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Sample records for mph1 requires mismatch

  1. 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...

  2. The Smc5/6 complex regulates the yeast Mph1 helicase at RNA-DNA hybrid-mediated DNA damage

    DEFF Research Database (Denmark)

    Lafuente-Barquero, Juan; Luke-Glaser, Sarah; Graf, Marco

    2017-01-01

    of Fanconi anemia protein M (FANCM), is required for cell viability in the absence of RNase H enzymes. The integrity of the Mph1 helicase domain is crucial to prevent the accumulation of RNA-DNA hybrids and RNA-DNA hybrid-dependent DNA damage, as determined by Rad52 foci. Mph1 forms foci when RNA-DNA hybrids...

  3. Heteroduplex DNA position defines the roles of the Sgs1, Srs2, and Mph1 helicases in promoting distinct recombination outcomes.

    Directory of Open Access Journals (Sweden)

    Katrina Mitchel

    Full Text Available The contributions of the Sgs1, Mph1, and Srs2 DNA helicases during mitotic double-strand break (DSB repair in yeast were investigated using a gap-repair assay. A diverged chromosomal substrate was used as a repair template for the gapped plasmid, allowing mismatch-containing heteroduplex DNA (hDNA formed during recombination to be monitored. Overall DSB repair efficiencies and the proportions of crossovers (COs versus noncrossovers (NCOs were determined in wild-type and helicase-defective strains, allowing the efficiency of CO and NCO production in each background to be calculated. In addition, the products of individual NCO events were sequenced to determine the location of hDNA. Because hDNA position is expected to differ depending on whether a NCO is produced by synthesis-dependent-strand-annealing (SDSA or through a Holliday junction (HJ-containing intermediate, its position allows the underlying molecular mechanism to be inferred. Results demonstrate that each helicase reduces the proportion of CO recombinants, but that each does so in a fundamentally different way. Mph1 does not affect the overall efficiency of gap repair, and its loss alters the CO-NCO by promoting SDSA at the expense of HJ-containing intermediates. By contrast, Sgs1 and Srs2 are each required for efficient gap repair, strongly promoting NCO formation and having little effect on CO efficiency. hDNA analyses suggest that all three helicases promote SDSA, and that Sgs1 and Srs2 additionally dismantle HJ-containing intermediates. The hDNA data are consistent with the proposed role of Sgs1 in the dissolution of double HJs, and we propose that Srs2 dismantles nicked HJs.

  4. Mte1 interacts with Mph1 and promotes crossover recombination and telomere maintenance

    DEFF Research Database (Denmark)

    Pinela da Silva, Sonia Cristina; Altmannova, Veronika; Luke-Glaser, Sarah

    2016-01-01

    Mph1 is a member of the conserved FANCM family of DNA motor proteins that play key roles in genome maintenance processes underlying Fanconi anemia, a cancer predisposition syndrome in humans. Here, we identify Mte1 as a novel interactor of the Mph1 helicase in Saccharomyces cerevisiae. In vitro...

  5. 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

  6. 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.

  7. On Business-Driven IT Security Management and Mismatches between Security Requirements in Firms, Industry Standards and Research Work

    Science.gov (United States)

    Frühwirth, Christian

    Industry managers have long recognized the vital importance of information security for their businesses, but at the same time they perceived security as a technology-driven rather then a business-driven field. Today, this notion is changing and security management is shifting from technology- to business-oriented approaches. Whereas there is evidence of this shift in the literature, this paper argues that security standards and academic work have not yet taken it fully into account. We examine whether this disconnect has lead to a misalignment of IT security requirements in businesses versus industry standards and academic research. We conducted 13 interviews with practitioners from 9 different firms to investigate this question. The results present evidence for a significant gap between security requirements in industry standards and actually reported security vulnerabilities. We further find mismatches between the prioritization of security factors in businesses, standards and real-world threats. We conclude that security in companies serves the business need of protecting information availability to keep the business running at all times.

