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Sample records for single locus mismatch

  1. Single-mismatch 2LSB embedding method of steganography

    OpenAIRE

    Khalind, Omed; Aziz, Benjamin

    2013-01-01

    This paper proposes a new method of 2LSB embedding steganography in still images. The proposed method considers a single mismatch in each 2LSB embedding between the 2LSB of the pixel value and the 2-bits of the secret message, while the 2LSB replacement overwrites the 2LSB of the image’s pixel value with 2-bits of the secret message. The number of bit-changes needed for the proposed method is 0.375 bits from the 2LSBs of the cover image, and is much less than the 2LSB replacement which is 0.5...

  2. Single locus complementary sex determination in Hymenoptera : an "unintelligent" design?

    NARCIS (Netherlands)

    Wilgenburg, Ellen van; Driessen, Gerard; Beukeboom, Leo W.

    2006-01-01

    The haplodiploid sex determining mechanism in Hymenoptera (males are haploid, females are diploid) has played an important role in the evolution of this insect order. In Hymenoptera sex is usually determined by a single locus, heterozygotes are female and hemizygotes are male. Under inbreeding,

  3. Single locus complementary sex determination in Hymenoptera: an "unintelligent" design?

    NARCIS (Netherlands)

    van Wilgenburg, E.; Driessen, G.J.J.; Beukeboom, L.W.

    2006-01-01

    The haplodiploid sex determining mechanism in Hymenoptera (males are haploid, females are diploid) has played an important role in the evolution of this insect order. In Hymenoptera sex is usually determined by a single locus, heterozygotes are female and hemizygotes are male. Under inbreeding,

  4. Extensive gene conversion at the PMS2 DNA mismatch repair locus.

    Science.gov (United States)

    Hayward, Bruce E; De Vos, Michel; Valleley, Elizabeth M A; Charlton, Ruth S; Taylor, Graham R; Sheridan, Eamonn; Bonthron, David T

    2007-05-01

    Mutations of the PMS2 DNA repair gene predispose to a characteristic range of malignancies, with either childhood onset (when both alleles are mutated) or a partially penetrant adult onset (if heterozygous). These mutations have been difficult to detect, due to interference from a family of pseudogenes located on chromosome 7. One of these, the PMS2CL pseudogene, lies within a 100-kb inverted duplication (inv dup), 700 kb centromeric to PMS2 itself on 7p22. Here, we show that the reference genomic sequences cannot be relied upon to distinguish PMS2 from PMS2CL, because of sequence transfer between the two loci. The 7p22 inv dup occurred prior to the divergence of modern ape species (15 million years ago [Mya]), but has undergone extensive sequence homogenization. This process appears to be ongoing, since there is considerable allelic diversity within the duplicated region, much of it derived from sequence exchange between PMS2 and PMS2CL. This sequence diversity can result in both false-positive and false-negative mutation analysis at this locus. Great caution is still needed in the design and interpretation of PMS2 mutation screens. 2007 Wiley-Liss, Inc.

  5. Single locus complementary sex determination in Hymenoptera: an "unintelligent" design?

    Directory of Open Access Journals (Sweden)

    Driessen Gerard

    2006-01-01

    Full Text Available Abstract The haplodiploid sex determining mechanism in Hymenoptera (males are haploid, females are diploid has played an important role in the evolution of this insect order. In Hymenoptera sex is usually determined by a single locus, heterozygotes are female and hemizygotes are male. Under inbreeding, homozygous diploid and sterile males occur which form a genetic burden for a population. We review life history and genetical traits that may overcome the disadvantages of single locus complementary sex determination (sl-CSD. Behavioural adaptations to avoid matings between relatives include active dispersal from natal patches and mating preferences for non-relatives. In non-social species, temporal and spatial segregation of male and female offspring reduces the burden of sl-CSD. In social species, diploid males are produced at the expense of workers and female reproductives. In some social species, diploid males and diploid male producing queens are killed by workers. Diploid male production may have played a role in the evolution or maintenance of polygyny (multiple queens and polyandry (multiple mating. Some forms of thelytoky (parthenogenetic female production increase homozygosity and are therefore incompatible with sl-CSD. We discuss a number of hypothetical adaptations to sl-CSD which should be considered in future studies of this insect order.

  6. Significance of single ventilation/perfusion mismatches in krypton-81m/technetium-99m lung scintigraphy

    International Nuclear Information System (INIS)

    Rosen, J.M.; Palestro, C.J.; Markowitz, D.; Alderson, P.O.

    1986-01-01

    The significance of a single area of ventilation/perfusion (V/P) mismatch in lung scans performed on patients suspected of pulmonary embolism (PE) was evaluated. Ten of 20 patients with this scan finding were found to have PE. An intermediate probability of PE was found with segmental (71%) or subsegmental (45%) single V/P mismatches. Seven of 16 patients with a single V/P mismatch and without a matching radiographic opacity had PE. Three of the four patients who had a V/P mismatch and a matching radiographic opacity were found to have PE. Multiview ventilation imaging with 81mKr was found to have advantages for the evaluation of single V/P mismatches. Based on the data available at this time, a single V/P mismatch suggests an intermediate probability of PE

  7. Mismatched single stranded antisense oligonucleotides can induce efficient dystrophin splice switching

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    Kole Ryszard

    2011-10-01

    Full Text Available Abstract Background Antisense oligomer induced exon skipping aims to reduce the severity of Duchenne muscular dystrophy by redirecting splicing during pre-RNA processing such that the causative mutation is by-passed and a shorter but partially functional Becker muscular dystrophy-like dystrophin isoform is produced. Normal exons are generally targeted to restore the dystrophin reading frame however, an appreciable subset of dystrophin mutations are intra-exonic and therefore have the potential to compromise oligomer efficiency, necessitating personalised oligomer design for some patients. Although antisense oligomers are easily personalised, it remains unclear whether all patient polymorphisms within antisense oligomer target sequences will require the costly process of producing and validating patient specific compounds. Methods Here we report preclinical testing of a panel of splice switching antisense oligomers, designed to excise exon 25 from the dystrophin transcript, in normal and dystrophic patient cells. These patient cells harbour a single base insertion in exon 25 that lies within the target sequence of an oligomer shown to be effective at removing exon 25. Results It was anticipated that such a mutation would compromise oligomer binding and efficiency. However, we show that, despite the mismatch an oligomer, designed and optimised to excise exon 25 from the normal dystrophin mRNA, removes the mutated exon 25 more efficiently than the mutation-specific oligomer. Conclusion This raises the possibility that mismatched AOs could still be therapeutically applicable in some cases, negating the necessity to produce patient-specific compounds.

  8. Femtomolar detection of single mismatches by discriminant analysis of DNA hybridization events using gold nanoparticles.

    Science.gov (United States)

    Ma, Xingyi; Sim, Sang Jun

    2013-03-21

    Even though DNA-based nanosensors have been demonstrated for quantitative detection of analytes and diseases, hybridization events have never been numerically investigated for further understanding of DNA mediated interactions. Here, we developed a nanoscale platform with well-designed capture and detection gold nanoprobes to precisely evaluate the hybridization events. The capture gold nanoprobes were mono-laid on glass and the detection probes were fabricated via a novel competitive conjugation method. The two kinds of probes combined in a suitable orientation following the hybridization with the target. We found that hybridization efficiency was markedly dependent on electrostatic interactions between DNA strands, which can be tailored by adjusting the salt concentration of the incubation solution. Due to the much lower stability of the double helix formed by mismatches, the hybridization efficiencies of single mismatched (MMT) and perfectly matched DNA (PMT) were different. Therefore, we obtained an optimized salt concentration that allowed for discrimination of MMT from PMT without stringent control of temperature or pH. The results indicated this to be an ultrasensitive and precise nanosensor for the diagnosis of genetic diseases.

  9. An unusual occurrence of repeated single allele variation on Y-STR locus DYS458

    OpenAIRE

    Shrivastava, Pankaj; Trivedi, Veena Ben; Jain, Toshi; Ali, Mehmood

    2016-01-01

    Six brothers were accused of gagging and raping a woman. A single male Y-STR profile was obtained from vaginal smear swab and clothes of the victim, which did not match with the DNA profile of the accused brothers. As a reference point, the blood sample of their father (aged 87 years) was also analyzed with the same kit. The Y-STR haplotype of all six brothers was found to be the same as that of their father except at locus DYS458. At this locus, while the eldest, second and fourth siblings s...

  10. An unusual occurrence of repeated single allele variation on Y-STR locus DYS458

    Directory of Open Access Journals (Sweden)

    Pankaj Shrivastava

    2016-09-01

    Full Text Available Six brothers were accused of gagging and raping a woman. A single male Y-STR profile was obtained from vaginal smear swab and clothes of the victim, which did not match with the DNA profile of the accused brothers. As a reference point, the blood sample of their father (aged 87 years was also analyzed with the same kit. The Y-STR haplotype of all six brothers was found to be the same as that of their father except at locus DYS458. At this locus, while the eldest, second and fourth siblings share allele 18 with their father, a loss of one repeat (allele 17 instead of 18 is observed in the third son while fifth and sixth siblings have allele 19 representing a gain of one repeat. Thus, two changes viz. a gain (twice and loss of one repeat at this locus in one generation is both interesting and unusual.

  11. A silent allele in the locus D5S818 contained within the PowerPlex®21 PCR Amplification Kit.

    Science.gov (United States)

    Chen, Ling; Tai, Yunchun; Qiu, Pingming; Du, Weian; Liu, Chao

    2015-11-01

    Three paternity tests cases were found with a single locus mismatch at the locus D5S818 with PowerPlex®21 PCR Amplification Kit (Promega). Forward and reverse primers were redesigned to type the samples again and to evaluate if there were alleles dropped out. The results showed the existence of a silent allele 12 in all the three families, due to a point mutation that changed cytosine to adenine at 90 nucleotides upstream from the 5' end of the AGAT repeat sequences in all the six individuals. A single locus mismatch due to a silent allele may occur in any locus using any kit. Therefore, we recommend using multiple kits to confirm the results in paternity testing cases with mismatches, especially when there is a single locus mismatch with homozygote involved. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Single-locus complementary sex determination in the inbreeding wasp Euodynerus foraminatus Saussure (Hymenoptera: Vespidae).

    Science.gov (United States)

    Stahlhut, J K; Cowan, D P

    2004-03-01

    The Hymenoptera have arrhenotokous haplodiploidy in which males normally develop from unfertilized eggs and are haploid, while females develop from fertilized eggs and are diploid. Multiple sex determination systems are known to underlie haplodiploidy, and the best understood is single-locus complementary sex determination (sl-CSD) in which sex is determined at a single polymorphic locus. Individuals heterozygous at the sex locus develop as females; individuals that are hemizygous (haploid) or homozygous (diploid) at the sex locus develop as males. sl-CSD can be detected with inbreeding experiments that produce diploid males in predictable proportions as well as sex ratio shifts due to diploid male production. This sex determination system is considered incompatible with inbreeding because the ensuing increase in homozygosity increases the production of diploid males that are inviable or infertile, imposing a high cost on matings between close relatives. However, in the solitary hunting wasp Euodynerus foraminatus, a species suspected of having sl-CSD, inbreeding may be common due to a high incidence of sibling matings at natal nests. In laboratory crosses with E. foraminatus, we find that sex ratios and diploid male production (detected as microsatellite heterozygosity) are consistent with sl-CSD, but not with other sex determination systems. This is the first documented example of sl-CSD in a hymenopteran with an apparent natural history of inbreeding, and thus presents a paradox for our understanding of hymenopteran genetics.

  13. Single locus affects embryonic segment polarity and multiple aspects of an adult evolutionary novelty

    Directory of Open Access Journals (Sweden)

    Saenko Suzanne V

    2010-08-01

    Full Text Available Abstract Background The characterization of the molecular changes that underlie the origin and diversification of morphological novelties is a key challenge in evolutionary developmental biology. The evolution of such traits is thought to rely largely on co-option of a toolkit of conserved developmental genes that typically perform multiple functions. Mutations that affect both a universal developmental process and the formation of a novelty might shed light onto the genetics of traits not represented in model systems. Here we describe three pleiotropic mutations with large effects on a novel trait, butterfly eyespots, and on a conserved stage of embryogenesis, segment polarity. Results We show that three mutations affecting eyespot size and/or colour composition in Bicyclus anynana butterflies occurred in the same locus, and that two of them are embryonic recessive lethal. Using surgical manipulations and analysis of gene expression patterns in developing wings, we demonstrate that the effects on eyespot morphology are due to changes in the epidermal response component of eyespot induction. Our analysis of morphology and of gene expression in mutant embryos shows that they have a typical segment polarity phenotype, consistent with the mutant locus encoding a negative regulator of Wingless signalling. Conclusions This study characterizes the segregation and developmental effects of alleles at a single locus that controls the morphology of a lineage-specific trait (butterfly eyespots and a conserved process (embryonic segment polarity and, specifically, the regulation of Wingless signalling. Because no gene with such function was found in the orthologous, highly syntenic genomic regions of two other lepidopterans, we hypothesize that our locus is a yet undescribed, possibly lineage-specific, negative regulator of the conserved Wnt/Wg pathway. Moreover, the fact that this locus interferes with multiple aspects of eyespot morphology and maps to a

  14. Unaccusative Mismatches in Japanese.

    Science.gov (United States)

    Tsujimura, Natsuko

    Two instances of unaccusative verb mismatches in Japanese are examined. An unaccusative mismatch is the situation in which a different accusative diagnostic singles out different classes of intransitive verbs within and across languages. One type of unaccusative mismatch has to do with group C verbs, or verbs of manner with protagonist control.…

  15. Natural selection maintains a single-locus leaf shape cline in Ivyleaf morning glory, Ipomoea hederacea.

    Science.gov (United States)

    Campitelli, Brandon E; Stinchcombe, John R

    2013-02-01

    Clines in phenotypic traits with an underlying genetic basis potentially implicate natural selection. However, neutral evolutionary processes such as random colonization, spatially restricted gene flow, and genetic drift could also result in similar spatial patterns, especially for single-locus traits because of their susceptibility to stochastic events. One way to distinguish between adaptive and neutral mechanisms is to compare the focal trait to neutral genetic loci to determine whether neutral loci demonstrate clinal variation (consistent with a neutral cline), or not. Ivyleaf morning glory, Ipomoea hederacea, exhibits a latitudinal cline for a Mendelian leaf shape polymorphism in eastern North America, such that lobed genotypes dominate northern populations and heart-shaped genotypes are restricted to southern populations. Here, we evaluate potential evolutionary mechanisms for this cline by first determining the allele frequencies at the leaf shape locus for 77 populations distributed throughout I. hederacea's range and then comparing the geographical pattern at this locus to neutral amplified fragment length polymorphism (AFLP) loci. We detected both significant clinal variation and high genetic differentiation at the leaf shape locus across all populations. In contrast, 99% of the putatively neutral loci do not display clinal variation, and I. hederacea populations show very little overall genetic differentiation, suggesting that there is a moderate level of gene flow. In addition, the leaf shape locus was identified as a major F(ST) outlier experiencing divergent selection, relative to all the AFLP loci. Together, these data strongly suggest that the cline in leaf shape is being maintained by spatially varying natural selection. © 2012 Blackwell Publishing Ltd.

  16. Fast and quantitative differentiation of single-base mismatched DNA by initial reaction rate of catalytic hairpin assembly.

    Science.gov (United States)

    Li, Chenxi; Li, Yixin; Xu, Xiao; Wang, Xinyi; Chen, Yang; Yang, Xiaoda; Liu, Feng; Li, Na

    2014-10-15

    The widely used catalytic hairpin assembly (CHA) amplification strategy generally needs several hours to accomplish one measurement based on the prevailingly used maximum intensity detection mode, making it less practical for assays where high throughput or speed is desired. To make the best use of the kinetic specificity of toehold domain for circuit reaction initiation, we developed a mathematical model and proposed an initial reaction rate detection mode to quantitatively differentiate the single-base mismatch. Using the kinetic mode, assay time can be reduced substantially to 10 min for one measurement with the comparable sensitivity and single-base mismatch differentiating ability as were obtained by the maximum intensity detection mode. This initial reaction rate based approach not only provided a fast and quantitative differentiation of single-base mismatch, but also helped in-depth understanding of the CHA system, which will be beneficial to the design of highly sensitive and specific toehold-mediated hybridization reactions. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. HIV control through a single nucleotide on the HLA-B locus

    DEFF Research Database (Denmark)

    Kløverpris, Henrik N; Harndahl, Mikkel; Leslie, Alasdair J

    2012-01-01

    Genetic variation within the HLA-B locus has the strongest impact on HIV disease progression of any polymorphisms within the human genome. However, identifying the exact mechanism involved is complicated by several factors. HLA-Bw4 alleles provide ligands for NK cells and for CD8 T cells, and str......Genetic variation within the HLA-B locus has the strongest impact on HIV disease progression of any polymorphisms within the human genome. However, identifying the exact mechanism involved is complicated by several factors. HLA-Bw4 alleles provide ligands for NK cells and for CD8 T cells......:02, which differ by only a single amino acid. Crucially, they occur primarily on identical HLA class I haplotypes and, as Bw6 alleles, do not act as NK cell ligands and are therefore largely unconfounded by other genetic factors. We show that in an outbred cohort (n = 2,093) of HIV C......-clade-infected individuals, a single amino acid change at position 9 of the HLA-B molecule critically affects peptide binding and significantly alters the cytotoxic T lymphocyte (CTL) epitopes targeted, measured directly ex vivo by gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assay (P = 2 × 10...

  18. J-integral analysis of heterogeneous mismatched girth welds in clamped single-edge notched tension specimens

    International Nuclear Information System (INIS)

    Hertelé, Stijn; De Waele, Wim; Verstraete, Matthias; Denys, Rudi; O'Dowd, Noel

    2014-01-01

    Flaw assessment procedures require a quantification of crack driving force, and such procedures are generally based on the assumption of weld homogeneity. However, welds generally have a heterogeneous microstructure, which will influence the crack driving force. This paper describes a stress-based methodology to assess complex heterogeneous welds using a J-based approach. Clamped single-edge notched tension specimens, representative of girth weld flaws, are analyzed and the influence of weld heterogeneity on crack driving force has been determined. The use of a modified limit load for heterogeneous welds is proposed, suitable for implementation in a ‘homogenized’ J-integral estimation scheme. It follows from an explicit modification of an existing solution for centre cracked tension specimens. The proposed solution provides a good estimate of crack driving force and any errors in the approximation may be accounted for by means of a small safety factor on load bearing capacity. - Highlights: • We present a crack driving force estimation procedure for heterogeneous welds. • The procedure is based on a ‘homogenized’ version of the EPRI equation. • Complex welds are translated into equivalent idealized mismatched welds. • The procedure is validated for clamped SE(T) specimens. • A mismatch limit load for clamped SE(T) specimens is developed

  19. Development of a Single Locus Sequence Typing (SLST) Scheme for Typing Bacterial Species Directly from Complex Communities.

    Science.gov (United States)

    Scholz, Christian F P; Jensen, Anders

    2017-01-01

    The protocol describes a computational method to develop a Single Locus Sequence Typing (SLST) scheme for typing bacterial species. The resulting scheme can be used to type bacterial isolates as well as bacterial species directly from complex communities using next-generation sequencing technologies.

  20. Nanoparticle-functionalized nucleic acids: A strategy for amplified electrochemical detection of some single-base mismatches

    Energy Technology Data Exchange (ETDEWEB)

    Ahangar, Laleh Enayati [Department of Chemistry, University of Isfahan, Isfahan 81746-73441 (Iran, Islamic Republic of); Mehrgardi, Masoud A., E-mail: m.mehrgardi@gmail.co [Department of Chemistry, University of Isfahan, Isfahan 81746-73441 (Iran, Islamic Republic of)

    2011-02-15

    In this study, nanoparticle-functionalized nucleic acids were employed to improve the sensitivity of electrochemical DNA biosensors that make capable them to detect different types of single-base mismatches (SBMs), including thermodynamically stable ones. The present biosensor was constructed by the immobilization of platinum nanoparticles (Pt-NPs) on the surface of a carbon paste electrode (CPE) via SH-functionalized DNA. A redox probe of 2-mercapto-1-methyl imidazole (MMI), which has different electrochemical behavior on Pt-NP and CPE, was used. This behavior helps to overcome the pinhole effect in DNA hybridization biosensors. Additionally, in the present biosensor, the positioning of the redox probe under the SBM in DNA, which decreases the sensitivity of most DNA biosensors, did not contribute to the observed electrochemical signal.

  1. Nanoparticle-functionalized nucleic acids: A strategy for amplified electrochemical detection of some single-base mismatches

    International Nuclear Information System (INIS)

    Ahangar, Laleh Enayati; Mehrgardi, Masoud A.

    2011-01-01

    In this study, nanoparticle-functionalized nucleic acids were employed to improve the sensitivity of electrochemical DNA biosensors that make capable them to detect different types of single-base mismatches (SBMs), including thermodynamically stable ones. The present biosensor was constructed by the immobilization of platinum nanoparticles (Pt-NPs) on the surface of a carbon paste electrode (CPE) via SH-functionalized DNA. A redox probe of 2-mercapto-1-methyl imidazole (MMI), which has different electrochemical behavior on Pt-NP and CPE, was used. This behavior helps to overcome the pinhole effect in DNA hybridization biosensors. Additionally, in the present biosensor, the positioning of the redox probe under the SBM in DNA, which decreases the sensitivity of most DNA biosensors, did not contribute to the observed electrochemical signal.

  2. Single nucleotide polymorphisms of DNA mismatch repair genes MSH2 and MLH1 confer susceptibility to esophageal cancer.

    Science.gov (United States)

    Sun, Ming-Zhong; Ju, Hui-Xiang; Zhou, Zhong-Wei; Jin, Hao; Zhu, Rong

    2014-01-01

    Defects in DNA mismatch repair genes like MSH2 and MLH1 confer increased risk of cancers. Here, single nucleotide polymorphisms (SNPs) in MSH2 and MLH1 were investigated for their potential contribution to the risk of esophageal cancer. This study recruited 614 participants from Affiliated Yancheng Hospital, School of Medicine, Southeast University, of which 289 were patients with esophageal cancer, and the remainder was healthy individuals who served as a control group. Two SNPs, MSH2 c.2063T>G and MLH1 IVS14-19A>G, were genotyped using PCR-RFLP. Statistical analysis was performed using chi-square test and logistic regression analysis. Carriers of the MSH2 c.2063G allele were at significantly higher risk for esophageal cancer compared to individuals with the TT genotype [OR = 3.36, 95% confidence interval (CI): 1.18-11.03]. The MLH1 IVS14-19A>G allele also conferred significantly increased (1.70-fold) for esophageal cancer compared to the AA genotype (OR = 1.70, 95% CI: 1.13-5.06). Further, the variant alleles interacted such that individuals with the susceptible genotypes at both MSH2 and MLH1 had a significantly exacerbated risk for esophageal cancer (OR = 12.38, 95% CI: 3.09-63.11). In brief, SNPs in the DNA mismatch repair genes MSH2 and MLH1 increase the risk of esophageal cancer. Molecular investigations are needed to uncover the mechanism behind their interaction effect.

  3. Is there a differential strength of specific HLA mismatches in kidney transplants?

    Science.gov (United States)

    Sasaki, N; Idica, A; Terasaki, P

    2008-05-01

    In this article we attempted to identify whether there is a specific mismatched antigen that might be detrimental to kidney transplant outcome. The frequency of function versus failure of transplant cases was tallied within subpopulations among a subset of the 2006 United Network for Organ Sharing transplant dataset. We examined 7998 cadaveric and 11,420 living donor kidney transplants that were mismatched for a single class I antigen. When tested by five different criteria, the results were relatively similar for the HLA class I, A- and B-locus mismatches. HLA A1 was identified as the single most dominant immunogenic mismatch. However, when the P values were multiplied by 68, the number of comparisons, A1 was only marginally significant. We concluded that at least for class I specificities, the 68 specificities were about equal immunogenicity in kidney transplantation.

  4. Effects of phylogenetic reconstruction method on the robustness of species delimitation using single-locus data.

    Science.gov (United States)

    Tang, Cuong Q; Humphreys, Aelys M; Fontaneto, Diego; Barraclough, Timothy G; Paradis, Emmanuel

    2014-10-01

    Coalescent-based species delimitation methods combine population genetic and phylogenetic theory to provide an objective means for delineating evolutionarily significant units of diversity. The generalised mixed Yule coalescent (GMYC) and the Poisson tree process (PTP) are methods that use ultrametric (GMYC or PTP) or non-ultrametric (PTP) gene trees as input, intended for use mostly with single-locus data such as DNA barcodes. Here, we assess how robust the GMYC and PTP are to different phylogenetic reconstruction and branch smoothing methods. We reconstruct over 400 ultrametric trees using up to 30 different combinations of phylogenetic and smoothing methods and perform over 2000 separate species delimitation analyses across 16 empirical data sets. We then assess how variable diversity estimates are, in terms of richness and identity, with respect to species delimitation, phylogenetic and smoothing methods. The PTP method generally generates diversity estimates that are more robust to different phylogenetic methods. The GMYC is more sensitive, but provides consistent estimates for BEAST trees. The lower consistency of GMYC estimates is likely a result of differences among gene trees introduced by the smoothing step. Unresolved nodes (real anomalies or methodological artefacts) affect both GMYC and PTP estimates, but have a greater effect on GMYC estimates. Branch smoothing is a difficult step and perhaps an underappreciated source of bias that may be widespread among studies of diversity and diversification. Nevertheless, careful choice of phylogenetic method does produce equivalent PTP and GMYC diversity estimates. We recommend simultaneous use of the PTP model with any model-based gene tree (e.g. RAxML) and GMYC approaches with BEAST trees for obtaining species hypotheses.

  5. High affinity γPNA sandwich hybridization assay for rapid detection of short nucleic acid targets with single mismatch discrimination.

    Science.gov (United States)

    Goldman, Johnathan M; Zhang, Li Ang; Manna, Arunava; Armitage, Bruce A; Ly, Danith H; Schneider, James W

    2013-07-08

    Hybridization analysis of short DNA and RNA targets presents many challenges for detection. The commonly employed sandwich hybridization approach cannot be implemented for these short targets due to insufficient probe-target binding strengths for unmodified DNA probes. Here, we present a method capable of rapid and stable sandwich hybridization detection for 22 nucleotide DNA and RNA targets. Stable hybridization is achieved using an n-alkylated, polyethylene glycol γ-carbon modified peptide nucleic acid (γPNA) amphiphile. The γPNA's exceptionally high affinity enables stable hybridization of a second DNA-based probe to the remaining bases of the short target. Upon hybridization of both probes, an electrophoretic mobility shift is measured via interaction of the n-alkane modification on the γPNA with capillary electrophoresis running buffer containing nonionic surfactant micelles. We find that sandwich hybridization of both probes is stable under multiple binding configurations and demonstrate single base mismatch discrimination. The binding strength of both probes is also stabilized via coaxial stacking on adjacent hybridization to targets. We conclude with a discussion on the implementation of the proposed sandwich hybridization assay as a high-throughput microRNA detection method.

  6. The Influence of Pelvic Incidence and Lumbar Lordosis Mismatch on Development of Symptomatic Adjacent Level Disease Following Single-Level Transforaminal Lumbar Interbody Fusion.

    Science.gov (United States)

    Tempel, Zachary J; Gandhoke, Gurpreet S; Bolinger, Bryan D; Khattar, Nicolas K; Parry, Philip V; Chang, Yue-Fang; Okonkwo, David O; Kanter, Adam S

    2017-06-01

    Annual incidence of symptomatic adjacent level disease (ALD) following lumbar fusion surgery ranges from 0.6% to 3.9% per year. Sagittal malalignment may contribute to the development of ALD. To describe the relationship between pelvic incidence-lumbar lordosis (PI-LL) mismatch and the development of symptomatic ALD requiring revision surgery following single-level transforaminal lumbar interbody fusion for degenerative lumbar spondylosis and/or low-grade spondylolisthesis. All patients who underwent a single-level transforaminal lumbar interbody fusion at either L4/5 or L5/S1 between July 2006 and December 2012 were analyzed for pre- and postoperative spinopelvic parameters. Using univariate and logistic regression analysis, we compared the spinopelvic parameters of those patients who required revision surgery against those patients who did not develop symptomatic ALD. We calculated the predictive value of PI-LL mismatch. One hundred fifty-nine patients met the inclusion criteria. The results noted that, for a 1° increase in PI-LL mismatch (preop and postop), the odds of developing ALD requiring surgery increased by 1.3 and 1.4 fold, respectively, which were statistically significant increases. Based on our analysis, a PI-LL mismatch of >11° had a positive predictive value of 75% for the development of symptomatic ALD requiring revision surgery. A high PI-LL mismatch is strongly associated with the development of symptomatic ALD requiring revision lumbar spine surgery. The development of ALD may represent a global disease process as opposed to a focal condition. Spine surgeons may wish to consider assessment of spinopelvic parameters in the evaluation of degenerative lumbar spine pathology. Copyright © 2017 by the Congress of Neurological Surgeons

  7. Single-Locus versus Multilocus Patterns of Local Adaptation to Climate in Eastern White Pine (Pinus strobus, Pinaceae.

    Directory of Open Access Journals (Sweden)

    Om P Rajora

    Full Text Available Natural plant populations are often adapted to their local climate and environmental conditions, and populations of forest trees offer some of the best examples of this pattern. However, little empirical work has focused on the relative contribution of single-locus versus multilocus effects to the genetic architecture of local adaptation in plants/forest trees. Here, we employ eastern white pine (Pinus strobus to test the hypothesis that it is the inter-genic effects that primarily drive climate-induced local adaptation. The genetic structure of 29 range-wide natural populations of eastern white pine was determined in relation to local climatic factors using both a reference set of SSR markers, and SNPs located in candidate genes putatively involved in adaptive response to climate. Comparisons were made between marker sets using standard single-locus outlier analysis, single-locus and multilocus environment association analyses and a novel implementation of Population Graphs. Magnitudes of population structure were similar between the two marker sets. Outlier loci consistent with diversifying selection were rare for both SNPs and SSRs. However, genetic distances based on the multilocus among population covariances (cGD were significantly more correlated to climate, even after correcting for spatial effects, for SNPs as compared to SSRs. Coalescent simulations confirmed that the differences in mutation rates between SSRs and SNPs did not affect the topologies of the Population Graphs, and hence values of cGD and their correlations with associated climate variables. We conclude that the multilocus covariances among populations primarily reflect adaptation to local climate and environment in eastern white pine. This result highlights the complexity of the genetic architecture of adaptive traits, as well as the need to consider multilocus effects in studies of local adaptation.

  8. Label-free DNA hybridization detection and single base-mismatch discrimination using CE-ICP-MS assay.

    Science.gov (United States)

    Li, Yan; Sun, Shao-kai; Yang, Jia-lin; Jiang, Yan

    2011-12-07

    Detecting a specific DNA sequence and discriminating single base-mismatch is critical to clinical diagnosis, paternity testing, forensic sciences, food and drug industry, pathology, genetics, environmental monitoring, and anti-bioterrorism. To this end, capillary electrophoresis (CE) coupled with the inductively coupled plasma mass spectrometry (ICP-MS) method is developed using the displacing interaction between the target ssDNA and the competitor Hg(2+) for the first time. The thymine-rich capture ssDNA 1 is interacted with the competitor Hg(2+), forming an assembled complex in a hairpin-structure between the thymine bases arrangement at both sides of the capture ssDNA 1. In the presence of a target ssDNA with stronger affinity than that of the competitor Hg(2+), the energetically favorable hybridization between capture ssDNA 1 and the target ssDNA destroys the hairpin-structure and releases the competitor as free Hg(2+), which was then read out and accurately quantified by CE-ICP-MS assay. Under the optimal CE separation conditions, free Hg(2+) ions and its capture ssDNA 1 adduct were baseline separated and detected on-line by ICP-MS; the increased peak intensity of free Hg(2+) against the concentration of perfectly complementary target ssDNA was linear over the concentration range of 30-600 nmol L(-1) with a limit of detection of 8 nmol L(-1) (3s, n = 11) in the pre-incubated mixture containing 1 μmol L(-1) Hg(2+) and 0.2 μmol L(-1) capture ssDNA 1. This new assay method is simple in design since any target ssDNA binding can in principle result in free Hg(2+) release by 6-fold Hg(2+) signal amplification, avoiding oligonucleotide labeling or assistance by excess signal transducer and signal reporter to read out the target. Due to element-specific detection of ICP-MS in our assay procedure, the interference from the autofluorescence of substrata was eliminated.

  9. Single-Molecule Titration in a Protein Nanoreactor Reveals the Protonation/Deprotonation Mechanism of a C:C Mismatch in DNA.

    Science.gov (United States)

    Ren, Hang; Cheyne, Cameron G; Fleming, Aaron M; Burrows, Cynthia J; White, Henry S

    2018-04-18

    Measurement of single-molecule reactions can elucidate microscopic mechanisms that are often hidden from ensemble analysis. Herein, we report the acid-base titration of a single DNA duplex confined within the wild-type α-hemolysin (α-HL) nanopore for up to 3 h, while monitoring the ionic current through the nanopore. Modulation between two states in the current-time trace for duplexes containing the C:C mismatch in proximity to the latch constriction of α-HL is attributed to the base flipping of the C:C mismatch. As the pH is lowered, the rate for the C:C mismatch to flip from the intra-helical state to the extra-helical state ( k intra-extra ) decreases, while the rate for base flipping from the extra-helical state to the intra-helical state ( k extra-intra ) remains unchanged. Both k intra-extra and k extra-intra are on the order of 1 × 10 -2 s -1 to 1 × 10 -1 s -1 and remain stable over the time scale of the measurement (several hours). Analysis of the pH-dependent kinetics of base flipping using a hidden Markov kinetic model demonstrates that protonation/deprotonation occurs while the base pair is in the intra-helical state. We also demonstrate that the rate of protonation is limited by transport of H + into the α-HL nanopore. Single-molecule kinetic isotope experiments exhibit a large kinetic isotope effect (KIE) for k intra-extra ( k H / k D ≈ 5) but a limited KIE for k extra-intra ( k H / k D ≈ 1.3), supporting our model. Our experiments correspond to the longest single-molecule measurements performed using a nanopore, and demonstrate its application in interrogating mechanisms of single-molecule reactions in confined geometries.

  10. Multilocus genetic models of handedness closely resemble single-locus models in explaining family data and are compatible with genome-wide association studies.

    Science.gov (United States)

    McManus, I C; Davison, Angus; Armour, John A L

    2013-06-01

    Right- and left-handedness run in families, show greater concordance in monozygotic than dizygotic twins, and are well described by single-locus Mendelian models. Here we summarize a large genome-wide association study (GWAS) that finds no significant associations with handedness and is consistent with a meta-analysis of GWASs. The GWAS had 99% power to detect a single locus using the conventional criterion of P < 5 × 10(-8) for the single locus models of McManus and Annett. The strong conclusion is that handedness is not controlled by a single genetic locus. A consideration of the genetic architecture of height, primary ciliary dyskinesia, and intelligence suggests that handedness inheritance can be explained by a multilocus variant of the McManus DC model, classical effects on family and twins being barely distinguishable from the single locus model. Based on the ENGAGE meta-analysis of GWASs, we estimate at least 40 loci are involved in determining handedness. © 2013 New York Academy of Sciences.

  11. Robust Power Decoupling Control Scheme for DC Side Split Decoupling Capacitor Circuit with Mismatched Capacitance in Single Phase System

    DEFF Research Database (Denmark)

    Yao, Wenli; Loh, Poh Chiang; Tang, Yi

    2016-01-01

    dc capacitor to realize power decoupling, but the conventional power decoupling control scheme for this half-bridge circuit is developed with equal storage capacitances, which may vary in practice and degrade the ac and dc performance. The intention of this paper is to quantify ac and dc...... imperfections when storage mismatch occurs, which may break the standard requirement such as IEEE 1547. As a consequence, a robust control scheme is then proposed for half-bridge circuit, which realized power decoupling by generating second order harmonic voltage on the split dc decoupling capacitor instead...

  12. Production of multiple bacteriocins from a single locus by gastrointestinal strains of Lactobacillus salivarius.

    Science.gov (United States)

    O'Shea, Eileen F; O'Connor, Paula M; Raftis, Emma J; O'Toole, Paul W; Stanton, Catherine; Cotter, Paul D; Ross, R Paul; Hill, Colin

    2011-12-01

    Bacteriocins produced by Lactobacillus salivarius isolates derived from a gastrointestinal origin have previously demonstrated efficacy for in vivo protection against Listeria monocytogenes infection. In this study, comparative genomic analysis was employed to investigate the intraspecies diversity of seven L. salivarius isolates of human and porcine intestinal origin, based on the genome of the well-characterized bacteriocin-producing strain L. salivarius UCC118. This revealed a highly conserved megaplasmid-borne gene cluster in these strains involved in the regulation and secretion of two-component class IIb bacteriocins. However, considerable intraspecific variation was observed in the structural genes encoding the bacteriocin peptides. They ranged from close relatives of abp118, such as salivaricin P, which differs by 2 amino acids, to completely novel bacteriocins, such as salivaricin T, which is characterized in this study. Salivaricin T inhibits closely related lactobacilli and bears little homology to previously characterized salivaricins. Interestingly, the two peptides responsible for salivaricin T activity, SalTα and SalTβ, share considerable identity with the component peptides of thermophilin 13, a bacteriocin produced by Streptococcus thermophilus. Furthermore, the salivaricin locus of strain DPC6488 also encodes an additional novel one-component class IId anti-listerial bacteriocin, salivaricin L. These findings suggest a high level of redundancy in the bacteriocins that can be produced by intestinal L. salivarius isolates using the same enzymatic production and export machinery. Such diversity may contribute to their ability to dominate and compete within the complex microbiota of the mammalian gut.

  13. Technical aspects of typing for HLA-DP alleles using allele-specific DNA in vitro amplification and sequence-specific oligonucleotide probes. Detection of single base mismatches

    DEFF Research Database (Denmark)

    Fugger, L; Morling, N; Ryder, L P

    1990-01-01

    The polymerase chain reaction (PCR) is an effective method for in vitro DNA amplification which combined with probing with synthetic oligonucleotides can be used for, e.g., HLA-typing. We have studied the technical aspects of HLA-DP typing with the technique. DNA from mononuclear nucleated cells...... was extracted with either a simple salting out method or phenol/chloroform. Both DNAs could be readily used for PCR. The MgC2 concentration of the PCR buffer and the annealing temperature of the thermal cycle of the PCR were the two most important variables. The MgCl2 concentration and the temperature must...... be carefully titrated for each primer pair in the PCR. The influence of mismatches between the primer and the DNA template were studied and we found that, by using primers differing only from each other at the 3' end, cross-amplification of closely homologous alleles could be avoided. Thus, single base...

  14. Development and validation of a single-tube multiple-locus variable number tandem repeat analysis for Klebsiella pneumoniae.

    Directory of Open Access Journals (Sweden)

    Antoinette A T P Brink

    Full Text Available Genotyping of Klebsiella pneumoniae is indispensable for management of nosocomial infections, monitoring of emerging strains--including extended-spectrum beta-lactamase (ESBL producers-, and general epidemiology. Such objectives require a high-resolution genotyping method with a fixed scheme that allows (1 long-term retrospective and prospective assessment, (2 objective result readout and (3 library storage for database development and exchangeable results. We have developed a multiple-locus variable number tandem repeat analysis (MLVA using a single-tube fluorescently primed multiplex PCR for 8 Variable Number Tandem Repeats (VNTRs and automated fragment size analysis. The type allocation scheme was optimized using 224 K. pneumoniae clinical isolates, which yielded 101 MLVA types. The method was compared to the gold standard multilocus sequence typing (MLST using a subset of these clinical isolates (n = 95 and found to be highly concordant, with at least as high a resolution but with considerably less hands-on time. Our results position this MLVA scheme as an appropriate, high-throughput and relatively low-cost tool for K. pneumoniae epidemiology.

  15. A single genetic locus in the phytopathogen Pantoea stewartii enables gut colonization and pathogenicity in an insect host.

    Science.gov (United States)

    Stavrinides, John; No, Alexander; Ochman, Howard

    2010-01-01

    Aphids are typically exposed to a variety of epiphytic and phytopathogenic bacteria, many of which have entomopathogenic potential. Here we describe the interaction between Pantoea stewartii ssp. stewartii DC283 (DC283), an enteric phytopathogen and causal agent of Stewart's wilt, and the pea aphid, Acyrthosiphon pisum. When ingested by aphids, DC283 establishes and aggregates in the crop and gut, preventing honeydew flow and excretion, resulting in aphid death in 72 h. A mutagenesis screen identified a single locus, termed ucp1 (youcannot pass), whose disruption abolishes aphid pathogenicity. Moreover, the expression of ucp1 in Escherichia coli is sufficient to mediate the hindgut aggregation phenotype by this normally avirulent species. Ucp1 is related to six other proteins in the DC283 genome, each having a common N-terminal region and a divergent C-terminus, but only ucp1 has a role in pathogenicity. Based on predicted motifs and secondary structure, Ucp1 is a membrane-bound protein that functions in bacterial adhesion and promotes the formation of aggregates that are lethal to the insect host. These results illustrate that the enteric plant pathogenic bacteria have the capacity to exploit alternative non-plant hosts, and retain genetic determinants for colonizing the gut.

  16. Multi-locus genotyping of bottom fermenting yeasts by single nucleotide polymorphisms indicative of brewing characteristics.

    Science.gov (United States)

    Ikushima, Shigehito; Tateishi, Yoshiyuki; Kanai, Keiko; Shimada, Emiko; Tanaka, Misa; Ishiguro, Tatsuji; Mizutani, Satoru; Kobayashi, Osamu

    2012-04-01

    Yeast plays a capital role in brewing fermentation and has a direct impact on flavor and aroma. For the evaluation of competent brewing strains during quality control or development of novel strains it is standard practice to perform fermentation tests, which are costly and time-consuming. Here, we have categorized DNA markers which enable to distinguish and to screen brewing strains more efficiently than ever before. Sequence analysis at 289 loci in the genomes of six bottom fermenting Saccharomyces pastorianus strains revealed that 30 loci contained single nucleotide polymorphisms (SNPs). By determining the nucleotide sequences at the SNP-loci in 26 other S. pastorianus strains and 20 strains of the top fermenting yeast Saccharomyces cerevisiae, almost all these strains could be discriminated solely on the basis of the SNPs. By comparing the fermentative phenotypes of these strains we found that some DNA markers showed a strong association with brewing characteristics, such as the production of ethyl acetate and hydrogen sulphide (H2S). Therefore, the DNA markers we identified will facilitate quality control and the efficient development of brewing yeast strains. Copyright © 2011 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  17. The cardiovascular implication of single nucleotide polymorphisms of chromosome 9p21 locus among Arab population

    Directory of Open Access Journals (Sweden)

    Ayman A El-Menyar

    2015-01-01

    Full Text Available Background: Based on several reports including genome-wide association studies, genetic variability has been linked with higher (nearly half susceptibility toward coronary artery disease (CAD. We aimed to evaluate the association of chromosome 9p21 single nucleotide polymorphisms (SNPs: rs2383207, rs10757278, and rs10757274 with the risk and severity of CAD among Arab population. Materials and Methods: A prospective observational case-control study was conducted between 2011 and 2012, in which 236 patients with CAD were recruited from the Heart Hospital in Qatar. Patients were categorized according to their coronary angiographic findings. Also, 152 healthy volunteers were studied to determine if SNPs are associated with risk of CAD. All subjects were genotyped for SNPs (rs2383207, rs2383206, rs10757274 and rs10757278 using allele-specific real-time polymerase chain reaction. Results: Patients with CAD had a mean age of 57 ± 10; of them 77% were males, 54% diabetics, and 25% had family history of CAD. All SNPs were in Hardy-Weinberg equilibrium except rs2383206, with call rate >97%. After adjusting for age, sex and body mass index, the carriers of GG genotype for rs2383207 have increased the risk of having CAD with odds ratio (OR of 1.52 (95% confidence interval [CI] = 1.01-2.961, P = 0.046. Also, rs2383207 contributed to CAD severity with adjusted OR 1.80 (95% CI = 1.04-3.12, P = 0.035 based on the dominant genetic model. The other SNPs (rs10757274 and rs10757278 showed no significant association with the risk of CAD or its severity. Conclusion: Among Arab population in Qatar, only G allele of rs2483207 SNP is significantly associated with risk of CAD and its severity.

  18. Lanthanum-Based Metal-Organic Frameworks for Specific Detection of Sudan Virus RNA Conservative Sequences down to Single-Base Mismatch.

    Science.gov (United States)

    Yang, Shui-Ping; Zhao, Wei; Hu, Pei-Pei; Wu, Ke-Yang; Jiang, Zhi-Hong; Bai, Li-Ping; Li, Min-Min; Chen, Jin-Xiang

    2017-12-18

    Reactions of La(NO 3 ) 3 ·6H 2 O with the polar, tritopic quaternized carboxylate ligands N-carboxymethyl-3,5-dicarboxylpyridinium bromide (H 3 CmdcpBr) and N-(4-carboxybenzyl)-3,5-dicarboxylpyridinium bromide (H 3 CbdcpBr) afford two water-stable metal-organic frameworks (MOFs) of {[La 4 (Cmdcp) 6 (H 2 O) 9 ]} n (1, 3D) and {[La 2 (Cbdcp) 3 (H 2 O) 10 ]} n (2, 2D). MOFs 1 and 2 absorb the carboxyfluorescein (FAM)-tagged probe DNA (P-DNA) and quench the fluorescence of FAM via a photoinduced electron transfer (PET) process. The nonemissive P-DNA@MOF hybrids thus formed in turn function as sensing platforms to distinguish conservative linear, single-stranded RNA sequences of Sudan virus with high selectivity and low detection limits of 112 and 67 pM, respectively (at a signal-to-noise ratio of 3). These hybrids also exhibit high specificity and discriminate down to single-base mismatch RNA sequences.

  19. Chiral-Selective Growth of Single-Walled Carbon Nanotubes on Lattice-Mismatched Epitaxial Cobalt Nanoparticles

    DEFF Research Database (Denmark)

    He, Maoshuai; Jiang, Hua; Liu, Bilu

    2013-01-01

    Controlling chirality in growth of single-walled carbon nanotubes (SWNTs) is important for exploiting their practical applications. For long it has been conceptually conceived that the structural control of SWNTs is potentially achievable by fabricating nanoparticle catalysts with proper structures......-resolution environmental transmission electron microscope at a low CO pressure was recorded. We achieved highly preferential growth of semiconducting SWNTs (~90%) with an exceptionally large population of (6, 5) tubes (53%) in an ambient CO atmosphere. Particularly, we also demonstrated high enrichment in (7, 6) and (9, 4......) at a low growth temperature. These findings open new perspectives both for structural control of SWNTs and for elucidating the growth mechanisms....

  20. Selective nanoscale growth of lattice mismatched materials

    Science.gov (United States)

    Lee, Seung-Chang; Brueck, Steven R. J.

    2017-06-20

    Exemplary embodiments provide materials and methods of forming high-quality semiconductor devices using lattice-mismatched materials. In one embodiment, a composite film including one or more substantially-single-particle-thick nanoparticle layers can be deposited over a substrate as a nanoscale selective growth mask for epitaxially growing lattice-mismatched materials over the substrate.

  1. A single high dose of escitalopram increases mismatch negativity without affecting processing negativity or P300 amplitude in healthy volunteers

    DEFF Research Database (Denmark)

    Wienberg, M; Glenthøj, Birte Yding; Jensen, K S

    2009-01-01

    processing. The present study was designed to replicate and further extent the results of our initial study on the effects of a low dose of escitalopram (10 mg) on MMN, PN and P300 amplitude. In a randomised, double-blind, cross-over experiment, 20 healthy male volunteers received either a single, orally...... administered dose of 15 mg escitalopram (a highly selective serotonin reuptake inhibitor (SSRI)) or placebo, after which their PN, MMN and P300 amplitude were assessed. Similar to our initial study with 10 mg escitalopram, 15 mg escitalopram significantly increased MMN, while it did not affect P300 amplitude....... In contrast to our initial study, however, the currently higher dose of escitalopram did not increase PN. Results support the view that a broad range of increased serotonergic activity enhances MMN, while the relationship between serotonin and PN seems more complex. The current study does not support...

  2. The influence of microstructure on the measurement of γ-γ'lattice mismatch in single-crystal Ni-base superalloys

    International Nuclear Information System (INIS)

    Faehrmann, M.; Wolf, J.G.; Pollock, T.M.

    1996-01-01

    Lattice mismatch in multicomponent high refractory single-crystalline Ni-base superalloys has been measured in situ by hot-stage X-ray diffraction. Prior to X-ray examination, all samples were subjected to long-term aging treatments at 1120 C to relieve coherency stresses. The resolution of the individual γ and γ' peaks at high Bragg angles in the X-ray spectra and the magnitude of the misfit was found to be sensitive to the microstructure of the material. When the precipitation of coherent γ' during cooling from the aging temperature could largely be suppressed, the corresponding matrix peaks were narrower and of higher intensity as compared with samples where cooling γ'was present. Also, a slightly larger misfit, 0.04%, was measured in the microstructures where the cooling γ' was not present. Procedures for deconvoluting X-ray data are outlined in detail, and the experimental results are discussed in terms of changes in phase compositions and misfit strains produced by the cooling γ'. (orig.)

  3. A “four-ferrocene” modified stem-loop structure as a probe for sensitive detection and single-base mismatch discrimination of DNA

    International Nuclear Information System (INIS)

    Chatelain, Grégory; Ripert, Micaël; Farre, Carole; Ansanay-Alex, Salomé; Chaix, Carole

    2012-01-01

    We report the use of a four-ferrocene modified oligonucleotide as a probe for DNA detection with a gold electrode microsystem. This oligonucleotide is synthesized by automated solid-phase synthesis with four successive ferrocene moieties at the 5′-end and a C6-thiol modifier group at the 3′-end. The grafting of this 4Fc-DNA probe on a gold electrode microsystem results in the appearance of the ferrocene redox couple in cyclic voltammetry. The probe sequence is a stem-loop structure that folds efficiently on the electrode, thus optimizing electron transfer. Such architecture serves as sensor for DNA detection which is based on hybridization. The resulting disposable voltammetric sensor allowed direct, reagentless DNA detection in a small volume (20 μL). Electrochemical response upon hybridization with complementary short sequence (30-base length) and long sequence (50-base length) strands was observed by differential pulse voltammetry. Current variations were compared. The longer the sequence, the greater the decrease in current. The system's detection limit was estimated at 3.5 pM (0.07 fmol in 20 μL) with the 50-base length target and provided a dynamic detection range between 3.5 pM and 5 nM. Single mismatch detection showed a good level of sensitivity. The system was regenerated twice with no significant loss of Fc signal. Finally, 1 pM sensitivity was reached with a long chain analog of DNA PCR products of Influenza virus.

  4. Relationship between the mismatch of 123I-BMIPP and 201Tl myocardial single-photon emission computed tomography and autonomic nervous system activity in patients with acute myocardial infarction

    International Nuclear Information System (INIS)

    Yamanaka, Hiroyuki; Suzuki, Takeshi; Kishida, Hiroshi; Nagasawa, Koichi; Takano, Teruo

    2006-01-01

    The purpose of this study was to elucidate the relationship between the mismatch of thallium-201 (Tl) and iodine-123-beta-methyl-iodophenyl-pentadecanoic acid (BMIPP) myocardial single-photon emission computed tomography (SPECT) and autonomic nervous system activity in myocardial infarction (MI) patients. The subjects were 40 patients (34 males, 6 females) who underwent examinations by 123 I-BMIPP and 201 Tl myocardial SPECT imaging and 24-hour Holter monitoring within a 3-day period 3 weeks after the onset of their first MI. R-R intervals were analyzed every hour over a period of 24 hours by fast Fourier transformation (FFT). High frequency (HF) and low frequency (LF) were defined as markers of cardiac vagal activity in the former and the LF/HF ratio as sympathetic activity. Greater or more extensive decreases in the BMIPP image than that in the Tl image were defined as a positive mismatch. Patients were divided into positive and negative mismatch groups of 20 patients each. There were no significant differences between the 2 groups in age, sex, site of infarction, max CK (creatine kinase), max CK-MB, or left ventricular ejection fraction. The incidences of clinical signs suggesting residual myocardial ischemia were significantly greater in the positive than in the negative mismatch group (P 123 I-BMIPP and 201 Tl myocardial SPECT 3 weeks after a first acute myocardial infarction with uncomplicated moderate or severe heart failure and decreased heart rate variability are related to residual myocardial ischemia. A combined assessment of heart rate variability in 24 hour Holter electrocardiogram (ECG) monitoring and perfusion-metabolism mismatch in 123 I-BMIPP and 201 Tl myocardial SPECT is useful for determining residual myocardial ischemia in the follow-up of those with acute myocardial infarction. (author)

  5. An Undergraduate Laboratory Experiment for Upper-Level Forensic Science, Biochemistry, or Molecular Biology Courses: Human DNA Amplification Using STR Single Locus Primers by Real-Time PCR with SYBR Green Detection

    Science.gov (United States)

    Elkins, Kelly M.; Kadunc, Raelynn E.

    2012-01-01

    In this laboratory experiment, real-time polymerase chain reaction (real-time PCR) was conducted using published human TPOX single-locus DNA primers for validation and various student-designed short tandem repeat (STR) primers for Combined DNA Index System (CODIS) loci. SYBR Green was used to detect the amplification of the expected amplicons. The…

  6. Genome-Wide Single-Nucleotide Polymorphisms Discovery and High-Density Genetic Map Construction in Cauliflower Using Specific-Locus Amplified Fragment Sequencing

    Science.gov (United States)

    Zhao, Zhenqing; Gu, Honghui; Sheng, Xiaoguang; Yu, Huifang; Wang, Jiansheng; Huang, Long; Wang, Dan

    2016-01-01

    Molecular markers and genetic maps play an important role in plant genomics and breeding studies. Cauliflower is an important and distinctive vegetable; however, very few molecular resources have been reported for this species. In this study, a novel, specific-locus amplified fragment (SLAF) sequencing strategy was employed for large-scale single nucleotide polymorphism (SNP) discovery and high-density genetic map construction in a double-haploid, segregating population of cauliflower. A total of 12.47 Gb raw data containing 77.92 M pair-end reads were obtained after processing and 6815 polymorphic SLAFs between the two parents were detected. The average sequencing depths reached 52.66-fold for the female parent and 49.35-fold for the male parent. Subsequently, these polymorphic SLAFs were used to genotype the population and further filtered based on several criteria to construct a genetic linkage map of cauliflower. Finally, 1776 high-quality SLAF markers, including 2741 SNPs, constituted the linkage map with average data integrity of 95.68%. The final map spanned a total genetic length of 890.01 cM with an average marker interval of 0.50 cM, and covered 364.9 Mb of the reference genome. The markers and genetic map developed in this study could provide an important foundation not only for comparative genomics studies within Brassica oleracea species but also for quantitative trait loci identification and molecular breeding of cauliflower. PMID:27047515

  7. The gastrointestinal manifestation of constitutional mismatch repair deficiency syndrome: from a single adenoma to polyposis-like phenotype and early onset cancer.

    Science.gov (United States)

    Levi, Z; Kariv, R; Barnes-Kedar, I; Goldberg, Y; Half, E; Morgentern, S; Eli, B; Baris, H N; Vilkin, A; Belfer, R G; Niv, Y; Elhasid, R; Dvir, R; Abu-Freha, N; Cohen, S

    2015-11-01

    Data on the clinical presentation of constitutional mismatch repair deficiency syndrome (CMMRD) is accumulating. However, as the extraintestinal manifestations are often fatal and occur at early age, data on the systematic evaluation of the gastrointestinal tract is scarce. Here we describe 11 subjects with verified biallelic carriage and who underwent colonoscopy, upper endoscopy and small bowel evaluation. Five subjects were symptomatic and in six subjects the findings were screen detected. Two subjects had colorectal cancer and few adenomatous polyps (19, 20 years), three subjects had polyposis-like phenotype (13, 14, 16 years), four subjects had few adenomatous polyps (8, 12-14 years) and two subjects had no polyps (both at age 6). Of the three subjects in the polyposis-like group, two subjects had already developed high-grade dysplasia or cancer and one subject had atypical juvenile polyps suggesting juvenile polyposis. Three out of the five subjects that underwent repeated exams had significant findings during short interval. The gastrointestinal manifestations of CMMRD are highly dependent upon age of examination and highly variable. The polyps may also resemble juvenile polyposis. Intensive surveillance according to current guidelines is mandatory. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Visual-perceptual mismatch in robotic surgery.

    Science.gov (United States)

    Abiri, Ahmad; Tao, Anna; LaRocca, Meg; Guan, Xingmin; Askari, Syed J; Bisley, James W; Dutson, Erik P; Grundfest, Warren S

    2017-08-01

    The principal objective of the experiment was to analyze the effects of the clutch operation of robotic surgical systems on the performance of the operator. The relative coordinate system introduced by the clutch operation can introduce a visual-perceptual mismatch which can potentially have negative impact on a surgeon's performance. We also assess the impact of the introduction of additional tactile sensory information on reducing the impact of visual-perceptual mismatch on the performance of the operator. We asked 45 novice subjects to complete peg transfers using the da Vinci IS 1200 system with grasper-mounted, normal force sensors. The task involves picking up a peg with one of the robotic arms, passing it to the other arm, and then placing it on the opposite side of the view. Subjects were divided into three groups: aligned group (no mismatch), the misaligned group (10 cm z axis mismatch), and the haptics-misaligned group (haptic feedback and z axis mismatch). Each subject performed the task five times, during which the grip force, time of completion, and number of faults were recorded. Compared to the subjects that performed the tasks using a properly aligned controller/arm configuration, subjects with a single-axis misalignment showed significantly more peg drops (p = 0.011) and longer time to completion (p sensors showed no difference between the different groups. The visual-perceptual mismatch created by the misalignment of the robotic controls relative to the robotic arms has a negative impact on the operator of a robotic surgical system. Introduction of other sensory information and haptic feedback systems can help in potentially reducing this effect.

  9. The Effect of Basepair Mismatch on DNA Strand Displacement

    OpenAIRE

    Broadwater, D.?W.?Bo; Kim, Harold?D.

    2016-01-01

    DNA strand displacement is a key reaction in DNA homologous recombination and DNA mismatch repair and is also heavily utilized in DNA-based computation and locomotion. Despite its ubiquity in science and engineering, sequence-dependent effects of displacement kinetics have not been extensively characterized. Here, we measured toehold-mediated strand displacement kinetics using single-molecule fluorescence in the presence of a single base pair mismatch. The apparent displacement rate varied si...

  10. Addressing the Resource Requirements Mismatch

    National Research Council Canada - National Science Library

    Braun, William

    2003-01-01

    ... on the other, appear to be developing a requirements-resource mismatch. The goals and objectives of the transformation rhetoric intuitively resonate with the military's increasingly technologic culture...

  11. Microsatellite and single nucleotide polymorphisms in the β-globin locus control region-hypersensitive Site 2: SPECIFICITY of Tunisian βs chromosomes.

    Science.gov (United States)

    Ben Mustapha, Maha; Moumni, Imen; Zorai, Amine; Douzi, Kaïs; Ghanem, Abderraouf; Abbes, Salem

    2012-01-01

    The diversity of sickle cell disease severity is attributed to several cis acting factors, among them the single nucleotide polymorphisms (SNPs) and (AT) rich region in the β-locus control region (β-LCR). This contains five DNase I hypersensitive sites (HS) located 6 to 22 kb upstream to the ϵ gene. The most important of these is the HS2 (5' β-LCR-HS2), characterized by the presence of three different SNPs and a microsatellite region known to be in association with β(S) chromosomes in various populations. The aim of this study was to present the molecular investigation of the 5' β-LCR-HS2 site in normal and sickle cell disease individuals in order to determine if there is any correlation or specificity between these molecular markers, the β(S) Tunisian chromosomes and phenotypical expression of sickle cell disease. One hundred and twenty-four chromosomes from Tunisian individuals (49 β(S) carriers and 13 normal individuals) were screened by polymerase chain reaction (PCR) and sequencing for the polymorphic short tandem microsatellite repeats (AT)(X)N(12)(AT)(Y) and the three SNPs (rs7119428, rs9736333 and rs60240093) of the 5' β-LCR-HS2. Twelve configurations of the microsatellite motif were found with an ancestral configuration elaborated by ClustalW software. Normal and mutated alleles were observed at the homozygous and heterozygous states for the three SNPs. Correlation between microsatellites and SNPs suggests that mutant SNP alleles were mainly associated, in the homozygous sickle cell disease phenotype, with the (AT)(8)N(12)GT(AT)(7) configuration, whereas, normal SNP alleles were associated with the (AT)(X)N(12)(AT)(11) configurations in normal β(A) chromosomes. The correlation of these various configurations with Hb F expression was also investigated. The principal component analysis (PCA) showed the correlation between the homozygous sickle cell disease phenotype, mutated SNP alleles and the Benin microsatellite configuration (AT)(8)N(12)GT

  12. Co-release of noradrenaline and dopamine in the cerebral cortex elicited by single train and repeated train stimulation of the locus coeruleus

    Directory of Open Access Journals (Sweden)

    Saba Pierluigi

    2005-05-01

    Full Text Available Abstract Background Previous studies by our group suggest that extracellular dopamine (DA and noradrenaline (NA may be co-released from noradrenergic nerve terminals in the cerebral cortex. We recently demonstrated that the concomitant release of DA and NA could be elicited in the cerebral cortex by electrical stimulation of the locus coeruleus (LC. This study analyses the effect of both single train and repeated electrical stimulation of LC on NA and DA release in the medial prefrontal cortex (mPFC, occipital cortex (Occ, and caudate nucleus. To rule out possible stressful effects of electrical stimulation, experiments were performed on chloral hydrate anaesthetised rats. Results Twenty min electrical stimulation of the LC, with burst type pattern of pulses, increased NA and DA both in the mPFC and in the Occ. NA in both cortices and DA in the mPFC returned to baseline within 20 min after the end of the stimulation period, while DA in the Occ reached a maximum increase during 20 min post-stimulation and remained higher than baseline values at 220 min post-stimulation. Local perfusion with tetrodotoxin (TTX, 10 μM markedly reduced baseline NA and DA in the mPFC and Occ and totally suppressed the effect of electrical stimulation in both areas. A sequence of five 20 min stimulations at 20 min intervals were delivered to the LC. Each stimulus increased NA to the same extent and duration as the first stimulus, whereas DA remained elevated at the time next stimulus was delivered, so that baseline DA progressively increased in the mPFC and Occ to reach about 130 and 200% the initial level, respectively. In the presence of the NA transport (NAT blocker desipramine (DMI, 100 μM, multiple LC stimulation still increased extracellular NA and DA levels. Electrical stimulation of the LC increased NA levels in the homolateral caudate nucleus, but failed to modify DA level. Conclusion The results confirm and extend that LC stimulation induces a concomitant

  13. Prosthesis-patient mismatch

    Directory of Open Access Journals (Sweden)

    Philippe Pibarot

    2011-04-01

    Full Text Available Prosthesis-patient mismatch (PPM is present when the effective orifice area of the inserted prosthetic valve is too small in relation to body size. Its main hemodynamic consequence is to generate higher than expected gradients through normally functioning prosthetic valves. The purpose of this review is to present an update on the present state of knowledge with regards to diagnosis, prognosis and prevention of PPM. PPM is a frequent occurrence (20%–70% of aortic valve replacements that has been shown to be associated with worse hemodynamics, less regression of left ventricular hypertrophy, more cardiac events, and lower survival. Moreover, as opposed to most other risk factors, PPM can largely be prevented by using a prospective strategy at the time of operation.

  14. Zero lattice mismatch and twin-free single crystalline ScN buffer layers for GaN growth on silicon

    Energy Technology Data Exchange (ETDEWEB)

    Lupina, L.; Zoellner, M. H.; Dietrich, B.; Capellini, G. [IHP, Im Technologiepark 25, 15236 Frankfurt, Oder (Germany); Niermann, T.; Lehmann, M. [Technische Universität Berlin, Institut für Optik und Atomare Physik, Straße des 17. Juni 135, 10623 Berlin (Germany); Thapa, S. B.; Haeberlen, M.; Storck, P. [SILTRONIC AG, Hanns-Seidel-Platz 4, 81737 München (Germany); Schroeder, T. [IHP, Im Technologiepark 25, 15236 Frankfurt, Oder (Germany); BTU Cottbus, Konrad-Zuse-Str. 1, 03046 Cottbus (Germany)

    2015-11-16

    We report the growth of thin ScN layers deposited by plasma-assisted molecular beam epitaxy on Sc{sub 2}O{sub 3}/Y{sub 2}O{sub 3}/Si(111) substrates. Using x-ray diffraction, Raman spectroscopy, and transmission electron microscopy, we find that ScN films grown at 600 °C are single crystalline, twin-free with rock-salt crystal structure, and exhibit a direct optical band gap of 2.2 eV. A high degree of crystalline perfection and a very good lattice matching between ScN and GaN (misfit < 0.1%) makes the ScN/Sc{sub 2}O{sub 3}/Y{sub 2}O{sub 3} buffer system a very promising template for the growth of high quality GaN layers on silicon.

  15. [Constitutional mismatch repair deficiency syndrome

    NARCIS (Netherlands)

    Jongmans, M.C.J.; Gidding, C.E.M.; Loeffen, J.; Wesseling, P.; Mensenkamp, A.; Hoogerbrugge, N.

    2015-01-01

    BACKGROUND: Constitutional mismatch repair deficiency (CMMR-D) syndrome is characterised by a significantly increased risk for developing cancer in childhood. It arises when both parents have a mutation in the same mismatch repair gene and pass it on to their child. CASE DESCRIPTION: An 8-year-old

  16. Comparison of semi-automated commercial rep-PCR fingerprinting, spoligotyping, 12-locus MIRU-VNTR typing and single nucleotide polymorphism analysis of the embB gene as molecular typing tools for Mycobacterium bovis.

    Science.gov (United States)

    Armas, Federica; Camperio, Cristina; Coltella, Luana; Selvaggini, Serena; Boniotti, Maria Beatrice; Pacciarini, Maria Lodovica; Di Marco Lo Presti, Vincenzo; Marianelli, Cinzia

    2017-08-04

    Highly discriminatory genotyping strategies are essential in molecular epidemiological studies of tuberculosis. In this study we evaluated, for the first time, the efficacy of the repetitive sequence-based PCR (rep-PCR) DiversiLab Mycobacterium typing kit over spoligotyping, 12-locus mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing and embB single nucleotide polymorphism (SNP) analysis for Mycobacterium bovis typing. A total of 49 M. bovis animal isolates were used. DNA was extracted and genomic DNA was amplified using the DiversiLab Mycobacterium typing kit. The amplified fragments were separated and detected using a microfluidics chip with Agilent 2100. The resulting rep-PCR-based DNA fingerprints were uploaded to and analysed using web-based DiversiLab software through Pearson's correlation coefficient. Rep-PCR DiversiLab grouped M. bovis isolates into ten different clusters. Most isolates sharing identical spoligotype, MIRU-VNTR profile or embB gene polymorphism were grouped into different rep-PCR clusters. Rep-PCR DiversiLab displayed greater discriminatory power than spoligotyping and embB SNP analysis but a lower resolution power than the 12-locus MIRU-VNTR analysis. MIRU-VNTR confirmed that it is superior to the other PCR-based methods tested here. In combination with spoligotyping and 12-locus MIRU-VNTR analysis, rep-PCR improved the discriminatory power for M. bovis typing.

