result contained undetermined terms and thus lacked predictive power. Both in 1987 and in 2001, attempts were made to derive the epsilon equation from first principles using a two-point closure, but their methods relied on a phenomenological assumption. The standard practice has thus been to employ a heuristic form of the equation that contains three empirical ingredients: two constants, c(sub 1 epsilon), and c(sub 2 epsilon), and a diffusion term D(sub epsilon) In this work, a two-point closure is employed, yielding the following results: 1) the empirical constants get replaced by c(sub 1), c(sub 2), which are now functions of Kappa and epsilon; 2) c(sub 1) and c(sub 2) are not independent because a general relation between the two that are valid for any Kappa and epsilon are derived; 3) c(sub 1), c(sub 2) become constant with values close to the empirical values c(sub 1 epsilon), c(sub epsilon 2), (i.e., homogenous flows); and 4) the empirical form of the diffusion term D(sub epsilon) is no longer needed because it gets substituted by the Kappa-epsilon dependence of c(sub 1), c(sub 2), which plays the role of the diffusion, together with the diffusion of the turbulent kinetic energy D(sub Kappa), which now enters the new equation (i.e., inhomogeneous flows). Thus, the three empirical ingredients c(sub 1 epsilon), c(sub epsilon 2), D (sub epsilon)are replaced by a single function c(sub 1)(Kappa, epsilon ) or c(sub 2)(Kappa, epsilon ), plus a D(sub Kappa)term. Three tests of the new equation for epsilon are presented: one concerning channel flow and two concerning the shear-driven planetary boundary layer (PBL).

  13. A whole transcriptomal linkage analysis of gene co-regulation in insecticide resistant house flies, Musca domestica

    OpenAIRE

    2013-01-01

    Background Studies suggest that not only is insecticide resistance conferred via multiple gene up-regulation, but it is mediated through the interaction of regulatory factors. However, no regulatory factors in insecticide resistance have yet been identified, and there has been no examination of the regulatory interaction of resistance genes. Our current study generated the first reference transcriptome from the adult house fly and conducted a whole transcriptome analysis for the multiple inse...

  14. A gene-based linkage map for Bicyclus anynana butterflies allows for a comprehensive analysis of synteny with the lepidopteran reference genome.

    Directory of Open Access Journals (Sweden)

    Patrícia Beldade

    2009-02-01

    Full Text Available Lepidopterans (butterflies and moths are a rich and diverse order of insects, which, despite their economic impact and unusual biological properties, are relatively underrepresented in terms of genomic resources. The genome of the silkworm Bombyx mori has been fully sequenced, but comparative lepidopteran genomics has been hampered by the scarcity of information for other species. This is especially striking for butterflies, even though they have diverse and derived phenotypes (such as color vision and wing color patterns and are considered prime models for the evolutionary and developmental analysis of ecologically relevant, complex traits. We focus on Bicyclus anynana butterflies, a laboratory system for studying the diversification of novelties and serially repeated traits. With a panel of 12 small families and a biphasic mapping approach, we first assigned 508 expressed genes to segregation groups and then ordered 297 of them within individual linkage groups. We also coarsely mapped seven color pattern loci. This is the richest gene-based map available for any butterfly species and allowed for a broad-coverage analysis of synteny with the lepidopteran reference genome. Based on 462 pairs of mapped orthologous markers in Bi. anynana and Bo. mori, we observed strong conservation of gene assignment to chromosomes, but also evidence for numerous large- and small-scale chromosomal rearrangements. With gene collections growing for a variety of target organisms, the ability to place those genes in their proper genomic context is paramount. Methods to map expressed genes and to compare maps with relevant model systems are crucial to extend genomic-level analysis outside classical model species. Maps with gene-based markers are useful for comparative genomics and to resolve mapped genomic regions to a tractable number of candidate genes, especially if there is synteny with related model species. This is discussed in relation to the identification of

  15. Asset Market Linkages in Crisis Periods

    NARCIS (Netherlands)

    P. Hartmann; S. Straetmans; C.G. de Vries (Casper)

    2001-01-01

    textabstractWe characterize asset return linkages during periods of stress by an extremal dependence measure. Contrary to correlation analysis, this non-parametric measure is not predisposed towards the normal distribution and can account for non-linear relationships. Our estimates for the G-5 count

  16. Asset Market Linkages in Crisis Periods

    NARCIS (Netherlands)

    P. Hartmann; S. Straetmans; C.G. de Vries (Casper)

    2001-01-01

    textabstractWe characterize asset return linkages during periods of stress by an extremal dependence measure. Contrary to correlation analysis, this non-parametric measure is not predisposed towards the normal distribution and can account for non-linear relationships. Our estimates for the G-5

  17. Covariant and infrared-free graviton two-point function in de Sitter spacetime II

    CERN Document Server

    Pejhan, Hamed

    2016-01-01

    The solution to the linearized Einstein equation in de Sitter (dS) spacetime and the corresponding two-point function are explicitly written down in a gauge with two parameters `$a$' and `$b$'. The quantization procedure, independent of the choice of the coordinate system, is based on a rigorous group theoretical approach. Our result takes the form of a universal spin-two (transverse-traceless) sector and a gauge-dependent spin-zero (pure-trace) sector. Scalar equations are derived for the structure functions of each part. We show that the spin-two sector can be written as the resulting action of a second-order differential operator (the spin-two projector) on a massless minimally coupled scalar field (the spin-two structure function). The operator plays the role of a symmetric rank-$2$ polarization tensor and has a spacetime dependence. The calculated spin-two projector grows logarithmically with distance and also no dS-invariant solution for either structure functions exist. We show that the logarithmically...

  18. Possible Complications of Ureteroscopy in Modern Endourological Era: Two-Point or “Scabbard” Avulsion

    Directory of Open Access Journals (Sweden)

    Andrius Gaizauskas

    2014-01-01

    Full Text Available Indication has led ureteroscopy to be a worldwide technique, with the expected appearance of multiple types of complications. Severe complications are possible including ureteral perforation or avulsion. Ureteral avulsion has been described as an upper urinary tract injury related to the action of blunt trauma, especially from traffic accidents, being the mechanism of injury, the result of an acute deceleration/acceleration movement. With the advent of endourology, that term is also applied to the extensive degloving injury resulting from a mechanism of stretching of the ureter that eventually breaks at the most weakened site, or ureteral avulsion is referred to as a discontinuation of the full thickness of the ureter. The paper presents a case report and literature review of the two-point or “scabbard” avulsion. The loss of long segment of the upper ureter, when end-to-end anastomosis is not technically feasible, presents a challenge to the urological surgeon. In the era of small calibre ureteroscopes these complications, due to growing incidence of renal stones will become more and more actual. Our message to other urologists is to know such a complication, to know the ways of treatment, and to analyse ureteroscopic signs, when to stop or pay attention.

  19. The Two-Point Correlation Function of Gamma-ray Bursts

    CERN Document Server

    Li, Ming-Hua

    2015-01-01

    In this paper, we examine the spacial distribution of gamma-ray bursts (GRBs) using a sample of 373 objects. We subdivide the GRB data into two redshift intervals over the redshift range $0two-point correlation function (2PCF), $\\xi(r)$ of the GRBs. In determining the separation distance of the GRB pairs, we consider two representative cosmological models: a cold dark matter universe plus a cosmological constant $\\Lambda$, with $(\\Omega_{{\\rm m}}, \\Omega_{{\\rm \\Lambda}})=(0.28,0.72)$ and an Einstein-de Sitter (EdS) universe, with $(\\Omega_{{\\rm m}}, \\Omega_{{\\rm \\Lambda}})=(1,0)$. We find a $z$-decreasing correlation of the GRB distribution, which is in agreement with the predictions of the current structure formation theory. We fit a power-law model $\\xi(r)=(r/r_0)^{-\\gamma}$ to the measured $\\xi(r)$ and obtain an amplitude and slope of $r_0= 1235.2 \\pm 342.6~h^{-1}$ Mpc and $\\gamma = 0.80\\pm 0.19 $ ($1\\sigma$ confidence level) over the scales $r=200$ to $10^4~h^{-1}$ Mpc. Our ...

  20. Exteroceptive aspects of nociception: insights from graphesthesia and two-point discrimination.

    Science.gov (United States)

    Mørch, Carsten Dahl; Andersen, Ole K; Quevedo, Alexandre S; Arendt-Nielsen, Lars; Coghill, Robert C

    2010-10-01

    The exteroceptive capabilities of the nociceptive system have long been thought to be considerably more limited than those of the tactile system. However, most investigations of spatio-temporal aspects of the nociceptive system have largely focused on intensity coding as consequence of spatial or temporal summation. Graphesthesia, the identification of numbers "written" on the skin, and assessment of the two-point discrimination thresholds were used to compare the exteroceptive capabilities of the tactile and nociceptive systems. Numbers were "written" on the forearm and the abdomen by tactile stimulation and by painful non-contact infrared laser heat stimulation. Subjects performed both graphesthesia tasks better than chance. The tactile graphesthesia tasks were performed with 89% (82-97%) correct responses on the forearm and 86% (79-94%) correct responses on the abdomen. Tactile graphesthesia tasks were significantly better than painful heat graphesthesia tasks that were performed with 31% (23-40%) and 44% (37-51%) correct responses on the forearm and abdomen, respectively. These findings demonstrate that the central nervous system is capable of assembling complex spatio-temporal patterns of nociceptive information from the body surface into unified mental objects with sufficient accuracy to enable behavioral discrimination.

  1. The real space clustering of galaxies in SDSS DR7: I. Two point correlation functions

    CERN Document Server

    Shi, Feng; Wang, Huiyuan; Zhang, Youcai; Mo, H J; Bosch, Frank C van den; Li, Shijie; Liu, Chengze; Lu, Yi; Tweed, Dylan; Yang, Lei

    2016-01-01

    Using a method to correct redshift space distortion (RSD) for individual galaxies, we present the measurements of real space two-point correlation functions (2PCFs) of galaxies in the Sloan Digital Sky Survey (SDSS) Data Release 7 (DR7). Galaxy groups selected from the SDSS are used as proxies of dark matter halos to correct the virial motions of galaxies in dark matter halos, and to reconstruct the large-scale velocity field. We use an ensemble of mock catalogs to demonstrate the reliability of our method. Over the range $0.2 < r < 20 h^{-1}{\\rm {Mpc}}$, the 2PCF measured directly in reconstructed real space is better than the measurement error due to cosmic variance, if the reconstruction uses the correct cosmology. Applying the method to the SDSS DR7, we construct a real space version of the main galaxy catalog, which contains 396,068 galaxies in the North Galactic Cap with redshifts in the range $0.01 \\leq z \\leq 0.12$. The Sloan Great Wall, the largest known structure in the nearby Universe, is not...

  2. Assessing Performance of Multipurpose Reservoir System Using Two-Point Linear Hedging Rule

    Science.gov (United States)

    Sasireka, K.; Neelakantan, T. R.

    2017-07-01

    Reservoir operation is the one of the important filed of water resource management. Innovative techniques in water resource management are focussed at optimizing the available water and in decreasing the environmental impact of water utilization on the natural environment. In the operation of multi reservoir system, efficient regulation of the release to satisfy the demand for various purpose like domestic, irrigation and hydropower can lead to increase the benefit from the reservoir as well as significantly reduces the damage due to floods. Hedging rule is one of the emerging techniques in reservoir operation, which reduce the severity of drought by accepting number of smaller shortages. The key objective of this paper is to maximize the minimum power production and improve the reliability of water supply for municipal and irrigation purpose by using hedging rule. In this paper, Type II two-point linear hedging rule is attempted to improve the operation of Bargi reservoir in the Narmada basin in India. The results obtained from simulation of hedging rule is compared with results from Standard Operating Policy, the result shows that the application of hedging rule significantly improved the reliability of water supply and reliability of irrigation release and firm power production.

  3. Phylogenetic and functional analysis of metagenome sequence from high-temperature archaeal habitats demonstrate linkages between metabolic potential and geochemistry

    Directory of Open Access Journals (Sweden)

    William P. Inskeep

    2013-05-01

    Full Text Available Geothermal habitats in Yellowstone National Park (YNP provide an unparalled opportunity to understand the environmental factors that control the distribution of archaea in thermal habitats. Here we describe, analyze and synthesize metagenomic and geochemical data collected from seven high-temperature sites that contain microbial communities dominated by archaea relative to bacteria. The specific objectives of the study were to use metagenome sequencing to determine the structure and functional capacity of thermophilic archaeal-dominated microbial communities across a pH range from 2.5 to 6.4 and to discuss specific examples where the metabolic potential correlated with measured environmental parameters and geochemical processes occurring in situ. Random shotgun metagenome sequence (~40-45 Mbase Sanger sequencing per site was obtained from environmental DNA extracted from high-temperature sediments and/or microbial mats and subjected to numerous phylogenetic and functional analyses. Analysis of individual sequences (e.g., MEGAN and G+C content and assemblies from each habitat type revealed the presence of dominant archaeal populations in all environments, 10 of whose genomes were largely reconstructed from the sequence data. Analysis of protein family occurrence, particularly of those involved in energy conservation, electron transport and autotrophic metabolism, revealed significant differences in metabolic strategies across sites consistent with differences in major geochemical attributes (e.g., sulfide, oxygen, pH. These observations provide an ecological basis for understanding the distribution of indigenous archaeal lineages across high temperature systems of YNP.

  4. Phylogenetic and Functional Analysis of Metagenome Sequence from High-Temperature Archaeal Habitats Demonstrate Linkages between Metabolic Potential and Geochemistry.

    Science.gov (United States)

    Inskeep, William P; Jay, Zackary J; Herrgard, Markus J; Kozubal, Mark A; Rusch, Douglas B; Tringe, Susannah G; Macur, Richard E; Jennings, Ryan deM; Boyd, Eric S; Spear, John R; Roberto, Francisco F

    2013-01-01

    Geothermal habitats in Yellowstone National Park (YNP) provide an unparalleled opportunity to understand the environmental factors that control the distribution of archaea in thermal habitats. Here we describe, analyze, and synthesize metagenomic and geochemical data collected from seven high-temperature sites that contain microbial communities dominated by archaea relative to bacteria. The specific objectives of the study were to use metagenome sequencing to determine the structure and functional capacity of thermophilic archaeal-dominated microbial communities across a pH range from 2.5 to 6.4 and to discuss specific examples where the metabolic potential correlated with measured environmental parameters and geochemical processes occurring in situ. Random shotgun metagenome sequence (∼40-45 Mb Sanger sequencing per site) was obtained from environmental DNA extracted from high-temperature sediments and/or microbial mats and subjected to numerous phylogenetic and functional analyses. Analysis of individual sequences (e.g., MEGAN and G + C content) and assemblies from each habitat type revealed the presence of dominant archaeal populations in all environments, 10 of whose genomes were largely reconstructed from the sequence data. Analysis of protein family occurrence, particularly of those involved in energy conservation, electron transport, and autotrophic metabolism, revealed significant differences in metabolic strategies across sites consistent with differences in major geochemical attributes (e.g., sulfide, oxygen, pH). These observations provide an ecological basis for understanding the distribution of indigenous archaeal lineages across high-temperature systems of YNP.

  5. A scoping analysis of peer-reviewed literature about linkages between aquaculture and determinants of human health.

    Science.gov (United States)

    Burns, Theresa E; Wade, Joy; Stephen, Craig; Toews, Lorraine

    2014-06-01

    For many of the world's poor, aquatic products are critical for food security and health. Because the global population is increasing as wild aquatic stocks are declining, aquaculture is an increasingly important source of aquatic products. We undertook a scoping review of the English-language peer-reviewed literature to evaluate how the research community has examined the impacts of aquaculture on four key determinants of human health: poverty, food security, food production sustainability, and gender equality. The review returned 156 primary research articles. Most research (75%) was focused in Asia, with limited research from Africa (10%) and South America (2%). Most research (80%) focused on freshwater finfish and shrimp production. We used qualitative content analysis of records which revealed 11 themes: famer income; the common environment; shared resources; integrated farming/ polyculture; employment; extensive vs. intensive production; local vs. distant ownership; food security; income equity; gender equality; and input costs. We used quantitative content analysis of records and full-text publications about freshwater finfish and shrimp aquaculture to record the frequency with which themes were represented and the positive or negative impacts of aquaculture associated with each theme. Scatter plots showed that no theme was identified in more than half of all articles and publications for both production types. Farmer income was a theme that was identified commonly and was positively impacted by both shrimp and fresh water finfish aquaculture. Polyculture, employment, and local ownership were identified less often as themes, but were also associated with positive impacts. The common environment and shared resources were more common themes in shrimp aquaculture than freshwater finfish aquaculture research, while polyculture and local ownership were more common themes in freshwater finfish aquaculture than shrimp aquaculture. Gender equality, employment, and

  6. 维基百科链接网络实证分析%Structural analysis on Wikipedia linkage network

    Institute of Scientific and Technical Information of China (English)

    王辉; 徐晓旻; 施佺

    2012-01-01

    理解维基百科词条链接网络的结构特征是深入而有效地应用维基百科的前提.基于2010年1月的数据,从度分布、权分布、宏观结构特征等角度对维基百科词条链接网络的结构特征展开实证分析.相关结果与2006年之前的维基百科词条链接网络展开对比,发现当前的维基百科网络仍然具有无标度网络特性;其宏观结构总体上满足bow-tie模型,但模型中的各组成部分比例发生了显著变化.因此,该研究对深入解析维基百科词条链接网络的结构特性具有理论和现实意义.%In order to make better use of Wikipedia, it is necessary to have a clear understanding of the structural features of word entry hyperlink network of Wikipedia. This paper conducted brief experimental analysis in aspects of degree distribution, weight distribution and marco structural analysis on Wikipedia crawled on January 2010. By comparing these characteristic with previous works done before 2006, it found that the Wikipedia hyperlink network still followed power-law distribution on degree and the marco structure still obeyed bow-tie model, however, the proportion of different components defined in bow-tie model varied significantly.

  7. Identifying nonlinear wave interactions in plasmas using two-point measurements a case study of Short Large Amplitude Magnetic Structures (SLAMS)

    CERN Document Server

    Dudok de Wit, T; Dunlop, M; Luehr, H

    1999-01-01

    A framework is described for estimating Linear growth rates and spectral energy transfers in turbulent wave-fields using two-point measurements. This approach, which is based on Volterra series, is applied to dual satellite data gathered in the vicinity of the Earth's bow shock, where Short Large Amplitude Magnetic Structures (SLAMS) supposedly play a leading role. The analysis attests the dynamic evolution of the SLAMS and reveals an energy cascade toward high-frequency waves.

  8. Refined mapping of the gene causing Familial Mediterranean fever, by linkage and homozygosity studies

    Energy Technology Data Exchange (ETDEWEB)

    Aksentijevich, I.; Pras, E.; Gruberg, L.; Helling, S.; Prosen, L.; Pras, M.; Kastner, D.L. (National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD (United States)); Shen, Y.; Holman, K.; Sutherland, G.R.; Richards, R.I. (Adelaide Children' s Hospital (Australia)); Ramsburg, M.; Dean, M. (Laboratory of Viral Carcinogenesis, Frederick, MD (United States)); Amos, C.I. (Laboratory of Skin Biology, Bethesda, MD (United States))

    1993-08-01

    Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by attacks of fever and serosal inflammation; the biochemical basis is unknown. The authors recently reported linkage of the gene causing FMF (designated [open quotes]MEF[close quotes]) to two markers on chromosome 16p. To map MEF more precisely, they have now tested nine 16p markers. Two-point and multipoint linkage analysis, as well as a study of recombinant haplotypes, placed MEF between D16S94 and D16S80, a genetic interval of about 9 cM. They also examined rates of homozygosity for markers in this region, among offspring of consanguineous marriages. For eight of nine markers, the rate of homozygosity among 26 affected inbred individuals was higher than that among their 20 unaffected sibs. Localizing MEF more precisely on the basis of homozygosity rates alone would be difficult, for two reasons: First, the FMF carrier frequency increases the chance that inbred offspring could have the disease without being homozygous by descent at MEF. Second, several of the markers in this region are relatively nonpolymorphic, with a high rate of homozygosity, regardless of their chromosomal location. 30 refs., 6 figs., 2 tabs.

  9. Toward the Integrated Framework Analysis of Linkages among Agrobiodiversity, Livelihood Diversification, Ecological Systems, and Sustainability amid Global Change

    Directory of Open Access Journals (Sweden)

    Karl S. Zimmerer

    2016-04-01

    Full Text Available Scientific and policy interest in the biological diversity of agriculture (agrobiodiversity is expanding amid global socioeconomic and environmental changes and sustainability interests. The majority of global agrobiodiversity is produced in smallholder food-growing. We use meta-analyses in an integrated framework to examine the interactions of smallholder agrobiodiversity with: (1 livelihood processes, especially migration, including impacts on agrobiodiversity as well as the interconnected resource systems of soil, water, and uncultivated habitats; and (2 plant-soil ecological systems. We hypothesize these interactions depend on: (1 scope of livelihood diversification and type resource system; and (2 plant residues and above-/belowground component ecological specificity. Findings show: (1 livelihood diversification is linked to varied environmental factors that range from rampant degradation to enhancing sustainability; and (2 significant ecological coupling of aboveground and soil agrobiodiversity (AGSOBIO assemblages. The environmental impacts of livelihood interactions correspond to variation of diversification (migration, on-farm diversification and resource system (i.e., agrobiodiversity per se, soil, water. Our findings also reveal mutually dependent interactions of aboveground and soil agrobiodiversity. Results identify livelihood diversification-induced reduction of environmental resource quality with lagged agrobiodiversity declines as a potentially major avenue of global change. Our contribution re-frames livelihood interactions to include both agrobiodiversity and ecological systems. We discuss this integrated social-environmental re-framing through the proposed spatial geographic schema of regional agri-food spaces with distinctive matrices of livelihood strategies and relations to biodiversity and resources. This re-framing can be used to integrate livelihood, agrobiodiversity, and ecological analysis and to guide policy and

  10. Linkage of organic anion transporter-1 to metabolic pathways through integrated "omics"-driven network and functional analysis.

    Science.gov (United States)

    Ahn, Sun-Young; Jamshidi, Neema; Mo, Monica L; Wu, Wei; Eraly, Satish A; Dnyanmote, Ankur; Bush, Kevin T; Gallegos, Tom F; Sweet, Douglas H; Palsson, Bernhard Ø; Nigam, Sanjay K

    2011-09-09

    The main kidney transporter of many commonly prescribed drugs (e.g. penicillins, diuretics, antivirals, methotrexate, and non-steroidal anti-inflammatory drugs) is organic anion transporter-1 (OAT1), originally identified as NKT (Lopez-Nieto, C. E., You, G., Bush, K. T., Barros, E. J., Beier, D. R., and Nigam, S. K. (1997) J. Biol. Chem. 272, 6471-6478). Targeted metabolomics in knockouts have shown that OAT1 mediates the secretion or reabsorption of many important metabolites, including intermediates in carbohydrate, fatty acid, and amino acid metabolism. This observation raises the possibility that OAT1 helps regulate broader metabolic activities. We therefore examined the potential roles of OAT1 in metabolic pathways using Recon 1, a functionally tested genome-scale reconstruction of human metabolism. A computational approach was used to analyze in vivo metabolomic as well as transcriptomic data from wild-type and OAT1 knock-out animals, resulting in the implication of several metabolic pathways, including the citric acid cycle, polyamine, and fatty acid metabolism. Validation by in vitro and ex vivo analysis using Xenopus oocyte, cell culture, and kidney tissue assays demonstrated interactions between OAT1 and key intermediates in these metabolic pathways, including previously unknown substrates, such as polyamines (e.g. spermine and spermidine). A genome-scale metabolic network reconstruction generated some experimentally supported predictions for metabolic pathways linked to OAT1-related transport. The data support the possibility that the SLC22 and other families of transporters, known to be expressed in many tissues and primarily known for drug and toxin clearance, are integral to a number of endogenous pathways and may be involved in a larger remote sensing and signaling system (Ahn, S. Y., and Nigam, S. K. (2009) Mol. Pharmacol. 76, 481-490, and Wu, W., Dnyanmote, A. V., and Nigam, S. K. (2011) Mol. Pharmacol. 79, 795-805). Drugs may alter metabolism by

  11. Characterization of mantle convection experiments using two-point correlation functions

    Science.gov (United States)

    Puster, Peter; Jordan, Thomas H.; Hager, Bradford H.