  8. Interaction of proliferating cell nuclear antigen with PMS2 is required for MutLα activation and function in mismatch repair.

    Science.gov (United States)

    Genschel, Jochen; Kadyrova, Lyudmila Y; Iyer, Ravi R; Dahal, Basanta K; Kadyrov, Farid A; Modrich, Paul

    2017-05-09

    Eukaryotic MutLα (mammalian MLH1-PMS2 heterodimer; MLH1-PMS1 in yeast) functions in early steps of mismatch repair as a latent endonuclease that requires a mismatch, MutSα/β, and DNA-loaded proliferating cell nuclear antigen (PCNA) for activation. We show here that human PCNA and MutLα interact specifically but weakly in solution to form a complex of approximately 1:1 stoichiometry that depends on PCNA interaction with the C-terminal endonuclease domain of the MutLα PMS2 subunit. Amino acid substitution mutations within a PMS2 C-terminal 721 QRLIAP motif attenuate or abolish human MutLα interaction with PCNA, as well as PCNA-dependent activation of MutLα endonuclease, PCNA- and DNA-dependent activation of MutLα ATPase, and MutLα function in in vitro mismatch repair. Amino acid substitution mutations within the corresponding yeast PMS1 motif ( 723 QKLIIP) reduce or abolish mismatch repair in vivo. Coupling of a weak allele within this motif ( 723 AKLIIP) with an exo1 Δ null mutation, which individually confer only weak mutator phenotypes, inactivates mismatch repair in the yeast cell.

  9. Characterization of a Highly Conserved Binding Site of Mlh1 Required for Exonuclease I-Dependent Mismatch Repair

    DEFF Research Database (Denmark)

    Dherin, Claudine; Gueneau, Emeric; Francin, Mathilde

    2009-01-01

    Mlh1 is an essential factor of mismatch repair (MMR) and meiotic recombination. It interacts through its C-terminal region with MutL homologs and proteins involved in DNA repair and replication. In this study, we identified the site of yeast Mlh1 critical for the interaction with Exo1, Ntg2......, and Sgs1 proteins, designated as site S2 by reference to the Mlh1/Pms1 heterodimerization site S1. We show that site S2 is also involved in the interaction between human MLH1 and EXO1 or BLM. Binding at this site involves a common motif on Mlh1 partners that we called the MIP-box for the Mlh1 interacting...... protein box. Direct and specific interactions between yeast Mlh1 and peptides derived from Exo1, Ntg2, and Sgs1 and between human MLH1 and peptide derived from EXO1 and BLM were measured with K(d) values ranging from 8.1 to 17.4 microM. In Saccharomyces cerevisiae, a mutant of Mlh1 targeted at site S2...

  10. 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.…

  11. Detecting scale violations in absence of mismatch requires music-syntactic analysis: a further look at the early right anterior negativity (ERAN).

    Science.gov (United States)

    Kalda, Tiina; Minati, Ludovico

    2012-07-01

    The purpose of this study was to determine whether infrequent scale violations in a sequence of in-key notes are detected when the deviants are matched for frequency of occurrence and preceding intervals with the control notes. We further investigated whether the detectability of scale violations is modulated by the presence of melodic context and by the level of musical training. Event related potentials were recorded from 14 musicians and 13 non-musicians. In non-musicians, the out-of-key notes elicited an early right anterior negativity (ERAN), which appeared prominently over right frontal sites only when presented within structured sequences; no effects were found when the out-of-key notes were presented within scrambled sequences. In musicians, the out-of-key notes elicited a similar bilateral ERAN in structured and scrambled sequences. Our findings suggest that scale information is processed at the level of music-syntactic analysis, and that the detection of deviants does not require activation of auditory sensory memory by mismatch effects. Scales are perceived as a broader context, not just as online interval relations. Additional melodic context information appears necessary to support the representation of scale deviants in non-musicians, but not in musically-trained individuals, likely as a consequence of stronger pre-existing representations.