  17. Impact of patient-prosthesis mismatch following aortic valve replacement on short-term survival: a retrospective single center analysis of 632 consecutive patients with isolated stented biological aortic valve replacement.

    Science.gov (United States)

    Hoffmann, Grischa; Ogbamicael, Selam Abraham; Jochens, Arne; Frank, Derk; Lutter, Georg; Cremer, Jochen; Petzina, Rainer

    2014-09-01

    The impact of patient-prosthesis mismatch (PPM) after aortic valve replacement (AVR) on short-term and long-term mortality remains controversial. The objective of this study was to evaluate the incidence and severity of PPM and its impact on short-term survival in a large cohort of patients treated with isolated stented biological AVR in a single institution. We analyzed retrospectively data of 632 consecutive patients with aortic stenosis undergoing isolated stented biological AVR between January 2007 and February 2012 at our institution. PPM was defined as an indexed effective orifice area ≤ 0.85 cm(2)/m(2). Statistical analyses were performed to identify influencing variables on valve size implanted. Of the 632 patients investigated, 46% were females and mean age was 71.9 ± 10.4 years. PPM was observed in 93.8% (593 of 632 patients). In 71% of the patients, moderate (0.65-0.85 cm(2)/m(2)) PPM was present and in 22.8% severe (body mass index, and body surface area as simultaneous predictors of the valve size implanted (R(2)= 0.39). PPM had no discernable impact on short-term survival, although it was present in 93.8% of our patients following isolated stented biological AVR. Georg Thieme Verlag KG Stuttgart · New York.

  18. A study on single nucleotide polymorphism of exon 7 T/C (locus 593 of platelet-activating factor acetylhydrolase gene in healthy Han population in the Shanghai region

    Directory of Open Access Journals (Sweden)

    Tian-bao XIA

    2012-08-01

    Full Text Available Objective To investigate the distribution of single nucleotide polymorphism (SNP in platelet-activating factor acetylhydrolase (PAF-AH gene exon 7 T/C (locus 593 in healthy Han population in Shanghai region and the features different from other races. Methods The SNP in PAF-AH gene exon 7 T/C (locus 593 was detected and analyzed by PCR and sequencing in 110 healthy Han people from Shanghai areas. The genotype and allele frequency were then calculated and compared with that in other races in combination with review of relevant literature. Results The amplified product of the SNP in PAF-AH gene exon 7 T/C (locus 593 was 240 bp in 110 healthy Han people, of whom 97 were with TT genotype and 13 with TC genotype, but no CC genotype was found. As to the allele frequency distribution, T type allele took the highest position, and C type followed. The genotype frequency of TT and TC was 88.2% and 11.8%, respectively, and they were markedly different from that in German population (0.95%, while not statistically significant different from that in British population (7.67%. Conclusions There exists SNP in PAF-AH gene exon 7 T/C (position 593 in healthy Han people in Shanghai region, with a higher frequency of T→C mutation. The mutational genotype frequency is found to be located at the locus 593 is 11.81%, and it is markedly different from that in German population, but not significantly different from that in British population.

  19. Highly parallel and short-acting amplification with locus-specific primers to detect single nucleotide polymorphisms by the DigiTag2 assay.

    Directory of Open Access Journals (Sweden)

    Nao Nishida

    Full Text Available The DigiTag2 assay enables analysis of a set of 96 SNPs using Kapa 2GFast HotStart DNA polymerase with a new protocol that has a total running time of about 7 hours, which is 6 hours shorter than the previous protocol. Quality parameters (conversion rate, call rate, reproducibility and concordance were at the same levels as when genotype calls were acquired using the previous protocol. Multiplex PCR with 192 pairs of locus-specific primers was available for target preparation in the DigiTag2 assay without the optimization of reaction conditions, and quality parameters had the same levels as those acquired with 96-plex PCR. The locus-specific primers were able to achieve sufficient (concentration of target amplicon ≥5 nM and specific (concentration of unexpected amplicons <2 nM amplification within 2 hours, were also able to achieve detectable amplifications even when working in a 96-plex or 192-plex form. The improved DigiTag2 assay will be an efficient platform for screening an intermediate number of SNPs (tens to hundreds of sites in the replication analysis after genome-wide association study. Moreover, highly parallel and short-acting amplification with locus-specific primers may thus facilitate widespread application to other PCR-based assays.

  20. The Effect of Basepair Mismatch on DNA Strand Displacement.

    Science.gov (United States)

    Broadwater, D W Bo; Kim, Harold D

    2016-04-12

    DNA strand displacement is a key reaction in DNA homologous recombination and DNA mismatch repair and is also heavily utilized in DNA-based computation and locomotion. Despite its ubiquity in science and engineering, sequence-dependent effects of displacement kinetics have not been extensively characterized. Here, we measured toehold-mediated strand displacement kinetics using single-molecule fluorescence in the presence of a single basepair mismatch. The apparent displacement rate varied significantly when the mismatch was introduced in the invading DNA strand. The rate generally decreased as the mismatch in the invader was encountered earlier in displacement. Our data indicate that a single base pair mismatch in the invader stalls branch migration and displacement occurs via direct dissociation of the destabilized incumbent strand from the substrate strand. We combined both branch migration and direct dissociation into a model, which we term the concurrent displacement model, and used the first passage time approach to quantitatively explain the salient features of the observed relationship. We also introduce the concept of splitting probabilities to justify that the concurrent model can be simplified into a three-step sequential model in the presence of an invader mismatch. We expect our model to become a powerful tool to design DNA-based reaction schemes with broad functionality. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  1. DNA Mismatch Binding and Antiproliferative Activity of Rhodium Metalloinsertors

    Science.gov (United States)

    Ernst, Russell J.; Song, Hang; Barton, Jacqueline K.

    2009-01-01

    Deficiencies in mismatch repair (MMR) are associated with carcinogenesis. Rhodium metalloinsertors bind to DNA base mismatches with high specificity and inhibit cellular proliferation preferentially in MMR-deficient cells versus MMR-proficient cells. A family of chrysenequinone diimine complexes of rhodium with varying ancillary ligands that serve as DNA metalloinsertors has been synthesized, and both DNA mismatch binding affinities and antiproliferative activities against the human colorectal carcinoma cell lines HCT116N and HCT116O, an isogenic model system for MMR deficiency, have been determined. DNA photocleavage experiments reveal that all complexes bind to the mismatch sites with high specificities; DNA binding affinities to oligonucleotides containing single base CA and CC mismatches, obtained through photocleavage titration or competition, vary from 104 to 108 M−1 for the series of complexes. Significantly, binding affinities are found to be inversely related to ancillary ligand size and directly related to differential inhibition of the HCT116 cell lines. The observed trend in binding affinity is consistent with the metalloinsertion mode where the complex binds from the minor groove with ejection of mismatched base pairs. The correlation between binding affinity and targeting of the MMR-deficient cell line suggests that rhodium metalloinsertors exert their selective biological effects on MMR-deficient cells through mismatch binding in vivo. PMID:19175313

  2. Comparative analysis of chimeric ZFP-, TALE- and Cas9-piggyBac transposases for integration into a single locus in human cells.

    Science.gov (United States)

    Luo, Wentian; Galvan, Daniel L; Woodard, Lauren E; Dorset, Dan; Levy, Shawn; Wilson, Matthew H

    2017-08-21

    Integrating DNA delivery systems hold promise for many applications including treatment of diseases; however, targeted integration is needed for improved safety. The piggyBac (PB) transposon system is a highly active non-viral gene delivery system capable of integrating defined DNA segments into host chromosomes without requiring homologous recombination. We systematically compared four different engineered zinc finger proteins (ZFP), four transcription activator-like effector proteins (TALE), CRISPR associated protein 9 (SpCas9) and the catalytically inactive dSpCas9 protein fused to the amino-terminus of the transposase enzyme designed to target the hypoxanthine phosphoribosyltransferase (HPRT) gene located on human chromosome X. Chimeric transposases were evaluated for expression, transposition activity, chromatin immunoprecipitation at the target loci, and targeted knockout of the HPRT gene in human cells. One ZFP-PB and one TALE-PB chimera demonstrated notable HPRT gene targeting. In contrast, Cas9/dCas9-PB chimeras did not result in gene targeting. Instead, the HPRT locus appeared to be protected from transposon integration. Supplied separately, PB permitted highly efficient isolation of Cas9-mediated knockout of HPRT, with zero transposon integrations in HPRT by deep sequencing. In summary, these tools may allow isolation of 'targeted-only' cells, be utilized to protect a genomic locus from transposon integration, and enrich for Cas9-mutated cells. Published by Oxford University Press on behalf of Nucleic Acids Research 2017.

  3. Selection, trans-species polymorphism, and locus identification of major histocompatibility complex class IIβ alleles of New World ranid frogs

    Science.gov (United States)

    Kiemnec-Tyburczy, Karen M.; Richmond, Jonathan Q.; Savage, Anna E.; Zamudio, Kelly R.

    2010-01-01

    Genes encoded by the major histocompatibility complex (MHC) play key roles in the vertebrate immune system. However, our understanding of the evolutionary processes and underlying genetic mechanisms shaping these genes is limited in many taxa, including amphibians, a group currently impacted by emerging infectious diseases. To further elucidate the evolution of the MHC in frogs (anurans) and develop tools for population genetics, we surveyed allelic diversity of the MHC class II ??1 domain in both genomic and complementary DNA of seven New World species in the genus Rana (Lithobates). To assign locus affiliation to our alleles, we used a "gene walking" technique to obtain intron 2 sequences that flanked MHC class II?? exon 2. Two distinct intron sequences were recovered, suggesting the presence of at least two class II?? loci in Rana. We designed a primer pair that successfully amplified an orthologous locus from all seven Rana species. In total, we recovered 13 alleles and documented trans-species polymorphism for four of the alleles. We also found quantitative evidence of selection acting on amino acid residues that are putatively involved in peptide binding and structural stability of the ??1 domain of anurans. Our results indicated that primer mismatch can result in polymerase chain reaction (PCR) bias, which influences the number of alleles that are recovered. Using a single locus may minimize PCR bias caused by primer mismatch, and the gene walking technique was an effective approach for generating single-copy orthologous markers necessary for future studies of MHC allelic variation in natural amphibian populations. ?? 2010 Springer-Verlag.

  4. Image simulation using LOCUS

    International Nuclear Information System (INIS)

    Strachan, J.D.; Roberts, J.A.

    1989-09-01

    The LOCUS data base program has been used to simulate images and to solve simple equations. This has been accomplished by making each record (which normally would represent a data entry)represent sequenced or random number pairs

  5. Reverse ventilation--perfusion mismatch

    International Nuclear Information System (INIS)

    Palmaz, J.C.; Barnett, C.A.; Reich, S.B.; Krumpe, P.E.; Farrer, P.A.

    1984-01-01

    Patients having lobar airway obstruction or consolidation usually have decreases of both ventilation and perfusion on lung scans. We report three patients in whom hypoxic vasoconstriction was apparently incomplete, resulting in a ''reversed'' ventilation-perfusion mismatch. Perfusion of the hypoxic lobe on the radionuclide scan was associated with metabolic alkalosis, pulmonary venous and pulmonary arterial hypertension in these patients

  6. Analytical Expressions for Harmonic Distortion at Low Frequencies due to Device Mismatch in CMOS Current Mirrors

    DEFF Research Database (Denmark)

    Bruun, Erik

    1999-01-01

    One of the origins of harmonic distortion in current mirrors is the inevitable mismatch between the mirror transistors. In this brief we examine both single current mirrors and complementary class AB current mirrors and develop analytical expressions for the mismatch induced harmonic distortion. ...

  7. Detecting deletions, insertions, and single nucleotide substitutions in cloned β-globin genes and new polymorphic nucleotide substitutions in β-globin genes in a Japanese population using ribonuclease cleavage at mismatches in RNA: DNA duplexes

    International Nuclear Information System (INIS)

    Hiyama, Keiko; Kodaira, Mieko; Satoh, Chiyoko.

    1990-08-01

    The applicability of ribonuclease (RNase) cleavage at mismatches in RNA:DNA duplexes (the RNase cleavage method) for determining nucleotide variant rates was examined in a Japanese population. DNA segments of various lengths obtained from four different regions of one normal and three thalassemic cloned human β-globin genes were inserted into transcription vectors. Sense and antisense RNA probes uniformly labeled with 32 P were prepared. When RNA probes of 771 nucleotides (nt) or less were hybridized with cloned DNAs and the resulting duplexes were treated with a mixture of RNases A and T1, the length of products agreed with theoretical values. Twelve possible mismatches were examined. Since both sense and antisense probes were used, uncleavable mismatches such as G:T and G:G which were made from one combination of RNA and DNA strands could be converted to the cleavable C:A and C:C mismatches, respectively, by using the opposite combination. Deletions and insertions of one (G), four(TTCT), five (ATTTT), and 10 (ATTTTATTTT) nt were easily detected. A polymorphic substitution of T to C at position 666 of the second intervening sequence (IVS2-666) of the β-globin gene was detected using genomic DNAs from cell lines established from the peripheral B lymphocytes of 59 unrelated Japanese from Hiroshima or those amplified by polymerase chain reaction (PCR). The frequency of the gene with C at the IVS2-666 (allele C) was 0.48 and that of the gene with T (allene T) was 0.52. Two new polymorphic substitutions of C to A and A to T were detected at nucleotide positions 1789 and 1945 from the capping site, respectively, using genomic DNAs amplified by PCR. We conclude that it would be feasible to use the RNase cleavage method combined with PCR for large-scale screening of variation in chromosomal DNA. (J.P.N.)

  8. [The impact of HLA haplotype and alleles mismatches of donor-recipient pairs on outcome of haploidentical hematopoietic stem cell transplantation with a third part cord blood unit].

    Science.gov (United States)

    Zhu, W J; He, J; Bao, X J; Yuan, X N; Li, Y; Xue, S L; Pan, Z J; Chen, J; Wu, D P

    2016-07-01

    To analyze allele mismatches of HLA- A, - B, - C, - DRB1, - DQB1 and haplotype mismatch of donor- recipient pairs on the outcome of haploidentical transplantation combined with a third part cord blood unit. 230 pairs of donor-recipient were performed HLA-A, B, C, DRB1, DQB1 typing using SBT and SSOP methods from January 2012 to December 2014. Pairs were divided into HLA- 5/10、6/10、7/10 and ≥8/10 groups according to HLA- A, B, C and DRB1 highresolution typing and matched degrees, the 3-year probability of overall survival (OS) for each group were 48.7%, 59.3%, 71.1%, 38.3% (P=0.068) respectively. HLA-6/10 matched group associated with significant favorable effect on OS compared with HLA- 5/10 matched one (P=0.041).When the HLA class I antigen matched on the recipient and donor, improved OS and event free survival (EFS) in HLA- 6/10 matched group than in HLA-5/10 matched one (P=0.017,P=0.088), especially in single HLA-A loci allele matched one (P=0.013,P=0.013), were observed. As to the third part cord blood unit, sharing the same haplotype with the recipient-donor pairs produced better platelet recovery than the misfit one (95.3%vs 86.2%,P= 0.007), similar result was found in terms of neutrophil recovery (98.8%vs 96.1% ,P=0.022). HLA locus mismatch and haplotype mismatch of the donor and recipient should be useful for selection of the most optimum donor. Co- infused of an unrelated cord blood unit sharing the same haplotype with the recipient-donor pairs could improve hematopoietic recovery.

  9. Educational Mismatch and Self-Employment

    Science.gov (United States)

    Bender, Keith A.; Roche, Kristen

    2013-01-01

    Previous research on educational mismatch concentrates on estimating its labor market consequences but with a focus on wage and salary workers. This paper examines the far less studied influence of mismatch on the self-employed. Using a sample of workers in science and engineering fields, results show larger earnings penalties for mismatch among…

  10. Endogenous Locus Reporter Assays.

    Science.gov (United States)

    Liu, Yaping; Hermes, Jeffrey; Li, Jing; Tudor, Matthew

    2018-01-01

    Reporter gene assays are widely used in high-throughput screening (HTS) to identify compounds that modulate gene expression. Traditionally a reporter gene assay is built by cloning an endogenous promoter sequence or synthetic response elements in the regulatory region of a reporter gene to monitor transcriptional activity of a specific biological process (exogenous reporter assay). In contrast, an endogenous locus reporter has a reporter gene inserted in the endogenous gene locus that allows the reporter gene to be expressed under the control of the same regulatory elements as the endogenous gene, thus more accurately reflecting the changes seen in the regulation of the actual gene. In this chapter, we introduce some of the considerations behind building a reporter gene assay for high-throughput compound screening and describe the methods we have utilized to establish 1536-well format endogenous locus reporter and exogenous reporter assays for the screening of compounds that modulate Myc pathway activity.

  11. [Constitutional mismatch repair deficiency syndrome].

    Science.gov (United States)

    Jongmans, Marjolijn C; Gidding, Corrie E; Loeffen, Jan; Wesseling, Pieter; Mensenkamp, Arjen; Hoogerbrugge, Nicoline

    2015-01-01

    Constitutional mismatch repair deficiency (CMMR-D) syndrome is characterised by a significantly increased risk for developing cancer in childhood. It arises when both parents have a mutation in the same mismatch repair gene and pass it on to their child. An 8-year-old girl was diagnosed with CMMR-D syndrome after she developed a brain tumour at the age of 4 and a T-cell non-Hodgkin lymphoma at the age of 6. She had multiple hyperpigmented skin lesions and died of myelodysplastic syndrome at the age of 11. In children with cancer CMMR-D syndrome can be recognized particularly if there are multiple primary malignancies and skin hyperpigmentations and hypopigmentations. The parents of these children are at high risk for colorectal and endometrial cancer (Lynch syndrome), amongst others.

  12. Outcomes of peripheral blood stem cell transplantation patients from HLA-mismatched unrelated donor with antithymocyte globulin (ATG)-Thymoglobulin versus ATG-Fresenius: a single-center study.

    Science.gov (United States)

    Huang, Wenrong; Zhao, Xiaoli; Tian, Yamin; Cao, Tingting; Li, Yanfen; Liu, Zhanxiang; Jing, Yu; Wang, Shuhong; Gao, Chunji; Yu, Li

    2015-02-01

    Although antithymocyte globulin (ATG) had been widely used in hematopoietic stem cell transplantation from unrelated donor due to its ability to prevent acute and chronic graft-versus-host disease (GVHD), the comparative efficacy and safety of ATG-Thymoglobulin (ATG-T) and ATG-Fresenius (ATG-F) in patients undergoing HLA-mismatched allogeneic peripheral blood stem cell transplantation from unrelated donors (UR-PBSCT) has not been evaluated. Retrospective analysis of patients who underwent HLA-mismatched UR-PBSCT between January 2003 and December 2013 and received pre-transplant ATG-T at a total dose of 10 mg/kg or ATG-F at a total dose of 20 mg/kg was performed. Patients who received ATG-T (n = 23) or ATG-F (n = 28) had similar baseline demographic, disease, and transplant characteristics. There were no significant between-groups differences in the probability of acute GVHD (P = 0.721) and chronic GVHD (P = 0.439). ATG-F was associated with nonsignificant trends toward higher disease-free survival at 3-year follow-up compared with ATG-T (45.7 ± 11.1 vs 61.3 ± 9.7 %, respectively, P = 0.07). A significantly greater proportion of ATG-T patients experienced high fever than ATG-F patients (P < 0.01) during ATG infusion. There was no difference in the rate of infection between the two treatment groups. There were less adverse effects comparing ATG-F with ATG-T. ATG-T at a total dose of 10 mg/kg and ATG-F at a total dose of 20 mg/kg had a similar clinical outcome in the setting of HLA-mismatched UR-PBSCT.

  13. The IGF2 Locus

    Science.gov (United States)

    Insulin-like growth factor 2 (IGF2) is a peptide hormone regulating various cellular processes such as proliferation and apoptosis. IGF2 is vital to embryo development. The IGF2 locus covers approximately 150-kb genomic region on human chromosome 11, containing two imprinted genes, IGF2 and H19, sha...

  14. Imagery mismatch negativity in musicians.

    Science.gov (United States)

    Herholz, Sibylle C; Lappe, Claudia; Knief, Arne; Pantev, Christo

    2009-07-01

    The present study investigated musical imagery in musicians and nonmusicians by means of magnetoencephalography (MEG). We used a new paradigm in which subjects had to continue familiar melodies in their mind and then judged if a further presented tone was a correct continuation of the melody. Incorrect tones elicited an imagery mismatch negativity (iMMN) in musicians but not in nonmusicians. This finding suggests that the MMN component can be based on an imagined instead of a sensory memory trace and that imagery of music is modulated by musical expertise.

  15. A rhodium(III) complex for high-affinity DNA base-pair mismatch recognition

    Science.gov (United States)

    Junicke, Henrik; Hart, Jonathan R.; Kisko, Jennifer; Glebov, Oleg; Kirsch, Ilan R.; Barton, Jacqueline K.

    2003-01-01

    A rhodium(III) complex, rac-[Rh(bpy)2phzi]3+ (bpy, 2,2′-bipyridine; phzi, benzo[a]phenazine-5,6-quinone diimine) has been designed as a sterically demanding intercalator targeted to destabilized mismatched sites in double-helical DNA. The complex is readily synthesized by condensation of the phenazine quinone with the corresponding diammine complex. Upon photoactivation, the complex promotes direct strand scission at single-base mismatch sites within the DNA duplex. As with the parent mismatch-specific reagent, [Rh(bpy)2(chrysi)]3+ [chrysene-5,6-quinone diimine (chrysi)], mismatch selectivity depends on the helix destabilization associated with mispairing. Unlike the parent chrysi complex, the phzi analogue binds and cleaves with high affinity and efficiency. The specific binding constants for CA, CC, and CT mismatches within a 31-mer oligonucleotide duplex are 0.3, 1, and 6 × 107 M−1, respectively; site-specific photocleavage is evident at nanomolar concentrations. Moreover, the specificity, defined as the ratio in binding affinities for mispaired vs. well paired sites, is maintained. The increase in affinity is attributed to greater stability in the mismatched site associated with stacking by the heterocyclic aromatic ligand. The high-affinity complex is also applied in the differential cleavage of DNA obtained from cell lines deficient in mismatch repair vs. those proficient in mismatch repair. Agreement is found between photocleavage by the mismatch-specific probes and deficiency in mismatch repair. This mismatch-specific targeting, therefore, offers a potential strategy for new chemotherapeutic design. PMID:12610209

  16. Multiple Locus Variable-Number Tandem-Repeat and Single-Nucleotide Polymorphism-Based Brucella Typing Reveals Multiple Lineages in Brucella melitensis Currently Endemic in China

    Directory of Open Access Journals (Sweden)

    Mingjun Sun

    2017-12-01

    Full Text Available Brucellosis is a worldwide zoonotic disease caused by Brucella spp. In China, brucellosis is recognized as a reemerging disease mainly caused by Brucella melitensis specie. To better understand the currently endemic B. melitensis strains in China, three Brucella genotyping methods were applied to 110 B. melitensis strains obtained in past several years. By MLVA genotyping, five MLVA-8 genotypes were identified, among which genotypes 42 (1-5-3-13-2-2-3-2 was recognized as the predominant genotype, while genotype 63 (1-5-3-13-2-3-3-2 and a novel genotype of 1-5-3-13-2-4-3-2 were second frequently observed. MLVA-16 discerned a total of 57 MLVA-16 genotypes among these Brucella strains, with 41 genotypes being firstly detected and the other 16 genotypes being previously reported. By BruMLSA21 typing, six sequence types (STs were identified, among them ST8 is the most frequently seen in China while the other five STs were firstly detected and designated as ST137, ST138, ST139, ST140, and ST141 by international multilocus sequence typing database. Whole-genome sequence (WGS-single-nucleotide polymorphism (SNP-based typing and phylogenetic analysis resolved Chinese B. melitensis strains into five clusters, reflecting the existence of multiple lineages among these Chinese B. melitensis strains. In phylogeny, Chinese lineages are more closely related to strains collected from East Mediterranean and Middle East countries, such as Turkey, Kuwait, and Iraq. In the next few years, MLVA typing will certainly remain an important epidemiological tool for Brucella infection analysis, as it displays a high discriminatory ability and achieves result largely in agreement with WGS-SNP-based typing. However, WGS-SNP-based typing is found to be the most powerful and reliable method in discerning Brucella strains and will be popular used in the future.

  17. Measurement of mismatch loss in CPV modul

    Science.gov (United States)

    Liu, Mingguo; Kinsey, Geoffrey S.; Bagienski, Will; Nayak, Adi; Garboushian, Vahan

    2012-10-01

    A setup capable of simultaneously measuring I-V curves of a full string and its individual cells has been developed. This setup enables us to measure mismatch loss from individual cells in concert with various string combinations under varying field conditions. Mismatch loss from cells to plates at different off-track angles and mismatch from plates to strings in Amonix system during normal operation have been investigated.

  18. The LOCUS interface to the MFE database

    International Nuclear Information System (INIS)

    Miner, W.H. Jr.

    1991-01-01

    The MFE database now consists of over 900 shots from TFTR, PDX, PLT, T-10, JT-60, TEXT, JET and ASDEX. A variety of discharge conditions is represented, ranging from single time slice Ohmic discharges to multiple time-slice auxiliary heated discharges. Included with most datasets is a reference that describes the experiment being performed when the data was taken. The MFE database is currently implemented under INGRES on a VAX that is on Internet. LOCUS, a database utility, developed at the Princeton Plasma Physics Laboratory is now available as an interface to the database. The LOCUS front end provides a graphic interface to the database from any generic graphics terminal that supports Tektronix 4010 emulation. It provides a variety of procedures for extracting, manipulating and graphing data from the MFE database. In order to demonstrate the capabilities of the LOCUS interface, the authors examine, in detail, one of the recently added JET, H-mode discharges. In this example, they address some new concepts such as monitor functions, which have been introduced in order to help users more fully understand the multiple time-slice datasets. They also describe some of the more advanced techniques available in LOCUS for data access and manipulation. Specific areas of interest that are discussed are searching for and retrieving datasets, graphics, data fitting, and linear regression analysis

  19. Spatial Mismatch: A Third Generation Survey.

    Science.gov (United States)

    Eagan, J. Vincent

    1999-01-01

    The spatial mismatch argument hypothesizes that racial discrimination in the housing market, together with the suburbanization of low skilled jobs, contributes significantly to the high unemployment and/or low wages of inner city minority workers. Surveys recent spatial mismatch literature and discusses policy alternatives, focusing on areas…

  20. Genotype-Phenotype Associations of the CD-Associated Single Nucleotide Polymorphism within the Gene Locus Encoding Protein Tyrosine Phosphatase Non-Receptor Type 22 in Patients of the Swiss IBD Cohort.

    Directory of Open Access Journals (Sweden)

    Marianne R Spalinger

    Full Text Available Protein tyrosine phosphatase non-receptor type 22 (PTPN22 plays an important role in immune cell function and intestinal homeostasis. The single nucleotide polymorphism (SNP rs2476601 within the PTPN22 gene locus results in aberrant function of PTPN22 protein and protects from Crohn's disease (CD. Here, we investigated associations of PTPN22 SNP rs2476601 in inflammatory bowel disease (IBD patients in the Swiss IBD Cohort Study (SIBDCS.2'028 SIBDCS patients (1173 CD and 855 ulcerative colitis (UC patients were included. The clinical characteristics were analysed for an association with the presence of the PTPN22 SNP rs2476601 genotypes 'homozygous variant' (AA, 'heterozygous' (GA and 'homozygous wild-type' (GG.13 patients (0.6% were homozygous variant (AA for the PTPN22 polymorphism, 269 (13.3% heterozygous variant (GA and 1'746 (86.1% homozygous wild-type (GG. In CD, AA and GA genotypes were associated with less use of steroids and antibiotics, and reduced prevalence of vitamin D and calcium deficiency. In UC the AA and GA genotype was associated with increased use of azathioprine and anti-TNF antibodies, but significantly less patients with the PTPN22 variant featured malabsorption syndrome (p = 0.026.Our study for the first time addressed how presence of SNP rs2476601 within the PTPN22 gene affects clinical characteristics in IBD-patients. Several factors that correlate with more severe disease were found to be less common in CD patients carrying the A-allele, pointing towards a protective role for this variant in affected CD patients. In UC patients however, we found the opposite trend, suggesting a disease-promoting effect of the A-allele.

  1. Zero energy buildings and mismatch compensation factors

    DEFF Research Database (Denmark)

    Lund, Henrik; Marszal, Anna Joanna; Heiselberg, Per

    2011-01-01

    This paper takes an overall energy system approach to analysing the mismatch problem of zero energy and zero emission buildings (ZEBs). The mismatch arises from hourly differences in energy production and consumption at the building level and results in the need for exchange of electricity via...... the public grid even though the building has an annual net-exchange of zero. This paper argues that, when looked upon from the viewpoint of the overall electricity supply system, a mismatch can be both negative and positive. Moreover, there are often both an element of levelling out mismatches between...... of the energy production unit. Based on historical data for the electricity supply area in western Denmark, this paper makes a first attempt to quantify mismatch compensation factors. The results indicate that such compensation factors are a little below one for buildings with photovoltaics (PV) and a little...

  2. Entanglement verification with detection efficiency mismatch

    Science.gov (United States)

    Zhang, Yanbao; Lütkenhaus, Norbert

    Entanglement is a necessary condition for secure quantum key distribution (QKD). When there is an efficiency mismatch between various detectors used in the QKD system, it is still an open problem how to verify entanglement. Here we present a method to address this problem, given that the detection efficiency mismatch is characterized and known. The method works without assuming an upper bound on the number of photons going to each threshold detector. Our results suggest that the efficiency mismatch affects the ability to verify entanglement: the larger the efficiency mismatch is, the smaller the set of entangled states that can be verified becomes. When there is no mismatch, our method can verify entanglement even if the method based on squashing maps [PRL 101, 093601 (2008)] fails.

  3. Bipolar disorder: Evidence for a major locus

    Energy Technology Data Exchange (ETDEWEB)

    Spence, M.A.; Flodman, P.L. [Univ. of California, Irvine, CA (United States); Sadovnick, A.D.; Ameli, H. [Univ. of British Columbia, Vancouver (Canada)] [and others

    1995-10-09

    Complex segregation analyses were conducted on families of bipolar I and bipolar II probands to delineate the mode of inheritance. The probands were ascertained from consecutive referrals to the Mood Disorder Service, University Hospital, University of British Columbia and diagnosed by DSM-III-R and Research Diagnostic Criteria. Data were available on over 1,500 first-degree relatives of the 186 Caucasian probands. The purpose of the analyses was to determine if, after correcting for age and birth cohort, there was evidence for a single major locus. Five models were fit to the data using the statistical package SAGE: (1) dominant, (2) recessive, (3) arbitrary mendelian inheritance, (4) environmental, and (5) no major effects. A single dominant, mendelian major locus was the best fitting of these models for the sample of bipolar I and II probands when only bipolar relatives were defined as affected (polygenic inheritance could not be tested). Adding recurrent major depression to the diagnosis {open_quotes}affected{close_quotes} for relatives reduced the evidence for a major locus effect. Our findings support the undertaking of linkage studies and are consistent with the analyses of the National Institutes of Mental Health (NIMH) Collaborative Study data by Rice et al. and Blangero and Elston. 39 refs., 4 tabs.

  4. Quality of Experience for Large Ultra-High-Resolution Tiled Displays with Synchronization Mismatch

    Directory of Open Access Journals (Sweden)

    Deshpande Sachin

    2011-01-01

    Full Text Available This paper relates to quality of experience when viewing images, video, or other content on large ultra-high-resolution displays made from individual display tiles. We define experiments to measure vernier acuity caused by synchronization mismatch for moving images. The experiments are used to obtain synchronization mismatch acuity threshold as a function of object velocity and as a function of occlusion or gap width. Our main motivation for measuring the synchronization mismatch vernier acuity is its relevance in the application of tiled display systems, which create a single contiguous image using individual discrete panels arranged in a matrix with each panel utilizing a distributed synchronization algorithm to display parts of the overall image. We also propose a subjective assessment method for perception evaluation of synchronization mismatch for large ultra-high-resolution tiled displays. For this, we design a synchronization mismatch measurement test video set for various tile configurations for various interpanel synchronization mismatch values. The proposed method for synchronization mismatch perception can evaluate tiled displays with or without tile bezels. The results from this work can help during design of low-cost tiled display systems, which utilize distributed synchronization mechanisms for a contiguous or bezeled image display.

  5. The Risk of Transplant Failure With HLA Mismatch in First Adult Kidney Allografts From Deceased Donors.

    Science.gov (United States)

    Williams, Robert C; Opelz, Gerhard; McGarvey, Chelsea J; Weil, E Jennifer; Chakkera, Harini A

    2016-05-01

    Since the beginning of the technology, there has been active debate about the role of human leucocyte antigen (HLA) matching in kidney allograft survival. Recent studies have reported diminishing importance of HLA matching, which have, in turn, been challenged by reports that suggest the continuing importance of these loci. Given the controversies, we examined the effect of HLA compatibility on kidney allograft survival by studying all first adult kidney transplants in the United States from a deceased donor. Using the United Network for Organ Sharing data, we identified first deceased donor kidney transplants between October 1, 1987, and December 31, 2013. Recipients were classified by their number of HLA mismatches. Cox multivariate regression analyses adjusting for recipient and donor transplant characteristics were performed to determine the impact of HLA compatibility on kidney allograft survival. Study cohort included 189 141 first adult kidney alone transplants, with a total of 994 558 years of kidney allograft follow-up time. Analyses adjusted for recipient and donor characteristics demonstrated a 13% higher risk (hazard ratio, 1.13; 95% confidence interval, 1.06-1.21) with 1 mismatch and a 64% higher risk (hazard ratio, 1.64, 95% confidence interval, 1.56-1.73) with 6 mismatches. Dividing the mismatch categories into 27 ordered permutations, and testing their 57 within mismatch category differences, demonstrated that all but 1 were equal, independent of locus. A significant linear relationship of hazard ratios was associated with HLA mismatch and affects allograft survival even during the recent periods of increasing success in renal transplantation.

  6. Relative impact of human leukocyte antigen mismatching and graft ischemic time after lung transplantation.

    Science.gov (United States)

    Brugière, Olivier; Thabut, Gabriel; Suberbielle, Caroline; Reynaud-Gaubert, Martine; Thomas, Pascal; Pison, Christophe; Saint Raymond, Christel; Mornex, Jean-François; Bertocchi, Michèle; Dromer, Claire; Velly, Jean-François; Stern, Marc; Philippe, Bruno; Dauriat, Gaëlle; Biondi, Giuseppina; Castier, Yves; Fournier, Michel

    2008-06-01

    Recent data strongly suggest that human leukocyte antigen (HLA) mismatching has a negative impact on development of bronchiolitis obliterans syndrome (BOS) and survival after lung transplantation (LTx). Because HLA matching is sometimes achieved by extending ischemic time in other solid-organ transplantation models and ischemic time is a risk factor per se for death after LTx, we sought to compare the theoretical benefit of HLA matching with the negative impact of lengthened ischemic time. In this collaborative study we compared the relative impact of HLA mismatching and ischemic time on BOS and survival in 182 LTx recipients. Using multivariate analyses, we observed a lower incidence of BOS (hazard ratio [HR] = 1.70, 95% confidence interval [CI]: 1.1 to 2.7, p = 0.03) and enhanced survival (HR = 1.91, 95% CI: 1.24 to 2.92, p = 0.01) in patients with zero or one HLA-A mismatch compared with those having two HLA-A mismatches. This beneficial effect on survival was equivalent to a reduction of ischemic time of 168 minutes. We observed a reduced incidence of BOS and a better survival rate in patients well-matched at the HLA-A locus, associated with an opposite effect of an enhanced ischemic time. This suggests that graft ischemic time should be taken into account in future studies of prospective HLA matching in LTx.

  7. Mismatch repair genes Mlh1 and Mlh3 modify CAG instability in Huntington's disease mice: genome-wide and candidate approaches.

    Science.gov (United States)

    Pinto, Ricardo Mouro; Dragileva, Ella; Kirby, Andrew; Lloret, Alejandro; Lopez, Edith; St Claire, Jason; Panigrahi, Gagan B; Hou, Caixia; Holloway, Kim; Gillis, Tammy; Guide, Jolene R; Cohen, Paula E; Li, Guo-Min; Pearson, Christopher E; Daly, Mark J; Wheeler, Vanessa C

    2013-10-01

    The Huntington's disease gene (HTT) CAG repeat mutation undergoes somatic expansion that correlates with pathogenesis. Modifiers of somatic expansion may therefore provide routes for therapies targeting the underlying mutation, an approach that is likely applicable to other trinucleotide repeat diseases. Huntington's disease Hdh(Q111) mice exhibit higher levels of somatic HTT CAG expansion on a C57BL/6 genetic background (B6.Hdh(Q111) ) than on a 129 background (129.Hdh(Q111) ). Linkage mapping in (B6x129).Hdh(Q111) F2 intercross animals identified a single quantitative trait locus underlying the strain-specific difference in expansion in the striatum, implicating mismatch repair (MMR) gene Mlh1 as the most likely candidate modifier. Crossing B6.Hdh(Q111) mice onto an Mlh1 null background demonstrated that Mlh1 is essential for somatic CAG expansions and that it is an enhancer of nuclear huntingtin accumulation in striatal neurons. Hdh(Q111) somatic expansion was also abolished in mice deficient in the Mlh3 gene, implicating MutLγ (MLH1-MLH3) complex as a key driver of somatic expansion. Strikingly, Mlh1 and Mlh3 genes encoding MMR effector proteins were as critical to somatic expansion as Msh2 and Msh3 genes encoding DNA mismatch recognition complex MutSβ (MSH2-MSH3). The Mlh1 locus is highly polymorphic between B6 and 129 strains. While we were unable to detect any difference in base-base mismatch or short slipped-repeat repair activity between B6 and 129 MLH1 variants, repair efficiency was MLH1 dose-dependent. MLH1 mRNA and protein levels were significantly decreased in 129 mice compared to B6 mice, consistent with a dose-sensitive MLH1-dependent DNA repair mechanism underlying the somatic expansion difference between these strains. Together, these data identify Mlh1 and Mlh3 as novel critical genetic modifiers of HTT CAG instability, point to Mlh1 genetic variation as the likely source of the instability difference in B6 and 129 strains and suggest that MLH1

  8. Mismatch repair genes Mlh1 and Mlh3 modify CAG instability in Huntington's disease mice: genome-wide and candidate approaches.

    Directory of Open Access Journals (Sweden)

    Ricardo Mouro Pinto

    2013-10-01

    Full Text Available The Huntington's disease gene (HTT CAG repeat mutation undergoes somatic expansion that correlates with pathogenesis. Modifiers of somatic expansion may therefore provide routes for therapies targeting the underlying mutation, an approach that is likely applicable to other trinucleotide repeat diseases. Huntington's disease Hdh(Q111 mice exhibit higher levels of somatic HTT CAG expansion on a C57BL/6 genetic background (B6.Hdh(Q111 than on a 129 background (129.Hdh(Q111 . Linkage mapping in (B6x129.Hdh(Q111 F2 intercross animals identified a single quantitative trait locus underlying the strain-specific difference in expansion in the striatum, implicating mismatch repair (MMR gene Mlh1 as the most likely candidate modifier. Crossing B6.Hdh(Q111 mice onto an Mlh1 null background demonstrated that Mlh1 is essential for somatic CAG expansions and that it is an enhancer of nuclear huntingtin accumulation in striatal neurons. Hdh(Q111 somatic expansion was also abolished in mice deficient in the Mlh3 gene, implicating MutLγ (MLH1-MLH3 complex as a key driver of somatic expansion. Strikingly, Mlh1 and Mlh3 genes encoding MMR effector proteins were as critical to somatic expansion as Msh2 and Msh3 genes encoding DNA mismatch recognition complex MutSβ (MSH2-MSH3. The Mlh1 locus is highly polymorphic between B6 and 129 strains. While we were unable to detect any difference in base-base mismatch or short slipped-repeat repair activity between B6 and 129 MLH1 variants, repair efficiency was MLH1 dose-dependent. MLH1 mRNA and protein levels were significantly decreased in 129 mice compared to B6 mice, consistent with a dose-sensitive MLH1-dependent DNA repair mechanism underlying the somatic expansion difference between these strains. Together, these data identify Mlh1 and Mlh3 as novel critical genetic modifiers of HTT CAG instability, point to Mlh1 genetic variation as the likely source of the instability difference in B6 and 129 strains and suggest

  9. Allorecognition of HLA-C mismatches by CD8+ T cells in hematopoietic stem cell transplantation is a complex interplay between mismatched peptide binding region residues, HLA-C expression and HLA-DPB1 disparities

    Directory of Open Access Journals (Sweden)

    Florence Bettens

    2016-12-01

    Full Text Available HLA-C locus mismatches are the most frequent class I disparities in unrelated hematopoietic stem cell transplantation (HSCT and have a detrimental impact on clinical outcome. Recently, a few retrospective clinical studies have reported some variability in the immunogenicity of HLA-C incompatibilities. To get better insight into presumably permissive HLA-C mismatches we have developed a one-way in vitro mixed lymphocyte reaction (MLR assay allowing to quantify activated CD56-CD137+CD8+ lymphocytes in HLA-C incompatible combinations. T cell-mediated alloresponses were correlated with genetic markers such as HLA-C mRNA expression and the number of amino acid mismatches in the α1/α2 domains (peptide binding region. Because of the high rate of HLA-DPB1 incompatibilities in HLA-A, B, C, DRB1 and DQB1 matched unrelated HSCT patient/donor pairs, the impact of HLA-DPB1 mismatching, a potential bystander of CD4+ T cell activation, was also considered. Heterogeneous alloresponses were measured in 63 HLA-C mismatched pairs with a positive assay in 52% of the combinations (2.3-18.6% activated CTLs, representing 24 different HLA-A~B~DRB1~DQB1 haplotypes. There was no correlation between measured alloresponses and mRNA expression of the mismatched HLA-C alleles. The HLA-C*03:03/03:04 mismatch did not induce any positive alloresponse in 5 MLRs. We also identified HLA-C*02:02 and HLA-C*06:02 as mismatched alleles with lower immunogenicity, and HLA-C*14:02 as a more immunogenic mismatch. A difference of at least 10 amino acid residues known to impact peptide/TCR binding and a bystander HLA-DPB1 incompatibility had a significant impact on CTL alloreactivity (p=0.021. The same HLA-C mismatch, when recognized by two different responders with the same HLA haplotypes, was recognized differently, emphasizing the role of the T-cell repertoire of responding cells. In conclusion, mismatched HLA-C alleles differing by10 or more amino acids in the peptide/TCR binding

  10. Fixation probability in a two-locus intersexual selection model.

    Science.gov (United States)

    Durand, Guillermo; Lessard, Sabin

    2016-06-01

    We study a two-locus model of intersexual selection in a finite haploid population reproducing according to a discrete-time Moran model with a trait locus expressed in males and a preference locus expressed in females. We show that the probability of ultimate fixation of a single mutant allele for a male ornament introduced at random at the trait locus given any initial frequency state at the preference locus is increased by weak intersexual selection and recombination, weak or strong. Moreover, this probability exceeds the initial frequency of the mutant allele even in the case of a costly male ornament if intersexual selection is not too weak. On the other hand, the probability of ultimate fixation of a single mutant allele for a female preference towards a male ornament introduced at random at the preference locus is increased by weak intersexual selection and weak recombination if the female preference is not costly, and is strong enough in the case of a costly male ornament. The analysis relies on an extension of the ancestral recombination-selection graph for samples of haplotypes to take into account events of intersexual selection, while the symbolic calculation of the fixation probabilities is made possible in a reasonable time by an optimizing algorithm. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Selective tumor cell death induced by irradiated riboflavin through recognizing DNA G-T mismatch.

    Science.gov (United States)

    Yuan, Yi; Zhao, Yongyun; Chen, Lianqi; Wu, Jiasi; Chen, Gangyi; Li, Sheng; Zou, Jiawei; Chen, Rong; Wang, Jian; Jiang, Fan; Tang, Zhuo

    2017-09-06

    Riboflavin (vitamin B2) has been thought to be a promising antitumoral agent in photodynamic therapy, though the further application of the method was limited by the unclear molecular mechanism. Our work reveals that riboflavin was able to recognize G-T mismatch specifically and induce single-strand breaks in duplex DNA targets efficiently under irradiation. In the presence of riboflavin, the photo-irradiation could induce the death of tumor cells that are defective in mismatch repair system selectively, highlighting the G-T mismatch as potential drug target for tumor cells. Moreover, riboflavin is a promising leading compound for further drug design due to its inherent specific recognition of the G-T mismatch. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  12. A teleofunctional account of evolutionary mismatch.

    Science.gov (United States)

    Cofnas, Nathan

    When the environment in which an organism lives deviates in some essential way from that to which it is adapted, this is described as "evolutionary mismatch," or "evolutionary novelty." The notion of mismatch plays an important role, explicitly or implicitly, in evolution-informed cognitive psychology, clinical psychology, and medicine. The evolutionary novelty of our contemporary environment is thought to have significant implications for our health and well-being. However, scientists have generally been working without a clear definition of mismatch. This paper defines mismatch as deviations in the environment that render biological traits unable, or impaired in their ability, to produce their selected effects (i.e., to perform their proper functions in Neander's sense). The machinery developed by Millikan in connection with her account of proper function, and with her related teleosemantic account of representation, is used to identify four major types, and several subtypes, of evolutionary mismatch. While the taxonomy offered here does not in itself resolve any scientific debates, the hope is that it can be used to better formulate empirical hypotheses concerning the effects of mismatch. To illustrate, it is used to show that the controversial hypothesis that general intelligence evolved as an adaptation to handle evolutionary novelty can, contra some critics, be formulated in a conceptually coherent way.

  13. Inferring Demographic History Using Two-Locus Statistics.

    Science.gov (United States)

    Ragsdale, Aaron P; Gutenkunst, Ryan N

    2017-06-01

    Population demographic history may be learned from contemporary genetic variation data. Methods based on aggregating the statistics of many single loci into an allele frequency spectrum (AFS) have proven powerful, but such methods ignore potentially informative patterns of linkage disequilibrium (LD) between neighboring loci. To leverage such patterns, we developed a composite-likelihood framework for inferring demographic history from aggregated statistics of pairs of loci. Using this framework, we show that two-locus statistics are more sensitive to demographic history than single-locus statistics such as the AFS. In particular, two-locus statistics escape the notorious confounding of depth and duration of a bottleneck, and they provide a means to estimate effective population size based on the recombination rather than mutation rate. We applied our approach to a Zambian population of Drosophila melanogaster Notably, using both single- and two-locus statistics, we inferred a substantially lower ancestral effective population size than previous works and did not infer a bottleneck history. Together, our results demonstrate the broad potential for two-locus statistics to enable powerful population genetic inference. Copyright © 2017 by the Genetics Society of America.

  14. Two-locus linkage analysis in multiple sclerosis (MS)

    Energy Technology Data Exchange (ETDEWEB)

    Tienari, P.J. (National Public Health Institute, Helsinki (Finland) Univ. of Helsinki (Finland)); Terwilliger, J.D.; Ott, J. (Columbia Univ., New York (United States)); Palo, J. (Univ. of Helsinki (Finland)); Peltonen, L. (National Public Health Institute, Helsinki (Finland))

    1994-01-15

    One of the major challenges in genetic linkage analyses is the study of complex diseases. The authors demonstrate here the use of two-locus linkage analysis in multiple sclerosis (MS), a multifactorial disease with a complex mode of inheritance. In a set of Finnish multiplex families, they have previously found evidence for linkage between MS susceptibility and two independent loci, the myelin basic protein gene (MBP) on chromosome 18 and the HLA complex on chromosome 6. This set of families provides a unique opportunity to perform linkage analysis conditional on two loci contributing to the disease. In the two-trait-locus/two-marker-locus analysis, the presence of another disease locus is parametrized and the analysis more appropriately treats information from the unaffected family member than single-disease-locus analysis. As exemplified here in MS, the two-locus analysis can be a powerful method for investigating susceptibility loci in complex traits, best suited for analysis of specific candidate genes, or for situations in which preliminary evidence for linkage already exists or is suggested. 41 refs., 6 tabs.

  15. A P300 brain-computer interface based on a modification of the mismatch negativity paradigm.

    Science.gov (United States)

    Jin, Jing; Sellers, Eric W; Zhou, Sijie; Zhang, Yu; Wang, Xingyu; Cichocki, Andrzej

    2015-05-01

    The P300-based brain-computer interface (BCI) is an extension of the oddball paradigm, and can facilitate communication for people with severe neuromuscular disorders. It has been shown that, in addition to the P300, other event-related potential (ERP) components have been shown to contribute to successful operation of the P300 BCI. Incorporating these components into the classification algorithm can improve the classification accuracy and information transfer rate (ITR). In this paper, a single character presentation paradigm was compared to a presentation paradigm that is based on the visual mismatch negativity. The mismatch negativity paradigm showed significantly higher classification accuracy and ITRs than a single character presentation paradigm. In addition, the mismatch paradigm elicited larger N200 and N400 components than the single character paradigm. The components elicited by the presentation method were consistent with what would be expected from a mismatch paradigm and a typical P300 was also observed. The results show that increasing the signal-to-noise ratio by increasing the amplitude of ERP components can significantly improve BCI speed and accuracy. The mismatch presentation paradigm may be considered a viable option to the traditional P300 BCI paradigm.

  16. JOB MISMATCH – EFFECTS ON WORK PRODUCTIVITY

    Directory of Open Access Journals (Sweden)

    Magdalena Velciu

    2017-12-01

    Full Text Available Job matching and finding the best person to the right job inside the right company has become one of the most important and actual challenges of productivity. Not only full employment but the match between the employee and the job, in terms of educational level or field of activity, qualifications and skills of workforce; all have been the new gain of work productivity. Present article synthesizes the theoretical and empirical findings on effects of job mismatch by selecting the main findings about influence of job mismatches on work productivity including both employees and companies sides. on short term overeducation and overqualification could have a positive effect on productivity for one company, but on long term, mismatched worker would be affected by decreasing job satisfaction and lower wages. Also, at macroeconomic level, from a perspective of economy as a whole, job mismatches mean a loss of resources and human capital and could have negative effects on overall productivity. The opposite effects stay at the crossing between the employees, companies, policies and future development. In fact the effects of skill mismatch and productivity is a lost of work potential through inefficient resource (reallocation.

  17. Tolerance of DNA Mismatches in Dmc1 Recombinase-mediated DNA Strand Exchange*

    Science.gov (United States)

    Borgogno, María V.; Monti, Mariela R.; Zhao, Weixing; Sung, Patrick; Argaraña, Carlos E.; Pezza, Roberto J.

    2016-01-01

    Recombination between homologous chromosomes is required for the faithful meiotic segregation of chromosomes and leads to the generation of genetic diversity. The conserved meiosis-specific Dmc1 recombinase catalyzes homologous recombination triggered by DNA double strand breaks through the exchange of parental DNA sequences. Although providing an efficient rate of DNA strand exchange between polymorphic alleles, Dmc1 must also guard against recombination between divergent sequences. How DNA mismatches affect Dmc1-mediated DNA strand exchange is not understood. We have used fluorescence resonance energy transfer to study the mechanism of Dmc1-mediated strand exchange between DNA oligonucleotides with different degrees of heterology. The efficiency of strand exchange is highly sensitive to the location, type, and distribution of mismatches. Mismatches near the 3′ end of the initiating DNA strand have a small effect, whereas most mismatches near the 5′ end impede strand exchange dramatically. The Hop2-Mnd1 protein complex stimulates Dmc1-catalyzed strand exchange on homologous DNA or containing a single mismatch. We observed that Dmc1 can reject divergent DNA sequences while bypassing a few mismatches in the DNA sequence. Our findings have important implications in understanding meiotic recombination. First, Dmc1 acts as an initial barrier for heterologous recombination, with the mismatch repair system providing a second level of proofreading, to ensure that ectopic sequences are not recombined. Second, Dmc1 stepping over infrequent mismatches is likely critical for allowing recombination between the polymorphic sequences of homologous chromosomes, thus contributing to gene conversion and genetic diversity. PMID:26709229

  18. Tolerance of DNA Mismatches in Dmc1 Recombinase-mediated DNA Strand Exchange.

    Science.gov (United States)

    Borgogno, María V; Monti, Mariela R; Zhao, Weixing; Sung, Patrick; Argaraña, Carlos E; Pezza, Roberto J

    2016-03-04

    Recombination between homologous chromosomes is required for the faithful meiotic segregation of chromosomes and leads to the generation of genetic diversity. The conserved meiosis-specific Dmc1 recombinase catalyzes homologous recombination triggered by DNA double strand breaks through the exchange of parental DNA sequences. Although providing an efficient rate of DNA strand exchange between polymorphic alleles, Dmc1 must also guard against recombination between divergent sequences. How DNA mismatches affect Dmc1-mediated DNA strand exchange is not understood. We have used fluorescence resonance energy transfer to study the mechanism of Dmc1-mediated strand exchange between DNA oligonucleotides with different degrees of heterology. The efficiency of strand exchange is highly sensitive to the location, type, and distribution of mismatches. Mismatches near the 3' end of the initiating DNA strand have a small effect, whereas most mismatches near the 5' end impede strand exchange dramatically. The Hop2-Mnd1 protein complex stimulates Dmc1-catalyzed strand exchange on homologous DNA or containing a single mismatch. We observed that Dmc1 can reject divergent DNA sequences while bypassing a few mismatches in the DNA sequence. Our findings have important implications in understanding meiotic recombination. First, Dmc1 acts as an initial barrier for heterologous recombination, with the mismatch repair system providing a second level of proofreading, to ensure that ectopic sequences are not recombined. Second, Dmc1 stepping over infrequent mismatches is likely critical for allowing recombination between the polymorphic sequences of homologous chromosomes, thus contributing to gene conversion and genetic diversity. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Mechanical behaviour of cracked welded structures including mismatch effect

    International Nuclear Information System (INIS)

    Hornet, P.

    2002-01-01

    The most important parameters for predicting more precisely the fracture behaviour of welded structures have been identified. In particular, the plasticity development at the crack tip in the ligament appeared as a major parameter to evaluate the yield load of such a complex structure. In this way defect assessments procedures have been developed or modified to take into account the mismatch effect that is to say the mechanical properties of the different material constituting the weld joint. This paper is a synthesis of the work done in the past at Electricite de France on this topic in regards with other work done in France or around the World. The most important parameters which control the plasticity development at the crack tip and so mainly influence the fracture behaviour of welded structures are underlined: the mismatch ratio (weld to base metal yield strength ratio), the mismatch ratio (weld to base metal yield strength ratio), the ligament size and the weld width. Moreover, commonly used fracture toughness testing procedures developed in case of homogeneous specimens cannot be used in a straight forward manner and so has to be modified to take into account the mismatch effect. Number or defect assessment procedures taking into account the mismatch effect by considering the yield load of the welded structure are shortly described. Then, the 'Equivalent Material Method' developed at EDF which allows a good prediction of the applied J-Integral at the crack tip is more detailed. This procedure includes not only both weld and base metal yield strength, the structure geometry, the crack size and the weld dimension using the yield load of the real structures but also includes the effect of both weld and base metal strain hardening exponents. Some validations of this method are proposed. Finally, the ability of finite element modelling to predict the behaviour of such welded structures is demonstrated by modelling real experiments: crack located in the middle of

  20. Mismatch and noise in modern IC processes

    CERN Document Server

    Marshall, Andrew

    2009-01-01

    Component variability, mismatch, and various noise effects are major contributors to design limitations in most modern IC processes. Mismatch and Noise in Modern IC Processes examines these related effects and how they affect the building block circuits of modern integrated circuits, from the perspective of a circuit designer.Variability usually refers to a large scale variation that can occur on a wafer to wafer and lot to lot basis, and over long distances on a wafer. This phenomenon is well understood and the effects of variability are included in most integrated circuit design with the use

  1. Correlation of volumetric mismatch and mismatch of Alberta Stroke program Early CT scores on CT perfusion maps

    International Nuclear Information System (INIS)

    Lin, Ke; Rapalino, Otto; Lee, Benjamin; Do, Kinh G.; Sussmann, Amado R.; Pramanik, Bidyut K.; Law, Meng

    2009-01-01

    We aimed to determine if volumetric mismatch between tissue at risk and tissue destined to infarct on computed tomography perfusion (CTP) can be described by the mismatch of Alberta Stroke Program Early CT Score (ASPECTS). Forty patients with nonlacunar middle cerebral artery infarct 6 s and <2.0 mL per 100 g, respectively. Two other raters assigned ASPECTS to the same MTT and CBV maps while blinded to the volumetric data. Volumetric mismatch was deemed present if ≥20%. ASPECTS mismatch (=CBV ASPECTS - MTT ASPECTS) was deemed present if ≥1. Correlation between the two types of mismatches was assessed by Spearman's coefficient (ρ). ROC curve analyses were performed to determine the optimal ASPECTS mismatch cut point for volumetric mismatch ≥20%, ≥50%, ≥100%, and ≥150%. Median volumetric mismatch was 130% (range 10.9-2,031%) with 31 (77.5%) being ≥20%. Median ASPECTS mismatch was 2 (range 0-6) with 26 (65%) being ≥1. ASPECTS mismatch correlated strongly with volumetric mismatch with ρ = 0.763 [95% CI 0.585-0.870], p < 0.0001. Sensitivity and specificity for volumetric mismatch ≥20% was 83.9% [95% CI 65.5-93.5] and 100% [95% CI 65.9-100], respectively, using ASPECTS mismatch ≥1. Volumetric mismatch ≥50%, ≥100%, and ≥150% were optimally identified using ASPECTS mismatch ≥1, ≥2, and ≥2, respectively. On CTP, ASPECTS mismatch showed strong correlation to volumetric mismatch. ASPECTS mismatch ≥1 was the optimal cut point for volumetric mismatch ≥20%. (orig.)

  2. Wavelength mismatch effect in electromagnetically induced absorption

    Energy Technology Data Exchange (ETDEWEB)

    Bharti, Vineet [Department of Physics, Indian Institute of Science, Bangalore 560012 (India); Wasan, Ajay [Department of Physics, Indian Institute of Technology, Roorkee 247667 (India); Natarajan, Vasant [Department of Physics, Indian Institute of Science, Bangalore 560012 (India)

    2016-07-15

    We present a theoretical investigation of the phenomenon of electromagnetically induced absorption (EIA) in a 4-level system consisting of vee and ladder subsystems. The four levels are coupled using one weak probe field, and two strong control fields. We consider an experimental realization using energy levels of Rb. This necessitates dealing with different conditions of wavelength mismatch—near-perfect match where all three wavelengths are approximately equal; partial mismatch where the wavelength of one control field is less than the other fields; and complete mismatch where all three wavelengths are unequal. We present probe absorption profiles with Doppler averaging at room temperature to account for experiments in a room temperature Rb vapor cell. Our analysis shows that EIA resonances can be studied using Rydberg states excited with diode lasers. - Highlights: • Wavelength mismatch effect is investigated in electromagnetically induced absorption (EIA). • An experimental realization of 4-level vee + ladder system using energy levels of rubidium atom is presented. • EIA resonances are studied under different conditions of wavelength mismatch. • Possibility of observation of EIA using Rydberg states excited with diode lasers.

  3. Educational Mismatch and the Careers of Scientists

    Science.gov (United States)

    Bender, Keith A.; Heywood, John S.

    2011-01-01

    Previous research confirms that many employees work in jobs not well matched to their skills and education, resulting in lower pay and job satisfaction. While this literature typically uses cross-sectional data, we examine the evolution of mismatch and its consequences over a career, by using a panel data set of scientists in the USA. The results…

  4. Wavelength mismatch effect in electromagnetically induced absorption

    International Nuclear Information System (INIS)

    Bharti, Vineet; Wasan, Ajay; Natarajan, Vasant

    2016-01-01

    We present a theoretical investigation of the phenomenon of electromagnetically induced absorption (EIA) in a 4-level system consisting of vee and ladder subsystems. The four levels are coupled using one weak probe field, and two strong control fields. We consider an experimental realization using energy levels of Rb. This necessitates dealing with different conditions of wavelength mismatch—near-perfect match where all three wavelengths are approximately equal; partial mismatch where the wavelength of one control field is less than the other fields; and complete mismatch where all three wavelengths are unequal. We present probe absorption profiles with Doppler averaging at room temperature to account for experiments in a room temperature Rb vapor cell. Our analysis shows that EIA resonances can be studied using Rydberg states excited with diode lasers. - Highlights: • Wavelength mismatch effect is investigated in electromagnetically induced absorption (EIA). • An experimental realization of 4-level vee + ladder system using energy levels of rubidium atom is presented. • EIA resonances are studied under different conditions of wavelength mismatch. • Possibility of observation of EIA using Rydberg states excited with diode lasers.

  5. Mismatch repair deficiency does not enhance ENU mutagenesis in the zebrafish germ line.

    NARCIS (Netherlands)

    Feitsma, H.; de Bruijn, E.; van de Belt, J.; Nijman, I.J.; Cuppen, E.

    2008-01-01

    S(N)1-type alkylating agents such as N-ethyl-N-nitrosourea (ENU) are very potent mutagens. They act by transferring their alkyl group to DNA bases, which, upon mispairing during replication, can cause single base pair mutations in the next replication cycle. As DNA mismatch repair (MMR) proteins are

  6. Indium arsenide-on-SOI MOSFETs with extreme lattice mismatch

    Science.gov (United States)

    Wu, Bin

    Both molecular beam epitaxy (MBE) and metal organic chemical vapor deposition (MOCVD) have been used to explore the growth of InAs on Si. Despite 11.6% lattice mismatch, planar InAs structures have been observed by scanning electron microscopy (SEM) when nucleating using MBE on patterned submicron Si-on-insulator (SOI) islands. Planar structures of size as large as 500 x 500 nm 2 and lines of width 200 nm and length a few microns have been observed. MOCVD growth of InAs also generates single grain structures on Si islands when the size is reduced to 100 x 100 nm2. By choosing SOI as the growth template, selective growth is enabled by MOCVD. Post-growth pattern-then-anneal process, in which MOCVD InAs is deposited onto unpatterned SOI followed with patterning and annealing of InAs-on-Si structure, is found to change the relative lattice parameters of encapsulated 17/5 nm InAs/Si island. Observed from transmission electron diffraction (TED) patterns, the lattice mismatch of 17/5 nm InAs/Si island reduces from 11.2 to 4.2% after being annealed at 800°C for 30 minutes. High-k Al2O3 dielectrics have been deposited by both electron-beam-enabled physical vapor deposition (PVD) and atomic layer deposition (ALD). Films from both techniques show leakage currents on the order of 10-9A/cm2, at ˜1 MV/cm electric field, breakdown field > ˜6 MV/cm, and dielectric constant > 6, comparable to those of reported ALD prior arts by Groner. The first MOSFETs with extreme lattice mismatch InAs-on-SOI channels using PVD Al2O3 as the gate dielectric are characterized. Channel recess was used to improve the gate control of the drain current.

  7. Locus of Control and Obesity

    Directory of Open Access Journals (Sweden)

    Florence eNeymotin

    2014-10-01

    Full Text Available In the developed world, the hazards associated with obesity have largely outstripped the risk of starvation. Obesity remains a difficult public health issue to address, due in large part to the many disciplines involved. A full understanding requires knowledge in the fields of genetics, endocrinology, psychology, sociology, economics, and public policy – among others. In this short review, which serves as an introduction to the Frontiers in Endocrinology research topic, we address one cross-disciplinary relationship: the interaction between the hunger/satiation neural circuitry, an individual’s perceived locus of control, and the risk for obesity. Mammals have evolved a complex system for modulating energy intake. Overlaid on this, in humans, there exists a wide variation in perceived locus of control – that is, the extent to which an individual believes to be in charge of the events that affect them. Whether one has primarily an internal or external locus of control itself affects, and is affected by, external and physiological factors and has been correlated with the risk for obesity. Thus, the path from hunger and satiation to an individual’s actual behavior may often be moderated by psychological factors, included among which is locus of control.

  8. Locus of control and obesity.

    Science.gov (United States)

    Neymotin, Florence; Nemzer, Louis R

    2014-01-01

    In the developed world, the hazards associated with obesity have largely outstripped the risk of starvation. Obesity remains a difficult public health issue to address, due in large part to the many disciplines involved. A full understanding requires knowledge in the fields of genetics, endocrinology, psychology, sociology, economics, and public policy - among others. In this short review, which serves as an introduction to the Frontiers in Endocrinology research topic, we address one cross-disciplinary relationship: the interaction between the hunger/satiation neural circuitry, an individual's perceived locus of control, and the risk for obesity. Mammals have evolved a complex system for modulating energy intake. Overlaid on this, in humans, there exists a wide variation in "perceived locus of control" - that is, the extent to which an individual believes to be in charge of the events that affect them. Whether one has primarily an internal or external locus of control itself affects, and is affected by, external and physiological factors and has been correlated with the risk for obesity. Thus, the path from hunger and satiation to an individual's actual behavior may often be moderated by psychological factors, included among which is locus of control.

  9. Circuit mismatch influence on performance of paralleling silicon carbide MOSFETs

    DEFF Research Database (Denmark)

    Li, Helong; Munk-Nielsen, Stig; Pham, Cam

    2014-01-01

    This paper focuses on circuit mismatch influence on performance of paralleling SiC MOSFETs. Power circuit mismatch and gate driver mismatch influences are analyzed in detail. Simulation and experiment results show the influence of circuit mismatch and verify the analysis. This paper aims to give...... suggestions on paralleling discrete SiC MOSFETs and designing layout of power modules with paralleled SiC MOSFETs dies....

  10. Locus-specific view of flax domestication history

    Science.gov (United States)

    Fu, Yong-Bi; Diederichsen, Axel; Allaby, Robin G

    2012-01-01

    Crop domestication has been inferred genetically from neutral markers and increasingly from specific domestication-associated loci. However, some crops are utilized for multiple purposes that may or may not be reflected in a single domestication-associated locus. One such example is cultivated flax (Linum usitatissimum L.), the earliest oil and fiber crop, for which domestication history remains poorly understood. Oil composition of cultivated flax and pale flax (L. bienne Mill.) indicates that the sad2 locus is a candidate domestication locus associated with increased unsaturated fatty acid production in cultivated flax. A phylogenetic analysis of the sad2 locus in 43 pale and 70 cultivated flax accessions established a complex domestication history for flax that has not been observed previously. The analysis supports an early, independent domestication of a primitive flax lineage, in which the loss of seed dispersal through capsular indehiscence was not established, but increased oil content was likely occurred. A subsequent flax domestication process occurred that probably involved multiple domestications and includes lineages that contain oil, fiber, and winter varieties. In agreement with previous studies, oil rather than fiber varieties occupy basal phylogenetic positions. The data support multiple paths of flax domestication for oil-associated traits before selection of the other domestication-associated traits of seed dispersal loss and fiber production. The sad2 locus is less revealing about the origin of winter tolerance. In this case, a single domestication-associated locus is informative about the history of domesticated forms with the associated trait while partially informative on forms less associated with the trait. PMID:22408732

  11. A Bulky Rhodium Complex Bound to an Adenosine-Adenosine DNA Mismatch: General Architecture of the Metalloinsertion Binding Mode†

    Science.gov (United States)

    Zeglis, Brian M.; Pierre, Valérie C.; Kaiser, Jens T.; Barton, Jacqueline K.