    1995-04-01

    Snapshots of the temperature T(r, phi, t), horizontal flow velocity u(r, phi, t), and radial flow velocity w(r, phi, t) obtained from numerical convection experiments of time-dependent flows in annular cylindrical geometry are taken to be samples of stationary, rotationally invariant random fields. For such a field f(r, phi, t), the spatio-temporal two-point correlation function, C(sub ff)(r, r-prime, delta, t(sub *)), is constructed by averaging over rotational transformations of this ensemble. To assess the structural differences among mantle convection experiments we construct three spartial subfunctions of C(sub ff)(r, r-prime, delta, t(sub *)): the rms variation, sigma(sub f)(r), the radial correlation function, R(sub f)(r, r-prime), and the angular correlation function, A(sub f)(r, delta). R(sub f)(r, r-prime) and A(sub f)(r, r-prime) are symmetric about the loci r = r-prime and delta = 0, respectively, where they achieve their maximum value of unity. The falloff of R(sub f) and A(sub f) away from their symmetry can be quantified by a correlation length rho(sub f)(r) and a correlation angle alpha(sub f)(r), which we define to be the half widths of the central peaks at the correlation level 0.75. The behavior of rho(sub f) is a diagnostic of radial structure, while alpha(sub f) measures average plume width. We have used two-point correlation functions of the temperature field (T-diagnostics) and flow velocity fields (V-diagnostics) to quantify some important aspects of mantle convection experiments. We explore the dependence of different correlation diagnostics on Rayleigh number, internal heating rate, and depth- and temperature-dependent viscosity. For isoviscous flows in an annulus, we show how radial averages of sigma(sub T), rho(sub T), and alpha(sub T) scale with Rayleigh number for various internal heating rates. A break in the power-law relationship at the transition from steady to time-dependent regimes is evident for rho(sub T) and alpha(sub T) but

  12. A NEW METHOD TO CORRECT FOR FIBER COLLISIONS IN GALAXY TWO-POINT STATISTICS

    Energy Technology Data Exchange (ETDEWEB)

    Guo Hong; Zehavi, Idit [Department of Astronomy, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106 (United States); Zheng Zheng [Department of Physics and Astronomy, University of Utah, 115 South 1400 East, Salt Lake City, UT 84112 (United States)

    2012-09-10

    In fiber-fed galaxy redshift surveys, the finite size of the fiber plugs prevents two fibers from being placed too close to one another, limiting the ability to study galaxy clustering on all scales. We present a new method for correcting such fiber collision effects in galaxy clustering statistics based on spectroscopic observations. The target galaxy sample is divided into two distinct populations according to the targeting algorithm of fiber placement, one free of fiber collisions and the other consisting of collided galaxies. The clustering statistics are a combination of the contributions from these two populations. Our method makes use of observations in tile overlap regions to measure the contributions from the collided population, and to therefore recover the full clustering statistics. The method is rooted in solid theoretical ground and is tested extensively on mock galaxy catalogs. We demonstrate that our method can well recover the projected and the full three-dimensional (3D) redshift-space two-point correlation functions (2PCFs) on scales both below and above the fiber collision scale, superior to the commonly used nearest neighbor and angular correction methods. We discuss potential systematic effects in our method. The statistical correction accuracy of our method is only limited by sample variance, which scales down with (the square root of) the volume probed. For a sample similar to the final SDSS-III BOSS galaxy sample, the statistical correction error is expected to be at the level of 1% on scales {approx}0.1-30 h {sup -1} Mpc for the 2PCFs. The systematic error only occurs on small scales, caused by imperfect correction of collision multiplets, and its magnitude is expected to be smaller than 5%. Our correction method, which can be generalized to other clustering statistics as well, enables more accurate measurements of full 3D galaxy clustering on all scales with galaxy redshift surveys.

  13. Giant cell tumor occurring in familial Paget's disease of bone: report of clinical characteristics and linkage analysis of a large pedigree.

    Science.gov (United States)

    Gianfrancesco, Fernando; Rendina, Domenico; Merlotti, Daniela; Esposito, Teresa; Amyere, Mustapha; Formicola, Daniela; Muscariello, Riccardo; De Filippo, Gianpaolo; Strazzullo, Pasquale; Nuti, Ranuccio; Vikkula, Mikka; Gennari, Luigi

    2013-02-01

    Neoplastic degeneration represents a rare but serious complication of Paget's disease of bone (PDB). Although osteosarcomas have been described in up to 1% of PDB cases, giant cell tumors are less frequent and mainly occur in patients with polyostotic disease. We recently characterized a large pedigree with 14 affected members of whom four developed giant cell tumors at pagetic sites. The high number of affected subjects across multiple generations allowed us to better characterize the clinical phenotype and look for possible susceptibility loci. Of interest, all the affected members had polyostotic PDB, but subjects developing giant cell tumors showed an increased disease severity with a reduced clinical response to bisphosphonate treatment and an increased prevalence of bone pain, deformities, and fractures. Together with an increased occurrence of common pagetic complications, affected patients of this pedigree also evidenced a fivefold higher prevalence of coronary artery disease with respect to either the unaffected family members or a comparative cohort of 150 unrelated PDB cases from the same geographical area. This association was further enhanced in the four cases with PDB and giant cell tumors, all of them developing coronary artery disease before 60 years of age. Despite the early onset and the severe phenotype, PDB patients from this pedigree were negative for the presence of SQSTM1 or TNFRSF11A mutations, previously associated with enhanced disease severity. Genome-wide linkage analysis identified six possible candidate regions on chromosomes 1, 5, 6, 8, 10, and 20. Because the chromosome 8 and 10 loci were next to the TNFRSF11B and OPTN genes, we extended the genetic screening to these two genes, but we failed to identify any causative mutation at both the genomic and transcription level, suggesting that a different genetic defect is associated with PDB and potentially giant cell tumor of bone in this pedigree. Copyright © 2013 American Society for

  14. Autosomal dominant familial spastic paraplegia: Tight linkage to chromosome 15q

    Energy Technology Data Exchange (ETDEWEB)

    Fink, J.K.; Wu, C.T.B.; Jones, S.M.

    1994-09-01

    Familial spastic paraplegia (FSP) (MIM No.18260) constitutes a clinically and genetically diverse group of disorders that share the primary feature of progressive, severe, lower extremity spasticity. FSP is classified according to the mode of inheritance and whether progressive spasticity occurs in isolation ({open_quotes}uncomplicated FSP{close_quotes}) or with other neurologic abnormalities ({open_quotes}complicated FSP{close_quotes}), including optic neuropathy, retinopathy, extrapyramidal disturbance, dementia, ataxia, ichthyosis, mental retardation, or deafness. Recently, autosomal dominant, uncomplicated FSP was shown to be genetically heterogeneous and tightly linked to a group of microsatellite markers on chromosome 14q in one large kindred. We examined 126 members of a non-consanguineous North American kindred of Irish descent. FSP was diagnosed in 31 living subjects who developed insidiously progressive gait disturbance between ages 12 and 35 years. Using genetic linkage analysis to microsatellite DNA polymorphisms, we showed that the FSP locus on chromosome 14q was exluded from linkage with the disorder in our family. Subsequently, we searched for genetic linkage between the disorder and microsatellite DNA polymorphisms spanning approximately 50% of the genome. We observed significantly positive, two-point maximum lod scores (Z) for markers on chromosome 15q: D15S128 (Z=9.70, {theta}=0.05), D15S165 (Z=3.30, {theta}=0.10), and UT511 (Z=3.86, {theta}=0.10). Our data clearly establishes that one locus for autosomal dominant, uncomplicated FSP is mapped to the pericentric region of chromosome 15q. Identifying genes responsible for chromosome 15q-linked and chromosome 14q-linked FSP will greatly advance our understanding of this condition and hopefully other inherited and degenerative brain and spinal cord disorders that are also characterized by axonal degeneration.

  15. Attitude reconstruction of ROSETTA's Lander PHILAE using two-point magnetic field observations by ROMAP and RPC-MAG

    Science.gov (United States)

    Heinisch, Philip; Auster, Hans-Ulrich; Richter, Ingo; Hercik, David; Jurado, Eric; Garmier, Romain; Güttler, Carsten; Glassmeier, Karl-Heinz

    2016-08-01

    As part of the European Space Agency's ROSETTA Mission the Lander PHILAE touched down on comet 67P/Churyumov-Gerasimenko on November 12, 2014. The magnetic field has been measured onboard the orbiter and the lander. The orbiter's tri-axial fluxgate magnetometer RPC-MAG is one of five sensors of the ROSETTA Plasma Consortium. The lander is also equipped with a tri-axial fluxgate magnetometer as part of the ROSETTA Lander Magnetometer and Plasma-Monitor package (ROMAP). This unique setup makes a two point measurement between the two spacecrafts in a relatively small distance of less than 50 km possible. Both magnetometers were switched on during the entire descent, the initial touchdown, the bouncing between the touchdowns and after the final touchdown. We describe a method for attitude determination by correlating magnetic low-frequency waves, which was tested under different conditions and finally used to reconstruct PHILAE's attitude during descent and after landing. In these cases the attitude could be determined with an accuracy of better than ± 5 °. These results were essential not only for PHILAE operations planning but also for the analysis of the obtained scientific data, because nominal sources for this information, like solar panel currents and camera pictures could not provide sufficient information due to the unexpected landing position.

  16. ANALYSIS OF CONTRIBUTIONS AND LINKAGES

    African Journals Online (AJOL)

    the other hand, Asawase Estate typifies control, rigid and top-down ... Kumasi is the second largest city in Ghana and the estwhile capital of the great ... of clothes and food etc. Currently, most ... photography and dressing making shops. These.

  17. Linkage analysis of bipolar illness with X-chromosome DNA markers: A susceptibility gene in Xq27-q28 cannot be excluded

    Energy Technology Data Exchange (ETDEWEB)

    De bruyn, A.; Raeymaekers, P.; Raes, G. [Univ. of Antwerp (Belgium)] [and others

    1994-12-15

    Transmission studies have supported the presence of a susceptibility gene for bipolar (BP) illness on the X-chromosome. Initial linkage studies with color blindness (CB), glucose-6-phosphate dehydrogenase (G6PD) deficiency, and the blood coagulation factor IX (F9) have suggested that a gene for BP illness is located in the Xq27-q28 region. We tested linkage with several DNA markers located in Xq27-q28 in 2 families, MAD3 and MAD4, that previously were linked to F9, and 7 newly ascertained families of BP probands. Linkage was also examined with the gene encoding the {alpha}3 subunit of the gamma-amino butyric acid receptor (GABRA3), a candidate gene for BP illness located in this region. The genetic data were analyzed with the LOD score method using age-dependent penetrance of an autosomal dominant disease gene and narrow and broad clinical models. In MAD3 and MAD4 the multipoint LOD score data suggested a localization of a BPI gene again near F9. In the 7 new families the overall linkage data excluded the Xq27-q28 region. However, if the families were grouped according to their proband`s phenotype BPI or BPII, a susceptibility gene for BPI disorder at the DXS52-F8 cluster could not be excluded. 48 refs., 2 figs., 3 tabs.

  18. Genomewide high-density SNP linkage analysis of non-BRCA1/2 breast cancer families identifies various candidate regions and has greater power than microsatellite studies

    NARCIS (Netherlands)

    A. González-Neira (Anna); J.M. Rosa-Rosa; A. Osorio (Ana); E. Gonzalez (Emilio); M.C. Southey (Melissa); O. Sinilnikova (Olga); H. Lynch (Henry); R.A. Oldenburg (Rogier); C.J. van Asperen (Christi); N. Hoogerbrugge (Nicoline); G. Pita (G.); P. Devilee (Peter); D. Goldgar (David); J. Benítez (Javier)

    2007-01-01

    textabstractBackground: The recent development of new high-throughput technologies for SNP genotyping has opened the possibility of taking a genome-wide linkage approach to the search for new candidate genes involved in heredity diseases. The two major breast cancer susceptibility genes BRCA1 and BR

  19. Construction of an intra-specific sweet cherry (Prunus avium L.) genetic linkage map and synteny analysis with the Prunus reference map

    Science.gov (United States)

    Linkage maps of the sweet cherry cultivar ‘Emperor Francis’ (EF) and the wild forest cherry ‘New York 54’ (NY) were constructed using primarily simple sequence repeat (SSR) markers and gene-derived markers with known positions on the Prunus reference map. The success rate for identifying SSR markers...

  20. Prenatal diagnosis of the carbohydrate-deficient glycoprotein syndrome type 1A (CDG1A) by a combination of enzymology and genetic linkage analysis after amniocentesis or chorionic villus sampling.

    Science.gov (United States)

    Charlwood, J; Clayton, P; Keir, G; Mian, N; Young, E; Winchester, B

    1998-07-01

    Two pregnancies at risk for the carbohydrate-deficient glycoprotein syndrome Type 1A (CDG1A, phosphomannomutase deficient) were monitored by enzyme and genetic linkage analyses. The index case in both families had a proven deficiency of phosphomannomutase (PMM). An unaffected fetus was predicted in family 1 following amniocentesis. Normal PMM activity was found in cultured amniotic fluid cells and there was no elevation of lysosomal enzymes in the amniotic fluid. Genetic linkage analysis using microsatellite markers closely linked to the CDG1A gene confirmed this prediction. A healthy child was born. In the second family direct assay of chorionic villi showed a profound deficiency of PMM and genetic linkage analysis showed the fetus to have the same haplotype as the proband. The pregnancy was terminated and a deficiency of PMM was confirmed in cultured fibroblasts from the fetus. Reliable prenatal diagnosis of CDG Type 1A (PMM-deficient) can be achieved by a combination of biochemical and molecular genetic tests.

  1. How home HIV testing and counselling with follow-up support achieves high testing coverage and linkage to treatment and prevention: a qualitative analysis from Uganda

    Directory of Open Access Journals (Sweden)

    Norma C Ware

    2016-06-01

    Full Text Available Introduction: The successes of HIV treatment scale-up and the availability of new prevention tools have raised hopes that the epidemic can finally be controlled and ended. Reduction in HIV incidence and control of the epidemic requires high testing rates at population levels, followed by linkage to treatment or prevention. As effective linkage strategies are identified, it becomes important to understand how these strategies work. We use qualitative data from The Linkages Study, a recent community intervention trial of community-based testing with linkage interventions in sub-Saharan Africa, to show how lay counsellor home HIV testing and counselling (home HTC with follow-up support leads to linkage to clinic-based HIV treatment and medical male circumcision services. Methods: We conducted 99 semi-structured individual interviews with study participants and three focus groups with 16 lay counsellors in Kabwohe, Sheema District, Uganda. The participant sample included both HIV+ men and women (N=47 and HIV-uncircumcised men (N=52. Interview and focus group audio-recordings were translated and transcribed. Each transcript was summarized. The summaries were analyzed inductively to identify emergent themes. Thematic concepts were grouped to develop general constructs and framing propositional statements. Results: Trial participants expressed interest in linking to clinic-based services at testing, but faced obstacles that eroded their initial enthusiasm. Follow-up support by lay counsellors intervened to restore interest and inspire action. Together, home HTC and follow-up support improved morale, created a desire to reciprocate, and provided reassurance that services were trustworthy. In different ways, these functions built links to the health service system. They worked to strengthen individuals’ general sense of capability, while making the idea of accessing services more manageable and familiar, thus reducing linkage barriers. Conclusions

  2. How home HIV testing and counselling with follow-up support achieves high testing coverage and linkage to treatment and prevention: a qualitative analysis from Uganda

    Science.gov (United States)

    Ware, Norma C; Wyatt, Monique A; Asiimwe, Stephen; Turyamureeba, Bosco; Tumwesigye, Elioda; van Rooyen, Heidi; Barnabas, Ruanne V; Celum, Connie L

    2016-01-01

    Introduction The successes of HIV treatment scale-up and the availability of new prevention tools have raised hopes that the epidemic can finally be controlled and ended. Reduction in HIV incidence and control of the epidemic requires high testing rates at population levels, followed by linkage to treatment or prevention. As effective linkage strategies are identified, it becomes important to understand how these strategies work. We use qualitative data from The Linkages Study, a recent community intervention trial of community-based testing with linkage interventions in sub-Saharan Africa, to show how lay counsellor home HIV testing and counselling (home HTC) with follow-up support leads to linkage to clinic-based HIV treatment and medical male circumcision services. Methods We conducted 99 semi-structured individual interviews with study participants and three focus groups with 16 lay counsellors in Kabwohe, Sheema District, Uganda. The participant sample included both HIV+ men and women (N=47) and HIV-uncircumcised men (N=52). Interview and focus group audio-recordings were translated and transcribed. Each transcript was summarized. The summaries were analyzed inductively to identify emergent themes. Thematic concepts were grouped to develop general constructs and framing propositional statements. Results Trial participants expressed interest in linking to clinic-based services at testing, but faced obstacles that eroded their initial enthusiasm. Follow-up support by lay counsellors intervened to restore interest and inspire action. Together, home HTC and follow-up support improved morale, created a desire to reciprocate, and provided reassurance that services were trustworthy. In different ways, these functions built links to the health service system. They worked to strengthen individuals’ general sense of capability, while making the idea of accessing services more manageable and familiar, thus reducing linkage barriers. Conclusions Home HTC with follow

  3. Experimental Study of the Convergence of Two-Point Cross-Correlation Toward the Green's Function

    Science.gov (United States)

    Gouedard, P.; Roux, P.; Campillo, M.; Verdel, A.; Campman, X.

    2007-12-01

    It has been shown theoretically by several authors that cross-correlation of the seismic motion recorded at two points could yield the Green's Function (GF) between these points. Convergence of cross-correlations toward the GF depends on sources positions and/or the nature of the wavefield. Direct waves from an even distribution of sources can be used to retrieve the GF. On the other hand, in an inhomogeneous medium, recording the diffuse field (coda) is theoretically sufficient to retrieve the GF whatever the sources distribution is. Since none of these two conditions (even distribution of sources or a perfectly diffuse field) is satisfied in practice, the question of convergence toward the GF has to be investigated with real data. A 3D exploration survey with sources and receivers on a dense grid offers such an opportunity. We used a high- resolution survey recorded by Petroleum Development Oman in North Oman. The data have been obtained in a 1x1~km area covered with 1600 geophones located on a 25x25~m-cell grid. Records are 4-seconds long. A unique feature of this survey is that vibrators (working in the [8-120~Hz] frequency band), were located on a similar grid shifted with respect to the receiver grid by half a cell (12.5~m) in both directions. This allows us to compare estimated GF's with measured direct waves (GF's) between the geophones. The shallow subsurface is highly heterogeneous and records include seismic coda. From this dataset, we selected two receiver locations (Ra and Rb) distant from d=158~m. We used both different sets of source locations and time windows to compute the cross-correlation between these two receivers. Then we compared the derivatives of correlation functions with the actual GF measured in Rb (resp.~Ra) for a source close to Ra (resp.~Rb). By doing so, we show the actual influence of source locations and scattering (governed by the records' selected time window) on the Signal-to-Noise Ratio (SNR) of the reconstructed GF. When using

  4. Groebner bases via linkage

    CERN Document Server

    Gorla, Elisa; Nagel, Uwe

    2010-01-01

    In this paper, we give a sufficient condition for a set $\\mathal G$ of polynomials to be a Gr\\"obner basis with respect to a given term-order for the ideal $I$ that it generates. Our criterion depends on the linkage pattern of the ideal $I$ and of the ideal generated by the initial terms of the elements of $\\mathcal G$. We then apply this criterion to ideals generated by minors and pfaffians. More precisely, we consider large families of ideals generated by minors or pfaffians in a matrix or a ladder, where the size of the minors or pfaffians is allowed to vary in different regions of the matrix or the ladder. We use the sufficient condition that we established to prove that the minors or pfaffians form a reduced Gr\\"obner basis for the ideal that they generate, with respect to any diagonal or anti-diagonal term-order. We also show that the corresponding initial ideal is Cohen-Macaulay. Our proof relies on known results in liaison theory, combined with a simple Hilbert function computation. In particular, our...

  5. POC CD4 Testing Improves Linkage to HIV Care and Timeliness of ART Initiation in a Public Health Approach: A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Lara Vojnov

    Full Text Available CD4 cell count is an important test in HIV programs for baseline risk assessment, monitoring of ART where viral load is not available, and, in many settings, antiretroviral therapy (ART initiation decisions. However, access to CD4 testing is limited, in part due to the centralized conventional laboratory network. Point of care (POC CD4 testing has the potential to address some of the challenges of centralized CD4 testing and delays in delivery of timely testing and ART initiation. We conducted a systematic review and meta-analysis to identify the extent to which POC improves linkages to HIV care and timeliness of ART initiation.We searched two databases and four conference sites between January 2005 and April 2015 for studies reporting test turnaround times, proportion of results returned, and retention associated with the use of point-of-care CD4. Random effects models were used to estimate pooled risk ratios, pooled proportions, and 95% confidence intervals.We identified 30 eligible studies, most of which were completed in Africa. Test turnaround times were reduced with the use of POC CD4. The time from HIV diagnosis to CD4 test was reduced from 10.5 days with conventional laboratory-based testing to 0.1 days with POC CD4 testing. Retention along several steps of the treatment initiation cascade was significantly higher with POC CD4 testing, notably from HIV testing to CD4 testing, receipt of results, and pre-CD4 test retention (all p<0.001. Furthermore, retention between CD4 testing and ART initiation increased with POC CD4 testing compared to conventional laboratory-based testing (p = 0.01. We also carried out a non-systematic review of the literature observing that POC CD4 increased the projected life expectancy, was cost-effective, and acceptable.POC CD4 technologies reduce the time and increase patient retention along the testing and treatment cascade compared to conventional laboratory-based testing. POC CD4 is, therefore, a useful tool

  6. The first-generation Daphnia magna linkage map

    Directory of Open Access Journals (Sweden)

    De Meester Luc

    2010-09-01

    Full Text Available Abstract Background Daphnia magna is a well-established model species in ecotoxicology, ecology and evolution. Several new genomics tools are presently under development for this species; among them, a linkage map is a first requirement for estimating the genetic background of phenotypic traits in quantitative trait loci (QTL studies and is also very useful in assembling the genome. It also enables comparative studies between D. magna and D. pulex, for which a linkage map already exists. Results Here we describe the first genetic linkage map of D. magna. We generated 214 F2 (intercross clonal lines as the foundation of the linkage analysis. The linkage map itself is based on 109 microsatellite markers, which produced ten major linkage groups ranging in size from 31.1 cM to 288.5 cM. The total size of this linkage map extends to 1211.6 Kosambi cM, and the average interval for the markers within linkage groups is 15.1 cM. The F2 clones can be used to map QTLs for traits that differ between the parental clones. We successfully mapped the location of two loci with infertility alleles, one inherited from the paternal clone (Iinb1 and the other from the maternal clone (Xinb3. Conclusions The D. magna linkage map presented here provides extensive coverage of the genome and a given density of markers that enable us to detect QTLs of moderate to strong effects. It is similar in size to the linkage map of D. pulex.

  7. A Statistical Approach to Crime Linkage

    OpenAIRE

    Porter, Michael D.

    2014-01-01

    The object of this paper is to develop a statistical approach to criminal linkage analysis that discovers and groups crime events that share a common offender and prioritizes suspects for further investigation. Bayes factors are used to describe the strength of evidence that two crimes are linked. Using concepts from agglomerative hierarchical clustering, the Bayes factors for crime pairs are combined to provide similarity measures for comparing two crime series. This facilitates crime series...

  8. Emergency Linkage Mode of Power Enterprise

    Directory of Open Access Journals (Sweden)

    Feng Jie

    2016-01-01

    Full Text Available Power emergency disposal needs take full advantage of the power enterprise within the external emergency power and resources. Based on analyzing and summarizing the relevant experience of domestic and foreign emergency linkage, this paper draws the Emergency Linkage subjects, Emergency Linkage contents, Emergency Linkage level, which are three key elements if power enterprise Emergency Linkage. Emergency Linkage subjects are divided into the two types of inner subjects and the external body; Emergency Linkage contents are in accordance with four phases of prevention, preparedness, response and recovery; Emergency Linkage level is divided into three levels of enterprise headquarter, provincial enterprise and incident unite. Binding power enterprise emergency management practice, this paper studies the internal Emergency Linkage modes (including horizontal mode and vertical mode, external Emergency Linkage mode and comprehensive Emergency Linkage Mode of power enterprise based on Fishbone Diagram and Process Management Technology.

  9. STAKEHOLDER LINKAGES FOR SUSTAINABLE LAND ...

    African Journals Online (AJOL)

    Osondu

    stakeholder interactions for SLM in the study areas. Key words: Stakeholders; farmer-expert linkages; resource management; Ethiopia ... management practices in many parts of Africa. Farmers .... chosen with consideration of distance to the.

  10. Two-point discrimination of the upper extremities of healthy Koreans in their 20’s

    Science.gov (United States)

    Koo, Ja-Pung; Kim, Soon-Hee; An, Ho-Jung; Moon, Ok-Gon; Choi, Jung-Hyun; Yun, Young-Dae; Park, Joo-Hyun; Min, Kyoung-Ok

    2016-01-01

    [Purpose] The present study attempted to measure two-point discrimination in the upper extremities of healthy Koreans in their 20’s. [Subjects and Methods] Using a three-point esthesiometer, we conducted an experiment with a group of 256 college students (128 male and 128 female), attending N University in Chonan, Republic of Korea. [Results] Females showed two-point discrimination at a shorter distance than males at the following points: (i) 5 cm above the elbow joint, the middle part, and 5 cm below the shoulder joint of the anterior upper arm; (ii) 5 cm above the elbow joint and 5 cm below the shoulder joint of the posterior upper arm; (iii) 5 cm above the front of the wrist joint of the forearm; 5 cm below the elbow joint, the palmar part of the distal interphalangeal joint of the thumb, the dorsal part of the distal interphalangeal joint of the middle and little fingers. It was also found that females showed greater two-point discrimination than males in distal regions rather than proximal regions. [Conclusion] The findings of this study will help establish normal values for two-point discrimination of upper extremities of young Koreans in their 20’s. PMID:27134375

  11. Two-point boundary value problems and exact controllability for several kinds of linear and nonlinear wave equations

    Energy Technology Data Exchange (ETDEWEB)

    Kong Dexing [Department of Mathematics, Zhejiang University, Hangzhou 310027 (China); Sun Qingyou, E-mail: qysun@cms.zju.edu.cn [Center of Mathematical Sciences, Zhejiang University, Hangzhou 310027 (China)

    2011-04-01

    All articles must In this paper we introduce some new concepts for second-order hyperbolic equations: two-point boundary value problem, global exact controllability and exact controllability. For several kinds of important linear and nonlinear wave equations arising from physics and geometry, we prove the existence of smooth solutions of the two-point boundary value problems and show the global exact controllability of these wave equations. In particular, we investigate the two-point boundary value problem for one-dimensional wave equation defined on a closed curve and prove the existence of smooth solution which implies the exact controllability of this kind of wave equation. Furthermore, based on this, we study the two-point boundary value problems for the wave equation defined on a strip with Dirichlet or Neumann boundary conditions and show that the equation still possesses the exact controllability in these cases. Finally, as an application, we introduce the hyperbolic curvature flow and obtain a result analogous to the well-known theorem of Gage and Hamilton for the curvature flow of plane curves.