  12. Reflex test reminders in required cancer synoptic templates decrease order entry error: An analysis of mismatch repair immunohistochemical orders to screen for Lynch syndrome

    Directory of Open Access Journals (Sweden)

    Mark R Kilgore

    2016-01-01

    Full Text Available Background: Endometrial carcinoma (EC is the most common extracolonic malignant neoplasm associated with Lynch syndrome (LS. LS is caused by autosomal dominant germline mutations in DNA mismatch repair (MMR genes. Screening for LS in EC is often evaluated by loss of immunohistochemical (IHC expression of DNA MMR enzymes MLH1, MSH2, MSH6, and PMS2 (MMR IHC. In July 2013, our clinicians asked that we screen all EC in patients ≤60 for loss of MMR IHC expression. Despite this policy, several cases were not screened or screening was delayed. We implemented an informatics-based approach to ensure that all women who met criteria would have timely screening. Subjects and Methods: Reports are created in PowerPath (Sunquest Information Systems, Tucson, AZ with custom synoptic templates. We implemented an algorithm on March 6, 2014 requiring pathologists to address MMR IHC in patients ≤60 with EC before sign out (S/O. Pathologists must answer these questions: is patient ≤60 (yes/no, if yes, follow-up questions (IHC done previously, ordered with addendum to follow, results included in report, N/A, or not ordered, if not ordered, one must explain. We analyzed cases from July 18, 2013 to August 31, 2016 preimplementation (PreImp and postimplementation (PostImp that met criteria. Data analysis was performed using the standard data package included with GraphPad Prism® 7.00 (GraphPad Software, Inc., La Jolla, CA, USA. Results: There were 147 patients who met criteria (29 PreImp and 118 PostImp. IHC was ordered in a more complete and timely fashion PostImp than PreImp. PreImp, 4/29 (13.8% cases did not get any IHC, but PostImp, only 4/118 (3.39% were missed (P = 0.0448. Of cases with IHC ordered, 60.0% (15/25 were ordered before or at S/O PreImp versus 91.2% (104/114 PostImp (P = 0.0004. Relative to day of S/O, the mean days of order delay were longer and more variable PreImp versus PostImp (12.9 ± 40.7 vs. -0.660 ± 1.15; P = 0.0227, with the average

  13. Reflex test reminders in required cancer synoptic templates decrease order entry error: An analysis of mismatch repair immunohistochemical orders to screen for Lynch syndrome.

    Science.gov (United States)

    Kilgore, Mark R; McIlwain, Carrie A; Schmidt, Rodney A; Norquist, Barbara M; Swisher, Elizabeth M; Garcia, Rochelle L; Rendi, Mara H

    2016-01-01

    Endometrial carcinoma (EC) is the most common extracolonic malignant neoplasm associated with Lynch syndrome (LS). LS is caused by autosomal dominant germline mutations in DNA mismatch repair (MMR) genes. Screening for LS in EC is often evaluated by loss of immunohistochemical (IHC) expression of DNA MMR enzymes MLH1, MSH2, MSH6, and PMS2 (MMR IHC). In July 2013, our clinicians asked that we screen all EC in patients ≤60 for loss of MMR IHC expression. Despite this policy, several cases were not screened or screening was delayed. We implemented an informatics-based approach to ensure that all women who met criteria would have timely screening. Reports are created in PowerPath (Sunquest Information Systems, Tucson, AZ) with custom synoptic templates. We implemented an algorithm on March 6, 2014 requiring pathologists to address MMR IHC in patients ≤60 with EC before sign out (S/O). Pathologists must answer these questions: is patient ≤60 (yes/no), if yes, follow-up questions (IHC done previously, ordered with addendum to follow, results included in report, N/A, or not ordered), if not ordered, one must explain. We analyzed cases from July 18, 2013 to August 31, 2016 preimplementation (PreImp) and postimplementation (PostImp) that met criteria. Data analysis was performed using the standard data package included with GraphPad Prism ® 7.00 (GraphPad Software, Inc., La Jolla, CA, USA). There were 147 patients who met criteria (29 PreImp and 118 PostImp). IHC was ordered in a more complete and timely fashion PostImp than PreImp. PreImp, 4/29 (13.8%) cases did not get any IHC, but PostImp, only 4/118 (3.39%) were missed ( P = 0.0448). Of cases with IHC ordered, 60.0% (15/25) were ordered before or at S/O PreImp versus 91.2% (104/114) PostImp ( P = 0.0004). Relative to day of S/O, the mean days of order delay were longer and more variable PreImp versus PostImp (12.9 ± 40.7 vs. -0.660 ± 1.15; P = 0.0227), with the average being before S/O PostImp. This algorithm