    2009-01-01

    Two crystal structures are determined for Δ-Rh(bpy)2(chrysi)3+ (chrysi = 5,6-chrysenequinone diimine) bound to the oligonucleotide duplex 5′-CGGAAATTACCG-3′ containing two adenosine-adenosine mismatches (italics) through metalloinsertion. Diffraction quality crystals with two different space groups (P3221 and P43212) were obtained under very similar crystallization conditions. In both structures, the bulky rhodium complex inserts into the two mismatched sites from the minor groove side, ejecting the mismatched bases into the major groove. The conformational changes are localized to the mismatched site; the metal complex replaces the mismatched base pair without an increase in base pair rise. The expansive metal complex is accommodated in the duplex by a slight opening in the phosphodiester backbone; all sugars retain a C2′-endo puckering, and flanking base pairs neither stretch nor shear. The structures differ, however, in that in one of the structures, an additional metal complex is bound by intercalation from the major groove at the central 5′-AT-3′ step. We conclude that this additional metal complex is intercalated into this central step because of crystal packing forces. The structures described here of Δ-Rh(bpy)2(chrysi)3+ bound to thermodynamically destabilized AA mismatches share critical features with binding by metalloinsertion in two other oligonucleotides containing different single base mismatches. These results underscore the generality of the metalloinsertion as a new mode of non-covalent binding by small molecules with a DNA duplex. PMID:19374348

  12. Recommended practice for fracture toughness testing of weldments with strength mismatch

    International Nuclear Information System (INIS)

    Hornet, P.; Eripret, C.; Wang, Y.Y.; Kirk, M.T.; Gordon, J.R.

    1997-01-01

    Fracture toughness testing requires relationships between experimentally measured quantities, such as load and displacement, and J and crack tip opening displacement (CTOD).The relationships provided in the presently codified procedures (ASTM E813, E1152, E1290 et BSI 7848:Part 1) were derived under the assumption that the specimens have homogeneous mechanical properties. However, these codified procedures are frequently used for testing of weldments despite their strong mechanical properties variations. As a result, the accuracy of the toughness values (J or CCTOD) is sometimes in question. Systematic finite element studies of mismatched single-edge-notched-bend specimens (SENB) having a crack on the centerline have been conducted to resolve this question. The effect of various parameters on these relationships, such as weld size, degree of mismatch, and crack depth, is investigated. The accuracy of the codified J and CTOD testing procedures when applied to the mismatched SE(B) specimens is examined. This systematic examination is extended to several newly proposed procedures, such as those from Joch et al. and Hornet and Eripret. New J and CTOD estimations procedures are proposed. The expected error in applying the codified and the new procedures are shown are proposed. The expected error in applying the codified and the new procedures are shown in terms of mismatch level and level width. Recommendations are made on the use of those procedures for a variety of weld mismatch and crack depth conditions. (authors)

  13. Symptom-Hemodynamic Mismatch and Heart Failure Event Risk

    Science.gov (United States)

    Lee, Christopher S.; Hiatt, Shirin O.; Denfeld, Quin E.; Mudd, James O.; Chien, Christopher; Gelow, Jill M.

    2014-01-01

    Background Heart failure (HF) is a heterogeneous condition of both symptoms and hemodynamics. Objective The goal of this study was to identify distinct profiles among integrated data on physical and psychological symptoms and hemodynamics, and quantify differences in 180-day event-risk among observed profiles. Methods A secondary analysis of data collected during two prospective cohort studies by a single group of investigators was performed. Latent class mixture modeling was used to identify distinct symptom-hemodynamic profiles. Cox proportional hazards modeling was used to quantify difference in event-risk (HF emergency visit, hospitalization or death) among profiles. Results The mean age (n=291) was 57±13 years, 38% were female, and 61% had class III/IV HF. Three distinct symptom-hemodynamic profiles were identified. 17.9% of patients had concordant symptoms and hemodynamics (i.e. moderate physical and psychological symptoms matched the comparatively hemodynamic profile), 17.9% had severe symptoms and average hemodynamics, and 64.2% had poor hemodynamics and mild symptoms. Compared to those in the concordant profile, both profiles of symptom-hemodynamic mismatch were associated with a markedly increased event-risk (severe symptoms hazards ratio = 3.38, p=0.033; poor hemodynamics hazards ratio = 3.48, p=0.016). Conclusions A minority of adults with HF have concordant symptoms and hemodynamics. Either profile of symptom-hemodynamic mismatch in HF is associated with a greater risk of healthcare utilization for HF or death. PMID:24988323

  14. Architectural mismatch issues in identity management deployment

    DEFF Research Database (Denmark)

    Andersen, Mads Schaarup

    2010-01-01

    Integrating Commercial Off-The-Shelf products in a company's software product portfolio offers business value, but introduces challenges from a software architecture perspective. In this paper, the research challenges in relation to identity management in the Danish municipality administration...... system called Opus, are outlined. Opus BRS is the identity management part of Opus. Opus integrates SAP, legacy mainframe systems, and other third party systems of the individual municipality. Each of these systems define their own software architecture and access control model, leading to architectural...... mismatch with an impact on security, usability, and maintainability. The research project is discussed and access control and identity provisioning are recognized as the major areas of interest in relation to the mismatch challenges. The project is carried out in close cooperation with KMD, one...

  15. Multiuser Random Coding Techniques for Mismatched Decoding

    OpenAIRE

    Scarlett, Jonathan; Martinez, Alfonso; Guillén i Fàbregas, Albert

    2016-01-01

    This paper studies multiuser random coding techniques for channel coding with a given (possibly suboptimal) decoding rule. For the mismatched discrete memoryless multiple-access channel, an error exponent is obtained that is tight with respect to the ensemble average, and positive within the interior of Lapidoth's achievable rate region. This exponent proves the ensemble tightness of the exponent of Liu and Hughes in the case of maximum-likelihood decoding. An equivalent dual form of Lapidoth...

  16. Thermodynamic characterization of tandem mismatches found in naturally occurring RNA

    Science.gov (United States)

    Christiansen, Martha E.; Znosko, Brent M.

    2009-01-01

    Although all sequence symmetric tandem mismatches and some sequence asymmetric tandem mismatches have been thermodynamically characterized and a model has been proposed to predict the stability of previously unmeasured sequence asymmetric tandem mismatches [Christiansen,M.E. and Znosko,B.M. (2008) Biochemistry, 47, 4329–4336], experimental thermodynamic data for frequently occurring tandem mismatches is lacking. Since experimental data is preferred over a predictive model, the thermodynamic parameters for 25 frequently occurring tandem mismatches were determined. These new experimental values, on average, are 1.0 kcal/mol different from the values predicted for these mismatches using the previous model. The data for the sequence asymmetric tandem mismatches reported here were then combined with the data for 72 sequence asymmetric tandem mismatches that were published previously, and the parameters used to predict the thermodynamics of previously unmeasured sequence asymmetric tandem mismatches were updated. The average absolute difference between the measured values and the values predicted using these updated parameters is 0.5 kcal/mol. This updated model improves the prediction for tandem mismatches that were predicted rather poorly by the previous model. This new experimental data and updated predictive model allow for more accurate calculations of the free energy of RNA duplexes containing tandem mismatches, and, furthermore, should allow for improved prediction of secondary structure from sequence. PMID:19509311

  17. Inferring relationships between pairs of individuals from locus heterozygosities

    Directory of Open Access Journals (Sweden)

    Spinetti Isabella

    2002-11-01

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

  18. Heterogenous mismatch-repair status in colorectal cancer

    DEFF Research Database (Denmark)

    Joost, Patrick; Veurink, Nynke; Holck, Susanne

    2014-01-01

    BACKGROUND: Immunohistochemical staining for mismatch repair proteins is efficient and widely used to identify mismatch repair defective tumors. The tumors typically show uniform and widespread loss of MMR protein staining. We identified and characterized colorectal cancers with alternative......, heterogenous mismatch repair protein staining in order to delineate expression patterns and underlying mechanisms. METHODS: Heterogenous staining patterns that affected at least one of the mismatch repair proteins MLH1, PMS2, MSH2 and MSH6 were identified in 14 colorectal cancers. Based on alternative....... CONCLUSIONS: Heterogenous mismatch repair status can be demonstrated in colorectal cancer. Though rare, attention to this phenomenon is recommended since it corresponds to differences in mismatch repair status that are relevant for correct classification. VIRTUAL SLIDES: The virtual slide(s) for this article...

  19. The Ties that Bind (the Igh Locus).

    Science.gov (United States)

    Krangel, Michael S

    2016-05-01

    Immunoglobulin heavy-chain locus V(D)J recombination requires a 3D chromatin organization which permits widely distributed variable (V) gene segments to contact distant diversity (D) and joining (J) gene segments. A recent study has identified key nodes in the locus interactome, paving the way for new molecular insights into how the locus is configured for recombination. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Possible roles for mismatch negativity in neuropsychiatry.

    Science.gov (United States)

    Gené-Cos, N; Ring, H A; Pottinger, R C; Barrett, G

    1999-01-01

    This article reviews research on the main characteristics of mismatch negativity (MMN) and its applications in neuropsychiatry. Event-related potentials (ERPs) have been used to study many aspects of information processing. Mismatch negativity is an early auditory ERP that has been identified as an index of an automatic (preconscious) alerting mechanism stimulating an individual to attend to unexpected environmental events. Disturbances of MMN may relate to abnormalities of auditory information processing contributing to the pathophysiology of neuropsychiatric conditions. The authors review (1) studies that have evaluated the electrophysiological aspects of MMN and (2) studies that have investigated the different applications of MMN in neuropsychiatry. The first part of this article describes the characteristics of MMN, its cerebral origins, and electrophysiological parameters. We then discuss the role of "echoic memory" as well as that of attention and vigilance. In the second part of the article, disturbances in MMN associated with schizophrenia, depressive illness, dementing processes, and other neuropsychiatric states are discussed. MMN is a preconscious cognitive ERP, the main generators and functions of which are well defined. Observations relating to the origins of MMN and its role in early auditory information processing together with its possible behavioral significance, combined with observations of MMN aberrations in psychiatric conditions, may provide novel insights into the pathophysiology of neuropsychiatric states.

  1. Mismatch removal via coherent spatial relations

    Science.gov (United States)

    Chen, Jun; Ma, Jiayi; Yang, Changcai; Tian, Jinwen

    2014-07-01

    We propose a method for removing mismatches from the given putative point correspondences in image pairs based on "coherent spatial relations." Under the Bayesian framework, we formulate our approach as a maximum likelihood problem and solve a coherent spatial relation between the putative point correspondences using an expectation-maximization (EM) algorithm. Our approach associates each point correspondence with a latent variable indicating it as being either an inlier or an outlier, and alternatively estimates the inlier set and recovers the coherent spatial relation. It can handle not only the case of image pairs with rigid motions but also the case of image pairs with nonrigid motions. To parameterize the coherent spatial relation, we choose two-view geometry and thin-plate spline as models for rigid and nonrigid cases, respectively. The mismatches could be successfully removed via the coherent spatial relations after the EM algorithm converges. The quantitative results on various experimental data demonstrate that our method outperforms many state-of-the-art methods, it is not affected by low initial correct match percentages, and is robust to most geometric transformations including a large viewing angle, image rotation, and affine transformation.

  2. Scale Mismatches in Management of Urban Landscapes

    Directory of Open Access Journals (Sweden)

    Sara T. Borgström

    2006-12-01

    Full Text Available Urban landscapes constitute the future environment for most of the world's human population. An increased understanding of the urbanization process and of the effects of urbanization at multiple scales is, therefore, key to ensuring human well-being. In many conventional natural resource management regimes, incomplete knowledge of ecosystem dynamics and institutional constraints often leads to institutional management frameworks that do not match the scale of ecological patterns and processes. In this paper, we argue that scale mismatches are particularly pronounced in urban landscapes. Urban green spaces provide numerous important ecosystem services to urban citizens, and the management of these urban green spaces, including recognition of scales, is crucial to the well-being of the citizens. From a qualitative study of the current management practices in five urban green spaces within the Greater Stockholm Metropolitan Area, Sweden, we found that 1 several spatial, temporal, and functional scales are recognized, but the cross-scale interactions are often neglected, and 2 spatial and temporal meso-scales are seldom given priority. One potential effect of the neglect of ecological cross-scale interactions in these highly fragmented landscapes is a gradual reduction in the capacity of the ecosystems to provide ecosystem services. Two important strategies for overcoming urban scale mismatches are suggested: 1 development of an integrative view of the whole urban social-ecological landscape, and 2 creation of adaptive governance systems to support practical management.

  3. Identification of a mismatch-specific endonuclease in hyperthermophilic Archaea

    OpenAIRE

    Ishino, Sonoko; Nishi, Yuki; Oda, Soichiro; Uemori, Takashi; Sagara, Takehiro; Takatsu, Nariaki; Yamagami, Takeshi; Shirai, Tsuyoshi; Ishino, Yoshizumi

    2016-01-01

    The common mismatch repair system processed by MutS and MutL and their homologs was identified in Bacteria and Eukarya. However, no evidence of a functional MutS/L homolog has been reported for archaeal organisms, and it is not known whether the mismatch repair system is conserved in Archaea. Here, we describe an endonuclease that cleaves double-stranded DNA containing a mismatched base pair, from the hyperthermophilic archaeon Pyrococcus furiosus. The corresponding gene revealed that the act...

  4. Currency Mismatch, Balance-sheet effect and Monetary Policy

    OpenAIRE

    Nakamura, Chikafumi

    2011-01-01

    This paper analyzes the impact of the currency mismatch between assets and liabilities on monetary policy. The currency mismatch causes macroeconomic instability through balance-sheet effects. To analyze the problem, we apply a small open economy dynamic stochastic general equilibrium model with international credit-market imperfections. As a result, despitethe currency mismatch and high trade openness, a targeting rule to address the terms of trade is not efficient. This result depends on...

  5. Mismatch negativity: clinical and other applications.

    Science.gov (United States)

    Näätänen, R; Escera, C

    2000-01-01

    The perspectives of application of the mismatch negativity (MMN), generated by the brain's automatic response to change in auditory stimulation, are discussed. In light of the fact that the MMN (and its magnetic equivalent MMNm) currently provides the only objective measure of the accuracy of the central auditory function, these perspectives appear very promising. The MMN can be measured in the absence of attention and task requirements, which makes it particularly suitable for testing different clinical populations and infants. Furthermore, the MMN enables one to evaluate the accuracy of auditory discrimination separately for any acoustic feature, such as frequency, intensity and duration, and for learned categories, such as the phonemes of a particular language. In addition, by measuring the decay of the MMN amplitude as a function of the interstimulus interval, it is possible to estimate the duration of sensory (echoic) memory. Copyright 2000 S. Karger AG, Basel

  6. Mismatch Negativity in Patients with Schizophrenia

    Directory of Open Access Journals (Sweden)

    Aleš Urban

    2007-01-01

    Full Text Available Cognitive deficit is considered to be a part of core dysfuncions in schizophrenia. It is associated with social impairment and influences the long-term course of the disorder. In addition to neuropsychological methods, event-related potentials can be used to study cognitive functions. In patients with schizophrenia an association was found between amplitude changes in slow negative component of evoked responses and infrequent deviations in a series of uniform stimuli. This amplitude change is known as „mismatch negativity“ (MMN. It is supposed to be independent of the focused attention and effort that otherwise interfere with neuropsychological testing. Recently accumulated knowledge on MMN as a possible preattentive measure of cognition supports its potential significance for neuropsychological assessment. It may be helpful in more precise diagnosis and functional evaluation of schizophrenia.

  7. Locus: mede-ontwikkelaar van inclusieve arbeidsorganisaties

    NARCIS (Netherlands)

    Beukema, Leni; de Lange, Annet; Wielenga-Meijer, Etty; Duijker, Theo; Hanstede, Bram

    2018-01-01

    in deze bijdrage wordt Locus beschreven, een netwerk waarin publieke partijen en grote, landelijk opererende bedrijven samenwerken om mensen met een afstand tot de arbeidsmarkt duurzaam aan het werk te helpen. Het hoofdstuk start met de ontstaansgeschiedenis en benadering van Locus. Vervolgens wordt

  8. Genetic analysis of the claret locus of Drosophila melanogaster

    International Nuclear Information System (INIS)

    Sequeira, W.; Nelson, C.R.; Szauter, P.

    1989-01-01

    The claret (ca) locus of Drosophila melanogaster comprises two separately mutable domains, one responsible for eye color and one responsible for proper disjunction of chromosomes in meiosis and early cleavage divisions. Previously isolated alleles are of three types: (1) alleles of the claret (ca) type that affect eye color only, (2) alleles of the claret-nondisjunctional (ca nd ) type that affect eye color and chromosome behavior, and (3) a meiotic mutation, non-claret disjunctional (ncd), that affects chromosome behavior only. In order to investigate the genetic structure of the claret locus, the authors have isolated 19 radiation-induced alleles of claret on the basis of the eye color phenotype. Two of these 19 new alleles are of the ca nd type, while 17 are of the ca type, demonstrating that the two domains do not often act as a single target for mutagenesis. This suggests that the two separately mutable functions are likely to be encoded by separate or overlapping genes rather than by a single gene. One of the new alleles of the ca nd type is a chromosome rearrangement with a breakpoint at the position of the claret locus. If this breakpoint is the cause of the mutant phenotype and there are no other mutations associated with the rearrangement, the two functions must be encoded by overlapping genes

  9. Constitutioneel ‘mismatch repair’-deficiëntiesyndroom

    NARCIS (Netherlands)

    Jongmans, Marjolijn C.; Gidding, Corrie E.; Loeffen, Jan; Wesseling, Pieter; Mensenkamp, Arjen; Hoogerbrugge, Nicoline

    2015-01-01

    Constitutional mismatch repair deficiency (CMMRD) syndrome is characterised by a significantly increased risk for developing cancer in childhood. It arises when both parents have a mutation in the same mismatch repair gene and pass it on to their child. Case description An 8yearold girl was

  10. Speaking Self-Assessment: Mismatches between Learners' and Teachers' Criteria

    Science.gov (United States)

    Babaii, Esmat; Taghaddomi, Shahin; Pashmforoosh, Roya

    2016-01-01

    Perceptual (mis)matches between teachers and learners are said to affect learning success or failure. Self-assessment, as a formative assessment tool, may, inter alia, be considered a means to minimize such mismatches. Therefore, the present study investigated the extent to which learners' assessment of their own speaking performance, before and…

  11. Mismatch-Shaping Serial Digital-to-Analog Converter

    DEFF Research Database (Denmark)

    Steensgaard-Madsen, Jesper; Moon, Un-Ku; Temes, Gabor C.

    1999-01-01

    A simple but accurate pseudo-passive mismatch-shaping D/A converter is described. A digital state machine is used to control the switching sequence of a symmetric two-capacitor network that performs the D/A conversion. The error caused by capacitor mismatch is uncorrelated with the input signal...

  12. Alignment to natural and imposed mismatches between the senses

    NARCIS (Netherlands)

    van der Kooij, K.; Brenner, E.; van Beers, R.J.; Schot, W.D.; Smeets, J.B.J.

    2013-01-01

    Does the nervous system continuously realign the senses so that objects are seen and felt in the same place? Conflicting answers to this question have been given. Research imposing a sensory mismatch has provided evidence that the nervous system realigns the senses to reduce the mismatch. Other

  13. Mismatch Repair Balances Leading and Lagging Strand DNA Replication Fidelity

    Science.gov (United States)

    2012-10-11

    Rev Mol Cell Biol 7: 335–346. 7. Li GM (2008) Mechanisms and functions of DNA mismatch repair. Cell Res 18: 85–98. 8. Pavlov YI, Mian IM, Kunkel TA...11: 165–170. 41. Li F, Tian L, Gu L, Li GM (2009) Evidence that nucleosomes inhibit mismatch repair in eukaryotic cells. J Biol Chem 284: 33056–33061

  14. Mismatch-Shaped Pseudo-Passive Two-Capacitor DAC

    DEFF Research Database (Denmark)

    Steensgaard-Madsen, Jesper; Moon, Un-Ku; Temes, Gabor C.

    1999-01-01

    A simple mismatch-shaping scheme is proposed for a two-capacitor DAC. Unlike in other mismatch-shaping systems, the shaped error is generated by direct filtering of a well-defined bounded signal, which can be generated as white noise. The operation is closely related to a specific digital...

  15. Influence of halo doping profiles on MOS transistor mismatch

    NARCIS (Netherlands)

    Andricciola, P.; Tuinhout, H.

    2009-01-01

    Halo implants are used in modern CMOS technology to reduce the short channel effect. However, the lateral non-uniformity of the channel doping has been proven to degenerate the mismatch performance. With this paper we want to discuss the influence of the halo profile on MOS transistor mismatch. The

  16. EL LOCUS DE DISTRIBUCION COMO COROLARIO DEL LOCUS DE CONTROL

    Directory of Open Access Journals (Sweden)

    Luisa Mayoral

    2009-01-01

    Full Text Available Este es un artículo científico acerca del Locus de Distribución, surgido de un estudio realizado con una población de docentes y alumnos universitarios. Respecto de los primeros, se ha indagado acerca de las atribuciones que se realizaban en torno a las recompensas y sanciones, que ellos distribuían a sus alumnos. Respecto de los segundos, se ha buscado determinar la valoración que estos realizaban de sus profesores, en términos de aquellas atribuciones. Para ello, se utilizaron dos paradigmas clásicamente empleados para verificar la existencia de una norma: el paradigma de la autopresentación (docentes, y el paradigma de los juicios (alumnos. La cuestión planteada fue determinar si en el caso de los comportamientos distributivos de refuerzos, las causas se atribuían a variables externas -en particular a los receptores de esos refuerzos- y si esas formas de atribución eran conocidas y valoradas o no, por los alumnos. De los resultados, surgió la confirmación de nuestra hipótesis de explicaciones externas en materia de comportamientos distributivos de sanciones en el ámbito de la docencia y la valoración positiva de estas atribuciones por los alumnos.

  17. An Inducible, Isogenic Cancer Cell Line System for Targeting the State of Mismatch Repair Deficiency

    Science.gov (United States)

    Bailis, Julie M.; Gordon, Marcia L.; Gurgel, Jesse L.; Komor, Alexis C.; Barton, Jacqueline K.; Kirsch, Ilan R.

    2013-01-01

    The DNA mismatch repair system (MMR) maintains genome stability through recognition and repair of single-base mismatches and small insertion-deletion loops. Inactivation of the MMR pathway causes microsatellite instability and the accumulation of genomic mutations that can cause or contribute to cancer. In fact, 10-20% of certain solid and hematologic cancers are MMR-deficient. MMR-deficient cancers do not respond to some standard of care chemotherapeutics because of presumed increased tolerance of DNA damage, highlighting the need for novel therapeutic drugs. Toward this goal, we generated isogenic cancer cell lines for direct comparison of MMR-proficient and MMR-deficient cells. We engineered NCI-H23 lung adenocarcinoma cells to contain a doxycycline-inducible shRNA designed to suppress the expression of the mismatch repair gene MLH1, and compared single cell subclones that were uninduced (MLH1-proficient) versus induced for the MLH1 shRNA (MLH1-deficient). Here we present the characterization of these MMR-inducible cell lines and validate a novel class of rhodium metalloinsertor compounds that differentially inhibit the proliferation of MMR-deficient cancer cells. PMID:24205301

  18. Variants of sequence family B Thermococcus kodakaraensis DNA polymerase with increased mismatch extension selectivity.

    Directory of Open Access Journals (Sweden)

    Claudia Huber

    Full Text Available Fidelity and selectivity of DNA polymerases are critical determinants for the biology of life, as well as important tools for biotechnological applications. DNA polymerases catalyze the formation of DNA strands by adding deoxynucleotides to a primer, which is complementarily bound to a template. To ensure the integrity of the genome, DNA polymerases select the correct nucleotide and further extend the nascent DNA strand. Thus, DNA polymerase fidelity is pivotal for ensuring that cells can replicate their genome with minimal error. DNA polymerases are, however, further optimized for more specific biotechnological or diagnostic applications. Here we report on the semi-rational design of mutant libraries derived by saturation mutagenesis at single sites of a 3'-5'-exonuclease deficient variant of Thermococcus kodakaraensis DNA polymerase (KOD pol and the discovery for variants with enhanced mismatch extension selectivity by screening. Sites of potential interest for saturation mutagenesis were selected by their proximity to primer or template strands. The resulting libraries were screened via quantitative real-time PCR. We identified three variants with single amino acid exchanges-R501C, R606Q, and R606W-which exhibited increased mismatch extension selectivity. These variants were further characterized towards their potential in mismatch discrimination. Additionally, the identified enzymes were also able to differentiate between cytosine and 5-methylcytosine. Our results demonstrate the potential in characterizing and developing DNA polymerases for specific PCR based applications in DNA biotechnology and diagnostics.

  19. Translocations affecting human immunoglobulin heavy chain locus

    Directory of Open Access Journals (Sweden)

    Sklyar I. V.

    2014-03-01

    Full Text Available Translocations involving human immunoglobulin heavy chain (IGH locus are implicated in different leukaemias and lymphomas, including multiple myeloma, mantle cell lymphoma, Burkitt’s lymphoma and diffuse large B cell lymphoma. We have analysed published data and identified eleven breakpoint cluster regions (bcr related to these cancers within the IgH locus. These ~1 kbp bcrs are specific for one or several types of blood cancer. Our findings could help devise PCR-based assays to detect cancer-related translocations, to identify the mechanisms of translocations and to help in the research of potential translocation partners of the immunoglobulin locus at different stages of B-cell differentiation.

  20. Generalized synchronization induced by noise and parameter mismatching in Hindmarsh-Rose neurons

    International Nuclear Information System (INIS)

    Wu Ying; Xu Jianxue; He Daihai; Earn, David J.D.

    2005-01-01

    Synchronization of two simple neuron models has been investigated in many studies. Thresholds for complete synchronization (CS) and phase synchronization (PS) have been obtained for coupling by diffusion or noise. In addition, it has been shown that it is possible for directional diffusion to induce generalized synchronization (GS) in a pair of neuron models even if the neurons are not identical (and differ in a single parameter). We study a system of two uncoupled, nonidentical Hindmarsh-Rose (HR) neurons and show that GS can be achieved by a combination of noise and changing the value of a second parameter in one of the neurons (the second parameter mismatch cancels the first). The significance of this approach will be the greatest in situations where the parameter that is originally mismatched cannot be controlled, but a suitable controllable parameter can be identified

  1. Origin of allelic diversity in antirrhinum S locus RNases.

    Science.gov (United States)

    Xue, Y; Carpenter, R; Dickinson, H G; Coen, E S

    1996-01-01

    In many plant species, self-incompatibility (SI) is genetically controlled by a single multiallelic S locus. Previous analysis of S alleles in the Solanaceae, in which S locus ribonucleases (S RNases) are responsible for stylar expression of SI, has demonstrated that allelic diversity predated speciation within this family. To understand how allelic diversity has evolved, we investigated the molecular basis of gametophytic SI in Antirrhinum, a member of the Scrophulariaceae, which is closely related to the Solanaceae. We have characterized three Antirrhinum cDNAs encoding polypeptides homologous to S RNases and shown that they are encoded by genes at the S locus. RNA in situ hybridization revealed that the Antirrhinum S RNase are primarily expressed in the stylar transmitting tissue. This expression is consistent with their proposed role in arresting the growth of self-pollen tubes. S alleles from the Scrophulariaceae form a separate group from those of the Solanaceae, indicating that new S alleles have been generated since these families separated (approximately 40 million years). We propose that the recruitment of an ancestral RNase gene into SI occurred during an early stage of angiosperm evolution and that, since that time, new alleles subsequently have arisen at a low rate. PMID:8672882

  2. Responses of prefrontal multisensory neurons to mismatching faces and vocalizations.

    Science.gov (United States)

    Diehl, Maria M; Romanski, Lizabeth M

    2014-08-20

    Social communication relies on the integration of auditory and visual information, which are present in faces and vocalizations. Evidence suggests that the integration of information from multiple sources enhances perception compared with the processing of a unimodal stimulus. Our previous studies demonstrated that single neurons in the ventrolateral prefrontal cortex (VLPFC) of the rhesus monkey (Macaca mulatta) respond to and integrate conspecific vocalizations and their accompanying facial gestures. We were therefore interested in how VLPFC neurons respond differentially to matching (congruent) and mismatching (incongruent) faces and vocalizations. We recorded VLPFC neurons during the presentation of movies with congruent or incongruent species-specific facial gestures and vocalizations as well as their unimodal components. Recordings showed that while many VLPFC units are multisensory and respond to faces, vocalizations, or their combination, a subset of neurons showed a significant change in neuronal activity in response to incongruent versus congruent vocalization movies. Among these neurons, we typically observed incongruent suppression during the early stimulus period and incongruent enhancement during the late stimulus period. Incongruent-responsive VLPFC neurons were both bimodal and nonlinear multisensory, fostering their ability to respond to changes in either modality of a face-vocalization stimulus. These results demonstrate that ventral prefrontal neurons respond to changes in either modality of an audiovisual stimulus, which is important in identity processing and for the integration of multisensory communication information. Copyright © 2014 the authors 0270-6474/14/3411233-11$15.00/0.

  3. A large duplication involving the IHH locus mimics acrocallosal syndrome.

    Science.gov (United States)

    Yuksel-Apak, Memnune; Bögershausen, Nina; Pawlik, Barbara; Li, Yun; Apak, Selcuk; Uyguner, Oya; Milz, Esther; Nürnberg, Gudrun; Karaman, Birsen; Gülgören, Ayan; Grzeschik, Karl-Heinz; Nürnberg, Peter; Kayserili, Hülya; Wollnik, Bernd

    2012-06-01

    Indian hedgehog (Ihh) signaling is a major determinant of various processes during embryonic development and has a pivotal role in embryonic skeletal development. A specific spatial and temporal expression of Ihh within the developing limb buds is essential for accurate digit outgrowth and correct digit number. Although missense mutations in IHH cause brachydactyly type A1, small tandem duplications involving the IHH locus have recently been described in patients with mild syndactyly and craniosynostosis. In contrast, a ∼600-kb deletion 5' of IHH in the doublefoot mouse mutant (Dbf) leads to severe polydactyly without craniosynostosis, but with craniofacial dysmorphism. We now present a patient resembling acrocallosal syndrome (ACS) with extensive polysyndactyly of the hands and feet, craniofacial abnormalities including macrocephaly, agenesis of the corpus callosum, dysplastic and low-set ears, severe hypertelorism and profound psychomotor delay. Single-nucleotide polymorphism (SNP) array copy number analysis identified a ∼900-kb duplication of the IHH locus, which was confirmed by an independent quantitative method. A fetus from a second pregnancy of the mother by a different spouse showed similar craniofacial and limb malformations and the same duplication of the IHH-locus. We defined the exact breakpoints and showed that the duplications are identical tandem duplications in both sibs. No copy number changes were observed in the healthy mother. To our knowledge, this is the first report of a human phenotype similar to the Dbf mutant and strikingly overlapping with ACS that is caused by a copy number variation involving the IHH locus on chromosome 2q35.

  4. 3D heteroepitaxy of mismatched semiconductors on silicon

    International Nuclear Information System (INIS)

    Falub, Claudiu V.; Kreiliger, Thomas; Isa, Fabio; Taboada, Alfonso G.; Meduňa, Mojmír; Pezzoli, Fabio; Bergamaschini, Roberto; Marzegalli, Anna; Müller, Elisabeth; Chrastina, Daniel; Isella, Giovanni; Neels, Antonia; Niedermann, Philippe; Dommann, Alex; Miglio, Leo; Känel, Hans von

    2014-01-01

    We present a method for monolithically integrating mismatched semiconductor materials with Si, coined three-dimensional (3D) heteroepitaxy. The method comprises the replacement of conventional, continuous epilayers by dense arrays of strain- and defect-free, micron-sized crystals. The crystals are formed by a combination of deep-patterning of the Si substrates and self-limited lateral expansion during the epitaxial growth. Consequently, the longstanding issues of crack formation and wafer bowing can be avoided. Moreover, threading dislocations can be eliminated by appropriately choosing pattern sizes, layer thicknesses and surface morphology, the latter being dependent on the growth temperature. We show this approach to be valid for various material combinations, pattern geometries and substrate orientations. We demonstrate that Ge crystals evolve into perfect structures away from the heavily dislocated interface with Si, by using a synchrotron X-ray beam focused to a spot a few hundred nanometers in size and by recording 3D reciprocal space maps along their height. Room temperature photoluminescence (PL) experiments reveal that the interband integrated PL intensity of the Ge crystals is enhanced by almost three orders of magnitude with respect to that of Ge epilayers directly grown on flat Si substrates. Electrical measurements performed on single heterojunction diodes formed between 3D Ge crystals and the Si substrate exhibit rectifying behavior with dark currents of the order of 1 mA/cm 2 . For GaAs the thermal strain relaxation as a function of pattern size is similar to that found for group IV materials. Significant differences exist, however, in the evolution of crystal morphology with pattern size, which more and more tends to a pyramidal shape defined by stable {111} facets with decreasing width of the Si pillars. - Highlights: • Νew method for integrating mismatched semiconductors • Arrays of three-dimensional epitaxial Ge and GaAs crystals on Si

  5. Culture, gender and locus of control

    DEFF Research Database (Denmark)

    Ottsen, Christina Lundsgaard; Johannessen, Kim Berg; Berntsen, Dorthe

    The current study is a cross-cultural comparison between the Middle East and Scandinavia. Two societies that offer a unique opportunity to examine gender differences in personal goals and how goals are affected by locus of control.......The current study is a cross-cultural comparison between the Middle East and Scandinavia. Two societies that offer a unique opportunity to examine gender differences in personal goals and how goals are affected by locus of control....

  6. Interobserver variability in the evaluation of mismatch repair protein immunostaining

    DEFF Research Database (Denmark)

    Klarskov, Louise Laurberg; Ladelund, Steen; Holck, Susanne

    2010-01-01

    Immunohistochemical staining for mismatch repair proteins has during recent years been established as a routine analysis in many pathology laboratories with the aim to identify tumors linked to the hereditary nonpolyposis colorectal cancer syndrome. Despite widespread application, data on reliabi......Immunohistochemical staining for mismatch repair proteins has during recent years been established as a routine analysis in many pathology laboratories with the aim to identify tumors linked to the hereditary nonpolyposis colorectal cancer syndrome. Despite widespread application, data...... on reliability are lacking. We therefore evaluated interobserver variability among 6 pathologists, 3 experienced gastrointestinal pathologists and 3 residents. In total, 225 immunohistochemically stained colorectal cancers were evaluated as having normal, weak, loss of, or nonevaluable mismatch repair protein...... variability was considerable, though experienced pathologists and residents reached the same level of consensus. Because results from immunohistochemical mismatch repair protein stainings are used for decisions on mutation analysis and as an aid in the interpretation of gene variants of unknown significance...

  7. Clinicopathologic factors identify sporadic mismatch repair-defective colon cancers

    DEFF Research Database (Denmark)

    Halvarsson, Britta; Anderson, Harald; Domanska, Katarina

    2008-01-01

    Identification of sporadic mismatch repair (MMR)-defective colon cancers is increasingly demanded for decisions on adjuvant therapies. We evaluated clinicopathologic factors for the identification of these prognostically favorable tumors. Histopathologic features in 238 consecutive colon cancers...

  8. Identification of a mismatch-specific endonuclease in hyperthermophilic Archaea.

    Science.gov (United States)

    Ishino, Sonoko; Nishi, Yuki; Oda, Soichiro; Uemori, Takashi; Sagara, Takehiro; Takatsu, Nariaki; Yamagami, Takeshi; Shirai, Tsuyoshi; Ishino, Yoshizumi

    2016-04-20

    The common mismatch repair system processed by MutS and MutL and their homologs was identified in Bacteria and Eukarya. However, no evidence of a functional MutS/L homolog has been reported for archaeal organisms, and it is not known whether the mismatch repair system is conserved in Archaea. Here, we describe an endonuclease that cleaves double-stranded DNA containing a mismatched base pair, from the hyperthermophilic archaeon Pyrococcus furiosus The corresponding gene revealed that the activity originates from PF0012, and we named this enzyme Endonuclease MS (EndoMS) as the mismatch-specific Endonuclease. The sequence similarity suggested that EndoMS is the ortholog of NucS isolated from Pyrococcus abyssi, published previously. Biochemical characterizations of the EndoMS homolog from Thermococcus kodakarensis clearly showed that EndoMS specifically cleaves both strands of double-stranded DNA into 5'-protruding forms, with the mismatched base pair in the central position. EndoMS cleaves G/T, G/G, T/T, T/C and A/G mismatches, with a more preference for G/T, G/G and T/T, but has very little or no effect on C/C, A/C and A/A mismatches. The discovery of this endonuclease suggests the existence of a novel mismatch repair process, initiated by the double-strand break generated by the EndoMS endonuclease, in Archaea and some Bacteria. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  9. Mismatch characteristics of optical parametric chirped pulse amplification

    Czech Academy of Sciences Publication Activity Database

    Novák, Ondřej; Turčičová, Hana; Divoký, Martin; Huynh, Jaroslav; Straka, Petr

    2014-01-01

    Roč. 11, č. 2 (2014), 1-7 ISSN 1612-2011 R&D Projects: GA ČR GA202/06/0814; GA MŠk(CZ) LC528 Institutional support: RVO:68378271 Keywords : phase matching * phase mismatch * beam mismatch * broadband amplification * parametric amplifiers * OPCPA * iodine laser Subject RIV: BH - Optics , Masers, Lasers Impact factor: 2.458, year: 2014

  10. Replication infidelity via a mismatch with Watson-Crick geometry.

    Science.gov (United States)

    Bebenek, Katarzyna; Pedersen, Lars C; Kunkel, Thomas A

    2011-02-01

    In describing the DNA double helix, Watson and Crick suggested that "spontaneous mutation may be due to a base occasionally occurring in one of its less likely tautomeric forms." Indeed, among many mispairing possibilities, either tautomerization or ionization of bases might allow a DNA polymerase to insert a mismatch with correct Watson-Crick geometry. However, despite substantial progress in understanding the structural basis of error prevention during polymerization, no DNA polymerase has yet been shown to form a natural base-base mismatch with Watson-Crick-like geometry. Here we provide such evidence, in the form of a crystal structure of a human DNA polymerase λ variant poised to misinsert dGTP opposite a template T. All atoms needed for catalysis are present at the active site and in positions that overlay with those for a correct base pair. The mismatch has Watson-Crick geometry consistent with a tautomeric or ionized base pair, with the pH dependence of misinsertion consistent with the latter. The results support the original idea that a base substitution can originate from a mismatch having Watson-Crick geometry, and they suggest a common catalytic mechanism for inserting a correct and an incorrect nucleotide. A second structure indicates that after misinsertion, the now primer-terminal G • T mismatch is also poised for catalysis but in the wobble conformation seen in other studies, indicating the dynamic nature of the pathway required to create a mismatch in fully duplex DNA.

  11. Replication infidelity via a mismatch with Watson–Crick geometry

    Science.gov (United States)

    Bebenek, Katarzyna; Pedersen, Lars C.; Kunkel, Thomas A.

    2011-01-01

    In describing the DNA double helix, Watson and Crick suggested that “spontaneous mutation may be due to a base occasionally occurring in one of its less likely tautomeric forms.” Indeed, among many mispairing possibilities, either tautomerization or ionization of bases might allow a DNA polymerase to insert a mismatch with correct Watson–Crick geometry. However, despite substantial progress in understanding the structural basis of error prevention during polymerization, no DNA polymerase has yet been shown to form a natural base–base mismatch with Watson–Crick-like geometry. Here we provide such evidence, in the form of a crystal structure of a human DNA polymerase λ variant poised to misinsert dGTP opposite a template T. All atoms needed for catalysis are present at the active site and in positions that overlay with those for a correct base pair. The mismatch has Watson–Crick geometry consistent with a tautomeric or ionized base pair, with the pH dependence of misinsertion consistent with the latter. The results support the original idea that a base substitution can originate from a mismatch having Watson–Crick geometry, and they suggest a common catalytic mechanism for inserting a correct and an incorrect nucleotide. A second structure indicates that after misinsertion, the now primer-terminal G•T mismatch is also poised for catalysis but in the wobble conformation seen in other studies, indicating the dynamic nature of the pathway required to create a mismatch in fully duplex DNA. PMID:21233421

  12. Position dependent mismatch discrimination on DNA microarrays – experiments and model

    Directory of Open Access Journals (Sweden)

    Michel Wolfgang

    2008-12-01

    Full Text Available Abstract Background The propensity of oligonucleotide strands to form stable duplexes with complementary sequences is fundamental to a variety of biological and biotechnological processes as various as microRNA signalling, microarray hybridization and PCR. Yet our understanding of oligonucleotide hybridization, in particular in presence of surfaces, is rather limited. Here we use oligonucleotide microarrays made in-house by optically controlled DNA synthesis to produce probe sets comprising all possible single base mismatches and base bulges for each of 20 sequence motifs under study. Results We observe that mismatch discrimination is mostly determined by the defect position (relative to the duplex ends as well as by the sequence context. We investigate the thermodynamics of the oligonucleotide duplexes on the basis of double-ended molecular zipper. Theoretical predictions of defect positional influence as well as long range sequence influence agree well with the experimental results. Conclusion Molecular zipping at thermodynamic equilibrium explains the binding affinity of mismatched DNA duplexes on microarrays well. The position dependent nearest neighbor model (PDNN can be inferred from it. Quantitative understanding of microarray experiments from first principles is in reach.

  13. Perspective on sequence evolution of microsatellite locus (CCGn in Rv0050 gene from Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Jin Ruiliang

    2011-08-01

    Full Text Available Abstract Background The mycobacterial genome is inclined to polymerase slippage and a high mutation rate in microsatellite regions due to high GC content and absence of a mismatch repair system. However, the exact molecular mechanisms underlying microsatellite variation have not been fully elucidated. Here, we investigated mutation events in the hyper-variable trinucleotide microsatellite locus MML0050 located in the Rv0050 gene of W-Beijing and non-W-Beijing Mycobacterium tuberculosis strains in order to gain insight into the genomic structure and activity of repeated regions. Results Size analysis indicated the presence of five alleles that differed in length by three base pairs. Moreover, nucleotide gains occurred more frequently than loses in this trinucleotide microsatellite. Mutation frequency was not completely related with the total length, though the relative frequency in the longest allele was remarkably higher than that in the shortest. Sequence analysis was able to detect seven alleles and revealed that point mutations enhanced the level of locus variation. Introduction of an interruptive motif correlated with the total allele length and genetic lineage, rather than the length of the longest stretch of perfect repeats. Finally, the level of locus variation was drastically different between the two genetic lineages. Conclusion The Rv0050 locus encodes the bifunctional penicillin-binding protein ponA1 and is essential to mycobacterial survival. Our investigations of this particularly dynamic genomic region provide insights into the overall mode of microsatellite evolution. Specifically, replication slippage was implicated in the mutational process of this microsatellite and a sequence-based genetic analysis was necessary to determine that point mutation events acted to maintain microsatellite size integrity while providing genomic diversity.

  14. HLA-DQ Mismatching and Kidney Transplant Outcomes.

    Science.gov (United States)

    Leeaphorn, Napat; Pena, Jeremy Ryan A; Thamcharoen, Natanong; Khankin, Eliyahu V; Pavlakis, Martha; Cardarelli, Francesca

    2018-05-07

    Recent evidence suggests that HLA epitope-mismatching at HLA-DQ loci is associated with the development of anti-DQ donor-specific antibodies and adverse graft outcomes. However, the clinical significance of broad antigen HLA-DQ mismatching for graft outcomes is not well examined. Using the United Network Organ Sharing/the Organ Procurement and Transplantation Network (UNOS/OPTN) data, patients with primary kidney transplants performed between 2005 and 2014 were included. Patients were classified as having either zero HLA-DQ mismatches, or one or two HLA-DQ mismatches. Primary outcomes were death-censored graft survival and incidence of acute rejection. A total of 93,782 patients were included. Of these, 22,730 (24%) and 71,052 (76%) received zero and one or two HLA-DQ mismatched kidneys, respectively. After adjusting for variables including HLA-ABDR, HLA-DQ mismatching was associated with a higher risk of graft loss in living kidney donor recipients with an adjusted hazard ratio (HR) of 1.18 (95% confidence interval [95% CI], 1.07 to 1.30; P HLA-DQ mismatching was associated with a higher risk of graft loss in deceased kidney donor recipients with cold ischemic time ≤17 hours (HR, 1.12; 95% CI, 1.02 to 1.27; P =0.002), but not in deceased kidney donor recipients with cold ischemic time >17 hours (HR, 0.97; 95% CI, 0.88 to 1.06; P =0.49) ( P value for interaction HLA-DQ mismatched kidneys had a higher incidence of acute rejection at 1 year, with adjusted odds ratios of 1.13 (95% CI, 1.03 to 1.23; P transplant recipients. Specific donor-DQ mismatches seemed to be associated with the risk of acute rejection and graft failure, whereas others did not. HLA-DQ mismatching is associated with lower graft survival independent of HLA-ABDR in living donor kidney transplants and deceased donor kidney transplants with cold ischemia time ≤17 hours, and a higher 1-year risk of acute rejection in living and deceased donor kidney transplants. Copyright © 2018 by the American

  15. Exome and Transcriptome Sequencing of Aedes aegypti Identifies a Locus That Confers Resistance to Brugia malayi and Alters the Immune Response

    KAUST Repository

    Juneja, Punita; Ariani, Cristina V.; Ho, Yung Shwen; Akorli, Jewelna; Palmer, William J.; Pain, Arnab; Jiggins, Francis M.

    2015-01-01

    to target protein-coding regions of the genome, and used association mapping in a wild Kenyan population to identify a single, dominant, sex-linked locus underlying resistance. This falls in a region of the genome where a resistance locus was previously

  16. Positive cooperativity of the specific binding between Hg2+ ion and T:T mismatched base pairs in duplex DNA

    International Nuclear Information System (INIS)

    Torigoe, Hidetaka; Miyakawa, Yukako; Ono, Akira; Kozasa, Tetsuo

    2012-01-01

    Highlights: ► Hg 2+ specifically bound with the T:T mismatched base pair at 1:1 molar ratio. ► The binding constant between Hg 2+ and the T:T mismatched base pair was 10 6 M −1 . ► The binding constant was larger than those for nonspecific metal–DNA interactions. ► The binding constant for the second Hg 2+ was larger than that for the first Hg 2+ . ► The positive cooperative binding was observed between Hg 2+ and multiple T:T. - Abstract: Metal-mediated base pairs by the interaction between metal ions and artificial bases in oligonucleotides have been developed for their potential applications in nanotechnology. We recently found that a natural T:T mismatched base pair bound with Hg 2+ ion to form a novel T–Hg–T base pair. Here, we examined the thermodynamic properties of the binding between Hg 2+ and each of the single and double T:T mismatched base pair duplex DNAs by isothermal titration calorimetry. Hg 2+ specifically bound with the T:T mismatched base pair at 1:1 molar ratio with 10 6 M −1 binding constant, which was significantly larger than those for nonspecific metal ion–DNA interactions. In the Hg 2+ –double T:T mismatched base pair interaction, the affinity for the second Hg 2+ binding was significantly larger than that for the first Hg 2+ binding. The positively cooperative binding may be favorable to align multiple Hg 2+ in duplex DNA for the application of the metal-mediated base pairs in nanotechnology.

  17. Hybrid male sterility in rice is due to epistatic interactions with a pollen killer locus.

    Science.gov (United States)

    Kubo, Takahiko; Yoshimura, Atsushi; Kurata, Nori

    2011-11-01

    In intraspecific crosses between cultivated rice (Oryza sativa) subspecies indica and japonica, the hybrid male sterility gene S24 causes the selective abortion of male gametes carrying the japonica allele (S24-j) via an allelic interaction in the heterozygous hybrids. In this study, we first examined whether male sterility is due solely to the single locus S24. An analysis of near-isogenic lines (NIL-F(1)) showed different phenotypes for S24 in different genetic backgrounds. The S24 heterozygote with the japonica genetic background showed male semisterility, but no sterility was found in heterozygotes with the indica background. This result indicates that S24 is regulated epistatically. A QTL analysis of a BC(2)F(1) population revealed a novel sterility locus that interacts with S24 and is found on rice chromosome 2. The locus was named Epistatic Factor for S24 (EFS). Further genetic analyses revealed that S24 causes male sterility when in combination with the homozygous japonica EFS allele (efs-j). The results suggest that efs-j is a recessive sporophytic allele, while the indica allele (EFS-i) can dominantly counteract the pollen sterility caused by S24 heterozygosity. In summary, our results demonstrate that an additional epistatic locus is an essential element in the hybrid sterility caused by allelic interaction at a single locus in rice. This finding provides a significant contribution to our understanding of the complex molecular mechanisms underlying hybrid sterility and microsporogenesis.

  18. Development of single locus DNA microsatellite markers in Oryctes ...

    Indian Academy of Sciences (India)

    Oryctes rhinoceros, commonly known as rhinoceros bee- tle, is an important pest in oil palm plantations. The pres- ence of this pest in replanting sites as early as six months ..... rhinoceros: breeding and damage on oil palm in an oil palm to oil.

  19. Homozygous germ-line mutation of the PMS2 mismatch repair gene: a unique case report of constitutional mismatch repair deficiency (CMMRD)

    OpenAIRE

    Ramchander, N. C.; Ryan, N. A. J.; Crosbie, E. J.; Evans, D. G.

    2017-01-01

    BackgroundConstitutional mismatch repair deficiency syndrome results from bi-allelic inheritance of mutations affecting the key DNA mismatch repair genes: MLH1, MSH2, MSH6 or PMS2. Individuals with bi-allelic mutations have a dysfunctional mismatch repair system from birth; as a result, constitutional mismatch repair deficiency syndrome is characterised by early onset malignancies. Fewer than 150 cases have been reported in the literature over the past 20 years. This is the first report of th...

  20. Neural mechanisms of mismatch negativity dysfunction in schizophrenia.

    Science.gov (United States)

    Lee, M; Sehatpour, P; Hoptman, M J; Lakatos, P; Dias, E C; Kantrowitz, J T; Martinez, A M; Javitt, D C

    2017-11-01

    Schizophrenia is associated with cognitive deficits that reflect impaired cortical information processing. Mismatch negativity (MMN) indexes pre-attentive information processing dysfunction at the level of primary auditory cortex. This study investigates mechanisms underlying MMN impairments in schizophrenia using event-related potential, event-related spectral decomposition (ERSP) and resting state functional connectivity (rsfcMRI) approaches. For this study, MMN data to frequency, intensity and duration-deviants were analyzed from 69 schizophrenia patients and 38 healthy controls. rsfcMRI was obtained from a subsample of 38 patients and 23 controls. As expected, schizophrenia patients showed highly significant, large effect size (P=0.0004, d=1.0) deficits in MMN generation across deviant types. In ERSP analyses, responses to deviants occurred primarily the theta (4-7 Hz) frequency range consistent with distributed corticocortical processing, whereas responses to standards occurred primarily in alpha (8-12 Hz) range consistent with known frequencies of thalamocortical activation. Independent deficits in schizophrenia were observed in both the theta response to deviants (P=0.021) and the alpha-response to standards (P=0.003). At the single-trial level, differential patterns of response were observed for frequency vs duration/intensity deviants, along with At the network level, MMN deficits engaged canonical somatomotor, ventral attention and default networks, with a differential pattern of engagement across deviant types (Pschizophrenia. In addition, differences in ERSP and rsfcMRI profiles across deviant types suggest potential differential engagement of underlying generator mechanisms.

  1. Microsatellites in the Eukaryotic DNA Mismatch Repair Genes as Modulators of Evolutionary Mutation Rate

    Science.gov (United States)

    Chang, Dong Kyung; Metzgar, David; Wills, Christopher; Boland, C. Richard

    2003-01-01

    All "minor" components of the human DNA mismatch repair (MMR) system-MSH3, MSH6, PMS2, and the recently discovered MLH3-contain mononucleotide microsatellites in their coding sequences. This intriguing finding contrasts with the situation found in the major components of the DNA MMR system-MSH2 and MLH1-and, in fact, most human genes. Although eukaryotic genomes are rich in microsatellites, non-triplet microsatellites are rare in coding regions. The recurring presence of exonal mononucleotide repeat sequences within a single family of human genes would therefore be considered exceptional.

  2. Fermi velocity mismatch effects in the tunneling characteristics of high-Tc superconductors

    International Nuclear Information System (INIS)

    Aponte, J.M.; Nunez-Regueiro, J.E.; Bellorin, A.; Octavio, M.

    1994-01-01

    We present a comparative study of the tunneling characteristics of point contacts in which one electrode was a superconducting single crystal of Bi 2 Sr 2 CaCu 2 O x and the other electrode was either a normal metal (N-HTSC point contact), or a non-superconducting rare earth metallic oxide (REMO-HTSC point contact), or another crystal of the same superconductor (HTSC'-HTSC point contact). We show that the mismatch of the Fermi velocities of the electrodes is in part responsible for the irreproducibility of most of the tunneling conductance curves observed in high temperature superconductors. (orig.)

  3. Impulsive synchronization and parameter mismatch of the three-variable autocatalator model

    International Nuclear Information System (INIS)

    Li, Yang; Liao, Xiaofeng; Li, Chuandong; Huang, Tingwen; Yang, Degang

    2007-01-01

    The synchronization problems of the three-variable autocatalator model via impulsive control approach are investigated; several theorems on the stability of impulsive control systems are also investigated. These theorems are then used to find the conditions under which the three-variable autocatalator model can be asymptotically controlled to the equilibrium point. This Letter derives some sufficient conditions for the stabilization and synchronization of a three-variable autocatalator model via impulsive control with varying impulsive intervals. Furthermore, we address the chaos quasi-synchronization in the presence of single-parameter mismatch. To illustrate the effectiveness of the new scheme, several numerical examples are given

  4. Direct Mismatch Characterization of femto-Farad Capacitors

    KAUST Repository

    Omran, Hesham

    2015-08-17

    Reducing the capacitance of programmable capacitor arrays, commonly used in analog integrated circuits, is necessary for low-energy applications. However, limited mismatch data is available for small capacitors. We report mismatch measurement for a 2fF poly-insulator-poly (PIP) capacitor, which is the smallest reported PIP capacitor to the best of the authors’ knowledge. Instead of using complicated custom onchip circuitry, direct mismatch measurement is demonstrated and verified using Monte Carlo Simulations and experimental measurements. Capacitive test structures composed of 9 bit programmable capacitor arrays (PCAs) are implemented in a low-cost 0:35m CMOS process. Measured data is compared to mismatch of large PIP capacitors, theoretical models, and recently published data. Measurement results indicate an estimated average relative standard deviation of 0.43% for the 2fF unit capacitor, which is better than the reported mismatch of metal-oxide-metal (MOM) fringing capacitors implemented in an advanced 32nm CMOS process.

  5. The Effect of Codon Mismatch on the Protein Translation System.

    Directory of Open Access Journals (Sweden)

    Dinglin Zhang

    Full Text Available Incorrect protein translation, caused by codon mismatch, is an important problem of living cells. In this work, a computational model was introduced to quantify the effects of codon mismatch and the model was used to study the protein translation of Saccharomyces cerevisiae. According to simulation results, the probability of codon mismatch will increase when the supply of amino acids is unbalanced, and the longer is the codon sequence, the larger is the probability for incorrect translation to occur, making the synthesis of long peptide chain difficult. By comparing to simulation results without codon mismatch effects taken into account, the fraction of mRNAs with bound ribosome decrease faster along the mRNAs, making the 5' ramp phenomenon more obvious. It was also found in our work that the premature mechanism resulted from codon mismatch can reduce the proportion of incorrect translation when the amino acid supply is extremely unbalanced, which is one possible source of high fidelity protein synthesis after peptidyl transfer.

  6. The Effect of Codon Mismatch on the Protein Translation System.

    Science.gov (United States)

    Zhang, Dinglin; Chen, Danfeng; Cao, Liaoran; Li, Guohui; Cheng, Hong

    2016-01-01

    Incorrect protein translation, caused by codon mismatch, is an important problem of living cells. In this work, a computational model was introduced to quantify the effects of codon mismatch and the model was used to study the protein translation of Saccharomyces cerevisiae. According to simulation results, the probability of codon mismatch will increase when the supply of amino acids is unbalanced, and the longer is the codon sequence, the larger is the probability for incorrect translation to occur, making the synthesis of long peptide chain difficult. By comparing to simulation results without codon mismatch effects taken into account, the fraction of mRNAs with bound ribosome decrease faster along the mRNAs, making the 5' ramp phenomenon more obvious. It was also found in our work that the premature mechanism resulted from codon mismatch can reduce the proportion of incorrect translation when the amino acid supply is extremely unbalanced, which is one possible source of high fidelity protein synthesis after peptidyl transfer.

  7. Direct Mismatch Characterization of femto-Farad Capacitors

    KAUST Repository

    Omran, Hesham; Elafandy, Rami T.; Arsalan, Muhammad; Salama, Khaled N.

    2015-01-01

    Reducing the capacitance of programmable capacitor arrays, commonly used in analog integrated circuits, is necessary for low-energy applications. However, limited mismatch data is available for small capacitors. We report mismatch measurement for a 2fF poly-insulator-poly (PIP) capacitor, which is the smallest reported PIP capacitor to the best of the authors’ knowledge. Instead of using complicated custom onchip circuitry, direct mismatch measurement is demonstrated and verified using Monte Carlo Simulations and experimental measurements. Capacitive test structures composed of 9 􀀀 bit programmable capacitor arrays (PCAs) are implemented in a low-cost 0:35m CMOS process. Measured data is compared to mismatch of large PIP capacitors, theoretical models, and recently published data. Measurement results indicate an estimated average relative standard deviation of 0.43% for the 2fF unit capacitor, which is better than the reported mismatch of metal-oxide-metal (MOM) fringing capacitors implemented in an advanced 32nm CMOS process.

  8. Locus of control in relation to flow

    Directory of Open Access Journals (Sweden)

    Celeste M Taylor

    2006-04-01

    Full Text Available The principal objective of the study was to examine the relationship between locus of control and optimal experience (flow in carrying out work and/or study activities. Two questionnaires measuring the aforementioned constructs were administered to a group of first and second-year Human Resource Management students (n=168 between the ages of 16 and 30. The results suggest that more frequent experience of flow is positively correlated with Autonomy and Internal Locus of Control. Limitations, lines of future research, implications and further contributions are discussed.

  9. Updated listing of haplotypes at the human phenylalanine hydroxylase (PAH) locus

    Energy Technology Data Exchange (ETDEWEB)

    Eisensmith, R.C.; Woo, S.L.C. (Baylor College of Medicine, Houston, TX (United States))

    1992-12-01

    Analysis of mutant PAH chromosomes has identified approximately 60 different single-base substitutions and deletions within the PAH locus. Nearly all of these molecular lesions are in strong linkage disequilibrium with specific RFLP haplotypes in different ethnic populations. Thus, haplotype analysis is not only useful for diagnostic purposes but is proving to be a valuable tool in population genetic studies of the origin and spread of phenylketonuria alleles in human populations. PCR-based methods have been developed to detect six of the eight polymorphic restriction sites used for determination of RFLP haplotypes at the PAH locus. A table of the proposed expanded haplotypes is given.

  10. Genetic mapping of the female mimic morph locus in the ruff

    Science.gov (United States)

    2013-01-01

    Background Ruffs (Aves: Philomachus pugnax) possess a genetic polymorphism for male mating behaviour resulting in three permanent alternative male reproductive morphs: (i) territorial ‘Independents’, (ii) non-territorial ‘Satellites’, and (iii) female-mimicking ‘Faeders’. Development into independent or satellite morphs has previously been shown to be due to a single-locus, two-allele autosomal Mendelian mode of inheritance at the Satellite locus. Here, we use linkage analysis to map the chromosomal location of the Faeder locus, which controls development into the Faeder morph, and draw further conclusions about candidate genes, assuming shared synteny with other birds. Results Segregation data on the Faeder locus were obtained from captive-bred pedigrees comprising 64 multi-generation families (N = 381). There was no evidence that the Faeder locus was linked to the Satellite locus, but it was linked with microsatellite marker Ppu020. Comparative mapping of ruff microsatellite markers against the chicken (Gallus gallus) and zebra finch (Taeniopygia guttata) genomes places the Ppu020 and Faeder loci on a region of chromosome 11 that includes the Melanocortin-1 receptor (MC1R) gene, which regulates colour polymorphisms in numerous birds and other vertebrates. Melanin-based colouration varies with life-history strategies in ruffs and other species, thus the MC1R gene is a strong candidate to play a role in alternative male morph determination. Conclusion Two unlinked loci appear to control behavioural development in ruffs. The Faeder locus is linked to Ppu020, which, assuming synteny, is located on avian chromosome 11. MC1R is a candidate gene involved in alternative male morph determination in ruffs. PMID:24256185

  11. Complex relationship between mismatch repair proteins and MBD4 during immunoglobulin class switch recombination.

    Science.gov (United States)

    Grigera, Fernando; Bellacosa, Alfonso; Kenter, Amy L

    2013-01-01

    Mismatch repair (MMR) safeguards against genomic instability and is required for efficient Ig class switch recombination (CSR). Methyl CpG binding domain protein 4 (MBD4) binds to MutL homologue 1 (MLH1) and controls the post-transcriptional level of several MMR proteins, including MutS homologue 2 (MSH2). We show that in WT B cells activated for CSR, MBD4 is induced and interacts with MMR proteins, thereby implying a role for MBD4 in CSR. However, CSR is in the normal range in Mbd4 deficient mice deleted for exons 2-5 despite concomitant reduction of MSH2. We show by comparison in Msh2(+/-) B cells that a two-fold reduction of MSH2 and MBD4 proteins is correlated with impaired CSR. It is therefore surprising that CSR occurs at normal frequencies in the Mbd4 deficient B cells where MSH2 is reduced. We find that a variant Mbd4 transcript spanning exons 1,6-8 is expressed in Mbd4 deficient B cells. This transcript can be ectopically expressed and produces a truncated MBD4 peptide. Thus, the 3' end of the Mbd4 locus is not silent in Mbd4 deficient B cells and may contribute to CSR. Our findings highlight a complex relationship between MBD4 and MMR proteins in B cells and a potential reconsideration of their role in CSR.

  12. Measurement of MOS current mismatch in the weak inversion region

    International Nuclear Information System (INIS)

    Forti, F.; Wright, M.E.

    1994-01-01

    The MOS transistor matching properties in the weak inversion region have not received, in the past, the attention that the mismatch in the strong inversion region has. The importance of weak inversion biased transistors in low power CMOS analog systems calls for more extensive data on the mismatch in this region of operation. The study presented in this paper was motivated by the need of controlling the threshold matching in a low power, low noise amplifier discriminator circuit used in a silicon radiation detector read-out, where both the transistor dimensions and the currents had to be kept to a minimum. The authors have measured the current matching properties of MOS transistors operated in the weak inversion region. They measured a total of about 1,400 PMOS and NMOS transistors produced in four different processes and report here the results in terms of mismatch dependence on current density, device dimensions, and substrate voltage, without using any specific model for the transistor

  13. High fitness costs of climate change-induced camouflage mismatch.

    Science.gov (United States)

    Zimova, Marketa; Mills, L Scott; Nowak, J Joshua

    2016-03-01

    Anthropogenic climate change has created myriad stressors that threaten to cause local extinctions if wild populations fail to adapt to novel conditions. We studied individual and population-level fitness costs of a climate change-induced stressor: camouflage mismatch in seasonally colour molting species confronting decreasing snow cover duration. Based on field measurements of radiocollared snowshoe hares, we found strong selection on coat colour molt phenology, such that animals mismatched with the colour of their background experienced weekly survival decreases up to 7%. In the absence of adaptive response, we show that these mortality costs would result in strong population-level declines by the end of the century. However, natural selection acting on wide individual variation in molt phenology might enable evolutionary adaptation to camouflage mismatch. We conclude that evolutionary rescue will be critical for hares and other colour molting species to keep up with climate change. © 2016 The Authors. Ecology Letters published by CNRS and John Wiley & Sons Ltd.

  14. Simulation studies of emittance growth in RMS mismatched beams

    International Nuclear Information System (INIS)

    Cucchetti, A.; Wangler, T.; Reiser, M.

    1991-01-01

    As shown in a separate paper, a charged-particle beam, whose rms size is not matched when injected into a transport channel or accelerator, has excess energy compared with that of a matched beam. If nonlinear space-charge forces are present and the mismatched beam transforms to a matched equilibrium state, rms-emittance growth will occur. The theory yields formulas for the possible rms-emittance growth, but not for the time it takes to achieve this growth. In this paper we present the results of systematic simulation studies for a mismatched 2-D round beam in an ideal transport channel with continuous linear focusing. Emittance growth rates obtained from the simulations for different amounts of mismatch and initial charge will be presented and the emittance growth will be compared with the theory. 6 refs., 7 figs

  15. Constitutional mismatch repair deficiency syndrome: Do we know it?

    Science.gov (United States)

    Ramachandra, C; Challa, Vasu Reddy; Shetty, Rachan

    2014-04-01

    Constitutional mismatch repair deficiency syndrome is a rare autosomal recessive syndrome caused by homozygous mutations in mismatch repair genes. This is characterized by the childhood onset of brain tumors, colorectal cancers, cutaneous manifestations of neurofibromatosis-1 like café au lait spots, hematological malignancies, and occasionally other rare malignancies. Here, we would like to present a family in which the sibling had glioblastoma, and the present case had acute lymphoblastic lymphoma and colorectal cancer. We would like to present this case because of its rarity and would add to literature.

  16. Advanced radar detection schemes under mismatched signal models

    CERN Document Server

    Bandiera, Francesco

    2009-01-01

    Adaptive detection of signals embedded in correlated Gaussian noise has been an active field of research in the last decades. This topic is important in many areas of signal processing such as, just to give some examples, radar, sonar, communications, and hyperspectral imaging. Most of the existing adaptive algorithms have been designed following the lead of the derivation of Kelly's detector which assumes perfect knowledge of the target steering vector. However, in realistic scenarios, mismatches are likely to occur due to both environmental and instrumental factors. When a mismatched signal

  17. Oscillating Evolution of a Mammalian Locus with Overlapping Reading Frames: An XLalphas/ALEX Relay.

    Directory of Open Access Journals (Sweden)

    2005-08-01

    Full Text Available XLalphas and ALEX are structurally unrelated mammalian proteins translated from alternative overlapping reading frames of a single transcript. Not only are they encoded by the same locus, but a specific XLalphas/ALEX interaction is essential for G-protein signaling in neuroendocrine cells. A disruption of this interaction leads to abnormal human phenotypes, including mental retardation and growth deficiency. The region of overlap between the two reading frames evolves at a remarkable speed: the divergence between human and mouse ALEX polypeptides makes them virtually unalignable. To trace the evolution of this puzzling locus, we sequenced it in apes, Old World monkeys, and a New World monkey. We show that the overlap between the two reading frames and the physical interaction between the two proteins force the locus to evolve in an unprecedented way. Namely, to maintain two overlapping protein-coding regions the locus is forced to have high GC content, which significantly elevates its intrinsic evolutionary rate. However, the two encoded proteins cannot afford to change too quickly relative to each other as this may impair their interaction and lead to severe physiological consequences. As a result XLalphas and ALEX evolve in an oscillating fashion constantly balancing the rates of amino acid replacements. This is the first example of a rapidly evolving locus encoding interacting proteins via overlapping reading frames, with a possible link to the origin of species-specific neurological differences.