  12. Critical two-point functions and the lace expansion for spread-out high-dimensional percolation and related models

    NARCIS (Netherlands)

    Van der Hofstad, R.; Hara, T.; Slade, G.

    2003-01-01

    We consider spread-out models of self-avoiding walk, bond percolation, lattice trees and bond lattice animals on ${\\mathbb{Z}^d}$, having long finite-range connections, above their upper critical dimensions $d=4$ (self-avoiding walk), $d=6$ (percolation) and $d=8$ (trees and animals). The two-point

  13. EXISTENCE OF POSITIVE SOLUTION TO TWO-POINT BOUNDARY VALUE PROBLEM FOR A SYSTEM OF SECOND ORDER ORDINARY DIFFERENTIAL EQUATIONS

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    In this paper, we consider a two-point boundary value problem for a system of second order ordinary differential equations. Under some conditions, we show the existence of positive solution to the system of second order ordinary differential equa-tions.

  14. HIGH ACCURACY FINITE VOLUME ELEMENT METHOD FOR TWO-POINT BOUNDARY VALUE PROBLEM OF SECOND ORDER ORDINARY DIFFERENTIAL EQUATIONS

    Institute of Scientific and Technical Information of China (English)

    王同科

    2002-01-01

    In this paper, a high accuracy finite volume element method is presented for two-point boundary value problem of second order ordinary differential equation, which differs fromthe high order generalized difference methods. It is proved that the method has optimal order er-ror estimate O(h3) in H1 norm. Finally, two examples show that the method is effective.

  15. Mapping Correlation of Two Point Sources in the Gamma-Ray Sky

    Energy Technology Data Exchange (ETDEWEB)

    Gibson, Alexander [SLAC National Accelerator Lab., Menlo Park, CA (United States)

    2015-08-20

    The Fermi Gamma-Ray Space Telescope has been taking data on high energy photons or γ rays since June 11th, 2008, and people have been cataloging and profiling point sources of these γ rays ever since. After roughly one year of being in operation over 1400 sources were cataloged. Now, in 2015 we have 3033 sources cataloged. With the increasing amount of sources it’s important to think about the limitations of likelihood analysis for highly correlated sources. In this paper I will present the problems of using likelihood analysis for sources that are highly correlated as well as show under what circumstances sources can be considered highly correlated. Dark matter over densities may show up as a point source, so it is a necessary step to learn how the two signals will interact to allow for a proper search for dark matter.

  16. International Environmental Problems, Issue Linkage and the European Union

    OpenAIRE

    Kroeze-Gil, J.

    2003-01-01

    This thesis explores the circumstances under which issue linkage can be applied to achieve cooperation on international environmental problems in general and on environmental problems in the European Union in particular. A major topic in this thesis is the development and analysis of cooperative and non-cooperative game theoretical methods of issue linkage that include imperfectly reversed interests. The relevance of the models is shown in the context of EU environmental decision making.

  17. Confirmation of linkage of Hypokalemic periodic paralysis to chromosome 1q31-32: Further evidence supporting CACNL1A3 as a candidate gene

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, K.; Knouff, C.; Gaskell, P.C. [Duke Univ. Medical Center, Durham, NC (United States)] [and others

    1994-09-01

    Hypokalemic periodic paralysis (HOKPP; MIM 170400) is one entity of a series of periodic paralyses characterized by episodic bouts of weakness with onset in the second to third decades. The hypokalemic form is defined by decreased serum potassium during a paralytic attack. HOKPP can occur in both familial and sporadic forms; the familal form is autosomal dominant with reduced penetrance in female gene carriers. Recently, Fontaine et al. have localized HOKPP to 1q31-32 in three multigenerational HOKPP families. The region of sub-localization includes the CACNL1A3 gene, making it a potential candidate for the genetic defect in HOKPP. We have ascertained and sampled 2 large multigenerational HOKPP pedigrees (N = 55 individuals with DNA) for linkage analysis. The families were initially screened for linkage with over 150 marker loci located throughout the genome. Analysis of the chromosome 1 markers D1S412, D1S413 and F13B gave significant evidence for linkage. The peak two-point lod score realized was Z = 4.34 at theta = 0.0 (D1S413). A sex-dependent penetrance of 80% was assumed, although varying the penetrance did not significantly alter the results. There was no evidence for heterogeneity. Multipoint analysis of the data defined the region between D1S238 and D1S245 (which contains the CACNL1A3 gene) as the most likely region (> 1000 odds) for the location of the HOKPP gene. There were no obligate recombinants among males or affected females for the CACNL1A3 (Z = 3.19, theta = 0.0), although several potential non-penetrant females were identified. These studies confirm linkage of HOPKK to chromosome 1 in an independent data set, lend further support of CACNL1A3 as a potential candidate gene, and give evidence for homogeneity in this disease.

  18. An SSR-based linkage map of yardlong bean (Vigna unguiculata (L.) Walp. subsp. unguiculata Sesquipedalis Group) and QTL analysis of pod length.

    Science.gov (United States)

    Kongjaimun, Alisa; Kaga, Akito; Tomooka, Norihiko; Somta, Prakit; Shimizu, Takehiko; Shu, Yujian; Isemura, Takehisa; Vaughan, Duncan A; Srinives, Peerasak

    2012-02-01

    Yardlong bean (Vigna unguiculata (L.) Walp. subsp. unguiculata Sesquipedalis Group) (2n = 2x = 22) is one of the most important vegetable legumes of Asia. The objectives of this study were to develop a genetic linkage map of yardlong bean using SSR makers from related Vigna species and to identify QTLs for pod length. The map was constructed from 226 simple sequence repeat (SSR) markers from cowpea (Vigna unguiculata (L.) Walp. subsp. unguiculata Unguiculata Group), azuki bean (Vigna angularis (Willd.) Ohwi & Ohashi), and mungbean (Vigna radiata (L.) Wilczek) in a BC(1)F(1) ((JP81610 × TVnu457) × JP81610) population derived from the cross between yardlong bean accession JP81610 and wild cowpea (Vigna unguiculata subsp. unguiculata var. spontanea) accession TVnu457. The markers were clustered into 11 linkage groups (LGs) spanning 852.4 cM in total length with a mean distance between adjacent markers of 3.96 cM. All markers on LG11 showed segregation distortion towards the homozygous yardlong bean JP81610 genotype. The markers on LG11 were also distorted in the rice bean (Vigna umbellata (Thunb.) Ohwi & Ohashi) map, suggesting the presence of common segregation distortion factors in Vigna species on this LG. One major and six minor QTLs were identified for pod length variation between yardlong bean and wild cowpea. Using flanking markers, six of the seven QTLs were confirmed in an F(2) population of JP81610 × TVnu457. The molecular linkage map developed and markers linked to pod length QTLs would be potentially useful for yardlong bean and cowpea breeding.

  19. Joint-multiple family linkage analysis predicts within-family variation better than single-family analysis of the maize nested association mapping population.

    Science.gov (United States)

    Ogut, F; Bian, Y; Bradbury, P J; Holland, J B

    2015-06-01

    Quantitative trait locus (QTL) mapping has been used to dissect the genetic architecture of complex traits and predict phenotypes for marker-assisted selection. Many QTL mapping studies in plants have been limited to one biparental family population. Joint analysis of multiple biparental families offers an alternative approach to QTL mapping with a wider scope of inference. Joint-multiple population analysis should have higher power to detect QTL shared among multiple families, but may have lower power to detect rare QTL. We compared prediction ability of single-family and joint-family QTL analysis methods with fivefold cross-validation for 6 diverse traits using the maize nested association mapping population, which comprises 25 biparental recombinant inbred families. Joint-family QTL analysis had higher mean prediction abilities than single-family QTL analysis for all traits at most significance thresholds, and was always better at more stringent significance thresholds. Most robust QTL (detected in >50% of data samples) were restricted to one family and were often not detected at high frequency by joint-family analysis, implying substantial genetic heterogeneity among families for complex traits in maize. The superior predictive ability of joint-family QTL models despite important genetic differences among families suggests that joint-family models capture sufficient smaller effect QTL that are shared across families to compensate for missing some rare large-effect QTL.

  20. A high-density screen for linkage in multiple sclerosis.

    Science.gov (United States)

    Sawcer, Stephen; Ban, Maria; Maranian, Mel; Yeo, Tai Wai; Compston, Alastair; Kirby, Andrew; Daly, Mark J; De Jager, Philip L; Walsh, Emily; Lander, Eric S; Rioux, John D; Hafler, David A; Ivinson, Adrian; Rimmler, Jacqueline; Gregory, Simon G; Schmidt, Silke; Pericak-Vance, Margaret A; Akesson, Eva; Hillert, Jan; Datta, Pameli; Oturai, Annette; Ryder, Lars P; Harbo, Hanne F; Spurkland, Anne; Myhr, Kjell-Morten; Laaksonen, Mikko; Booth, David; Heard, Robert; Stewart, Graeme; Lincoln, Robin; Barcellos, Lisa F; Hauser, Stephen L; Oksenberg, Jorge R; Kenealy, Shannon J; Haines, Jonathan L

    2005-09-01

    To provide a definitive linkage map for multiple sclerosis, we have genotyped the Illumina BeadArray linkage mapping panel (version 4) in a data set of 730 multiplex families of Northern European descent. After the application of stringent quality thresholds, data from 4,506 markers in 2,692 individuals were included in the analysis. Multipoint nonparametric linkage analysis revealed highly significant linkage in the major histocompatibility complex (MHC) on chromosome 6p21 (maximum LOD score [MLS] 11.66) and suggestive linkage on chromosomes 17q23 (MLS 2.45) and 5q33 (MLS 2.18). This set of markers achieved a mean information extraction of 79.3% across the genome, with a Mendelian inconsistency rate of only 0.002%. Stratification based on carriage of the multiple sclerosis-associated DRB1*1501 allele failed to identify any other region of linkage with genomewide significance. However, ordered-subset analysis suggested that there may be an additional locus on chromosome 19p13 that acts independent of the main MHC locus. These data illustrate the substantial increase in power that can be achieved with use of the latest tools emerging from the Human Genome Project and indicate that future attempts to systematically identify susceptibility genes for multiple sclerosis will have to involve large sample sizes and an association-based methodology.

  1. A sib-pair analysis study of 15 candidate genes in French families with morbid obesity: indication for linkage with islet 1 locus on chromosome 5q.

    Science.gov (United States)

    Clément, K; Dina, C; Basdevant, A; Chastang, N; Pelloux, V; Lahlou, N; Berlan, M; Langin, D; Guy-Grand, B; Froguel, P

    1999-02-01

    As part of an ongoing search for susceptibility genes in obese families, we performed linkage analyses in 101 French families between qualitative and quantitative traits related to morbid obesity and polymorphisms located in or near 15 candidate genes whose products are involved in body weight regulation. These included cholecystokinin A and B receptors (CCK-AR and CCK-BR), glucagon-like peptide 1 receptor (GLP-1R), the LIM/homeodomain islet-1 gene (Isl-1), the caudal-type homeodomain 3 (CDX-3), the uncoupling protein 1 (UCP-1), the beta3-adrenoceptor (beta3-AR), the fatty acid-binding protein 2 (FABP-2), the hormone-sensitive lipase (HSL), the lipoprotein lipase (LPL), the apoprotein-C2 (apo-C2), the insulin receptor substrate-1 (IRS-1), the peroxisome proliferator-activated receptor-gamma (PPAR-gamma), tumor necrosis factor-alpha (TNF-alpha), and the liver carnitine palmitoyltransferase-1 (CPT-1). Phenotypes related to obesity such as BMI, adult life body weight gain, fasting leptin, insulin, fasting glycerol, and free fatty acids were used for nonparametric sib-pair analyses. A weak indication for linkage was obtained between the Isl-1 locus and obesity status defined by a z score over one SD of BMI (n = 226 sib pairs, pi = 0.54 +/- 0.02, P = 0.03). Moreover, a suggestive indication for linkage was found between the Isl-1 locus and BMI and leptin values (P = 0.001 and 0.0003, respectively) and leptin adjusted for BMI (P = 0.0001). Multipoint analyses for leptin trait with Isl-1 and two flanking markers (D5S418 and D5S407) showed that the logarithm of odds (LOD) score is 1.73, coinciding with the Isl-1 locus. Although marginally positive indications for linkage in subgroups of families were found with IRS-1, CPT-1, and HSL loci, our data suggested that these genes are not major contributors to obesity. Whether an obesity susceptibility gene (Isl-1 itself or another nearby gene) lies on chromosome 5q should be determined by further analyses.

  2. Cooperative terrain model acquisition by two point-robots in planar polygonal terrains

    Energy Technology Data Exchange (ETDEWEB)

    Rao, N.S.V.; Protopopescu, V.

    1994-11-29

    We address the model acquisition problem for an unknown terrain by a team of two robots. The terrain may be cluttered by a finite number of polygonal obstacles with unknown shapes and positions. The robots are point-sized and equipped with visual sensors which acquire all visible parts of the terrain by scanning from their locations. The robots communicate with each other via wireless connection. The performance is measured by the number of the sensor (scan) operations which are assumed to be the most time-consuming/expensive of all the robot operations. We employ the restricted visibility graph methods in a hierarchiacal setup. For terrains with convex obstacles, the sensing time can be halved compared to a single robot implementation. For terrains with concave corners, the performance of the algorithm depends on the number of concave regions and their depths. A hierarchical decomposition of the restricted visibility graph into 2-connected components and trees is considered. Performance for the 2-robot team is expressed in terms of sizes of 2-connected components, and the sizes and diameters of the trees. The proposed algorithm and analysis can be applied to the methods based on Voronoi diagram and trapezoidal decomposition.

  3. Forecasts on neutrino mass constraints from the redshift-space two-point correlation function

    Science.gov (United States)

    Petracca, F.; Marulli, F.; Moscardini, L.; Cimatti, A.; Carbone, C.; Angulo, R. E.

    2016-11-01

    We provide constraints on the accuracy with which the neutrino mass fraction, fν, can be estimated when exploiting measurements of redshift-space distortions, describing in particular how the error on neutrino mass depends on three fundamental parameters of a characteristic galaxy redshift survey: density, halo bias and volume. In doing this, we make use of a series of dark matter halo catalogues extracted from the BASICC simulation. The mock data are analysed via a Markov Chain Monte Carlo likelihood analysis. We find a fitting function that well describes the dependence of the error on bias, density and volume, showing a decrease in the error as the bias and volume increase, and a decrease with density down to an almost constant value for high-density values. This fitting formula allows us to produce forecasts on the precision achievable with future surveys on measurements of the neutrino mass fraction. For example, a Euclid-like spectroscopic survey should be able to measure the neutrino mass fraction with an accuracy of δfν ≈ 3.1 × 10-3 (which is equivalent to δ∑mν ≈ 0.039eV), using redshift-space clustering once all the other cosmological parameters are kept fixed to the ΛCDM case.

  4. Genetic linkage mapping of the dehydroepiandrosterone sulfotransferase (STD) gene on the chromosome 19q13.3 region

    Energy Technology Data Exchange (ETDEWEB)

    Durocher, F.; Morissette, J.; Dufort, I.; Simard, J.; Luu-The, V. [Laval Univ. Quebec (Canada)

    1995-10-10

    In the human liver and adrenal, there is a single hydroxysteroid sulfotransferase, which catalyzes the transformation of dehydroepiandrosterone to dehydroepiandrosterone sulfate, the most abundantly circulating steroid in humans, and also catalyzes the sulfation of a series of other 3{beta}-hydroxysteroids as well as cholesterol. Dehydroepiandrosterone sulfate serves as precursor for the formation of active androgens and estrogens in several peripheral tissues, indicating that hydroxysteroid sulfotransferase plays a pivotal role in controlling the hormonal action of sex steroids by regulating their bioavailability. We recently elucidated the structure of the gene encoding hydroxysteroid sulfotransferase (STD), also designated dehydroepiandrosterone sulfotransferase, which spans 17 kb and contains six exons. The STD gene was preliminarily assigned to chromosome 19 by polymerase chain reaction (PCR) amplification of DNA from a panel of human/rodent somatic cell hybrids. To locate the STD gene, the novel biallelic polymorphism found in intron 2 was genotyped in eight CEPH reference families by direct sequencing of PCR products. Two-point linkage analysis was first performed between the latter polymorphism and chromosome 19 markers from Genethon and NIH/CEPH. The closest linkage was observed with D19S412 (Z{sub max} = 9.23; {theta}{sub max} 0.038) and HRC (Z{sub max} =5.95; {theta}{sub max}0.036), located on the 19q13.3 region. A framework map including six Genethon markers flanking the polymorphic STD gene was created by multipoint linkage analysis. Thereafter, a high-resolution genetic map of the region was constructed, yielding to the following order: qter-D19S414-D19S224-D19S420-D19S217-(APOC2-D19S412)-(STD-HRC)-KLK-D19S22-D19S180-PRKCG-D19S418-tel. 24 refs., 2 figs.

  5. Genetic linkage of familial granulomatous inflammatory arthritis, skin rash, and uveitis to chromosome 16

    Energy Technology Data Exchange (ETDEWEB)

    Tromp, G.; Kuivaniemi, H.; Ala-Kokko, L. [Thomas Jefferson Univ., Philadelphia, PA (United States)] [and others

    1996-11-01

    Blau syndrome (MIM 186580), first described in a large, three-generation kindred, is an autosomal, dominantly inherited disease characterized by multiorgan, tissue-specific inflammation. Its clinical phenotype includes granulomatous arthritis, skin rash, and uveitis and probably represents a subtype of a group of clinical entities referred to as {open_quotes}familial granulomatosis.{close_quotes} It is the sole human model with recognizably Mendelian inheritance for a variety of multisystem inflammatory diseases affecting a significant percentage of the population. A genomewide search for the Blau susceptibility locus was undertaken after karyotypic analysis revealed no abnormalities. Sixty-two of the 74-member pedigree were genotyped with dinucleotide-repeat markers. Linkage analysis was performed under dominant model of inheritance with reduced penetrance. The marker D16S298 gave a maximum LOD score of 3.75 at {theta} = .04, with two-point analysis. LOD scores for flanking markers were consistent and placed the Blau susceptibility locus within the 16p12-q21 interval. 46 refs., 3 figs., 3 tabs.

  6. On a two-point boundary value problem for second-order differential inclusions on Riemannian manifolds

    Directory of Open Access Journals (Sweden)

    Andrei V. Obukhovskiĭ

    2003-05-01

    Full Text Available We consider second-order differential inclusions on a Riemannian manifold with lower semicontinuous right-hand sides. Several existence theorems for solutions of two-point boundary value problem are proved to be interpreted as controllability of special mechanical systems with control on nonlinear configuration spaces. As an application, a statement of controllability under extreme values of controlling force is obtained.

  7. Genetic linkage analysis of the lesser grain borer Rhyzopertha dominica identifies two loci that confer high-level resistance to the fumigant phosphine.

    Science.gov (United States)

    Schlipalius, David I; Cheng, Qiang; Reilly, Paul E B; Collins, Patrick J; Ebert, Paul R

    2002-01-01

    High levels of inheritable resistance to phosphine in Rhyzopertha dominica have recently been detected in Australia and in an effort to isolate the genes responsible for resistance we have used random amplified DNA fingerprinting (RAF) to produce a genetic linkage map of R. dominica. The map consists of 94 dominant DNA markers with an average distance between markers of 4.6 cM and defines nine linkage groups with a total recombination distance of 390.1 cM. We have identified two loci that are responsible for high-level resistance. One provides approximately 50x resistance to phosphine while the other provides 12.5x resistance and in combination, the two genes act synergistically to provide a resistance level 250x greater than that of fully susceptible beetles. The haploid genome size has been determined to be 4.76 x 10(8) bp, resulting in an average physical distance of 1.2 Mbp per map unit. No recombination has been observed between either of the two resistance loci and their adjacent DNA markers in a population of 44 fully resistant F5 individuals, which indicates that the genes are likely to reside within 0.91 cM (1.1 Mbp) of the DNA markers. PMID:12072472

  8. JLIN: A java based linkage disequilibrium plotter

    Directory of Open Access Journals (Sweden)

    McCaskie Pamela A

    2006-02-01

    Full Text Available Abstract Background A great deal of effort and expense are being expended internationally in attempts to detect genetic polymorphisms contributing to susceptibility to complex human disease. Techniques such as Linkage Disequilibrium mapping are being increasingly used to examine and compare markers across increasingly large datasets. Visualisation techniques are becoming essential to analyse the ever-growing volume of data and results available with any given analysis. Results JLIN (Java LINkage disequilibrium plotter is a software package designed for customisable, intuitive visualisation of Linkage Disequilibrium (LD across all common computing platforms. Customisation allows the user to choose particular visualisations, statistical measures and measurement ranges. JLIN also allows the user to export images of the LD visualisation in several common document formats. Conclusion JLIN allows the user to visually compare and contrast the results of a range of statistical measures on the input dataset(s. These measures include the commonly used D' and r2 statistics and empirical p-values. JLIN has a number of unique and novel features that improve on existing LD visualisation tools.

  9. Extension of normal values on sensory function for facial areas using clinical tests on touch and two-point discrimination.

    Science.gov (United States)

    Vriens, J P M; van der Glas, H W

    2009-11-01

    The threshold value of a sensory test provides a numerical measure of the sensory function. In order to decide whether a threshold value from an affected site indicates 'abnormal' sensory function, it can be compared with normal values from a healthy control population. The aim of this study was to extend current information on normal values for static light touch and static two-point discrimination for facial sites. Using simple hand-held devices, 95% upper limits of confidence intervals of threshold values were determined for facial sites other than those studied previously and for a large sample of 100 healthy subjects. The MacKinnon-Dellon Disk-Criminator and the Aesthesiometer were used to measure novel normal values of two-point discrimination. As threshold values for two-point discrimination from the Aesthesiometer were similar to those obtained using the Disk-Criminator, the use of the Aesthesiometer might not be indicated. Apart from the Pressure Specified Sensory Device (a device with pressure control), Semmes-Weinstein nylon monofilaments and the Disk-Criminator are useful devices for studying sensory function, in particular under clinical test conditions in which easy and fast application are advantageous.

  10. Rigid internal fixation of zygoma fractures: A comparison of two-point and three-point fixation

    Directory of Open Access Journals (Sweden)

    Parashar Atul

    2007-01-01

    Full Text Available Background: Displaced fractures of the zygomatic bone can result in significant functional and aesthetic sequelae. Therefore the treatment must achieve adequate and stable reduction at fracture sites so as to restore the complex multidimensional relationship of the zygoma to the surrounding craniofacial skeleton. Many experimental biophysical studies have compared stability of zygoma after one, two and three-point fixation with mini plates. We conducted a prospective clinical study comparing functional and aesthetic results of two-point and three-point fixation with mini plates in patients with fractures of zygoma. Materials and Methods: Twenty-two patients with isolated zygomatic fractures over a period of one year were randomly assigned into two-point and three-point fixation groups. Results of fixation were analyzed after completion of three months. This included clinical, radiological and photographic evaluation. Results: The three-point fixation group maintained better stability at fracture sites resulting in decreased incidence of dystopia and enophthalmos. This group also had better malar projection and malar height as measured radiologically, when compared with the two-point fixation group. Conclusion: We recommend three-point rigid fixation of fractured zygoma after accurate reduction so as to maintain adequate stabilization against masticatory forces during fracture healing phase.

  11. Association and linkage analysis of COL1A1 and AHSG gene polymorphisms with femoral neck bone geometric parameters in both Caucasian and Chinese nuclear families

    Institute of Scientific and Technical Information of China (English)

    Hui JIANG; Shu-feng LEI; Su-mei XIAO; Yuan CHEN; Xiao SUN; Fang YANG; Li-ming LI; Shun WU; Hong-wen DENC

    2007-01-01

    Aim: To simultaneously investigate the contribution of the alpha 1 chain of col-lagen type 1 (COL1A1) and alpha2-HS-glycoprotein (AHSG) genes to the varia-tion of bone geometric parameters in both Caucasians and Chinese. Methods: Six hundred and five Caucasian individuals from 157 nuclear families and 1228 Chi-nese subjects from 400 nuclear families were genotyped at the AHSG-Sacl, COL1A1-PCOL2 and Sp1 polymorphisms using polymerase chain reaction (PCR)-restric-tion fragment length polymorphism (RFLP). 5 FN bone geometric parameters were calculated based on bone mineral density and bone area of femoral neck (FN)measured by dual energy X-ray absorptiometry. Population stratification, total family association, within-family association, and linkage tests were performed by the quantitative transmission disequilibrium test program. Results: The t-test showed the significant differences of all bone geometric phenotypes (except ED)between Caucasians and Chinese in the offspring using both unadjusted and adjusted (by age, height, weight, and gender) data. In Caucasians, we found significant within-family association results between the COL1A1-Sp1 polymor-phism (rs1800012) and cross sectional area (CSA), cortical thickness (CT),endocortical diameter (ED), buckling ratio (BR) (P=0.018, 0.002, 0.023, and 0.001,respectively); the COL1A1-Sp1 polymorphism also detected significant linkage with BR (P=0.039). In the population of China, the within-family associations between the COL1A1-PCOL2 polymorphism (rs1107946) and CT, BR were signifi-cant (P=0.012 and 0.008, respectively). Furthermore, evidence of linkage were observed between the AHSG-SacI polymorphism (rs4918) and CT, BR (P--0.042 and 0.014, respectively) in Caucasians, but not in Chinese. Conclusion: Our results suggest that the COL1A1 gene may have significantly association with bone geometry in both Caucasians and Chinese, and the AHSG gene may be linked to bone geometry in Caucasians, but not in Chinese. This study

  12. Comprehensive analysis of APOE and selected proximate markers for late-onset Alzheimer's disease: patterns of linkage disequilibrium and disease/marker association.