  14. 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.

  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. 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.

  17. 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

  18. 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

  19. 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…

  20. [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.

  1. 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

  2. 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)

  3. 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.

  4. 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

  5. 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.

  6. 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…

  7. 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.

  8. 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

  9. 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...

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  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. 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.

  18. 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

  19. 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.)

  20. 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/

  1. 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

  2. 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.

  3. 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.

  4. 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…

  5. 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.

  6. 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

  7. 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....

  8. 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)

  9. 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...

  10. 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...

  11. 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

  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. Correction for spectral mismatch effects on the calibration of a solar cell when using a solar simulator

    Energy Technology Data Exchange (ETDEWEB)

    Seaman, C.H.

    1981-01-15

    A general expression has been derived to enable calculation of the calibration error resulting from simulator-solar AMX spectral mismatch and from reference cell-test cell spectral mismatch. The information required includes the relative spectral response of the reference cell, the relative spectral response of the cell under test, and the relative spectral irradiance of the simulator (over the spectral range defined by cell response). The spectral irradiance of the solar AMX is assumed to be known.

  14. 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

  15. 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)

  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. 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...

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. 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...

  5. 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...

  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. 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

  8. 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…

  9. 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...

  10. 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

  11. 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

  12. 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...

  13. 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

  14. 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

  15. Components of a Fanconi-like pathway control Pso2-independent DNA interstrand crosslink repair in yeast.

    Directory of Open Access Journals (Sweden)

    Thomas A Ward

    Full Text Available Fanconi anemia (FA is a devastating genetic disease, associated with genomic instability and defects in DNA interstrand cross-link (ICL repair. The FA repair pathway is not thought to be conserved in budding yeast, and although the yeast Mph1 helicase is a putative homolog of human FANCM, yeast cells disrupted for MPH1 are not sensitive to ICLs. Here, we reveal a key role for Mph1 in ICL repair when the Pso2 exonuclease is inactivated. We find that the yeast FANCM ortholog Mph1 physically and functionally interacts with Mgm101, a protein previously implicated in mitochondrial DNA repair, and the MutSα mismatch repair factor (Msh2-Msh6. Co-disruption of MPH1, MGM101, MSH6, or MSH2 with PSO2 produces a lesion-specific increase in ICL sensitivity, the elevation of ICL-induced chromosomal rearrangements, and persistence of ICL-associated DNA double-strand breaks. We find that Mph1-Mgm101-MutSα directs the ICL-induced recruitment of Exo1 to chromatin, and we propose that Exo1 is an alternative 5'-3' exonuclease utilised for ICL repair in the absence of Pso2. Moreover, ICL-induced Rad51 chromatin loading is delayed when both Pso2 and components of the Mph1-Mgm101-MutSα and Exo1 pathway are inactivated, demonstrating that the homologous recombination stages of ICL repair are inhibited. Finally, the FANCJ- and FANCP-related factors Chl1 and Slx4, respectively, are also components of the genetic pathway controlled by Mph1-Mgm101-MutSα. Together this suggests that a prototypical FA-related ICL repair pathway operates in budding yeast, which acts redundantly with the pathway controlled by Pso2, and is required for the targeting of Exo1 to chromatin to execute ICL repair.

  16. 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...

  17. 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...

  18. 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.

  19. 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

  20. 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...

  1. 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.