  18. Root locus analysis and design of the adaptation process in active noise control.

    Science.gov (United States)

    Tabatabaei Ardekani, Iman; Abdulla, Waleed H

    2012-10-01

    This paper applies root locus theory to develop a graphical tool for the analysis and design of adaptive active noise control systems. It is shown that the poles of the adaptation process performed in these systems move on typical trajectories in the z-plane as the adaptation step-size varies. Based on this finding, the dominant root of the adaptation process and its trajectory can be determined. The first contribution of this paper is formulating parameters of the adaptation process root locus. The next contribution is introducing a mechanism for modifying the trajectory of the dominant root in the root locus. This mechanism creates a single open loop zero in the original root locus. It is shown that appropriate localization of this zero can cause the dominant root of the locus to be pushed toward the origin, and thereby the adaptation process becomes faster. The validity of the theoretical findings is confirmed in an experimental setup which is implemented using real-time multi-threading and multi-core processing techniques.

  19. The Impact of Locus of Control on Language Achievement

    Science.gov (United States)

    Nodoushan, Mohammad Ali Salmani

    2012-01-01

    This study hypothesized that students' loci of control affected their language achievement. 198 (N = 198) EFL students took the Rotter's (1966) locus of control test and were classified as locus-internal (ni = 78), and locus-external (ne = 120). They then took their ordinary courses and at the end of the semester, they were given their exams.…

  20. Self-Esteem, Locus of Control, and Student Achievement.

    Science.gov (United States)

    Sterbin, Allan; Rakow, Ernest

    The direct effects of locus of control and self-esteem on standardized test scores were studied. The relationships among the standardized test scores and measures of locus of control and self-esteem for 12,260 students from the National Education Longitudinal Study 1994 database were examined, using the same definition of locus of control and…

  1. Mismatch of Vocational Graduates: What Penalty on French Labour Market?

    Science.gov (United States)

    Beduwe, Catherine; Giret, Jean-Francois

    2011-01-01

    This study explores individual effects of educational mismatch on wages, job satisfaction and on-the-job-search on French labour market. We distinguish between horizontal matches (job matches with field of studies) and vertical matches (job matches the level of qualification) on the one hand and skills matches (worker's assessment) on the other…

  2. DNA mismatch repair, genome instability and cancer in zebrafish

    NARCIS (Netherlands)

    Feitsma, H.

    2008-01-01

    The objective of this study was to find out whether the zebrafish can be an appropriate model for studying DNA repair and cancer. For this purpose three fish lines were used that lack components of an important mechanism for the repair of small DNA damage: DNA mismatch repair. These fish are

  3. Mismatch repair genes in Lynch syndrome: a review

    Directory of Open Access Journals (Sweden)

    Felipe Cavalcanti Carneiro da Silva

    Full Text Available Lynch syndrome represents 1-7% of all cases of colorectal cancer and is an autosomal-dominant inherited cancer predisposition syndrome caused by germline mutations in deoxyribonucleic acid (DNA mismatch repair genes. Since the discovery of the major human genes with DNA mismatch repair function, mutations in five of them have been correlated with susceptibility to Lynch syndrome: mutS homolog 2 (MSH2; mutL homolog 1 (MLH1; mutS homolog 6 (MSH6; postmeiotic segregation increased 2 (PMS2; and postmeiotic segregation increased 1 (PMS1. It has been proposed that one additional mismatch repair gene, mutL homolog 3 (MLH3, also plays a role in Lynch syndrome predisposition, but the clinical significance of mutations in this gene is less clear. According to the InSiGHT database (International Society for Gastrointestinal Hereditary Tumors, approximately 500 different LS-associated mismatch repair gene mutations are known, primarily involving MLH1 (50% and MSH2 (40%, while others account for 10%. Much progress has been made in understanding the molecular basis of Lynch Syndrome. Molecular characterization will be the most accurate way of defining Lynch syndrome and will provide predictive information of greater accuracy regarding the risks of colon and extracolonic cancer and enable optimal cancer surveillance regimens.

  4. Review: Clinical aspects of hereditary DNA Mismatch repair gene mutations

    NARCIS (Netherlands)

    Sijmons, Rolf H.; Hofstra, Robert M. W.

    Inherited mutations of the DNA Mismatch repair genes MLH1, MSH2, MSH6 and PMS2 can result in two hereditary tumor syndromes: the adult-onset autosomal dominant Lynch syndrome, previously referred to as Hereditary Non-Polyposis Colorectal Cancer (HNPCC) and the childhood-onset autosomal recessive

  5. Educational Mismatch and Spatial Flexibility in Italian Local Labour Markets

    Science.gov (United States)

    Croce, Giuseppe; Ghignoni, Emanuela

    2015-01-01

    According to recent literature, this paper highlights the relevance of spatial mobility as an explanatory factor of the individual risk of job-education mismatch. To investigate this causal link, we use individual information about daily home-to-work commuting time and choices to relocate in a different local area to get a job. Our model takes…

  6. Mismatch repair deficiency in colorectal cancer patients in a low ...

    African Journals Online (AJOL)

    2013-02-06

    Feb 6, 2013 ... This is 10% of the rate reported in First-World countries. In high-incidence areas, the rate of abnormal mismatch repair gene expression in colorectal cancers is 2 - 7%. Objectives. The aim of this study was to determine the prevalence of hMLH1- and hMSH2-deficient colorectal cancer in the. Northern Cape.

  7. Clinicopathologic factors identify sporadic mismatch repair-defective colon cancers

    DEFF Research Database (Denmark)

    Halvarsson, Britta; Anderson, Harald; Domanska, Katarina

    2008-01-01

    Identification of sporadic mismatch repair (MMR)-defective colon cancers is increasingly demanded for decisions on adjuvant therapies. We evaluated clinicopathologic factors for the identification of these prognostically favorable tumors. Histopathologic features in 238 consecutive colon cancers...... and excluded 61.5% of the tumors from MMR testing. This clinicopathologic index thus successfully selects MMR-defective colon cancers. Udgivelsesdato: 2008-Feb...

  8. Magnetic source localization of early visual mismatch response

    NARCIS (Netherlands)

    Susac, A.; Heslenfeld, D.J.; Huonker, R.; Supek, S.

    2014-01-01

    Previous studies have reported a visual analogue of the auditory mismatch negativity (MMN) response that is based on sensory memory. The neural generators and attention dependence of the visual MMN (vMMN) still remain unclear. We used magnetoencephalography (MEG) and spatio-temporal source

  9. Hydrophobic mismatch triggering texture defects in membrane gel domains

    DEFF Research Database (Denmark)

    Dreier, J.; Brewer, J.R.; Simonsen, Adam Cohen

    2013-01-01

    higher mismatch values correlate with a vortex-type texture. The defect pattern created during early growth persists in larger domains, and a minimal model incorporating the anisotropic line tension and the vortex energy can rationalize this finding. The results suggest that the lipid composition...

  10. BEPS Action 2: Neutralizing the Effects on Hybrid Mismatch Arrangements

    NARCIS (Netherlands)

    de Boer, R.; Marres, O.

    2015-01-01

    Curbing tax arbitrage is one of the main priorities of the Organization for Economic Cooperation and Development (OECD) (endorsed by the G20 and the G8) ever since the public debate on base erosion fully erupted. Neutralizing the effect of hybrid mismatch arrangements has become Action No. 2 of the

  11. Conformations of MutS in DNA mismatch repair

    NARCIS (Netherlands)

    F.S. Groothuizen (Flora)

    2015-01-01

    markdownabstract__Abstract__ Prior to cell division, the DNA containing the genetic information of a cell has to be copied. During this process, errors are sometimes incorporated (so-called mismatches), which may cause genetic abnormalities in future cells. To prevent this, cells contain a DNA

  12. Channel normalization technique for speech recognition in mismatched conditions

    CSIR Research Space (South Africa)

    Kleynhans, N

    2008-11-01

    Full Text Available , where one wishes to use any available training data for a variety of purposes. Research into a new channel normalization (CN) technique for channel mismatched speech recognition is presented. A process of inverse linear filtering is used in order...

  13. Supply and Demand Mismatches in Training: Can Anything Be Done?

    Science.gov (United States)

    Castro, Claudio de Moura; de Andrade, Antonio Cabral

    1990-01-01

    Vocational training often fails to provide what employers need and students want. To correct supply/demand mismatches requires improving feedback from employers, increasing the flow of information, bringing schools closer to businesses, rewarding institutions for successful employment of graduates, and providing incentives for entrepreneurs. (SK)

  14. Pathological assessment of mismatch repair gene variants in Lynch syndrome

    DEFF Research Database (Denmark)

    Rasmussen, Lene Juel; Heinen, Christopher D; Royer-Pokora, Brigitte

    2012-01-01

    Lynch syndrome (LS) is caused by germline mutations in DNA mismatch repair (MMR) genes and is the most prevalent hereditary colorectal cancer syndrome. A significant proportion of variants identified in MMR and other common cancer susceptibility genes are missense or noncoding changes whose...

  15. Mismatch-shaping switching for two-capacitor DAC

    DEFF Research Database (Denmark)

    Steensgaard-Madsen, Jesper; Moon, U.; Temes, G.C.

    1998-01-01

    A mismatch-shaping scheme is proposed for a two-capacitor digital-to-analogue converter (DAC). It uses a delta-sigma loop for finding the optimal switching sequence for each input word. Simulations indicate that the scheme can be used for the realisation of DACs with 16 bit linearity and SNR...

  16. SKILLS MISMATCH OF THE YOUNG PEOPLE AT THE EUROPEAN LEVEL

    Directory of Open Access Journals (Sweden)

    Hatos Roxana

    2015-07-01

    Full Text Available Transition from school to work is a main issue with many fields of study. Studies on transition from school to work, have highlight the importance of two categories of factors at the level of the individual formal proceedings which may affect how easy it is to graduate to integrate into the labor market: 1 so far as the educational systems are transmitting specific competences as compared with those general and 2 so far as there are direct links between employers and the education system. In this way, are reduced the costs of selection and allocation for employers. A poor articulation between educational institutions and the labor market produce a high level of unmatched competences of assimilated by formal education and competencies required of the labor market (skill mismatch (Parodi et al., 2012. The surveys with European employers reflect particular difficulties that they are experiencing in employment vacancies. Investigation on the European companies in the spring of 2013 found that 40% of the firms in the EU have difficulty in finding employees with suitable qualification (CEDEFOP-European Center for the Development of the Vocational Training, 2014. Skills mismatch is a generic term that refers to various types of imbalances between skills and competences offered and those required in the labor market. Concept has become one intensely discussed and submitted to measurement in international research on the background concerns the under-utilization human resource. Numerous opinion polls with employers come to the same unexpected conclusion - that despite high unemployment many posts can't find occupants satisfactorily prepared and identify the causes: most of them criticized the lack of skills of the candidates or the absence of skills specific to the workplace. Based on the latest studies on international databases have built a set of questions that, through secondary analysis, we tried to find answers. Questions that we try to give answer

  17. Hybrid Sterility Locus on Chromosome X Controls Meiotic Recombination Rate in Mouse.

    Directory of Open Access Journals (Sweden)

    Maria Balcova

    2016-04-01

    Full Text Available Meiotic recombination safeguards proper segregation of homologous chromosomes into gametes, affects genetic variation within species, and contributes to meiotic chromosome recognition, pairing and synapsis. The Prdm9 gene has a dual role, it controls meiotic recombination by determining the genomic position of crossover hotspots and, in infertile hybrids of house mouse subspecies Mus m. musculus (Mmm and Mus m. domesticus (Mmd, it further functions as the major hybrid sterility gene. In the latter role Prdm9 interacts with the hybrid sterility X 2 (Hstx2 genomic locus on Chromosome X (Chr X by a still unknown mechanism. Here we investigated the meiotic recombination rate at the genome-wide level and its possible relation to hybrid sterility. Using immunofluorescence microscopy we quantified the foci of MLH1 DNA mismatch repair protein, the cytological counterparts of reciprocal crossovers, in a panel of inter-subspecific chromosome substitution strains. Two autosomes, Chr 7 and Chr 11, significantly modified the meiotic recombination rate, yet the strongest modifier, designated meiotic recombination 1, Meir1, emerged in the 4.7 Mb Hstx2 genomic locus on Chr X. The male-limited transgressive effect of Meir1 on recombination rate parallels the male-limited transgressive role of Hstx2 in hybrid male sterility. Thus, both genetic factors, the Prdm9 gene and the Hstx2/Meir1 genomic locus, indicate a link between meiotic recombination and hybrid sterility. A strong female-specific modifier of meiotic recombination rate with the effect opposite to Meir1 was localized on Chr X, distally to Meir1. Mapping Meir1 to a narrow candidate interval on Chr X is an important first step towards positional cloning of the respective gene(s responsible for variation in the global recombination rate between closely related mouse subspecies.

  18. Hybrid Sterility Locus on Chromosome X Controls Meiotic Recombination Rate in Mouse.

    Science.gov (United States)

    Balcova, Maria; Faltusova, Barbora; Gergelits, Vaclav; Bhattacharyya, Tanmoy; Mihola, Ondrej; Trachtulec, Zdenek; Knopf, Corinna; Fotopulosova, Vladana; Chvatalova, Irena; Gregorova, Sona; Forejt, Jiri

    2016-04-01

    Meiotic recombination safeguards proper segregation of homologous chromosomes into gametes, affects genetic variation within species, and contributes to meiotic chromosome recognition, pairing and synapsis. The Prdm9 gene has a dual role, it controls meiotic recombination by determining the genomic position of crossover hotspots and, in infertile hybrids of house mouse subspecies Mus m. musculus (Mmm) and Mus m. domesticus (Mmd), it further functions as the major hybrid sterility gene. In the latter role Prdm9 interacts with the hybrid sterility X 2 (Hstx2) genomic locus on Chromosome X (Chr X) by a still unknown mechanism. Here we investigated the meiotic recombination rate at the genome-wide level and its possible relation to hybrid sterility. Using immunofluorescence microscopy we quantified the foci of MLH1 DNA mismatch repair protein, the cytological counterparts of reciprocal crossovers, in a panel of inter-subspecific chromosome substitution strains. Two autosomes, Chr 7 and Chr 11, significantly modified the meiotic recombination rate, yet the strongest modifier, designated meiotic recombination 1, Meir1, emerged in the 4.7 Mb Hstx2 genomic locus on Chr X. The male-limited transgressive effect of Meir1 on recombination rate parallels the male-limited transgressive role of Hstx2 in hybrid male sterility. Thus, both genetic factors, the Prdm9 gene and the Hstx2/Meir1 genomic locus, indicate a link between meiotic recombination and hybrid sterility. A strong female-specific modifier of meiotic recombination rate with the effect opposite to Meir1 was localized on Chr X, distally to Meir1. Mapping Meir1 to a narrow candidate interval on Chr X is an important first step towards positional cloning of the respective gene(s) responsible for variation in the global recombination rate between closely related mouse subspecies.

  19. Novel Non-Histocompatibility Antigen Mismatched Variants Improve the Ability to Predict Antibody-Mediated Rejection Risk in Kidney Transplant

    Directory of Open Access Journals (Sweden)

    Silvia Pineda

    2017-12-01

    Full Text Available Transplant rejection is the critical clinical end-point limiting indefinite survival after histocompatibility antigen (HLA mismatched organ transplantation. The predominant cause of late graft loss is antibody-mediated rejection (AMR, a process whereby injury to the organ is caused by donor-specific antibodies, which bind to HLA and non-HLA (nHLA antigens. AMR is incompletely diagnosed as donor/recipient (D/R matching is only limited to the HLA locus and critical nHLA immunogenic antigens remain to be identified. We have developed an integrative computational approach leveraging D/R exome sequencing and gene expression to predict clinical post-transplant outcome. We performed a rigorous statistical analysis of 28 highly annotated D/R kidney transplant pairs with biopsy-confirmed clinical outcomes of rejection [either AMR or T-cell-mediated rejection (CMR] and no-rejection (NoRej, identifying a significantly higher number of mismatched nHLA variants in AMR (ANOVA—p-value = 0.02. Using Fisher’s exact test, we identified 123 variants associated mainly with risk of AMR (p-value < 0.001. In addition, we applied a machine-learning technique to circumvent the issue of statistical power and we found a subset of 65 variants using random forest, that are predictive of post-tx AMR showing a very low error rate. These variants are functionally relevant to the rejection process in the kidney and AMR as they relate to genes and/or expression quantitative trait loci (eQTLs that are enriched in genes expressed in kidney and vascular endothelium and underlie the immunobiology of graft rejection. In addition to current D/R HLA mismatch evaluation, additional mismatch nHLA D/R variants will enhance the stratification of post-tx AMR risk even before engraftment of the organ. This innovative study design is applicable in all solid organ transplants, where the impact of mitigating AMR on graft survival may be greater, with considerable benefits on

  20. Pleiotropic roles of Clostridium difficile sin locus

    Science.gov (United States)

    Ou, Junjun; Dupuy, Bruno

    2018-01-01

    Clostridium difficile is the primary cause of nosocomial diarrhea and pseudomembranous colitis. It produces dormant spores, which serve as an infectious vehicle responsible for transmission of the disease and persistence of the organism in the environment. In Bacillus subtilis, the sin locus coding SinR (113 aa) and SinI (57 aa) is responsible for sporulation inhibition. In B. subtilis, SinR mainly acts as a repressor of its target genes to control sporulation, biofilm formation, and autolysis. SinI is an inhibitor of SinR, so their interaction determines whether SinR can inhibit its target gene expression. The C. difficile genome carries two sinR homologs in the operon that we named sinR and sinR’, coding for SinR (112 aa) and SinR’ (105 aa), respectively. In this study, we constructed and characterized sin locus mutants in two different C. difficile strains R20291 and JIR8094, to decipher the locus’s role in C. difficile physiology. Transcriptome analysis of the sinRR’ mutants revealed their pleiotropic roles in controlling several pathways including sporulation, toxin production, and motility in C. difficile. Through various genetic and biochemical experiments, we have shown that SinR can regulate transcription of key regulators in these pathways, which includes sigD, spo0A, and codY. We have found that SinR’ acts as an antagonist to SinR by blocking its repressor activity. Using a hamster model, we have also demonstrated that the sin locus is needed for successful C. difficile infection. This study reveals the sin locus as a central link that connects the gene regulatory networks of sporulation, toxin production, and motility; three key pathways that are important for C. difficile pathogenesis. PMID:29529083

  1. The algebraic locus of Feynman integrals

    OpenAIRE

    Kol, Barak

    2016-01-01

    In the Symmetries of Feynman Integrals (SFI) approach, a diagram's parameter space is foliated by orbits of a Lie group associated with the diagram. SFI is related to the important methods of Integrations By Parts and of Differential Equations. It is shown that sometimes there exist a locus in parameter space where the set of SFI differential equations degenerates into an algebraic equation, thereby enabling a solution in terms of integrals associated with degenerations of the diagram. This i...

  2. The mating type locus (MAT and sexual reproduction of Cryptococcus heveanensis: insights into the evolution of sex and sex-determining chromosomal regions in fungi.

    Directory of Open Access Journals (Sweden)

    Banu Metin

    2010-05-01

    Full Text Available Mating in basidiomycetous fungi is often controlled by two unlinked, multiallelic loci encoding homeodomain transcription factors or pheromones/pheromone receptors. In contrast to this tetrapolar organization, Cryptococcus neoformans/Cryptococcus gattii have a bipolar mating system, and a single biallelic locus governs sexual reproduction. The C. neoformans MAT locus is unusually large (>100 kb, contains >20 genes, and enhances virulence. Previous comparative genomic studies provided insights into how this unusual MAT locus might have evolved involving gene acquisitions into two unlinked loci and fusion into one contiguous locus, converting an ancestral tetrapolar system to a bipolar one. Here we tested this model by studying Cryptococcus heveanensis, a sister species to the pathogenic Cryptococcus species complex. An extant sexual cycle was discovered; co-incubating fertile isolates results in the teleomorph (Kwoniella heveanensis with dikaryotic hyphae, clamp connections, septate basidia, and basidiospores. To characterize the C. heveanensis MAT locus, a fosmid library was screened with C. neoformans/C. gattii MAT genes. Positive fosmids were sequenced and assembled to generate two large probably unlinked MAT gene clusters: one corresponding to the homeodomain locus and the other to the pheromone/receptor locus. Strikingly, two divergent homeodomain genes (SXI1, SXI2 are present, similar to the bE/bW Ustilago maydis paradigm, suggesting one or the other homeodomain gene was recently lost in C. neoformans/C. gattii. Sequencing MAT genes from other C. heveanensis isolates revealed a multiallelic homeodomain locus and at least a biallelic pheromone/receptor locus, similar to known tetrapolar species. Taken together, these studies reveal an extant C. heveanensis sexual cycle, define the structure of its MAT locus consistent with tetrapolar mating, and support the proposed evolutionary model for the bipolar Cryptococcus MAT locus revealing

  3. Skill effort: A new theoretical perspective on the relation between skills, skill use, mismatches, and wages

    NARCIS (Netherlands)

    van der Velden, Rolf; Bijlsma, Ineke

    2017-01-01

    Mismatches between workers’ skills and job demands have large negative effects on productivity, job satisfaction, and other outcomes. Current approaches to measure the impact of skills and skill mismatches on wages fail to specify the mechanism through which skills and mismatches may affect

  4. Mismatch discrimination of lipidated DNA and LNA-probes (LiNAs) in hybridization-controlled liposome assembly

    DEFF Research Database (Denmark)

    Jakobsen, Ulla; Vogel, Stefan

    2016-01-01

    Assays for mismatch discrimination and detection of single nucleotide variations by hybridization-controlled assembly of liposomes, which do not require tedious surface chemistry, are versatile for both DNA and RNA targets. We report herein a comprehensive study on different DNA and LNA (locked...... assay in the context of mismatch discrimination and SNP detection are presented. The advantages of membrane-anchored LiNA-probes compared to chemically attached probes on solid nanoparticles (e.g. gold nanoparticles) are described. Key functionalities such as non-covalent attachment of LiNA probes...... without the need for long spacers and the inherent mobility of membrane-anchored probes in lipid-bilayer membranes will be described for several different probe designs....

  5. Response of unirradiated and irradiated PWR fuel rods tested under power-cooling-mismatch conditions

    International Nuclear Information System (INIS)

    MacDonald, P.E.; Quapp, W.J.; Martinson, Z.R.; McCardell, R.K.; Mehner, A.S.

    1978-01-01

    This report summarizes the results from the single-rod power-cooling-mismatch (PCM) and irradiation effects (IE) tests conducted to date in the Power Burst Facility (PBF) at the U.S. DOE Idaho National Engineering Laboratory. This work was performed for the U.S. NRC under contact to the Department of Energy. These tests are part of the NRC Fuel Behavior Program, which is designed to provide data for the development and verification of analytical fuel behavior models that are used to predict fuel response to abnormal or postulated accident conditions in commercial LWRs. The mechanical, chemical and thermal response of both previously unirradiated and previously irradiated LWR-type fuel rods tested under power-cooling-mismatch condition is discussed. A brief description of the test designs is presented. The results of the PCM thermal-hydraulic studies are summarized. Primary emphasis is placed on the behavior of the fuel and cladding during and after stable film boiling. (orig.) [de

  6. Study of cover source mismatch in steganalysis and ways to mitigate its impact

    Science.gov (United States)

    Kodovský, Jan; Sedighi, Vahid; Fridrich, Jessica

    2014-02-01

    When a steganalysis detector trained on one cover source is applied to images from a different source, generally the detection error increases due to the mismatch between both sources. In steganography, this situation is recognized as the so-called cover source mismatch (CSM). The drop in detection accuracy depends on many factors, including the properties of both sources, the detector construction, the feature space used to represent the covers, and the steganographic algorithm. Although well recognized as the single most important factor negatively affecting the performance of steganalyzers in practice, the CSM received surprisingly little attention from researchers. One of the reasons for this is the diversity with which the CSM can manifest. On a series of experiments in the spatial and JPEG domains, we refute some of the common misconceptions that the severity of the CSM is tied to the feature dimensionality or their "fragility." The CSM impact on detection appears too difficult to predict due to the effect of complex dependencies among the features. We also investigate ways to mitigate the negative effect of the CSM using simple measures, such as by enlarging the diversity of the training set (training on a mixture of sources) and by employing a bank of detectors trained on multiple different sources and testing on a detector trained on the closest source.

  7. Fuzzy Backstepping Sliding Mode Control for Mismatched Uncertain System

    Directory of Open Access Journals (Sweden)

    H. Q. Hou

    2014-06-01

    Full Text Available Sliding mode controllers have succeeded in many control problems that the conventional control theories have difficulties to deal with; however it is practically impossible to achieve high-speed switching control. Therefore, in this paper an adaptive fuzzy backstepping sliding mode control scheme is derived for mismatched uncertain systems. Firstly fuzzy sliding mode controller is designed using backstepping method based on the Lyapunov function approach, which is capable of handling mismatched problem. Then fuzzy sliding mode controller is designed using T-S fuzzy model method, it can improve the performance of the control systems and their robustness. Finally this method of control is applied to nonlinear system as a case study; simulation results are also provided the performance of the proposed controller.

  8. Hydrophobic mismatch in gramicidin A'/lecithin systems

    International Nuclear Information System (INIS)

    Watnick, P.I.; Chan, S.I.; Dea, P.

    1990-01-01

    Gramicidin A' (GA') has been added to three lipid systems of varying hydrophobic thickness: dimyristoyllecithin (DML), dipalmitoyllecithin (DPL), and distearoyllecithin (DSL). The similarity in length between the hydrophobic portion of GA' and the hydrocarbon chains of the lipid bilayers has been studied by using 31 P and 2 H NMR. Hydrophobic mismatch has been found to be most severe in the DML bilayer system and minimal in the case of DSL. In addition, the effects of hydrophobic mismatch on the cooperative properties of the bilayer have been obtained from 2 H NMR relaxation measurements. The results indicate that incorporation of the peptide into the bilayer disrupts the cooperative director fluctuations characteristic of pure multilamellar lipid dispersions. Finally, the GA'/lecithin ratio at which the well-known transformation from bilayer to reverse hexagonal (H II ) phase occurs is shown to depend on the acyl chain length of the phospholipid. A rationale is proposed for this chain length dependence

  9. Work-Education Mismatch: An Endogenous Theory of Professionalization.

    Science.gov (United States)

    Ghaffarzadegan, Navid; Xue, Yi; Larson, Richard C

    2017-09-16

    We model the education-workforce pipeline and offer an endogenous theory of professionalization and ever-higher degree attainment. We introduce two mechanisms that act on the education enterprise, causing the number of educated people to increase dramatically with relatively short-term changes in the job market. Using our illustrative dynamic model, we argue that the system is susceptible to small changes and the introduced self-driving growth engines are adequate to over-incentivize degree attainment. We also show that the mechanisms magnify effects of short-term recessions or technological changes, and create long-term waves of mismatch between workforce and jobs. The implication of the theory is degree inflation, magnified pressures on those with lower degrees, underemployment, and job market mismatch and inefficiency.

  10. A Computational Model for Biomechanical Effects of Arterial Compliance Mismatch

    Directory of Open Access Journals (Sweden)

    Fan He

    2015-01-01

    Full Text Available Background. Compliance mismatch is a negative factor and it needs to be considered in arterial bypass grafting. Objective. A computational model was employed to investigate the effects of arterial compliance mismatch on blood flow, wall stress, and deformation. Methods. The unsteady blood flow was assumed to be laminar, Newtonian, viscous, and incompressible. The vessel wall was assumed to be linear elastic, isotropic, and incompressible. The fluid-wall interaction scheme was constructed using the finite element method. Results. The results show that there are identical wall shear stress waveforms, wall stress, and strain waveforms at different locations. The comparison of the results demonstrates that wall shear stresses and wall strains are higher while wall stresses are lower at the more compliant section. The differences promote the probability of intimal thickening at some locations. Conclusions. The model is effective and gives satisfactory results. It could be extended to all kinds of arteries with complicated geometrical and material factors.

  11. Clinical predictors of prosthesis-patient mismatch after aortic valve replacement for aortic stenosis

    Directory of Open Access Journals (Sweden)

    Luis M Astudillo

    2012-01-01

    Full Text Available OBJECTIVE: We sought to ascertain predictors of Patient Prosthesis Mismatch, an independent predictor of mortality, in patients with aortic stenosis using bioprosthetic valves. METHOD: We analyzed 2,107 sequential surgeries. Patient Prosthesis Mismatch was calculated using the effective orifice area of the prosthesis divided by the patient's body surface area. We defined nonsignificant, moderate, and severe Patient Prosthesis Mismatch as effective orifice area indexes of .0.85 cm²/m, 0.85-0.66 cm²/m², and <0.65 cm²/m², respectively. RESULTS: A total of 311 bioprosthetic patients were identified. The incidence of nonsignificant, moderate, and severe Patient Prosthesis Mismatch was 41%, 42, and 16%, respectively. Severe Patient Prosthesis Mismatch was significantly more prevalent in females (82%. In severe Patient Prosthesis Mismatch, the perfusion and the crossclamp times were considerably lower when compared with nonsignificant Patient Prosthesis Mismatch and moderate Patient Prosthesis Mismatch. Patients with severe Patient Prosthesis Mismatch had a significantly higher likelihood of spending time in the intensive care unit and a significantly longer length of stay in the hospital. Body surface area was not different in severe Patient Prosthesis Mismatch when compared with nonsignificant Patient Prosthesis Mismatch. In-hospital mortality in patients with nonsignificant, moderate, and severe Patient Prosthesis Mismatch was 2.3%, 6.1%, and 8%, respectively. Minimally invasive surgery was significantly associated with moderate Patient Prosthesis Mismatch in 49% of the patients, but not with severe Patient Prosthesis Mismatch. CONCLUSION: Severe Patient Prosthesis Mismatch is more common in females, but not in those with minimal available body surface area. Though operative times were shorter in these patients, intensive care unit and hospital lengths of stay were longer. Surgeons and cardiologists should be cognizant of these clinical

  12. Addressing private sector currency mismatches in emerging Europe

    OpenAIRE

    Jeromin Zettelmeyer; Piroska M. Nagy; Stephen Jeffrey

    2010-01-01

    This paper provides a survey of the theoretical and empirical literature on the dollarisation of corporate and household liabilities; presents evidence on the causes of FX lending specifically in transition economies; and proposes a set of criteria to help decide on the right policy response based on country characteristics. These criteria particularly affect the extent to which regulation should be part of the policy response. Regulation to contain FX mismatches is useful in relatively advan...

  13. Artemisinin Resistance-Associated Polymorphisms at the K13-Propeller Locus Are Absent in Plasmodium falciparum Isolates from Haiti

    Science.gov (United States)

    Carter, Tamar E.; Boulter, Alexis; Existe, Alexandre; Romain, Jean R.; St. Victor, Jean Yves; Mulligan, Connie J.; Okech, Bernard A.

    2015-01-01

    Antimalarial drugs are a key tool in malaria elimination programs. With the emergence of artemisinin resistance in southeast Asia, an effort to identify molecular markers for surveillance of resistant malaria parasites is underway. Non-synonymous mutations in the kelch propeller domain (K13-propeller) in Plasmodium falciparum have been associated with artemisinin resistance in samples from southeast Asia, but additional studies are needed to characterize this locus in other P. falciparum populations with different levels of artemisinin use. Here, we sequenced the K13-propeller locus in 82 samples from Haiti, where limited government oversight of non-governmental organizations may have resulted in low-level use of artemisinin-based combination therapies. We detected a single-nucleotide polymorphism (SNP) at nucleotide 1,359 in a single isolate. Our results contribute to our understanding of the global genomic diversity of the K13-propeller locus in P. falciparum populations. PMID:25646258

  14. Educational mismatch in the labour market: overqualification and its implications

    Directory of Open Access Journals (Sweden)

    Marija Bečić

    2013-12-01

    Full Text Available Educational mismatch as a labour market disruption has lately attracted the interest of many economic experts and scholars. This interest is spurred by considerable improvements in the educational profile of the population, combined with changes in the demand for highly-qualified workers linked to technological developments. The mismatch can appear if an increase in highly-qualified workforce supply is not accom - panied by an equal growth in the demand. Overqualification is one such type of mismatch: it means that knowledge and skills acquired during formal education remain unused in the workplace. Many economies face this problem that can have negative consequences for individuals, businesses, and the government alike. This paper provides an overview of the basic concepts related to overqualification, focusing on the possible implications of this phenomenon, given that employee dissatisfaction can affect businesses and their productivity, and ultimately, the country as a whole. Systematization of previous research and analysis of the basic concepts related to overqualification can contribute to the literature in economics of education in Croatia and create a foundation for future research

  15. The Scientist and the Educational Development Team: An Impedance Mismatch?

    Science.gov (United States)

    Pompea, S. M.

    2001-05-01

    This talk describes my experiences and those of several other scientists who have worked on teams to develop new instructional materials and programs. At each stage of the development process we try to communicate our skills and experiences to the rest of the development team. In turn, the experiences of non-scientist educators on the team must be communicated to us. However, in many cases there is an "impedance mismatch" which makes communication difficult. One primary source of this mismatch is the scientist's lack of experience with schools, students, teachers, school administrators, museums, and the public. The result of this mismatch can leave the scientist in one limited, but useful role: proofreader and critic. Unfortunately, this can hardly be described as a partnership. This talk gives some advice, based on 25 years of educational materials and program development work, on how to avoid such a limited role. The talk would be appropriate for those scientists who want to lead, inspire, or significantly contribute to educational initiatives and to share in the frustration and the rewards enjoyed by professional educators and professional educational developers. S. Pompea is an adjunct faculty member of Steward Observatory of the University of Arizona.

  16. Aspects related to fracture toughness of mismatch welds

    International Nuclear Information System (INIS)

    Kumar, Suranjit; Khan, I.A.; Bhasin, V.; Vaze, K.K.

    2011-01-01

    In this work effect of weld strength mismatch and weld slenderness on plastic η factor was systematically examined. Solutions presented here are based on extensive two-dimensional finite element analysis. Results of FE analysis has shown that for homogeneous specimens plastic η -factor does not vary significantly with material strain hardening index. Plastic η -factors for non-hardening material models were in better agreement with ASTM solutions than for hardening material models. For mismatch welded specimens analyses were performed on Compact tension (CT) and three points bend (TPB) specimens. Studies were performed for both hardening as well as elastic-perfectly plastic (non-hardening) material models. Results of finite element analysis have shown that unlike homogeneous specimens there is an influence of material strain hardening on plastic η -factor. For over match welds plastic η -factor evaluated for non-hardening material model are lower while for under match welds use of non-hardening material model gives higher value as compare to that of hardening material model. However, it was observed that for over match welds use of ASTM based plastic η -factors (valid for homogeneous specimens) gives the higher values than actual plastic η -factors (evaluated for both hardening as well as non-hardening material model) of mismatch welded specimens. This in turn would lead to un-conservative estimate of fracture toughness and vice versa is true for under-matched welds. (author)

  17. Overexpression of the DNA mismatch repair factor, PMS2, confers hypermutability and DNA damage tolerance.

    Science.gov (United States)

    Gibson, Shannon L; Narayanan, Latha; Hegan, Denise Campisi; Buermeyer, Andrew B; Liskay, R Michael; Glazer, Peter M

    2006-12-08

    Inherited defects in genes associated with DNA mismatch repair (MMR) have been linked to familial colorectal cancer. Cells deficient in MMR are genetically unstable and demonstrate a tolerance phenotype in response to certain classes of DNA damage. Some sporadic human cancers also show abnormalities in MMR gene function, typically due to diminished expression of one of the MutL homologs, MLH1. Here, we report that overexpression of the MutL homolog, human PMS2, can also cause a disruption of the MMR pathway in mammalian cells, resulting in hypermutability and DNA damage tolerance. A mouse fibroblast cell line carrying a recoverable lambda phage shuttle vector for mutation detection was transfected with either a vector designed to express hPMS2 or with an empty vector control. Cells overexpressing hPMS2 were found to have elevated spontaneous mutation frequencies at the cII reporter gene locus. They also showed an increase in the level of mutations induced by the alkylating agent, methynitrosourea (MNU). Clonogenic survival assays demonstrated increased survival of the PMS2-overexpressing cells following exposure to MNU, consistent with the induction of a damage tolerance phenotype. Similar results were seen in cells expressing a mutant PMS2 gene, containing a premature stop codon at position 134 and representing a variant found in an individual with familial colon cancer. These results show that dysregulation of PMS2 gene expression can disrupt MMR function in mammalian cells and establish an additional carcinogenic mechanism by which cells can develop genetic instability and acquire resistance to cytotoxic cancer therapies.

  18. Analysis of fast neutron-generated mutants at the Arabidopsis thaliana HY4 locus

    International Nuclear Information System (INIS)

    Bruggemann, E.; Handwerger, K.; Essex, C.; Storz, G.

    1996-01-01

    Ionizing radiation is expected to produce mutants with deletions or other chromosomal rearrangements. These mutants are useful for a variety of purposes, such as creating null alleles and cloning genes whose existence is known only from their mutant phenotype; however, only a few mutations generated by ionizing radiation have been characterized at the molecular level in Arabidopsis thaliana. Twenty fast neutron-generated alleles of the Arabidopsis HY4 locus, which encodes a blue light receptor, CRY1, were isolated and characterized. Nine of the mutant alleles displayed normal genetic behavior. The other 11 mutant alleles were poorly transmitted through the male gametophyte and were lethal in homozygous plants. Southern blot analysis demonstrated that alleles of the first group generally contain small or moderate-sized deletions at HY4, while alleles of the second group contain large deletions at this locus. These results demonstrate that fast neutrons can produce a range of deletions at a single locus in Arabidopsis. Many of these deletions would be suitable for cloning by genomic subtraction or representational difference analysis. The results also suggest the presence of an essential locus adjacent to HY4. (author)

  19. Genomewide scan identifies susceptibility locus for dyslexia on Xq27 in an extended Dutch family.

    Science.gov (United States)

    de Kovel, C G F; Hol, F A; Heister, J G A M; Willemen, J J H T; Sandkuijl, L A; Franke, B; Padberg, G W

    2004-09-01

    Dyslexia is a common disorder with a strong genetic component, but despite significant research effort, the aetiology is still largely unknown. To identify loci contributing to dyslexia risk. This was a genomewide linkage analysis in a single large family. Dutch families with at least two first degree relatives suffering from dyslexia participated in the study. Participants were recruited through an advertisement campaign in papers and magazines. The main outcome measure was linkage between genetic markers and dyslexia phenotype. Using parametric linkage analysis, we found strong evidence for a locus influencing dyslexia on Xq27.3 (multipoint lod = 3.68). Recombinations in two family members flanked an 8 cM region, comprising 11 currently confirmed genes. All four males carrying the risk haplotype had very low scores on the reading tests. The presentation in females was more variable, but 8/9 females carrying the risk haplotype were diagnosed dyslexic by our composite score, so we considered the putative risk allele to be dominant with reduced penetrance. Linkage was not found in an additional collection of affected sibling pairs. A locus influencing dyslexia risk is probably located between markers DXS1227 and DXS8091 on the X chromosome, closely situated to a locus indicated by a published genome scan of English sibling pairs. Although the locus may not be a common cause for dyslexia, the relatively small and gene poor region offers hope to identify the responsible gene.

  20. Insertional inactivation of a chromosomal locus that modulates expression of potential virulence determinants in Staphylococcus aureus.

    Science.gov (United States)

    Cheung, A L; Wolz, C; Yeaman, M R; Bayer, A S

    1995-06-01

    A single insertion of transposon Tn551 into a unique chromosomal locus of Staphylococcus aureus ISP479C has resulted in a pleiotropic effect on the expression of both extracellular and cell wall proteins. In particular, the expression of cell wall protein A and clumping activity with fibrinogen were rendered undetectable in the mutant 1E3 compared with the parent. The secretion of alpha-hemolysin in mutant 1E3 was modestly increased. Southern blot and phenotypic analyses indicated that this locus is distinct from agr, xpr, and sar, three previously described global regulatory loci. Transduction experiments demonstrated that the genotype associated with mutant 1E3 could be transferred back into the parental strain ISP479C. The transductant 1E3-2 displayed a phenotypic profile similar to that of the original mutant. Northern (RNA) blot studies showed that this locus may be involved in modulating target genes at the mRNA level. In the rabbit endocarditis model, there was a significant decrease in both the infectivity rate and intravegetation bacterial density with mutant 1E3 compared with the parent at an inoculum of 10(3) CFU. Since protein A and the fibrinogen-binding protein(s) are major surface proteins that may mediate bacterial adhesion to host tissues, this locus may be an important genetic element involved in the expression of virulence determinants in S. aureus.

  1. Expression of transgenes targeted to the Gt(ROSA26Sor locus is orientation dependent.

    Directory of Open Access Journals (Sweden)

    Douglas Strathdee

    2006-12-01

    Full Text Available Targeting transgenes to a chosen location in the genome has a number of advantages. A single copy of the DNA construct can be inserted by targeting into regions of chromatin that allow the desired developmental and tissue-specific expression of the transgene.In order to develop a reliable system for reproducibly expressing transgenes it was decided to insert constructs at the Gt(ROSA26Sor locus. A cytomegalovirus (CMV promoter was used to drive expression of the Tetracycline (tet transcriptional activator, rtTA2(s-M2, and test the effectiveness of using the ROSA26 locus to allow transgene expression. The tet operator construct was inserted into one allele of ROSA26 and a tet responder construct controlling expression of EGFP was inserted into the other allele.Expression of the targeted transgenes was shown to be affected by both the presence of selectable marker cassettes and by the orientation of the transgenes with respect to the endogenous ROSA26 promoter. These results suggest that transcriptional interference from the endogenous gene promoter or from promoters in the selectable marker cassettes may be affecting transgene expression at the locus. Additionally we have been able to determine the optimal orientation for transgene expression at the ROSA26 locus.

  2. A two-locus model of spatially varying stabilizing or directional selection on a quantitative trait.

    Science.gov (United States)

    Geroldinger, Ludwig; Bürger, Reinhard

    2014-06-01

    The consequences of spatially varying, stabilizing or directional selection on a quantitative trait in a subdivided population are studied. A deterministic two-locus two-deme model is employed to explore the effects of migration, the degree of divergent selection, and the genetic architecture, i.e., the recombination rate and ratio of locus effects, on the maintenance of genetic variation. The possible equilibrium configurations are determined as functions of the migration rate. They depend crucially on the strength of divergent selection and the genetic architecture. The maximum migration rates are investigated below which a stable fully polymorphic equilibrium or a stable single-locus polymorphism can exist. Under stabilizing selection, but with different optima in the demes, strong recombination may facilitate the maintenance of polymorphism. However usually, and in particular with directional selection in opposite direction, the critical migration rates are maximized by a concentrated genetic architecture, i.e., by a major locus and a tightly linked minor one. Thus, complementing previous work on the evolution of genetic architectures in subdivided populations subject to diversifying selection, it is shown that concentrated architectures may aid the maintenance of polymorphism. Conditions are obtained when this is the case. Finally, the dependence of the phenotypic variance, linkage disequilibrium, and various measures of local adaptation and differentiation on the parameters is elaborated. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Field-of-study mismatch and overqualification: labour market correlates and their wage penalty

    Directory of Open Access Journals (Sweden)

    Guillermo Montt

    2017-01-01

    Full Text Available Abstract Field-of-study mismatch occurs when a worker, trained in a particular field, works in another field. This study draws on the Survey of Adult Skills (PIAAC to explore how skill supply and labour market demand dynamics influence mismatch. It updates cross-national estimates on mismatch and estimates the mismatch wage penalty. Findings suggest that around 40% of workers are mismatched by field at their qualification level, 11% overqualified in their field and 13% overqualified and working outside their field. The saturation of the field in the labour market and the transferability of the fields’ skills predict the incidence of field-of-study mismatch and overqualification. Workers who are mismatched by field only suffer a wage penalty if they are overqualified.

  4. Locus of control and online learning

    Directory of Open Access Journals (Sweden)

    Suretha Esterhuysen

    2004-10-01

    Full Text Available The integration of online learning in university courses is considered to be both inevitable and necessary. Thus there is an increasing need to raise awareness among educators and course designers about the critical issues impacting on online learning. The aim of this study, therefore, was to assess the differences between two groups of first-year Business Sciences learners (online and conventional learners in terms of biographic and demographic characteristics and locus of control. The study population consisted of 586 first-year learners of whom 185 completed the Locus of Control Inventory (LCI. The results show that the two groups of learners do not differ statistically significantly from each other with respect to locus of control. The findings and their implications are also discussed. Opsomming Die integrasie van aanlyn-leer in universiteitskursusse word beskou as sowel onafwendbaar as noodsaaklik. Daar is dus ’n toenemende behoefte om bewustheid onder opvoedkundiges en kursusontwerpers te kweek oor die kritiese aspekte wat ’n impak op aanlyn-leer het (Morgan, 1996. Daarom was die doel van hierdie ondersoek om die verskille tussen twee groepe eerstejaarleerders in Bestuurs- en Ekonomiese Wetenskap (aanlyn en konvensionele leerders te bepaal ten opsigte van biografiese en demografiese eienskappe en lokus van beheer. Die populasie het bestaan uit 586 eerstejaarleerders waarvan 185 die Lokus van Beheer Vraelys voltooi het. Die resultate toon dat die twee groepe leerders nie statisties beduidend van mekaar verskil het met betrekking tot lokus van beheer nie. Die bevindinge en implikasies word ook bespreek.

  5. Designing Epigenome Editors: Considerations of Biochemical and Locus Specificities.

    Science.gov (United States)

    Sen, Dilara; Keung, Albert J

    2018-01-01

    The advent of locus-specific protein recruitment technologies has enabled a new class of studies in chromatin biology. Epigenome editors enable biochemical modifications of chromatin at almost any specific endogenous locus. Their locus specificity unlocks unique information including the functional roles of distinct modifications at specific genomic loci. Given the growing interest in using these tools for biological and translational studies, there are many specific design considerations depending on the scientific question or clinical need. Here we present and discuss important design considerations and challenges regarding the biochemical and locus specificities of epigenome editors. These include how to account for the complex biochemical diversity of chromatin; control for potential interdependency of epigenome editors and their resultant modifications; avoid sequestration effects; quantify the locus specificity of epigenome editors; and improve locus specificity by considering concentration, affinity, avidity, and sequestration effects.

  6. Cut Locus Construction using Deformable Simplicial Complexes

    DEFF Research Database (Denmark)

    Misztal, Marek Krzysztof; Bærentzen, Jakob Andreas; Anton, François

    2011-01-01

    In this paper we present a method for appproximating cut loci for a given point p on Riemannian 2D manifolds, closely related to the notion of Voronoi diagrams. Our method finds the cut locus by advecting a front of points equally distant from p along the geodesics originating at p and finding...... the domain to have disk topology. We test our method for tori of revolution and compare our results to the benchmark ones from [2]. The method, however, is generic and can be easily adapted to construct cut loci for other manifolds of genera other than 1....

  7. Numerical simulations of material mismatch and ductile crack growth

    Energy Technology Data Exchange (ETDEWEB)

    Oestby, Erling

    2002-07-01

    Both the global geometry and inhomogeneities in material properties will influence the fracture behaviour of structures in presence of cracks. In this thesis numerical simulations have been used to investigate how some aspects of both these issues affect the conditions at the crack-tip. The thesis is organised in an introduction chapter, summarising the major findings and conclusions, a review chapter, presenting the main aspects of the developments in the field of fracture mechanics, and three research papers. Paper I considers the effect of mismatch in hardening exponent on the local near-tip stress field for stationary interface cracks in bi-materials under small scale yielding conditions. It is demonstrated that the stress level in the weaker material increases compared to what is found in the homogeneous material for the same globally applied load level, with the effect being of increasing importance as the crack-tip is approached. Although a coupling between the radial and angular dependence of the stress fields exists, the evolving stress field can still be normalised with the applied J. The effect on the increase in stress level can closely be characterised by the difference in hardening exponent, {delta}n, termed the hardening mismatch, and is more or less independent of the absolute level of hardening in the two materials. Paper II and Ill deal with the effects of geometry, specimen size, hardening level and yield stress mismatch in relation to ductile crack growth. The ductile crack growth is simulated through use of the Gurson model. In Paper H the effect of specimen size on the crack growth resistance is investigated for deep cracked bend and shallow cracked tensile specimens. At small amounts of crack growth the effect of specimen size on the crack growth resistance is small, but a more significant effect is found for larger amounts of crack growth. The crack growth resistance decreases in smaller specimens loaded in tension, whereas the opposite is

  8. TaMSH7: A cereal mismatch repair gene that affects fertility in transgenic barley (Hordeum vulgare L.

    Directory of Open Access Journals (Sweden)

    Langridge Peter

    2007-12-01

    Full Text Available Abstract Background Chromosome pairing, recombination and DNA repair are essential processes during meiosis in sexually reproducing organisms. Investigating the bread wheat (Triticum aestivum L. Ph2 (Pairing homoeologous locus has identified numerous candidate genes that may have a role in controlling such processes, including TaMSH7, a plant specific member of the DNA mismatch repair family. Results Sequencing of the three MSH7 genes, located on the short arms of wheat chromosomes 3A, 3B and 3D, has revealed no significant sequence divergence at the amino acid level suggesting conservation of function across the homoeogroups. Functional analysis of MSH7 through the use of RNAi loss-of-function transgenics was undertaken in diploid barley (Hordeum vulgare L.. Quantitative real-time PCR revealed several T0 lines with reduced MSH7 expression. Positive segregants from two T1 lines studied in detail showed reduced MSH7 expression when compared to transformed controls and null segregants. Expression of MSH6, another member of the mismatch repair family which is most closely related to the MSH7 gene, was not significantly reduced in these lines. In both T1 lines, reduced seed set in positive segregants was observed. Conclusion Results presented here indicate, for the first time, a distinct functional role for MSH7 in vivo and show that expression of this gene is necessary for wild-type levels of fertility. These observations suggest that MSH7 has an important function during meiosis and as such remains a candidate for Ph2.

  9. A rule of seven in Watson-Crick base-pairing of mismatched sequences.

    Science.gov (United States)

    Cisse, Ibrahim I; Kim, Hajin; Ha, Taekjip

    2012-05-13

    Sequence recognition through base-pairing is essential for DNA repair and gene regulation, but the basic rules governing this process remain elusive. In particular, the kinetics of annealing between two imperfectly matched strands is not well characterized, despite its potential importance in nucleic acid-based biotechnologies and gene silencing. Here we use single-molecule fluorescence to visualize the multiple annealing and melting reactions of two untethered strands inside a porous vesicle, allowing us to precisely quantify the annealing and melting rates. The data as a function of mismatch position suggest that seven contiguous base pairs are needed for rapid annealing of DNA and RNA. This phenomenological rule of seven may underlie the requirement for seven nucleotides of complementarity to seed gene silencing by small noncoding RNA and may help guide performance improvement in DNA- and RNA-based bio- and nanotechnologies, in which off-target effects can be detrimental.

  10. Relationships between locus of control and paranormal beliefs.

    Science.gov (United States)

    Newby, Robert W; Davis, Jessica Boyette

    2004-06-01

    The present study investigated the associations between scores on paranormal beliefs, locus of control, and certain psychological processes such as affect and cognitions as measured by the Linguistic Inquiry and Word Count. Analysis yielded significant correlations between scores on Locus of Control and two subscales of Tobacyk's (1988) Revised Paranormal Beliefs Scale, New Age Philosophy and Traditional Paranormal Beliefs. A step-wise multiple regression analysis indicated that Locus of Control was significantly related to New Age Philosophy. Other correlations were found between Tobacyk's subscales, Locus of Control, and three processes measured by the Linguistic Inquiry and Word Count.

  11. Impact of locus of control on health message effectiveness.

    Science.gov (United States)

    Kong, Ying; Shen, Fuyuan

    2011-10-01

    This article examined how individuals' locus of control might moderate the effect of health message frames. An experiment was conducted whereby participants read either individual- or social-responsibility message frames after their locus of control was primed. Results indicated that messages presented in individual-responsibility frames were more persuasive when people were primed with internal locus of control, whereas social-responsibility framed appeals were more persuasive when people were primed with external locus of control. These results were found for individuals in both high and low cognitive load conditions. Theoretical and practical implications of the findings are discussed.

  12. Genetic and physical analysis of a YAC contig spanning the fungal disease resistance locus Asc of tomato (Lycopersicon esculentum)

    NARCIS (Netherlands)

    Mesbah, L.A.; Kneppers, T.J.A.; Takken, F.L.W.; Laurent, P.; Hille, J.; Nijkamp, H.J.J.

    1998-01-01

    The Alternaria stem canker disease of tomato is caused by the necrotrophic fungal pathogen Alternaria alternata f. sp. lycopersici (AAL). The fungus produces AAL toxins that kill the plant tissue. Resistance to the fungus segregates as a single locus, called Asc, and has been genetically mapped on

  13. Genetic and physical analysis of a YAC contig spannig the fungal disease resistance locus Asc of tomato (Lycopersicon esculentum)

    NARCIS (Netherlands)

    Mesbah, L.A.; Kneppers, T.J.A.; Takken, F.L.W.; Laurent, P.J.F.; Hille, J.; Nijkamp, H.J.J.

    1999-01-01

    The Alternaria in stem canker disease of tomato is caused by the necrotrophic fungal pathogen Alternaria alternata f. sp. lycopersici (AAL). The fungus produces AAL toxins that kill the plant tissue. Resistance to the fungus segregates as a single locus, called Asc, and has been genetically mapped

  14. Genetic variation at the PCSK9 locus, low density lipoproteins, response to pravastatin and coronary heart disease: results from PROSPER

    Science.gov (United States)

    Caucasian carriers of the T allele at R46L in the proprotein convertase subtilisin/kexin type 9 (PCSK9) locus have been reported to have 15% lower low-density lipoprotein (LDL) cholesterol (C) levels and 47% lower coronary heart disease (CHD) risk. Our objective was to examine two PCSK9 single nucle...

  15. Genetic and environmental influences on the relationship between flow proneness, locus of control and behavioral inhibition.

    Directory of Open Access Journals (Sweden)

    Miriam A Mosing

    Full Text Available Flow is a psychological state of high but subjectively effortless attention that typically occurs during active performance of challenging tasks and is accompanied by a sense of automaticity, high control, low self-awareness, and enjoyment. Flow proneness is associated with traits and behaviors related to low neuroticism such as emotional stability, conscientiousness, active coping, self-esteem and life satisfaction. Little is known about the genetic architecture of flow proneness, behavioral inhibition and locus of control--traits also associated with neuroticism--and their interrelation. Here, we hypothesized that individuals low in behavioral inhibition and with an internal locus of control would be more likely to experience flow and explored the genetic and environmental architecture of the relationship between the three variables. Behavioral inhibition and locus of control was measured in a large population sample of 3,375 full twin pairs and 4,527 single twins, about 26% of whom also scored the flow proneness questionnaire. Findings revealed significant but relatively low correlations between the three traits and moderate heritability estimates of .41, .45, and .30 for flow proneness, behavioral inhibition, and locus of control, respectively, with some indication of non-additive genetic influences. For behavioral inhibition we found significant sex differences in heritability, with females showing a higher estimate including significant non-additive genetic influences, while in males the entire heritability was due to additive genetic variance. We also found a mainly genetically mediated relationship between the three traits, suggesting that individuals who are genetically predisposed to experience flow, show less behavioral inhibition (less anxious and feel that they are in control of their own destiny (internal locus of control. We discuss that some of the genes underlying this relationship may include those influencing the function of

  16. Genetic and environmental influences on the relationship between flow proneness, locus of control and behavioral inhibition.

    Science.gov (United States)

    Mosing, Miriam A; Pedersen, Nancy L; Cesarini, David; Johannesson, Magnus; Magnusson, Patrik K E; Nakamura, Jeanne; Madison, Guy; Ullén, Fredrik

    2012-01-01

    Flow is a psychological state of high but subjectively effortless attention that typically occurs during active performance of challenging tasks and is accompanied by a sense of automaticity, high control, low self-awareness, and enjoyment. Flow proneness is associated with traits and behaviors related to low neuroticism such as emotional stability, conscientiousness, active coping, self-esteem and life satisfaction. Little is known about the genetic architecture of flow proneness, behavioral inhibition and locus of control--traits also associated with neuroticism--and their interrelation. Here, we hypothesized that individuals low in behavioral inhibition and with an internal locus of control would be more likely to experience flow and explored the genetic and environmental architecture of the relationship between the three variables. Behavioral inhibition and locus of control was measured in a large population sample of 3,375 full twin pairs and 4,527 single twins, about 26% of whom also scored the flow proneness questionnaire. Findings revealed significant but relatively low correlations between the three traits and moderate heritability estimates of .41, .45, and .30 for flow proneness, behavioral inhibition, and locus of control, respectively, with some indication of non-additive genetic influences. For behavioral inhibition we found significant sex differences in heritability, with females showing a higher estimate including significant non-additive genetic influences, while in males the entire heritability was due to additive genetic variance. We also found a mainly genetically mediated relationship between the three traits, suggesting that individuals who are genetically predisposed to experience flow, show less behavioral inhibition (less anxious) and feel that they are in control of their own destiny (internal locus of control). We discuss that some of the genes underlying this relationship may include those influencing the function of dopaminergic neural

  17. Characterization of the bovine type I IFN locus: rearrangements, expansions, and novel subfamilies

    Directory of Open Access Journals (Sweden)

    Walker Angela M

    2009-04-01

    Full Text Available Abstract Background The Type I interferons (IFN have major roles in the innate immune response to viruses, a function that is believed to have led to expansion in the number and complexity of their genes, although these genes have remained confined to single chromosomal region in all mammals so far examined. IFNB and IFNE define the limits of the locus, with all other Type I IFN genes except IFNK distributed between these boundaries, strongly suggesting that the locus has broadened as IFN genes duplicated and then evolved into a series of distinct families. Results The Type I IFN locus in Bos taurus has undergone significant rearrangement and expansion compared to mouse and human, however, with the constituent genes separated into two sub-loci separated by >700 kb. The IFNW family is greatly expanded, comprising 24 potentially functional genes and at least 8 pseudogenes. The IFNB (n = 6, represented in human and mouse by one copy, are also present as multiple copies in Bos taurus. The IFNT, which encode a non-virally inducible, ruminant-specific IFN secreted by the pre-implantation conceptus, are represented by three genes and two pseudogenes. The latter have sequences intermediate between IFNT and IFNW. A new Type I IFN family (IFNX of four members, one of which is a pseudogene, appears to have diverged from the IFNA lineage at least 83 million years ago, but is absent in all other sequenced genomes with the possible exception of the horse, a non-ruminant herbivore. Conclusion In summary, we have provided the first comprehensive annotation of the Type I IFN locus in Bos taurus, thereby providing an insight into the functional evolution of the Type I IFN in ruminants. The diversity and global spread of the ruminant species may have required an expansion of the Type I IFN locus and its constituent genes to provide broad anti-viral protection required for foraging and foregut fermentation.

  18. Mismatch negativity, social cognition, and functional outcomes in patients after traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Hui-yan Sun

    2015-01-01

    Full Text Available Mismatch negativity is generated automatically, and is an early monitoring indicator of neuronal integrity impairment and functional abnormality in patients with brain injury, leading to decline of cognitive function. Antipsychotic medication cannot affect mismatch negativity. The present study aimed to explore the relationships of mismatch negativity with neurocognition, daily life and social functional outcomes in patients after brain injury. Twelve patients with traumatic brain injury and 12 healthy controls were recruited in this study. We examined neurocognition with the Wechsler Adult Intelligence Scale-Revised China, and daily and social functional outcomes with the Activity of Daily Living Scale and Social Disability Screening Schedule, respectively. Mismatch negativity was analyzed from electroencephalogram recording. The results showed that mismatch negativity amplitudes decreased in patients with traumatic brain injury compared with healthy controls. Mismatch negativity amplitude was negatively correlated with measurements of neurocognition and positively correlated with functional outcomes in patients after traumatic brain injury. Further, the most significant positive correlations were found between mismatch negativity in the fronto-central region and measures of functional outcomes. The most significant positive correlations were also found between mismatch negativity at the FCz electrode and daily living function. Mismatch negativity amplitudes were extremely positively associated with Social Disability Screening Schedule scores at the Fz electrode in brain injury patients. These experimental findings suggest that mismatch negativity might efficiently reflect functional outcomes in patients after traumatic brain injury.

  19. Effect of agmatine on locus coeruleus neuron activity: possible involvement of nitric oxide

    Science.gov (United States)

    Ruiz-Durántez, Eduardo; Ruiz-Ortega, José A; Pineda, Joseba; Ugedo, Luisa

    2002-01-01

    To investigate whether agmatine (the proposed endogenous ligand for imidazoline receptors) controls locus coeruleus neuron activity and to elucidate its mechanism of action, we used single-unit extracellular recording techniques in anaesthetized rats. Agmatine (10, 20 and 40 μg, i.c.v.) increased in a dose-related manner the firing rate of locus coeruleus neurons (maximal increase: 95±13% at 40 μg). I1-imidazoline receptor ligands stimulate locus coeruleus neuron activity through an indirect mechanism originated in the paragigantocellularis nucleus via excitatory amino acids. However, neither electrolytic lesions of the paragigantocellularis nucleus nor pretreatment with the excitatory amino acid antagonist kynurenic acid (1 μmol, i.c.v.) modified agmatine effect (10 μg, i.c.v.). After agmatine administration (20 μg, i.c.v.), dose-response curves for the effect of clonidine (0.625 – 10 μg kg−1 i.v.) or morphine (0.3 – 4.8 mg kg−1 i.v.) on locus coeruleus neurons were not different from those obtained in the control groups. Pretreatment with the nitric oxide synthase inhibitors Nω-nitro-L-arginine (10 μg, i.c.v.) or Nω-nitro-L-arginine methyl ester (100 μg, i.c.v.) but not with the less active stereoisomer Nω-nitro-D-arginine methyl ester (100 μg, i.c.v.) completely blocked agmatine effect (10 and 40 μg, i.c.v.). Similarly, when agmatine (20 pmoles) was applied into the locus coeruleus there was an increase that was blocked by Nω-nitro-L-arginine methyl ester (100 μg, i.c.v.) in the firing rate of the locus coeruleus neurons (maximal increase 53±11% and 14±10% before and after nitric oxide synthase inhibition, respectively). This study demonstrates that agmatine stimulates the firing rate of locus coeruleus neurons via a nitric oxide synthase-dependent mechanism located in this nucleus. PMID:11877321

  20. Doublethink and scale mismatch polarize policies for an invasive tree

    Science.gov (United States)

    Roberts, Caleb P.; Uden, Daniel R.; Allen, Craig R.; Twidwell, Dirac

    2018-01-01

    Mismatches between invasive species management policies and ecological knowledge can lead to profound societal consequences. For this reason, natural resource agencies have adopted the scientifically-based density-impact invasive species curve to guide invasive species management. We use the density-impact model to evaluate how well management policies for a native invader (Juniperus virginiana) match scientific guidelines. Juniperus virginiana invasion is causing a sub-continental regime shift from grasslands to woodlands in central North America, and its impacts span collapses in endemic diversity, heightened wildfire risk, and crashes in grazing land profitability. We (1) use land cover data to identify the stage of Juniperus virginiana invasion for three ecoregions within Nebraska, USA, (2) determine the range of invasion stages at individual land parcel extents within each ecoregion based on the density-impact model, and (3) determine policy alignment and mismatches relative to the density-impact model in order to assess their potential to meet sustainability targets and avoid societal impacts as Juniperus virginiana abundance increases. We found that nearly all policies evidenced doublethink and policy-ecology mismatches, for instance, promoting spread of Juniperus virginiana regardless of invasion stage while simultaneously managing it as a native invader in the same ecoregion. Like other invasive species, theory and literature for this native invader indicate that the consequences of invasion are unlikely to be prevented if policies fail to prioritize management at incipient invasion stages. Theory suggests a more realistic approach would be to align policy with the stage of invasion at local and ecoregion management scales. There is a need for scientists, policy makers, and ecosystem managers to move past ideologies governing native versus non-native invader classification and toward a framework that accounts for the uniqueness of native species invasions

  1. Rhabdomyosarcoma in patients with constitutional mismatch-repair-deficiency syndrome.

    Science.gov (United States)

    Kratz, C P; Holter, S; Etzler, J; Lauten, M; Pollett, A; Niemeyer, C M; Gallinger, S; Wimmer, K

    2009-06-01

    Biallelic germline mutations in the mismatch repair genes MLH1, MSH2, MSH6 or PMS2 cause a recessive childhood cancer syndrome characterised by early-onset malignancies and signs reminiscent of neurofibromatosis type 1 (NF1). Alluding to the underlying genetic defect, we refer to this syndrome as constitutional mismatch repair-deficiency (CMMR-D) syndrome. The tumour spectrum of CMMR-D syndrome includes haematological neoplasias, brain tumours and Lynch syndrome-associated tumours. Other tumours, such as neuroblastoma, Wilm tumour, ovarian neuroectodermal tumour or infantile myofibromatosis, have so far been found only in individual cases. We analysed two consanguineous families that had members with suspected CMMR-D syndrome who developed rhabdomyosarcoma among other neoplasias. In the first family, we identified a pathogenic PMS2 mutation for which the affected patient was homozygous. In family 2, immunohistochemistry analysis showed isolated loss of PMS2 expression in all tumours in the affected patients, including rhabdomyosarcoma itself and the surrounding normal tissue. Together with the family history and microsatellite instability observed in one tumour this strongly suggests an underlying PMS2 alteration in family 2 also. Together, these two new cases show that rhabdomyosarcoma and possibly other embryonic tumours, such as neuroblastoma and Wilm tumour, belong to the tumour spectrum of CMMR-D syndrome. Given the clinical overlap of CMMR-D syndrome with NF1, we suggest careful examination of the family history in patients with embryonic tumours and signs of NF1 as well as analysis of the tumours for loss of one of the mismatch repair genes and microsatellite instability. Subsequent mutation analysis will lead to a definitive diagnosis of the underlying disorder.

  2. Mismatch analysis of humeral nailing. Antegrade versus retrograde insertion

    International Nuclear Information System (INIS)

    Mahaisavariya, B.; Jiamwatthanachai, P.; Aroonjarattham, P.; Aroonjarattham, K.; Wongcumchang, M.; Sitthiseripratip, K.