    Science.gov (United States)

    Yu, Chang-En; Seltman, Howard; Peskind, Elaine R; Galloway, Nichole; Zhou, Peter X; Rosenthal, Elisabeth; Wijsman, Ellen M; Tsuang, Debby W; Devlin, Bernie; Schellenberg, Gerard D

    2007-06-01

    The epsilon(4) allele of APOE confers a two- to fourfold increased risk for late-onset Alzheimer's disease (LOAD), but LOAD pathology does not all fit neatly around APOE. It is conceivable that genetic variation proximate to APOE contributes to LOAD risk. Therefore, we investigated the degree of linkage disequilibrium (LD) for a comprehensive set of 50 SNPs in and surrounding APOE using a substantial Caucasian sample of 1100 chromosomes. SNPs in APOE were further molecularly haplotyped to determine their phases. One set of SNPs in TOMM40, roughly 15 kb upstream of APOE, showed intriguing LD with the epsilon(4) allele and was strongly associated with the risk for developing LOAD. However, when all the SNPs were entered into a logit model, only the effect of APOE epsilon(4) remained significant. These observations diminish the possibility that loci in the TOMM40 gene may have a major effect on the risk for LOAD in Caucasians.

  13. Comprehensive Analysis of APOE and Selected Proximate Markers for Late-onset Alzheimer Disease: Pattern of Linkage Disequilibrium and Disease/Marker Association

    Science.gov (United States)

    Yu, Chang-En; Seltman, Howard; Peskind, Elaine R.; Galloway, Nichole; Zhou, Peter X.; Rosenthal, Elisabeth; Wijsman, Ellen M.; Tsuang, Debby W.; Devlin, Bernie; Schellenberg, Gerard D.

    2007-01-01

    The ε4 allele of APOE confers a two- to four-fold increased risk for late-onset Alzheimer’s disease (LOAD), but LOAD pathology does not all fit neatly around APOE. It is conceivable that genetic variation proximate to APOE contributes to LOAD risk. Therefore, we investigated the degree of linkage disequilibrium (LD) for a comprehensive set of 50 SNPs in and surrounding the APOE using a substantial Caucasian sample of 1100 chromosomes. SNPs in APOE were further molecular haplotyped to determine their phases. One set of SNPs in TOMM40, roughly 15 Kb upstream of APOE, showed intriguing LD with the ε4 allele, and were strongly associated with the risk for developing AD. However, when all the SNPs were entered into a logit model, only the effect of APOE ε4 remained significant. These observations diminish the possibility that loci in the TOMM40 may have a major effect on the risk of LOAD in Caucasians. PMID:17434289

  14. Data Linkage: A powerful research tool with potential problems

    Directory of Open Access Journals (Sweden)

    Scott Ian

    2010-12-01

    Full Text Available Abstract Background Policy makers, clinicians and researchers are demonstrating increasing interest in using data linked from multiple sources to support measurement of clinical performance and patient health outcomes. However, the utility of data linkage may be compromised by sub-optimal or incomplete linkage, leading to systematic bias. In this study, we synthesize the evidence identifying participant or population characteristics that can influence the validity and completeness of data linkage and may be associated with systematic bias in reported outcomes. Methods A narrative review, using structured search methods was undertaken. Key words "data linkage" and Mesh term "medical record linkage" were applied to Medline, EMBASE and CINAHL databases between 1991 and 2007. Abstract inclusion criteria were; the article attempted an empirical evaluation of methodological issues relating to data linkage and reported on patient characteristics, the study design included analysis of matched versus unmatched records, and the report was in English. Included articles were grouped thematically according to patient characteristics that were compared between matched and unmatched records. Results The search identified 1810 articles of which 33 (1.8% met inclusion criteria. There was marked heterogeneity in study methods and factors investigated. Characteristics that were unevenly distributed among matched and unmatched records were; age (72% of studies, sex (50% of studies, race (64% of studies, geographical/hospital site (93% of studies, socio-economic status (82% of studies and health status (72% of studies. Conclusion A number of relevant patient or population factors may be associated with incomplete data linkage resulting in systematic bias in reported clinical outcomes. Readers should consider these factors in interpreting the reported results of data linkage studies.

  15. Linkage analysis of water use among industrial sectors in China%我国行业水资源消耗的关联度分析

    Institute of Scientific and Technical Information of China (English)

    和夏冰; 王媛; 张宏伟; 王文琴; 王丽丽

    2012-01-01

    The aim of this paper was to study the behaviour of the productive sectors of the Chinese economy as direct and indirect consumers of water. Industrial water consumption linkages analysis was empolyed, based on hypothetical extraction method. By comparing the direct water consumption with vertical integrated water consumption based on the input-output data of water utilization in 2007 in China, direct water consumption of each sector was not equal to water required to meet final demand of itself. In view of the economy, the total of direct water consumption of all sectors was equivalent to the total of water required to meet final demand of themselves. Water resource transferred among productive sectors. In the supply-chain, upstream sectors such as agriculture and basic industry, met their final demand by the internal exchange of production, and transferred a large number of water resource to their downstream sectors by intermediate input. On the contrary, downstream sectors such as light industry and high-technology industry, transferred a great quantity of water resource from their upstream sectors, because their direct water consumption was unable to meet the final demand. In this way, water resource was transferred from upstream to downstream step by step to maintain the production and exchange in economy. If the final demand did not have a change, industrial restructuring was just to divert the sector with a high-water-consumption from a place to the other. Therefore, the total water consumption of the economy did not have a change. This paper revealed the regular of industrial water consumption so as to provide a fresh perspective of structure adjustment and more scientific basis of policy-making.%选取2007年相关数据进行整理分析,应用基于假设抽取法的水资源消耗产业关联度计量模型,比较各行业水资源的直接消耗和纵向集成消耗,定量测算出我国行业间水资源的流动转移情况.通过分析得到:不同

  16. Resource linkages and sustainable development

    Science.gov (United States)

    Anouti, Yahya

    prices we estimate that the demand for gasoline could be reduced by 7.8 percent and that of diesel by 5.9 percent. This would lead to not only reduction in the associated negative externalities, but also to the generation of more than USD400 billion in revenues for governments. However, the partial equilibrium analysis in essay one ignores the general equilibrium effects that will be mainly driven by how the government spends the subsidy. In essay 2, we build the case for phasing out these subsidies and accompanying that by a welfare compensating cash transfer. In order to evaluate the impact of that on consumer's welfare, we develop a numerical model for Saudi Arabia in a general equilibrium setting to discuss a phase out of transport fuel subsidies that is. Results show that the Saudi government can increase its consumers' welfare up to five percentage points. In case the cash transfer is adjusted to keep consumers' utility at the pre-reform level, the required compensating transfer would leave the government with three percentage points of additional revenues. Finally, we highlight policy implications of phasing out the transport fuel subsidies. Finally, in essay 3 we turn our focus to the application of local content policies in the oil and gas sector. There is limited literature that investigates economic linkages from the extractive industries, assesses intertemporal tradeoffs, and guides the design of efficient and sustainable policies. Our contribution in this essay is three-fold. First, we present the first comprehensive analysis of economic linkages from the oil and gas sector across 48 countries. Then, we analyze the economic distortions from applying local content policies using a Hotelling type optimal control model with an international oil company maximizing its profits subject to a local content requirement. Finally, we investigate the presence of a socially optimal local content level when the social planner maximizing the net benefits from the

  17. 基于铰链四杆机构运动学的解析法及ADAMS仿真%KINEMATIC ANALYSIS OF THE PLANAR FOUR BAR LINKAGE MECHANISM BASED ON ANALYTIC METHOD AND ADAMS SIMULATION

    Institute of Scientific and Technical Information of China (English)

    何伟; 李震; 王建彬; 张建华

    2011-01-01

    At present, the main method for kinematic analysis of the Planar Four Bar Linkage Mechanism are analytic method and ADAMS simulation. Both of them can get the motion law of the machinery. On the one hand this paper uses the analytical method to deduce the motion law of the machinery, and solve it by MATLAB, then plot the motion of linkage and racker. On the other hand, uses ADAMS simulation to compare the results.%目前研究铰链四杆机构运动规律的主要方法有解析法和ADAMS仿真,这两种方法都能得到该机构的运动规律,下面将采用解析法中的复数矢量法,对曲柄角速度恒定的铰链四杆机构的运动规律进行推导,并采用MATLAB求解,绘出连杆和摇杆的运动规律图;同时通过ADAMS仿真进行对比验证。从而比较两种方法的结果.

  18. Constructing dense genetic linkage maps

    NARCIS (Netherlands)

    Jansen, J.; Jong, de A.G.; Ooijen, van J.W.

    2001-01-01

    This paper describes a novel combination of techniques for the construction of dense genetic linkage maps. The construction of such maps is hampered by the occurrence of even small proportions of typing errors. Simulated annealing is used to obtain the best map according to the optimality criterion:

  19. North-South Business Linkages

    DEFF Research Database (Denmark)

    Sørensen, Olav Jull; Kuada, John

    2006-01-01

    Based on empirical studies of linkages between TNCs and local firms in India, Malaysia, Vietnam, Ghana and South Africa, five themes are discussed and related to present theoretical perspectives. The themes are (1) Linakge Governance; (2) Globalisation and the dynamics in developing countries (the...

  20. Fracture resistance, two point bending strength and morphological characteristics of pulpless teeth restored with fiber-reinforced composite posts

    Directory of Open Access Journals (Sweden)

    Alfredo Tibúrcio Nunes Pires

    2012-09-01

    Full Text Available Introduction: Fiber-reinforced composite posts (FRC posts have been used for tooth reinforcement after endodontic treatment. The mechanical characteristics of FRC posts can influence the clinical prognostic. Objective: The aim of this study was to evaluate the flexural strength and fracture resistance of commercially available FRC posts Material and methods: Fourteen human single-rooted premolars with completely formed apices were selected and received endodontic treatment. The specimens were divided into two groups related to the post system: i Group A – cylindrical-conical fiber-reinforced post (White post DC, FGM, and ii group B – conical fiber-reinforced post (EXACTO, Angelus. The fracture resistance was evaluated and two point bending tests were carried out. The glass fiber characteristics and the tag penetration of the luting material into the radicular dentin structure were evaluated through scanning electronic microscopy in an illustrative way. One-way ANOVA and Tukey’s HSD test (α = 0.05 were applied. Results: The values obtained for fracture resistance and two point bending test were, respectively, 399.29 N and 109.5 N for group A, and 386.25 N and 119.5 N for group B. No significant differences in strength values among the groups were found. Conclusion: There were no significant statistical differences between the two post groups regarding to fracture strength and two point bending strength. It can be concluded that the posts selected for this study performed satisfactorily in terms of mechanical properties so that they can be used for tooth reinforcement after endodontic treatment.

  1. Surgical treatment of zygomatic bone fracture using two points fixation versus three point fixation-a randomised prospective clinical trial

    Directory of Open Access Journals (Sweden)

    Rana Majeed

    2012-04-01

    Full Text Available Abstract Background The zygoma plays an important role in the facial contour for both cosmetic and functional reasons; therefore zygomatic bone injuries should be properly diagnosed and adequately treated. Comparison of various surgical approaches and their complications can only be done objectively using outcome measurements which in turn require protocol management and long-term follow up. The preference for open reduction and internal fixation of zygomatic fractures at three points has continued to grow in response to observations of inadequate results from two point and one point fixation techniques. The objectives of this study were to compare the efficacy of zygomatic bone after treatment with ORIF using 2 point fixation and ORIF using 3 point fixation and compare the outcome of two procedures. Methods 100 patients were randomly divided equally into two groups. In group A, 50 patients were treated by ORIF using two point fixation by miniplates and in group B, 50 patients were treated by ORIF using three point fixation by miniplates. They were evaluated for their complications during and after surgery with their advantages and disadvantages and the difference between the two groups was observed. Results A total of 100 fractures were sustained. We found that postoperative complication like decreased malar height and vertical dystopia was more common in those patients who were treated by two point fixation than those who were treated with three point fixation. Conclusions Based on this study open reduction and internal fixation using three point fixation by miniplates is the best available method for the treatment zygomatic bone fractures.

  2. Explicit Proof of Equivalence of Two-Point Functions in the Two Formalisms of Thermal Field Theory

    Institute of Scientific and Technical Information of China (English)

    ZHOU Bang-Rong

    2002-01-01

    We give an explicit proof of equivalence of the two-point function to one-loop order in the two formalisms of thermal λ3 theory based on the expressions in the real-time formalism and indicate that the key point of completing the proof is to separate carefully the imaginary part of the zero-temperature loop integralfrom relevant expressions and this fact will certainly be very useful for examination of the equivalent problem of two formalisms of thermal field theory in other theories, including the one of the propagators for scalar bound states in an NJL model.

  3. Two-point estimate method for probabilistic optimal power flow computation including wind farms with correlated parameters

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xue; Cao, Jia; Du, Dajun [Shanghai Univ. (China). Key Lab. of Power Station Automation Technology

    2013-07-01

    This paper is concerned with the probabilistic optimal power flow (POPF) calculation including wind farms with correlated parameters which contains nodal injections. The two-point estimate method (2PEM) is employed to solve the POPF. Moreover, the correlation samples between nodal injections and line parameters are generated by Cholesky Factorization method. Simulation results show that 2PEM is feasible and effective to solve the POPF including wind farms with correlated parameters, while the 2PEM has higher computation precision and consume less CPU time than Monte Carlo Simulation.

  4. Doppler term in the galaxy two-point correlation function: wide-angle, velocity, Doppler lensing and cosmic acceleration effects

    OpenAIRE

    Raccanelli, Alvise; Bertacca, Daniele; Jeong, Donghui; Neyrinck, Mark C.; Szalay, Alexander S.

    2016-01-01

    We study the parity-odd part (that we shall call Doppler term) of the linear galaxy two-point correlation function that arises from wide-angle, velocity, Doppler lensing and cosmic acceleration effects. As it is important at low redshift and at large angular separations, the Doppler term is usually neglected in the current generation of galaxy surveys. For future wide-angle galaxy surveys such as Euclid, SPHEREx and SKA, however, we show that the Doppler term must be included. The effect of t...

  5. On the solution of two-point linear differential eigenvalue problems. [numerical technique with application to Orr-Sommerfeld equation

    Science.gov (United States)

    Antar, B. N.

    1976-01-01

    A numerical technique is presented for locating the eigenvalues of two point linear differential eigenvalue problems. The technique is designed to search for complex eigenvalues belonging to complex operators. With this method, any domain of the complex eigenvalue plane could be scanned and the eigenvalues within it, if any, located. For an application of the method, the eigenvalues of the Orr-Sommerfeld equation of the plane Poiseuille flow are determined within a specified portion of the c-plane. The eigenvalues for alpha = 1 and R = 10,000 are tabulated and compared for accuracy with existing solutions.

  6. ON THE EXISTENCE OF SOLUTION OF A NONLINEAR TWO-POINT BOUNDARY VALUE PROBLEM ARISING FROM A LIQUID METAL FLOW

    Institute of Scientific and Technical Information of China (English)

    Cheng Xiaoliang; Ying Weiting

    2005-01-01

    In this paper, we discuss the existence of solution of a nonlinear two-point boundary value problem with a positive parameter Q arising in the study of surfacetension-induced flows of a liquid metal or semiconductor. By applying the Schauder's fixed-point theorem, we prove that the problem admits a solution for 0 ≤ Q ≤ 14.306.It improves the result of 0 ≤ Q < 1 in [2] and 0 ≤ Q ≤ 13.213 in [3].

  7. Exploitation of linkage learning in evolutionary algorithms

    CERN Document Server

    Chen, Ying-ping

    2010-01-01

    The exploitation of linkage learning is enhancing the performance of evolutionary algorithms. This monograph examines recent progress in linkage learning, with a series of focused technical chapters that cover developments and trends in the field.

  8. Joint positioning sense, perceived force level and two-point discrimination tests of young and active elderly adults

    Directory of Open Access Journals (Sweden)

    Priscila G. Franco

    2015-08-01

    Full Text Available Background: Changes in the proprioceptive system are associated with aging. Proprioception is important to maintaining and/or recovering balance and to reducing the risk of falls.Objective:To compare the performance of young and active elderly adults in three proprioceptive tests.Method:Twenty-one active elderly participants (66.9±5.5 years and 21 healthy young participants (24.6±3.9 years were evaluated in the following tests: perception of position of the ankle and hip joints, perceived force level of the ankle joint, and two-point discrimination of the sole of the foot.Results:No differences (p>0.05 were found between groups for the joint position and perceived force level. On the other hand, the elderly participants showed lower sensitivity in the two-point discrimination (higher threshold when compared to the young participants (p < 0.01.Conclusion:Except for the cutaneous plantar sensitivity, the active elderly participants had maintained proprioception. Their physical activity status may explain similarities between groups for the joint position sense and perceived force level, however it may not be sufficient to prevent sensory degeneration with aging.

  9. Exact two-point resistance, and the simple random walk on the complete graph minus N edges

    Energy Technology Data Exchange (ETDEWEB)

    Chair, Noureddine, E-mail: n.chair@ju.edu.jo

    2012-12-15

    An analytical approach is developed to obtain the exact expressions for the two-point resistance and the total effective resistance of the complete graph minus N edges of the opposite vertices. These expressions are written in terms of certain numbers that we introduce, which we call the Bejaia and the Pisa numbers; these numbers are the natural generalizations of the bisected Fibonacci and Lucas numbers. The correspondence between random walks and the resistor networks is then used to obtain the exact expressions for the first passage and mean first passage times on this graph. - Highlights: Black-Right-Pointing-Pointer We obtain exact formulas for the two-point resistance of the complete graph minus N edges. Black-Right-Pointing-Pointer We obtain also the total effective resistance of this graph. Black-Right-Pointing-Pointer We modified Schwatt's formula on trigonometrical power sum to suit our computations. Black-Right-Pointing-Pointer We introduced the generalized bisected Fibonacci and Lucas numbers: the Bejaia and the Pisa numbers. Black-Right-Pointing-Pointer The first passage and mean first passage times of the random walks have exact expressions.

  10. The covariant and infrared-free graviton two-point function in de Sitter space-time

    CERN Document Server

    Pejhan, Hamed

    2015-01-01

    In this paper, the two-point function of linearized gravitons on de Sitter (dS) space is presented. Technically, respecting the dS ambient space notation, the field equation is given by the coordinate-independent Casimir operators of the de Sitter group. Analogous to the quantization of the electromagnetic field in Minkowski space, the field equation admits gauge solutions. The notation allows to exhibit the formalism of Gupta-Bleuler triplets for the present field in exactly the same manner as it occurs for the electromagnetic field. In this regard, centering on the traceless part, the field solution is written as a product of a generalized polarization tensor and a minimally coupled massless scalar field. Then, admitting a de Sitter-invariant vacuum through the so-called "Krein Space Quantization", the de Sitter fully covariant two-point function is calculated. This function is interestingly free of pathological large distance behavior (infrared divergence). Moreover, the pure-trace part (conformal sector) ...

  11. Gauge-invariant two-point correlator of energy density in deconfining SU(2) Yang-Mills thermodynamics

    CERN Document Server

    Keller, Jochen

    2008-01-01

    The thesis is considering aspects of SU(2) Yang-Mills thermodynamics in its deconfining high-temperature phase. We calculate the two-point correlation function of the energy density of the photon in a thermalized gas, at first in the conventional U(1) gauge theory, followed by a calculation, where the photon is identified with the massless gauge mode in deconfining SU(2) Yang-Mills thermodynamics. Apart from the fact, that this calculation is interesting from a technical point of view, we can consider several aspects of phenomenological relevance. Since we interpret the two-point correlator of energy density as a measure for the energy transfer, and thus for the electromagnetic interaction of microscopic objects, such as atoms immersed into a photon gas, we are able to give an explanation for the unexpected stability of cold, innergalactic clouds consisting of atomic hydrogen. Subsequently, we evaluate the spatial string tension in deconfining SU(2) Yang-Mills thermodynamics, which can be regarded as measure ...

  12. An international collaborative family-based whole genome quantitative trait linkage scan for myopic refractive error

    DEFF Research Database (Denmark)

    Abbott, Diana; Li, Yi-Ju; Guggenheim, Jeremy A;

    2012-01-01

    To investigate quantitative trait loci linked to refractive error, we performed a genome-wide quantitative trait linkage analysis using single nucleotide polymorphism markers and family data from five international sites.......To investigate quantitative trait loci linked to refractive error, we performed a genome-wide quantitative trait linkage analysis using single nucleotide polymorphism markers and family data from five international sites....

  13. RAPD linkage mapping in a longleaf pine x slash pine F1 family.

    Science.gov (United States)

    Kubisiak, T L; Nelson, C D; Nance, W L; Stine, M

    1995-06-01

    Random amplified polymorphic DNAs (RAPDs) were used to construct linkage maps of the parent of a longleaf pine (Pinus palustris Mill.) slash pine (Pinus elliottii Englm.) F1 family. A total of 247 segregating loci [233 (1∶1), 14 (3∶1)] and 87 polymorphic (between parents), but non-segregating, loci were identified. The 233 loci segregating 1∶1 (testcross configuration) were used to construct parent-specific linkage maps, 132 for the longleaf-pine parent and 101 for the slash-pine parent. The resulting linkage maps consisted of 122 marker loci in 18 groups (three or more loci) and three pairs (1367.5 cM) for longleaf pine, and 91 marker loci in 13 groups and six pairs for slash pine (952.9 cM). Genome size estimates based on two-point linkage data ranged from 2348 to 2392 cM for longleaf pine, and from 2292 to 2372 cM for slash pine. Linkage of 3∶1 loci to testcross loci in each of the parental maps was used to infer further linkages within maps, as well as potentially homologous counterparts between maps. Three of the longleaf-pine linkage groups appear to be potentially homologous counterparts to four different slash-pine linkage groups. The number of heterozygous loci (previously testcross in parents) per F1 individual, ranged from 96 to 130. With the 87 polymorphic, but non-segregating, loci that should also be heterozygous in the F1 progeny, a maximum of 183-217 heterozygous loci could be available for mapping early height growth (EHG) loci and for applying genomic selection in backcross populations.

  14. Use of land facets to design linkages for climate change.

    Science.gov (United States)

    Brost, Brian M; Beier, Paul

    2012-01-01

    Least-cost modeling for focal species is the most widely used method for designing conservation corridors and linkages. However, these linkages have been based on current species' distributions and land cover, both of which will change with large-scale climate change. One method to develop corridors that facilitate species' shifting distributions is to incorporate climate models into their design. But this approach is enormously complex and prone to error propagation. It also produces outputs at a grain size (km2) coarser than the grain at which conservation decisions are made. One way to avoid these problems is to design linkages for the continuity and interspersion of land facets, or recurring landscape units of relatively uniform topography and soils. This coarse-filter approach aims to conserve the arenas of biological activity rather than the temporary occupants of those arenas. In this paper, we demonstrate how land facets can be defined in a rule-based and adaptable way, and how they can be used for linkage design in the face of climate change. We used fuzzy c-means cluster analysis to define land facets with respect to four topographic variables (elevation, slope angle, solar insolation, and topographic position), and least-cost analysis to design linkages that include one corridor per land facet. To demonstrate the flexibility of our procedures, we designed linkages using land facets in three topographically diverse landscapes in Arizona, USA. Our procedures can use other variables, including soil variables, to define land facets. We advocate using land facets to complement, rather than replace, existing focal species approaches to linkage design. This approach can be used even in regions lacking land cover maps and is not affected by the bias and patchiness common in species occurrence data.

  15. New algorithms for solving third- and fifth-order two point boundary value problems based on nonsymmetric generalized Jacobi Petrov-Galerkin method.

    Science.gov (United States)

    Doha, E H; Abd-Elhameed, W M; Youssri, Y H

    2015-09-01

    Two families of certain nonsymmetric generalized Jacobi polynomials with negative integer indexes are employed for solving third- and fifth-order two point boundary value problems governed by homogeneous and nonhomogeneous boundary conditions using a dual Petrov-Galerkin method. The idea behind our method is to use trial functions satisfying the underlying boundary conditions of the differential equations and the test functions satisfying the dual boundary conditions. The resulting linear systems from the application of our method are specially structured and they can be efficiently inverted. The use of generalized Jacobi polynomials simplify the theoretical and numerical analysis of the method and also leads to accurate and efficient numerical algorithms. The presented numerical results indicate that the proposed numerical algorithms are reliable and very efficient.

  16. Genotyping by Sequencing for SNP-Based Linkage Map Construction and QTL Analysis of Chilling Requirement and Bloom Date in Peach [Prunus persica (L. Batsch].