  2. Influence of excitation light rejection on forward model mismatch in optical tomography

    International Nuclear Information System (INIS)

    Hwang, K; Pan, T; Joshi, A; Rasmussen, J C; Bangerth, W; Sevick-Muraca, E M

    2006-01-01

    Fluorescence enhanced tomography for molecular imaging requires low background for detection and accurate image reconstruction. In this contribution, we show that excitation light leakage is responsible for elevated background and can be minimized with the use of gradient index (GRIN) lenses when using fibre optics to collect propagated fluorescence light from tissue or other biological media. We show that the model mismatch between frequency-domain photon migration (FDPM) measurements and the diffusion approximation prediction is decreased when GRIN lenses are placed prior to the interference filters to provide efficient excitation light rejection. Furthermore, model mismatch is correlated to the degree of excitation light leakage. This work demonstrates the importance of proper light filtering when designing fluorescence optical imaging and tomography

  3. A new measure of skill mismatch: theory and evidence from PIAAC

    Directory of Open Access Journals (Sweden)

    Michele Pellizzari

    2017-01-01

    Full Text Available Abstract This paper proposes a new measure of skill mismatch to be applied to the recent OECD Survey of Adult Skills (PIAAC. The measure is derived from a formal theory and combines information about skill proficiency, self-reported mismatch and skill use. The theoretical foundations underling this measure allow identifying minimum and maximum skill requirements for each occupation and to classify workers into three groups: the well-matched, the under-skilled and the over-skilled. The availability of skill use data further permits the computation of the degree of under- and over-usage of skills in the economy. The empirical analysis is carried out using the first round of the PIAAC data, allowing comparisons across skill domains, labour market statuses and countries.

  4. Analytical model of mismatched photovoltaic fields by means of Lambert W-function

    Energy Technology Data Exchange (ETDEWEB)

    Petrone, G.; Spagnuolo, G. [DIIIE, Universita di Salerno, Via Ponte Don Melillo, Fisciano (SA) (Italy); Vitelli, M. [DII, Seconda Universita di Napoli, Real Casa dell' Annunziata, Aversa (CE) (Italy)

    2007-11-06

    A new model of photovoltaic (PV) fields is introduced in this paper. It allows the simulation of a PV generator whose subsections, e.g. cells, groups of cells, panels or group of panels, work under different solar irradiation values and/or at different temperatures. Moreover, different nominal characteristics, rated power, production technology, shape and area can be settled for different subsections. Consequently, the proposed model is able to describe the behaviour of matched as well as mismatched PV fields. It results into a non linear system of equations, which includes bypass and blocking diodes models and is characterized by a sparse Jacobian matrix. The numerical model is reliable and requires a moderate computational burdensome, both in terms of memory use and processor speed. Numeric simulations confirm the accuracy and cheapness of the approach. The proposed model is used to simulate the drawbacks associated to mismatching during maximum power point tracking (MPPT) of the PV generator. (author)

  5. Role of DNA mismatch repair and p53 in signaling induction of apoptosis by alkylating agents.

    Science.gov (United States)

    Hickman, M J; Samson, L D

    1999-09-14

    All cells are unavoidably exposed to chemicals that can alkylate DNA to form genotoxic damage. Among the various DNA lesions formed, O(6)-alkylguanine lesions can be highly cytotoxic, and we recently demonstrated that O(6)-methylguanine (O(6)MeG) and O(6)-chloroethylguanine (O(6)CEG) specifically initiate apoptosis in hamster cells. Here we show, in both hamster and human cells, that the MutSalpha branch of the DNA mismatch repair pathway (but not the MutSbeta branch) is absolutely required for signaling the initiation of apoptosis in response to O(6)MeGs and is partially required for signaling apoptosis in response to O(6)CEGs. Further, O(6)MeG lesions signal the stabilization of the p53 tumor suppressor, and such signaling is also MutSalpha-dependent. Despite this, MutSalpha-dependent apoptosis can be executed in a p53-independent manner. DNA mismatch repair status did not influence the response of cells to other inducers of p53 and apoptosis. Thus, it appears that mismatch repair status, rather than p53 status, is a strong indicator of the susceptibility of cells to alkylation-induced apoptosis. This experimental system will allow dissection of the signal transduction events that couple a specific type of DNA base lesion with the final outcome of apoptotic cell death.