    2011-01-01

    Closed humeral nailing is now considered an alternative treatment for humeral-shaft fracture. The nail can be inserted with either the antegrade or retrograde method. We investigated and compared the problem of geometric mismatch of the humeral nail to the humerus between the two methods of insertion. The study was performed using virtual simulation based on computed tomography (CT) data of 76 Thai cadaveric humeri and the commonly used Russell-Taylor humeral nail 8 mm in diameter and 220 mm long. Mismatch of the nail to the intact humerus was analyzed and compared between the antegrade and retrograde nailing approaches. The results showed: the diameter of the medullary canal averaged 7.9-13.8 mm; the minimal reaming diameter to accommodate virtual nail insertion averaged 8.8-14.8 mm for the antegrade and 8.8-29.3 mm for the retrograde approach; the minimal reaming thickness of the inner cortex averaged 0.1-1.5 mm for the antegrade and 0.1-9.9 mm for the retrograde approach; the percentages of cortical bone removed prior to nail insertion were 3.8-107.1% and 3.8-1,287.6% for the antegrade and retrograde approaches, respectively; the eccentricity of the nail-medullary canal center were 0.4-3.4 and 0.4-10.6 mm for the antegrade and retrograde approaches, respectively. Less mismatching occurred with antegrade nailing than with the retrograde approach. Retrograde nailing requires excessive reaming at the distal part of the humerus to accommodate nail insertion. This may create bone weakness and the risk of supracondylar fracture. (author)

  3. Doublethink and scale mismatch polarize policies for an invasive tree

    Science.gov (United States)

    Roberts, Caleb P.; Uden, Daniel R.; Allen, Craig R.; Twidwell, Dirac

    2018-01-01

    Mismatches between invasive species management policies and ecological knowledge can lead to profound societal consequences. For this reason, natural resource agencies have adopted the scientifically-based density-impact invasive species curve to guide invasive species management. We use the density-impact model to evaluate how well management policies for a native invader (Juniperus virginiana) match scientific guidelines. Juniperus virginiana invasion is causing a sub-continental regime shift from grasslands to woodlands in central North America, and its impacts span collapses in endemic diversity, heightened wildfire risk, and crashes in grazing land profitability. We (1) use land cover data to identify the stage of Juniperus virginiana invasion for three ecoregions within Nebraska, USA, (2) determine the range of invasion stages at individual land parcel extents within each ecoregion based on the density-impact model, and (3) determine policy alignment and mismatches relative to the density-impact model in order to assess their potential to meet sustainability targets and avoid societal impacts as Juniperus virginiana abundance increases. We found that nearly all policies evidenced doublethink and policy-ecology mismatches, for instance, promoting spread of Juniperus virginiana regardless of invasion stage while simultaneously managing it as a native invader in the same ecoregion. Like other invasive species, theory and literature for this native invader indicate that the consequences of invasion are unlikely to be prevented if policies fail to prioritize management at incipient invasion stages. Theory suggests a more realistic approach would be to align policy with the stage of invasion at local and ecoregion management scales. There is a need for scientists, policy makers, and ecosystem managers to move past ideologies governing native versus non-native invader classification and toward a framework that accounts for the uniqueness of native species

  4. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer

    OpenAIRE

    Bojesen, Stig E; Pooley, Karen A; Johnatty, Sharon E; Beesley, Jonathan; Michailidou, Kyriaki; Tyrer, Jonathan P; Edwards, Stacey L; Pickett, Hilda A; Shen, Howard C; Smart, Chanel E; Hillman, Kristine M; Mai, Phuong L; Lawrenson, Kate; Stutz, Michael D; Lu, Yi

    2013-01-01

    TERT-locus single nucleotide polymorphisms (SNPs) and leucocyte telomere measures are reportedly associated with risks of multiple cancers. Using the iCOGs chip, we analysed ~480 TERT-locus SNPs in breast (n=103,991), ovarian (n=39,774) and BRCA1 mutation carrier (11,705) cancer cases and controls. 53,724 participants have leucocyte telomere measures. Most associations cluster into three independent peaks. Peak 1 SNP rs2736108 minor allele associates with longer telomeres (P=5.8×10−7), reduce...

  5. Mismatch repair status and synchronous metastases in colorectal cancer

    DEFF Research Database (Denmark)

    Nordholm-Carstensen, Andreas; Krarup, Peter-Martin; Morton, Dion

    2015-01-01

    The causality between the metastatic potential, mismatch repair status (MMR) and survival in colorectal cancer (CRC) is complex. This study aimed to investigate the impact of MMR in CRC on the occurrence of synchronous metastases (SCCM) and survival in patients with SCCM on a national basis....... A nationwide cohort study of 6,692 patients diagnosed with CRC between 2010 and 2012 was conducted. Data were prospectively entered into the Danish Colorectal Cancer Group's database and merged with data from the Danish Pathology Registry and the National Patient Registry. Multivariable and multinomial...

  6. Unagreement is an Illusion: Apparent person mismatches and nominal structure

    OpenAIRE

    Höhn, Georg F.K.

    2015-01-01

    This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s11049-015-9311-y This paper proposes an analysis of unagreement, a phenomenon involving an apparent mismatch between a definite third person plural subject and first or second person plural subject agreement observed in various null subject languages (e.g. Spanish, Modern Greek and Bulgarian), but notoriously absent in others (e.g. Italian, European Portuguese). A cross-lingu...

  7. Locus - ASTRA | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available switchLanguage; BLAST Search Image Search Home About Archive Update History Data ...URL: ftp://ftp.biosciencedbc.jp/archive/astra/LATEST/astra_locus.zip File size: 887 KB Simple search URL htt...icing type (ex. cassette) About This Database Database Description Download License Update History of This Database Site Policy | Contact Us Locus - ASTRA | LSDB Archive ...

  8. Is this Red Spot the Blue Spot (locus ceruleum)?

    Energy Technology Data Exchange (ETDEWEB)

    Choe, Won Sick; Lee, Yu Kyung; Lee, Min Kyung; Hwang, Kyung Hoon [Gachon University Gil Hospital, Incheon (Korea, Republic of)

    2010-06-15

    The authors report brain images of 18F-FDG-PET in a case of schizophrenia. The images showed strikingly increased bilateral uptake in the locus ceruleum. The locus ceruleum is called the blue spot and known to be a center of the norepinephrinergic system.

  9. Metacognition: As a Predictor of One's Academic Locus of Control

    Science.gov (United States)

    Arslan, Serhat; Akin, Ahmet

    2014-01-01

    The purpose of this study is to examine the effect of metacognition on one's academic locus of control. The study's sample group consists of 451 university students enrolled in various programs at Sakarya University, Turkey. In this study, the Metacognitive Awareness Inventory and the Academic Locus of Control Scale were used. The correlations and…

  10. Personality and Locus of Control among School Children

    Science.gov (United States)

    Pandya, Archana A.; Jogsan, Yogesh A.

    2013-01-01

    The main purpose of this investigation is to find out the sex differences in personality traits and locus of control among school children. A total 60 children (30 boys and 30 girls) were taken as a sample. The research tool for personality, children personality questionnaire was used, which was made by Cattell and Porter. Locus of control was…

  11. Physical Attractiveness, Locus of Control, Sex Role, and Conversational Assertiveness.

    Science.gov (United States)

    Campbell, Keith F.; And Others

    1990-01-01

    Analyzes the relationship among physical attractiveness, locus of control, sex role orientation, and assertiveness in undergraduate students. Reviews videotapes of mixed-sex student groups engaged in discussion. Finds an internal locus of control positively correlated with assertiveness. Uses a behavioral measure of assertiveness rather than…

  12. Locus of control and investment in risky assets

    NARCIS (Netherlands)

    Salamanca Acosta, N.; de Grip, A.; Fouarge, D.; Montizaan, R.M.

    2013-01-01

    Using representative household panel data, we show that the investment behavior of households is related to the economic locus of control of household heads. A household’s internal locus of control in economic issues is positively related to its decision to hold risky assets as well as its share of

  13. Locus of control and investment in risky assets

    NARCIS (Netherlands)

    Salamanca, N.; de Grip, A.; Fouarge, D.; Montizaan, R.M.

    2013-01-01

    Using representative household panel data, we show that the investment behavior of households is related to the economic locus of control of household heads. A household's internal locus of control in economic issues is positively related to its decision to hold risky assets as well as its share of

  14. Is this Red Spot the Blue Spot (locus ceruleum)?

    International Nuclear Information System (INIS)

    Choe, Won Sick; Lee, Yu Kyung; Lee, Min Kyung; Hwang, Kyung Hoon

    2010-01-01

    The authors report brain images of 18F-FDG-PET in a case of schizophrenia. The images showed strikingly increased bilateral uptake in the locus ceruleum. The locus ceruleum is called the blue spot and known to be a center of the norepinephrinergic system.

  15. Method of Measuring the Mismatch of Parasitic Capacitance in MEMS Accelerometer Based on Regulating Electrostatic Stiffness

    Directory of Open Access Journals (Sweden)

    Xianshan Dong

    2018-03-01

    Full Text Available For the MEMS capacitive accelerometer, parasitic capacitance is a serious problem. Its mismatch will deteriorate the performance of accelerometer. Obtaining the mismatch of the parasitic capacitance precisely is helpful for improving the performance of bias and scale. Currently, the method of measuring the mismatch is limited in the direct measuring using the instrument. This traditional method has low accuracy for it would lead in extra parasitic capacitive and have other problems. This paper presents a novel method based on the mechanism of a closed-loop accelerometer. The strongly linear relationship between the output of electric force and the square of pre-load voltage is obtained through theoretical derivation and validated by experiment. Based on this relationship, the mismatch of parasitic capacitance can be obtained precisely through regulating electrostatic stiffness without other equipment. The results can be applied in the design of decreasing the mismatch and electrical adjusting for eliminating the influence of the mismatch.

  16. Escala de Locus de controle ELCO/TELEBRÁS Scale of Locus of control - ELCO

    Directory of Open Access Journals (Sweden)

    Luiz Pasquali

    1998-01-01

    Full Text Available Com base na teoria de Rotter e Escala de Levenson foi elaborada uma escala de Locus de Controle Organizacional (ELCO, composta por 28 itens. A escala foi validada com uma amostra de 350 empregados do Sistema Telebrás. Verificou-se a presença dos 2 fatores previstos na teoria, a saber: internalidade e externalidade, aparecendo a escala de externalidade, com 18 itens, bem estruturada (alfa = 0.81 e a de internalidade, com 10 itens, deixando a desejar no que se refere à consistência interna (alfa = 0.66. Com os dados desta pesquisa foi feita também análise do Locus de Controle desses mesmos empregados. A constatação mais saliente foi a de que o nível de internalidade caiu com o aumento do nível escolar e o aumento da experiência profissional desses mesmos empregados. Estes resultados surpreendentes foram interpretados em termos da situação típica da empresa, que está passando por um período de transição, a saber: a passagem da condição de empresa estatal para empresa privada, o que seria motivo da perda de confiança dos empregados na própria competência, particularmente por parte daqueles com maior competência intelectual e maior experiência profissional. Fez-se igualmente reparos na qualidade psicométrica da escala e da própria teoria do Locus de controle, no sentido de que esta precisa ser melhor axiomatizada para possibilitar a elaboração de escalas mais precisas para a medida dos construtos que propõe.A scale with 28 items, the Organizational Locus of Control (ELCO, was built based on Rotter’s theory and Levenson’s scale. ELCO was validated on a sample of 350 employees of Telebrás, a governmental firm in Brazil. As foreseen from the theory, a principal-axis factoring showed the presence of the expected two factors, namely internal and external locus of control. The external locus of control factor, composed of 18 items, showed good internal consistency (alpha =.81 whereas the internal factor, with 10 items

  17. Haematopoietic transplants combining a single unrelated cord blood unit and mobilized haematopoietic stem cells from an adult HLA-mismatched third party donor. Comparable results to transplants from HLA-identical related donors in adults with acute leukaemia and myelodysplastic syndromes.

    Science.gov (United States)

    Sebrango, Ana; Vicuña, Isabel; de Laiglesia, Almudena; Millán, Isabel; Bautista, Guiomar; Martín-Donaire, Trinidad; Regidor, Carmen; Cabrera, Rafael; Fernandez, Manuel N

    2010-06-01

    We describe results of the strategy, developed by our group, of co-infusion of mobilized haematopoietic stem cells as a support for single-unit unrelated cord blood transplant (dual CB/TPD-MHSC transplants) for treatment of haematological malignancies in adults, and a comparative analysis of results obtained using this strategy and transplants performed with mobilized haematopoietic stem cells from related HLA-identical donors (RTD) for treatment of adults with acute leukaemia and myelodysplastic syndromes. Our data show that the dual CB/TPD-MHSC transplant strategy results in periods of post-transplant neutropenia, final rates of full donor chimerism and transplant-related mortality rates comparable to those of the RTD. Final survival outcomes are comparable in adults transplanted because of acute leukaemia, with different incidences of the complications that most influence these: a higher incidence of infections related to late recovery of protective immunity dependent on T cell functions, and a lower incidence of serious acute graft-versus-host disease and relapses. Recent advances in cord blood transplant techniques allow allogeneic haematopoietic stem cell transplantation (HSCT) to be a viable option for almost every patient who may benefit from this therapeutic approach. Development of innovative strategies to improve the post-transplant recovery of T cells function is currently the main challenge to further improving the possibilities of unrelated cord blood transplantation. Copyright © 2010 Elsevier Ltd. All rights reserved.

  18. Spatial mismatch, wages and unemployment in metropolitan areas in Brazil

    Directory of Open Access Journals (Sweden)

    Ana Maria Bonomi Barufi

    2017-12-01

    Full Text Available The spatial mismatch hypothesis states that a lack of connection to job opportunities may affect an individual’s prospects in the labour market, especially for low-skilled workers. This phenomenon is especially observed in large urban areas, in which low-skilled minorities tend to live far away from jobs and face geographical barriers to finding and keeping jobs. This paper aims to investigate whether this negative relationship between spatial mismatch and labour market outcomes is valid in Brazil after controlling for individual characteristics. Our conclusions indicate that there is no clear relation between different measures of accessibility to jobs and the probability of being unemployed. However, for wages there is a clear correlation, which is stronger in larger metropolitan areas in the country. Given the exploratory nature of this work, our results still rely on strong identification hypotheses to avoid potential bias related to simultaneous location decisions of workers and firms within the city. Even if these conditions do not hold, the results are still meaningful as they provide a better understanding of the conditional distribution of wages and the unemployment rate in the biggest metropolitan areas of Brazil.

  19. Effects of aging on neuromagnetic mismatch responses to pitch changes.

    Science.gov (United States)

    Cheng, Chia-Hsiung; Baillet, Sylvain; Hsiao, Fu-Jung; Lin, Yung-Yang

    2013-06-07

    Although aging-related alterations in the auditory sensory memory and involuntary change discrimination have been widely studied, it remains controversial whether the mismatch negativity (MMN) or its magnetic counterpart (MMNm) is modulated by physiological aging. This study aimed to examine the effects of aging on mismatch activity to pitch deviants by using a whole-head magnetoencephalography (MEG) together with distributed source modeling analysis. The neuromagnetic responses to oddball paradigms consisting of standards (1000 Hz, p=0.85) and deviants (1100 Hz, p=0.15) were recorded in healthy young (n=20) and aged (n=18) male adults. We used minimum norm estimate of source reconstruction to characterize the spatiotemporal neural dynamics of MMNm responses. Distributed activations to MMNm were identified in the bilateral fronto-temporo-parietal areas. Compared to younger participants, the elderly exhibited a significant reduction of cortical activation in bilateral superior temporal guri, superior temporal sulci, inferior fontal gyri, orbitofrontal cortices and right inferior parietal lobules. In conclusion, our results suggest an aging-related decline in auditory sensory memory and automatic change detection as indexed by MMNm. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  20. Mismatch repair proficiency is not required for radioenhancement by gemcitabine

    International Nuclear Information System (INIS)

    Bree, Chris van; Rodermond, Hans M.; Vos, Judith de; Haveman, Jaap; Franken, Nicolaas

    2005-01-01

    Purpose: Mismatch repair (MMR) proficiency has been reported to either increase or decrease radioenhancement by 24-h incubations with gemcitabine. This study aimed to establish the importance of MMR for radioenhancement by gemcitabine after short-exposure, high-dose treatment and long-exposure, low-dose treatment. Methods and Materials: Survival of MMR-deficient HCT116 and MMR-proficient HCT116 + 3 cells was analyzed by clonogenic assays. Mild, equitoxic gemcitabine treatments (4 h, 0.1 μM vs. 24 h, 6 nM) were combined with γ-irradiation to determine the radioenhancement with or without recovery. Gemcitabine metabolism and cell-cycle effects were evaluated by high-performance liquid chromatography analysis and bivariate flow cytometry. Results: Radioenhancement after 4 h of 0.1 μM of gemcitabine was similar in both cell lines, but the radioenhancement after 24 h of 6 nM of gemcitabine was reduced in MMR-proficient cells. No significant differences between both cell lines were observed in the gemcitabine metabolism or cell-cycle effects after these treatments. Gemcitabine radioenhancement after recovery was also lower in MMR-proficient cells than in MMR-deficient cells. Conclusion: Mismatch repair proficiency decreases radioenhancement by long incubations of gemcitabine but does not affect radioenhancement by short exposures to a clinically relevant gemcitabine dose. Our data suggest that MMR contributes to the recovery from gemcitabine treatment

  1. Donor-Recipient Size Mismatch in Paediatric Renal Transplantation

    Directory of Open Access Journals (Sweden)

    J. Donati-Bourne

    2014-01-01

    Full Text Available Introduction. End stage renal failure in children is a rare but devastating condition, and kidney transplantation remains the only permanent treatment option. The aim of this review was to elucidate the broad surgical issues surrounding the mismatch in size of adult kidney donors to their paediatric recipients. Methods. A comprehensive literature search was undertaken on PubMed, MEDLINE, and Google Scholar for all relevant scientific articles published to date in English language. Manual search of the bibliographies was also performed to supplement the original search. Results. Size-matching kidneys for transplantation into children is not feasible due to limited organ availability from paediatric donors, resulting in prolonged waiting list times. Transplanting a comparatively large adult kidney into a child may lead to potential challenges related to the surgical incision and approach, vessel anastomoses, wound closure, postoperative cardiovascular stability, and age-correlated maturation of the graft. Conclusion. The transplantation of an adult kidney into a size mismatched paediatric recipient significantly reduces waiting times for surgery; however, it presents further challenges in terms of both the surgical procedure and the post-operative management of the patient’s physiological parameters.

  2. Strategy to avoid patient-prosthesis mismatch: aortic root enlargement.

    Science.gov (United States)

    Srivastava, Dharmendra Kumar; Sanki, Prokash; Bhattacharya, Subhankar; Siddique, Javed Veqar

    2014-02-01

    The choice of a valve with an effective orifice area matching the body surface area and providing efficient hemodynamics is an important factor affecting mortality and morbidity in patients undergoing aortic valve replacement. Our preventative strategy was to implant a larger prosthetic valve by aortic root enlargement using the Nunez procedure in 17 patients between February 2010 and January 2011. The decision to enlarge the aortic root was taken when the 19-mm sizer could not be negotiated easily through the aortic root, or on the basis of body surface area of the patient or type of prosthesis available. Postoperative reductions in peak and mean pressure gradients across aortic valve of 12.8-16.5 and 10.2-12.6 mm Hg, respectively, were observed. Postoperative effective orifice areas of the aortic valves were 1.1-1.5 cm(2). By upsizing the aortic valve, we were able to eliminate patient-prosthesis mismatch in 5 patients, and reduce severe patient-prosthesis mismatch to moderate in 11. Aortic root enlargement is a safe procedure. Therefore, cardiac surgeons should not be reluctant to enlarge the aortic root with an autologous pericardial patch to permit implantation of an adequate size of aortic valve prosthesis, with minimal additional aortic crossclamp time and no added cost.

  3. Counting the mismatches - lung ventilation/perfusion subtraction index

    International Nuclear Information System (INIS)

    Anderson, T.C.; Evans, S.G.; Larcos, G.; Farlow, D.C.

    1998-01-01

    Full text: There is potential for interobserver variability in interpretation of ventilation/perfusion (V/Q) scans. Objective quantification of V/Q mismatch could be useful. Thus, the aim of this study is to determine the validity of image subtraction in a group of 27 patients (11 men, 8 women; mean age 59.4 years [range 21-81 years])investigated by V/Q scans for suspected pulmonary emboli. A standard 6 view V/Q scan was obtained with two cobalt markers used on the anterior and posterior surfaces for image alignment. Ventilation images were normalised to the perfusion using an area of normal ventilation and perfusion. With the use of automated, and if required, manual alignment, perfusion images were subtracted from ventilation, with a median filter applied. A summed index of mismatch for each lung scan was calculated from the difference. This index was then retrospectively compared to the result reported by one of four experienced physicians. Two patients with chronic obstructive airways disease were excluded from analysis. We conclude that high probability V/Q scans can be differentiated from low probability studies using this index; further prospective investigation in a larger cohort is warranted

  4. Somatosensory mismatch response in young and elderly adults

    Directory of Open Access Journals (Sweden)

    Juho M. Strömmer

    2014-10-01

    Full Text Available Aging is associated with cognitive decline and alterations in early perceptual processes. Studies in the auditory and visual modalities have shown that the mismatch negativity (or the mismatch response, MMR, an event-related potential (ERP elicited by a deviant stimulus in a background of homogenous events, diminishes with aging and cognitive decline. However, the effects of aging on the somatosensory MMR are not known. In the current study, we recorded ERPs to electrical pulses to different fingers of the left hand in a passive oddball experiment in young (22–36 years and elderly (66–95 years adults engaged in a visual task. The MMR was found to deviants as compared to standards at two latency ranges: 180–220 ms and 250–290 ms post-stimulus onset. At 180–220 ms, within the young, the MMR was found at medial electrode sites, whereas aged did not show any amplitude difference between the stimulus types at the same latency range. At 250–290 ms, the MMR was evident with attenuated amplitude and narrowed scalp distribution among aged (Fz compared to young (fronto-centrally and lateral parietal sites. Hence, the results reveal that the somatosensory change detection mechanism is altered in aging. The somatosensory MMR can be used as a reliable measure of age-related changes in sensory-cognitive functions.

  5. Thermal Resistance across Interfaces Comprising Dimensionally Mismatched Carbon Nanotube-Graphene Junctions in 3D Carbon Nanomaterials

    Directory of Open Access Journals (Sweden)

    Jungkyu Park

    2014-01-01

    Full Text Available In the present study, reverse nonequilibrium molecular dynamics is employed to study thermal resistance across interfaces comprising dimensionally mismatched junctions of single layer graphene floors with (6,6 single-walled carbon nanotube (SWCNT pillars in 3D carbon nanomaterials. Results obtained from unit cell analysis indicate the presence of notable interfacial thermal resistance in the out-of-plane direction (along the longitudinal axis of the SWCNTs but negligible resistance in the in-plane direction along the graphene floor. The interfacial thermal resistance in the out-of-plane direction is understood to be due to the change in dimensionality as well as phonon spectra mismatch as the phonons propagate from SWCNTs to the graphene sheet and then back again to the SWCNTs. The thermal conductivity of the unit cells was observed to increase nearly linearly with an increase in cell size, that is, pillar height as well as interpillar distance, and approaches a plateau as the pillar height and the interpillar distance approach the critical lengths for ballistic thermal transport in SWCNT and single layer graphene. The results indicate that the thermal transport characteristics of these SWCNT-graphene hybrid structures can be tuned by controlling the SWCNT-graphene junction characteristics as well as the unit cell dimensions.

  6. Bifunctional Rhodium Intercalator Conjugates as Mismatch-Directing DNA Alkylating Agents

    OpenAIRE

    Schatzschneider, Ulrich; Barton, Jacqueline K.

    2004-01-01

    A conjugate of a DNA mismatch-specific rhodium intercalator, containing the bulky chrysenediimine ligand, and an aniline mustard has been prepared, and targeting of mismatches in DNA by this conjugate has been examined. The preferential alkylation of mismatched over fully matched DNA is found by a mobility shift assay at concentrations where untethered organic mustards show little reaction. The binding site of the Rh intercalator was determined by DNA photocleavage, and the position of covale...

  7. Visualization of uncorrelated, tandem symmetry mismatches in the internal genome packaging apparatus of bacteriophage T7.

    Science.gov (United States)

    Guo, Fei; Liu, Zheng; Vago, Frank; Ren, Yue; Wu, Weimin; Wright, Elena T; Serwer, Philip; Jiang, Wen

    2013-04-23

    Motor-driven packaging of a dsDNA genome into a preformed protein capsid through a unique portal vertex is essential in the life cycle of a large number of dsDNA viruses. We have used single-particle electron cryomicroscopy to study the multilayer structure of the portal vertex of the bacteriophage T7 procapsid, the recipient of T7 DNA in packaging. A focused asymmetric reconstruction method was developed and applied to selectively resolve neighboring pairs of symmetry-mismatched layers of the portal vertex. However, structural features in all layers of the multilayer portal vertex could not be resolved simultaneously. Our results imply that layers with mismatched symmetries can join together in several different relative orientations, and that orientations at different interfaces assort independently to produce structural isomers, a process that we call combinatorial assembly isomerism. This isomerism explains rotational smearing in previously reported asymmetric reconstructions of the portal vertex of T7 and other bacteriophages. Combinatorial assembly isomerism may represent a new regime of structural biology in which globally varying structures assemble from a common set of components. Our reconstructions collectively validate previously proposed symmetries, compositions, and sequential order of T7 portal vertex layers, resolving in tandem the 5-fold gene product 10 (gp10) shell, 12-fold gp8 portal ring, and an internal core stack consisting of 12-fold gp14 adaptor ring, 8-fold bowl-shaped gp15, and 4-fold gp16 tip. We also found a small tilt of the core stack relative to the icosahedral fivefold axis and propose that this tilt assists DNA spooling without tangling during packaging.

  8. Health Locus of Control尺度開発の歴史(社会科学編)

    OpenAIRE

    吉田, 由美; Yumi, YOSHIDA; 千葉県立衛生短期大学(看護学); Chiba College of Health Science

    1994-01-01

    This article describes the origins history of Health Locus of Control scales. First, Rotter's social learing theory, which is the theoretical background of the Health Locus of Control construct, is outlined. The scale and research trends of Locus of Control concept, and those of Health Locus of Control concept which are based on Locus of Control, are then reviewed. Finally, Health Locus of Control is discussed with regard to the implications for health education.

  9. Interaction of the E. coli DNA G:T-mismatch endonuclease (vsr protein) with oligonucleotides containing its target sequence.

    Science.gov (United States)

    Turner, D P; Connolly, B A

    2000-12-15

    The Escherichia coli vsr endonuclease recognises G:T base-pair mismatches in double-stranded DNA and initiates a repair pathway by hydrolysing the phosphate group 5' to the incorrectly paired T. The enzyme shows a preference for G:T mismatches within a particular sequence context, derived from the recognition site of the E. coli dcm DNA-methyltransferase (CC[A/T]GG). Thus, the preferred substrate for the vsr protein is (CT[A/T]GG), where the underlined T is opposed by a dG base. This paper provides quantitative data for the interaction of the vsr protein with a number of oligonucleotides containing G:T mismatches. Evaluation of specificity constant (k(st)/K(D); k(st)=rate constant for single turnover, K(D)=equilibrium dissociation constant) confirms vsr's preference for a G:T mismatch within a hemi-methylated dcm sequence, i.e. the best substrate is a duplex (both strands written in the 5'-3' orientation) composed of CT[A/T]GG and C(5Me)C[T/A]GG. Conversion of the mispaired T (underlined) to dU or the d(5Me)C to dC gave poorer substrates. No interaction was observed with oligonucleotides that lacked a G:T mismatch or did not possess a dcm sequence. An analysis of the fraction of active protein, by "reverse-titration" (i.e. adding increasing amounts of DNA to a fixed amount of protein followed by gel-mobility shift analysis) showed that less than 1% of the vsr endonuclease was able to bind to the substrate. This was confirmed using "competitive titrations" (where competitor oligonucleotides are used to displace a (32)P-labelled nucleic acid from the vsr protein) and burst kinetic analysis. This result is discussed in the light of previous in vitro and in vivo data which indicate that the MutL protein may be needed for full vsr activity. Copyright 2000 Academic Press.

  10. Twisting right to left: A…A mismatch in a CAG trinucleotide repeat overexpansion provokes left-handed Z-DNA conformation.

    Directory of Open Access Journals (Sweden)

    Noorain Khan

    2015-04-01

    Full Text Available Conformational polymorphism of DNA is a major causative factor behind several incurable trinucleotide repeat expansion disorders that arise from overexpansion of trinucleotide repeats located in coding/non-coding regions of specific genes. Hairpin DNA structures that are formed due to overexpansion of CAG repeat lead to Huntington's disorder and spinocerebellar ataxias. Nonetheless, DNA hairpin stem structure that generally embraces B-form with canonical base pairs is poorly understood in the context of periodic noncanonical A…A mismatch as found in CAG repeat overexpansion. Molecular dynamics simulations on DNA hairpin stems containing A…A mismatches in a CAG repeat overexpansion show that A…A dictates local Z-form irrespective of starting glycosyl conformation, in sharp contrast to canonical DNA duplex. Transition from B-to-Z is due to the mechanistic effect that originates from its pronounced nonisostericity with flanking canonical base pairs facilitated by base extrusion, backbone and/or base flipping. Based on these structural insights we envisage that such an unusual DNA structure of the CAG hairpin stem may have a role in disease pathogenesis. As this is the first study that delineates the influence of a single A…A mismatch in reversing DNA helicity, it would further have an impact on understanding DNA mismatch repair.

  11. Genetic and clinical determinants of constitutional mismatch repair deficiency syndrome: report from the constitutional mismatch repair deficiency consortium.

    Science.gov (United States)

    Bakry, Doua; Aronson, Melyssa; Durno, Carol; Rimawi, Hala; Farah, Roula; Alharbi, Qasim Kholaif; Alharbi, Musa; Shamvil, Ashraf; Ben-Shachar, Shay; Mistry, Matthew; Constantini, Shlomi; Dvir, Rina; Qaddoumi, Ibrahim; Gallinger, Steven; Lerner-Ellis, Jordan; Pollett, Aaron; Stephens, Derek; Kelies, Steve; Chao, Elizabeth; Malkin, David; Bouffet, Eric; Hawkins, Cynthia; Tabori, Uri

    2014-03-01

    Constitutional mismatch repair deficiency (CMMRD) is a devastating cancer predisposition syndrome for which data regarding clinical manifestations, molecular screening tools and management are limited. We established an international CMMRD consortium and collected comprehensive clinical and genetic data. Molecular diagnosis of tumour and germline biospecimens was performed. A surveillance protocol was developed and implemented. Overall, 22/23 (96%) of children with CMMRD developed 40 different tumours. While childhood CMMRD related tumours were observed in all families, Lynch related tumours in adults were observed in only 2/14 families (p=0.0007). All children with CMMRD had café-au-lait spots and 11/14 came from consanguineous families. Brain tumours were the most common cancers reported (48%) followed by gastrointestinal (32%) and haematological malignancies (15%). Importantly, 12 (30%) of these were low grade and resectable cancers. Tumour immunohistochemistry was 100% sensitive and specific in diagnosing mismatch repair (MMR) deficiency of the corresponding gene while microsatellite instability was neither sensitive nor specific as a diagnostic tool (psyndrome where family history of cancer may not be contributory. Screening tumours and normal tissues using immunohistochemistry for abnormal expression of MMR gene products may help in diagnosis and early implementation of surveillance for these children. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. EL LOCUS DE DISTRIBUCION COMO COROLARIO DEL LOCUS DE CONTROL (THE LOCUS OF DISTRIBUTION AS A COROLLARY TO THE LOCUS OF CONTROL

    Directory of Open Access Journals (Sweden)

    Mayoral Luisa

    2009-08-01

    Full Text Available Resumen: Este es un artículo científico acerca del Locus de Distribución, surgido de un estudio realizado con una población de docentes y alumnos universitarios. Respecto de los primeros, se ha indagado acerca de las atribuciones que se realizaban en torno a las recompensas y sanciones, que ellos distribuían a sus alumnos.Respecto de los segundos, se ha buscado determinar la valoración que estos realizaban de sus profesores, en términos de aquellas atribuciones. Para ello, se utilizaron dos paradigmas clásicamente empleados para verificar la existencia de una norma: el paradigma de la autopresentación (docentes, y el paradigma de los j uicios (alumnos. La cuestión planteada fue determinar si en el caso de los comportamientos distributivos de refuerzos, las causas se atribuían a variables externas -en particular a los receptores de esos refuerzos- y si esas formas de atribución eran conocidas y valoradas o no, por los alumnos. De los resultados, surgió la confirmación de nuestra hipótesis de explicaciones externas en materia de comportamientos distributivos de sanciones en el ámbito de la docencia y la valoración positiva de estas atribuciones por los alumnos.Abstract:This one is a scientific article brings over of the Locus of Distribution, arisen from a study realized with a population of teachers and university pupils. Respect of the first ones, it has been investigated brings over of the attributions that were concerning around the reinforcements which they were distributing to pupils. Respect of the second ones, one has sought to determine the valuation that these realized of the teachers, in terms of those attributions. For it, two paradigms were in use classic used to check the existence of a norm: the paradigm of the auto-presentation (teachers, and the paradigm of the judgments (pupils The raised question was to determine if in case of the distributive behaviours of reinforcements, the reasons were assuming to external

  13. Diagnostic criteria for constitutional mismatch repair deficiency syndrome

    DEFF Research Database (Denmark)

    Wimmer, Katharina; Kratz, Christian P; Vasen, Hans F A

    2014-01-01

    Constitutional mismatch repair deficiency (CMMRD) syndrome is a distinct childhood cancer predisposition syndrome that results from biallelic germline mutations in one of the four MMR genes, MLH1, MSH2, MSH6 or PMS2. The tumour spectrum is very broad, including mainly haematological, brain....... They include multiple hyperpigmented and hypopigmented skin areas, brain malformations, pilomatricomas, a second childhood malignancy, a Lynch syndrome (LS)-associated tumour in a relative and parental consanguinity. According to the scoring system, CMMRD should be suspected in any cancer patient who reaches...... patient. Tumours highly specific for CMMRD syndrome are assigned three points, malignancies overrepresented in CMMRD two points and all other malignancies one point. According to their specificity for CMMRD and their frequency in the general population, additional features are weighted with 1-2 points...

  14. Temporal span of human echoic memory and mismatch negativity: revisited.

    Science.gov (United States)

    Jääskeläinen, I P; Hautamäki, M; Näätänen, R; Ilmoniemi, R J

    1999-04-26

    The stimulus onset asynchrony (SOA)-related decrease in mismatch negativity (MMN) amplitude has been used to infer a putative auditory sensory memory duration of 4-10 s. However, both increased standard-to-standard (SSA) and standard-to-deviant (SDA) gaps could contribute to the effect. Fourteen subjects were presented with standard and deviant tones with short (0.35 s) and long (3.5 s) SOAs. In addition, the SSA and SDA were separately manipulated to test the relative contributions of slower rate of standard tone presentation and longer SDA gap to the SOA-related decrease in MMN amplitude. The MMN amplitude decreased with long SOA by 61%. Increases in SSA and SDA resulted in intermediate 47% and 31% decreases, these manipulations explaining 67% of the long SOA effect (pechoic memory length cannot be directly inferred from an MMN-SOA dependency function.

  15. Mismatch of Cultural Dimensions in an Urban Medical Educational Environment

    Directory of Open Access Journals (Sweden)

    Bethany Malone

    2013-01-01

    Full Text Available Objective. To identify cultural dimensions and their potential mismatches between attending physicians and their residents and medical students. Methods. We surveyed faculty and students, both undergraduates and postgraduate resident physicians, at the SUNY Downstate College of Medicine, using Hofstede’s VSM-08 questionnaire, and calculated cultural dimensions, including the Power-Distance Index (PDI, Individualism (IDV, Masculinity (MAS, Uncertainty Avoidance Index (UAI, and Long-term Outlook (LTO. Correlations between faculty and student demographic data and cultural dimensions were calculated (SPSS. Results. There were 237 student and resident respondents and 96 faculty respondents. Comparing all faculty and student respondents, significant differences were found in four of five cultural dimensions, with faculty scoring higher in MAS, and lower in PDI, IDV, UAI, and LTO. Conclusions. These differences may be important in the design and implementation of a medical educational curriculum, and, particularly, in the measurement and evaluation of educational outcomes.

  16. The mismatch between the cultures of journalism and science

    Energy Technology Data Exchange (ETDEWEB)

    Gelbspan, R.

    2000-06-01

    This presentation provided some insight into the journalist's perspective on climate change with particular consideration to the way the U.S. media portrays the issue. The author draws on thirty years of experience in journalism when he portrays the economic and political aspects of climate change along with the critical issues of journalism ethics as they relate to the coverage of the climate crisis. This paper also highlighted the campaign of deception by the fossil fuel lobby in the United States. The objective of this presentation is to address the link between inadequate media coverage and the lack of a political constituency in the United States regarding this issue. It was emphasized that there is a communication mismatch between science and journalism. Some suggestions were presented which would help scientists communicate their ideas to the press more effectively.

  17. Skill Mismatch of Graduates in a Local Labour Market

    Directory of Open Access Journals (Sweden)

    Enrico Marelli

    2014-06-01

    Full Text Available In this paper we first review the (potential and actual role of the Universities for the local economies in which they operate, especially considering the implications deriving from the degree of skill mismatch (over-education in a local labour market. Then, in the second part of the paper, we realise an empirical investigation based on administrative information of an Italian University matched with the data of the job centres of the local (provincial labour market in order to reconstruct the characteristics of the university-to-work transitions of graduates. Our results have important policy implications, since for local development it is crucial, among other things, to make the best use of all human resources and especially those with the highest educational level.

  18. Fast damping in mismatched high intensity beam transportation

    Directory of Open Access Journals (Sweden)

    V. Variale

    2001-08-01

    Full Text Available A very fast damping of beam envelope oscillation amplitudes was recently observed in simulations of high intensity beam transport, through periodic FODO cells, in mismatched conditions [V. Variale, Nuovo Cimento Soc. Ital. Fis. 112A, 1571–1582 (1999 and T. Clauser et al., in Proceedings of the Particle Accelerator Conference, New York, 1999 (IEEE, Piscataway, NJ, 1999, p. 1779]. A Landau damping mechanism was proposed at the origin of observed effect. In this paper, to further investigate the source of this fast damping, extensive simulations have been carried out. The results presented here support the interpretation of the mechanism at the origin of the fast damping as a Landau damping effect.

  19. Three perspectives on the mismatch between measures of material poverty.

    Science.gov (United States)

    Hick, Rod

    2015-03-01

    The two most prominent measures of material poverty within contemporary European poverty analysis are low income and material deprivation. However, it is by now well-known that these measures identify substantially different people as being poor. In this research note, I seek to demonstrate that there are at least three ways to understand the mismatch between low income and material deprivation, relating to three different forms of identification: identifying poor households, identifying groups at risk of poverty and identifying trends in material poverty over time. Drawing on data from the British Household Panel Survey, I show that while low income and material deprivation identify very different households as being poor, and display distinct trends over time, in many cases they identify the same groups at being at risk of material poverty. © London School of Economics and Political Science 2014.

  20. Microsatellite Instability Use in Mismatch Repair Gene Sequence Variant Classification

    Directory of Open Access Journals (Sweden)

    Bryony A. Thompson

    2015-03-01

    Full Text Available Inherited mutations in the DNA mismatch repair genes (MMR can cause MMR deficiency and increased susceptibility to colorectal and endometrial cancer. Microsatellite instability (MSI is the defining molecular signature of MMR deficiency. The clinical classification of identified MMR gene sequence variants has a direct impact on the management of patients and their families. For a significant proportion of cases sequence variants of uncertain clinical significance (also known as unclassified variants are identified, constituting a challenge for genetic counselling and clinical management of families. The effect on protein function of these variants is difficult to interpret. The presence or absence of MSI in tumours can aid in determining the pathogenicity of associated unclassified MMR gene variants. However, there are some considerations that need to be taken into account when using MSI for variant interpretation. The use of MSI and other tumour characteristics in MMR gene sequence variant classification will be explored in this review.

  1. Efficient and reproducible identification of mismatch repair deficient colon cancer

    DEFF Research Database (Denmark)

    Joost, Patrick; Bendahl, Pär-Ola; Halvarsson, Britta

    2013-01-01

    BACKGROUND: The identification of mismatch-repair (MMR) defective colon cancer is clinically relevant for diagnostic, prognostic and potentially also for treatment predictive purposes. Preselection of tumors for MMR analysis can be obtained with predictive models, which need to demonstrate ease...... of application and favorable reproducibility. METHODS: We validated the MMR index for the identification of prognostically favorable MMR deficient colon cancers and compared performance to 5 other prediction models. In total, 474 colon cancers diagnosed ≥ age 50 were evaluated with correlation between...... clinicopathologic variables and immunohistochemical MMR protein expression. RESULTS: Female sex, age ≥60 years, proximal tumor location, expanding growth pattern, lack of dirty necrosis, mucinous differentiation and presence of tumor-infiltrating lymphocytes significantly correlated with MMR deficiency. Presence...

  2. Relation of organizational citizenship behavior and locus of control.

    Science.gov (United States)

    Turnipseed, David L; Bacon, Calvin M

    2009-12-01

    The relation of organizational citizenship behavior and locus of control was assessed in a sample of 286 college students (52% men; M age = 24 yr.) who worked an average of 26 hr. per week. Measures were Spector's Work Locus of Control Scale and Podsakoff, et al.'s Organization Citizenship Behavior scale. Hierarchical multiple regressions indicated positive association of scores on work locus of control with scores on each of the four tested dimensions of organizational citizenship, as well as total organizational citizenship behavior.

  3. Genome-wide association study identifies a single major locus contributing to survival into old age; the APOE locus revisited

    DEFF Research Database (Denmark)

    Deelen, Joris; Beekman, Marian; Uh, Hae-Won

    2011-01-01

    By studying the loci which contribute to human longevity, we aim to identify mechanisms that contribute to healthy aging. To identify such loci, we performed a genome-wide association study (GWAS) comparing 403 unrelated nonagenarians from long-living families included in the Leiden Longevity Stu...

  4. Mismatch management for optical and matter-wave quadratic solitons

    International Nuclear Information System (INIS)

    Driben, R.; Oz, Y.; Malomed, B. A.; Gubeskys, A.; Yurovsky, V. A.

    2007-01-01

    We propose a way to control solitons in χ (2) (quadratically nonlinear) systems by means of periodic modulation imposed on the phase-mismatch parameter ('mismatch management', MM). It may be realized in the cotransmission of fundamental-frequency (FF) and second-harmonic (SH) waves in a planar optical waveguide via a long-period modulation of the usual quasi-phase-matching pattern of ferroelectric domains. In an altogether different physical setting, the MM may also be implemented by dint of the Feshbach resonance in a harmonically modulated magnetic field in a hybrid atomic-molecular Bose-Einstein condensate (BEC), with the atomic and molecular mean fields (MFs) playing the roles of the FF and SH, respectively. Accordingly, the problem is analyzed in two different ways. First, in the optical model, we identify stability regions for spatial solitons in the MM system, in terms of the MM amplitude and period, using the MF equations for spatially inhomogeneous configurations. In particular, an instability enclave is found inside the stability area. The robustness of the solitons is also tested against variation of the shape of the input pulse, and a threshold for the formation of stable solitons is found in terms of the power. Interactions between stable solitons are virtually unaffected by the MM. The second method (parametric approximation), going beyond the MF description, is developed for spatially homogeneous states in the BEC model. It demonstrates that the MF description is valid for large modulation periods, while, at smaller periods, non-MF components acquire gain, which implies destruction of the MF under the action of the high-frequency MM

  5. Mlh1-Mlh3, a Meiotic Crossover and DNA Mismatch Repair Factor, Is a Msh2-Msh3-stimulated Endonuclease*

    Science.gov (United States)

    Rogacheva, Maria V.; Manhart, Carol M.; Chen, Cheng; Guarne, Alba; Surtees, Jennifer; Alani, Eric

    2014-01-01

    Crossing over between homologous chromosomes is initiated in meiotic prophase in most sexually reproducing organisms by the appearance of programmed double strand breaks throughout the genome. In Saccharomyces cerevisiae the double-strand breaks are resected to form three prime single-strand tails that primarily invade complementary sequences in unbroken homologs. These invasion intermediates are converted into double Holliday junctions and then resolved into crossovers that facilitate homolog segregation during Meiosis I. Work in yeast suggests that Msh4-Msh5 stabilizes invasion intermediates and double Holliday junctions, which are resolved into crossovers in steps requiring Sgs1 helicase, Exo1, and a putative endonuclease activity encoded by the DNA mismatch repair factor Mlh1-Mlh3. We purified Mlh1-Mlh3 and showed that it is a metal-dependent and Msh2-Msh3-stimulated endonuclease that makes single-strand breaks in supercoiled DNA. These observations support a direct role for an Mlh1-Mlh3 endonuclease activity in resolving recombination intermediates and in DNA mismatch repair. PMID:24403070

  6. Autism, fever, epigenetics and the locus coeruleus.

    Science.gov (United States)

    Mehler, Mark F; Purpura, Dominick P

    2009-03-01

    Some children with autism spectrum disorders (ASD) exhibit improved behaviors and enhanced communication during febrile episodes. We hypothesize that febrigenesis and the behavioral-state changes associated with fever in autism depend upon selective normalization of key components of a functionally impaired locus coeruleus-noradrenergic (LC-NA) system. We posit that autistic behaviors result from developmental dysregulation of LC-NA system specification and neural network deployment and modulation linked to the core behavioral features of autism. Fever transiently restores the modulatory functions of the LC-NA system and ameliorates autistic behaviors. Fever-induced reversibility of autism suggests preserved functional integrity of widespread neural networks subserving the LC-NA system and specifically the subsystems involved in mediating the cognitive and behavioral repertoires compromised in ASD. Alterations of complex gene-environmental interactions and associated epigenetic mechanisms during seminal developmental critical periods are viewed as instrumental in LC-NA dysregulation as emphasized by the timing and severity of prenatal maternal stressors on autism prevalence. Our hypothesis has implications for a rational approach to further interrogate the interdisciplinary etiology of ASD and for designing novel biological detection systems and therapeutic agents that target the LC-NA system's diverse network of pre- and postsynaptic receptors, intracellular signaling pathways and dynamic epigenetic remodeling processes involved in their regulation and functional plasticity.

  7. Birth defects and aplastic anemia: differences in polycyclic hydrocarbon toxicity associated with the Ah locus. [Mice

    Energy Technology Data Exchange (ETDEWEB)

    Nebert, D.W.; Levitt, R.C.; Jensen, N.M.; Lambert, G.H.; Felton, J.S.

    1977-01-01

    The balance between cytochrome(s) P/sub 1/-450 and other forms of P-450 in the liver, and probably many nonhepatic tissues as well, appears to be important in the toxicity, carcinogenicity, mutagenicity, and teratogenicity of numerous compounds. Thus, allelic differences in a single gene--the Ah locus-- can have profound effects on the susceptibility of mice to drug toxicity and cancer. There is evidence for the Ah lous in the human. Striking increases in the incidence of stillborns, reorptions,and malformations caused by 3-methylcholanthrene or 7,12-dimethylbenz(a)anthracene were observed in the aromatic hydrocarbon responsive C57BL/6N,C3H/HeN, and BALB/cAnN inbred strains, compared with the genetically nonresponsive AKR/N. These data suggest that an association exists between the Ah locus and teratogenesis. Although numerous teratogenic differences among inbred mouse strains have been previously reported, this study is unique in that the genetic differences in teratogenicity observed were predicted in advance, on the basis of known differences in polycyclic hydrocarbon metabolism regulated by the Ah locus.

  8. New polymorphisms within the variable number tandem repeat (VNTR) 7 locus of Mycobacterium avium subsp. paratuberculosis.

    Science.gov (United States)

    Fawzy, Ahmad; Zschöck, Michael; Ewers, Christa; Eisenberg, Tobias

    2016-06-01

    Variable number tandem repeat (VNTR) is a frequently employed typing method of Mycobacterium avium paratuberculosis (MAP) isolates. Based on whole genome sequencing in a previous study, allelic diversity at some VNTR loci seems to over- or under-estimate the actual phylogenetic variance among isolates. Interestingly, two closely related isolates on one farm showed polymorphism at the VNTR 7 locus, raising concerns about the misleading role that it might play in genotyping. We aimed to investigate the underlying basis of VNTR 7-polymorphism by analyzing sequence data for published genomes and field isolates of MAP and other M. avium complex (MAC) members. In contrast to MAP strains from cattle, strains from sheep displayed an "imperfect" repeat within VNTR 7, which was identical to respective allele types in other MAC genomes. Subspecies- and strain-specific single nucleotide polymorphisms (SNPs) and two novel (16 and 56 bp) repeats were detected. Given the combination of the three existing repeats, there are at least five different patterns for VNTR 7. The present findings highlight a higher polymorphism and probable instability of VNTR 7 locus that needs to be considered and challenged in future studies. Until then, sequencing of this locus in future studies is important to correctly assign the underlying allele types.(1). Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Fixation Probability in a Two-Locus Model by the Ancestral Recombination–Selection Graph

    Science.gov (United States)

    Lessard, Sabin; Kermany, Amir R.

    2012-01-01

    We use the ancestral influence graph (AIG) for a two-locus, two-allele selection model in the limit of a large population size to obtain an analytic approximation for the probability of ultimate fixation of a single mutant allele A. We assume that this new mutant is introduced at a given locus into a finite population in which a previous mutant allele B is already segregating with a wild type at another linked locus. We deduce that the fixation probability increases as the recombination rate increases if allele A is either in positive epistatic interaction with B and allele B is beneficial or in no epistatic interaction with B and then allele A itself is beneficial. This holds at least as long as the recombination fraction and the selection intensity are small enough and the population size is large enough. In particular this confirms the Hill–Robertson effect, which predicts that recombination renders more likely the ultimate fixation of beneficial mutants at different loci in a population in the presence of random genetic drift even in the absence of epistasis. More importantly, we show that this is true from weak negative epistasis to positive epistasis, at least under weak selection. In the case of deleterious mutants, the fixation probability decreases as the recombination rate increases. This supports Muller’s ratchet mechanism to explain the accumulation of deleterious mutants in a population lacking recombination. PMID:22095080

  10. A new polymorphic pepsinogen locus (Pg-2) in the rat (Rattus norvegicus).

    Science.gov (United States)

    Hamada, S; Yamada, J; Bender, K; Adams, M

    1987-07-01

    Only two types of pepsinogens, which are products of the Pg-1 locus, are present in rat urine. In gastric mucosa, however, additional pepsinogen isozymes are expressed. We have found a polymorphism for rat gastric mucosa pepsinogen using agarose gel electrophoresis. Some inbred rat strains expressed a pepsinogen band, while others did not. The trait was found to be controlled by a single autosomal locus. We tentatively designated the locus as Pg-2 with two alleles, Pg-2a for the one controlling presence of the band and Pg-2o for the one controlling absence. Linkage analysis using BN and TM strains revealed that Pg-2 was closely linked to Pg-1 (3.7 +/- 1.8 cM), and that it did not belong to LG I (Hbb and p), LG II (Acon-1 and Mup-1), LG IV (Hao-1 and Svp-1), LG V (Es-1 and Es-3), LG VI (Gc and h), LG IX (RT1), LG X (Fh and Pep-3), nor a LG containing Ahd-2 (as yet undetermined).

  11. Immunotherapy holds the key to cancer treatment and prevention in constitutional mismatch repair deficiency (CMMRD) syndrome

    NARCIS (Netherlands)

    Westdorp, Harm; Kolders, Sigrid; Hoogerbrugge, Nicoline; de Vries, I Jolanda M; Jongmans, Marjolijn C.J.; Schreibelt, Gerty

    2017-01-01

    Monoallelic germline mutations in one of the DNA mismatch repair (MMR) genes cause Lynch syndrome, with a high lifetime risks of colorectal and endometrial cancer at adult age. Less well known, is the constitutional mismatch repair deficiency (CMMRD) syndrome caused by biallelic germline mutations

  12. Constitutional mismatch repair deficiency in a healthy child : On the spot diagnosis?

    NARCIS (Netherlands)

    Suerink, Manon; Potjer, Thomas P.; Versluijs, A. B.; Ten Broeke, Sanne W.; Tops, Carli M.; Wimmer, K.; Nielsen, M.

    2018-01-01

    Constitutional mismatch repair deficiency (CMMRD) is a rare, recessively inherited childhood cancer predisposition syndrome caused by biallelic germline mutations in one of the mismatch repair genes. The CMMRD phenotype overlaps with that of neurofibromatosis type 1 (NF1), since many patients have

  13. Educational mismatches for second generation migrants. An analysis of applied science graduates in the Netherlands

    NARCIS (Netherlands)

    Falcke, Swantje; Meng, Christoph; Nollen, Romy

    2016-01-01

    Educational mismatches, i.e. diferences between the education attained and required for a job have been found to negatively affect earnings and job satisfaction and thus lead to a lower return to education. In this paper we aim to see whether immigrants are more prone to educational mismatches and

  14. Resonance Polarization and Phase-Mismatched CARS of Pheophytin b Excited in the Qy Band

    NARCIS (Netherlands)

    de Boeij, W.P.; Lucassen, G.W.; Lucassen, Gerald; Otto, Cornelis; Greve, Jan

    1993-01-01

    Resonance polarization and phase-mismatched coherent anti-Stokes Raman scattering (CARS) measurements were performed on pheophytin b dissolved in acetone excited in the Qy absorption band, where strong broad fluorescence makes spontaneous Raman spectroscopy impossible. The phase-mismatching

  15. Scandiatransplant acceptable mismatch program (STAMP) a bridge to transplanting highly immunized patients

    DEFF Research Database (Denmark)

    Koefoed-Nielsen, Pernille; Weinreich, I; Bengtsson, M

    2017-01-01

    BACKGROUND: Highly immunized patients are a challenge for organ transplantation programs. One way of increasing the likelihood of transplantation in this group of patients is to expand the possible donations by defining acceptable HLA mismatches. In the Scandiatransplant Acceptable Mismatch Program...

  16. The effect of atom mismatch on the fragility of supercooled Lennard-Jones binary mixtures

    International Nuclear Information System (INIS)

    Sun Minhua; Sun Yongli; Wang Aiping; Ma Congxiao; Li Jiayun; Cheng Weidong; Liu Fang

    2006-01-01

    The shear viscosity of the well-known binary Lennard-Jones mixture is simulated under constant temperature and constant volume conditions (NVT) by a molecular-dynamics (MD) method. The effect of atomic size mismatch on the fragility parameter and glass-forming ability is studied. The fragility parameters calculated from shear viscosity data decrease with the increment of the atomic size mismatch. The value of the fragility changes from 168.963 to 22.976 when the mismatch changes from 0.023 to 0.25. It is shown that the fragility parameter is sensitive to the atomic size mismatch. The calculated pair distribution functions and mean square displacements indicate that the glass-forming ability increases with the atomic size mismatch

  17. DNA Mismatch Repair and Oxidative DNA Damage: Implications for Cancer Biology and Treatment

    International Nuclear Information System (INIS)

    Bridge, Gemma; Rashid, Sukaina; Martin, Sarah A.

    2014-01-01

    Many components of the cell, including lipids, proteins and both nuclear and mitochondrial DNA, are vulnerable to deleterious modifications caused by reactive oxygen species. If not repaired, oxidative DNA damage can lead to disease-causing mutations, such as in cancer. Base excision repair and nucleotide excision repair are the two DNA repair pathways believed to orchestrate the removal of oxidative lesions. However, recent findings suggest that the mismatch repair pathway may also be important for the response to oxidative DNA damage. This is particularly relevant in cancer where mismatch repair genes are frequently mutated or epigenetically silenced. In this review we explore how the regulation of oxidative DNA damage by mismatch repair proteins may impact on carcinogenesis. We discuss recent studies that identify potential new treatments for mismatch repair deficient tumours, which exploit this non-canonical role of mismatch repair using synthetic lethal targeting

  18. DNA Mismatch Repair and Oxidative DNA Damage: Implications for Cancer Biology and Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Bridge, Gemma; Rashid, Sukaina; Martin, Sarah A., E-mail: sarah.martin@qmul.ac.uk [Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ (United Kingdom)

    2014-08-05

    Many components of the cell, including lipids, proteins and both nuclear and mitochondrial DNA, are vulnerable to deleterious modifications caused by reactive oxygen species. If not repaired, oxidative DNA damage can lead to disease-causing mutations, such as in cancer. Base excision repair and nucleotide excision repair are the two DNA repair pathways believed to orchestrate the removal of oxidative lesions. However, recent findings suggest that the mismatch repair pathway may also be important for the response to oxidative DNA damage. This is particularly relevant in cancer where mismatch repair genes are frequently mutated or epigenetically silenced. In this review we explore how the regulation of oxidative DNA damage by mismatch repair proteins may impact on carcinogenesis. We discuss recent studies that identify potential new treatments for mismatch repair deficient tumours, which exploit this non-canonical role of mismatch repair using synthetic lethal targeting.

  19. Bifunctional rhodium intercalator conjugates as mismatch-directing DNA alkylating agents.

    Science.gov (United States)

    Schatzschneider, Ulrich; Barton, Jacqueline K

    2004-07-21

    A conjugate of a DNA mismatch-specific rhodium intercalator, containing the bulky chrysenediimine ligand, and an aniline mustard has been prepared, and targeting of mismatches in DNA by this conjugate has been examined. The preferential alkylation of mismatched over fully matched DNA is found by a mobility shift assay at concentrations where untethered organic mustards show little reaction. The binding site of the Rh intercalator was determined by DNA photocleavage, and the position of covalent modification was established on the basis of the enhanced depurination associated with N-alkylation. The site-selective alkylation at mismatched DNA renders these conjugates useful tools for the covalent tagging of DNA base pair mismatches and new chemotherapeutic design.

  20. Selective Cytotoxicity of Rhodium Metalloinsertors in Mismatch Repair-Deficient Cells†

    Science.gov (United States)

    Ernst, Russell J.; Komor, Alexis C.; Barton, Jacqueline K.

    2011-01-01

    Mismatches in DNA occur naturally during replication and as a result of endogenous DNA damaging agents, but the mismatch repair (MMR) pathway acts to correct mismatches before subsequent rounds of replication. Rhodium metalloinsertors bind to DNA mismatches with high affinity and specificity and represent a promising strategy to target mismatches in cells. Here we examine the biological fate of rhodium metalloinsertors bearing dipyridylamine ancillary ligands in cells deficient in MMR versus those that are MMR-proficient. These complexes are shown to exhibit accelerated cellular uptake which permits the observation of various cellular responses, including disruption of the cell cycle, monitored by flow cytometry assays, and induction of necrosis, monitored by dye exclusion and caspase inhibition assays, that occur preferentially in the MMR-deficient cell line. These cellular responses provide insight into the mechanisms underlying the selective activity of this novel class of targeted anti-cancer agents. PMID:22103240

  1. A locus for isolated cataract on human Xp.

    Science.gov (United States)

    Francis, P J; Berry, V; Hardcastle, A J; Maher, E R; Moore, A T; Bhattacharya, S S

    2002-02-01

    To genetically map the gene causing isolated X linked cataract in a large European pedigree. Using the patient registers at Birmingham Women's Hospital, UK, we identified and examined 23 members of a four generation family with nuclear cataract. Four of six affected males also had complex congenital heart disease. Pedigree data were collated and leucocyte DNA extracted from venous blood. Linkage analysis by PCR based microsatellite marker genotyping was used to identify the disease locus and mutations within candidate genes screened by direct sequencing. The disease locus was genetically refined to chromosome Xp22, within a 3 cM linkage interval flanked by markers DXS9902 and DXS999 (Zmax=3.64 at theta=0 for marker DXS8036). This is the first report of a locus for isolated inherited cataract on the X chromosome. The disease interval lies within the Nance-Horan locus suggesting allelic heterogeneity. The apparent association with congenital cardiac anomalies suggests a possible new oculocardiac syndrome.

  2. Multidimensional profiles of health locus of control in Hispanic Americans.

    Science.gov (United States)

    Champagne, Brian R; Fox, Rina S; Mills, Sarah D; Sadler, Georgia Robins; Malcarne, Vanessa L

    2016-10-01

    Latent profile analysis identified health locus of control profiles among 436 Hispanic Americans who completed the Multidimensional Health Locus of Control scales. Results revealed four profiles: Internally Oriented-Weak, -Moderate, -Strong, and Externally Oriented. The profile groups were compared on sociocultural and demographic characteristics, health beliefs and behaviors, and physical and mental health outcomes. The Internally Oriented-Strong group had less cancer fatalism, religiosity, and equity health attributions, and more alcohol consumption than the other three groups; the Externally Oriented group had stronger equity health attributions and less alcohol consumption. Deriving multidimensional health locus of control profiles through latent profile analysis allows examination of the relationships of health locus of control subtypes to health variables. © The Author(s) 2015.

  3. 240 INFLUENCES OF PEER RELATIONS AND LOCUS OF ...

    African Journals Online (AJOL)

    Financial recklessness is a behavior that has far reaching negative .... between consumer financial knowledge, income and locus of control on financial ... Their interactions with their peers increased their internal motivations and thus helped.

  4. Emotional intelligence and locus of control of adult patients with ...

    African Journals Online (AJOL)

    2011-03-15

    Mar 15, 2011 ... Keywords: breast cancer, treatment, positive psychology, emotional intelligence, locus of control ... branches are organised in a hierarchy with perception of ..... Asian. Development Bank Knowledge Solutions [serial online].

  5. LOCUS OF CONTROL AND JOB SATISFACTION: PSU EMPLOYEES

    Directory of Open Access Journals (Sweden)

    Lakshman Vijayashree

    2011-11-01

    Full Text Available Previous research studies have demonstrated that internal/external locus of control impacts jobsatisfaction. The present study thus aims to analyze type of locus of control and its relation with jobsatisfaction. The study will be of great help for organization to understand and know what type oflocus of control their employees has and how it has an impact on job satisfaction.The objectives of this study were: 1- To identify the type of Locus of Control (i.e. Internal orExternal present in Public Sector Units (PSU in Bangalore and 2- To analyze the impact of differenttype of Locus of Control on job satisfaction of PSU Employees. Further hypothesis was also set tocheck the relationship between locus of control and job satisfaction. In addition, the relationshipbetween different demographic factors was also examined. The tool used for this study was LocoInventory. The concept of locus of control by Levenson (1972 was used to develop Loco Inventory(Locus of Control in Organization Inventory. The survey used a questionnaire, which had thirty fivestatements which highlights the factors that determine the locus of control and job satisfaction levelof the employees. The Ratio, ANOVA, and Correlation analysis were used as statistical techniquesfor analysis.The results indicate that there is a positive correlation between internal locus of control and jobsatisfaction as well as between External (other locus of control and job satisfaction. And in case ofExternal (Chance locus of control and job satisfaction there exists partial positive correlation. As perthis study Job satisfaction level among the employees is also good as the mean is 17, which is closerto maximum scale value of 25. As per ANOVA table there is a significant variance betweeninternality and age as well as between externality (chance and age. There is no significantrelationship between internality and demographic factors like gender and education. There is nosignificant relationship between

  6. Scale Mismatches in Social-Ecological Systems: Causes, Consequences, and Solutions

    Directory of Open Access Journals (Sweden)

    Graeme S. Cumming

    2006-06-01

    Full Text Available Scale is a concept that transcends disciplinary boundaries. In ecology and geography, scale is usually defined in terms of spatial and temporal dimensions. Sociological scale also incorporates space and time, but adds ideas about representation and organization. Although spatial and temporal location determine the context for social and ecological dynamics, social-ecological interactions can create dynamic feedback loops in which humans both influence and are influenced by ecosystem processes. We hypothesize that many of the problems encountered by societies in managing natural resources arise because of a mismatch between the scale of management and the scale(s of the ecological processes being managed. We use examples from southern Africa and the southern United States to address four main questions: (1 What is a "scale mismatch?" (2 How are scale mismatches generated? (3 What are the consequences of scale mismatches? (4 How can scale mismatches be resolved? Scale mismatches occur when the scale of environmental variation and the scale of social organization in which the responsibility for management resides are aligned in such a way that one or more functions of the social-ecological system are disrupted, inefficiencies occur, and/or important components of the system are lost. They are generated by a wide range of social, ecological, and linked social-ecological processes. Mismatches between the scales of ecological processes and the institutions that are responsible for managing them can contribute to a decrease in social-ecological resilience, including the mismanagement of natural resources and a decrease in human well-being. Solutions to scale mismatches usually require institutional changes at more than one hierarchical level. Long-term solutions to scale mismatch problems will depend on social learning and the development of flexible institutions that can adjust and reorganize in response to changes in ecosystems. Further research is

  7. The relationship between locus of control and career advancement

    OpenAIRE

    2014-01-01

    M.Com. (Industrial Psychology) The objective which career of this study advancement is was to investigate the extent to contingent on the personality construct locus of control. In order to achieve this, empirical research was conducted in a South African organisation. A survey questionnaire measuring career advancement and locus of control was completed by 152 subjects. The hypothesis which was formulated was that people with higher rates of career advancement would be more internal and t...

  8. Analysis of the ABCA4 genomic locus in Stargardt disease

    DEFF Research Database (Denmark)

    Zernant, Jana; Xie, Yajing Angela; Ayuso, Carmen

    2014-01-01

    excluded since they were not conserved in non-human primates, were frequent in African populations and, therefore, represented ancestral, and not disease-associated, variants. The sequence variability in the ABCA4 locus is extensive and the non-coding sequences do not harbor frequent mutations in STGD...... patients of European-American descent. Defining disease-associated alleles in the ABCA4 locus requires exceptionally well characterized large cohorts and extensive analyses by a combination of various approaches....

  9. Science Study For A Low Cost Upper Atmosphere Sounder (LOCUS)

    Science.gov (United States)

    Gerber, D.; Swinyard, B. M.; Ellison, B. N.; Siddans, R.; Kerridge, B. J.; Plane, J. M. C.; Feng, W.

    2013-12-01

    We present the findings of an initial science study to define the spectral bands for the proposed Mesosphere / Lower Thermosphere (MLT) sounder LOCUS. The LOCUS mission (Fig 1) uses disruptive technologies to make key MLT species detectable globally by satellite remote sensing for the first time. This presentation summarises the technological and scientific foundation on which the current 4-band Terahertz (THz) and sub- millimetre wave (SMW) instrument configuration was conceived.

  10. Gold-based optical biosensor for single-mismatched DNA detection using salt-induced hybridization

    DEFF Research Database (Denmark)

    Zhan, Zongrui; Ma, Xingyi; Cao, Cuong

    2011-01-01

    In this study, a gold nanoparticle (Au-NP)-based detection method for sensitive and specific DNA-based diagnostic applications is described. A sandwich format consisting of Au-NPs/DNA/PMP (Streptavidin-coated MagnetSphere Para-Magnetic Particles) was fabricated. PMPs captured and separated target...

  11. [Health locus of control of patients in disease management programmes].

    Science.gov (United States)

    Schnee, M; Grikscheit, F

    2013-06-01

    Health locus of control beliefs plays a major role in improving self-management skills of the chronically ill - a main goal in disease management programmes (DMP). This study aims at characterising participants in disease management regarding their health locus of control. Data are based on 4 cross-sectional postal surveys between spring and autumn of 2006 and 2007 within the Health Care Monitor of the Bertelsmann Foundation. Among the 6 285 respondents, 1 266 are chronically ill and not enrolled in a DMP and 327 are participating in a DMP. A high internal locus of control (HLC) occurs significantly less often in DMP patients than in normal chronically ill patients (and healthy people) controlling for age, gender and social class. With increasing age, a high internal locus of control is also significantly less likely. When comparing healthy people, the chronically ill and the DMP participants a social gradient of a high internal locus of control belief can be observed. The weaker internal and higher doctor-related external locus of control of DMP participants should be carefully observed by the physician when trying to strengthen the patients' self-management skills. Evaluators of DMP should take into account the different baselines of DMP patients and relevant control groups and incorporate these differences into the evaluation. © Georg Thieme Verlag KG Stuttgart · New York.