    Directory of Open Access Journals (Sweden)

    Douglas Gary Bielenberg

    Full Text Available Low-cost, high throughput genotyping methods are crucial to marker discovery and marker-assisted breeding efforts, but have not been available for many 'specialty crops' such as fruit and nut trees. Here we apply the Genotyping-By-Sequencing (GBS method developed for cereals to the discovery of single nucleotide polymorphisms (SNPs in a peach F2 mapping population. Peach is a genetic and genomic model within the Rosaceae and will provide a template for the use of this method with other members of this family. Our F2 mapping population of 57 genotypes segregates for bloom time (BD and chilling requirement (CR and we have extensively phenotyped this population. The population derives from a selfed F1 progeny of a cross between 'Hakuho' (high CR and 'UFGold' (low CR. We were able to successfully employ GBS and the TASSEL GBS pipeline without modification of the original methodology using the ApeKI restriction enzyme and multiplexing at an equivalent of 96 samples per Illumina HiSeq 2000 lane. We obtained hundreds of SNP markers which were then used to construct a genetic linkage map and identify quantitative trait loci (QTL for BD and CR.

  17. QTL Analysis of Spike Morphological Traits and Plant Height in Winter Wheat (Triticum aestivum L. Using a High-Density SNP and SSR-Based Linkage Map

    Directory of Open Access Journals (Sweden)

    Huijie Zhai

    2016-11-01

    Full Text Available Wheat yield can be enhanced by modifying the spike morphology and the plant height. In this study, a population of 191 F9 recombinant inbred lines (RILs was developed from a cross between two winter cultivars Yumai 8679 and Jing 411. A dense genetic linkage map with 10,816 markers was constructed by incorporating single nucleotide polymorphism (SNP and simple sequence repeat (SSR marker information. Five spike morphological traits and plant height were evaluated under nine environments for the RILs and parental lines, and the number of detected environmentally stable QTLs were 18 and 3, respectively. The 1RS/1BL (rye translocation increased both spike length and spikelet number with constant spikelet compactness. The QPht.cau-2D.1 was identical to gene Rht8, which decreased spike length without modifying spikelet number. Notably, four novel QTLs locating on chromosomes 1AS (QSc.cau-1A.1, 2DS (QSc.cau-2D.1 and 7BS (QSl.cau-7B.1 and QSl.cau-7B.2 were firstly identified in this study, which provide further insights into the genetic factors that shaped the spike morphology in wheat. Moreover, SNP markers tightly linked to previously reported QTLs will eventually facilitate future studies including their positional cloning or marker-assisted selection.

  18. [Linkage of environmental and health data: health risk analysis of the Rio de Janeiro water supply by using geographical information systems].

    Science.gov (United States)

    Barcellos, C; Coutinho, K; Pina, M F; Magalhães, M M; Paola, J C; Santos, S M

    1998-01-01

    Exposure assessment of population groups is based on linkage of environmental and health data. This relationship can be hard to establish due to spatial and temporal lags in data sets. Environmental data generally refer to scattered sampling points, while epidemiological data integrate periods of time within administrative territories. GIS can be used as a basis for organizing health-related and environmental data sets. We examined potential health risk in the Rio de Janeiro city water supply based on the overlay of information layers containing data on the presence and quality of water supply services. We used census tracts as the primary georeferenced data, since they contain information on how households are supplied, water supply pipes, sources, and reservoirs, and water quality according to the monitoring program. Population groups exposed to risks were located and quantified using spatial operations among these layers and adopting different risk criteria. The main problems related to water supply are located on the northern slope of the Tijuca Mountain Range (involving the absence or poor quality of water) and in the western area of the city of Rio, where the population relies on alternative water supply sources. The different origins, objectives, and structures of data have to be analyzed critically, and GIS can be used as a data validation tool as well as an instrument for detailed identification of inconsistencies.

  19. New Approach for Solving a Class of Doubly Singular Two-Point Boundary Value Problems Using Adomian Decomposition Method

    Directory of Open Access Journals (Sweden)

    Randhir Singh

    2012-01-01

    Full Text Available We propose two new modified recursive schemes for solving a class of doubly singular two-point boundary value problems. These schemes are based on Adomian decomposition method (ADM and new proposed integral operators. We use all the boundary conditions to derive an integral equation before establishing the recursive schemes for the solution components. Thus we develop recursive schemes without any undetermined coefficients while computing successive solution components, whereas several previous recursive schemes have done so. This modification also avoids solving a sequence of nonlinear algebraic or transcendental equations for the undetermined coefficients with multiple roots, which is required to complete calculation of the solution by several earlier modified recursion schemes using the ADM. The approximate solution is computed in the form of series with easily calculable components. The effectiveness of the proposed approach is tested by considering four examples and results are compared with previous known results.

  20. The influence of age on pressure perception of static and moving two-point discrimination in normal subjects.

    Science.gov (United States)

    Kaneko, Atsushi; Asai, Noriyoshi; Kanda, Tadashi

    2005-01-01

    The purpose of the present study was to determine the effect of age on digital pressure perception as measured by two-point discrimination (2PD) testing. The subjects were 177 normal volunteers ranging in age from 20 to 79 years. Perceptible pressure of static and moving 2PD was measured on the index finger and little finger, using the Pressure-specifying Sensory Device. The threshold of pressure perception increased significantly with advancing age in both static and moving 2PD tests. There was a marked increase in subjects older than 60 years. Pressure perception was significantly higher for static 2PD than for moving 2PD in subjects 70-79 years of age. The threshold of pressure perception for static and moving 2PD gradually increased with advancing age, and was markedly elevated in subjects older than 60 years.

  1. Transforming activity of the c-Ha-ras oncogene having two point mutations in codons 12 and 61.

    Science.gov (United States)

    Sekiya, T; Prassolov, V S; Fushimi, M; Nishimura, S

    1985-09-01

    A recombinant plasmid carrying the human c-Ha-ras gene with two point mutations in codons 12 and 61 was constructed and its transforming activity on mouse NIH 3T3 cells was compared with those of genes with a single mutation in either codon 12 or 61. Quantitative analyses revealed that the gene with two mutations had essentially the same transforming activity as the genes with single mutations. These results indicate that a single mutation of the c-Ha-ras gene in either codon 12 or 61 is sufficient to activate the gene and that neither of the two mutation sites involved in activation of the gene needs to be intact for transforming activity.

  2. Synthesis of Intermittent-Motion Linkages with Slight Difference in Length Between Links

    Institute of Scientific and Technical Information of China (English)

    CHEN Xin-bo; YU Zhen

    2006-01-01

    The design of intermittent-motion linkages using traditional methods iS usually complicated.In this paper,(1)a new method for realizing intermittent motion,using linkages with a slight difference in length between links,is studied;(2)some new types of intermittent-motion linkages and their software for visual analysis and design are developed;and(3)influences of some design parameters on intermittent.motion characteristics are clarifled.Results confirmed that the theory and the software are useful,making the synthesis of intermittent-motion linkages clear and easy.

  3. 插床六杆机构运动学和静力学分析%Kinematics and statics analysis for six bar linkage in slotting machine

    Institute of Scientific and Technical Information of China (English)

    叶素娣; 徐敬华

    2015-01-01

    In the slotting machine the slotting tool moved up and down which is directly related to the cutting efficiency for work-piece. The vector model of slotting machine six bar linkage is established,matlab/simulink integral module method is used to establish the simulation diagram,reasonable initial conditions are set up to visualize displacement,velocity and acceleration curve. The friction force is always tangent to the friction circle,and its moment to hinge center is contrary to the relative angular velocity,the static equi-librium equations are solved of each components. Ultimately the active parts should be applied to the driving moment on the law of the change over time.%插床中插刀的上下往复运动直接关系到工件切削的效率。建立插床六杆机构的矢量模型,用Matlab/Simulink中的积分模块建立仿真框图,设置合理的初始条件,将插刀的位移、速度和加速度曲线规律可视化。对机构作计及摩擦力的静力分析,通过摩擦圆和相对角速度判断运动副所受摩擦总反力的方向,依次求解各个构件的静力平衡方程式,得出主动件上所能克服的等效阻力矩,并用Matlab软件得出等效阻力矩随时间变化的规律。

  4. Changes in satellite-derived spring vegetation green-up date and its linkage to climate in China from 1982 to 2010: a multimethod analysis.

    Science.gov (United States)

    Cong, Nan; Wang, Tao; Nan, Huijuan; Ma, Yuecun; Wang, Xuhui; Myneni, Ranga B; Piao, Shilong

    2013-03-01

    The change in spring phenology is recognized to exert a major influence on carbon balance dynamics in temperate ecosystems. Over the past several decades, several studies focused on shifts in spring phenology; however, large uncertainties still exist, and one understudied source could be the method implemented in retrieving satellite-derived spring phenology. To account for this potential uncertainty, we conducted a multimethod investigation to quantify changes in vegetation green-up date from 1982 to 2010 over temperate China, and to characterize climatic controls on spring phenology. Over temperate China, the five methods estimated that the vegetation green-up onset date advanced, on average, at a rate of 1.3 ± 0.6 days per decade (ranging from 0.4 to 1.9 days per decade) over the last 29 years. Moreover, the sign of the trends in vegetation green-up date derived from the five methods were broadly consistent spatially and for different vegetation types, but with large differences in the magnitude of the trend. The large intermethod variance was notably observed in arid and semiarid vegetation types. Our results also showed that change in vegetation green-up date is more closely correlated with temperature than with precipitation. However, the temperature sensitivity of spring vegetation green-up date became higher as precipitation increased, implying that precipitation is an important regulator of the response of vegetation spring phenology to change in temperature. This intricate linkage between spring phenology and precipitation must be taken into account in current phenological models which are mostly driven by temperature. © 2012 Blackwell Publishing Ltd.

  5. 一种磁链轨迹跟踪的PWM方法及其特性分析%PWM method of flux linkage trajectory tracking and analysis of its characteristics

    Institute of Scientific and Technical Information of China (English)

    吴德会; 柳振凉; 夏晓昊; 张忠远

    2013-01-01

    A frequency control underlying implementation of induction motor was suggested based on flux linkage trajectory tracking.By changing the operate mode of inverter,the actual flux linkage was produced to tracking the reference flux linkage circle,and the corresponding pulse width modulation (PWM) waveform was also generated.The basic theoretical computing equation was deduced,a specific control strategy was suggested,and the characteristics of the PWM waveform generated was analyzed.Simulations and experimental results show that the modulation index is up to 1,and the voltage utilization is same as SVPWM,while 15.47% higher than SPWM.Furthermore,the existence of error upper limit was verified,which provides a quantitative basis for further analysis of the accuracy.%提出一种基于磁链轨迹跟踪策略的电动机变频调速方法.该方法不通过空间电压矢量的合成,而直接通过实际磁链矢量来跟踪基准磁链圆轨迹,再由跟踪的结果决定逆变器的开关状态模式,从而实现对脉冲宽度调制(PWM)波的调制输出.对该方法的基本原理进行推导,给出具体的控制策略,并对其产生的PWM波形特性进行系统分析.仿真及物理实验结果表明,该方法幅度调制比可达到1,电压利用率与空间矢量脉宽调制(SVPWM)方法相同,比正弦波脉宽调制(SPWM)提高15.47%;同时验证了其跟踪误差上限的存在性,为进一步分析该方法精确度提供了定量依据.该方法为变频调速的底层实现提供了另一种可行的途径.

  6. International Environmental Problems, Issue Linkage and the European Union

    NARCIS (Netherlands)

    Kroeze-Gil, J.

    2003-01-01

    This thesis explores the circumstances under which issue linkage can be applied to achieve cooperation on international environmental problems in general and on environmental problems in the European Union in particular. A major topic in this thesis is the development and analysis of cooperative and

  7. Pedigree with frontotemporal lobar degeneration – motor neuron disease and Tar DNA binding protein-43 positive neuropathology: genetic linkage to chromosome 9

    Directory of Open Access Journals (Sweden)

    Loy Clement T

    2008-08-01

    Full Text Available Abstract Background Frontotemporal lobar degeneration (FTLD represents a clinically, pathologically and genetically heterogenous neurodegenerative disorder, often complicated by neurological signs such as motor neuron-related limb weakness, spasticity and paralysis, parkinsonism and gait disturbances. Linkage to chromosome 9p had been reported for pedigrees with the neurodegenerative disorder, frontotemporal lobar degeneration (FTLD and motor neuron disease (MND. The objective in this study is to identify the genetic locus in a multi-generational Australian family with FTLD-MND. Methods Clinical review and standard neuropathological analysis of brain sections from affected pedigree members. Genome-wide scan using microsatellite markers and single nucleotide polymorphism fine mapping. Examination of candidate genes by direct DNA sequencing. Results Neuropathological examination revealed cytoplasmic deposition of the TDP-43 protein in three affected individuals. Moreover, we identify a family member with clinical Alzheimer's disease, and FTLD-Ubiquitin neuropathology. Genetic linkage and haplotype analyses, defined a critical region between markers D9S169 and D9S1845 on chromosome 9p21. Screening of all candidate genes within this region did not reveal any novel genetic alterations that co-segregate with disease haplotype, suggesting that one individual carrying a meiotic recombination may represent a phenocopy. Re-analysis of linkage data using the new affection status revealed a maximal two-point LOD score of 3.24 and a multipoint LOD score of 3.41 at marker D9S1817. This provides the highest reported LOD scores from a single FTLD-MND pedigree. Conclusion Our reported increase in the minimal disease region should inform other researchers that the chromosome 9 locus may be more telomeric than predicted by published recombination boundaries. Moreover, the existence of a family member with clinical Alzheimer's disease, and who shares the disease

  8. Human bZIP transcription factor gene NRL: structure, genomic sequence, and fine linkage mapping at 14q11.2 and negative mutation analysis in patients with retinal degeneration.

    Science.gov (United States)

    Farjo, Q; Jackson, A; Pieke-Dahl, S; Scott, K; Kimberling, W J; Sieving, P A; Richards, J E; Swaroop, A

    1997-10-15

    The NRL gene encodes an evolutionarily conserved basic motif-leucine zipper transcription factor that is implicated in regulating the expression of the photoreceptor-specific gene rhodopsin. NRL is expressed in postmitotic neuronal cells and in lens during embryonic development, but exhibits a retina-specific pattern of expression in the adult. To understand regulation of NRL expression and to investigate its possible involvement in retinopathies, we have determined the complete sequence of the human NRL gene, identified a polymorphic (CA)n repeat (identical to D14S64) within the NRL-containing cosmid, and refined its location by linkage analysis. Since a locus for autosomal recessive retinitis pigmentosa (arRP) has been linked to markers at 14q11 and since mutations in rhodopsin can lead to RP, we sequenced genomic PCR products of the NRL gene and of the rhodopsin-Nrl response element from a panel of patients representing independent families with inherited retinal degeneration. The analysis did not reveal any causative mutations in this group of patients. These investigations provide the basis for delineating the DNA sequence elements that regulate NRL expression in distinct neuronal cell types and should assist in the analysis of NRL as a candidate gene for inherited diseases/syndromes affecting visual function. Copyright 1997 Academic Press.

  9. Assessment of styling performance in hair gels and hair sprays by means of a new two-point stiffness test.

    Science.gov (United States)

    Hoessel, Peter; Riemann, Solveig; Knebl, Robert; Schroeder, Jens; Schuh, Gerd; Castillo, Catalina

    2010-01-01

    A new two-point bending stiffness method on flat hair strands was developed and validated after application of hair styling gels and hair styling sprays. A special mold was used to align single hair fibers after applying the formulations to the hair. The styling gels used contain different commercially available thickeners and styling polymers, e.g., carbomer, acrylates/beheneth-25 methacrylate copolymer, Polyquaternium-86, PVP, VP/VA copolymers, and VP/methacrylamide/vinylimidazole copolymer. Evaluation of hair sprays was performed after spray application on flat hair strands. Commercially available hair styling resins were used, e.g. acrylates/t-butylacrylamide copolymer, octylacrylamide/acrylates/butylaminoethyl methacrylate copolymer, and VP/VA copolymer (30:70). The new stiffness test method provided the best correlation with practically relevant sensory assessments on hair strands and a panel test in which styling gels were evaluated. However, we did not observe a correlation between the new stiffness method on flat hair strands and practical assessments in hair spray application. We postulate that different polymer/hair composites are responsible for these discrepancies. Hairs on model heads for half-side testing are spot-welded after spray application, while hairs are seam-welded in the stiffness test after alignment of single hair fibers. This alignment is necessary to achieve reproducible results.

  10. Existence of solutions of nonlinear two-point boundary value problems for 4nth-order nonlinear differential equation

    Institute of Scientific and Technical Information of China (English)

    高永馨

    2002-01-01

    Studies the existence of solutions of nonlinear two point boundary value problems for nonlinear 4n-th-order differential equation y(4n)= f( t,y,y' ,y",… ,y(4n-1) ) (a) with the boundary conditions g2i(y(2i) (a) ,y(2i+1) (a)) = 0,h2i(y(2i) (c) ,y(2i+1) (c)) = 0, (I= 0,1,…,2n - 1 ) (b) where the functions f, gi and hi are continuous with certain monotone properties. For the boundary value problems of nonlinear nth order differential equation y(n) = f(t,y,y',y",… ,y(n-1)) many results have been given at the present time. But the existence of solutions of boundary value problem (a), (b) studied in this paper has not been covered by the above researches. Moreover, the corollary of the important theorem in this paper, I.e. Existence of solutions of the boundary value problem. Y(4n) = f(t,y,y',y",… ,y(4n-1) ) a2iy(2i) (at) + a2i+1y(2i+1) (a) = b2i ,c2iy(2O ( c ) + c2i+1y(2i+1) ( c ) = d2i, ( I = 0,1 ,…2n - 1) has not been dealt with in previous works.

  11. Differences in two-point discrimination and sensory threshold in the blind between braille and text reading: a pilot study.

    Science.gov (United States)

    Noh, Ji-Woong; Park, Byoung-Sun; Kim, Mee-Young; Lee, Lim-Kyu; Yang, Seung-Min; Lee, Won-Deok; Shin, Yong-Sub; Kang, Ji-Hye; Kim, Ju-Hyun; Lee, Jeong-Uk; Kwak, Taek-Yong; Lee, Tae-Hyun; Kim, Ju-Young; Kim, Junghwan

    2015-06-01

    [Purpose] This study investigated two-point discrimination (TPD) and the electrical sensory threshold of the blind to define the effect of using Braille on the tactile and electrical senses. [Subjects and Methods] Twenty-eight blind participants were divided equally into a text-reading and a Braille-reading group. We measured tactile sensory and electrical thresholds using the TPD method and a transcutaneous electrical nerve stimulator. [Results] The left palm TPD values were significantly different between the groups. The values of the electrical sensory threshold in the left hand, the electrical pain threshold in the left hand, and the electrical pain threshold in the right hand were significantly lower in the Braille group than in the text group. [Conclusion] These findings make it difficult to explain the difference in tactility between groups, excluding both palms. However, our data show that using Braille can enhance development of the sensory median nerve in the blind, particularly in terms of the electrical sensory and pain thresholds.

  12. The redshift-space two-point correlation functions of galaxies and groups in the Nearby Optical Galaxy sample

    CERN Document Server

    Giuricin, G; Girardi, M; Mezzetti, M; Marinoni, C; Giuricin, Giuliano; Samurovic, Srdjan; Girardi, Marisa; Mezzetti, Marino; Marinoni, Christian

    2001-01-01

    We use the two-point correlation function in redshift space, $\\xi(s)$, to study the clustering of the galaxies and groups of the Nearby Optical Galaxy (NOG) sample, which is a nearly all-sky, complete, magnitude-limited sample of $\\sim$7000 bright and nearby optical galaxies. The correlation function of galaxies is well described by a power law, $\\xi(s)=(s/s_0)^{-\\gamma}$, with slope $\\gamma\\sim1.5$ and $s_0\\sim6.4 h^{-1}$Mpc (on scales $2.7 - 12 h^{-1}$Mpc), in agreement with previous results of several redshift surveys of optical galaxies. We confirm the existence of morphological segregation between early- and late-type galaxies and, in particular, we find a gradual decreasing of the strength of clustering from the S0 galaxies to the late-type spirals, on intermediate scales. Furthermore, luminous galaxies turn out to be more clustered than dim galaxies. The luminosity segregation, which is significant for both early- and late-type objects, starts to become appreciable only for galaxies brighter than $M_B\\...

  13. The Solution of Two-Point Boundary Value Problem of a Class of Duffing-Type Systems with Non-C1 Perturbation Term

    Directory of Open Access Journals (Sweden)

    Jiang Zhengxian

    2009-01-01

    Full Text Available This paper deals with a two-point boundary value problem of a class of Duffing-type systems with non-C1 perturbation term. Several existence and uniqueness theorems were presented.

  14. Validation of an instrument to measure inter-organisational linkages in general practice

    Directory of Open Access Journals (Sweden)

    Cheryl Amoroso

    2007-11-01

    Full Text Available Purpose: Linkages between general medical practices and external services are important for high quality chronic disease care. The purpose of this research is to describe the development, evaluation and use of a brief tool that measures the comprehensiveness and quality of a general practice’s linkages with external providers for the management of patients with chronic disease. In this study, clinical linkages are defined as the communication, support, and referral arrangements between services for the care and assistance of patients with chronic disease. Methods: An interview to measure surgery-level (rather than individual clinician-level clinical linkages was developed, piloted, reviewed, and evaluated with 97 Australian general practices. Two validated survey instruments were posted to patients, and a survey of locally available services was developed and posted to participating Divisions of General Practice (support organisations. Hypotheses regarding internal validity, association with local services, and patient satisfaction were tested using factor analysis, logistic regression and multilevel regression models. Results: The resulting General Practice Clinical Linkages Interview (GP-CLI is a nine-item tool with three underlying factors: referral and advice linkages, shared care and care planning linkages, and community access and awareness linkages. Local availability of chronic disease services has no affect on the comprehensiveness of services with which practices link, however comprehensiveness of clinical linkages has an association with patient assessment of access, receptionist services, and of continuity of care in their general practice. Conclusions: The GP-CLI may be useful to researchers examining comparable health care systems for measuring the comprehensiveness and quality of linkages at a general practice-level with related services, possessing both internal and external validity. The tool can be used with large samples

  15. Robustness of linkage strategy that leads to large-scale cooperation.

    Science.gov (United States)

    Inaba, Misato; Takahashi, Nobuyuki; Ohtsuki, Hisashi

    2016-11-21

    One of the most well-known models to characterize cooperation among unrelated individuals is Social dilemma (SD). However there is no consensus about how to solve the SD by itself. Since SDs are often embedded in other social interactions, including indirect reciprocity games (IR), human can coordinate their behaviors across multiple games. Such coordination is called 'linkage'. Recently linkage has been considered as a promising solution to resolve SDs, since excluding SD defectors (i.e. those who defected in SD) from indirectly reciprocal relationships functions as a costless sanction. A previous study performed mathematical modeling and revealed that a linkage strategy, which cooperates in SD and engages in the Standing strategy in IR based on the recipients' behaviors in both SD and IR, was an ESS against a non-linkage strategy which defects in SD and engages in the Standing strategy in IR based on recipients' behaviors only in IR (Panchanathan and Boyd, 2004). In order to investigate the robustness of the linkage strategy, we devised a non-linkage strategy, which cooperates in SD but does not link two games. First, we conducted a mathematical analysis and demonstrated that the linkage strategy was not an ESS against cooperating non-linkage strategy. Second, we conducted a series of agent-based computer simulations to examine how the strategies perform in situations in which various types of errors can occur. Our results showed that the linkage strategy was an ESS only when there are implementation errors in SD. However, the equilibrium of the linkage strategy was unstable when there are perception errors. Since we know that humans are not free from perception errors in their social life, future studies will need to show how perception errors can be overcome in order to provide support for the conclusion that linkage is a plausible solution to SDs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Linkages between NAMA - LEDS - MRV

    DEFF Research Database (Denmark)

    Agyemang-Bonsu, William; Benioff, Ron; Cox, Sadie

    Low Emission Development Strategies (LEDS), Nationally Appropriate Mitigation Actions (NAMAs) and Monitoring, Reporting and Verification (MRV) are three of the key conceptual components emerging as part of the global architecture for a new climate agreement by 2015. The three components are devel......Low Emission Development Strategies (LEDS), Nationally Appropriate Mitigation Actions (NAMAs) and Monitoring, Reporting and Verification (MRV) are three of the key conceptual components emerging as part of the global architecture for a new climate agreement by 2015. The three components...... how the three components are conceptually interlinked. Identifying the linkages can inform the work on each component and strengthen coordination of work in the context of the three big partnerships; the International Partnership on Mitigation and MRV, the LEDS Global Partnership and the NAMA...