  6. Understanding the Transfer Deficit: Contextual Mismatch, Proactive Interference, and Working Memory Affect Toddlers' Video-Based Transfer.

    Science.gov (United States)

    Choi, Koeun; Kirkorian, Heather L; Pempek, Tiffany A

    2017-04-17

    Researchers tested the impact of contextual mismatch, proactive interference, and working memory (WM) on toddlers' transfer across contexts. Forty-two toddlers (27-34 months) completed four object-retrieval trials, requiring memory updating on Trials 2-4. Participants watched hiding events on a tablet computer. Search performance was tested using another tablet (match) or a felt board (mismatch). WM was assessed. On earlier search trials, WM predicted transfer in both conditions, and toddlers in the match condition outperformed those in the mismatch condition; however, the benefit of contextual match and WM decreased over trials. Contextual match apparently increased proactive interference on later trials. Findings are interpreted within existing accounts of the transfer deficit, and a combined account is proposed. © 2017 The Authors. Child Development © 2017 Society for Research in Child Development, Inc.

  7. 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

  8. 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...

  9. Involvement of DNA mismatch repair in the maintenance of heterochromatic DNA stability in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Basanta K Dahal

    2017-10-01

    Full Text Available Heterochromatin contains a significant part of nuclear DNA. Little is known about the mechanisms that govern heterochromatic DNA stability. We show here that in the yeast Saccharomyces cerevisiae (i DNA mismatch repair (MMR is required for the maintenance of heterochromatic DNA stability, (ii MutLα (Mlh1-Pms1 heterodimer, MutSα (Msh2-Msh6 heterodimer, MutSβ (Msh2-Msh3 heterodimer, and Exo1 are involved in MMR at heterochromatin, (iii Exo1-independent MMR at heterochromatin frequently leads to the formation of Pol ζ-dependent mutations, (iv MMR cooperates with the proofreading activity of Pol ε and the histone acetyltransferase Rtt109 in the maintenance of heterochromatic DNA stability, (v repair of base-base mismatches at heterochromatin is less efficient than repair of base-base mismatches at euchromatin, and (vi the efficiency of repair of 1-nt insertion/deletion loops at heterochromatin is similar to the efficiency of repair of 1-nt insertion/deletion loops at euchromatin.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. Index mismatch aberration correction over long working distances using spatial light modulation.

    Science.gov (United States)

    Gjonaj, Bergin; Johnson, Patrick; Bonn, Mischa; Domke, Katrin F

    2012-11-20

    For many microscopy applications, millimeters-long free working distances (LWD) are required. However, the high resolution and contrast of LWD objectives operated in air are lost when introducing glass and/or liquid with the sample. We propose to use spatial light modulation to correct for such beam aberrations caused by refractive index mismatches. Focusing a monochromatic laser beam with a 10 mm working distance air objective (50×, 0.5 NA) through air, glass, and water, we manage to restore a sharp, intense focus (FWHMLWD air objectives, extending their usage beyond applications in air.

  20. Role of DNA mismatch repair and p53 in signaling induction of apoptosis by alkylating agents

    OpenAIRE

    Hickman, Mark J.; Samson, Leona D.

    1999-01-01

    All cells are unavoidably exposed to chemicals that can alkylate DNA to form genotoxic damage. Among the various DNA lesions formed, O6-alkylguanine lesions can be highly cytotoxic, and we recently demonstrated that O6-methylguanine (O6MeG) and O6-chloroethylguanine (O6CEG) specifically initiate apoptosis in hamster cells. Here we show, in both hamster and human cells, that the MutSα branch of the DNA mismatch repair pathway (but not the MutSβ branch) is absolutely required for signaling the ...