  12. Neurolinguistic programming training, trait anxiety, and locus of control.

    Science.gov (United States)

    Konefal, J; Duncan, R C; Reese, M A

    1992-06-01

    Training in the neurolinguistic programming techniques of shifting perceptual position, visual-kinesthetic dissociation, timelines, and change-history, all based on experiential cognitive processing of remembered events, leads to an increased awareness of behavioral contingencies and a more sensitive recognition of environmental cues which could serve to lower trait anxiety and increase the sense of internal control. This study reports on within-person and between-group changes in trait anxiety and locus of control as measured on the Spielberger State-Trait Anxiety Inventory and Wallston, Wallston, and DeVallis' Multiple Health Locus of Control immediately following a 21-day residential training in neurolinguistic programming. Significant with-in-person decreases in trait-anxiety scores and increases in internal locus of control scores were observed as predicted. Chance and powerful other locus of control scores were unchanged. Significant differences were noted on trait anxiety and locus of control scores between European and U.S. participants, although change scores were similar for the two groups. These findings are consistent with the hypothesis that this training may lower trait-anxiety scores and increase internal locus of control scores. A matched control group was not available, and follow-up was unfortunately not possible.

  13. DNA modification study of major depressive disorder: beyond locus-by-locus comparisons.

    Science.gov (United States)

    Oh, Gabriel; Wang, Sun-Chong; Pal, Mrinal; Chen, Zheng Fei; Khare, Tarang; Tochigi, Mamoru; Ng, Catherine; Yang, Yeqing A; Kwan, Andrew; Kaminsky, Zachary A; Mill, Jonathan; Gunasinghe, Cerisse; Tackett, Jennifer L; Gottesman, Irving I; Willemsen, Gonneke; de Geus, Eco J C; Vink, Jacqueline M; Slagboom, P Eline; Wray, Naomi R; Heath, Andrew C; Montgomery, Grant W; Turecki, Gustavo; Martin, Nicholas G; Boomsma, Dorret I; McGuffin, Peter; Kustra, Rafal; Petronis, Art

    2015-02-01

    Major depressive disorder (MDD) exhibits numerous clinical and molecular features that are consistent with putative epigenetic misregulation. Despite growing interest in epigenetic studies of psychiatric diseases, the methodologies guiding such studies have not been well defined. We performed DNA modification analysis in white blood cells from monozygotic twins discordant for MDD, in brain prefrontal cortex, and germline (sperm) samples from affected individuals and control subjects (total N = 304) using 8.1K CpG island microarrays and fine mapping. In addition to the traditional locus-by-locus comparisons, we explored the potential of new analytical approaches in epigenomic studies. In the microarray experiment, we detected a number of nominally significant DNA modification differences in MDD and validated selected targets using bisulfite pyrosequencing. Some MDD epigenetic changes, however, overlapped across brain, blood, and sperm more often than expected by chance. We also demonstrated that stratification for disease severity and age may increase the statistical power of epimutation detection. Finally, a series of new analytical approaches, such as DNA modification networks and machine-learning algorithms using binary and quantitative depression phenotypes, provided additional insights on the epigenetic contributions to MDD. Mapping epigenetic differences in MDD (and other psychiatric diseases) is a complex task. However, combining traditional and innovative analytical strategies may lead to identification of disease-specific etiopathogenic epimutations. Copyright © 2015 Society of Biological Psychiatry. All rights reserved.

  14. Insertional inactivation of a chromosomal locus that modulates expression of potential virulence determinants in Staphylococcus aureus.

    OpenAIRE

    Cheung, A L; Wolz, C; Yeaman, M R; Bayer, A S

    1995-01-01

    A single insertion of transposon Tn551 into a unique chromosomal locus of Staphylococcus aureus ISP479C has resulted in a pleiotropic effect on the expression of both extracellular and cell wall proteins. In particular, the expression of cell wall protein A and clumping activity with fibrinogen were rendered undetectable in the mutant 1E3 compared with the parent. The secretion of alpha-hemolysin in mutant 1E3 was modestly increased. Southern blot and phenotypic analyses indicated that this l...

  15. Detection of a molecular deletion at the DXS732 locus in a patient with X-linked hypohidrotic ectodermal dysplasia (EDA), with the identification of a unique junctional fragment

    Energy Technology Data Exchange (ETDEWEB)

    Zonana, J.; Gault, J.; Jones, M.; Browne, D.; Litt, M. (Oregon Health Sciences Univ., Portland (United States)); Davies, K.J.P.; Clarke, A.; Thomas, N.S.T. (Univ. of Wales, Cardiff (United Kingdom)); Brockdorff, N.; Rastan, S. (Medical Research Council Clinical Research Centre, Harrow (United Kingdom))

    1993-01-01

    X-linked hypohidrotic ectodermal dysplasia (EDA) has been localized to the Xq12-q13.1. A panel of genomic DNA samples from 80 unrelated males with EDA has been screened for deletions at seven genetic loci within the Xq12-13 region. A single individual was identified with a deletion at the DXS732 locus by hybridization with the mouse genomic probe pcos169E/4. This highly conserved DNA probe is from locus DXCrc169, which is tightly linked to the Ta locus, the putative mouse homologue of EDA. The proband had the classical phenotype of EDA, with no other phenotypic abnormalities, and a normal cytogenetic analysis. A human genomic DNA clone, homologous to pcos169E/4, was isolated from a human X-chromosome cosmid library. On hybridization with the cosmid, the proband was found to be only partially deleted at the DXS732 locus, with a unique junctional fragment identified in the proband and in three of his maternal relatives. This is the first determination of carrier status for EDA in females, by direct mutation analysis. Failure to detect deletion of the other loci tested in the proband suggests that the DXS732 locus is the closest known locus to the EDA gene. Since the DXS732 locus contains a highly conserved sequence, it must be considered to be a candidate locus for the EDA gene itself. 18 refs., 3 figs., 1 tab.

  16. Collocation mismatch uncertainties in satellite aerosol retrieval validation

    Science.gov (United States)

    Virtanen, Timo H.; Kolmonen, Pekka; Sogacheva, Larisa; Rodríguez, Edith; Saponaro, Giulia; de Leeuw, Gerrit

    2018-02-01

    Satellite-based aerosol products are routinely validated against ground-based reference data, usually obtained from sun photometer networks such as AERONET (AEROsol RObotic NETwork). In a typical validation exercise a spatial sample of the instantaneous satellite data is compared against a temporal sample of the point-like ground-based data. The observations do not correspond to exactly the same column of the atmosphere at the same time, and the representativeness of the reference data depends on the spatiotemporal variability of the aerosol properties in the samples. The associated uncertainty is known as the collocation mismatch uncertainty (CMU). The validation results depend on the sampling parameters. While small samples involve less variability, they are more sensitive to the inevitable noise in the measurement data. In this paper we study systematically the effect of the sampling parameters in the validation of AATSR (Advanced Along-Track Scanning Radiometer) aerosol optical depth (AOD) product against AERONET data and the associated collocation mismatch uncertainty. To this end, we study the spatial AOD variability in the satellite data, compare it against the corresponding values obtained from densely located AERONET sites, and assess the possible reasons for observed differences. We find that the spatial AOD variability in the satellite data is approximately 2 times larger than in the ground-based data, and the spatial variability correlates only weakly with that of AERONET for short distances. We interpreted that only half of the variability in the satellite data is due to the natural variability in the AOD, and the rest is noise due to retrieval errors. However, for larger distances (˜ 0.5°) the correlation is improved as the noise is averaged out, and the day-to-day changes in regional AOD variability are well captured. Furthermore, we assess the usefulness of the spatial variability of the satellite AOD data as an estimate of CMU by comparing the

  17. TALE nickase mediates high efficient targeted transgene integration at the human multi-copy ribosomal DNA locus.

    Science.gov (United States)

    Wu, Yong; Gao, Tieli; Wang, Xiaolin; Hu, Youjin; Hu, Xuyun; Hu, Zhiqing; Pang, Jialun; Li, Zhuo; Xue, Jinfeng; Feng, Mai; Wu, Lingqian; Liang, Desheng

    2014-03-28

    Although targeted gene addition could be stimulated strikingly by a DNA double strand break (DSB) created by either zinc finger nucleases (ZFNs) or TALE nucleases (TALENs), the DSBs are really mutagenic and toxic to human cells. As a compromised solution, DNA single-strand break (SSB) or nick has been reported to mediate high efficient gene addition but with marked reduction of random mutagenesis. We previously demonstrated effective targeted gene addition at the human multicopy ribosomal DNA (rDNA) locus, a genomic safe harbor for the transgene with therapeutic potential. To improve the transgene integration efficiency by using TALENs while lowering the cytotoxicity of DSBs, we created both TALENs and TALE nickases (TALENickases) targeting this multicopy locus. A targeting vector which could integrate a GFP cassette at the rDNA locus was constructed and co-transfected with TALENs or TALENickases. Although the fraction of GFP positive cells using TALENs was greater than that using TALENickases during the first few days after transfection, it reduced to a level less than that using TALENickases after continuous culture. Our findings showed that the TALENickases were more effective than their TALEN counterparts at the multi-copy rDNA locus, though earlier studies using ZFNs and ZFNickases targeting the single-copy loci showed the reverse. Besides, TALENickases mediated the targeted integration of a 5.4 kb fragment at a frequency of up to 0.62% in HT1080 cells after drug selection, suggesting their potential application in targeted gene modification not being limited at the rDNA locus. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Auditory mismatch negativity in schizophrenia: topographic evaluation with a high-density recording montage.

    Science.gov (United States)

    Hirayasu, Y; Potts, G F; O'Donnell, B F; Kwon, J S; Arakaki, H; Akdag, S J; Levitt, J J; Shenton, M E; McCarley, R W

    1998-09-01

    The mismatch negativity, a negative component in the auditory event-related potential, is thought to index automatic processes involved in sensory or echoic memory. The authors' goal in this study was to examine the topography of auditory mismatch negativity in schizophrenia with a high-density, 64-channel recording montage. Mismatch negativity topography was evaluated in 23 right-handed male patients with schizophrenia who were receiving medication and in 23 nonschizophrenic comparison subjects who were matched in age, handedness, and parental socioeconomic status. The Positive and Negative Syndrome Scale was used to measure psychiatric symptoms. Mismatch negativity amplitude was reduced in the patients with schizophrenia. They showed a greater left-less-than-right asymmetry than comparison subjects at homotopic electrode pairs near the parietotemporal junction. There were correlations between mismatch negativity amplitude and hallucinations at left frontal electrodes and between mismatch negativity amplitude and passive-apathetic social withdrawal at left and right frontal electrodes. Mismatch negativity was reduced in schizophrenia, especially in the left hemisphere. This finding is consistent with abnormalities of primary or adjacent auditory cortex involved in auditory sensory or echoic memory.

  19. Measurement errors in multifrequency bioelectrical impedance analyzers with and without impedance electrode mismatch

    International Nuclear Information System (INIS)

    Bogónez-Franco, P; Nescolarde, L; Bragós, R; Rosell-Ferrer, J; Yandiola, I

    2009-01-01

    The purpose of this study is to compare measurement errors in two commercially available multi-frequency bioimpedance analyzers, a Xitron 4000B and an ImpediMed SFB7, including electrode impedance mismatch. The comparison was made using resistive electrical models and in ten human volunteers. We used three different electrical models simulating three different body segments: the right-side, leg and thorax. In the electrical models, we tested the effect of the capacitive coupling of the patient to ground and the skin–electrode impedance mismatch. Results showed that both sets of equipment are optimized for right-side measurements and for moderate skin–electrode impedance mismatch. In right-side measurements with mismatch electrode, 4000B is more accurate than SFB7. When an electrode impedance mismatch was simulated, errors increased in both bioimpedance analyzers and the effect of the mismatch in the voltage detection leads was greater than that in current injection leads. For segments with lower impedance as the leg and thorax, SFB7 is more accurate than 4000B and also shows less dependence on electrode mismatch. In both devices, impedance measurements were not significantly affected (p > 0.05) by the capacitive coupling to ground

  20. Snowshoe hares display limited phenotypic plasticity to mismatch in seasonal camouflage

    Science.gov (United States)

    Zimova, Marketa; Mills, L. Scott; Lukacs, Paul M.; Mitchell, Michael S.

    2014-01-01

    As duration of snow cover decreases owing to climate change, species undergoing seasonal colour moults can become colour mismatched with their background. The immediate adaptive solution to this mismatch is phenotypic plasticity, either in phenology of seasonal colour moults or in behaviours that reduce mismatch or its consequences. We observed nearly 200 snowshoe hares across a wide range of snow conditions and two study sites in Montana, USA, and found minimal plasticity in response to mismatch between coat colour and background. We found that moult phenology varied between study sites, likely due to differences in photoperiod and climate, but was largely fixed within study sites with only minimal plasticity to snow conditions during the spring white-to-brown moult. We also found no evidence that hares modify their behaviour in response to colour mismatch. Hiding and fleeing behaviours and resting spot preference of hares were more affected by variables related to season, site and concealment by vegetation, than by colour mismatch. We conclude that plasticity in moult phenology and behaviours in snowshoe hares is insufficient for adaptation to camouflage mismatch, suggesting that any future adaptation to climate change will require natural selection on moult phenology or behaviour.

  1. Humming along or buzzing off? The elusive consequences of plant-pollinator mismatches

    Directory of Open Access Journals (Sweden)

    Jason Ryan Straka

    2014-08-01

    Full Text Available Temporal mismatches among plants and pollinators, driven by climate change, are considered a potential cause of population declines of these mutualists. However, field studies demonstrating population declines as a result of climate-driven phenological mismatches are uncommon, and the extent to which mismatches will be a problem in the future remains unclear. We revisit predicted consequences of climate-driven phenological mismatch in plant-pollinator systems by identifying nine previously-applied assumptions that are violated or insufficiently understood in real systems. Briefly, the assumptions are: (1 Dates of first-flowering (DFF or dates of first activity (DFA correctly describe phenology, and disparities between DFF and DFA represent the magnitude of mismatch. (2 “Optimal” matches are measured correctly. (3 Advancement of DFF or DFA will be the primary phenological change in the future. (4 Future phenological shifts will be independent for each species. (5 All plant-pollinator interactions are equally effective. (6 Populations of plants and pollinators are limited by mutualistic interactions. Some previous models have also assumed that the effects of future mismatches will not be influenced by (7 emergence of novel interactions, (8 competition or facilitation from altered co-flowering and co-flight, and (9 phenotypic plasticity and rapid adaptive evolution of phenology. Those assumptions affect the direction, extent, and accuracy of predicted consequences of future phenological mismatch. In discussing them, we identify important topics for future research in pollination ecology.

  2. Parametric Adaptive Radar Detector with Enhanced Mismatched Signals Rejection Capabilities

    Directory of Open Access Journals (Sweden)

    Liu Bin

    2010-01-01

    Full Text Available We consider the problem of adaptive signal detection in the presence of Gaussian noise with unknown covariance matrix. We propose a parametric radar detector by introducing a design parameter to trade off the target sensitivity with sidelobes energy rejection. The resulting detector merges the statistics of Kelly's GLRT and of the Rao test and so covers Kelly's GLRT and the Rao test as special cases. Both invariance properties and constant false alarm rate (CFAR behavior for this detector are studied. At the analysis stage, the performance of the new receiver is assessed and compared with several traditional adaptive detectors. The results highlight better rejection capabilities of this proposed detector for mismatched signals. Further, we develop two two-stage detectors, one of which consists of an adaptive matched filter (AMF followed by the aforementioned detector, and the other is obtained by cascading a GLRT-based Subspace Detector (SD and the proposed adaptive detector. We show that the former two-stage detector outperforms traditional two-stage detectors in terms of selectivity, and the latter yields more robustness.

  3. Integrated analysis of mismatch repair system in malignant astrocytomas.

    Directory of Open Access Journals (Sweden)

    Irene Rodríguez-Hernández

    Full Text Available Malignant astrocytomas are the most aggressive primary brain tumors with a poor prognosis despite optimal treatment. Dysfunction of mismatch repair (MMR system accelerates the accumulation of mutations throughout the genome causing uncontrolled cell growth. The aim of this study was to characterize the MMR system defects that could be involved in malignant astrocytoma pathogenesis. We analyzed protein expression and promoter methylation of MLH1, MSH2 and MSH6 as well as microsatellite instability (MSI and MMR gene mutations in a set of 96 low- and high-grade astrocytomas. Forty-one astrocytomas failed to express at least one MMR protein. Loss of MSH2 expression was more frequent in low-grade astrocytomas. Loss of MLH1 expression was associated with MLH1 promoter hypermethylation and MLH1-93G>A promoter polymorphism. However, MSI was not related with MMR protein expression and only 5% of tumors were MSI-High. Furthermore, the incidence of tumors carrying germline mutations in MMR genes was low and only one glioblastoma was associated with Lynch syndrome. Interestingly, survival analysis identified that tumors lacking MSH6 expression presented longer overall survival in high-grade astrocytoma patients treated only with radiotherapy while MSH6 expression did not modify the prognosis of those patients treated with both radiotherapy and chemotherapy. Our findings suggest that MMR system alterations are a frequent event in malignant astrocytomas and might help to define a subgroup of patients with different outcome.

  4. Sensory memory during physiological aging indexed by mismatch negativity (MMN).

    Science.gov (United States)

    Ruzzoli, Manuela; Pirulli, Cornelia; Brignani, Debora; Maioli, Claudio; Miniussi, Carlo

    2012-03-01

    Physiological aging affects early sensory-perceptual processes. The aim of this experiment was to evaluate changes in auditory sensory memory in physiological aging using the Mismatch Negativity (MMN) paradigm as index. The MMN is a marker recorded through the electroencephalogram and is used to evaluate the integrity of the memory system. We adopted a new, faster paradigm to look for differences between 3 groups of subjects of different ages (young, middle age and older adults) as a function of short or long intervals between stimuli. We found that older adults did not show MMN at long interval condition and that the duration of MMN varied according to the participants' age. The current study provides electrophysiological evidence supporting the theory that the encoding of stimuli is preserved during normal aging, whereas the maintenance of sensory memory is impaired. Considering the advantage offered by the MMN paradigm used here, these data might be a useful reference point for the assessment of auditory sensory memory in pathological aging (e.g., in neurodegenerative diseases). Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Frontal Theta Activity Supports Detecting Mismatched Information in Visual Working Memory.

    Science.gov (United States)

    Liang, Tengfei; Hu, Zhonghua; Liu, Qiang

    2017-01-01

    During the comparison stage of visual working memory (VWM) processing, detecting the mismatch between the external sensory input and internal representations is a crucial cognitive ability for human, but the neural mechanism behind it remains largely unclear. The present study investigated the role of frontal theta power in detecting the mismatched information in VWM in a delayed matching task. A control task required to compare two simultaneously presented visual figures was also designed as a contrast to exclude the possibility that frontal theta activity just reflecting the non-memory-related behavioral conflicts. To better characterize the control mechanisms shaped by the frontal theta oscillation in human VWM, colored shapes were adopted as materials while both the task-relevant shape feature and task-irrelevant color feature could be mismatched. We found that the response times of participants were significantly delayed under the relevant- and irrelevant-mismatch conditions in both tasks and the conjunction-mismatch condition in delayed matching task. While our EEG data showed that increased frontal theta power was only observed under the relevant- and conjunction-mismatch conditions in the delayed matching task, but not the control task. These findings suggest that the frontal distributed theta activity observed here reflects the detection of mismatched information during the comparison stage of VWM, rather than the response-related conflicts. Furthermore, it is consistent with the proposal that theta-band oscillation can act as a control mechanism in working memory function so that the target-mismatched information in VWM could be successfully tracked. We also propose a possible processing structure to explain the neural dynamics underlying the mismatch detection process in VWM.

  6. Frontal Theta Activity Supports Detecting Mismatched Information in Visual Working Memory

    Directory of Open Access Journals (Sweden)

    Tengfei Liang

    2017-10-01

    Full Text Available During the comparison stage of visual working memory (VWM processing, detecting the mismatch between the external sensory input and internal representations is a crucial cognitive ability for human, but the neural mechanism behind it remains largely unclear. The present study investigated the role of frontal theta power in detecting the mismatched information in VWM in a delayed matching task. A control task required to compare two simultaneously presented visual figures was also designed as a contrast to exclude the possibility that frontal theta activity just reflecting the non-memory-related behavioral conflicts. To better characterize the control mechanisms shaped by the frontal theta oscillation in human VWM, colored shapes were adopted as materials while both the task-relevant shape feature and task-irrelevant color feature could be mismatched. We found that the response times of participants were significantly delayed under the relevant- and irrelevant-mismatch conditions in both tasks and the conjunction-mismatch condition in delayed matching task. While our EEG data showed that increased frontal theta power was only observed under the relevant- and conjunction-mismatch conditions in the delayed matching task, but not the control task. These findings suggest that the frontal distributed theta activity observed here reflects the detection of mismatched information during the comparison stage of VWM, rather than the response-related conflicts. Furthermore, it is consistent with the proposal that theta-band oscillation can act as a control mechanism in working memory function so that the target-mismatched information in VWM could be successfully tracked. We also propose a possible processing structure to explain the neural dynamics underlying the mismatch detection process in VWM.

  7. Cocktail mismatch effects in 4πβ liquid scintillation spectrometry: implications based on the systematics of 3H detection efficiency and quench indicating parameter variations with total cocktail mass (volume) and H2O fraction

    International Nuclear Information System (INIS)

    Colle, R.

    1997-01-01

    Detection efficiency changes for 3 H by 4πβ liquid scintillation (LS) spectrometry cannot be adequately monitored by quench indicating parameters when the quench changes are the result of multiple causal factors (e.g. simultaneously varying cocktail sizes and composition). In consequence, some kinds of cocktail mismatches (between LS counting sources) introduce errors that result from efficiency changes that cannot be fully accounted for by quench monitoring compensations. These cocktails mismatch effects are examined for comparative 3 H measurements and for 3 H-standard efficiency tracing methods for the assay of other β-emitting radionuclides. Inherent errors can occur in both types of radionuclide assays, as demonstrated with realistic case examples, unless cocktails are very closely matched. The magnitude of the cocktail mismatch effect (and attendant errors) can range from being virtually negligible (particularly for high-energy β-emitting nuclides and for slight single-variable cocktail composition mismatches) to be being very significant for high-precision metrology and standardizations (particularly with easily quenched, low-energy β emitters and for mismatches due to both varying cocktail constituents and concentrations). The findings presented here support the need to understand fully the quenching systematics of a given LS system (combination of cocktails and spectrometer) and the need for very careful control of cocktail preparations. (author)

  8. A Mismatch EndoNuclease Array-Based Methodology (MENA) for Identifying Known SNPs or Novel Point Mutations.

    Science.gov (United States)

    Comeron, Josep M; Reed, Jordan; Christie, Matthew; Jacobs, Julia S; Dierdorff, Jason; Eberl, Daniel F; Manak, J Robert

    2016-04-05

    Accurate and rapid identification or confirmation of single nucleotide polymorphisms (SNPs), point mutations and other human genomic variation facilitates understanding the genetic basis of disease. We have developed a new methodology (called MENA (Mismatch EndoNuclease Array)) pairing DNA mismatch endonuclease enzymology with tiling microarray hybridization in order to genotype both known point mutations (such as SNPs) as well as identify previously undiscovered point mutations and small indels. We show that our assay can rapidly genotype known SNPs in a human genomic DNA sample with 99% accuracy, in addition to identifying novel point mutations and small indels with a false discovery rate as low as 10%. Our technology provides a platform for a variety of applications, including: (1) genotyping known SNPs as well as confirming newly discovered SNPs from whole genome sequencing analyses; (2) identifying novel point mutations and indels in any genomic region from any organism for which genome sequence information is available; and (3) screening panels of genes associated with particular diseases and disorders in patient samples to identify causative mutations. As a proof of principle for using MENA to discover novel mutations, we report identification of a novel allele of the beethoven (btv) gene in Drosophila, which encodes a ciliary cytoplasmic dynein motor protein important for auditory mechanosensation.

  9. Capacitor Mismatch Error Cancellation Technique for a Successive Approximation A/D Converter

    DEFF Research Database (Denmark)

    Zheng, Zhiliang; Moon, Un-Ku; Steensgaard-Madsen, Jesper

    1999-01-01

    An error cancellation technique is described for suppressing capacitor mismatch in a successive approximation A/D converter. At the cost of a 50% increase in conversion time, the first-order capacitor mismatch error is cancelled. Methods for achieving top-plate parasitic insensitive operation...... are described, and the use of a gain- and offset-compensated opamp is explained. SWITCAP simulation results show that the proposed 16-bit SAR ADC can achieve an SNDR of over 91 dB under non-ideal conditions, including 1% 3 sigma nominal capacitor mismatch, 10-20% randomized parasitic capacitors, 66 dB opamp...

  10. Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database

    DEFF Research Database (Denmark)

    Thompson, Bryony A; Spurdle, Amanda B; Plazzer, John-Paul

    2014-01-01

    and apply a standardized classification scheme to constitutional variants in the Lynch syndrome-associated genes MLH1, MSH2, MSH6 and PMS2. Unpublished data submission was encouraged to assist in variant classification and was recognized through microattribution. The scheme was refined by multidisciplinary...... are now possible for 1,370 variants that were not obviously protein truncating from nomenclature. This large-scale endeavor will facilitate the consistent management of families suspected to have Lynch syndrome and demonstrates the value of multidisciplinary collaboration in the curation......The clinical classification of hereditary sequence variants identified in disease-related genes directly affects clinical management of patients and their relatives. The International Society for Gastrointestinal Hereditary Tumours (InSiGHT) undertook a collaborative effort to develop, test...

  11. Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database

    NARCIS (Netherlands)

    Thompson, Bryony A.; Spurdle, Amanda B.; Plazzer, John-Paul; Greenblatt, Marc S.; Akagi, Kiwamu; Al-Mulla, Fahd; Bapat, Bharati; Bernstein, Inge; Capella, Gabriel; den Dunnen, Johan T.; du Sart, Desiree; Fabre, Aurelie; Farrell, Michael P.; Farrington, Susan M.; Frayling, Ian M.; Frebourg, Thierry; Goldgar, David E.; Heinen, Christopher D.; Holinski-Feder, Elke; Kohonen-Corish, Maija; Robinson, Kristina Lagerstedt; Leung, Suet Yi; Martins, Alexandra; Moller, Pal; Morak, Monika; Nystrom, Minna; Peltomaki, Paivi; Pineda, Marta; Qi, Ming; Ramesar, Rajkumar; Rasmussen, Lene Juel; Royer-Pokora, Brigitte; Scott, Rodney J.; Sijmons, Rolf; Tavtigian, Sean V.; Tops, Carli M.; Weber, Thomas; Wijnen, Juul; Woods, Michael O.; Macrae, Finlay; Genuardi, Maurizio

    The clinical classification of hereditary sequence variants identified in disease-related genes directly affects clinical management of patients and their relatives. The International Society for Gastrointestinal Hereditary Tumours (InSiGHT) undertook a collaborative effort to develop, test and

  12. Differentiation of schizophrenia patients from healthy subjects by mismatch negativity and neuropsychological tests.

    Directory of Open Access Journals (Sweden)

    Yi-Ting Lin

    Full Text Available BACKGROUND: Schizophrenia is a heterogeneous disorder with diverse presentations. The current and the proposed DSM-V diagnostic system remains phenomenologically based, despite the fact that several neurobiological and neuropsychological markers have been identified. A multivariate approach has better diagnostic utility than a single marker method. In this study, the mismatch negativity (MMN deficit of schizophrenia was first replicated in a Han Chinese population, and then the MMN was combined with several neuropsychological measurements to differentiate schizophrenia patients from healthy subjects. METHODOLOGY/PRINCIPAL FINDINGS: 120 schizophrenia patients and 76 healthy controls were recruited. Each subject received examinations for duration MMN, Continuous Performance Test, Wisconsin Card Sorting Test, and Wechsler Adult Intelligence Scale Third Edition (WAIS-III. The MMN was compared between cases and controls, and important covariates were investigated. Schizophrenia patients had significantly reduced MMN amplitudes, and MMN decreased with increasing age in both patient and control groups. None of the neuropsychological indices correlated with MMN. Predictive multivariate logistic regression models using the MMN and neuropsychological measurements as predictors were developed. Four predictors, including MMN at electrode FCz and three scores from the WAIS-III (Arithmetic, Block Design, and Performance IQ were retained in the final predictive model. The model performed well in differentiating patients from healthy subjects (percentage of concordant pairs: 90.5%. CONCLUSIONS/SIGNIFICANCE: MMN deficits were found in Han Chinese schizophrenia patients. The multivariate approach combining biomarkers from different modalities such as electrophysiology and neuropsychology had a better diagnostic utility.

  13. C-Terminal Fluorescent Labeling Impairs Functionality of DNA Mismatch Repair Proteins

    Science.gov (United States)

    Brieger, Angela; Plotz, Guido; Hinrichsen, Inga; Passmann, Sandra; Adam, Ronja; Zeuzem, Stefan

    2012-01-01

    The human DNA mismatch repair (MMR) process is crucial to maintain the integrity of the genome and requires many different proteins which interact perfectly and coordinated. Germline mutations in MMR genes are responsible for the development of the hereditary form of colorectal cancer called Lynch syndrome. Various mutations mainly in two MMR proteins, MLH1 and MSH2, have been identified so far, whereas 55% are detected within MLH1, the essential component of the heterodimer MutLα (MLH1 and PMS2). Most of those MLH1 variants are pathogenic but the relevance of missense mutations often remains unclear. Many different recombinant systems are applied to filter out disease-associated proteins whereby fluorescent tagged proteins are frequently used. However, dye labeling might have deleterious effects on MutLα's functionality. Therefore, we analyzed the consequences of N- and C-terminal fluorescent labeling on expression level, cellular localization and MMR activity of MutLα. Besides significant influence of GFP- or Red-fusion on protein expression we detected incorrect shuttling of single expressed C-terminal GFP-tagged PMS2 into the nucleus and found that C-terminal dye labeling impaired MMR function of MutLα. In contrast, N-terminal tagged MutLαs retained correct functionality and can be recommended both for the analysis of cellular localization and MMR efficiency. PMID:22348133

  14. C-terminal fluorescent labeling impairs functionality of DNA mismatch repair proteins.

    Directory of Open Access Journals (Sweden)

    Angela Brieger

    Full Text Available The human DNA mismatch repair (MMR process is crucial to maintain the integrity of the genome and requires many different proteins which interact perfectly and coordinated. Germline mutations in MMR genes are responsible for the development of the hereditary form of colorectal cancer called Lynch syndrome. Various mutations mainly in two MMR proteins, MLH1 and MSH2, have been identified so far, whereas 55% are detected within MLH1, the essential component of the heterodimer MutLα (MLH1 and PMS2. Most of those MLH1 variants are pathogenic but the relevance of missense mutations often remains unclear. Many different recombinant systems are applied to filter out disease-associated proteins whereby fluorescent tagged proteins are frequently used. However, dye labeling might have deleterious effects on MutLα's functionality. Therefore, we analyzed the consequences of N- and C-terminal fluorescent labeling on expression level, cellular localization and MMR activity of MutLα. Besides significant influence of GFP- or Red-fusion on protein expression we detected incorrect shuttling of single expressed C-terminal GFP-tagged PMS2 into the nucleus and found that C-terminal dye labeling impaired MMR function of MutLα. In contrast, N-terminal tagged MutLαs retained correct functionality and can be recommended both for the analysis of cellular localization and MMR efficiency.

  15. A massive parallel sequencing workflow for diagnostic genetic testing of mismatch repair genes

    Science.gov (United States)

    Hansen, Maren F; Neckmann, Ulrike; Lavik, Liss A S; Vold, Trine; Gilde, Bodil; Toft, Ragnhild K; Sjursen, Wenche

    2014-01-01

    The purpose of this study was to develop a massive parallel sequencing (MPS) workflow for diagnostic analysis of mismatch repair (MMR) genes using the GS Junior system (Roche). A pathogenic variant in one of four MMR genes, (MLH1, PMS2, MSH6, and MSH2), is the cause of Lynch Syndrome (LS), which mainly predispose to colorectal cancer. We used an amplicon-based sequencing method allowing specific and preferential amplification of the MMR genes including PMS2, of which several pseudogenes exist. The amplicons were pooled at different ratios to obtain coverage uniformity and maximize the throughput of a single-GS Junior run. In total, 60 previously identified and distinct variants (substitutions and indels), were sequenced by MPS and successfully detected. The heterozygote detection range was from 19% to 63% and dependent on sequence context and coverage. We were able to distinguish between false-positive and true-positive calls in homopolymeric regions by cross-sample comparison and evaluation of flow signal distributions. In addition, we filtered variants according to a predefined status, which facilitated variant annotation. Our study shows that implementation of MPS in routine diagnostics of LS can accelerate sample throughput and reduce costs without compromising sensitivity, compared to Sanger sequencing. PMID:24689082

  16. Mismatch repair deficiency does not enhance ENU mutagenesis in the zebrafish germ line.

    Science.gov (United States)

    Feitsma, Harma; de Bruijn, Ewart; van de Belt, Jose; Nijman, Isaac J; Cuppen, Edwin

    2008-07-01

    S(N)1-type alkylating agents such as N-ethyl-N-nitrosourea (ENU) are very potent mutagens. They act by transferring their alkyl group to DNA bases, which, upon mispairing during replication, can cause single base pair mutations in the next replication cycle. As DNA mismatch repair (MMR) proteins are involved in the recognition of alkylation damage, we hypothesized that ENU-induced mutation rates could be increased in a MMR-deficient background, which would be beneficial for mutagenesis approaches. We applied a standard ENU mutagenesis protocol to adult zebrafish deficient in the MMR gene msh6 and heterozygous controls to study the effect of MMR on ENU-induced DNA damage. Dose-dependent lethality was found to be similar for homozygous and heterozygous mutants, indicating that there is no difference in ENU resistance. Mutation discovery by high-throughput dideoxy resequencing of genomic targets in outcrossed progeny of the mutagenized fish did also not reveal any differences in germ line mutation frequency. These results may indicate that the maximum mutation load for zebrafish has been reached with the currently used, highly optimized ENU mutagenesis protocol. Alternatively, the MMR system in the zebrafish germ line may be saturated very rapidly, thereby having a limited effect on high-dose ENU mutagenesis.

  17. HLA-inferred extended haplotype disparity level is more relevant than the level of HLA mismatch alone for the patients survival and GvHD in T cell-replate hematopoietic stem cell transplantation from unrelated donor.

    Science.gov (United States)

    Nowak, Jacek; Nestorowicz, Klaudia; Graczyk-Pol, Elzbieta; Mika-Witkowska, Renata; Rogatko-Koros, Marta; Jaskula, Emilia; Koscinska, Katarzyna; Madej, Sylwia; Tomaszewska, Agnieszka; Nasilowska-Adamska, Barbara; Szczepinski, Andrzej; Halaburda, Kazimierz; Dybko, Jaroslaw; Kuliczkowski, Kazimierz; Czerw, Tomasz; Giebel, Sebastian; Holowiecki, Jerzy; Baranska, Malgorzata; Pieczonka, Anna; Wachowiak, Jacek; Czyz, Anna; Gil, Lidia; Lojko-Dankowska, Anna; Komarnicki, Mieczyslaw; Bieniaszewska, Maria; Kucharska, Agnieszka; Hellmann, Andrzej; Gronkowska, Anna; Jedrzejczak, Wieslaw W; Markiewicz, Miroslaw; Koclega, Anna; Kyrcz-Krzemien, Slawomira; Mielcarek, Monika; Kalwak, Krzysztof; Styczynski, Jan; Wysocki, Mariusz; Drabko, Katarzyna; Wojcik, Beata; Kowalczyk, Jerzy; Gozdzik, Jolanta; Pawliczak, Daria; Gwozdowicz, Slawomir; Dziopa, Joanna; Szlendak, Urszula; Witkowska, Agnieszka; Zubala, Marta; Gawron, Agnieszka; Warzocha, Krzysztof; Lange, Andrzej

    2018-06-01

    Serious risks in unrelated hematopoietic stem cell transplantation (HSCT) including graft versus host disease (GvHD) and mortality are associated with HLA disparity between donor and recipient. The increased risks might be dependent on disparity in not-routinely-tested multiple polymorphisms in genetically dense MHC region, being organized in combinations of two extended MHC haplotypes (Ehp). We assessed the clinical role of donor-recipient Ehp disparity levels in N = 889 patients by the population-based detection of HLA allele phase mismatch. We found increased GvHD incidences and mortality rates with increasing Ehp mismatch level even with the same HLA mismatch level. In multivariate analysis HLA mismatch levels were excluded from models and Ehp disparity level remained independent prognostic factor for high grade acute GvHD (p = 0.000037, HR = 10.68, 95%CI 5.50-32.5) and extended chronic GvHD (p < 0.000001, HR = 15.51, CI95% 5.36-44.8). In group with single HLA mismatch, patients with double Ehp disparity had worse 5-year overall survival (45% vs. 56%, p = 0.00065, HR = 4.05, CI95% 1.69-9.71) and non-relapse mortality (40% vs. 31%, p = 0.00037, HR = 5.63, CI95% 2.04-15.5) than patients with single Ehp disparity. We conclude that Ehp-linked factors contribute to the high morbidity and mortality in recipients given HLA-mismatched unrelated transplant and Ehp matching should be considered in clinical HSCT. Copyright © 2018. Published by Elsevier Inc.

  18. Mood As Cumulative Expectation Mismatch: A Test of Theory Based on Data from Non-verbal Cognitive Bias Tests

    Directory of Open Access Journals (Sweden)

    Camille M. C. Raoult

    2017-12-01

    Full Text Available Affective states are known to influence behavior and cognitive processes. To assess mood (moderately long-term affective states, the cognitive judgment bias test was developed and has been widely used in various animal species. However, little is known about how mood changes, how mood can be experimentally manipulated, and how mood then feeds back into cognitive judgment. A recent theory argues that mood reflects the cumulative impact of differences between obtained outcomes and expectations. Here expectations refer to an established context. Situations in which an established context fails to match an outcome are then perceived as mismatches of expectation and outcome. We take advantage of the large number of studies published on non-verbal cognitive bias tests in recent years (95 studies with a total of 162 independent tests to test whether cumulative mismatch could indeed have led to the observed mood changes. Based on a criteria list, we assessed whether mismatch had occurred with the experimental procedure used to induce mood (mood induction mismatch, or in the context of the non-verbal cognitive bias procedure (testing mismatch. For the mood induction mismatch, we scored the mismatch between the subjects’ potential expectations and the manipulations conducted for inducing mood whereas, for the testing mismatch, we scored mismatches that may have occurred during the actual testing. We then investigated whether these two types of mismatch can predict the actual outcome of the cognitive bias study. The present evaluation shows that mood induction mismatch cannot well predict the success of a cognitive bias test. On the other hand, testing mismatch can modulate or even inverse the expected outcome. We think, cognitive bias studies should more specifically aim at creating expectation mismatch while inducing mood states to test the cumulative mismatch theory more properly. Furthermore, testing mismatch should be avoided as much as possible

  19. Human mismatch repair protein hMutLα is required to repair short slipped-DNAs of trinucleotide repeats.

    Science.gov (United States)

    Panigrahi, Gagan B; Slean, Meghan M; Simard, Jodie P; Pearson, Christopher E

    2012-12-07

    Mismatch repair (MMR) is required for proper maintenance of the genome by protecting against mutations. The mismatch repair system has also been implicated as a driver of certain mutations, including disease-associated trinucleotide repeat instability. We recently revealed a requirement of hMutSβ in the repair of short slip-outs containing a single CTG repeat unit (1). The involvement of other MMR proteins in short trinucleotide repeat slip-out repair is unknown. Here we show that hMutLα is required for the highly efficient in vitro repair of single CTG repeat slip-outs, to the same degree as hMutSβ. HEK293T cell extracts, deficient in hMLH1, are unable to process single-repeat slip-outs, but are functional when complemented with hMutLα. The MMR-deficient hMLH1 mutant, T117M, which has a point mutation proximal to the ATP-binding domain, is defective in slip-out repair, further supporting a requirement for hMLH1 in the processing of short slip-outs and possibly the involvement of hMHL1 ATPase activity. Extracts of hPMS2-deficient HEC-1-A cells, which express hMLH1, hMLH3, and hPMS1, are only functional when complemented with hMutLα, indicating that neither hMutLβ nor hMutLγ is sufficient to repair short slip-outs. The resolution of clustered short slip-outs, which are poorly repaired, was partially dependent upon a functional hMutLα. The joint involvement of hMutSβ and hMutLα suggests that repeat instability may be the result of aberrant outcomes of repair attempts.

  20. Mutation at the Human D1S80 Minisatellite Locus

    Directory of Open Access Journals (Sweden)

    Kuppareddi Balamurugan

    2012-01-01

    Full Text Available Little is known about the general biology of minisatellites. The purpose of this study is to examine repeat mutations from the D1S80 minisatellite locus by sequence analysis to elucidate the mutational process at this locus. This is a highly polymorphic minisatellite locus, located in the subtelomeric region of chromosome 1. We have analyzed 90,000 human germline transmission events and found seven (7 mutations at this locus. The D1S80 alleles of the parentage trio, the child, mother, and the alleged father were sequenced and the origin of the mutation was determined. Using American Association of Blood Banks (AABB guidelines, we found a male mutation rate of 1.04×10-4 and a female mutation rate of 5.18×10-5 with an overall mutation rate of approximately 7.77×10-5. Also, in this study, we found that the identified mutations are in close proximity to the center of the repeat array rather than at the ends of the repeat array. Several studies have examined the mutational mechanisms of the minisatellites according to infinite allele model (IAM and the one-step stepwise mutation model (SMM. In this study, we found that this locus fits into the one-step mutation model (SMM mechanism in six out of seven instances similar to STR loci.

  1. Band anticrossing effects in highly mismatched semiconductor alloys

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Junqiao [Univ. of California, Berkeley, CA (United States)

    2002-01-01

    The first five chapters of this thesis focus on studies of band anticrossing (BAC) effects in highly electronegativity- mismatched semiconductor alloys. The concept of bandgap bowing has been used to describe the deviation of the alloy bandgap from a linear interpolation. Bowing parameters as large as 2.5 eV (for ZnSTe) and close to zero (for AlGaAs and ZnSSe) have been observed experimentally. Recent advances in thin film deposition techniques have allowed the growth of semiconductor alloys composed of significantly different constituents with ever- improving crystalline quality (e.g., GaAs1-xNx and GaP1-xNx with x ~< 0.05). These alloys exhibit many novel and interesting properties including, in particular, a giant bandgap bowing (bowing parameters > 14 eV). A band anticrossing model has been developed to explain these properties. The model shows that the predominant bowing mechanism in these systems is driven by the anticrossing interaction between the localized level associated with the minority component and the band states of the host. In this thesis I discuss my studies of the BAC effects in these highly mismatched semiconductors. It will be shown that the results of the physically intuitive BAC model can be derived from the Hamiltonian of the many-impurity Anderson model. The band restructuring caused by the BAC interaction is responsible for a series of experimental observations such as a large bandgap reduction, an enhancement of the electron effective mass, and a decrease in the pressure coefficient of the fundamental gap energy. Results of further experimental investigations of the optical properties of quantum wells based on these materials will be also presented. It will be shown that the BAC interaction occurs not only between localized states and conduction band states at the Brillouin zone center, but also exists over all of k-space. Finally, taking ZnSTe and ZnSeTe as examples, I show that BAC also

  2. Mismatch repair and treatment resistance in ovarian cancer

    International Nuclear Information System (INIS)

    Helleman, Jozien; Staveren, Iris L van; Dinjens, Winand NM; Kuijk, Patricia F van; Ritstier, Kirsten; Ewing, Patricia C; Burg, Maria EL van der; Stoter, Gerrit; Berns, Els MJJ

    2006-01-01

    The treatment of ovarian cancer is hindered by intrinsic or acquired resistance to platinum-based chemotherapy. The aim of this study is to determine the frequency of mismatch repair (MMR) inactivation in ovarian cancer and its association with resistance to platinum-based chemotherapy. We determined, microsatellite instability (MSI) as a marker for MMR inactivation (analysis of BAT25 and BAT26), MLH1 promoter methylation status (methylation specific PCR on bisulfite treated DNA) and mRNA expression of MLH1, MSH2, MSH3, MSH6 and PMS2 (quantitative RT-PCR) in 75 ovarian carcinomas and eight ovarian cancer cell lines MSI was detected in three of the eight cell lines i.e. A2780 (no MLH1 mRNA expression due to promoter methylation), SKOV3 (no MLH1 mRNA expression) and 2774 (no altered expression of MMR genes). Overall, there was no association between cisplatin response and MMR status in these eight cell lines. Seven of the 75 ovarian carcinomas showed MLH1 promoter methylation, however, none of these showed MSI. Forty-six of these patients received platinum-based chemotherapy (11 non-responders, 34 responders, one unknown response). The resistance seen in the eleven non-responders was not related to MSI and therefore also not to MMR inactivation. No MMR inactivation was detected in 75 ovarian carcinoma specimens and no association was seen between MMR inactivation and resistance in the ovarian cancer cell lines as well as the ovarian carcinomas. In the discussion, the results were compared to that of twenty similar studies in the literature including in total 1315 ovarian cancer patients. Although no association between response and MMR status was seen in the primary tumor the possible role of MMR inactivation in acquired resistance deserves further investigation

  3. Mismatch repair and treatment resistance in ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Helleman, Jozien; Staveren, Iris L van [Department of Medical Oncology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Dinjens, Winand NM [Department of Pathology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Kuijk, Patricia F van; Ritstier, Kirsten [Department of Medical Oncology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Ewing, Patricia C [Department of Pathology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Burg, Maria EL van der; Stoter, Gerrit [Department of Medical Oncology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Berns, Els MJJ [Department of Medical Oncology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Erasmus MC, Department of Medical Oncology, Josephine Nefkens Institute, Room Be424, P.O. Box 1738, 3000 DR (Netherlands)

    2006-07-31

    The treatment of ovarian cancer is hindered by intrinsic or acquired resistance to platinum-based chemotherapy. The aim of this study is to determine the frequency of mismatch repair (MMR) inactivation in ovarian cancer and its association with resistance to platinum-based chemotherapy. We determined, microsatellite instability (MSI) as a marker for MMR inactivation (analysis of BAT25 and BAT26), MLH1 promoter methylation status (methylation specific PCR on bisulfite treated DNA) and mRNA expression of MLH1, MSH2, MSH3, MSH6 and PMS2 (quantitative RT-PCR) in 75 ovarian carcinomas and eight ovarian cancer cell lines MSI was detected in three of the eight cell lines i.e. A2780 (no MLH1 mRNA expression due to promoter methylation), SKOV3 (no MLH1 mRNA expression) and 2774 (no altered expression of MMR genes). Overall, there was no association between cisplatin response and MMR status in these eight cell lines. Seven of the 75 ovarian carcinomas showed MLH1 promoter methylation, however, none of these showed MSI. Forty-six of these patients received platinum-based chemotherapy (11 non-responders, 34 responders, one unknown response). The resistance seen in the eleven non-responders was not related to MSI and therefore also not to MMR inactivation. No MMR inactivation was detected in 75 ovarian carcinoma specimens and no association was seen between MMR inactivation and resistance in the ovarian cancer cell lines as well as the ovarian carcinomas. In the discussion, the results were compared to that of twenty similar studies in the literature including in total 1315 ovarian cancer patients. Although no association between response and MMR status was seen in the primary tumor the possible role of MMR inactivation in acquired resistance deserves further investigation.

  4. Mismatch repair and treatment resistance in ovarian cancer

    Directory of Open Access Journals (Sweden)

    van der Burg Maria EL

    2006-07-01

    Full Text Available Abstract Background The treatment of ovarian cancer is hindered by intrinsic or acquired resistance to platinum-based chemotherapy. The aim of this study is to determine the frequency of mismatch repair (MMR inactivation in ovarian cancer and its association with resistance to platinum-based chemotherapy. Methods We determined, microsatellite instability (MSI as a marker for MMR inactivation (analysis of BAT25 and BAT26, MLH1 promoter methylation status (methylation specific PCR on bisulfite treated DNA and mRNA expression of MLH1, MSH2, MSH3, MSH6 and PMS2 (quantitative RT-PCR in 75 ovarian carcinomas and eight ovarian cancer cell lines Results MSI was detected in three of the eight cell lines i.e. A2780 (no MLH1 mRNA expression due to promoter methylation, SKOV3 (no MLH1 mRNA expression and 2774 (no altered expression of MMR genes. Overall, there was no association between cisplatin response and MMR status in these eight cell lines. Seven of the 75 ovarian carcinomas showed MLH1 promoter methylation, however, none of these showed MSI. Forty-six of these patients received platinum-based chemotherapy (11 non-responders, 34 responders, one unknown response. The resistance seen in the eleven non-responders was not related to MSI and therefore also not to MMR inactivation. Conclusion No MMR inactivation was detected in 75 ovarian carcinoma specimens and no association was seen between MMR inactivation and resistance in the ovarian cancer cell lines as well as the ovarian carcinomas. In the discussion, the results were compared to that of twenty similar studies in the literature including in total 1315 ovarian cancer patients. Although no association between response and MMR status was seen in the primary tumor the possible role of MMR inactivation in acquired resistance deserves further investigation.

  5. Beyond the real world: attention debates in auditory mismatch negativity.

    Science.gov (United States)

    Chung, Kyungmi; Park, Jin Young

    2018-04-11

    The aim of this study was to address the potential for the auditory mismatch negativity (aMMN) to be used in applied event-related potential (ERP) studies by determining whether the aMMN would be an attention-dependent ERP component and could be differently modulated across visual tasks or virtual reality (VR) stimuli with different visual properties and visual complexity levels. A total of 80 participants, aged 19-36 years, were assigned to either a reading-task (21 men and 19 women) or a VR-task (22 men and 18 women) group. Two visual-task groups of healthy young adults were matched in age, sex, and handedness. All participants were instructed to focus only on the given visual tasks and ignore auditory change detection. While participants in the reading-task group read text slides, those in the VR-task group viewed three 360° VR videos in a random order and rated how visually complex the given virtual environment was immediately after each VR video ended. Inconsistent with the finding of a partial significant difference in perceived visual complexity in terms of brightness of virtual environments, both visual properties of distance and brightness showed no significant differences in the modulation of aMMN amplitudes. A further analysis was carried out to compare elicited aMMN amplitudes of a typical MMN task and an applied VR task. No significant difference in the aMMN amplitudes was found across the two groups who completed visual tasks with different visual-task demands. In conclusion, the aMMN is a reliable ERP marker of preattentive cognitive processing for auditory deviance detection.

  6. Mismatch negativity in chronic schizophrenia and first-episode schizophrenia.

    Science.gov (United States)

    Salisbury, Dean F; Shenton, Martha E; Griggs, Carlye B; Bonner-Jackson, Aaron; McCarley, Robert W

    2002-08-01

    Mismatch negativity (MMN) is an event-related brain potential that is sensitive to stimulus deviation from a repetitive pattern. The MMN is thought primarily to reflect the activity of sensory memory, with, at most, moderate influences of higher-level cognitive processes, such as attention. The MMN is reported to be reduced in patients with chronic schizophrenia. However, it is unknown whether MMN is reduced in patients with first-episode schizophrenia (at first hospitalization). Subject groups comprised patients with chronic schizophrenia (n = 16) and older control subjects (n = 13), and patients with first-episode schizophrenia (n = 21) and younger control subjects (n = 27). The MMN was visualized by subtracting the averaged event-related brain potential to standard tones (1 kHz [95% of all tones]) from the event-related brain potential to pitch-deviant tones (1.2 kHz [5% of all tones]). The MMN voltage was the mean voltage from 100 to 200 milliseconds. Pitch-deviant MMN was reduced by approximately 47% in patients with chronic illness along the sagittal midline relative to controls. The MMN was not reduced in patients with first-episode schizophrenia. All 4 groups showed approximately 64% larger MMN to pitch-deviant tones over the right hemisphere compared with the left hemisphere. The pitch-deviant MMN reductions present in patients with chronic schizophrenia are not present at first hospitalization. The sensory, echoic memory functions indexed by MMN seem unaffected early in the schizophrenia disease process. Reductions in MMN amplitude may develop over time and index the progression of the disorder, although that can only be definitively determined by longitudinal assessments.

  7. Processing of unattended facial emotions: a visual mismatch negativity study.

    Science.gov (United States)

    Stefanics, Gábor; Csukly, Gábor; Komlósi, Sarolta; Czobor, Pál; Czigler, István

    2012-02-01

    Facial emotions express our internal states and are fundamental in social interactions. Here we explore whether the repetition of unattended facial emotions builds up a predictive representation of frequently encountered emotions in the visual system. Participants (n=24) were presented peripherally with facial stimuli expressing emotions while they performed a visual detection task presented in the center of the visual field. Facial stimuli consisted of four faces of different identity, but expressed the same emotion (happy or fearful). Facial stimuli were presented in blocks of oddball sequence (standard emotion: p=0.9, deviant emotion: p=0.1). Event-related potentials (ERPs) to the same emotions were compared when the emotions were deviant and standard, respectively. We found visual mismatch negativity (vMMN) responses to unattended deviant emotions in the 170-360 ms post-stimulus range over bilateral occipito-temporal sites. Our results demonstrate that information about the emotional content of unattended faces presented at the periphery of the visual field is rapidly processed and stored in a predictive memory representation by the visual system. We also found evidence that differential processing of deviant fearful faces starts already at 70-120 ms after stimulus onset. This finding shows a 'negativity bias' under unattended conditions. Differential processing of fearful deviants were more pronounced in the right hemisphere in the 195-275 ms and 360-390 ms intervals, whereas processing of happy deviants evoked larger differential response in the left hemisphere in the 360-390 ms range, indicating differential hemispheric specialization for automatic processing of positive and negative affect. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Effect of aripiprazole on mismatch negativity (MMN in schizophrenia.

    Directory of Open Access Journals (Sweden)

    Zhenhe Zhou

    Full Text Available BACKGROUND: Cognitive deficits are considered core symptoms of the schizophrenia. Cognitive function has been found to be a better predictor of functional outcome than symptom levels. Changed mismatch negativity (MMN reflects abnormalities of early auditory processing in schizophrenia. Up to now, no studies for the effects of aripiprazole on MMN in schizophrenia have been reported. METHODOLOGY/PRINCIPAL FINDINGS: Subjects included 26 patients with schizophrenia, and 26 controls. Psychopathology was rated in patients with the Positive and Negative Syndrome Scale (PANSS at baseline, after 4- and 8-week treatments with aripiprazole. Auditory stimuli for ERP consisted of 100 millisecond/1000 Hz standards, intermixed with 100 millisecond/1500 Hz frequency deviants and 250 millisecond/1000 Hz duration deviants. EEG was recorded at Fz. BESA 5.1.8 was used to perform data analysis. MMN waveforms were obtained by subtracting waveforms elicited by standards from waveforms elicited by frequency- or duration-deviant stimuli. Aripiprazole decreased all PANSS. Patients showed smaller mean amplitudes of frequency and duration MMN at baseline than did controls. A repeated measure ANOVA with sessions (i.e., baseline, 4- and 8-week treatments and MMN type (frequency vs. duration as within-subject factors revealed no significant MMN type or MMN type × session main effect for MMN amplitudes. Session main effect was significant. LSD tests demonstrated significant differences between MMN amplitudes at 8 weeks and those at both baseline and 4 weeks. There was significant negative correlation between changes in amplitudes of frequency and duration MMN and changes in PANSS total scores at baseline and follow-up periods. CONCLUSIONS: Aripiprazole improved the amplitudes of MMN. MMN offers objective evidence that treatment with the aripiprazole may ameliorate preattentive deficits in schizophrenia.

  9. Mismatched racial identities, colourism, and health in Toronto and Vancouver.

    Science.gov (United States)

    Veenstra, Gerry

    2011-10-01

    Using original telephone survey data collected from adult residents of Toronto (n = 685) and Vancouver (n = 814) in 2009, I investigate associations between mental and physical health and variously conceived racial identities. An 'expressed racial identity' is a self-identification with a racial grouping that a person will readily express to others when asked to fit into official racial classifications presented by Census forms, survey researchers, insurance forms, and the like. Distinguishing between Asian, Black, South Asian, and White expressed racial identities, I find that survey respondents expressing Black identity are the most likely to report high blood pressure or hypertension, a risk that is slightly attenuated by socioeconomic status, and that respondents expressing Asian identity are the most likely to report poorer self-rated mental health and self-rated overall health, risks that are not explained by socioeconomic status. I also find that darker-skinned Black respondents are more likely than lighter-skinned Black respondents to report poor health outcomes, indicating that colourism, processes of discrimination which privilege lighter-skinned people of colour over their darker-skinned counterparts, exists and has implications for well-being in Canada as it does in the United States. Finally, 'reflected racial identity' refers to the racial identity that a person believes that others tend to perceive him or her to be. I find that expressed and reflected racial identities differ from one another for large proportions of self-expressed Black and South Asian respondents and relatively few self-expressed White and Asian respondents. I also find that mismatched racial identities correspond with relatively high risks of various poor health outcomes, especially for respondents who consider themselves White but believe that others tend to think they are something else. I conclude by presenting a framework for conceptualizing multifaceted suites of racial

  10. Evaluating Mismatch Repair Deficiency in Pancreatic Adenocarcinoma: Challenges and Recommendations.

    Science.gov (United States)

    Hu, Zishuo I; Shia, Jinru; Stadler, Zsofia K; Varghese, Anna M; Capanu, Marinela; Salo-Mullen, Erin; Lowery, Maeve A; Diaz, Luis A; Mandelker, Diana; Yu, Kenneth H; Zervoudakis, Alice; Kelsen, David P; Iacobuzio-Donahue, Christine A; Klimstra, David S; Saltz, Leonard B; Sahin, Ibrahim H; O'Reilly, Eileen M

    2018-03-15

    Purpose: Immune checkpoint inhibition has been shown to generate profound and durable responses in mismatch repair deficient (MMR-D) solid tumors and has elicited interest in detection tools and strategies to guide therapeutic decision-making. Herein we address questions on the appropriate screening, detection methods, patient selection, and initiation of therapy for MMR-D pancreatic ductal adenocarcinoma (PDAC) and assess the utility of next-generation sequencing (NGS) in providing additional prognostic and predictive information for MMR-D PDAC. Experimental Design: Archival and prospectively acquired samples and matched normal DNA from N = 833 PDAC cases were analyzed using a hybridization capture-based, NGS assay designed to perform targeted deep sequencing of all exons and selected introns of 341 to 468 cancer-associated genes. A computational program using NGS data derived the MSI status from the tumor-normal paired genome sequencing data. Available germline testing, IHC, and microsatellite instability (MSI) PCR results were reviewed to assess and confirm MMR-D and MSI status. Results: MMR-D in PDAC is a rare event among PDAC patients (7/833), occurring at a frequency of 0.8%. Loss of MMR protein expression by IHC, high mutational load, and elevated MSIsensor scores were correlated with MMR-D PDAC. All 7 MMR-D PDAC patients in the study were found to have Lynch syndrome. Four (57%) of the MMR-D patients treated with immune checkpoint blockade had treatment benefit (1 complete response, 2 partial responses, 1 stable disease). Conclusions: An integrated approach of germline testing and somatic analyses of tumor tissues in advanced PDAC using NGS may help guide future development of immune and molecularly directed therapies in PDAC patients. Clin Cancer Res; 24(6); 1326-36. ©2018 AACR . ©2018 American Association for Cancer Research.

  11. Sex-specific effects of naturally occurring variants in the dopamine receptor D2 locus on insulin secretion and Type 2 diabetes susceptibility

    NARCIS (Netherlands)

    Guigas, B.; Leeuw van Weenen, J.E. de; van Leeuwen, N.; Simonis-Bik, A.M.; Haeften, T.W. van; Nijpels, G.; Houwing-Duistermaat, J.J.; Beekman, M.; Deelen, J.; Havekes, L.M.; Penninx, B.W.J.H.; Vogelzangs, N.; Riet, E. van 't; Dehghan, A.; Hofman, A.; Witteman, J.C.; Uitterlinden, A.G.; Grarup, N.; Jørgensen, T.; Witte, D.R.; Lauritzen, T.; Hansen, T.; Pedersen, O.; Hottenga, J.; Romijn, J.A.; Diamant, M.; Kramer, M.H.H.; Heine, R.J.; Willemsen, G.; Dekker, J.M.; Eekhoff, E.M.; Pijl, H.; Geus, E.J. de; Slagboom, P.E.; Hart, L.M. 't

    2014-01-01

    Aims: Modulation of dopamine receptor D2 (DRD2) activity affects insulin secretion in both rodents and isolated pancreatic β-cells. We hypothesized that single nucleotide polymorphisms in the DRD2/ANKK1 locus may affect susceptibility to Type 2 diabetes in humans. Methods: Four potentially

  12. AIDS Health Locus of Control, Self-Efficacy for Safer Sexual Practices, and Future Time Orientation as Predictors of Condom Use in African American College Students

    Science.gov (United States)

    Burns, Myron J.; Dillon, Frank R.

    2005-01-01

    This study examined the relationship between self-reported frequency of condom use (by self or partner during the past 6 months and lifetime), locus of control, self-efficacy, and future time orientation among African American college students who were single and sexually active during the past year. Data were collected from 106 undergraduate…

  13. A candidate type 2 diabetes polymorphism near the HHEX locus affects acute glucose-stimulated insulin release in European populations: results from the EUGENE2 study

    DEFF Research Database (Denmark)

    Staiger, Harald; Stancáková, Alena; Zilinskaite, Jone

    2008-01-01

    OBJECTIVE: In recent genome-wide association studies, two single nucleotide polymorphisms (SNPs) near the HHEX locus were shown to be more frequent in type 2 diabetic patients than in control subjects. Based on HHEX's function during embryonic development of the ventral pancreas in mice, we inves...

  14. Unraveling of the polymorphic C lambda 2-C lambda 3 amplification and the Ke+Oz- polymorphism in the human Ig lambda locus

    NARCIS (Netherlands)

    M. van der Burg (Mirjam); B.H. Barendregt (Barbara); E.J. van Gastel-Mol (Ellen); T. Tümkaya (Talip); A.W. Langerak (Anton); J.J.M. van Dongen (Jacques)

    2002-01-01

    textabstractTwo polymorphisms of the human Ig(lambda) (IGL) locus have been described. The first polymorphism concerns a single, 2- or 3-fold amplification of 5.4 kb of DNA in the C(lambda)2-C(lambda)3 region. The second polymorphism is the Mcg(-)Ke(+)Oz(-) isotype, which has

  15. Minimizing the effect of process mismatch in a neuromorphic system using spike-timing-dependent adaptation.

    Science.gov (United States)

    Cameron, Katherine; Murray, Alan

    2008-05-01

    This paper investigates whether spike-timing-dependent plasticity (STDP) can minimize the effect of mismatch within the context of a depth-from-motion algorithm. To improve noise rejection, this algorithm contains a spike prediction element, whose performance is degraded by analog very large scale integration (VLSI) mismatch. The error between the actual spike arrival time and the prediction is used as the input to an STDP circuit, to improve future predictions. Before STDP adaptation, the error reflects the degree of mismatch within the prediction circuitry. After STDP adaptation, the error indicates to what extent the adaptive circuitry can minimize the effect of transistor mismatch. The circuitry is tested with static and varying prediction times and chip results are presented. The effect of noisy spikes is also investigated. Under all conditions the STDP adaptation is shown to improve performance.

  16. A Direct Adaptive Control Approach in the Presence of Model Mismatch

    Science.gov (United States)

    Joshi, Suresh M.; Tao, Gang; Khong, Thuan

    2009-01-01

    This paper considers the problem of direct model reference adaptive control when the plant-model matching conditions are violated due to abnormal changes in the plant or incorrect knowledge of the plant's mathematical structure. The approach consists of direct adaptation of state feedback gains for state tracking, and simultaneous estimation of the plant-model mismatch. Because of the mismatch, the plant can no longer track the state of the original reference model, but may be able to track a new reference model that still provides satisfactory performance. The reference model is updated if the estimated plant-model mismatch exceeds a bound that is determined via robust stability and/or performance criteria. The resulting controller is a hybrid direct-indirect adaptive controller that offers asymptotic state tracking in the presence of plant-model mismatch as well as parameter deviations.

  17. Perceived match or mismatch on the Gottman conflict styles: associations with relationship outcome variables.

    Science.gov (United States)

    Busby, Dean M; Holman, Thomas B

    2009-12-01

    Gottman has proposed that there are 3 functional styles of conflict management in couple relationships, labeled Avoidant, Validating, and Volatile, and 1 dysfunctional style, labeled Hostile. Using a sample of 1,983 couples in a committed relationship, we test the association of perceived matches or mismatches on these conflict styles with relationship outcome variables. The results indicate that 32% of the participants perceive there is a mismatch with their conflict style and that of their partner. The Volatile-Avoidant mismatch was particularly problematic and was associated with more stonewalling, relationship problems, and lower levels of relationship satisfaction and stability than the Validating matched style and than other mismatched styles. The most problematic style was the Hostile style. Contrary to existing assumptions by Gottman, the 3 matched functional styles were not equivalent, as the Validating Style was associated with substantially better results on relationship outcome measures than the Volatile and Avoidant styles.

  18. The conceptual mismatch: transportation stressors and experiences for low-income adults.

    Science.gov (United States)

    2015-10-01

    Physical access to jobs has long been identified as a barrier to employment and earnings, with prior : research identifying the spatial mismatch between suburban entry-level jobs and low-income workers. : However, existing transportation resear...

  19. Mismatch or cumulative stress : Toward an integrated hypothesis of programming effects

    NARCIS (Netherlands)

    Nederhof, Esther; Schmidt, Mathias V.

    2012-01-01

    This paper integrates the cumulative stress hypothesis with the mismatch hypothesis, taking into account individual differences in sensitivity to programming. According to the cumulative stress hypothesis, individuals are more likely to suffer from disease as adversity accumulates. According to the

  20. New Spectral Method for Halo Particle Definition in Intense Mis-matched Beams

    Energy Technology Data Exchange (ETDEWEB)

    Dorf, Mikhail A.; Davidson, Ronald C.; Startsev, Edward A.

    2011-04-27

    An advanced spectral analysis of a mis-matched charged particle beam propagating through a periodic focusing transport lattice is utilized in particle-in-cell (PIC) simulations. It is found that the betatron frequency distribution function of a mismatched space-charge-dominated beam has a bump-on-tail structure attributed to the beam halo particles. Based on this observation, a new spectral method for halo particle definition is proposed that provides the opportunity to carry out a quantitative analysis of halo particle production by a beam mismatch. In addition, it is shown that the spectral analysis of the mismatch relaxation process provides important insights into the emittance growth attributed to the halo formation and the core relaxation processes. Finally, the spectral method is applied to the problem of space-charge transport limits.

  1. Immunohistochemistry for PMS2 and MSH6 alone can replace a four antibody panel for mismatch repair deficiency screening in colorectal adenocarcinoma.