  17. Investigation of a 2D two-point maximum entropy regularization method for signal-to-noise ratio enhancement: application to CT polymer gel dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Jirasek, A [Department of Physics and Astronomy, University of Victoria, Victoria BC V8W 3P6 (Canada); Matthews, Q [Department of Physics and Astronomy, University of Victoria, Victoria BC V8W 3P6 (Canada); Hilts, M [Medical Physics, BC Cancer Agency-Vancouver Island Centre, Victoria BC V8R 6V5 (Canada); Schulze, G [Michael Smith Laboratories, University of British Columbia, Vancouver BC V6T 1Z4 (Canada); Blades, M W [Department of Chemistry, University of British Columbia, Vancouver BC V6T 1Z1 (Canada); Turner, R F B [Michael Smith Laboratories, University of British Columbia, Vancouver BC V6T 1Z4 (Canada); Department of Chemistry, University of British Columbia, Vancouver BC V6T 1Z1 (Canada); Department of Electrical and Computer Engineering, University of British Columbia, Vancouver BC V6T 1Z4 (Canada)

    2006-05-21

    This study presents a new method of image signal-to-noise ratio (SNR) enhancement by utilizing a newly developed 2D two-point maximum entropy regularization method (TPMEM). When utilized as an image filter, it is shown that 2D TPMEM offers unsurpassed flexibility in its ability to balance the complementary requirements of image smoothness and fidelity. The technique is evaluated for use in the enhancement of x-ray computed tomography (CT) images of irradiated polymer gels used in radiation dosimetry. We utilize a range of statistical parameters (e.g. root-mean square error, correlation coefficient, error histograms, Fourier data) to characterize the performance of TPMEM applied to a series of synthetic images of varying initial SNR. These images are designed to mimic a range of dose intensity patterns that would occur in x-ray CT polymer gel radiation dosimetry. Analysis is extended to a CT image of a polymer gel dosimeter irradiated with a stereotactic radiation therapy dose distribution. Results indicate that TPMEM performs strikingly well on radiation dosimetry data, significantly enhancing the SNR of noise-corrupted images (SNR enhancement factors >15 are possible) while minimally distorting the original image detail (as shown by the error histograms and Fourier data). It is also noted that application of this new TPMEM filter is not restricted exclusively to x-ray CT polymer gel dosimetry image data but can in future be extended to a wide range of radiation dosimetry data.

  18. Investigation of a 2D two-point maximum entropy regularization method for signal-to-noise ratio enhancement: application to CT polymer gel dosimetry.

    Science.gov (United States)

    Jirasek, A; Matthews, Q; Hilts, M; Schulze, G; Blades, M W; Turner, R F B

    2006-05-21

    This study presents a new method of image signal-to-noise ratio (SNR) enhancement by utilizing a newly developed 2D two-point maximum entropy regularization method (TPMEM). When utilized as an image filter, it is shown that 2D TPMEM offers unsurpassed flexibility in its ability to balance the complementary requirements of image smoothness and fidelity. The technique is evaluated for use in the enhancement of x-ray computed tomography (CT) images of irradiated polymer gels used in radiation dosimetry. We utilize a range of statistical parameters (e.g. root-mean square error, correlation coefficient, error histograms, Fourier data) to characterize the performance of TPMEM applied to a series of synthetic images of varying initial SNR. These images are designed to mimic a range of dose intensity patterns that would occur in x-ray CT polymer gel radiation dosimetry. Analysis is extended to a CT image of a polymer gel dosimeter irradiated with a stereotactic radiation therapy dose distribution. Results indicate that TPMEM performs strikingly well on radiation dosimetry data, significantly enhancing the SNR of noise-corrupted images (SNR enhancement factors >15 are possible) while minimally distorting the original image detail (as shown by the error histograms and Fourier data). It is also noted that application of this new TPMEM filter is not restricted exclusively to x-ray CT polymer gel dosimetry image data but can in future be extended to a wide range of radiation dosimetry data.

  19. Van der Waals like behavior and equal area law of two point correlation function of f(R) AdS black holes

    CERN Document Server

    Mo, Jie-Xiong; Lin, Ze-Tao; Zeng, Xiao-Xiong

    2016-01-01

    To gain holographic insight into critical phenomena of $f(R)$ AdS black holes, we investigate their two point correlation function, which are dual to the geodesic length in the bulk. We solve the equation of motion constrained by the boundary condition numerically and probe both the effect of boundary region size and $f(R)$ gravity. Moreover, we introduce an analogous specific heat related to $\\delta L$. It is shown in the $T-\\delta L$ graph for the case $Qanalysis to determine the first order phase transition temperature $T_*$ and remove the unstable branch in $T-\\delta L$ curve with a bar $T=T_*$. It is shown that the values of free energy are influenced by the parameter $b$ showing the impact of $f(R)$ gravity. However, to one's surprise, the numerical result of $T_*$ turns out to be $0.2847050173$ for ...

  20. Extent of linkage disequilibrium in chicken

    NARCIS (Netherlands)

    Aerts, J.; Megens, H.J.W.C.; Veenendaal, T.; Ovcharenko, I.; Crooijmans, R.P.M.A.; Gordon, L.; Stubbs, L.; Groenen, M.A.M.; Rodoinov, A.; Gaginskaya, E.

    2007-01-01

    Many of the economically important traits in chicken are multifactorial and governed by multiple genes located at different quantitative trait loci (QTLs). The optimal marker density to identify these QTLs in linkage and association studies is largely determined by the extent of linkage

  1. A genetic linkage map of hexaploid naked oat constructed with SSR markers

    Institute of Scientific and Technical Information of China (English)

    Gaoyuan; Song; Pengjie; Huo; Bin; Wu; Zongwen; Zhang

    2015-01-01

    Naked oat is a unique health food crop in China. Using 202 F2 individuals derived from a hybrid between the variety 578 and the landrace Sanfensan, we constructed a genetic linkage map consisting of 22 linkage groups covering 2070.50 c M and including 208 simple sequence repeat(SSR) markers. The minimum distance between adjacent markers was0.01 c M and the average was 9.95 c M. Each linkage group contained 2–22 markers. The largest linkage group covered 174.40 c M and the shortest one covered 36.80 c M, with an average of 94.11 c M. Thirty-six markers(17.3%) showing distorted segregation were distributed across linkage groups LG5 to LG22. This map complements published oat genetic maps and is applicable for quantitative trait locus analysis, gene cloning and molecular marker-assisted selection.

  2. 乡村旅游中土地流转与开发策略的联动博弈分析%Rural Tourism in the Land Transfer and Development Strategy of the Linkage Game Analysis

    Institute of Scientific and Technical Information of China (English)

    刘赟

    2014-01-01

    The introduction of a new land transfer policy had a significant impact on rural land use and promoted to achieve scale effects of land-use basis. This paper set rural tourism as a research object, used the application of game analysis method to analyze the rural tourism industry development process of land transfer and linkage, analysed the demand of stake-holders in the different demands of the land transfer, and made the effective suggestion for rural tourism development strategy and sustainable development.%新型土地流转政策的出台对农村土地利用产生了重大影响,为实现土地利用的规模化效应奠定了基础。以乡村旅游作为研究对象,应用博弈分析法分析乡村旅游产业发展过程中土地流转和旅游开发策略的联动关系,剖析利益相关者在土地流转中的不同诉求,为乡村旅游的土地开发策略和可持续发展提供有效建议。

  3. Hereditary spastic paraplegia: LOD-score considerations for confirmation of linkage in a heterogeneous trait

    Energy Technology Data Exchange (ETDEWEB)

    Dube, M.P.; Kibar, Z.; Rouleau, G.A. [McGill Univ., Quebec (Canada)] [and others

    1997-03-01

    Hereditary spastic paraplegia (HSP) is a degenerative disorder of the motor system, defined by progressive weakness and spasticity of the lower limbs. HSP may be inherited as an autosomal dominant (AD), autosomal recessive, or an X-linked trait. AD HSP is genetically heterogeneous, and three loci have been identified so far: SPG3 maps to chromosome 14q, SPG4 to 2p, and SPG4a to 15q. We have undertaken linkage analysis with 21 uncomplicated AD families to the three AD HSP loci. We report significant linkage for three of our families to the SPG4 locus and exclude several families by multipoint linkage. We used linkage information from several different research teams to evaluate the statistical probability of linkage to the SPG4 locus for uncomplicated AD HSP families and established the critical LOD-score value necessary for confirmation of linkage to the SPG4 locus from Bayesian statistics. In addition, we calculated the empirical P-values for the LOD scores obtained with all families with computer simulation methods. Power to detect significant linkage, as well as type I error probabilities, were evaluated. This combined analytical approach permitted conclusive linkage analyses on small to medium-size families, under the restrictions of genetic heterogeneity. 19 refs., 1 fig., 1 tab.

  4. No linkage and association of atopy to chromosome 16 including the interleukin-4 receptor gene

    DEFF Research Database (Denmark)

    Haagerup, A; Bjerke, T; Schiøtz, P O

    2001-01-01

    BACKGROUND: Several susceptibility genes for atopy have been suggested in recent years. Few have been investigated as intensively as the interleukin-4-receptor alpha (IL4Ralpha) gene on chromosome 16. The results remain in dispute. Therefore, in a robust design, we tested for association of type I...... and evaluated by the transmission disequilibrium test (TDT). Multipoint linkage analysis and exclusion mapping were conducted with sib-pairs analyzed for 17 microsatellite markers. RESULTS: No evidence for association or linkage to the IL4R polymorphisms was found (P values: 0.12-0.90). Linkage analysis did...

  5. Comprehensive evaluation of antibiotics emission and fate in the river basins of China: source analysis, multimedia modeling, and linkage to bacterial resistance.

    Science.gov (United States)

    Zhang, Qian-Qian; Ying, Guang-Guo; Pan, Chang-Gui; Liu, You-Sheng; Zhao, Jian-Liang

    2015-06-02

    Antibiotics are widely used in humans and animals, but there is a big concern about their negative impacts on ecosystem and human health after use. So far there is a lack of information on emission inventory and environmental fate of antibiotics in China. We studied national consumption, emissions, and multimedia fate of 36 frequently detected antibiotics in China by market survey, data analysis, and level III fugacity modeling tools. Based on our survey, the total usage for the 36 chemicals was 92700 tons in 2013, an estimated 54000 tons of the antibiotics was excreted by human and animals, and eventually 53800 tons of them entered into the receiving environment following various wastewater treatments. The fugacity model successfully predicted environmental concentrations (PECs) in all 58 river basins of China, which are comparable to the reported measured environmental concentrations (MECs) available in some basins. The bacterial resistance rates in the hospitals and aquatic environments were found to be related to the PECs and antibiotic usages, especially for those antibiotics used in the most recent period. This is the first comprehensive study which demonstrates an alarming usage and emission of various antibiotics in China.

  6. Genetic linkage studies in familial partial epilepsy: Exclusion of the human chromosome regions syntenic to the El-1 mouse locus

    Energy Technology Data Exchange (ETDEWEB)

    Lopes-Cendes, I. [Montreal General Hospital (Canada); Mulley, J.C. [Alelaide Children`s Hospital (Canada); Andermann, E. [Montreal Neurological Institute and Hospital, Quebec (Canada)] [and others

    1994-09-01

    Recently, six families with a familial form of partial epilepsy were described. All pedigrees showed autosomal dominant inheritance with incomplete penetrance. Affected individuals present with predominantly nocturnal seizures with frontal lobe semiology. In 1959, a genetic mouse model for partial epilepsy, the El mouse, was reported. In the El mouse, a major seizure susceptibility gene, El-1, segregates in an autosomal dominant fashion and has been localized to a region distal to the centromere of mouse chromosome 9. Comparative genetic maps between man and mouse have been used for prediction of localization of several human disease genes. Because the region of mouse chromosome 9 that is the most likely to contain the El-1 locus is syntenic to regions on human chromosomes 3q21-p22, 3q21-q23.3, 6q12 and 15q24, we adopted the candidate gene approach as an initial linkage strategy. Twenty-two polymorphic microsatellite markers covering these regions were used for genotyping individuals in the three larger families ascertained, two of which are Australian and one French-Canadian. Negative two-point lod scores were obtained separately for each family. The analysis of all three families combined significantly excludes the candidate regions on chromosomes 3, 6 and 15.

  7. The REBUS-MCNP linkage.

    Energy Technology Data Exchange (ETDEWEB)

    Stevens, J. G.; Nuclear Engineering Division

    2009-04-24

    The Reduced Enrichment Research and Test Reactor (RERTR) Program uses the REBUS-PC computer code to provide reactor physics and core design information such as neutron flux distributions in space, energy, and time, and to track isotopic changes in fuel and neutron absorbers with burnup. REBUS-PC models the complete fuel cycle including shuffling capability. REBUS-PC evolved using the neutronic capabilities of multi-group diffusion theory code DIF3D 9.0, but was extended to apply the continuous energy Monte Carlo code MCNP for one-group fluxes and cross-sections. The linkage between REBUS-PC and MCNP has recently been modernized and extended, as described in this manual. REBUS-PC now calls MCNP via a system call so that the user can apply any valid MCNP executable. The interface between REBUS-PC and MCNP requires minimal changes to an existing MCNP model, and little additional input. The REBUS-MCNP interface can also be used in conjunction with DIF3D neutronics to update an MCNP model with fuel compositions predicted using a DIF3D based depletion.

  8. The phenotypic difference discards sib-pair QTL linkage information

    Energy Technology Data Exchange (ETDEWEB)

    Wright, F.A. [Univ. of California, San Diego, CA (United States)]|[Univ. of Texas, El Paso, TX (United States)

    1997-03-01

    Kruglyak and Lander provide an important synthesis of methods for (IBD) sib-pair linkage mapping, with an emphasis on the use of complete multipoint inheritance information for each sib pair. These procedures are implemented in the computer program MAPMAKER/SIBS, which performs interval mapping for dichotomous and quantitative traits. The authors present three methods for mapping quantitative trait loci (QTLs): a variant of the commonly used Haseman-Elston regression approach, a maximum-likelihood procedure involving variance components, and a rank-based nonparametric procedure. These approaches and related work use the magnitude of the difference in the sibling phenotype values for each sib pair as the observation for analysis. Linkage is detected if siblings sharing more alleles IBD have similar phenotypes (i.e., a small difference in the phenotype values), while siblings sharing fewer alleles IBD have less similar phenotypes. Such techniques have been used to detect linkage for a number of quantitative traits. However, the exclusive reliance on the phenotypic differences may be due in large part to historical inertia. A likelihood argument is presented here to show that, under certain classical assumptions, the phenotypic differences do not contain the full likelihood information for QTL mapping. Furthermore, considerable gains in power to detect linkage can be achieved with an expanded likelihood model. The development here is related to previous work, which incorporates the full set of phenotypic data using likelihood and robust quasi-likelihood methods. The purpose of this letter is not to endorse a particular approach but to spur research in alternative and perhaps more powerful linkage tests. 17 refs.

  9. A comparison between a refined two-point model for the limited tokamak SOL and self-consistent plasma turbulence simulations

    Science.gov (United States)

    Wersal, C.; Ricci, P.; Loizu, J.

    2017-04-01

    A refined two-point model is derived from the drift-reduced Braginskii equations for the limited tokamak scrape-off layer (SOL) by balancing the parallel and perpendicular transport of plasma and heat and taking into account the plasma–neutral interaction. The model estimates the electron temperature drop along a field line, from a region far from the limiter to the limiter plates. Self-consistent first-principles turbulence simulations of the SOL plasma including its interaction with neutral atoms are performed with the GBS code and compared to the refined two-point model. The refined two-point model is shown to be in very good agreement with the turbulence simulation results.

  10. DYNAMIC DESIGN OF VARIABLE SPEED PLANAR LINKAGES

    Institute of Scientific and Technical Information of China (English)

    Yao Yanan; Yan Hongsen; Zou Huijun

    2005-01-01

    A method for improving dynamic characteristics of planar linkages by actively varying the speed function of the input link is presented. Design criteria and constraints for the dynamic design of variable speed planar linkages are developed. Both analytical and optimization approaches for determining suitable input speed functions to minimize the driving torque, the shaking moment, or both simultaneously of planar linkages, subject to various design requirements and constraints, are derived.Finally, some examples are given to illustrate the design procedure and to verify its feasibility.

  11. Revisiting van der Waals like behavior of f(R AdS black holes via the two point correlation function

    Directory of Open Access Journals (Sweden)

    Jie-Xiong Mo

    2017-05-01

    Full Text Available Van der Waals like behavior of f(R AdS black holes is revisited via two point correlation function, which is dual to the geodesic length in the bulk. The equation of motion constrained by the boundary condition is solved numerically and both the effect of boundary region size and f(R gravity are probed. Moreover, an analogous specific heat related to δL is introduced. It is shown that the T−δL graphs of f(R AdS black holes exhibit reverse van der Waals like behavior just as the T−S graphs do. Free energy analysis is carried out to determine the first order phase transition temperature T⁎ and the unstable branch in T−δL curve is removed by a bar T=T⁎. It is shown that the first order phase transition temperature is the same at least to the order of 10−10 for different choices of the parameter b although the values of free energy vary with b. Our result further supports the former finding that charged f(R AdS black holes behave much like RN-AdS black holes. We also check the analogous equal area law numerically and find that the relative errors for both the cases θ0=0.1 and θ0=0.2 are small enough. The fitting functions between log⁡|T−Tc| and log⁡|δL−δLc| for both cases are also obtained. It is shown that the slope is around 3, implying that the critical exponent is about 2/3. This result is in accordance with those in former literatures of specific heat related to the thermal entropy or entanglement entropy.

  12. Linkage disequilibrium in wild mice.

    Directory of Open Access Journals (Sweden)

    Cathy C Laurie

    2007-08-01

    Full Text Available Crosses between laboratory strains of mice provide a powerful way of detecting quantitative trait loci for complex traits related to human disease. Hundreds of these loci have been detected, but only a small number of the underlying causative genes have been identified. The main difficulty is the extensive linkage disequilibrium (LD in intercross progeny and the slow process of fine-scale mapping by traditional methods. Recently, new approaches have been introduced, such as association studies with inbred lines and multigenerational crosses. These approaches are very useful for interval reduction, but generally do not provide single-gene resolution because of strong LD extending over one to several megabases. Here, we investigate the genetic structure of a natural population of mice in Arizona to determine its suitability for fine-scale LD mapping and association studies. There are three main findings: (1 Arizona mice have a high level of genetic variation, which includes a large fraction of the sequence variation present in classical strains of laboratory mice; (2 they show clear evidence of local inbreeding but appear to lack stable population structure across the study area; and (3 LD decays with distance at a rate similar to human populations, which is considerably more rapid than in laboratory populations of mice. Strong associations in Arizona mice are limited primarily to markers less than 100 kb apart, which provides the possibility of fine-scale association mapping at the level of one or a few genes. Although other considerations, such as sample size requirements and marker discovery, are serious issues in the implementation of association studies, the genetic variation and LD results indicate that wild mice could provide a useful tool for identifying genes that cause variation in complex traits.

  13. [Dystroglycan linkage and muscular dystrophy].

    Science.gov (United States)

    Shimizu, Teruo

    2002-11-01

    Dystroglycan is a key complex between basal lamina laminin, extracellularly and membrano-cytoskeleton, intracellularly. The damage of this linkage is turned out to cause muscular dystrophies. Dystroglycan knockout is lethal. Dystroglycan-associated intracellular proteins such as dystrophin, dystrobrevin, sarcoglycans, plectin and caveolin-3 are responsible for causing severe (Duchenne type) and moderate forms (Becker, LGMDs). Laminin, dystroglycan-binding extracellular protein, is deficient in the most severe form of congenital muscular dystrophy with normal intelligence and eye. Recently, a remarkable progress is made in most severe forms of congenital muscular dystrophy with anomalies of brain and eye such as Fukuyama type (Japan) and muscle-eye-brain disease (Finland). The gene product for Fukuyama type, fukutin, belongs to a family of glycosylation enzymes in bacteria and yeast. Since alpha-dystroglycan contains 14-15 o-glycans, ser/thr-mannose 2-1 GlcNAc 4-1 Gal 3-2 Sial in the middle third mucin-domain and the sial-o-glycan is essential for laminin-binding, and since alpha-dystroglycan is defective in Fukuyama type sarcolemma with anti both sugar moiety- and peptide-antidodies, defective fukutin causes incomplete o-glycosylation of alpha-dystroglycan. In '02, it is clarified that a glycosylation enzyme, POMGnT1 which modifies GlcNAc onto ser/thr-mannose, is defective in 6 MEB patients. The loss of the enzyme activity is turned out to lose alpha-dystroglycan from sarcolemma of MEB. These data strongly suggests that o-glycosylation defect of alpha-dystroglycan causes the most severe congenital muscular dystrophy such as Fukuyama type, MEB and Walker Warburg syndrome.

  14. Missing Linkages in California's Landscape [ds420

    Data.gov (United States)

    California Department of Resources — The critical need for conserving landscape linkages first came to the forefront of conservation thinking in California in November 2000, when a statewide interagency...

  15. Connectivity and Linkages Between Isolated Habitat

    Data.gov (United States)

    California Department of Resources — Proposed areas where connectiviy and linkages between isolated habitat on the San Joaquin Valley floor and natural lands in the surrounding foothills should be...

  16. Paroxysmal dystonic choreoathetosis: Tight linkage to chromosome 2q

    Energy Technology Data Exchange (ETDEWEB)

    Fink, J.K.; Rainier, S.; Wilkowski, J.; Jones, S.M. [Univ. of Michigan, Ann Arbor, MI (United States)] [and others

    1996-07-01

    Paroxysmal dystonic choreoathetosis (PDC) is characterized by attacks of involuntary movements that last up to several hours and occur at rest both spontaneously and following caffeine or alcohol consumption. We analyzed a Polish-American kindred with autosomal dominant PDC and identified tight linkage between the disorder and microsatellite markers on chromosome 2q (maximum two-point LOD score 4.77; recombination fraction 0). Our results clearly establish the existence of a locus for autosomal dominant PDC on distal chromosome 2q. The fact that three other paroxysmal neurological disorders (periodic ataxia with myokymia and hypo- and hyperkalemic periodic paralysis) are due to mutation in ion-channel genes raises the possibility that PDC is also due to an ion-channel gene mutation. It is noteworthy that a cluster of sodium-channel genes is located on distal chromosome 2q, near the PDC locus. Identifying the PDC locus on chromosome 2q will facilitate discovery whether PDC is genetically homogeneous and whether other paroxysmal movement disorders are also genetically linked to the PDC locus. 28 refs., 2 figs., 1 tab.

  17. On the problem of mass dependence of the two-point function of the real scalar free massive field on the light cone

    Energy Technology Data Exchange (ETDEWEB)

    Ullrich, Peter [Institut fuer Informatik, TU Muenchen, Boltzmannstrasse 3, D-85748 Garching (Germany); Werner, Ernst [Institut fuer Physik, Universitaet Regensburg, Universitaetsstrasse 31, D-93040 Regensburg (Germany)

    2006-05-19

    We investigate the generally assumed inconsistency in light cone quantum field theory that the restriction of a massive, real scalar free field to the nullplane {sigma} = {l_brace}x{sup 0} + x{sup 3} = 0{r_brace} is independent of mass (Leutwyler, Klauder and Streit 1970 Nuovo Cimento A 66 536), but the restriction of the two-point function is mass dependent (see, e.g., Nakanishi and Yamawaki 1977 Nucl. Phys. B 122 15; Yamawaki K 1997 Proc. Int. Workshop New Nonperturbative Methods and Quantization on the Light Cone (Les Houches, France) Preprint hep-th/9707141). We resolve this inconsistency by showing that the two-point function has no canonical restriction to {sigma} in the sense of distribution theory. Only the so-called tame restriction of the two-point function, which we have introduced in (Ullrich P 2004 Uniqueness in the characteristic Cauchy problem of the Klein-Gordon equation and tame restrictions of generalized functions Preprint math-ph/0408022 (submitted)) exists. Furthermore, we show that this tame restriction is indeed independent of the mass. Hence the inconsistency is induced by the erroneous assumption that the two-point function has a (canonical) restriction to {sigma}.

  18. The Application of Two-Point Touch Cane Technique to Theories of Motor Control and Learning Implications for Orientation and Mobility Training.

    Science.gov (United States)

    Croce, Ronald V.; Jacobson, William H.

    1986-01-01

    Basic behavioral processes involved in motor control based on theories of motor control and learning are outlined using the teaching of two-point touch cane technique as an application of the theories. The authors assert the importance of repetition, practice, and sufficient learning time. (Author/CL)

  19. Mode-sum construction of the covariant graviton two-point function in the Poincaré patch of de Sitter space

    Science.gov (United States)

    Fröb, Markus B.; Higuchi, Atsushi; Lima, William C. C.

    2016-06-01

    We construct the graviton two-point function for a two-parameter family of linear covariant gauges in n -dimensional de Sitter space. The construction is performed via the mode-sum method in the Bunch-Davies vacuum in the Poincaré patch, and a Fierz-Pauli mass term is introduced to regularize the infrared (IR) divergences. The resulting two-point function is de Sitter invariant and free of IR divergences in the massless limit (for a certain range of parameters), although analytic continuation with respect to the mass for the pure-gauge sector of the two-point function is necessary for this result. This general result agrees with the propagator obtained by analytic continuation from the sphere [Phys. Rev. D 34, 3670 (1986); Classical Quantum Gravity 18, 4317 (2001)]. However, if one starts with strictly zero mass theory, the IR divergences are absent only for a specific value of one of the two parameters, with the other parameter left generic. These findings agree with recent calculations in the Landau (exact) gauge [J. Math. Phys. 53, 122502 (2012)], where IR divergences do appear in the spin-two (tensor) part of the two-point function. However, we find the strength (including the sign) of the IR divergence to be different from the one found in this reference.