    Science.gov (United States)

    Hall, Geoffrey; Clarkson, Adele; Shi, Amanda; Langford, Eileen; Leung, Helen; Eckstein, Robert P; Gill, Anthony J

    2010-01-01

    Currently, testing for mismatch repair deficiency in colorectal cancers is initiated by performing immunohistochemistry with four antibodies (MLH1, PMS2, MSH2 and MSH6). If any one of these stains is negative the tumour is considered microsatellite unstable and, if clinical circumstances warrant it, the patient is offered genetic testing for Lynch's syndrome. Due to the binding properties of the mismatch repair heterodimer complexes, gene mutation and loss of MLH1 and MSH2 invariably result in the degradation of PMS2 and MSH6, respectively, but the converse is not true. We propose that staining for PMS2 and MSH6 alone will be sufficient to detect all cases of mismatch repair deficiency and should replace routine screening with all four antibodies. The electronic database of the department of Anatomical Pathology, Royal North Shore Hospital, Sydney, Australia, was searched for all colorectal carcinomas on which a four panel immunohistochemical microsatellite instability screen was performed. An audit of the slides for concordant loss of MLH1-PMS2 and MSH2-MSH6 was then undertaken. Unusual or discordant cases were reviewed and, in some cases, re-stained to confirm the staining pattern. Of 344 cases of colorectal cancer which underwent four antibody immunohistochemistry, 104 displayed loss of at least one mismatch repair protein. Of these, 100 showed concordant mismatch repair loss (i.e., loss of MLH1 and PMS2 or loss of MSH2 and MSH6). The four discordant cases comprised two single negative cases (1 MSH6 negative/MSH2 positive case, 1 PMS2 negative/MLH1 positive) and two triple negative (both MLH1/PMS2/MSH6 negative). The microsatellite instability (MSI) group showed a relatively high median age (69.3 years) due to the departmental policy of testing all cases with possible MSI morphology regardless of age. The sensitivity and specificity of a two panel test comprised of PMS2 and MSH6, compared to a four panel test, is 100%. No false negatives or positives were

  2. A homozygous PMS2 founder mutation with an attenuated constitutional mismatch repair deficiency phenotype.

    Science.gov (United States)

    Li, Lili; Hamel, Nancy; Baker, Kristi; McGuffin, Michael J; Couillard, Martin; Gologan, Adrian; Marcus, Victoria A; Chodirker, Bernard; Chudley, Albert; Stefanovici, Camelia; Durandy, Anne; Hegele, Robert A; Feng, Bing-Jian; Goldgar, David E; Zhu, Jun; De Rosa, Marina; Gruber, Stephen B; Wimmer, Katharina; Young, Barbara; Chong, George; Tischkowitz, Marc D; Foulkes, William D

    2015-05-01

    Inherited mutations in DNA mismatch repair genes predispose to different cancer syndromes depending on whether they are mono-allelic or bi-allelic. This supports a causal relationship between expression level in the germline and phenotype variation. As a model to study this relationship, our study aimed to define the pathogenic characteristics of a recurrent homozygous coding variant in PMS2 displaying an attenuated phenotype identified by clinical genetic testing in seven Inuit families from Northern Quebec. Pathogenic characteristics of the PMS2 mutation NM_000535.5:c.2002A>G were studied using genotype-phenotype correlation, single-molecule expression detection and single genome microsatellite instability analysis. This PMS2 mutation generates a de novo splice site that competes with the authentic site. In homozygotes, expression of the full-length protein is reduced to a level barely detectable by conventional diagnostics. Median age at primary cancer diagnosis is 22 years among 13 NM_000535.5:c.2002A>G homozygotes, versus 8 years in individuals carrying bi-allelic truncating mutations. Residual expression of full-length PMS2 transcript was detected in normal tissues from homozygotes with cancers in their 20s. Our genotype-phenotype study of c.2002A>G illustrates that an extremely low level of PMS2 expression likely delays cancer onset, a feature that could be exploited in cancer preventive intervention. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  3. Exploring the relationship between educational mismatch, earnings and job satisfaction in the tourism industry

    OpenAIRE

    Lillo-Bañuls, Adelaida; Casado-Díaz, José M.

    2015-01-01

    This article analyses the interrelationship between educational mismatch, wages and job satisfaction in the Spanish tourism sector in the first years of the global economic crisis. It is shown that there is a much higher incidence of over-education among workers in the Spanish tourism sector than in the rest of the economy despite this sector recording lower educational levels. This study estimates two models to analyse the influence of the educational mismatch on wages and job satisfaction f...

  4. DNA mismatch repair deficiency in sporadic colorectal cancer and Lynch Syndrome

    OpenAIRE

    Poulogiannis , George; Frayling , Ian; Arends , Mark

    2009-01-01

    Abstract DNA mismatch repair (MMR) deficiency is one of the best understood forms of genetic instability in colorectal cancer (CRC), and is characterised by the loss of function of the MMR pathway. Failure to repair replication-associated errors due to a defective MMR system allows persistence of mismatch mutations all over the genome, but especially in regions of repetitive DNA known as microsatellites, giving rise to the phenomenon of microsatellite instability (MSI). A high freq...

  5. Patient - implant dimension mismatch in total knee arthroplasty: Is it worth worrying? An Indian scenario

    Directory of Open Access Journals (Sweden)

    Jai Thilak

    2016-01-01

    Full Text Available Background: The correct sizing of the components in both anteroposterior and mediolateral (ML dimensions is crucial for the success of a total knee arthroplasty (TKA. The size of the implants selected is based on the intraoperative measurements. The currently used TKA implants available to us are based on morphometric measurements obtained from a Western/Caucasian population. Hence, the risk of component ML mismatch is more common in Asian sub-population, as they are of a smaller built and stature. This study aims to look into the following aspects agnitude of the ML mismatch between the femoral component and the patient′s anatomical dimension, evaluation of gender variations in distal femur dimensions, and gender-wise and implant-wise correlation of ML mismatch. Materials and Methods: Intraoperatively, the distal femoral dimensions were measured using sterile calipers after removing the osteophytes and compared with the ML dimension of the implant used. ML mismatch length thus obtained is correlated with the various parameters. Results: Males showed larger distal femoral dimensions when compared to females. Males had larger ML mismatch. None of the implants used perfectly matched the patient′s anatomical dimensions. Patients with larger mismatch had lower scorings at 2 years postoperative followup. Conclusion: Implant manufacturers need to design more options of femoral implants for a better fit in our subset of patients. The exact magnitude of mismatch which can cause functional implications need to be made out. The mismatch being one of the important factors for the success of the surgery, we should focus more on this aspect.

  6. Impact of aortic prosthesis-patient mismatch on left ventricular mass regression.

    Science.gov (United States)

    Alassal, Mohamed A; Ibrahim, Bedir M; Elsadeck, Nabil

    2014-06-01

    Prostheses used for aortic valve replacement may be small in relation to body size, causing prosthesis-patient mismatch and delaying left ventricular mass regression. This study examined the effect of prosthesis-patient mismatch on regression of left ventricular mass after aortic valve replacement. We prospectively studied 96 patients undergoing aortic valve replacement between 2007 and 2012. Mean and peak gradients and indexed effective orifice area were measured by transthoracic echocardiography at 3 and 6 months postoperatively. Patient-prosthesis mismatch was defined as indexed effective orifice area ≤0.85 cm(2)·m(-2). Moderate prosthesis-patient mismatch was present in 25% of patients. There were no significant differences in demographic and operative data between patients with and without prosthesis-patient mismatch. Left ventricular dimensions, posterior wall thickness, transvalvular gradients, and left ventricular mass decreased significantly after aortic valve replacement in both groups. The interventricular septal diameter and left ventricular mass index regression, and left ventricular ejection fraction were better in patients without prosthesis-patient mismatch. There was a significant positive correlation between the postoperative indexed effective orifice area of each valve prosthesis and the rate of left ventricular mass regression. Prosthesis-patient mismatch leads to higher transprosthetic gradients and impaired left ventricular mass regression. A small-sized valve prosthesis does not necessarily result in prosthesis-patient mismatch, and may be perfectly adequate in patient with small body size. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  7. Detecting mismatches of bird migration stopover and tree phenology in response to changing climate

    Science.gov (United States)

    Kellermann, Jherime L.; van Riper, Charles

    2015-01-01

    Migratory birds exploit seasonal variation in resources across latitudes, timing migration to coincide with the phenology of food at stopover sites. Differential responses to climate in phenology across trophic levels can result in phenological mismatch; however, detecting mismatch is sensitive to methodology. We examined patterns of migrant abundance and tree flowering, phenological mismatch, and the influence of climate during spring migration from 2009 to 2011 across five habitat types of the Madrean Sky Islands in southeastern Arizona, USA. We used two metrics to assess phenological mismatch: synchrony and overlap. We also examined whether phenological overlap declined with increasing difference in mean event date of phenophases. Migrant abundance and tree flowering generally increased with minimum spring temperature but depended on annual climate by habitat interactions. Migrant abundance was lowest and flowering was highest under cold, snowy conditions in high elevation montane conifer habitat while bird abundance was greatest and flowering was lowest in low elevation riparian habitat under the driest conditions. Phenological synchrony and overlap were unique and complementary metrics and should both be used when assessing mismatch. Overlap declined due to asynchronous phenologies but also due to reduced migrant abundance or flowering when synchrony was actually maintained. Overlap declined with increasing difference in event date and this trend was strongest in riparian areas. Montane habitat specialists may be at greatest risk of mismatch while riparian habitat could provide refugia during dry years for phenotypically plastic species. Interannual climate patterns that we observed match climate change projections for the arid southwest, altering stopover habitat condition.

  8. BatMis: a fast algorithm for k-mismatch mapping.

    Science.gov (United States)

    Tennakoon, Chandana; Purbojati, Rikky W; Sung, Wing-Kin

    2012-08-15

    Second-generation sequencing (SGS) generates millions of reads that need to be aligned to a reference genome allowing errors. Although current aligners can efficiently map reads allowing a small number of mismatches, they are not well suited for handling a large number of mismatches. The efficiency of aligners can be improved using various heuristics, but the sensitivity and accuracy of the alignments are sacrificed. In this article, we introduce Basic Alignment tool for Mismatches (BatMis)--an efficient method to align short reads to a reference allowing k mismatches. BatMis is a Burrows-Wheeler transformation based aligner that uses a seed and extend approach, and it is an exact method. Benchmark tests show that BatMis performs better than competing aligners in solving the k-mismatch problem. Furthermore, it can compete favorably even when compared with the heuristic modes of the other aligners. BatMis is a useful alternative for applications where fast k-mismatch mappings, unique mappings or multiple mappings of SGS data are required. BatMis is written in C/C++ and is freely available from http://code.google.com/p/batmis/

  9. [Observation and analysis on mutation of routine STR locus].

    Science.gov (United States)

    Li, Qiu-yang; Feng, Wei-jun; Yang, Qin-gen

    2005-05-01

    To observe and analyze the characteristic of mutation at STR locus. 27 mutant genes observed in 1211 paternity testing cases were checked by PAGE-silver stained and PowerPlex 16 System Kit and validated by sequencing. Mutant genes locate on 15 loci. The pattern of mutation was accord with stepwise mutation model. The mutation ratio of male-to-female was 8:1 and correlated to the age of father. Mutation rate is correlated to the geometric mean of the number of homogeneous repeats of locus. The higher the mean, the higher the mutation rate. These loci are not so appropriate for use in paternity testing.

  10. Genetic and physical maps around the sex-determining M-locus of the dioecious plant asparagus.

    Science.gov (United States)

    Telgmann-Rauber, Alexa; Jamsari, Ari; Kinney, Michael S; Pires, J Chris; Jung, Christian

    2007-09-01

    Asparagus officinalis L. is a dioecious plant. A region called the M-locus located on a pair of homomorphic sex chromosomes controls the sexual dimorphism in asparagus. The aim of this work was to clone the region determining sex in asparagus from its position in the genome. The structure of the region encompassing M should be investigated and compared to the sex-determining regions in other dioecious model species. To establish an improved basis for physical mapping, a high-resolution genetic map was enriched with AFLP markers closely linked to the target locus by carrying out a bulked segregant analysis. By screening a BAC library with AFLP- and STS-markers followed by chromosome walking, a physical map with eight contigs could be established. However, the gaps between the contigs could not be closed due to a plethora of repetitive elements. Surprisingly, two of the contigs on one side of the M-locus did not overlap although they have been established with two markers, which mapped in a distance as low as 0.25 cM flanking the sex locus. Thus, the clustering of the markers indicates a reduced recombination frequency within the M-region. On the opposite side of the M-locus, a contig was mapped in a distance of 0.38 cM. Four closely linked BAC clones were partially sequenced and 64 putative ORFs were identified. Interestingly, only 25% of the ORFs showed sequence similarity to known proteins and ESTs. In addition, an accumulation of repetitive sequences and a low gene density was revealed in the sex-determining region of asparagus. Molecular cytogenetic and sequence analysis of BACs flanking the M-locus indicate that the BACs contain highly repetitive sequences that localize to centromeric and pericentromeric locations on all asparagus chromosomes, which hindered the localization of the M-locus to the single pair of sex chromosomes. We speculate that dioecious Silene, papaya and Asparagus species may represent three stages in the evolution of XX, XY sex

  11. Analysis of positional candidate genes in the AAA1 susceptibility locus for abdominal aortic aneurysms on chromosome 19

    Directory of Open Access Journals (Sweden)

    Ferrell Robert E

    2011-01-01

    Full Text Available Abstract Background Abdominal aortic aneurysm (AAA is a complex disorder with multiple genetic risk factors. Using affected relative pair linkage analysis, we previously identified an AAA susceptibility locus on chromosome 19q13. This locus has been designated as the AAA1 susceptibility locus in the Online Mendelian Inheritance in Man (OMIM database. Methods Nine candidate genes were selected from the AAA1 locus based on their function, as well as mRNA expression levels in the aorta. A sample of 394 cases and 419 controls was genotyped for 41 SNPs located in or around the selected nine candidate genes using the Illumina GoldenGate platform. Single marker and haplotype analyses were performed. Three genes (CEBPG, PEPD and CD22 were selected for DNA sequencing based on the association study results, and exonic regions were analyzed. Immunohistochemical staining of aortic tissue sections from AAA and control individuals was carried out for the CD22 and PEPD proteins with specific antibodies. Results Several SNPs were nominally associated with AAA (p CEBPG, peptidase D (PEPD, and CD22. Haplotype analysis found a nominally associated 5-SNP haplotype in the CEBPG/PEPD locus, as well as a nominally associated 2-SNP haplotype in the CD22 locus. DNA sequencing of the coding regions revealed no variation in CEBPG. Seven sequence variants were identified in PEPD, including three not present in the NCBI SNP (dbSNP database. Sequencing of all 14 exons of CD22 identified 20 sequence variants, five of which were in the coding region and six were in the 3'-untranslated region. Five variants were not present in dbSNP. Immunohistochemical staining for CD22 revealed protein expression in lymphocytes present in the aneurysmal aortic wall only and no detectable expression in control aorta. PEPD protein was expressed in fibroblasts and myofibroblasts in the media-adventitia border in both aneurysmal and non-aneurysmal tissue samples. Conclusions Association testing

  12. Pms2 and uracil-DNA glycosylases act jointly in the mismatch repair pathway to generate Ig gene mutations at A-T base pairs.

    Science.gov (United States)

    Girelli Zubani, Giulia; Zivojnovic, Marija; De Smet, Annie; Albagli-Curiel, Olivier; Huetz, François; Weill, Jean-Claude; Reynaud, Claude-Agnès; Storck, Sébastien

    2017-04-03

    During somatic hypermutation (SHM) of immunoglobulin genes, uracils introduced by activation-induced cytidine deaminase are processed by uracil-DNA glycosylase (UNG) and mismatch repair (MMR) pathways to generate mutations at G-C and A-T base pairs, respectively. Paradoxically, the MMR-nicking complex Pms2/Mlh1 is apparently dispensable for A-T mutagenesis. Thus, how detection of U:G mismatches is translated into the single-strand nick required for error-prone synthesis is an open question. One model proposed that UNG could cooperate with MMR by excising a second uracil in the vicinity of the U:G mismatch, but it failed to explain the low impact of UNG inactivation on A-T mutagenesis. In this study, we show that uracils generated in the G1 phase in B cells can generate equal proportions of A-T and G-C mutations, which suggests that UNG and MMR can operate within the same time frame during SHM. Furthermore, we show that Ung -/- Pms2 -/- mice display a 50% reduction in mutations at A-T base pairs and that most remaining mutations at A-T bases depend on two additional uracil glycosylases, thymine-DNA glycosylase and SMUG1. These results demonstrate that Pms2/Mlh1 and multiple uracil glycosylases act jointly, each one with a distinct strand bias, to enlarge the immunoglobulin gene mutation spectrum from G-C to A-T bases. © 2017 Girelli Zubani et al.

  13. Sex-specific effects of naturally occurring variants in the dopamine receptor D2 locus on insulin secretion and Type 2 diabetes susceptibility

    DEFF Research Database (Denmark)

    Guigas, B; de Leeuw van Weenen, J E; van Leeuwen, N

    2014-01-01

    AIMS: Modulation of dopamine receptor D2 (DRD2) activity affects insulin secretion in both rodents and isolated pancreatic β-cells. We hypothesized that single nucleotide polymorphisms in the DRD2/ANKK1 locus may affect susceptibility to Type 2 diabetes in humans. METHODS: Four potentially....... In addition, 340 Dutch subjects underwent a 2-h hyperglycaemic clamp to investigate insulin secretion. Since sexual dimorphic associations related to DRD2 polymorphisms have been previously reported, we also performed a gender-stratified analysis. RESULTS: rs1800497 at the DRD2/ANKK1 locus was associated...

  14. Experimental J estimation from a load-cmod curve for mis-matched SENB and CCT specimens

    International Nuclear Information System (INIS)

    Hornet, P.; Eripret, Ch.; Hao, S.

    1997-01-01

    This paper addresses the problem of the determination of the J-integral from experimentally measured quantities for mismatched Single Notched Bend specimens (SENB) or through thickness Centre Cracked panels loaded in Tension (CCT). Commonly, the experimental J-integral is calculated from the area under the load versus load-line displacement curve. Nevertheless, in the case of gross-section yielding, which can occur for short cracked specimens or overmatching cases, this methodology mis-estimates the effective J-integral. A new proposal, based on analytical considerations is made to estimate the J-integral from the area under load versus CMOD curves. This proposal is validated by 2D and 3D finite element analyses. (authors)

  15. Effect of epitaxial strain and lattice mismatch on magnetic and transport behaviors in metamagnetic FeRh thin films

    Science.gov (United States)

    Xie, Yali; Zhan, Qingfeng; Shang, Tian; Yang, Huali; Wang, Baomin; Tang, Jin; Li, Run-Wei

    2017-05-01

    We grew 80 nm FeRh films on different single crystals with various lattice constants. FeRh films on SrTiO3 (STO) and MgO substrates exhibit an epitaxial growth of 45° in-plane structure rotation. In contrast, FeRh on LaAlO3 (LAO) displays a mixed epitaxial growth of both 45° in-plane structure rotation and cube-on-cube relationships. Due to the different epitaxial growth strains and lattice mismatch values, the critical temperature for the magnetic phase transition of FeRh can be changed between 405 and 360 K. In addition, the external magnetic field can shift this critical temperature to low temperature in different rates for FeRh films grown on different substrates. The magnetoresistance appears a maximum value at different temperatures between 320 and 380 K for FeRh films grown on different substrates.

  16. Effect of epitaxial strain and lattice mismatch on magnetic and transport behaviors in metamagnetic FeRh thin films

    Directory of Open Access Journals (Sweden)

    Yali Xie

    2017-05-01

    Full Text Available We grew 80 nm FeRh films on different single crystals with various lattice constants. FeRh films on SrTiO3 (STO and MgO substrates exhibit an epitaxial growth of 45° in-plane structure rotation. In contrast, FeRh on LaAlO3 (LAO displays a mixed epitaxial growth of both 45° in-plane structure rotation and cube-on-cube relationships. Due to the different epitaxial growth strains and lattice mismatch values, the critical temperature for the magnetic phase transition of FeRh can be changed between 405 and 360 K. In addition, the external magnetic field can shift this critical temperature to low temperature in different rates for FeRh films grown on different substrates. The magnetoresistance appears a maximum value at different temperatures between 320 and 380 K for FeRh films grown on different substrates.

  17. Heterotic trait locus (HTL) mapping identifies intra-locus interactions that underlie reproductive hybrid vigor in Sorghum bicolor.

    Science.gov (United States)

    Ben-Israel, Imri; Kilian, Benjamin; Nida, Habte; Fridman, Eyal

    2012-01-01

    Identifying intra-locus interactions underlying heterotic variation among whole-genome hybrids is a key to understanding mechanisms of heterosis and exploiting it for crop and livestock improvement. In this study, we present the development and first use of the heterotic trait locus (HTL) mapping approach to associate specific intra-locus interactions with an overdominant heterotic mode of inheritance in a diallel population using Sorghum bicolor as the model. This method combines the advantages of ample genetic diversity and the possibility of studying non-additive inheritance. Furthermore, this design enables dissecting the latter to identify specific intra-locus interactions. We identified three HTLs (3.5% of loci tested) with synergistic intra-locus effects on overdominant grain yield heterosis in 2 years of field trials. These loci account for 19.0% of the heterotic variation, including a significant interaction found between two of them. Moreover, analysis of one of these loci (hDPW4.1) in a consecutive F2 population confirmed a significant 21% increase in grain yield of heterozygous vs. homozygous plants in this locus. Notably, two of the three HTLs for grain yield are in synteny with previously reported overdominant quantitative trait loci for grain yield in maize. A mechanism for the reproductive heterosis found in this study is suggested, in which grain yield increase is achieved by releasing the compensatory tradeoffs between biomass and reproductive output, and between seed number and weight. These results highlight the power of analyzing a diverse set of inbreds and their hybrids for unraveling hitherto unknown allelic interactions mediating heterosis.

  18. Homozygous germ-line mutation of the PMS2 mismatch repair gene: a unique case report of constitutional mismatch repair deficiency (CMMRD).

    Science.gov (United States)

    Ramchander, N C; Ryan, N A J; Crosbie, E J; Evans, D G

    2017-04-05

    Constitutional mismatch repair deficiency syndrome results from bi-allelic inheritance of mutations affecting the key DNA mismatch repair genes: MLH1, MSH2, MSH6 or PMS2. Individuals with bi-allelic mutations have a dysfunctional mismatch repair system from birth; as a result, constitutional mismatch repair deficiency syndrome is characterised by early onset malignancies. Fewer than 150 cases have been reported in the literature over the past 20 years. This is the first report of the founder PMS2 mutation - NM_000535.5:c.1500del (p.Val501TrpfsTer94) in exon 11 and its associated cancers in this family. The proband is 30 years old and is alive today. She is of Pakistani ethnic origin and a product of consanguinity. She initially presented aged 24 with painless bleeding per-rectum from colorectal polyps and was referred to clinical genetics. Clinical examination revealed two café-au-lait lesions, lichen planus, and a dermoid cyst. Her sister had been diagnosed in childhood with an aggressive brain tumour followed by colorectal cancer. During follow up, the proband developed 37 colorectal adenomatous polyps, synchronous ovarian and endometrial adenocarcinomas, and ultimately a metachronous gastric adenocarcinoma. DNA sequencing of peripheral lymphocytes revealed a bi-allelic inheritance of the PMS2 mutation NM_000535.5:c.1500del (p.Val501TrpfsTer94) in exon 11. Ovarian tumour tissue demonstrated low microsatellite instability. To date, she has had a total abdominal hysterectomy, bilateral salpingo-oophorectomy, and a total gastrectomy. Aspirin and oestrogen-only hormone replacement therapy provide some chemoprophylaxis and manage postmenopausal symptoms, respectively. An 18-monthly colonoscopy surveillance programme has led to the excision of three high-grade dysplastic colorectal tubular adenomatous polyps. The proband's family pedigree displays multiple relatives with cancers including a likely case of 'true' Turcot syndrome. Constitutional mismatch repair

  19. The DAOA/G30 locus and affective disorders: haplotype based association study in a polydiagnostic approach

    Directory of Open Access Journals (Sweden)

    Knapp Michael

    2010-07-01

    Full Text Available Abstract Background The DAOA/G30 (D-amino acid oxidase activator gene complex at chromosomal region 13q32-33 is one of the most intriguing susceptibility loci for the major psychiatric disorders, although there is no consensus about the specific risk alleles or haplotypes across studies. Methods In a case-control sample of German descent (affective psychosis: n = 248; controls: n = 188 we examined seven single nucleotide polymorphisms (SNPs around DAOA/G30 (rs3916966, rs1935058, rs2391191, rs1935062, rs947267, rs3918342, and rs9558575 for genetic association in a polydiagnostic approach (ICD 10; Leonhard's classification. Results No single marker showed evidence of overall association with affective disorder neither in ICD10 nor Leonhard's classification. Haplotype analysis revealed no association with recurrent unipolar depression or bipolar disorder according to ICD10, within Leonhard's classification manic-depression was associated with a 3-locus haplotype (rs2391191, rs1935062, and rs3916966; P = 0.022 and monopolar depression with a 5-locus combination at the DAOA/G30 core region (P = 0.036. Conclusion Our data revealed potential evidence for partially overlapping risk haplotypes at the DAOA/G30 locus in Leonhard's affective psychoses, but do not support a common genetic contribution of the DAOA/G30 gene complex to the pathogenesis of affective disorders.

  20. Mismatch and misalignment: dark haloes and satellites of disc galaxies

    Science.gov (United States)

    Deason, A. J.; McCarthy, I. G.; Font, A. S.; Evans, N. W.; Frenk, C. S.; Belokurov, V.; Libeskind, N. I.; Crain, R. A.; Theuns, T.

    2011-08-01

    We study the phase-space distribution of satellite galaxies associated with late-type galaxies in the GIMIC suite of simulations. GIMIC consists of resimulations of five cosmologically representative regions from the Millennium Simulation, which have higher resolution and incorporate baryonic physics. Whilst the disc of the galaxy is well aligned with the inner regions (r˜ 0.1r200) of the dark matter halo, both in shape and angular momentum, there can be substantial misalignments at larger radii (r˜r200). Misalignments of >45° are seen in ˜30 per cent of our sample. We find that the satellite population aligns with the shape (and angular momentum) of the outer dark matter halo. However, the alignment with the galaxy is weak owing to the mismatch between the disc and dark matter halo. Roughly 20 per cent of the satellite systems with 10 bright galaxies within r200 exhibit a polar spatial alignment with respect to the galaxy - an orientation reminiscent of the classical satellites of the Milky Way. We find that a small fraction (˜10 per cent) of satellite systems show evidence for rotational support which we attribute to group infall. There is a bias towards satellites on prograde orbits relative to the spin of the dark matter halo (and to a lesser extent with the angular momentum of the disc). This preference towards co-rotation is stronger in the inner regions of the halo where the most massive satellites accreted at relatively early times are located. We attribute the anisotropic spatial distribution and angular momentum bias of the satellites at z= 0 to their directional accretion along the major axes of the dark matter halo. The satellite galaxies have been accreted relatively recently compared to the dark matter mass and have experienced less phase-mixing and relaxation - the memory of their accretion history can remain intact to z= 0. Understanding the phase-space distribution of the z= 0 satellite population is key for studies that estimate the host halo

  1. Adaptation to diverse nitrogen-limited environments by deletion or extrachromosomal element formation of the GAP1 locus

    DEFF Research Database (Denmark)

    Gresham, D.; Usaite, Renata; Germann, S.M.

    2010-01-01

    and deletions at the GAP1 locus. GAP1 encodes the general amino acid permease, which transports amino acids across the plasma membrane. We identified a self-propagating extrachromosomal circular DNA molecule that results from intrachromosomal recombination between long terminal repeats (LTRs) flanking GAP1....... Extrachromosomal DNA circles (GAP1(circle)) contain GAP1, the replication origin ARS1116, and a single hybrid LTR derived from recombination between the two flanking LTRs. Formation of the GAP1(circle) is associated with deletion of chromosomal GAP1 (gap1 Delta) and production of a single hybrid LTR at the GAP1...

  2. Significant Locus and Metabolic Genetic Correlations Revealed in Genome-Wide Association Study of Anorexia Nervosa.

    Science.gov (United States)

    Duncan, Laramie; Yilmaz, Zeynep; Gaspar, Helena; Walters, Raymond; Goldstein, Jackie; Anttila, Verneri; Bulik-Sullivan, Brendan; Ripke, Stephan; Thornton, Laura; Hinney, Anke; Daly, Mark; Sullivan, Patrick F; Zeggini, Eleftheria; Breen, Gerome; Bulik, Cynthia M

    2017-09-01

    The authors conducted a genome-wide association study of anorexia nervosa and calculated genetic correlations with a series of psychiatric, educational, and metabolic phenotypes. Following uniform quality control and imputation procedures using the 1000 Genomes Project (phase 3) in 12 case-control cohorts comprising 3,495 anorexia nervosa cases and 10,982 controls, the authors performed standard association analysis followed by a meta-analysis across cohorts. Linkage disequilibrium score regression was used to calculate genome-wide common variant heritability (single-nucleotide polymorphism [SNP]-based heritability [h 2 SNP ]), partitioned heritability, and genetic correlations (r g ) between anorexia nervosa and 159 other phenotypes. Results were obtained for 10,641,224 SNPs and insertion-deletion variants with minor allele frequencies >1% and imputation quality scores >0.6. The h 2 SNP of anorexia nervosa was 0.20 (SE=0.02), suggesting that a substantial fraction of the twin-based heritability arises from common genetic variation. The authors identified one genome-wide significant locus on chromosome 12 (rs4622308) in a region harboring a previously reported type 1 diabetes and autoimmune disorder locus. Significant positive genetic correlations were observed between anorexia nervosa and schizophrenia, neuroticism, educational attainment, and high-density lipoprotein cholesterol, and significant negative genetic correlations were observed between anorexia nervosa and body mass index, insulin, glucose, and lipid phenotypes. Anorexia nervosa is a complex heritable phenotype for which this study has uncovered the first genome-wide significant locus. Anorexia nervosa also has large and significant genetic correlations with both psychiatric phenotypes and metabolic traits. The study results encourage a reconceptualization of this frequently lethal disorder as one with both psychiatric and metabolic etiology.

  3. Characterisation of monotreme caseins reveals lineage-specific expansion of an ancestral casein locus in mammals.

    Science.gov (United States)

    Lefèvre, Christophe M; Sharp, Julie A; Nicholas, Kevin R

    2009-01-01

    Using a milk-cell cDNA sequencing approach we characterised milk-protein sequences from two monotreme species, platypus (Ornithorhynchus anatinus) and echidna (Tachyglossus aculeatus) and found a full set of caseins and casein variants. The genomic organisation of the platypus casein locus is compared with other mammalian genomes, including the marsupial opossum and several eutherians. Physical linkage of casein genes has been seen in the casein loci of all mammalian genomes examined and we confirm that this is also observed in platypus. However, we show that a recent duplication of beta-casein occurred in the monotreme lineage, as opposed to more ancient duplications of alpha-casein in the eutherian lineage, while marsupials possess only single copies of alpha- and beta-caseins. Despite this variability, the close proximity of the main alpha- and beta-casein genes in an inverted tail-tail orientation and the relative orientation of the more distant kappa-casein genes are similar in all mammalian genome sequences so far available. Overall, the conservation of the genomic organisation of the caseins indicates the early, pre-monotreme development of the fundamental role of caseins during lactation. In contrast, the lineage-specific gene duplications that have occurred within the casein locus of monotremes and eutherians but not marsupials, which may have lost part of the ancestral casein locus, emphasises the independent selection on milk provision strategies to the young, most likely linked to different developmental strategies. The monotremes therefore provide insight into the ancestral drivers for lactation and how these have adapted in different lineages.

  4. Evaluation of potential regulatory function of breast cancer risk locus at 6q25.1.

    Science.gov (United States)

    Sun, Yaqiong; Ye, Chuanzhong; Guo, Xingyi; Wen, Wanqing; Long, Jirong; Gao, Yu-Tang; Shu, Xiao Ou; Zheng, Wei; Cai, Qiuyin

    2016-02-01

    In a genome-wide association study conducted among Chinese women, we identified the single nucleotide polymorphism (SNP) rs2046210 at 6q25.1 for breast cancer risk. To explore a potential regulatory role for this risk locus, we measured expression levels of nine genes at the locus in breast cancer tissue and adjacent normal tissue samples obtained from 67 patients recruited in the Shanghai Breast Cancer Study. We found that rs2046210 had a statistically significant association with the expression levels of the AKAP12 and ESR1 genes in adjacent normal breast tissues. Women who carry the AA/AG risk genotypes had higher expressions of these two genes compared to those who carry G/G genotypes (P = 0.02 and 0.04 for the AKAP12 and ESR1, respectively). However, no significant differences of SNP rs2046210 with gene expression levels were found in tumor tissues. In The Cancer Genome Atlas samples, the AA/AG risk genotypes of SNP rs2046210 were associated with a significantly higher expression level of the AKAP12 gene and a lower level of the ESR1 gene in tumor tissue. Functional analysis using ENCODE data revealed that SNP rs7763637, which is in strong linkage disequilibrium with SNP rs2046210, is likely a potential functional variant, regulating the AKAP12 gene. Taken together, these results from our study suggest that the association between the 6q25.1 locus and breast cancer risk may be mediated through SNPs that regulate expressions of the AKAP12 gene. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Identification of candidate regions for a novel Usher syndrome type II locus.

    Science.gov (United States)

    Ben Rebeh, Imen; Benzina, Zeineb; Dhouib, Houria; Hadjamor, Imen; Amyere, Mustapha; Ayadi, Leila; Turki, Khalil; Hammami, Bouthaina; Kmiha, Noureddine; Kammoun, Hassen; Hakim, Bochra; Charfedine, Ilhem; Vikkula, Miikka; Ghorbel, Abdelmonem; Ayadi, Hammadi; Masmoudi, Saber

    2008-09-19

    Chronic diseases affecting the inner ear and the retina cause severe impairments to our communication systems. In more than half of the cases, Usher syndrome (USH) is the origin of these double defects. Patients with USH type II (USH2) have retinitis pigmentosa (RP) that develops during puberty, moderate to severe hearing impairment with downsloping pure-tone audiogram, and normal vestibular function. Four loci and three genes are known for USH2. In this study, we proposed to localize the gene responsible for USH2 in a consanguineous family of Tunisian origin. Affected members underwent detailed ocular and audiologic characterization. One Tunisian family with USH2 and 45 healthy controls unrelated to the family were recruited. Two affected and six unaffected family members attended our study. DNA samples of eight family members were genotyped with polymorphic markers. Two-point and multipoint LOD scores were calculated using Genehunter software v2.1. Sequencing was used to investigate candidate genes. Haplotype analysis showed no significant linkage to any known USH gene or locus. A genome-wide screen, using microsatellite markers, was performed, allowing the identification of three homozygous regions in chromosomes 2, 4, and 15. We further confirmed and refined these three regions using microsatellite and single-nucleotide polymorphisms. With recessive mode of inheritance, the highest multipoint LOD score of 1.765 was identified for the candidate regions on chromosomes 4 and 15. The chromosome 15 locus is large (55 Mb), underscoring the limited number of meioses in the consanguineous pedigree. Moreover, the linked, homozygous chromosome 15q alleles, unlike those of the chromosome 2 and 4 loci, are infrequent in the local population. Thus, the data strongly suggest that the novel locus for USH2 is likely to reside on 15q. Our data provide a basis for the localization and the identification of a novel gene implicated in USH2, most likely localized on 15q.

  6. Advancing the match-mismatch framework for large herbivores in the Arctic: Evaluating the evidence for a trophic mismatch in caribou.

    Directory of Open Access Journals (Sweden)

    David Gustine

    Full Text Available Climate-induced shifts in plant phenology may adversely affect animals that cannot or do not shift the timing of their reproductive cycle. The realized effect of potential trophic "mismatches" between a consumer and its food varies with the degree to which species rely on dietary income and stored capital. Large Arctic herbivores rely heavily on maternal capital to reproduce and give birth near the onset of the growing season but are they vulnerable to trophic mismatch? We evaluated the long-term changes in the temperatures and characteristics of the growing seasons (1970-2013, and compared growing conditions and dynamics of forage quality for caribou at peak parturition, peak lactation, and peak forage biomass, and plant senescence between two distinct time periods over 36 years (1977 and 2011-13. Despite advanced thaw dates (7-12 days earlier, increased growing season lengths (15-21 days longer, and consistent parturition dates, we found no decline in forage quality and therefore no evidence within this dataset for a trophic mismatch at peak parturition or peak lactation from 1977 to 2011-13. In Arctic ungulates that use stored capital for reproduction, reproductive demands are largely met by body stores deposited in the previous summer and autumn, which reduces potential adverse effects of any mismatch between food availability and timing of parturition. Climate-induced effects on forages growing in the summer and autumn ranges, however, do correspond with the demands of female caribou and their offspring to gain mass for the next reproductive cycle and winter. Therefore, we suggest the window of time to examine the match-mismatch framework in Arctic ungulates is not at parturition but in late summer-autumn, where the multiplier effects of small changes in forage quality are amplified by forage abundance, peak forage intake, and resultant mass gains in mother-offspring pairs.

  7. Rank-based characterization of pollen assemblages collected by honey bees using a multi-locus metabarcoding approach.

    Science.gov (United States)

    Richardson, Rodney T; Lin, Chia-Hua; Quijia, Juan O; Riusech, Natalia S; Goodell, Karen; Johnson, Reed M

    2015-11-01

    Difficulties inherent in microscopic pollen identification have resulted in limited implementation for large-scale studies. Metabarcoding, a relatively novel approach, could make pollen analysis less onerous; however, improved understanding of the quantitative capacity of various plant metabarcode regions and primer sets is needed to ensure that such applications are accurate and precise. We applied metabarcoding, targeting the ITS2, matK, and rbcL loci, to characterize six samples of pollen collected by honey bees, Apis mellifera. Additionally, samples were analyzed by light microscopy. We found significant rank-based associations between the relative abundance of pollen types within our samples as inferred by the two methods. Our findings suggest metabarcoding data from plastid loci, as opposed to the ribosomal locus, are more reliable for quantitative characterization of pollen assemblages. Furthermore, multilocus metabarcoding of pollen may be more reliable than single-locus analyses, underscoring the need for discovering novel barcodes and barcode combinations optimized for molecular palynology.

  8. FISH-mapping of the 5S rDNA locus in chili peppers (Capsicum-Solanaceae).

    Science.gov (United States)

    Aguilera, Patricia M; Debat, Humberto J; Scaldaferro, Marisel A; Martí, Dardo A; Grabiele, Mauro

    2016-03-01

    We present here the physical mapping of the 5S rDNA locus in six wild and five cultivated taxa of Capsicum by means of a genus-specific FISH probe. In all taxa, a single 5S locus per haploid genome that persistently mapped onto the short arm of a unique metacentric chromosome pair at intercalar position, was found. 5S FISH signals of almost the same size and brightness intensity were observed in all the analyzed taxa. This is the first cytological characterization of the 5S in wild taxa of Capsicum by using a genus-derived probe, and the most exhaustive and comprehensive in the chili peppers up to now. The information provided here will aid the cytomolecular characterization of pepper germplasm to evaluate variability and can be instrumental to integrate physical, genetic and genomic maps already generated in the genus.

  9. In situ mapping of the hsp70 locus in seven species of the willistoni group of Drosophila

    International Nuclear Information System (INIS)

    Bonorino, C.B.C.; Valente, V.L.S.; Pereira, M.; Alonso, C.E.V.; Abdelhay, E.

    1993-01-01

    The hsp70 locus was mapped by in situ hybridization of a biotinylated probe (p PW 229) to the polythene chromosomes of seven species of the willistoni group of Drosophila. In all of them, the probe hybridized mainly at a single site of the third chromosome, corresponding in each case to a heat-induced puff site. Southern blot analysis comparing the Eco RI digested DNA of the willistoni species with D. melanogaster revealed that a large segment of DNA homologous to the hsp 70 probe detected in D. melanogaster does not exist in the willistoni group. These results suggested that this locus is not duplicated in the willistoni group as it is in the melanogaster. (author)

  10. Locus of Control and Technology Adoption in Developing Country Agriculture

    DEFF Research Database (Denmark)

    Abay, Kibrom Araya; Blalock, Garrick; Berhane, Guush

    2017-01-01

    and psychological explanations for the low rates of adoption of profitable agricultural technologies in Sub-Saharan Africa. Our results highlight that improving farmers’ non-cognitive skills (locus of control) may facilitate technology adoption and agricultural transformation. More generally, the results suggest...

  11. AUTOMATIC GENERATION OF ROOT LOCUS PLOTS FOR LINEAR ...

    African Journals Online (AJOL)

    Design and analysis of control systems often become difficult due to the complexity of the system model and the design techniques involved. This paper presents the development of a Tools Box in Microsoft Excel for control engineer that uses root locus as a time domain technique for system design and analysis. The Tool ...

  12. Male-pattern baldness susceptibility locus at 20p11.

    NARCIS (Netherlands)

    Richards, J.B.; Yuan, X.; Geller, F.; Waterworth, D.; Bataille, V.; Glass, D.; Song, K.; Waeber, G.; Vollenweider, P.; Aben, K.K.H.; Kiemeney, L.A.L.M.; Walters, B.; Soranzo, N.; Thorsteinsdottir, U.; Kong, A.; Rafnar, T.; Deloukas, P.; Sulem, P.; Stefansson, H.; Stefansson, K.; Spector, T.D.; Mooser, V.

    2008-01-01

    We conducted a genome-wide association study for androgenic alopecia in 1,125 men and identified a newly associated locus at chromosome 20p11.22, confirmed in three independent cohorts (n = 1,650; OR = 1.60, P = 1.1 x 10(-14) for rs1160312). The one man in seven who harbors risk alleles at both

  13. (PLWHA): influence of social support, self-esteem, health locus

    African Journals Online (AJOL)

    Coping among people living with HIV/AIDS (PLWHA): influence of social support, self-esteem, health locus of control and gender. ... approach, social support should be in the front burner, society should be sensitized to the importance of social support that is culturally appropriate and behaviour modification focused.

  14. Relationship Among Achievement Motivation, Self-Esteem, Locus of ...

    African Journals Online (AJOL)

    The thrust of the study was to examine the relationship among achievement motivation, self-esteem, locus of control and academic performance of university students in a Nigerian University. The purpose was to determine the extent university student\\'s academic performance was influenced by these criterion variables.

  15. Locus of control and learning strategies as predictors of academic ...

    African Journals Online (AJOL)

    The aim of the research was to determine the relationships which exist between academic success, learning strategies and locus of control. In order to achieve this aim a small-scale quantitative study, utilising two inventories, was done. The first measuring instrument is the Learning and Study Strategies Inventory, which is ...

  16. Y-Chromosome short tandem repeat, typing technology, locus ...

    African Journals Online (AJOL)

    Aghomotsegin

    2015-07-08

    Jul 8, 2015 ... Y-Chromosome short tandem repeat, typing technology, locus information and allele frequency in different population: A review. Muhanned Abdulhasan Kareem1, Ameera Omran Hussein2 and Imad Hadi Hameed2*. 1Babylon University, Centre of Environmental Research, Hilla City, Iraq. 2Department of ...

  17. Influence of Locus Control on Real and Perceived Relationships ...

    African Journals Online (AJOL)

    They included the Nowicki-Strickland Internal – External Locus of Control Scale for children by Nowicki and Strickland (1973) and Emotional – Social Loneliness Inventory by Vincenzi and Grabosky, (1987). A cross sectional survey design was used while regression analysis and multivariate statistics were used in data ...

  18. Screening for genomic rearrangements at BRCA1 locus in Iranian ...

    Indian Academy of Sciences (India)

    2016-08-26

    Aug 26, 2016 ... Home; Journals; Journal of Genetics; Volume 92; Issue 1. Screening for genomic rearrangements at BRCA1 locus in Iranian women with breast cancer using multiplex ligation-dependent probe amplification. Vahid R. Yassaee Babak Emamalizadeh Mir Davood Omrani. Research Note Volume 92 Issue 1 ...

  19. Gender, Age and Locus of Control as Correlates of Remedial ...

    African Journals Online (AJOL)

    Gender, Age and Locus of Control as Correlates of Remedial Learners' Attitude towards English Language. ... These findings have far-reaching implications for adult and non-formal education practitioners and other stakeholders interested in improving the lots of several learners out there, in English language. Keywords: ...

  20. Sex Differences in Locus of Control, Helplessness, Hopelessness, and Depression.

    Science.gov (United States)

    Kolotkin, Richard A.; And Others

    This experiment investigated: (1) relationships among locus of control, attributional style, and depression; (2) if a depressogenic attributional style could be empirically isolated; and (3) if reliable relationships existed between attribution and depression when depression was operationalized using different instruments. Subjects completed the…

  1. Demographic Determinants of Locus of Control among Medical ...

    African Journals Online (AJOL)

    The Levenson Multidimensional Locus of Control Inventory and a Socio - demographic data collection sheet were used to collect data from 262 (183 males and 79 females) students selected through convenience sampling. Data were th analyzed using the 16th version of the SPPS. Percentages, means, t-test and ANOVA ...

  2. The Influence of Locus of Control on Student Financial Behavior

    Science.gov (United States)

    Britt, Sonya; Cumbie, Julie A.; Bell, Mary M.

    2013-01-01

    Data on psychological influences of financial behaviors has not been well addressed in student populations, which is concerning given the high levels of general and financial stress experienced by college students. The findings of this study indicate that college students with an external locus of control exhibit the worst financial behaviors.…

  3. Dealing with Malfunction: Locus of Control in Web-Conferencing

    Science.gov (United States)

    Klebl, Michael

    2014-01-01

    This paper considers how students deal with malfunctions that occur during the use of web conferencing systems in learning arrangements. In a survey among participants in online courses that make use of a web-conferencing system (N = 129), the relationship between a preference for internal or external locus of control and the perception of…

  4. Influences of peer relations and locus of control on students ...

    African Journals Online (AJOL)

    Effort to checkmate extravagance and maximize gain is the focus of all organizations more in this period of global financial crisis. There is need therefore to checkmate unnecessary financial spending. This study examines the influence of the variables, peer relations and locus of control, on such spending among University ...

  5. Exploring Learner Autonomy: Language Learning Locus of Control in Multilinguals

    Science.gov (United States)

    Peek, Ron

    2016-01-01

    By using data from an online language learning beliefs survey (n?=?841), defining language learning experience in terms of participants' multilingualism, and using a domain-specific language learning locus of control (LLLOC) instrument, this article examines whether more experienced language learners can also be seen as more autonomous language…

  6. A multi-locus phylogenetic evaluation of Diaporthe (Phomopsis)

    NARCIS (Netherlands)

    Udayanga, D.; Liu, X.; Crous, P.W.; McKenzie, E.H.C.; Chukeatirote, E.; Hyde, K.D.

    2012-01-01

    The genus Diaporthe (Phomopsis) includes important plant pathogenic fungi with wide host ranges and geographic distributions. In the present study, phylogenetic species recognition in Diaporthe is re-evaluated using a multi-locus phylogeny based on a combined data matrix of rDNA ITS, and partial

  7. Relationship between internet addiction and academic locus of ...

    African Journals Online (AJOL)

    The study identified the various internet activities engaged in by students in a Nigerian University and examined the relationship between internet addiction and their academic locus of control. The sample was made of 250 students selected from a University in Nigeria. An instrument tagged “Questionnaire on Students' ...

  8. Arousal, exploration and the locus coeruleus-norepinephrine system

    NARCIS (Netherlands)

    Jepma, Marieke

    2011-01-01

    The studies described in this thesis address a range of topics related to arousal, exploration, temporal attention, and the locus coeruleus-norepinephrine (LC-NE) system. Chapters 2 and 3 report two studies that investigated a recent theory about the role of the LC-NE system in the regulation of the

  9. Locus of Control and Likelihood of Nuclear War: Two Studies.

    Science.gov (United States)

    Erdahl, Paul; Rounds, James B.

    The Nuclear Locus of Control (NLOC) scales were constructed to assess beliefs as to whether nuclear war and nuclear policy decisions are, or can be, influenced by oneself, powerful others, or chance. Three scales measuring internal, powerful others, and chance nuclear LOC show internal consistency estimates (Cronbach's Alpha) of .87, .76, and .85,…

  10. Strengthening Locus Standi in Human Rights Litigation in Zimbabwe ...

    African Journals Online (AJOL)

    MJM Venter

    2016-05-30

    May 30, 2016 ... approach is likely to impact on the right to access to justice and human rights protection. 2. Locus standi ... Committee on Economic, Social and Cultural Rights General Comment 9: The. Domestic .... animosity towards an accused, in bad faith and without any warrant, were to rule that the question raised by ...

  11. Should Farmers' Locus of Control Be Used in Extension?

    Science.gov (United States)

    Nuthall, Peter L.

    2010-01-01

    To explore whether Farmers' Locus of Control (LOC) could be useful in agricultural extension programmes to improve managerial ability. This test records a farmer's belief in her/his control over production outcomes. A mail survey of 2300 New Zealand farmers was used to obtain a range of variables, and to measure their LOC using a question set…

  12. DNA marker mining of ILSTS035 microsatellite locus on ...

    Indian Academy of Sciences (India)

    Unknown

    We describe tests for detecting and locating quantitative trait loci (QTL) for traits in Hanwoo cattle. From results of a permutation test to detect QTL for marbling, we selected the microsatellite locus ILSTS035 on chromosome 6 for further analysis. K-means clustering analysis applied to five traits and nine DNA markers in ...

  13. Determination of the yield locus by means of temperature measurement

    NARCIS (Netherlands)

    Banabic, D.; Huetink, Han

    2006-01-01

    The paper presents a theoretical background of the thermo-graphical method of determining the yield locus. The analytical expression of the temperature variation of the specimen deformed in the elastic state is determined starting from the first law of thermodynamics. The experimental method for

  14. Response to selection in finite locus models with nonadditive effects

    NARCIS (Netherlands)

    Esfandyari, Hadi; Henryon, Mark; Berg, Peer; Thomasen, Jørn Rind; Bijma, Piter; Sørensen, Anders Christian

    2017-01-01

    Under the finite-locus model in the absence of mutation, the additive genetic variation is expected to decrease when directional selection is acting on a population, according to quantitative-genetic theory. However, some theoretical studies of selection suggest that the level of additive

  15. Locus of control and investment in risky assets

    NARCIS (Netherlands)

    Salamanca Acosta, Nicolas; de Grip, A.; Fouarge, Didier; Montizaan, Raymond

    2016-01-01

    We show that household heads with a strong internal economic locus of control are more likely to hold equity and hold a larger share of equity in their investment portfolio. This relation holds when we control for economic preferences and possible confounders such as financial literacy,

  16. 40 CFR 798.5195 - Mouse biochemical specific locus test.

    Science.gov (United States)

    2010-07-01

    ...-induced variants are bred to determine the genetic nature of the change. (f) Data and reports—(1... SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Genetic Toxicity § 798.5195 Mouse...) A biochemical specific locus mutation is a genetic change resulting from a DNA lesion causing...

  17. Emotional intelligence and locus of control of adult patients with ...

    African Journals Online (AJOL)

    Background: This article investigates emotional intelligence and locus of control in an adult breast cancer population receiving treatment. Gaining insight into these constructs will contribute to improving breast cancer patients' psychological well-being and to reducing physical vulnerability to disease before and during ...

  18. The Locus of Metaphorical Persuasion: An Empirical Test.

    Science.gov (United States)

    Hitchon, Jacqueline C.

    1997-01-01

    Investigates whether the locus of persuasion of the metaphor "A is B" lies in the valence of B, as widely assumed, or in the valence of the metaphor ground, what A and B share. Indicates that global affect toward B does not transfer onto A and that metaphorical persuasion is a distinct process meriting further investigation. (SR)

  19. Social support, locus of control, and psychological well-being

    NARCIS (Netherlands)

    van der Zee, KI; Buunk, BP; Sanderman, R

    1997-01-01

    Social support seems to be positively related to psychological well-being. Studies have shown that individual differences exist in the ability to mobilize and use sources of support. The current study focused on locus of control as a personality factor that might be related to this ability, In 2

  20. Locus of Control and Neuropsychological Performance in Chronic Alcoholics.

    Science.gov (United States)

    Shelton, M. D.; And Others

    1982-01-01

    Examined correlated neuropsychological performance in male chronic alcoholics and non-alcoholic controls. Results showed external locus of control (LOC-E) scores to predict performance on neuropsychological tests in alcoholics but not in controls. Suggests the LOC-E variables cannot account for the widespread differences between the groups on…

  1. New distal marker closely linked to the fragile X locus

    NARCIS (Netherlands)

    Hulsebos, T. J.; Oostra, B. A.; Broersen, S.; Smits, A.; van Oost, B. A.; Westerveld, A.

    1991-01-01

    We have isolated II-10, a new X-chromosomal probe that identifies a highly informative two-allele TaqI restriction fragment length polymorphism at locus DXS466. Using somatic cell hybrids containing distinct portions of the long arm of the X chromosome, we could localize DXS466 between DXS296 and

  2. DMPD: The Lps locus: genetic regulation of host responses to bacteriallipopolysaccharide. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 10669111 The Lps locus: genetic regulation of host responses to bacteriallipopolysaccharide. Qur...e The Lps locus: genetic regulation of host responses to bacteriallipopolysaccharide. Authors Qur

  3. [Relationship between work locus of control and occupational stress in oil workers].

    Science.gov (United States)

    Meng, Xian-Hai; He, Ya-Hui; Yu, Shan-Fa; Qi, Xiu-Ying

    2008-12-01

    To investigate general states of the work locus of control and explore the relationship between work locus of control and occupational stress in oil workers. 582 oil workers were investigated by using the General Questionnaire and Occupational Stress Measure Inventory. There were significant differences in WCLS score between two age groups (= 30 years old group and locus of control; values of role ambiguity, working prospect, depression and social support were higher in the group of external locus of control (P locus of control had positive relation with role ambiguity, working prospect, depression, and social support, and negative with interpersonal relationship, promotion, participation, task consistency, challenge, job satisfaction, mental health, self-esteem and coping strategies. In the regression analysis, work locus of control was the major predictive factor of work satisfaction. Work locus of control is associated with many occupational stress factors. The group of extrinsic work locus of control experience more stress in oil workers.

  4. An optimized pentaplex PCR for detecting DNA mismatch repair-deficient colorectal cancers.

    Directory of Open Access Journals (Sweden)

    Ajay Goel

    2010-02-01

    Full Text Available Microsatellite instability (MSI is used to screen colorectal cancers (CRC for Lynch Syndrome, and to predict outcome and response to treatment. The current technique for measuring MSI requires DNA from normal and neoplastic tissues, and fails to identify tumors with specific DNA mismatch repair (MMR defects. We tested a panel of five quasi-monomorphic mononucleotide repeat markers amplified in a single multiplex PCR reaction (pentaplex PCR to detect MSI.We investigated a cohort of 213 CRC patients, comprised of 114 MMR-deficient and 99 MMR-proficient tumors. Immunohistochemical (IHC analysis evaluated the expression of MLH1, MSH2, PMS2 and MSH6. MSI status was defined by differences in the quasi-monomorphic variation range (QMVR from a pool of normal DNA samples, and measuring differences in allele lengths in tumor DNA.Amplification of 426 normal alleles allowed optimization of the QMVR at each marker, and eliminated the requirement for matched reference DNA to define MSI in each sample. Using > or = 2/5 unstable markers as the criteria for MSI resulted in a sensitivity of 95.6% (95% CI = 90.1-98.1% and a positive predictive value of 100% (95% CI = 96.6%-100%. Detection of MSH6-deficiency was limited using all techniques. Data analysis with a three-marker panel (BAT26, NR21 and NR27 was comparable in sensitivity (97.4% and positive predictive value (96.5% to the five marker panel. Both approaches were superior to the standard approach to measuring MSI.An optimized pentaplex (or triplex PCR offers a facile, robust, very inexpensive, highly sensitive, and specific assay for the identification of MSI in CRC.

  5. Meta-analysis of mismatch negativity to simple versus complex deviants in schizophrenia.

    Science.gov (United States)

    Avissar, Michael; Xie, Shanghong; Vail, Blair; Lopez-Calderon, Javier; Wang, Yuanjia; Javitt, Daniel C

    2018-01-01

    Mismatch negativity (MMN) deficits in schizophrenia (SCZ) have been studied extensively since the early 1990s, with the vast majority of studies using simple auditory oddball task deviants that vary in a single acoustic dimension such as pitch or duration. There has been a growing interest in using more complex deviants that violate more abstract rules to probe higher order cognitive deficits. It is still unclear how sensory processing deficits compare to and contribute to higher order cognitive dysfunction, which can be investigated with later attention-dependent auditory event-related potential (ERP) components such as a subcomponent of P300, P3b. In this meta-analysis, we compared MMN deficits in SCZ using simple deviants to more complex deviants. We also pooled studies that measured MMN and P3b in the same study sample and examined the relationship between MMN and P3b deficits within study samples. Our analysis reveals that, to date, studies using simple deviants demonstrate larger deficits than those using complex deviants, with effect sizes in the range of moderate to large. The difference in effect sizes between deviant types was reduced significantly when accounting for magnitude of MMN measured in healthy controls. P3b deficits, while large, were only modestly greater than MMN deficits (d=0.21). Taken together, our findings suggest that MMN to simple deviants may still be optimal as a biomarker for SCZ and that sensory processing dysfunction contributes significantly to MMN deficit and disease pathophysiology. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Prosthesis-patient mismatch after transcatheter aortic valve implantation with the Medtronic-Corevalve bioprosthesis.

    Science.gov (United States)

    Jilaihawi, Hasan; Chin, Derek; Spyt, Tomasz; Jeilan, Mohamed; Vasa-Nicotera, Mariuca; Bence, Johan; Logtens, Elaine; Kovac, Jan

    2010-04-01

    Prosthesis-patient mismatch (P-PM) is an important determinant of morbidity and mortality following open aortic valve replacement. The aims of this study were to report its incidence and determinants following transcatheter aortic valve implantation (TAVI) with the Corevalve bioprosthesis, which have-thus far-not been described. Patients with severe calcific aortic stenosis received TAVI with the Corevalve bioprosthesis via transfemoral route. Following TAVI, moderate P-PM was defined as indexed aortic valve effective orifice area (AVAi) Clinical, echocardiographic, and procedural factors relating to P-PM were studied. Optimal device position was defined on fluoroscopy as final position of the proximal aspect of the Corevalve stent frame 5-10 mm below the native aortic annulus. Between January 2007 and January 2009, 50 consecutive patients underwent TAVI in a single centre with the Corevalve bioprosthesis. Mean age was 82.8 years (SD 5.9; 70-93) and 48% were male. P-PM occurred in 16 of 50 cases (32%). Optimal position was achieved in 50% of cases. P-PM was unrelated to age, annulus size, LVOT size, Corevalve size, aortic angulation, ejection fraction, and sex. It was inversely correlated to optimal position (Spearman rho r = -0.34, P = 0.015). Those with optimal positioning had a 16% incidence of P-PM relative to 48% of those with suboptimal positioning (Pearson chi(2) P = 0.015). The incidence of P-PM following TAVI with the Corevalve bioprosthesis is compared favourably with that seen after AVR with conventional open stented bioprostheses and its occurrence is influenced by device positioning.

  7. Perifoveal function in patients with North Carolina macular dystrophy: the importance of accounting for fixation locus.

    Science.gov (United States)

    Seiple, William; Szlyk, Janet P; Paliga, Jennifer; Rabb, Maurice F

    2006-04-01

    To quantify the extent of visual function losses in patients with North Carolina Macular Dystrophy (NCMD) and to demonstrate the importance of accounting for eccentric fixation when making comparisons with normal data. Five patients with NCMD who were from a single family were examined. Multifocal electroretinograms (mfERGs) and psychophysical assessments of acuity and luminance visual field sensitivities were measured throughout the central retina. Comparisons of responses from equivalent retinal areas were accomplished by shifting normal templates to be centered at the locus of fixation for each patient. Losses of psychophysically measured visual function in patients with NCMD extend to areas adjacent to the locations of visible lesions. The multifocal ERG amplitude was reduced only within the area of visible lesion. Multifocal ERG implicit times were delayed throughout the entire central retinal area assessed. ERG timing is a sensitive assay of retinal function, and our results indicate that NCMD has a widespread effect at the level of the mid and outer retina. The findings also demonstrated that it is necessary to account for fixation locus and to ensure that equivalent retinal areas are compared when testing patients with macular disease who have eccentric fixation.

  8. A major locus on mouse chromosome 18 controls XX sex reversal in Odd Sex (Ods) mice.

    Science.gov (United States)

    Qin, Yangjun; Poirier, Christophe; Truong, Cavatina; Schumacher, Armin; Agoulnik, Alexander I; Bishop, Colin E

    2003-03-01

    We have previously reported a dominant mouse mutant, Odd sex (Ods), in which XX Ods/+ mice on the FVB/N background show complete sex reversal, associated with expression of Sox9 in the fetal gonads. Remarkably, when crossed to the A/J strain approximately 95% of the (AXFVB) F(1) XX Ods/+ mice developed as fully fertile, phenotypic females, the remainder developing as males or hermaphrodites. Using a (AXFVB) F(2) population, we conducted a genome-wide linkage scan to identify the number and chromosomal location of potential Ods modifier genes. A single major locus termed Odsm1 was mapped to chromosome 18, tightly linked to D18Mit189 and D18Mit210. Segregation at this locus could account for the presence of sex reversal in 100% of XX Ods/+ mice which develop as males, for the absence of sex reversal in approximately 92% of XX Ods/+ mice which develop as females, and for the mixed sexual phenotype in approximately 72% of XX Ods/+ mice that develop with ambiguous genitalia. We propose that homozygosity for the FVB-derived allele strongly favors Ods sex reversal, whereas homozygosity for the A/J-derived allele inhibits it. In mice heterozygous at Odsm1, the phenotypic outcome, male, female or hermaphrodite, is determined by a complex interaction of several minor modifying loci. The close proximity of Smad2, Smad7 and Smad4 to D18Mit189/210 provides a potential mechanism through which Odsm1 might act.

  9. Identification of a novel percent mammographic density locus at 12q24.

    Science.gov (United States)

    Stevens, Kristen N; Lindstrom, Sara; Scott, Christopher G; Thompson, Deborah; Sellers, Thomas A; Wang, Xianshu; Wang, Alice; Atkinson, Elizabeth; Rider, David N; Eckel-Passow, Jeanette E; Varghese, Jajini S; Audley, Tina; Brown, Judith; Leyland, Jean; Luben, Robert N; Warren, Ruth M L; Loos, Ruth J F; Wareham, Nicholas J; Li, Jingmei; Hall, Per; Liu, Jianjun; Eriksson, Louise; Czene, Kamila; Olson, Janet E; Pankratz, V Shane; Fredericksen, Zachary; Diasio, Robert B; Lee, Adam M; Heit, John A; DeAndrade, Mariza; Goode, Ellen L; Vierkant, Robert A; Cunningham, Julie M; Armasu, Sebastian M; Weinshilboum, Richard; Fridley, Brooke L; Batzler, Anthony; Ingle, James N; Boyd, Norman F; Paterson, Andrew D; Rommens, Johanna; Martin, Lisa J; Hopper, John L; Southey, Melissa C; Stone, Jennifer; Apicella, Carmel; Kraft, Peter; Hankinson, Susan E; Hazra, Aditi; Hunter, David J; Easton, Douglas F; Couch, Fergus J; Tamimi, Rulla M; Vachon, Celine M

    2012-07-15

    Percent mammographic density adjusted for age and body mass index (BMI) is one of the strongest risk factors for breast cancer and has a heritable component that remains largely unidentified. We performed a three-stage genome-wide association study (GWAS) of percent mammographic density to identify novel genetic loci associated with this trait. In stage 1, we combined three GWASs of percent density comprised of 1241 women from studies at the Mayo Clinic and identified the top 48 loci (99 single nucleotide polymorphisms). We attempted replication of these loci in 7018 women from seven additional studies (stage 2). The meta-analysis of stage 1 and 2 data identified a novel locus, rs1265507 on 12q24, associated with percent density, adjusting for age and BMI (P = 4.43 × 10(-8)). We refined the 12q24 locus with 459 additional variants (stage 3) in a combined analysis of all three stages (n = 10 377) and confirmed that rs1265507 has the strongest association in the 12q24 region (P = 1.03 × 10(-8)). Rs1265507 is located between the genes TBX5 and TBX3, which are members of the phylogenetically conserved T-box gene family and encode transcription factors involved in developmental regulation. Understanding the mechanism underlying this association will provide insight into the genetics of breast tissue composition.

  10. Upper tract urothelial carcinomas: frequency of association with mismatch repair protein loss and lynch syndrome.

    Science.gov (United States)

    Harper, Holly L; McKenney, Jesse K; Heald, Brandie; Stephenson, Andrew; Campbell, Steven C; Plesec, Thomas; Magi-Galluzzi, Cristina

    2017-01-01

    Increased risk for upper tract urothelial carcinoma is described in patients with Lynch syndrome, caused by germline mutations in mismatch repair genes. We aimed to identify the frequency of mismatch repair protein loss in upper tract urothelial carcinoma and its potential for identifying an association with Lynch syndrome. We queried our database to identify upper tract urothelial carcinomas. Patients were cross-referenced for history of colorectal carcinoma or other common Lynch syndrome-associated neoplasms to enrich for potential Lynch syndrome cases. Tumor histopathologic characteristics were reviewed and each case was analyzed for loss of mismatch repair proteins, MLH1, MSH2, MSH6, and PMS2, by immunohistochemistry. Of 444 patients with upper tract urothelial carcinoma, a subset of 215 (encompassing 30 with upper tract urothelial carcinoma and another common Lynch syndrome-associated neoplasm) was analyzed for loss of mismatch repair protein expression. Of 30 patients with Lynch syndrome-associated neoplasms, six had documented Lynch syndrome, including two with Muir-Torre syndrome. Mismatch repair protein loss was identified in 7% of total upper tract urothelial carcinomas and 30% of patients with Lynch syndrome-associated neoplasms (including all patients with Lynch syndrome/Muir-Torre syndrome). Of patients without history of Lynch syndrome-associated neoplasms, 5 of 184 (2.7%) had loss of mismatch repair protein expression. Twelve cases with mismatch repair protein loss demonstrated loss of MSH2 and MSH6, and 2 had isolated loss of MSH6. MLH1 and PMS2 expression were consistently retained. Although increased intratumoral lymphocytes, inverted growth, pushing tumor-stromal interface, and lack of nuclear pleomorphism were more commonly seen in cases with mismatch repair protein loss, only intratumoral lymphocytes and presence of pushing borders were statistically significant. MLH1 and PMS2 testing appear to have little utility in upper tract urothelial

  11. A cut locus for finite graphs and the farthest point mapping

    DEFF Research Database (Denmark)

    Maddaloni, Alessandro; Zamfirescu, Carol T.

    2016-01-01

    We reflect upon an analogue of the cut locus, a notion classically studied in Differential Geometry, for finite graphs. The cut locus C(x) of a vertex x shall be the graph induced by the set of all vertices y with the property that no shortest path between x and z, z≠y, contains y. The cut locus ...

  12. Reframing Student Affairs Leadership: An Analysis of Organizational Frames of Reference and Locus of Control

    Science.gov (United States)

    Tull, Ashley; Freeman, Jerrid P.

    2011-01-01

    Examined in this study were the identified frames of reference and locus of control used by 478 student affairs administrators. Administrator responses were examined to identify frames of reference most commonly used and their preference order. Locus of control most commonly used and the relationship between frames of reference and locus of…

  13. Locus of Control in Offenders and Alleged Offenders with Learning Disabilities

    Science.gov (United States)

    Goodman, Wendy; Leggett, Janice; Garrett, Tanya

    2007-01-01

    Locus of control can be a useful measure of treatment outcome in offenders from the general population. However, there is little information regarding locus of control and offenders with learning disabilities. Existing measures of locus of control use complex language and abstract ideas that may not be accessible to individuals in this group. A…

  14. Rasch Analysis of the Locus-of-Hope Scale. Brief Report

    Science.gov (United States)

    Gadiana, Leny G.; David, Adonis P.

    2015-01-01

    The Locus-of-Hope Scale (LHS) was developed as a measure of the locus-of-hope dimensions (Bernardo, 2010). The present study adds to the emerging literature on locus-of-hope by assessing the psychometric properties of the LHS using Rasch analysis. The results from the Rasch analyses of the four subscales of LHS provided evidence on the…

  15. On the Relation of Locus of Control and L2 Reading and Writing Achievement

    Science.gov (United States)

    Ghonsooly, Behzad; Shirvan, Majid Elahi

    2011-01-01

    Locus of control, a psychological construct, has been the focus of attention in recent decades. Psychologists have discussed the effect of locus of control on achieving life goals in social/psychological interactions. While learning a foreign language involves both social interactions and psychological processes, the role and relation of locus of…

  16. Evaluation of diffusion-perfusion mismatch for determining indication for emergency endovascular revascularization

    International Nuclear Information System (INIS)

    Masuda, Atsushi; Miki, Takanori; Matsumoto, Hiroaki

    2010-01-01

    We evaluated the usefulness of assessing by diffusion-perfusion mismatch (D/P mismatch) whether there is adaptation of neuroendovascular revascularization for acute ischemic stroke out of intravenous tissue plasminogen activator (IV t-PA). We retrospectively analyzed 24 patients who underwent D/P mismatch and endovascular treatment between October 2005 and September 2008. This investigation included stroke patients with a National Institutes of Health Stroke Scale (NIHSS) score less than 4. Sixteen acute ischemic stroke patients had an NIHSS score greater than 5. Eight patients (50%) had a favorable neurological outcome (modified Rankin Scale 0 to 2). Eight acute ischemic stroke patients had an NIHSS score equal to or less than 4. Four patients who underwent emergency endovascular treatment on admission had a favorable neurological outcome, but 3 patients treated for progressive stroke after admission all had a poor prognosis. Evaluating D/P mismatch was useful for determining the adaptation of emergency neuroendovascular revascularization for acute ischemic stroke out of IV t-PA. Acute ischemic stroke patients with an NIHSS score equal to or less than 4 and diffusion/perfusion mismatch need careful observation to enable endovascular treatment immediately after progressive stroke. (author)

  17. Molecular dynamics simulation of thin film interfacial strength dependency on lattice mismatch

    International Nuclear Information System (INIS)

    Yang, Zhou; Lian, Jie; Wang, Junlan

    2013-01-01

    Laser-induced thin film spallation experiments have been previously developed to characterize the intrinsic interfacial strength of thin films. In order to gain insights of atomic level thin film debonding processes and the interfacial strength dependence on film/substrate lattice structures, in this study, molecular dynamics simulations of thin film interfacial failure under laser-induced stress waves were performed. Various loading amplitudes and pulse durations were employed to identify the optimum simulation condition. Stress propagation as a function of time was revealed in conjunction with the interface structures. Parametric studies confirmed that while the interfacial strength between a thin film and a substrate does not depend on the film thickness and the duration of the laser pulse, a thicker film and a shorter duration do provide advantage to effectively load the interface to failure. With the optimized simulation condition, further studies were focused on bulk Au/Au bi-crystals with mismatched orientations, and Ni/Al, Cu/Al, Cu/Ag and Cu/Au bi-crystals with mismatched lattices. The interfacial strength was found to decrease with increasing orientation mismatch and lattice mismatch but more significantly dominated by the bonding elements' atomic structure and valence electron occupancy. - Highlights: • Molecular dynamics simulation was done on stress wave induced thin film spallation. • Atomic structure was found to be a primary strength determining factor. • Lattice mismatch was found to be a secondary strength determining factor

  18. Influences of Device and Circuit Mismatches on Paralleling Silicon Carbide MOSFETs

    DEFF Research Database (Denmark)

    Li, Helong; Munk-Nielsen, Stig; Wang, Xiongfei

    2016-01-01

    This paper addresses the influences of device and circuit mismatches on paralleling the Silicon Carbide (SiC) MOSFETs. Comprehensive theoretical analysis and experimental validation from paralleled discrete devices to paralleled dies in multichip power modules are first presented. Then, the influ......This paper addresses the influences of device and circuit mismatches on paralleling the Silicon Carbide (SiC) MOSFETs. Comprehensive theoretical analysis and experimental validation from paralleled discrete devices to paralleled dies in multichip power modules are first presented. Then......, the influence of circuit mismatch on paralleling SiC MOSFETs is investigated and experimentally evaluated for the first time. It is found that the mismatch of the switching loop stray inductance can also lead to on-state current unbalance with inductive output current, in addition to the on-state resistance...... of the device. It further reveals that circuit mismatches and a current coupling among the paralleled dies exist in a SiC MOSFET multichip power module, which is critical for the transient current distribution in the power module. Thus, a power module layout with an auxiliary source connection is developed...

  19. HLA Mismatching Strategies for Solid Organ Transplantation – A Balancing Act

    Science.gov (United States)

    Zachary, Andrea A.; Leffell, Mary S.

    2016-01-01

    HLA matching provides numerous benefits in organ transplantation including better graft function, fewer rejection episodes, longer graft survival, and the possibility of reduced immunosuppression. Mismatches are attended by more frequent rejection episodes that require increased immunosuppression that, in turn, can increase the risk of infection and malignancy. HLA mismatches also incur the risk of sensitization, which can reduce the opportunity and increase waiting time for a subsequent transplant. However, other factors such as donor age, donor type, and immunosuppression protocol, can affect the benefit derived from matching. Furthermore, finding a well-matched donor may not be possible for all patients and usually prolongs waiting time. Strategies to optimize transplantation for patients without a well-matched donor should take into account the immunologic barrier represented by different mismatches: what are the least immunogenic mismatches considering the patient’s HLA phenotype; should repeated mismatches be avoided; is the patient sensitized to HLA and, if so, what are the strengths of the patient’s antibodies? This information can then be used to define the HLA type of an immunologically optimal donor and the probability of such a donor occurring. A probability that is considered to be too low may require expanding the donor population through paired donation or modifying what is acceptable, which may require employing treatment to overcome immunologic barriers such as increased immunosuppression or desensitization. Thus, transplantation must strike a balance between the risk associated with waiting for the optimal donor and the risk associated with a less than optimal donor. PMID:28003816

  20. Luminescent platinum(II) complexes with functionalized N-heterocyclic carbene or diphosphine selectively probe mismatched and abasic DNA

    OpenAIRE

    Che, CM; Chen, T; To, WP; Zou, T; FUNG, SK; Lok, CN; YANG, C; Cao, B

    2016-01-01

    The selective targeting of mismatched DNA overexpressed in cancer cells is an appealing strategy in designing cancer diagnosis and therapy protocols. Few luminescent probes that specifically detect intracellular mismatched DNA have been reported. Here we used Pt(II) complexes with luminescence sensitive to subtle changes in the local environment and report several Pt(II) complexes that selectively bind to and identify DNA mismatches. We evaluated the complexes' DNA-binding characteristics by ...

  1. Measuring strand discontinuity-directed mismatch repair in yeast Saccharomyces cerevisiae by cell-free nuclear extracts.

    Science.gov (United States)

    Yuan, Fenghua; Lai, Fangfang; Gu, Liya; Zhou, Wen; El Hokayem, Jimmy; Zhang, Yanbin

    2009-05-01

    Mismatch repair corrects biosynthetic errors generated during DNA replication, whose deficiency causes a mutator phenotype and directly underlies hereditary non-polyposis colorectal cancer and sporadic cancers. Because of remarkably high conservation of the mismatch repair machinery between the budding yeast (Saccharomyces cerevisiae) and humans, the study of mismatch repair in yeast has provided tremendous insights into the mechanisms of this repair pathway in humans. In addition, yeast cells possess an unbeatable advantage over human cells in terms of the easy genetic manipulation, the availability of whole genome deletion strains, and the relatively low cost for setting up the system. Although many components of eukaryotic mismatch repair have been identified, it remains unclear if additional factors, such as DNA helicase(s) and redundant nuclease(s) besides EXO1, participate in eukaryotic mismatch repair. To facilitate the discovery of novel mismatch repair factors, we developed a straightforward in vitro cell-free repair system. Here, we describe the practical protocols for preparation of yeast cell-free nuclear extracts and DNA mismatch substrates, and the in vitro mismatch repair assay. The validity of the cell-free system was confirmed by the mismatch repair deficient yeast strain (Deltamsh2) and the complementation assay with purified yeast MSH2-MSH6.

  2. Characterization of a Multipeptide Lantibiotic Locus in Streptococcus pneumoniae.

    Science.gov (United States)

    Maricic, Natalie; Anderson, Erica S; Opipari, AnneMarie E; Yu, Emily A; Dawid, Suzanne

    2016-01-26

    Bacterial communities are established through a combination of cooperative and antagonistic interactions between the inhabitants. Competitive interactions often involve the production of antimicrobial substances, including bacteriocins, which are small antimicrobial peptides that target other community members. Despite the nearly ubiquitous presence of bacteriocin-encoding loci, inhibitory activity has been attributed to only a small fraction of gene clusters. In this study, we characterized a novel locus (the pld locus) in the pathogen Streptococcus pneumoniae that drives the production of a bacteriocin called pneumolancidin, which has broad antimicrobial activity. The locus encodes an unusual tandem array of four inhibitory peptides, three of which are absolutely required for antibacterial activity. The three peptide sequences are similar but appear to play distinct roles in regulation and inhibition. A modification enzyme typically found in loci encoding a class of highly modified bacteriocins called lantibiotics was required for inhibitory activity. The production of pneumolancidin is controlled by a two-component regulatory system that is activated by the accumulation of modified peptides. The locus is located on a mobile element that has been found in many pneumococcal lineages, although not all elements carry the pld genes. Intriguingly, a minimal region containing only the genes required for pneumolancidin immunity was found in several Streptococcus mitis strains. The pneumolancidin-producing strain can inhibit nearly all pneumococci tested to date and provided a competitive advantage in vivo. These peptides not only represent a unique strategy for bacterial competition but also are an important resource to guide the development of new antimicrobials. Successful colonization of a polymicrobial host surface is a prerequisite for the subsequent development of disease for many bacterial pathogens. Bacterial factors that directly inhibit the growth of neighbors

  3. Distinct mutational signatures characterize concurrent loss of polymerase proofreading and mismatch repair.

    Science.gov (United States)

    Haradhvala, N J; Kim, J; Maruvka, Y E; Polak, P; Rosebrock, D; Livitz, D; Hess, J M; Leshchiner, I; Kamburov, A; Mouw, K W; Lawrence, M S; Getz, G

    2018-05-01

    Fidelity of DNA replication is maintained using polymerase proofreading and the mismatch repair pathway. Tumors with loss of function of either mechanism have elevated mutation rates with characteristic mutational signatures. Here we report that tumors with concurrent loss of both polymerase proofreading and mismatch repair function have mutational patterns that are not a simple sum of the signatures of the individual alterations, but correspond to distinct, previously unexplained signatures: COSMIC database signatures 14 and 20. We then demonstrate that in all five cases in which the chronological order of events could be determined, polymerase epsilon proofreading alterations precede the defect in mismatch repair. Overall, we illustrate that multiple distinct mutational signatures can result from different combinations of a smaller number of mutational processes (of either damage or repair), which can influence the interpretation and discovery of mutational signatures.

  4. Receiver IQ mismatch estimation in PDM CO-OFDM system using training symbol

    Science.gov (United States)

    Peng, Dandan; Ma, Xiurong; Yao, Xin; Zhang, Haoyuan

    2017-07-01

    Receiver in-phase/quadrature (IQ) mismatch is hard to mitigate at the receiver via using conventional method in polarization division multiplexed (PDM) coherent optical orthogonal frequency division multiplexing (CO-OFDM) system. In this paper, a novel training symbol structure is proposed to estimate IQ mismatch and channel distortion. Combined this structure with Gram Schmidt orthogonalization procedure (GSOP) algorithm, we can get lower bit error rate (BER). Meanwhile, based on this structure one estimation method is deduced in frequency domain which can achieve the estimation of IQ mismatch and channel distortion independently and improve the system performance obviously. Numerical simulation shows that the proposed two methods have better performance than compared method at 100 Gb/s after 480 km fiber transmission. Besides, the calculation complexity is also analyzed.

  5. An IQ mismatch calibration and compensation technique for wideband wireless transceivers

    International Nuclear Information System (INIS)

    Peng Jin; Zhou Liguo; Yao Heng; Yuan Fang; Shi Yin; Fang Zhi

    2014-01-01

    An IQ mismatch calibration and compensation technique based on the digital baseband for wideband wireless communication transmitters is proposed. The digital baseband transmits the signal used for IQ mismatch calibration. The signal passes through the RF transmitter path, the calibration loop (which is composed of a square power detector and a band-pass filter in the RF transceiver) and the variable gain amplifier of the receiver. The digital baseband samples the signal for IQ mismatch estimation and compensates for it. Compared with the self-calibration technique in the RF chip, the proposed technique saves area and power consumption for the wireless local area network solution. This technique has been successfully used for the 802.11n system and satisfies the requirement of the standard by achieving over 50 dB image suppression. (semiconductor integrated circuits)

  6. Dominant phonon polarization conversion across dimensionally mismatched interfaces: Carbon-nanotube-graphene junction

    Science.gov (United States)

    Shi, Jingjing; Lee, Jonghoon; Dong, Yalin; Roy, Ajit; Fisher, Timothy S.; Ruan, Xiulin

    2018-04-01

    Dimensionally mismatched interfaces are emerging for thermal management applications, but thermal transport physics remains poorly understood. Here we consider the carbon-nanotube-graphene junction, which is a dimensionally mismatched interface between one- and two-dimensional materials and is the building block for carbon-nanotube (CNT)-graphene three-dimensional networks. We predict the transmission function of individual phonon modes using the wave packet method; surprisingly, most incident phonon modes show predominantly polarization conversion behavior. For instance, longitudinal acoustic (LA) polarizations incident from CNTs transmit mainly into flexural transverse (ZA) polarizations in graphene. The frequency stays the same as the incident mode, indicating elastic transmission. Polarization conversion is more significant as the phonon wavelength increases. We attribute such unique phonon polarization conversion behavior to the dimensional mismatch across the interface, and it opens significantly new phonon transport channels as compared to existing theories where polarization conversion is neglected.

  7. Two-year-olds' sensitivity to subphonemic mismatch during online spoken word recognition.

    Science.gov (United States)

    Paquette-Smith, Melissa; Fecher, Natalie; Johnson, Elizabeth K

    2016-11-01

    Sensitivity to noncontrastive subphonemic detail plays an important role in adult speech processing, but little is known about children's use of this information during online word recognition. In two eye-tracking experiments, we investigate 2-year-olds' sensitivity to a specific type of subphonemic detail: coarticulatory mismatch. In Experiment 1, toddlers viewed images of familiar objects (e.g., a boat and a book) while hearing labels containing appropriate or inappropriate coarticulation. Inappropriate coarticulation was created by cross-splicing the coda of the target word onto the onset of another word that shared the same onset and nucleus (e.g., to create boat, the final consonant of boat was cross-spliced onto the initial CV of bone). We tested 24-month-olds and 29-month-olds in this paradigm. Both age groups behaved similarly, readily detecting the inappropriate coarticulation (i.e., showing better recognition of identity-spliced than cross-spliced items). In Experiment 2, we asked how children's sensitivity to subphonemic mismatch compared to their sensitivity to phonemic mismatch. Twenty-nine-month-olds were presented with targets that contained either a phonemic (e.g., the final consonant of boat was spliced onto the initial CV of bait) or a subphonemic mismatch (e.g., the final consonant of boat was spliced onto the initial CV of bone). Here, the subphonemic (coarticulatory) mismatch was not nearly as disruptive to children's word recognition as a phonemic mismatch. Taken together, our findings support the view that 2-year-olds, like adults, use subphonemic information to optimize online word recognition.

  8. Cervical Cord-Canal Mismatch: A New Method for Identifying Predisposition to Spinal Cord Injury.

    Science.gov (United States)

    Nouri, Aria; Montejo, Julio; Sun, Xin; Virojanapa, Justin; Kolb, Luis E; Abbed, Khalid M; Cheng, Joseph S

    2017-12-01

    The risk for spinal cord injuries (SCIs) ranging from devastating traumatic injuries, compression because of degenerative pathology, and neurapraxia is increased in patients with congenital spinal stenosis. Classical diagnostic criteria include an absolute anteroposterior diameter of spinal cord, which varies across patients, independent of canal size. Recent large magnetic resonance imaging studies of population cohorts have allowed newer methods to emerge that account for both cord and canal size by measuring a spinal cord occupation ratio (SCOR). A SCOR defined as ≥70% on midsagittal imaging or ≥80% on axial imaging appears to be an effective method of identifying cord-canal mismatch, but requires further validation. Cord-canal size mismatch predisposes patients to SCI because of 1) less space within the canal lowering the amount of degenerative changes needed for cord compression, and 2) less cerebrospinal fluid surrounding the spinal cord decreasing the ability to absorb kinetic forces directed at the spine. Patients with cord-canal mismatch have been reported to be at a substantially higher risk of traumatic SCI, and present with degenerative cervical myelopathy at a younger age than patients without cord-canal mismatch. However, neurologic outcome after SCI has occurred does not appear to be different in patients with or without a cord-canal mismatch. Recognition that canal and cord size are both factors which predispose to SCI supports that cord-canal size mismatch rather than a narrow cervical canal in isolation should be viewed as the underlying mechanism predisposing to SCI. Copyright © 2017. Published by Elsevier Inc.

  9. Educational mismatch and health status among foreign-born workers in Sweden.

    Science.gov (United States)

    Dunlavy, A C; Garcy, A M; Rostila, M

    2016-04-01

    Foreign-born workers have been shown to experience poorer working conditions than native-born workers. Yet relationships between health and educational mismatch have been largely overlooked among foreign-born workers. This study uses objective and self-reported measures of educational mismatch to compare the prevalence of educational mismatch among native (n = 2359) and foreign-born (n = 1789) workers in Sweden and to examine associations between educational mismatch and poor self-rated health. Findings from weighted multivariate logistic regression which controlled for social position and individual-level demographic characteristics suggested that over-educated foreign-born workers had greater odds ratios for poor-self rated health compared to native-born matched workers. This association was particularly evident among men (OR = 2.14, 95% CI: 1.04-4.39) and women (OR = 2.13, 95% CI: 1.12-4.03) from countries outside of Western Europe, North America, and Australia/New Zealand. Associations between under-education and poor-self rated health were also found among women from countries outside of Western Europe, North America, and Australia/New Zealand (OR = 2.02, 95% CI: 1.27-3.18). These findings suggest that educational mismatch may be an important work-related social determinant of health among foreign-born workers. Future studies are needed to examine the effects of long-term versus short-term states of educational mismatch on health and to study relationships over time. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Convergent transmission of RNAi guide-target mismatch information across Argonaute internal allosteric network.

    Science.gov (United States)

    Joseph, Thomas T; Osman, Roman

    2012-01-01

    In RNA interference, a guide strand derived from a short dsRNA such as a microRNA (miRNA) is loaded into Argonaute, the central protein in the RNA Induced Silencing Complex (RISC) that silences messenger RNAs on a sequence-specific basis. The positions of any mismatched base pairs in an miRNA determine which Argonaute subtype is used. Subsequently, the Argonaute-guide complex binds and silences complementary target mRNAs; certain Argonautes cleave the target. Mismatches between guide strand and the target mRNA decrease cleavage efficiency. Thus, loading and silencing both require that signals about the presence of a mismatched base pair are communicated from the mismatch site to effector sites. These effector sites include the active site, to prevent target cleavage; the binding groove, to modify nucleic acid binding affinity; and surface allosteric sites, to control recruitment of additional proteins to form the RISC. To examine how such signals may be propagated, we analyzed the network of internal allosteric pathways in Argonaute exhibited through correlations of residue-residue interactions. The emerging network can be described as a set of pathways emanating from the core of the protein near the active site, distributed into the bulk of the protein, and converging upon a distributed cluster of surface residues. Nucleotides in the guide strand "seed region" have a stronger relationship with the protein than other nucleotides, concordant with their importance in sequence selectivity. Finally, any of several seed region guide-target mismatches cause certain Argonaute residues to have modified correlations with the rest of the protein. This arises from the aggregation of relatively small interaction correlation changes distributed across a large subset of residues. These residues are in effector sites: the active site, binding groove, and surface, implying that direct functional consequences of guide-target mismatches are mediated through the cumulative effects of

  11. Convergent transmission of RNAi guide-target mismatch information across Argonaute internal allosteric network.

    Directory of Open Access Journals (Sweden)

    Thomas T Joseph

    Full Text Available In RNA interference, a guide strand derived from a short dsRNA such as a microRNA (miRNA is loaded into Argonaute, the central protein in the RNA Induced Silencing Complex (RISC that silences messenger RNAs on a sequence-specific basis. The positions of any mismatched base pairs in an miRNA determine which Argonaute subtype is used. Subsequently, the Argonaute-guide complex binds and silences complementary target mRNAs; certain Argonautes cleave the target. Mismatches between guide strand and the target mRNA decrease cleavage efficiency. Thus, loading and silencing both require that signals about the presence of a mismatched base pair are communicated from the mismatch site to effector sites. These effector sites include the active site, to prevent target cleavage; the binding groove, to modify nucleic acid binding affinity; and surface allosteric sites, to control recruitment of additional proteins to form the RISC. To examine how such signals may be propagated, we analyzed the network of internal allosteric pathways in Argonaute exhibited through correlations of residue-residue interactions. The emerging network can be described as a set of pathways emanating from the core of the protein near the active site, distributed into the bulk of the protein, and converging upon a distributed cluster of surface residues. Nucleotides in the guide strand "seed region" have a stronger relationship with the protein than other nucleotides, concordant with their importance in sequence selectivity. Finally, any of several seed region guide-target mismatches cause certain Argonaute residues to have modified correlations with the rest of the protein. This arises from the aggregation of relatively small interaction correlation changes distributed across a large subset of residues. These residues are in effector sites: the active site, binding groove, and surface, implying that direct functional consequences of guide-target mismatches are mediated through the

  12. Characterization and genetic mapping of a Photoperiod-sensitive dwarf 1 locus in rice (Oryza sativa L.).

    Science.gov (United States)

    Li, Riqing; Xia, Jixing; Xu, Yiwei; Zhao, Xiucai; Liu, Yao-Guang; Chen, Yuanling

    2014-01-01

    Plant height is an important agronomic trait for crop architecture and yield. Most known factors determining plant height function in gibberellin or brassinosteroid biosynthesis or signal transduction. Here, we report a japonica rice (Oryza sativa ssp. japonica) dominant dwarf mutant, Photoperiod-sensitive dwarf 1 (Psd1). The Psd1 mutant showed impaired cell division and elongation, and a severe dwarf phenotype under long-day conditions, but nearly normal growth in short-day. The plant height of Psd1 mutant could not be rescued by gibberellin or brassinosteroid treatment. Genetic analysis with R1 and F2 populations determined that Psd1 phenotype was controlled by a single dominant locus. Linkage analysis with 101 tall F2 plants grown in a long-day season, which were derived from a cross between Psd1 and an indica cultivar, located Psd1 locus on chromosome 1. Further fine-mapping with 1017 tall F2 plants determined this locus on an 11.5-kb region. Sequencing analysis of this region detected a mutation site in a gene encoding a putative lipid transfer protein; the mutation produces a truncated C-terminus of the protein. This study establishes the genetic foundation for understanding the molecular mechanisms regulating plant cell division and elongation mediated by interaction between genetic and environmental factors.

  13. Molecular alterations underlying the spontaneous and γ-ray-induced point mutations at the white locus of Drosophila Melanogaster

    International Nuclear Information System (INIS)

    Aleksandrova, M.V.; Lapidus, I.L.; Aleksandrov, I.D.; Karpovskij, A.L.

    1996-01-01

    The white locus in D.Melanogaster was selected as a target gene for the study of the mutational spectra of spontaneously arising and radiation-induced gene mutations in a whole organism. Analysis of 6 spontaneous and 73 γ-ray-induced white mutations by a combination of cytological, genetic and molecular techniques revealed that on the chromosomal and genetic levels all spontaneous mutations showed themselves to be point mutants. The share of such mutants among all heritable radiation-induced gene mutations is about 40%, whereas the rest ones are due to exchange breaks (8%) as well as multilocus, single-locus or partial-locus (intragenic) deletions (52%). The DNAs from 4 spontaneous and 17 γ-ray-induced point mutants were analysed by Southern blot-hybridization. The three spontaneous and 7 radiation mutants showed an altered DNA sequence at the left (distal) half of the white gene due to insertion or DNA rearrangement. The rest (58%) of the radiation-induced point mutations did not indicate any alternations in this part of the gene as detected by this technique and probes employed. 15 refs., 3 figs., 1 tab

  14. Refined localization of the Prieto-syndrome locus

    Energy Technology Data Exchange (ETDEWEB)

    Martinez, F.; Prieto, F. [Unidad de Genetica, Valencia (Spain); Gal, A. [Universitaets-Krankenhaus Eppendorf, Hamburg (Germany)

    1996-07-12

    PRS designates the locus for a syndromal form of X-linked mental retardation (Prieto syndrome) characterized by minor facial anomalies, ear malformation, abnormal growth of teeth, clinodactyly, sacral dimple, patellar luxation, malformation of lower limbs, abnormalities of the fundus of the eye, and subcortical cerebral atrophy. Linkage analysis localized the disease locus between DXS84 (Xp21.1) and DXS255. Here we present additional linkage data that provide further support and refinement of this localization. Individual III-18 gave birth to a male, currently aged 2 7/12 years, who clearly shows delayed psychomotor development. He began to walk at 23 months and his speech is delayed. In addition, he shows the characteristic facial anomalies, {open_quotes}dysplastic{close_quotes} ears, sacral dimple, and clinodactyly, as do all other affected males in this family. 7 refs., 1 tab.

  15. Space-charge driven emittance growth in a 3D mismatched anisotropic beam

    International Nuclear Information System (INIS)

    Qiang, J.; Ryne, R.D.; Hofmann, I.

    2002-01-01

    In this paper we present a 3D simulation study of the emittance growth in a mismatched anisotropic beam. The equipartitioning driven by a 4th order space-charge resonance can be significantly modified by the presence of mismatch oscillation and halo formation. This causes emittance growth in both the longitudinal and transverse directions which could drive the beam even further away from equipartition. The averaged emittance growth per degree freedom follows the upper bound of the 2D free energy limit plus the contributions from equipartitioning

  16. Investigating methods for determining mismatch in near side vehicle impacts - biomed 2009.

    Science.gov (United States)

    Loftis, Kathryn; Martin, R Shayn; Meredith, J Wayne; Stitzel, Joel

    2009-01-01

    This study investigates vehicle mismatch in severe side-impact motor vehicle collisions. Research conducted by the Insurance Institute for Highway Safety has determined that vehicle mismatch often leads to very severe injuries for occupants in the struck vehicle, because the larger striking vehicle does not engage the lower sill upon impact, resulting in severe intrusions into the occupant compartment. Previous studies have analyzed mismatched collisions according to vehicle type, not by the difference in vehicle height and weight. It is hypothesized that the combination of a heavier striking vehicle at a taller height results in more intrusion for the struck vehicle and severe injury for the near side occupant. By analyzing Crash Injury Research and Engineering Network (CIREN) data and occupant injury severity, it is possible to study intrusion and injuries that occur due to vehicle mismatch. CIREN enrolls seriously injured occupants involved in motor vehicle crashes (MVC) across the United States. From the Toyota-Wake Forest University CIREN center, 23 near side impact cases involving two vehicles were recorded. Only 3 of these seriously injured occupant cases were not considered mismatched according to vehicle curb weight, and only 2 were not considered vehicle mismatched according to height differences. The mismatched CIREN cases had an average difference in vehicle curb weight of 737.0 kg (standard deviation of 646.8) and an average difference in vehicle height of 16.38 cm (standard deviation of 7.186). There were 13 occupants with rib fractures, 12 occupants with pelvic fractures, 9 occupants with pulmonary contusion, and 5 occupants with head injuries, among other multiple injuries. The average Injury Severity Score (ISS) for these occupants was 27, with a standard deviation of 16. The most serious injuries resulted in an Abbreviated Injury Scale (AIS) of 5, which included 3 occupants. Each of these AIS 5 injuries were to different body regions on different

  17. Effects of frequency mismatch on a self-consistent arbitrary amplitude cyclotron resonance laser accelerator

    International Nuclear Information System (INIS)

    Pakter, R.; Schneider, R.S.; Rizzato, F.B.

    1993-01-01

    The cyclotron-resonance laser accelerator (CRLA), where a coherent electromagnetic wave may transfer a large amount of energy to a beam of electrons gravitating in a guide magnetic field is studied. This large amount of transferred energy takes place due to the autoresonance mechanism where, under some ideal conditions, an initial wave-particle synchronism is self-sustained throughout the accelerating period. An improved analysis of the mentioned self-consistent wave-particle interaction, taking into account a possible frequency mismatch between wave and particles. It is also shown how the frequency mismatch can compensate the dispersion effects. (L.C.J.A.)

  18. Idiopathic pulmonary fibrosis. A rare cause of scintigraphic ventilation-perfusion mismatch

    International Nuclear Information System (INIS)

    Pochis, W.T.; Krasnow, A.Z.; Collier, B.D.; Mewissen, M.W.; Almagro, U.A.; Hellman, R.S.; Isitman, A.T.

    1990-01-01

    A case of idiopathic pulmonary fibrosis with multiple areas of mismatch on ventilation-perfusion lung imaging in the absence of pulmonary embolism is presented. Idiopathic pulmonary fibrosis is one of the few nonembolic diseases producing a pulmonary ventilation-perfusion mismatch. In this condition, chest radiographs may not detect the full extent of disease, and xenon-133 ventilation imaging may be relatively insensitive to morbid changes in small airways. Thus, when examining patients with idiopathic pulmonary fibrosis, one should be aware that abnormal perfusion imaging patterns without matching ventilation abnormalities are not always due to embolism. In this setting, contrast pulmonary angiography is often needed for accurate differential diagnosis

  19. Structure Transformation and Coherent Interface in Large Lattice-Mismatched Nanoscale Multilayers

    Directory of Open Access Journals (Sweden)

    J. Y. Xie

    2013-01-01

    Full Text Available Nanoscale Al/W multilayers were fabricated by DC magnetron sputtering and characterized by transmission electron microscopy and high-resolution electron microscopy. Despite the large lattice mismatch and significantly different lattice structures between Al and W, a structural transition from face-centered cubic to body-centered cubic in Al layers was observed when the individual layer thickness was reduced from 5 nm to 1 nm, forming coherent Al/W interfaces. For potential mechanisms underlying the observed structure transition and forming of coherent interfaces, it was suggested that the reduction of interfacial energy and high stresses induced by large lattice-mismatch play a crucial role.

  20. Idiopathic pulmonary fibrosis. A rare cause of scintigraphic ventilation-perfusion mismatch

    Energy Technology Data Exchange (ETDEWEB)

    Pochis, W.T.; Krasnow, A.Z.; Collier, B.D.; Mewissen, M.W.; Almagro, U.A.; Hellman, R.S.; Isitman, A.T. (Medical College of Wisconsin, Milwaukee (USA))

    1990-05-01

    A case of idiopathic pulmonary fibrosis with multiple areas of mismatch on ventilation-perfusion lung imaging in the absence of pulmonary embolism is presented. Idiopathic pulmonary fibrosis is one of the few nonembolic diseases producing a pulmonary ventilation-perfusion mismatch. In this condition, chest radiographs may not detect the full extent of disease, and xenon-133 ventilation imaging may be relatively insensitive to morbid changes in small airways. Thus, when examining patients with idiopathic pulmonary fibrosis, one should be aware that abnormal perfusion imaging patterns without matching ventilation abnormalities are not always due to embolism. In this setting, contrast pulmonary angiography is often needed for accurate differential diagnosis.

  1. Significance of angular mismatch between vertebral endplate and prosthetic endplate in lumbar total disc replacement.

    Science.gov (United States)

    Lee, Chong Suh; Chung, Sung Soo; Oh, Sung Kyun; You, Je Wook

    2011-05-01

    A retrospective study. To determine whether angular mismatch between the vertebral endplate and prosthetic endplate during lumbar total disc replacement (L-TDR) affects the radiological and clinical outcomes. A prosthesis anchored to the vertebral body by using a large central keel carries an inherent risk of angular mismatch between the vertebral endplate and prosthetic endplate at a segment with a greater degree of lordosis, such as L5-S1. Theoretically, this angular mismatch can cause several problems, such as segmental hyperlordosis, anterior positioning of the upper prosthesis, posterior prosthetic edge subsidence, decreased range of motion (ROM), and a poor clinical outcome. This study evaluated 64 prosthetic levels of 56 patients who were implanted with L-TDR between June 2002 and February 2006. There were 38 and 26 prosthetic levels at the L4-5 and L5-S1, respectively. The mean follow-up period was 25.6 (12 to 49) months. The angle of mismatch between the lower endplate of the upper vertebral body and the upper prosthetic plate, segmental flexion/extension ROM, segmental lordosis angle at extension, distance from the posterior wall of the vertebral body to the posterior prosthetic edge were measured by obtaining radiographs. Clinically, the Visual Analogue Scale and Oswestry Disability Index were also evaluated. The angular mismatches between the upper vertebra and prosthesis at L4-5 and L5-S1 were 1.6 degree and 5.6 degree, respectively (P body to the posterior edge of the prosthesis in L5-S1 were 6.8 degree (4 to 13), 12.8 degree (8 to 17), and 3.8 mm (1 to 6 mm) in patients with an angular mismatch of 0.05). Angular mismatch was more common in L5-S1 than in L4-5. L-TDR at the most lordotic level, L5-S1, and implantation of an upper prosthesis with a mismatched angle seem to be the causes of a reduced segmental ROM, increased segmental lordosis, and anterior malpositioning of the prosthesis. However, these changes do not affect the clinical outcomes of

  2. An invasive social insect overcomes genetic load at the sex locus.

    Science.gov (United States)

    Gloag, Rosalyn; Ding, Guiling; Christie, Joshua R; Buchmann, Gabriele; Beekman, Madeleine; Oldroyd, Benjamin P

    2016-11-07

    Some invasive hymenopteran social insects found new populations with very few reproductive individuals. This is despite the high cost of founder effects for such insects, which generally require heterozygosity at a single locus-the complementary sex determiner, csd-to develop as females. Individuals that are homozygous at csd develop as either infertile or subfertile diploid males or not at all. Furthermore, diploid males replace the female workers that are essential for colony function. Here we document how the Asian honey bee (Apis cerana) overcame the diploid male problem during its invasion of Australia. Natural selection prevented the loss of rare csd alleles due to genetic drift and corrected the skew in allele frequencies caused by founder effects to restore high average heterozygosity. Thus, balancing selection can alleviate the genetic load at csd imposed by severe bottlenecks, and so facilitate invasiveness.

  3. Fine-Mapping of the 1p11.2 Breast Cancer Susceptibility Locus

    DEFF Research Database (Denmark)

    Horne, Hisani N; Chung, Charles C; Zhang, Han

    2016-01-01

    rs11249433 in 45,276 breast cancer cases and 48,998 controls of European, Asian and African ancestry from 50 studies in the Breast Cancer Association Consortium. Genotyping was done using iCOGS, a custom-built array. Due to the complicated nature of the region on chr1p11.2: 120......The Cancer Genetic Markers of Susceptibility genome-wide association study (GWAS) originally identified a single nucleotide polymorphism (SNP) rs11249433 at 1p11.2 associated with breast cancer risk. To fine-map this locus, we genotyped 92 SNPs in a 900kb region (120,505,799-121,481,132) flanking......,300,000-120,505,798, that lies near the centromere and contains seven duplicated genomic segments, we restricted analyses to 429 SNPs excluding the duplicated regions (42 genotyped and 387 imputed). Per-allelic associations with breast cancer risk were estimated using logistic regression models adjusting for study and ancestry...

  4. Characterization of a Multipeptide Lantibiotic Locus in Streptococcus pneumoniae

    Directory of Open Access Journals (Sweden)

    Natalie Maricic

    2016-01-01

    Full Text Available Bacterial communities are established through a combination of cooperative and antagonistic interactions between the inhabitants. Competitive interactions often involve the production of antimicrobial substances, including bacteriocins, which are small antimicrobial peptides that target other community members. Despite the nearly ubiquitous presence of bacteriocin-encoding loci, inhibitory activity has been attributed to only a small fraction of gene clusters. In this study, we characterized a novel locus (the pld locus in the pathogen Streptococcus pneumoniae that drives the production of a bacteriocin called pneumolancidin, which has broad antimicrobial activity. The locus encodes an unusual tandem array of four inhibitory peptides, three of which are absolutely required for antibacterial activity. The three peptide sequences are similar but appear to play distinct roles in regulation and inhibition. A modification enzyme typically found in loci encoding a class of highly modified bacteriocins called lantibiotics was required for inhibitory activity. The production of pneumolancidin is controlled by a two-component regulatory system that is activated by the accumulation of modified peptides. The locus is located on a mobile element that has been found in many pneumococcal lineages, although not all elements carry the pld genes. Intriguingly, a minimal region containing only the genes required for pneumolancidin immunity was found in several Streptococcus mitis strains. The pneumolancidin-producing strain can inhibit nearly all pneumococci tested to date and provided a competitive advantage in vivo. These peptides not only represent a unique strategy for bacterial competition but also are an important resource to guide the development of new antimicrobials.

  5. 'Locus of control', health-related quality of life, emotional distress and disability in Parkinson's disease.

    Science.gov (United States)

    Rizza, Federica; Gison, Annalisa; Bonassi, Stefano; Dall'Armi, Valentina; Tonto, Francesca; Giaquinto, Salvatore

    2017-06-01

    This cross-sectional study evaluated locus of control and its subscales in Parkinson's disease. A total of 50 consecutive Parkinson's disease participants and 50 healthy volunteers (control group) were enrolled. External locus of control was significantly higher in Parkinson's disease participants, whereas internal locus of control had no significant differences. External locus of control and internal locus of control were correlated in control group, but not in Parkinson's disease. In Parkinson's disease participants, external locus of control was negatively associated with health-related quality of life as well as positively associated with emotional distress and disease severity (but not with disability). After adjusting to confound variables, the associations remained. On the other hand, internal locus of control was negatively associated with depression.

  6. The Effects of Locus of Control and Task Difficulty on Procrastination.

    Science.gov (United States)

    Janssen, Tracy; Carton, John S

    1999-12-01

    The authors investigated the effects of locus of control expectancies and task difficulty on procrastination. Forty-two college students were administered an academic locus of control scale and a task that was similar to a typical college homework assignment. The students were randomly assigned to 1 of 2 task difficulty levels. Although none of the results involving task difficulty was significant, several results involving locus of control were significant. Specifically, analyses revealed that students with internal locus of control expectancies tended to begin working on the assignment sooner than students with external locus of control expectancies. In addition, students with internal locus of control completed and returned the assignment sooner than students with external locus of control. The results are discussed within the context of J. B. Rotter's (1966, 1975, 1982) social learning theory.

  7. Population genetics of the HRAS1 minisatellite locus

    Energy Technology Data Exchange (ETDEWEB)

    Devlin, B.; Risch, N. (Yale Univ., New Haven, CT (United States)); Krontiris, T. (Tufts Univ., Boston, MA (United States) New England Medical Center Hospital, Boston, MA (United States))

    1993-12-01

    Several years ago it was reported that rare HRAS1 VNTR alleles occurred more frequently in US Caucasian cancer patients than in unaffected controls. Such an association, in theory, could be caused by undetected population heterogeneity. Also, in a study clearly relevant to this issue, it was recently reported that significant deviations from Hardy-Weinberg equilibrium exist at this locus in a sample of US Caucasians. These considerations motivate population genetic analysis of the HRAS1 locus. From published studies of the HRAS1 VNTR locus, which classified alleles into types, the authors found only small differences in the allele frequency distributions of samples from various European nations, although there were larger differences among ethnic groups (African American, Caucasian, and Oriental). In an analysis of variation of rare-allele frequencies among samples from four European nations, most of the variance was attributable to molecular methodology, and very little of the variance was accounted for by nationality. In addition, the authors showed that mixture of European subpopulations should result in only minor deviations from expected genotype proportions in a Caucasian database and demonstrated that there was no significant deviation from Hardy-Weinberg equilibrium in the HRAS1 data. 35 refs., 4 tabs.

  8. Molecular Mapping of PMR1, a Novel Locus Conferring Resistance to Powdery Mildew in Pepper (Capsicum annuum

    Directory of Open Access Journals (Sweden)

    Jinkwan Jo

    2017-12-01

    Full Text Available Powdery mildew, caused by Leveillula taurica, is a major fungal disease affecting greenhouse-grown pepper (Capsicum annuum. Powdery mildew resistance has a complex mode of inheritance. In the present study, we investigated a novel powdery mildew resistance locus, PMR1, using two mapping populations: 102 ‘VK515' F2:3 families (derived from a cross between resistant parental line ‘VK515R' and susceptible parental line ‘VK515S' and 80 ‘PM Singang' F2 plants (derived from the F1 ‘PM Singang' commercial hybrid. Genetic analysis of the F2:3 ‘VK515' and F2 ‘PM Singang' populations revealed a single dominant locus for inheritance of the powdery mildew resistance trait. Genetic mapping showed that the PMR1 locus is located on syntenic regions of pepper chromosome 4 in a 4-Mb region between markers CZ2_11628 and HRM4.1.6 in ‘VK515R'. Six molecular markers including one SCAR marker and five SNP markers were localized to a region 0 cM from the PMR1 locus. Two putative nucleotide-binding site leucine-rich repeat (NBS-LRR-type disease resistance genes were identified in this PMR1 region. Genotyping-by-sequencing (GBS and genetic mapping analysis revealed suppressed recombination in the PMR1 region, perhaps due to alien introgression. In addition, a comparison of species-specific InDel markers as well as GBS-derived SNP markers indicated that C. baccatum represents a possible source of such alien introgression of powdery mildew resistance into ‘VK515R'. The molecular markers developed in this study will be especially helpful for marker-assisted selection in pepper breeding programs for powdery mildew resistance.

  9. Molecular Mapping of PMR1, a Novel Locus Conferring Resistance to Powdery Mildew in Pepper (Capsicum annuum).

    Science.gov (United States)

    Jo, Jinkwan; Venkatesh, Jelli; Han, Koeun; Lee, Hea-Young; Choi, Gyung Ja; Lee, Hee Jae; Choi, Doil; Kang, Byoung-Cheorl

    2017-01-01

    Powdery mildew, caused by Leveillula taurica , is a major fungal disease affecting greenhouse-grown pepper ( Capsicum annuum ). Powdery mildew resistance has a complex mode of inheritance. In the present study, we investigated a novel powdery mildew resistance locus, PMR1 , using two mapping populations: 102 'VK515' F 2:3 families (derived from a cross between resistant parental line 'VK515R' and susceptible parental line 'VK515S') and 80 'PM Singang' F 2 plants (derived from the F 1 'PM Singang' commercial hybrid). Genetic analysis of the F 2:3 'VK515' and F 2 'PM Singang' populations revealed a single dominant locus for inheritance of the powdery mildew resistance trait. Genetic mapping showed that the PMR1 locus is located on syntenic regions of pepper chromosome 4 in a 4-Mb region between markers CZ2_11628 and HRM4.1.6 in 'VK515R'. Six molecular markers including one SCAR marker and five SNP markers were localized to a region 0 cM from the PMR1 locus. Two putative nucleotide-binding site leucine-rich repeat (NBS-LRR)-type disease resistance genes were identified in this PMR1 region. Genotyping-by-sequencing (GBS) and genetic mapping analysis revealed suppressed recombination in the PMR1 region, perhaps due to alien introgression. In addition, a comparison of species-specific InDel markers as well as GBS-derived SNP markers indicated that C. baccatum represents a possible source of such alien introgression of powdery mildew resistance into 'VK515R'. The molecular markers developed in this study will be especially helpful for marker-assisted selection in pepper breeding programs for powdery mildew resistance.

  10. The effect of family climate on risky driving of young novices: the moderating role of attitude and locus of control.

    Science.gov (United States)

    Carpentier, Aline; Brijs, Kris; Declercq, Katrien; Brijs, Tom; Daniels, Stijn; Wets, Geert

    2014-12-01

    The aim of the study was to examine the relative importance of young novice drivers' family climate on their driving behavior. A sample of young novice drivers (N=171) between the age of 17 and 24, who held their permanent (or temporary) driver's license for no longer than one year, participated. The questionnaire included items related to the participants' family climate, 3 socio-cognitive determinants (i.e., attitude, locus of control and social norm), and risky driving behaviors. We expected both family climate and the socio-cognitive determinants to exert a direct effect on risky driving. Furthermore we hypothesized that the socio-cognitive determinants would moderate the impact of family climate on risky driving. The results showed that the effect of family climate on risky driving only originated from one single factor (i.e., noncommitment). Besides that, the results confirmed the importance of the three socio-cognitive determinants to the degree that attitude, locus of control, and social norm significantly predicted the self-reported risky driving. In line of what we hypothesized, attitude moderated the relationship between noncommitment and risky driving. Lastly, we found an unexpected three-way interaction which indicated that locus of control moderated the relation between noncommitment and risky driving only when young drivers' attitude was risk-supportive. We recommend scholars and practitioners to take into account the interaction between external sources of influence (such as an individual's family climate) and more personally oriented dispositions (such as an individual's attitude, social norm and locus of control) when trying to explain and change young novices' risky driving. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. High-resolution mapping of the x-linked hypohidrotic ectodermal dysplasia (EDA) locus

    Energy Technology Data Exchange (ETDEWEB)

    Zonana, J.; Jones, M.; Litt, M.; Kramer, P.; Browne, D.; Becker, H.W. (Oregon Health Sciences Univ., Portland, OR (United States)); Brockdorff, N.; Rastan, S. (Medical Council Clinical Research Centre, Harrow (United Kingdom)); Davies, K.P.; Clarke, A. (Univ. of Wales College of Medicine, Cardiff (United Kingdom)) (and others)

    1992-11-01

    The X-linked hypohidrotic ectodermal dysplasia (EDA) locus has been previously localized to the subchromosomal region Xq11-q21.1. The authors have extended previous linkage studies and analyzed linkage between the EDA locus and 10 marker loci, including five new loci, in 41 families. Four of the marker loci showed no recombination with the EDA locus, and six other loci were also linked to the EDA locus with recombination fractions of .009-.075. Multipoint analysis gave support to the placement of the PGK1P1 locus proximal to the EDA locus and the DXS453 and PGK1 loci distal to EDA. Further ordering of the loci could be inferred from a human-rodent somatic cell hybrid derived from an affected female with EDA and an X;9 translocation and from studies of an affected male with EDA and a submicroscopic deletion. Three of the proximal marker loci, which showed no recombination with the EDA locus, when used in combination, were informative in 92% of females. The closely linked flanking polymorphic loci DXS339 and DXS453 had heterozygosites of 72% and 76%, respectively, and when used jointly, they were doubly informative in 52% of females. The human DXS732 locus was defined by a conserved mouse probe pcos169E/4 (DXCrc169 locus) that consegregates with the mouse tabby (Ta) locus, a potential homologue to the EDA locus. The absence of recombination between EDA and the DXSA732 locus lends support to the hypothesis that the DXCrc169 locus in the mouse and the DXS732 locus in humans may contain candidate sequences for the Ta and EDA genes, respectively. 36 refs., 1 fig., 5 tabs.

  12. Plasmons in Dimensionally Mismatched Coulomb Coupled Graphene Systems.

    Science.gov (United States)

    Badalyan, S M; Shylau, A A; Jauho, A P

    2017-09-22

    We calculate the plasmon dispersion relation for Coulomb coupled metallic armchair graphene nanoribbons and doped monolayer graphene. The crossing of the plasmon curves, which occurs for uncoupled 1D and 2D systems, is split by the interlayer Coulomb coupling into a lower and an upper plasmon branch. The upper branch exhibits an unusual behavior with end points at finite q. Accordingly, the structure factor shows either a single or a double peak behavior, depending on the plasmon wavelength. The new plasmon structure is relevant to recent experiments, its properties can be controlled by varying the system parameters and be used in plasmonic applications.

  13. Locus de Controle e escolha do método anticoncepcional Locus de Control y método anticonceptivo elegido Locus of Control and choice of contraceptive method

    Directory of Open Access Journals (Sweden)

    Aline Salheb Alves

    2007-06-01

    Full Text Available Objetivou-se avaliar a relação entre o Locus de Controle e o tipo de método contraceptivo escolhido. Foi utilizada a Escala Multidimensional de Locus de Controle de Levenson e entrevistadas 191 mulheres. As usuárias de preservativo masculino apresentaram maior Internalidade do que as usuárias de injetável mensal. Quanto ao locus Externalidade Outros Poderosos, as usuárias de implante apresentavam menor externalidade do que as usuárias de preservativo masculino, laqueadura, injetável trimestral e DIU. Considerando-se o locus Externalidade Acaso, as usuárias de implante apresentaram menores escores do que as mulheres que optaram pela laqueadura, injetável trimestral e DIU. Observou-se ainda, menor Externalidade Acaso entre as usuárias de injetável mensal em relação às mulheres que fizeram opção pelo injetável trimestral.El objetivo es validar la relación entre el Locus de Control y el tipo de método anticonceptivo elegido. Fue usada la Escala Multidimensional de Locus de Control de Levenson. Fueron entrevistadas 191 mujeres. Las usuarias de condón masculino presentaron Internalidad más grande que las usuarias de inyectable mensual. Considerado el Locus Externalidad - Otro poderoso, las usuarias de implante presentaron menor externalidad de que las usuarias de condón masculino, laqueadura, inyectable trimestral y DIU. Considerado el Locus Externalidad - Quizá, las usuarias del implante presentaron menores resultados que las mujeres que eligieron por la laqueadura, inyectable trimestral y DIU. Se observo que las mujeres usuarias de inyectable mensual presentaron menor Externalidad - Quizá que las mujeres usuarias de inyectable trimestral.The purpose was to assess the relationship between locus of control and the contraceptive method chosen. It was used the Levenson's Multidimensional Locus of Control Scale and 191 women was interviewed. Users of male condoms presented greater Internality than the monthly contraceptive

  14. The Role of Education Pathways in the Relationship between Job Mismatch, Wages and Job Satisfaction: A Panel Estimation Approach

    Science.gov (United States)

    Mavromaras, Kostas; Sloane, Peter; Wei, Zhang

    2012-01-01

    This paper examines the outcome of over-skilling and over-education on wages and job satisfaction of full-time employees in Australia between 2001 and 2008. We employ a random effects probit model with Mundlak corrections. We find differences by type of mismatch, education pathway, and gender. We categorise reported mismatches as genuine…

  15. Circuit mismatch and current coupling effect influence on paralleling SiC MOSFETs in multichip power modules

    DEFF Research Database (Denmark)

    Li, Helong; Beczkowski, Szymon; Munk-Nielsen, Stig

    2015-01-01

    This paper reveals that there are circuit mismatches and a current coupling effect in the direct bonded copper (DBC) layout of a silicon carbide (SiC) MOSFET multichip power module. According to the modelling and the mathematic analysis of the DBC layout, the mismatch of the common source stray i...

  16. Impact of prosthesis-patient mismatch on early and late mortality after aortic valve replacement

    NARCIS (Netherlands)

    Koene, Bart M.; Hamad, Mohamed A. Soliman; Bouma, Wobbe; Mariani, Massimo A.; Peels, Kathinka C.; van Dantzig, Jan-Melle; van Straten, Albert H.

    2013-01-01

    Background: The influence of prosthesis-patient mismatch (PPM) on survival after aortic valve replacement (AVR) remains controversial. In this study, we sought to determine the effect of PPM on early (30 days) after AVR or AVR combined with coronary artery bypass grafting (AVR with CABG). Methods:

  17. Labour Market Mismatch among UK Graduates: An Analysis Using REFLEX Data

    Science.gov (United States)

    McGuinness, Seamus; Sloane, Peter J.

    2011-01-01

    There is much disagreement in the literature over the extent to which graduates are mismatched in the labour market and the reasons for this. In this paper we utilise the Flexible Professional in the Knowledge Society (REFLEX) data set to cast light on these issues, based on data for UK graduates. We find substantial pay penalties for…

  18. Developmental changes in mismatch responses to mandarin consonants and lexical tones from early to middle childhood.

    Directory of Open Access Journals (Sweden)

    Huei-Mei Liu

    Full Text Available The purpose of this study was to use mismatch responses (MMRs to explore the dynamic changes of Mandarin speech perception abilities from early to middle childhood. Twenty preschoolers, 18 school-aged children, and 26 adults participated in this study. Two sets of synthesized speech stimuli varying in Mandarin consonant (alveolo-palatal affricate vs. fricative and lexical tone features (rising vs. contour tone were used to examine the developmental course of speech perception abilities. The results indicated that only the adult group demonstrated typical early mismatch negativity (MMN responses, suggesting that the ability to discriminate specific speech cues in Mandarin consonant and lexical tone is a continuing process in preschool- and school-aged children. Additionally, distinct MMR patterns provided evidence indicating diverse developmental courses to different speech characteristics. By incorporating data from the two speech conditions, we propose using MMR profiles consisting of mismatch negativity (MMN, positive mismatch response (p-MMR, and late discriminative negativity (LDN as possible brain indices to investigate speech perception development.

  19. Solvent effects on hydrogen bonds in Watson-Crick, mismatched, and modified DNA base pairs

    NARCIS (Netherlands)

    Poater, Jordi; Swart, Marcel; Guerra, Celia Fonseca; Bickelhaupt, F. Matthias

    2012-01-01

    We have theoretically analyzed a complete series of Watson–Crick and mismatched DNA base pairs, both in gas phase and in solution. Solvation causes a weakening and lengthening of the hydrogen bonds between the DNA bases because of the stabilization of the lone pairs involved in these bonds. We have

  20. A Database to Support the Interpretation of Human Mismatch Repair Gene Variants

    NARCIS (Netherlands)

    Ou, Jianghua; Niessen, Renee C.; Vonk, Jan; Westers, Helga; Hofstra, Robert M. W.; Sijmons, Rolf H.

    Germline mutations in the mismatch repair (MMR) genes MLH1, MSH2, MSH6, or PMS2 can cause Lynch syndrome. This syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC), is an autosomal dominantly-inherited disorder predominantly characterized by colorectal and endometrial cancer.

  1. Optimizing the face Paradigm of BCI system by modified Mismatch Negative paradigm

    Directory of Open Access Journals (Sweden)

    Siejie Zhou

    2016-10-01

    Full Text Available Many recent studies have focused on improving the performance of event-related potential (ERP based brain computer interfaces (BCIs. The use of a face pattern has been shown to obtain high classification accuracies and information transfer rates (ITRs by evoking discriminative ERPs (N200 and N400 in addition to P300 potentials. Recently, it has been proved that the performance of traditional P300-based BCIs could be improved through a modification of the mismatch pattern. In this paper, a mismatch inverted face pattern (MIF-pattern was presented to improve the performance of the inverted face pattern (IF-pattern, one of the state of the art patterns used in visual-based BCI systems. Ten subjects attended in this experiment. The result showed that the mismatch inverted face pattern could evoke significantly larger vertex positive potentials (p<0.05 and N400s (p<0.05 compared to the inverted face pattern. The classification accuracy (mean accuracy is 99.58% and ITRs (mean bit rate is 27.88 bit/min of the mismatch inverted face pattern was significantly higher than that of the inverted face pattern (p<0.05.

  2. What do Educational Mismatches tell us about Skill Mismachtes? A Cross-country Analysis

    NARCIS (Netherlands)

    Allen, Jim; de Weert, Egbert

    2007-01-01

    The relationship between higher education and employment is commonly interpreted in terms of the extent to which the higher education sector is providing graduates with the knowledge and skills to match employment needs. It is assumed that a mismatch between working in a job and level or field of

  3. Sector-Based Analysis of the Education-Occupation Mismatch in the Turkish Labor Market

    Science.gov (United States)

    Mercan, Murat Anil; Karakas, Mesut; Citci, Sadettin Haluk; Babacan, Mehmet

    2015-01-01

    The aim of this study was to investigate the existence of sectorial undereducation and overeducation problems in the Turkish labor market. In order to cope with this issue, the 2009 Household Labor Force Survey (TurkStat), which covers 145,934 individuals within 27 sectors, was utilized. An objective measure of education-occupation mismatch based…

  4. Surface reconstruction: An effective method for the growth of mismatched materials

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Yu; Zheng, Beining; Wu, Xiaofeng; Yuan, Long; Wu, Jie; Guo, Hongping; Huang, Keke; Feng, Shouhua, E-mail: shfeng@mail.jlu.edu.cn

    2016-01-01

    Graphical abstract: High quality thin film of GaSb was fabricated with molecular beam epitaxy technique on the reconstructed Si(1 1 1) surface. - Highlights: • Surface reconstruction formed by different surface treatments controls the heteroepitaxial growth. • Mismatched stress can be effectively released when the mismatched material epi-film tilts out of the epitaxial interface plane to create a coincidence-site lattice. • GaSb films grown on Si(1 1 1)-(5√3 × 5√3)-Sb surface show better crystal quality and morphology for its self-assembled 2D fishbone structure. - Abstract: The crystalline quality of epitaxial films depends on the degree of lattice match between substrates and films. Here, we report a growth strategy for large mismatched epi-films to grow GaSb films on Si(1 1 1) substrates. The epitaxial strategy can be influenced by controlling the surface reconstructions of Sb-treated Si(1 1 1). The film with the best quality was grown on Si(1 1 1)-(5√3 × 5√3)-Sb surface due to the stress release and the formation of a self-assembled 2D fishbone structure. Controlled surface engineering provides an effective pathway towards the growth of the large mismatched materials.

  5. Frequent mismatch-repair defects link prostate cancer to Lynch syndrome

    DEFF Research Database (Denmark)

    Dominguez-Valentin, Mev; Joost, Patrick; Therkildsen, Christina

    2016-01-01

    were high-grade tumors with Gleason scores 8-10. Prostate cancer was associated with mutations in MSH2, MLH1 and MSH6 with loss of the respective mismatch repair protein in 69 % of the tumors, though a MSI-high phenotype was restricted to 13 % of the tumors. The cumulative risk of prostate cancer...

  6. Physical and functional interactions between Werner syndrome helicase and mismatch-repair initiation factors

    DEFF Research Database (Denmark)

    Saydam, Nurten; Kanagaraj, Radhakrishnan; Dietschy, Tobias

    2007-01-01

    is poorly understood. Here we show that WRN physically interacts with the MSH2/MSH6 (MutSalpha), MSH2/MSH3 (MutSbeta) and MLH1/PMS2 (MutLalpha) heterodimers that are involved in the initiation of mismatch repair (MMR) and the rejection of homeologous recombination. MutSalpha and MutSbeta can strongly...

  7. Skill mismatch and skill use in developed countries: Evidence from the PIAAC study

    NARCIS (Netherlands)

    Allen, J.P.; Levels, M.; van der Velden, R.K.W.

    2013-01-01

    In this paper we develop and test a new set of measures of skill mismatches, based on data on skill levels and skill use in the domains of literacy and numeracy from the PIAAC project. The measures we develop represent the extent of skill use relative to one’s own skill level. We test the measures

  8. Mismatch in working hours and affective commitment : Differential relationships for distinct employee groups

    NARCIS (Netherlands)

    Emmerik, I.J. Hetty van; Sanders, Karin

    2005-01-01

    Purpose – This study examined the relationship between two types of mismatch (i.e. non-correspondence between preferred and actual number of hours), and affective commitment. It was argued that specific groups of employees, i.e. women and part-time working employees, attach more importance to their

  9. A skill mismatch for migrant workers? Evidence from WageIndicator survey data

    NARCIS (Netherlands)

    Tijdens, K.; van Klaveren, M.; Galgóczi, B.; Leschke, J.; Watt, A.

    2012-01-01

    Are overeducation and undereducation more common among migrants compared to domestic workers? If so, are overeducation and undereducation similar across migrants from various home countries and across various host countries? This chapter is aimed at unravelling the incidence of skill mismatch,

  10. A match-mismatch test of a stage model of behaviour change in tobacco smoking

    NARCIS (Netherlands)

    Dijkstra, A; Conijn, B; De Vries, H

    Aims An innovation offered by stage models of behaviour change is that of stage-matched interventions. Match-mismatch studies are the primary test of this idea but also the primary test of the validity of stage models. This study aimed at conducting such a test among tobacco smokers using the Social

  11. Robust MOE Detector for DS-CDMA Systems with Signature Waveform Mismatch

    Science.gov (United States)

    Lin, Tsui-Tsai

    In this letter, a decision-directed MOE detector with excellent robustness against signature waveform mismatch is proposed for DS-CDMA systems. Both the theoretic analysis and computer simulation results demonstrate that the proposed detector can provide better SINR performance than that of conventional detectors.

  12. The role of the bacterial mismatch repair system in SOS-induced mutagenesis: a theoretical background

    International Nuclear Information System (INIS)

    Belov, O.V.; Kapralov, M.I.; Chuluunbaatar, O.; Sweilam, N.H.

    2012-01-01

    A theoretical study is performed of the possible role of the methyl-directed mismatch repair system in the ultraviolet-induced mutagenesis of Escherichia coli bacterial cells. For this purpose, a mathematical model of the bacterial mismatch repair system is developed. Within this model, the key pathways of this type of repair are simulated on the basis of modern experimental data related to its mechanisms. Here we have modelled in detail five main pathways of DNA misincorporation removal with different DNA exonucleases. Using our calculations, we have tested the hypothesis that the bacterial mismatch repair system is responsible for the removal of the nucleotides misincorporated by DNA polymerase V (the UmuD' 2 C complex) during ultraviolet-induced SOS response. For the theoretical analysis of the mutation frequency, we have combined the proposed mathematical approach with the model of SOS-induced mutagenesis in the E.coli bacterial cell developed earlier. Our calculations support the hypothesis that methyl-directed mismatch repair influences the mutagenic effect of ultraviolet radiation

  13. The match-mismatch model of emotion processing styles and emotion regulation strategies in fibromyalgia.

    NARCIS (Netherlands)

    Geenen, R.; Ooijen-van der Linden, L. van; Lumley, M.A.; Bijlsma, J.W.J.; Middendorp, H. van

    2012-01-01

    OBJECTIVE: Individuals differ in their style of processing emotions (e.g., experiencing affects intensely or being alexithymic) and their strategy of regulating emotions (e.g., expressing or reappraising). A match-mismatch model of emotion processing styles and emotion regulation strategies is

  14. Aortic valve prosthesis-patient mismatch and exercise capacity in adult patients with congenital heart disease

    NARCIS (Netherlands)

    van Slooten, Ymkje J.; Melle, van Joost P.; Freling, Hendrik G.; Bouma, Berto J.; van Dijk, Arie P. J.; Jongbloed, Monique R. M.; Post, Martijn C.; Sieswerda, Gertjan T.; in 't Veld, Anna Huis; Ebels, Tjark; Voors, Adriaan A.; Pieper, Petronella G.

    Objectives To report the prevalence of aortic valve prosthesis patient mismatch (PPM) in an adult population with congenital heart disease (CHD) and its impact on exercise capacity. Adults with congenital heart disease (ACHD) with a history of aortic valve replacement may outgrow their prosthesis

  15. Aortic valve prosthesis-patient mismatch and exercise capacity in adult patients with congenital heart disease

    NARCIS (Netherlands)

    van Slooten, Ymkje J.; van Melle, Joost P.; Freling, Hendrik G.; Bouma, Berto J.; van Dijk, Arie Pj; Jongbloed, Monique Rm; Post, Martijn C.; Sieswerda, Gertjan T.; Huis In 't Veld, Anna; Ebels, Tjark; Voors, Adriaan A.; Pieper, Petronella G.

    2016-01-01

    To report the prevalence of aortic valve prosthesis-patient mismatch (PPM) in an adult population with congenital heart disease (CHD) and its impact on exercise capacity. Adults with congenital heart disease (ACHD) with a history of aortic valve replacement may outgrow their prosthesis later in

  16. Job Supply and Demand for University Graduates in Spain: A (Relative) Mismatch Perspective

    Science.gov (United States)

    Parellada, Marti; Duch, Nestor; Alvarez, Montserrat

    2009-01-01

    This article provides an analysis of job supply by Spanish firms and the demand for work, and the mismatch that occurs between these two variables. Data are taken for the year 2006, with particular attention to jobs offered by firms that require people with university degrees or other higher education qualifications. Demand and supply are broken…

  17. Density dependence and microevolution interactively determine effects of phenology mismatch on population dynamics

    NARCIS (Netherlands)

    Reed, T.; Gienapp, P.; Visser, M.E.

    2015-01-01

    Life cycle events in plants and animals are typically adaptively tuned to anticipate predictable seasonal changes in environmental conditions or resources. Climate change is expected to affect the temporal component of species’ interactions, e.g. by creating a mismatch between a predator's breeding

  18. Localization by interaural time difference (ITD): Effects of interaural frequency mismatch

    International Nuclear Information System (INIS)

    Bonham, B.H.; Lewis, E.R.

    1999-01-01

    A commonly accepted physiological model for lateralization of low-frequency sounds by interaural time delay (ITD) stipulates that binaural comparison neurons receive input from frequency-matched channels from each ear. Here, the effects of hypothetical interaural frequency mismatches on this model are reported. For this study, the cat close-quote s auditory system peripheral to the binaural comparison neurons was represented by a neurophysiologically derived model, and binaural comparison neurons were represented by cross-correlators. The results of the study indicate that, for binaural comparison neurons receiving input from one cochlear channel from each ear, interaural CF mismatches may serve to either augment or diminish the effective difference in ipsilateral and contralateral axonal time delays from the periphery to the binaural comparison neuron. The magnitude of this increase or decrease in the effective time delay difference can be up to 400 μs for CF mismatches of 0.2 octaves or less for binaural neurons with CFs between 250 Hz and 2.5 kHz. For binaural comparison neurons with nominal CFs near 500 Hz, the 25-μs effective time delay difference caused by a 0.012-octave CF mismatch is equal to the ITD previously shown to be behaviorally sufficient for the cat to lateralize a low-frequency sound source. copyright 1999 Acoustical Society of America.

  19. Ductile Crack Initiation Criterion with Mismatched Weld Joints Under Dynamic Loading Conditions.

    Science.gov (United States)

    An, Gyubaek; Jeong, Se-Min; Park, Jeongung

    2018-03-01

    Brittle failure of high toughness steel structures tends to occur after ductile crack initiation/propagation. Damages to steel structures were reported in the Hanshin Great Earthquake. Several brittle failures were observed in beam-to-column connection zones with geometrical discontinuity. It is widely known that triaxial stresses accelerate the ductile fracture of steels. The study examined the effects of geometrical heterogeneity and strength mismatches (both of which elevate plastic constraints due to heterogeneous plastic straining) and loading rate on critical conditions initiating ductile fracture. This involved applying the two-parameter criterion (involving equivalent plastic strain and stress triaxiality) to estimate ductile cracking for strength mismatched specimens under static and dynamic tensile loading conditions. Ductile crack initiation testing was conducted under static and dynamic loading conditions using circumferentially notched specimens (Charpy type) with/without strength mismatches. The results indicated that the condition for ductile crack initiation using the two parameter criterion was a transferable criterion to evaluate ductile crack initiation independent of the existence of strength mismatches and loading rates.

  20. Geographic Skills Mismatch, Job Search, and Race. Discussion Paper No. 1288-04

    Science.gov (United States)

    Stoll, Michael A.

    2004-01-01

    This paper examines whether a geographic skills mismatch exists between the location of less-educated minorities, in particular African Americans, and high-skill job concentrations, and if so, whether it contributes to the relatively poor employment outcomes of this group. It explores these questions by examining data on the recent geographic…