  20. 家族性不宁腿综合征候选基因的连锁分析%Linkage Analysis of the Candidate Genes of Familial Restless Legs Syndrome

    Institute of Scientific and Technical Information of China (English)

    李靖; 胡兰靛; 王维郡; 陈宇光; 孔祥银

    2003-01-01

    This research was performed to investigate the relationship between 16 candidate genes responsible for dopaminergic transmission or iron metabolism and familial restless legs syndrome.Genotyping was performed in a Han restless legs syndrome family using the technique of fluorescence-based genescan with the microsatellite markers selected in chromosomal regions flanking the candidate genes.Classical linkage analysis was conducted under the autosomal dominant genetic mode.Results showed that all of the LOD scores at recombination fraction 0.00 are smaller than -2.00,which indicated that these loci were not linked to familial restless legs syndrome.No linkage was found between the candidate genes and RLS in this family.Familial restless legs syndrome may be caused by another gene related to dopaminergic transmission and iron metabolism or there is new mechanism involved in this disease.%不宁腿综合征(restless legs syndrome,RLS)是以下肢部出现蚁行样及酸、麻、胀等不适感而使肢体不得休息为特征的一组病症.由于症状常在晚间发作并导致运动不安,患者长期入睡困难,经受严重的继发性失眠.作为一种常见的神经系统疾病,RLS发病率高达5%,其中原发性RLS多呈阳性家族史,表现为单基因决定的常染色体显性遗传.现在,人们普遍认为RLS的发生很可能与神经系统内多巴胺能功能异常和脑内铁缺乏有关,并初步建立了脑铁-多巴胺能系统的致病模型.为了探求脑铁-多巴胺能系统在RLS中的作用,选择了与脑铁-多巴胺能系统相关的16个疾病候选基因,在每个候选基因附近染色体区域内选取若干个微卫星多态标记,应用微卫星引物荧光标记-基因扫描技术,对一个汉族家族性不宁腿综合征家系进行了基因分型和常染色体显性遗传模式下的连锁分析,试图从分子遗传学层面上确认或排除一些可能与RLS相关的重要候选基因.结果显示,当重组系数θ=0.00

  1. Driving torque reduction in linkage mechanisms using joint compliance for robot head

    Science.gov (United States)

    Zhong, Chunhao; Yang, Xiaojun

    2015-09-01

    The conventional linkage mechanisms with compliant joint have been widely studied and implemented for increasing the adaptability of the mechanism to external contacts. However, the analysis of how compliant joints in linkage mechanism can reduce the energy consumption isn't still studied deeply. In a mobile service robot head, the actions of blinking the eyes and moving the eyeballs are realized by the planar linkage mechanism respectively. Therefore, minimizing the driving torques through motion trajectories for the linkage mechanism, which will be beneficial to extend the working time for mobile service robots. The dynamic modeling of the linkage mechanism with springs-loaded compliant joint is established. An optimization procedure for obtaining the optimal parameters of springs is proposed for minimizing the max value of driving torques within a range of desired operating conditions. The Simulations prove that the linkage mechanism with compliant joints can effectively reduce the driving torques, and reduce the energy consumption consequently. The framework can also be applied in other similar applications to reduce the driving torque and save energy. Compared with previous efforts, this is the first attempt that the linkage mechanism with complaint joint is applied in the robot head for reducing the driving torque.

  2. SSR and EST-SSR-based genetic linkage map of cassava (Manihot esculenta Crantz).

    Science.gov (United States)

    Sraphet, Supajit; Boonchanawiwat, Athipong; Thanyasiriwat, Thanwanit; Boonseng, Opas; Tabata, Satoshi; Sasamoto, Shigemi; Shirasawa, Kenta; Isobe, Sachiko; Lightfoot, David A; Tangphatsornruang, Sithichoke; Triwitayakorn, Kanokporn

    2011-04-01

    Simple sequence repeat (SSR) markers provide a powerful tool for genetic linkage map construction that can be applied for identification of quantitative trait loci (QTL). In this study, a total of 640 new SSR markers were developed from an enriched genomic DNA library of the cassava variety 'Huay Bong 60' and 1,500 novel expressed sequence tag-simple sequence repeat (EST-SSR) loci were developed from the Genbank database. To construct a genetic linkage map of cassava, a 100 F(1) line mapping population was developed from the cross Huay Bong 60 by 'Hanatee'. Polymorphism screening between the parental lines revealed that 199 SSRs and 168 EST-SSRs were identified as novel polymorphic markers. Combining with previously developed SSRs, we report a linkage map consisted of 510 markers encompassing 1,420.3 cM, distributed on 23 linkage groups with a mean distance between markers of 4.54 cM. Comparison analysis of the SSR order on the cassava linkage map and the cassava genome sequences allowed us to locate 284 scaffolds on the genetic map. Although the number of linkage groups reported here revealed that this F(1) genetic linkage map is not yet a saturated map, it encompassed around 88% of the cassava genome indicating that the map was almost complete. Therefore, sufficient markers now exist to encompass most of the genomes and efficiently map traits in cassava.

  3. Record Linkage system in a complex relational database - MINPHIS example.

    Science.gov (United States)

    Achimugu, Philip; Soriyan, Abimbola; Oluwagbemi, Oluwatolani; Ajayi, Anu

    2010-01-01

    In the health sector, record linkage is of paramount importance as clinical data can be distributed across different data repositories leading to duplication. Record Linkage is the process of tracking duplicate records that actually refers to the same entity. This paper proposes a fast and efficient method for duplicates detection within the healthcare domain. The first step is to standardize the data in the database using SQL. The second is to match similar pair records, and third step is to organize records into match and non-match status. The system was developed in Unified Modeling Language and Java. In the batch analysis of 31, 177 "supposedly" distinct identities, our method isolates 25, 117 true unique records and 6, 060 suspected duplicates using a healthcare system called MINPHIS (Made in Nigeria Primary Healthcare Information System) as the test bed.

  4. High-resolution gene mapping using admixture linkage disequilibrium

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    This note reports simulation study on the rate of decay in linkage dis equilibrium (LD) in mixed populations over multiple discrete generations and explores the usefulness of the LD analysis in high-resolution gene mapping. The results indicate that the smaller the recombination fraction and the fewer generati ons since admixtureevent, the higher power of the approach in gene mapping. The expected estimate of recombination fraction would give an estimate that is slig htly biased upwards, if relevant genes are in tight linkage. The estimated recom bination fraction is usually larger than the true value within 2-5 generations. From generations 10-20, the mean estimates are in good agreement with the true value. The method presented here enables estimation of means and corresponding confidence intervals of the recombination fraction at any number of generations.

  5. 西瓜遗传图谱构建及果实相关性状QTL分析%Construction of a Genetic Linkage Map and QTL Analysis of Fruit-Associated Traits in Watermelon

    Institute of Scientific and Technical Information of China (English)

    刘传奇; 高鹏; 栾非时

    2014-01-01

    electrophoresis was used to detect the digestion products. SSR markers in this experiment were come from the published literature. The products of SSR-PCR were detected by polyacrylamid gel electrophoresis. All the molecular data were tested by chi-square. Markers which were confirmed the proportion 1﹕2﹕1 were chosen for the genetic linkage map. The genetic linkage map was constructed by Mapmaker/Exp version 3.0. The markers were grouped with the order ‘Group’. The number of the markers in the group which was less than 8 was sequenced faultlessly with the order ‘Compare’, which was more than 8 was ordered with the order ‘Try’. Map Chart 2.1 was used for drawing this genetic linkage map. QTL Network 2.0 was used for QTL analysis. 1 000 times repeats were done with the replacement testing, the critical threshold was P=0.005, and the method of constructing the map was composite interval mapping. The whole genome was scanned on every chromosome with 1 cM walking speed. QTL additive effect and epistatic effect were analyzed by the software.[Result]This genetic linkage map contained 16 linkage groups and included 87 CAPS markers and SSR markers. The map was 1 484.3 cM and the average distance between two makers was 15.46 cM. Mapping the QTL of the fruit-associated traits and analyzed by software QTL Network 2.0, and a total of 8 additive QTL and one pair of epistatic QTL were detected. Among the additive loci, 1 is for fruit shape index(QFSI 1), 1 for center brix (QCBR), 1 for center flesh firmness(QCFF), 1 for edge flesh firmness(QEFF), 1 for seed length(QSL), and 3 for seed width(QSWD 1,QSWD 2,QSWD 3). The epistatic loci,FSI 2 andFSI 3arefor fruit shape index. Phenotypic contribution rate of 10% or more have six QTL, which explained 11.7% -18.8% of the genetic variation. All of the QTL explained 7.12%-18.8% of the phenotypic variation.[Conclusion]A molecular genetic linkage map composed mainly of CAPS markers was constructed. Eight additive QTL and one pair of

  6. Effect of Linkage Disequilibrium on the Identification of Functional Variants

    Science.gov (United States)

    Thomas, Alun; Abel, Haley J; Di, Yanming; Faye, Laura L; Jin, Jing; Liu, Jin; Wu, Zheyan; Paterson, Andrew D

    2011-01-01

    We summarize the contributions of Group 9 of Genetic Analysis Workshop 17. This group addressed the problems of linkage disequilibrium and other longer range forms of allelic association when evaluating the effects of genotypes on phenotypes. Issues raised by long-range associations, whether a result of selection, stratification, possible technical errors, or chance, were less expected but proved to be important. Most contributors focused on regression methods of various types to illustrate problematic issues or to develop adaptations for dealing with high-density genotype assays. Study design was also considered, as was graphical modeling. Although no method emerged as uniformly successful, most succeeded in reducing false-positive results either by considering clusters of loci within genes or by applying smoothing metrics that required results from adjacent loci to be similar. Two unexpected results that questioned our assumptions of what is required to model linkage disequilibrium were observed. The first was that correlations between loci separated by large genetic distances can greatly inflate single-locus test statistics, and, whether the result of selection, stratification, possible technical errors, or chance, these correlations seem overabundant. The second unexpected result was that applying principal components analysis to genome-wide genotype data can apparently control not only for population structure but also for linkage disequilibrium. PMID:22128051

  7. How Strong are the Linkages between Real Estate and Other Sectors in China?

    OpenAIRE

    Wenlang Zhang; Gaofeng Han; Steven Chan

    2014-01-01

    International experience points to the critical role of stable property markets in maintaining financial stability. In China, the real estate sector has become increasingly important for the economy, but existing evidence has likely understated its importance as its linkages with other sectors have not been taken into account. This paper attempts to shed some light on these linkages which occur through both real and financial channels. Our analysis based on input-output tables shows that the ...

  8. How Strong are the Linkages between Real Estate and Other Sectors in China?

    OpenAIRE

    Wenlang Zhang; Gaofeng Han; Steven Chan

    2014-01-01

    International experience points to the critical role of stable property markets in maintaining financial stability. In China, the real estate sector has become increasingly important for the economy, but existing evidence has likely understated its importance as its linkages with other sectors have not been taken into account. This paper attempts to shed some light on these linkages which occur through both real and financial channels. Our analysis based on input-output tables shows that the ...

  9. A new episodic ataxia syndrome with linkage to chromosome 19q13.

    Science.gov (United States)

    Kerber, Kevin A; Jen, Joanna C; Lee, Hane; Nelson, Stanley F; Baloh, Robert W

    2007-05-01

    Multiple episodic ataxia phenotypes and genotypes have been described. To describe a new episodic ataxia syndrome. Genomewide linkage analysis with dense single nucleotide polymorphism arrays. University clinic. Patients Family with lifelong episodes of ataxia and normal interictal examination results. Suggestive linkage (logarithm of odds score, 3.27) to a 10-centimorgan region on chromosome 19q13. A new dominantly inherited episodic ataxia syndrome is linked to chromosome 19q.

  10. Comparing linkage designs based on land facets to linkage designs based on focal species.

    Science.gov (United States)

    Brost, Brian M; Beier, Paul

    2012-01-01

    Least-cost modeling for focal species is the most widely used method for designing conservation corridors and linkages. However, these designs depend on today's land covers, which will be altered by climate change. We recently proposed an alternative approach based on land facets (recurring landscape units of relatively uniform topography and soils). The rationale is that corridors with high continuity of individual land facets will facilitate movement of species associated with each facet today and in the future. Conservation practitioners might like to know whether a linkage design based on land facets is likely to provide continuity of modeled breeding habitat for species needing connectivity today, and whether a linkage for focal species provides continuity and interspersion of land facets. To address these questions, we compared linkages designed for focal species and land facets in three landscapes in Arizona, USA. We used two variables to measure linkage utility, namely distances between patches of modeled breeding habitat for 5-16 focal species in each linkage, and resistance profiles for focal species and land facets between patches connected by the linkage. Compared to focal species designs, linkage designs based on land facets provided as much or more modeled habitat connectivity for 25 of 28 species-landscape combinations, failing only for the three species with the most narrowly distributed habitat. Compared to land facets designs, focal species linkages provided lower connectivity for about half the land facets in two landscapes. In areas where a focal species approach to linkage design is not possible, our results suggest that conservation practitioners may be able to implement a land facets approach with some confidence that the linkage design would serve most potential focal species. In areas where focal species designs are possible, we recommend using the land facet approach to complement, rather than replace, focal species approaches.

  11. An enhanced linkage map of the sheep genome comprising more than 1000 loci.

    Science.gov (United States)

    Maddox, J F; Davies, K P; Crawford, A M; Hulme, D J; Vaiman, D; Cribiu, E P; Freking, B A; Beh, K J; Cockett, N E; Kang, N; Riffkin, C D; Drinkwater, R; Moore, S S; Dodds, K G; Lumsden, J M; van Stijn, T C; Phua, S H; Adelson, D L; Burkin, H R; Broom, J E; Buitkamp, J; Cambridge, L; Cushwa, W T; Gerard, E; Galloway, S M; Harrison, B; Hawken, R J; Hiendleder, S; Henry, H M; Medrano, J F; Paterson, K A; Schibler, L; Stone, R T; van Hest, B

    2001-07-01

    A medium-density linkage map of the ovine genome has been developed. Marker data for 550 new loci were generated and merged with the previous sheep linkage map. The new map comprises 1093 markers representing 1062 unique loci (941 anonymous loci, 121 genes) and spans 3500 cM (sex-averaged) for the autosomes and 132 cM (female) on the X chromosome. There is an average spacing of 3.4 cM between autosomal loci and 8.3 cM between highly polymorphic [polymorphic information content (PIC) > or = 0.7] autosomal loci. The largest gap between markers is 32.5 cM, and the number of gaps of > 20 cM between loci, or regions where loci are missing from chromosome ends, has been reduced from 40 in the previous map to 6. Five hundred and seventy-three of the loci can be ordered on a framework map with odds of > 1000 : 1. The sheep linkage map contains strong links to both the cattle and goat maps. Five hundred and seventy-two of the loci positioned on the sheep linkage map have also been mapped by linkage analysis in cattle, and 209 of the loci mapped on the sheep linkage map have also been placed on the goat linkage map. Inspection of ruminant linkage maps indicates that the genomic coverage by the current sheep linkage map is comparable to that of the available cattle maps. The sheep map provides a valuable resource to the international sheep, cattle, and goat gene mapping community.

  12. A first linkage map of pecan cultivars based on RAPD and AFLP markers.

    Science.gov (United States)

    Beedanagari, Sudheer R; Dove, Sue K; Wood, Bruce W; Conner, Patrick J

    2005-04-01

    We report here the first genetic linkage maps of pecan [Carya illinoinensis (Wangenh.) K. Koch], using random amplified polymorphic DNA (RAPD) and amplified fragment length polymorphism (AFLP) markers. Independent maps were constructed for the cultivars 'Pawnee' and 'Elliot' using the double pseudo-testcross mapping strategy and 120 F1 seedlings from a full-sib family. A total of 477 markers, including 217 RAPD, 258 AFLP, and two morphological markers were used in linkage analysis. The 'Pawnee' linkage map has 218 markers, comprising 176 testcross and 42 intercross markers placed in 16 major and 13 minor (doublets and triplets) linkage groups. The 'Pawnee' linkage map covered 2,227 cM with an average map distance of 12.7 cM between adjacent markers. The 'Elliot' linkage map has 174 markers comprising 150 testcross and 22 intercross markers placed in 17 major and nine minor linkage groups. The 'Elliot' map covered 1,698 cM with an average map distance of 11.2 cM between adjacent markers. Segregation ratios for dichogamy type and stigma color were not significantly different from 1:1, suggesting that both traits are controlled by single loci with protogyny and green stigmas dominant to protandry and red stigmas. These loci were tightly linked (1.9 cM) and were placed in 'Elliot' linkage group 16. These linkage maps are an important first step towards the detection of genes controlling horticulturally important traits such as nut size, nut maturity date, kernel quality, and disease resistance.

  13. Genetic linkage heterogeneity in the fragile X syndrome.

    Science.gov (United States)

    Brown, W T; Gross, A C; Chan, C B; Jenkins, E C

    1985-01-01

    Genetic linkage between a factor IX DNA restriction fragment length polymorphism (RFLP) and the fragile X chromosome marker was analyzed in eight fragile X pedigrees and compared to eight previously reported pedigrees. A large pedigree with apparently full penetrance in all male members showed a high frequency of recombination. A lod score of -7.39 at theta = 0 and a maximum score of 0.26 at theta = 0.32 were calculated. A second large pedigree with a nonpenetrant male showed tight linkage with a maximum lod score of 3.13 at theta = 0, a result similar to one large pedigree with a nonpenetrant male previously reported. The differences in lod scores seen in these large pedigrees suggested there was genetic heterogeneity in linkage between families which appeared to relate to the presence of nonpenetrant males. The combined lod score for the three pedigrees with nonpenetrant males was 6.84 at theta = 0. For the 13 other pedigrees without nonpenetrant males the combined lod score was -21.81 at theta = 0, with a peak of 0.98 at theta = 0.28. When lod scores from all 16 families were combined, the value was -15.14 at theta = 0 and the overall maximum was 5.13 at theta = 0.17. To determine whether genetic heterogeneity was present, three statistical tests for heterogeneity were employed. First, a "predivided-sample" test was used. The 16 pedigrees were divided into two classes, NP and P, based upon whether or not any nonpenetrant males were detected in the pedigree. This test gave evidence for significant genetic heterogeneity whether the three large pedigrees with seven or more informative males (P less than 0.005), the eight pedigrees with three informative males (P less than 0.001), or all 16 pedigrees (P less than 0.001) were included in the analysis. Second, Morton's large sample test was employed. Significant heterogeneity was present when the analysis was restricted to the three large pedigrees (P less than 0.025), or to the eight pedigrees with informative males

  14. Fine mapping quantitative trait loci under selective phenotyping strategies based on linkage and linkage disequilibrium criteria

    DEFF Research Database (Denmark)

    Ansari-Mahyari, S; Berg, P; Lund, M S

    2009-01-01

    In fine mapping of a large-scale experimental population where collection of phenotypes are very expensive, difficult to record or time-demanding, selective phenotyping could be used to phenotype the most informative individuals. Linkage analyses based sampling criteria (LAC) and linkage...... disequilibrium-based sampling criteria (LDC) for selecting individuals to phenotype are compared to random phenotyping in a quantitative trait loci (QTL) verification experiment using stochastic simulation. Several strategies based on LAC and LDC for selecting the most informative 30%, 40% or 50% of individuals...... for phenotyping to extract maximum power and precision in a QTL fine mapping experiment were developed and assessed. Linkage analyses for the mapping was performed for individuals sampled on LAC within families and combined linkage disequilibrium and linkage analyses was performed for individuals sampled across...

  15. Evolution of zygotic linkage disequilibrium in a finite local population.

    Directory of Open Access Journals (Sweden)

    Xin-Sheng Hu

    Full Text Available One crucial feature of zygotic linkage disequilibrium (LD analysis is its direct use of diploid genotyping data, irrespective of the type of mating system. Previous theories from an evolutionary perspective mainly focus on gametic LD, but the equivalent development for zygotic LD is not available. Here I study the evolution of zygotic LD and the covariances between gametic and zygotic LDs or between distinct zygotic LDs in a finite local population under constant immigration from a continent population. I derive the analytical theory under genetic hitchhiking effects or in a neutral process. Results indicate that zygotic LDs (diploid level are more informative than gametic LD (haploid level in indicating the effects of different evolutionary forces. Zygotic LDs may be greater than or comparable to gametic LD under the epistatic selection process, but smaller than gametic LD under the non epistatic selection process. The covariances between gametic and zygotic LDs are strongly affected by the mating system, linkage distance, and genetic drift effects, but weakly affected by seed and pollen flow and natural selection. The covariances between different zygotic LDs are generally robust to the effects of gene flow, selection, and linkage distance, but sensitive to the effects of genetic drift and mating system. Consistent patterns exist for the covariances between the zygotic LDs for the two-locus genotypes with one common genotype at one locus or without any common genotype at each locus. The results highlight that zygotic LDs can be applied to detecting natural population history.

  16. [Effectiveness of expression of tdh gene of Vibrio parahaemolyticus depends on two point mutations in promoter region].

    Science.gov (United States)

    Shalu, O A; Pisanov, R V; Monakhova, E V

    2012-12-01

    A molecular-biological study of the clinical strains of Vibrio parahaemolyticus that contain genes of thermostable direct hemolysin Tdh) and Tdh-related hemolysin (Trh). Using Southern blot hybridization, it is shown that genomes of strains that carry determinants of both hemolysins (tdh(+)-trh+) represent a single copy, whereas in tdh2+RH+ strains, there are two copies (tdh1 and tdh2). All of the examined tdh+trh+ and some of the tdh+trh strains either did not express the tdh gene or did not express the tdh gene (Kanagawa negative or KP-) or expressed it weakly and not often (Kanagawa intermediate, KP+), unlike several Kanagawa positive tdh+trh- strains. To establish the reasons for KP -/+ phenotypes, tdh, tdh11, and tdh2 genes of 13 strains isolated in Russia and neighboring foreign countries were sequenced, followed by the biotransformation analysis of the obtained sequences, as well as a comparison with those of a number of strains presented in GenBank. The results revealed that the weak expression of the tdh gene depends, not only on one point mutation in the promoter region (substitution of A for G in the -35 region), as was thought previously, but also on the second substitution (G for A in the -3 position relative to the -10 sequence), which is quite sufficient when the former is absent. Therefore, the reversion of KP -/+ strains that contain one of these substitutions can take place as a result of a single reverse point mutation, and they should be considered potentially dangerous. Strains that contain both substitutions may revert with lesser probability because, in this case, both mutations are necessary.

  17. Prospective comparison of liver stiffness measurements between two point wave elastography methods: Virtual ouch quantification and elastography point quantification

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Hyun Suk; Lee, Jeong Min; Yoon, Jeong Hee; Lee, Dong Ho; Chang, Won; Han, Joon Koo [Seoul National University Hospital, Seoul (Korea, Republic of)

    2016-09-15

    To prospectively compare technical success rate and reliable measurements of virtual touch quantification (VTQ) elastography and elastography point quantification (ElastPQ), and to correlate liver stiffness (LS) measurements obtained by the two elastography techniques. Our study included 85 patients, 80 of whom were previously diagnosed with chronic liver disease. The technical success rate and reliable measurements of the two kinds of point shear wave elastography (pSWE) techniques were compared by χ{sup 2} analysis. LS values measured using the two techniques were compared and correlated via Wilcoxon signed-rank test, Spearman correlation coefficient, and 95% Bland-Altman limit of agreement. The intraobserver reproducibility of ElastPQ was determined by 95% Bland-Altman limit of agreement and intraclass correlation coefficient (ICC). The two pSWE techniques showed similar technical success rate (98.8% for VTQ vs. 95.3% for ElastPQ, p = 0.823) and reliable LS measurements (95.3% for VTQ vs. 90.6% for ElastPQ, p = 0.509). The mean LS measurements obtained by VTQ (1.71 ± 0.47 m/s) and ElastPQ (1.66 ± 0.41 m/s) were not significantly different (p = 0.209). The LS measurements obtained by the two techniques showed strong correlation (r = 0.820); in addition, the 95% limit of agreement of the two methods was 27.5% of the mean. Finally, the ICC of repeat ElastPQ measurements was 0.991. Virtual touch quantification and ElastPQ showed similar technical success rate and reliable measurements, with strongly correlated LS measurements. However, the two methods are not interchangeable due to the large limit of agreement.

  18. "Two-point" assembling of Zn(II) and Co(II) metalloporphyrins derivatized with a crown ether substituent in Langmuir and Langmuir-Blodgett films.

    Science.gov (United States)

    Noworyta, Krzysztof; Marczak, Renata; Tylenda, Rafal; Sobczak, Janusz W; Chitta, Raghu; Kutner, Wlodzimierz; D'Souza, Francis

    2007-02-27

    The effect of "two-point" interactions of Zn(II) and Co(II) metalloporphyrins, bearing 15-crown-5 ether peripheral substituents, on their assembling in Langmuir and Langmuir-Blodgett (LB) films was investigated. That is, simultaneously, the central metal ion of the porphyrin was axially ligated by a nitrogen-containing ligand in the emerged part of the Langmuir film on one hand, and a suitably selected cation pertaining in the subphase solution was supramolecularly complexed by the crown ether moiety in the submerged part of the film on the other. The compression and polarity properties of the Langmuir films of the derivatized free-base 5,10,15-triphenyl-20-(benzo-15-crown-5)porphyrin, H2(TPMCP), and the corresponding cobalt(II) and zinc(II) metalloporphyrins, denoted as Co(TPMCP) and Zn(TPCMP), respectively, as well as inclusion complexes of the metalloporphyrins with selected cations were investigated. For the axial ligation of Zn(II) and Co(II), pyrazine (pyz) and 4,4'-bipyridnine (bpy) aromatic as well as piperazine (ppz) and 1,4-diazabicyclo[2.2.2]octane (DABCO) cyclic heteroaliphatic ligands were selected. The films were formed on the water subphase solution in the absence and presence of LiCl, NaCl, or NH4Cl. The Langmuir films were built of monolayer J-type aggregates of tilted porphyrin macrocycles. The porphyrins formed rather labile complexes with the cations in the subphase. Nevertheless, the XPS analysis revealed that these cations were LB transferred together with the porphyrins onto solid substrates. In the Co(TPMCP) Langmuir films formed on the water subphases, Co(II) was complexed by aromatic but not cyclic heteroaliphatic ligands, while, in these films formed on the NaCl subphase solutions, the metalloporphyrin was also complexed by DABCO. In Langmuir films spread on alkaline subphase solutions, both aromatic and heteroaliphatic ligands formed complexes with Co(TPMCP) of different stoichiometries. The X-ray reflectivity and GIXD measurements

  19. Linear models for joint association and linkage QTL mapping

    Directory of Open Access Journals (Sweden)

    Fernando Rohan L

    2009-09-01

    Full Text Available Abstract Background Populational linkage disequilibrium and within-family linkage are commonly used for QTL mapping and marker assisted selection. The combination of both results in more robust and accurate locations of the QTL, but models proposed so far have been either single marker, complex in practice or well fit to a particular family structure. Results We herein present linear model theory to come up with additive effects of the QTL alleles in any member of a general pedigree, conditional to observed markers and pedigree, accounting for possible linkage disequilibrium among QTLs and markers. The model is based on association analysis in the founders; further, the additive effect of the QTLs transmitted to the descendants is a weighted (by the probabilities of transmission average of the substitution effects of founders' haplotypes. The model allows for non-complete linkage disequilibrium QTL-markers in the founders. Two submodels are presented: a simple and easy to implement Haley-Knott type regression for half-sib families, and a general mixed (variance component model for general pedigrees. The model can use information from all markers. The performance of the regression method is compared by simulation with a more complex IBD method by Meuwissen and Goddard. Numerical examples are provided. Conclusion The linear model theory provides a useful framework for QTL mapping with dense marker maps. Results show similar accuracies but a bias of the IBD method towards the center of the region. Computations for the linear regression model are extremely simple, in contrast with IBD methods. Extensions of the model to genomic selection and multi-QTL mapping are straightforward.

  20. Prospective blind comparative clinical study of two point fixation of zygomatic complex fracture using wire and mini plates

    Directory of Open Access Journals (Sweden)

    Gandi Lakshmi N

    2012-03-01

    Full Text Available Abstract Background The zygomatic maxillary complex (ZMC fractures are one of the most frequent injuries of the facial skeleton due to its position and facial contour. Assaults, road traffic accidents and falls are the principal etiologic factors that may cause fractures of zygomatic bone. The different fixation methods are applied to treat the zygomatic bone fractures, with many more classifications which have been described in the literature for the ease of management. The type of the fracture, its severity and associated facial fractures usually interferes the treatment modality. Purpose of study The aim of this paper is to show the results of 18yrs prospective blind comparative study using wire and plate osteosynthesis which needed open reduction and internal fixation involving Type II to Type IV Spissel and Schroll ZMC fractures. Materials and methods Total 80 cases included in the study out of 1780 ZMC cases which were treated using wire and plate osteosynthesis over a period of 18 yrs, involving only Type II to Type IV Spissel and Schroll ZMC fractures. Other types excluded from study to prevent observer bias. All the fixations carried out through Standard Dingman's incision using stainless steel 26 gauze wire and titanium 1.5 mm mini plate system under general anesthesia by single maxillofacial surgeon and evaluated by another maxillofacial surgeon who is blinded for surgical procedure after 2 and 4 wks of follow-up for facial symmetry, wound healing, functional assessment (mouth opening, diplopia, and sensory disturbance. All the data tabulated in Excel software (Microsoft for statistical analysis. P-value calculated to know the Significance of treatment modality in all aspects. Results Result shows no significant p-values indicating both the operating techniques are equally efficient in the surgical management of ZMC fracture. Conclusion Osteosynthesis by mini plates is simple, logical and effective treatment compared to wire

  1. Quarter-sweep Gauss-Seidel method with quadratic spline scheme applied to fourth order two-point boundary value problems

    Science.gov (United States)

    Mohd Fauzi, Norizyan Izzati; Sulaiman, Jumat

    2013-04-01

    The aim of this paper is to describe the application of Quarter-Sweep Gauss-Seidel (QSGS) iterative method using quadratic spline scheme for solving fourth order two-point linear boundary value problems. In the line to derive approximation equations, firstly the fourth order problems need to be reduced onto a system of second-order two-point boundary value problems. Then two linear systems have been constructed via discretization process by using the corresponding quarter-sweep quadratic spline approximation equations. The generated linear systems have been solved using the proposed QSGS iterative method to show the superiority over Full-Sweep Gauss-Seidel (FSGS) and Half-Sweep Gauss-Seidel (HSGS) methods. Computational results are provided to illustrate that the effectiveness of the proposed QSGS method is more superior in terms of computational time and number of iterations as compared to other tested methods.

  2. Stueckelberg massive electromagnetism in de Sitter and anti-de Sitter spacetimes: Two-point functions and renormalized stress-energy tensors

    CERN Document Server

    Belokogne, Andrei; Queva, Julien

    2016-01-01

    By considering Hadamard vacuum states, we first construct the two-point functions associated with Stueckelberg massive electromagnetism in de Sitter and anti-de Sitter spacetimes. Then, from the general formalism developed in [A. Belokogne and A. Folacci, Phys. Rev. D \\textbf{93}, 044063 (2016)], we obtain an exact analytical expression for the vacuum expectation value of the renormalized stress-energy tensor of the massive vector field propagating in these maximally symmetric spacetimes.

  3. Existence of Positive Solutions for Two-Point Boundary Value Problems of Nonlinear Finite Discrete Fractional Differential Equations and Its Application

    OpenAIRE

    Caixia Guo; Jianmin Guo; Ying Gao; Shugui Kang

    2016-01-01

    This paper is concerned with the two-point boundary value problems of nonlinear finite discrete fractional differential equations. On one hand, we discuss some new properties of the Green function. On the other hand, by using the main properties of Green function and the Krasnoselskii fixed point theorem on cones, some sufficient conditions for the existence of at least one or two positive solutions for the boundary value problem are established.

  4. Inter-organizational linkages and resource dependence

    Directory of Open Access Journals (Sweden)

    Rod B. McNaughton

    2014-12-01

    Full Text Available Few studies have examined the relationship between inter-industry, inter-corporate ownership (ICO patterns and inter-industry resource exchange patterns. Using data from Statistics Canada, this paper reveals a positive association between the degree of ICO linkages and the degree of input–output dependence among Canadian industry groups. This provides empirical support for the primary assertion of resource dependence theory: that corporations employ ICO linkages to manage their input–output dependence resulting from recurrent resource exchanges. This research differs from extant tests of resource dependence in that it uses data for the population of firms (over a size threshold in Canada and includes all forms of interdependence between enterprises. The findings suggest scenarios in which corporations can adopt ICO linkages to manage resource dependence and reduce transaction costs.

  5. Intragroup Emotions: Physiological Linkage and Social Presence

    Science.gov (United States)

    Järvelä, Simo; Kätsyri, Jari; Ravaja, Niklas; Chanel, Guillaume; Henttonen, Pentti

    2016-01-01

    We investigated how technologically mediating two different components of emotion—communicative expression and physiological state—to group members affects physiological linkage and self-reported feelings in a small group during video viewing. In different conditions the availability of second screen text chat (communicative expression) and visualization of group level physiological heart rates and their dyadic linkage (physiology) was varied. Within this four person group two participants formed a physically co-located dyad and the other two were individually situated in two separate rooms. We found that text chat always increased heart rate synchrony but HR visualization only with non-co-located dyads. We also found that physiological linkage was strongly connected to self-reported social presence. The results encourage further exploration of the possibilities of sharing group member's physiological components of emotion by technological means to enhance mediated communication and strengthen social presence. PMID:26903913

  6. Intragroup emotions: physiological linkage and social presence

    Directory of Open Access Journals (Sweden)

    Simo eJärvelä

    2016-02-01

    Full Text Available We investigated how technologically mediating two different components of emotion – communicative expression and physiological state – to group members affects physiological linkage and self-reported feelings in a small group during video viewing. In different conditions the availability of second screen text chat (communicative expression and visualization of group level physiological heart rates and their dyadic linkage (physiology was varied. Within this four person group two participants formed a physically co-located dyad and the other two were individually situated in two separate rooms. We found that text chat always increased heart rate synchrony but HR visualization only with non-co-located dyads. We also found that physiological linkage was strongly connected to self-reported social presence. The results encourage further exploration of the possibilities of sharing group member’s physiological components of emotion by technological means to enhance mediated communication and strengthen social presence.

  7. Mode-sum construction of the covariant graviton two-point function in the Poincar\\'e patch of de Sitter space

    CERN Document Server

    Fröb, Markus B; Lima, William C C

    2016-01-01

    We construct the graviton two-point function for a two-parameter family of linear covariant gauges in n-dimensional de Sitter space. The construction is performed via the mode-sum method in the Bunch-Davies vacuum in the Poincar\\'e patch, and a Fierz-Pauli mass term is introduced to regularize the infrared (IR) divergences. The resulting two-point function is de Sitter-invariant, and free of IR divergences in the massless limit (for a certain range of parameters) though analytic continuation with respect to the mass for the pure-gauge sector of the two-point function is necessary for this result. This general result agrees with the propagator obtained by analytic continuation from the sphere [Phys. Rev. D 34, 3670 (1986); Class. Quant. Grav. 18, 4317 (2001)]. However, if one starts with strictly zero mass theory, the IR divergences are absent only for a specific value of one of the two parameters, with the other parameter left generic. These findings agree with recent calculations in the Landau (exact) gauge ...

  8. Linkage and linkage disequilibrium in chromosome band 1p36 in American Chaldeans with inflammatory bowel disease.

    Science.gov (United States)

    Cho, J H; Nicolae, D L; Ramos, R; Fields, C T; Rabenau, K; Corradino, S; Brant, S R; Espinosa, R; LeBeau, M; Hanauer, S B; Bodzin, J; Bonen, D K

    2000-05-22

    The idiopathic inflammatory bowel diseases (IBDs), consisting of Crohn's disease and ulcerative colitis, are complex genetic disorders involving chronic inflammation of the intestines. Multiple genetic loci have been implicated through genome-wide searches, but refinement of localization sufficient to undertake positional cloning efforts has been problematic. This difficulty can be obviated through identification of ancestrally shared regions in genetic isolates, such as the Chaldean population, a Roman Catholic group from Iraq. We analyzed four multiply affected American Chaldean families with inflammatory bowel disease not known to be related. We observed evidence for linkage and linkage disequilibrium in precisely the same region of chromosome band 1p36 reported previously in an outbred population. Maximal evidence for linkage was observed near D1S1597 by multipoint analysis (MLOD = 3.01, P = 6.1 x 10(-5)). A shared haplotype (D1S507 to D1S1628) was observed over 27 cM between two families. There was homozygous sharing of a 5 cM portion of that haplotype in one family and over a <1 cM region in the second family. Homozygous sharing of this haplotype near D1S2697 and D1S3669 was observed in one individual in a third multiply affected family, with heterozygous sharing in a fourth family. Linkage in outbred families as well as in this genetic isolate indicates that a pathophysiologically crucial IBD susceptibility gene is located in 1p36. These findings provide a unique opportunity to refine the localization and identify a major susceptibility gene for a complex genetic disorder.

  9. Some methods for blindfolded record linkage

    Directory of Open Access Journals (Sweden)

    Christen Peter

    2004-06-01

    Full Text Available Abstract Background The linkage of records which refer to the same entity in separate data collections is a common requirement in public health and biomedical research. Traditionally, record linkage techniques have required that all the identifying data in which links are sought be revealed to at least one party, often a third party. This necessarily invades personal privacy and requires complete trust in the intentions of that party and their ability to maintain security and confidentiality. Dusserre, Quantin, Bouzelat and colleagues have demonstrated that it is possible to use secure one-way hash transformations to carry out follow-up epidemiological studies without any party having to reveal identifying information about any of the subjects – a technique which we refer to as "blindfolded record linkage". A limitation of their method is that only exact comparisons of values are possible, although phonetic encoding of names and other strings can be used to allow for some types of typographical variation and data errors. Methods A method is described which permits the calculation of a general similarity measure, the n-gram score, without having to reveal the data being compared, albeit at some cost in computation and data communication. This method can be combined with public key cryptography and automatic estimation of linkage model parameters to create an overall system for blindfolded record linkage. Results The system described offers good protection against misdeeds or security failures by any one party, but remains vulnerable to collusion between or simultaneous compromise of two or more parties involved in the linkage operation. In order to reduce the likelihood of this, the use of last-minute allocation of tasks to substitutable servers is proposed. Proof-of-concept computer programmes written in the Python programming language are provided to illustrate the similarity comparison protocol. Conclusion Although the protocols described in

  10. The planar two point algorithm

    NARCIS (Netherlands)

    O. Booij; Z. Zivkovic

    2009-01-01

    Vision-based localization, mapping and navigation is often performed by searching for corresponding image points and estimating the epipolar geometry. It is known that the possible relative poses of a camera mounted on a mobile robot that moves over a planar ground floor, has two degrees of freedom.

  11. Effectiveness of service linkages in primary mental health care: a narrative review part 1

    Directory of Open Access Journals (Sweden)

    Parker Sharon

    2011-04-01

    Full Text Available Abstract Background With the move to community care and increased involvement of generalist health care providers in mental health, the need for health service partnerships has been emphasised in mental health policy. Within existing health system structures the active strategies that facilitate effective partnership linkages are not clear. The objective of this study was to examine the evidence from peer reviewed literature regarding the effectiveness of service linkages in primary mental health care. Methods A narrative and thematic review of English language papers published between 1998 and 2009. Studies of analytic, descriptive and qualitative designs from Australia, New Zealand, UK, Europe, USA and Canada were included. Data were extracted to examine what service linkages have been used in studies of collaboration in primary mental health care. Findings from the randomised trials were tabulated to show the proportion that demonstrated clinical, service delivery and economic benefits. Results A review of 119 studies found ten linkage types. Most studies used a combination of linkage types and so the 42 RCTs were grouped into four broad linkage categories for meaningful descriptive analysis of outcomes. Studies that used multiple linkage strategies from the suite of "direct collaborative activities" plus "agreed guidelines" plus "communication systems" showed positive clinical (81%, service (78% and economic (75% outcomes. Most evidence of effectiveness came from studies of depression. Long term benefits were attributed to medication concordance and the use of case managers with a professional background who received expert supervision. There were fewer randomised trials related to collaborative care of people with psychosis and there were almost none related to collaboration with the wider human service sectors. Because of the variability of study types we did not exclude on quality or attempt to weight findings according to power or effect

  12. Linkage disequilibrium fine mapping of quantitative trait loci: A simulation study

    Directory of Open Access Journals (Sweden)

    Pérez-Enciso Miguel

    2003-09-01

    Full Text Available Abstract Recently, the use of linkage disequilibrium (LD to locate genes which affect quantitative traits (QTL has received an increasing interest, but the plausibility of fine mapping using linkage disequilibrium techniques for QTL has not been well studied. The main objectives of this work were to (1 measure the extent and pattern of LD between a putative QTL and nearby markers in finite populations and (2 investigate the usefulness of LD in fine mapping QTL in simulated populations using a dense map of multiallelic or biallelic marker loci. The test of association between a marker and QTL and the power of the test were calculated based on single-marker regression analysis. The results show the presence of substantial linkage disequilibrium with closely linked marker loci after 100 to 200 generations of random mating. Although the power to test the association with a frequent QTL of large effect was satisfactory, the power was low for the QTL with a small effect and/or low frequency. More powerful, multi-locus methods may be required to map low frequent QTL with small genetic effects, as well as combining both linkage and linkage disequilibrium information. The results also showed that multiallelic markers are more useful than biallelic markers to detect linkage disequilibrium and association at an equal distance.

  13. Visualization of pairwise and multilocus linkage disequilibrium structure using latent forests.

    Directory of Open Access Journals (Sweden)

    Raphaël Mourad

    Full Text Available Linkage disequilibrium study represents a major issue in statistical genetics as it plays a fundamental role in gene mapping and helps us to learn more about human history. The linkage disequilibrium complex structure makes its exploratory data analysis essential yet challenging. Visualization methods, such as the triangular heat map implemented in Haploview, provide simple and useful tools to help understand complex genetic patterns, but remain insufficient to fully describe them. Probabilistic graphical models have been widely recognized as a powerful formalism allowing a concise and accurate modeling of dependences between variables. In this paper, we propose a method for short-range, long-range and chromosome-wide linkage disequilibrium visualization using forests of hierarchical latent class models. Thanks to its hierarchical nature, our method is shown to provide a compact view of both pairwise and multilocus linkage disequilibrium spatial structures for the geneticist. Besides, a multilocus linkage disequilibrium measure has been designed to evaluate linkage disequilibrium in hierarchy clusters. To learn the proposed model, a new scalable algorithm is presented. It constrains the dependence scope, relying on physical positions, and is able to deal with more than one hundred thousand single nucleotide polymorphisms. The proposed algorithm is fast and does not require phase genotypic data.

  14. Probing Heterogeneity and Bonding at Silica Surfaces through Single-Molecule Investigation of Base-Mediated Linkage Failure.

    Science.gov (United States)

    Lupo, Katherine M; Hinton, Daniel A; Ng, James D; Padilla, Nicolas A; Goldsmith, Randall H

    2016-09-13

    The nature of silica surfaces is relevant to many chemical systems, including heterogeneous catalysis and chromatographies utilizing functionalized-silica stationary phases. Surface linkages must be robust to achieve wide and reliable applicability. However, silyl ether-silica support linkages are known to be susceptible to detachment when exposed to basic conditions. We use single-molecule spectroscopy to examine the rate of surface linkage failure upon exposure to base at a variety of deposition conditions. Kinetic analysis elucidates the role of thermal annealing and addition of blocking layers in increasing stability. Critically, it was found that successful surface modification strategies alter the rate at which base molecules approach the silica surface as opposed to reducing surface linkage reactivity. Our results also demonstrate that the innate structural diversity of the silica surface is likely the cause of observed heterogeneity in surface-linkage disruption kinetics.

  15. Producer Services, Manufacturing Linkages, and Trade

    NARCIS (Netherlands)

    J.F. François (Joseph); J. Kepler; J. Woerz

    2007-01-01

    textabstractWorking with a mix of panel data on goods and services trade for the OECD for 1994-2004, combined with social accounts data (i.e. data on intermediate linkages) for 78 countries benchmarked to the panel midpoint, we examine the role of services as inputs in manufacturing, with a particul

  16. The Barley Chromosome 5 Linkage Map

    DEFF Research Database (Denmark)

    Jensen, J.; Jørgensen, Jørgen Helms

    1975-01-01

    : wst5 (white streaks), necl (necrotic leaf spots), Ml-nn (powdery mildew resistance), and Pa4 (leaf rust resistance). Further, the two sections of the map are united, and the precision of the map is improved. A system for designating the positions of the loci on the linkage map is proposed. A 0...

  17. A RAD-based linkage map and comparative genomics in the gudgeons (genus Gnathopogon, Cyprinidae

    Directory of Open Access Journals (Sweden)

    Kakioka Ryo

    2013-01-01

    Full Text Available Abstract Background The construction of linkage maps is a first step in exploring the genetic basis for adaptive phenotypic divergence in closely related species by quantitative trait locus (QTL analysis. Linkage maps are also useful for comparative genomics in non-model organisms. Advances in genomics technologies make it more feasible than ever to study the genetics of adaptation in natural populations. Restriction-site associated DNA (RAD sequencing in next-generation sequencers facilitates the development of many genetic markers and genotyping. We aimed to construct a linkage map of the gudgeons of the genus Gnathopogon (Cyprinidae for comparative genomics with the zebrafish Danio rerio (a member of the same family as gudgeons and for the future QTL analysis of the genetic architecture underlying adaptive phenotypic evolution of Gnathopogon. Results We constructed the first genetic linkage map of Gnathopogon using a 198 F2 interspecific cross between two closely related species in Japan: river-dwelling Gnathopogon elongatus and lake-dwelling Gnathopogon caerulescens. Based on 1,622 RAD-tag markers, a linkage map spanning 1,390.9 cM with 25 linkage groups and an average marker interval of 0.87 cM was constructed. We also identified a region involving female-specific transmission ratio distortion (TRD. Synteny and collinearity were extensively conserved between Gnathopogon and zebrafish. Conclusions The dense SNP-based linkage map presented here provides a basis for future QTL analysis. It will also be useful for transferring genomic information from a “traditional” model fish species, zebrafish, to screen candidate genes underlying ecologically important traits of the gudgeons.

  18. A RAD-based linkage map and comparative genomics in the gudgeons (genus Gnathopogon, Cyprinidae)

    Science.gov (United States)

    2013-01-01

    Background The construction of linkage maps is a first step in exploring the genetic basis for adaptive phenotypic divergence in closely related species by quantitative trait locus (QTL) analysis. Linkage maps are also useful for comparative genomics in non-model organisms. Advances in genomics technologies make it more feasible than ever to study the genetics of adaptation in natural populations. Restriction-site associated DNA (RAD) sequencing in next-generation sequencers facilitates the development of many genetic markers and genotyping. We aimed to construct a linkage map of the gudgeons of the genus Gnathopogon (Cyprinidae) for comparative genomics with the zebrafish Danio rerio (a member of the same family as gudgeons) and for the future QTL analysis of the genetic architecture underlying adaptive phenotypic evolution of Gnathopogon. Results We constructed the first genetic linkage map of Gnathopogon using a 198 F2 interspecific cross between two closely related species in Japan: river-dwelling Gnathopogon elongatus and lake-dwelling Gnathopogon caerulescens. Based on 1,622 RAD-tag markers, a linkage map spanning 1,390.9 cM with 25 linkage groups and an average marker interval of 0.87 cM was constructed. We also identified a region involving female-specific transmission ratio distortion (TRD). Synteny and collinearity were extensively conserved between Gnathopogon and zebrafish. Conclusions The dense SNP-based linkage map presented here provides a basis for future QTL analysis. It will also be useful for transferring genomic information from a “traditional” model fish species, zebrafish, to screen candidate genes underlying ecologically important traits of the gudgeons. PMID:23324215

  19. Molecular Genetic Diagnostics of Prader-Willi Syndrome: a Validation of Linkage Analysis for the Chinese Population%普拉德-威利综合征的分子遗传诊断:一种连锁分析方法的初步建立

    Institute of Scientific and Technical Information of China (English)

    李洪义; 孟舒; 陈争; 李海飞; 杜敏联; 马华梅; 魏海云; 段红蕾; 郑辉; 闻人庆; 宋新明

    2007-01-01

    普拉德-威利综合征(Prader-Willi Syndrome,PWS)是一种基因组印记相关的疾病,是引起肥胖最常见的遗传综合征.分子和细胞遗传学检查对于该病早期诊断非常重要.通过选择PWS典型缺失区域内、外的STR遗传标记,初步建立了一种适用于中国人群的PWS核心家庭连锁分析方法,并用该方法确定了一例缺失型和一例异源单亲二体型PWS患者,经甲基化特异性PCR和高分辨染色体核型分析验证上述结果正确.同时,该连锁分析方法可以具体区分PWS的分子发病类型,从而为PWS家庭的遗传咨询提供信息,并为进一步研究PWS基因型和表型的关系提供了可能.%Prader-Willi Syndrome (PWS) is a genetic disorder that is difficult to detect, particularly at an early age. PWS is caused by disruption of normal, epigenetically controlled gene function in the chromosome 15q11-q13 region. Clinical symptoms are difficult to diagnose in infants and only become clearer at later ages as the patients develop hyperphagia and morbid obesity. Molecular genetic tests are able to definitively diagnose PWS and allow early diagnosis of the syndrome. High resolution cytogenetic testing, methylation-specific PCR (MS-PCR), and linkage analysis are routinely used to diagnose PWS. To establish a linkage analysis method for Chinese patients, this study identified a useful set of STR markers in the typical PWS deletion and adjacent area, for linkage analysis in two Chinese families with PWS offspring. Using this method, the authors confirmed that one patient had a paternal deletion in chromosome 15q11-q13 and the other patient had maternal uniparental heterodisomy of chromosome 15. MS-PCR and high resolution chromosome G-banding also confirmed this diagnosis. This linkage analysis method can detect both deletion and uniparental disomy, thus providing valuable information for genetic counseling and the opportunity to analyze the relationship between the genotype and

  20. Linkage of preaxial polydactyly type 2 to 7q36

    Energy Technology Data Exchange (ETDEWEB)

    Hing, A.V.; Slaugh, R.; Dowton, S.B. [Washington Univ. School of Medicine, St. Louis, MO (United States)] [and others

    1995-08-28

    We have characterized a 6-generation North American Caucasian kindred segregating one form of preaxial polydactyly type 2 (PPD-2). We demonstrate linkage to the 7q36 region and describe a submicroscopic telomeric chromosomal deletion in phase with the PPD-2 phenotype. Recently, several kindreds segregating triphalangeal thumb (TPT) with and without associated hand anomalies (syndactyly and/or postaxial polydactyly) have also been linked to the subtelomeric region of chromosome 7q. We demonstrate by haplotype analysis that our North American pedigree represents a PPD allele that is independent of the founder PPD allele present in the previously described kindreds. 23 refs., 5 figs., 2 tabs.