  1. Power-Cooling-Mismatch Test Series Test PCM-7. Experiment operating specifications

    International Nuclear Information System (INIS)

    Sparks, D.T.; Smith, R.H.; Stanley, C.J.

    1979-02-01

    The experiment operating specifications for the Power-Cooling-Mismatch (PCM) Test PCM-7 to be conducted in the Power Burst Facility are described. The PCM Test Series was designed on the basis of a parametric evaluation of fuel behavior response with cladding temperature, rod internal pressure, time in film boiling, and test rod power being the variable parameters. The test matrix, defined in the PCM Experiment Requirements Document (ERD), encompasses a wide range of situations extending from pre-CHF (critical heat flux) PCMs to long duration operation in stable film boiling leading to rod failure

  2. 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…

  3. 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

  4. 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.

  5. 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

  6. 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…

  7. 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.

  8. 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...

  9. 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

  10. 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...

  11. 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

  12. 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

  13. 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...

  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. 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

  17. Physical interaction between components of DNA mismatch repair and nucleotide excision repair

    International Nuclear Information System (INIS)

    Bertrand, P.; Tishkoff, D.X.; Filosi, N.; Dasgupta, R.; Kolodner, R.D.

    1998-01-01

    Nucleotide excision repair (NER) and DNA mismatch repair are required for some common processes although the biochemical basis for this requirement is unknown. Saccharomyces cerevisiae RAD14 was identified in a two-hybrid screen using MSH2 as 'bait,' and pairwise interactions between MSH2 and RAD1, RAD2, RAD3, RAD10, RAD14, and RAD25 subsequently were demonstrated by two-hybrid analysis. MSH2 coimmunoprecipitated specifically with epitope-tagged versions of RAD2, RAD10, RAD14, and RAD25. MSH2 and RAD10 were found to interact in msh3 msh6 and mlh1 pms1 double mutants, suggesting a direct interaction with MSH2. Mutations in MSH2 increased the UV sensitivity of NER-deficient yeast strains, and msh2 mutations were epistatic to the mutator phenotype observed in NER-deficient strains. These data suggest that MSH2 and possibly other components of DNA mismatch repair exist in a complex with NER proteins, providing a biochemical and genetical basis for these proteins to function in common processes

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. 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...

  4. 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

  5. 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.

  6. 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)

  7. 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.

  8. 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

  9. Do educational requirements in vacancies match the educational attainments of job-holders? An analysis of web-based data for 279 occupations in the Czech Republic

    NARCIS (Netherlands)

    Tijdens, K.; Beblavý, M.; Thum-Thysen, A.

    2015-01-01

    European labour market policies aim to develop an early-warning tool for mismatches by monitoring job vacancies. Few studies have been able to measure these mismatches, among others because systematic information on educational requirements in vacancies is lacking. Our study explores mismatch for

  10. 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

  11. 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....

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Shape forming by thermal expansion mismatch and shape memory locking in polymer/elastomer laminates

    Science.gov (United States)

    Yuan, Chao; Ding, Zhen; Wang, T. J.; Dunn, Martin L.; Qi, H. Jerry

    2017-10-01

    This paper studies a novel method to fabricate three-dimensional (3D) structure from 2D thermo-responsive shape memory polymer (SMP)/elastomer bilayer laminate. In this method, the shape change is actuated by the thermal mismatch strain between the SMP and the elastomer layers upon heating. However, the glass transition behavior of the SMP locks the material into a new 3D shape that is stable even upon cooling. Therefore, the second shape becomes a new permanent shape of the laminate. A theoretical model that accounts for the temperature-dependent thermomechanical behavior of the SMP material and thermal mismatch strain between the two layers is developed to better understand the underlying physics. Model predictions and experiments show good agreement and indicate that the theoretical model can well predict the bending behavior of the bilayer laminate. The model is then used in the optimal design of geometrical configuration and material selection. The latter also illustrates the requirement of thermomechanical behaviors of the SMP to lock the shape. Based on the fundamental understandings, several self-folding structures are demonstrated by the bilayer laminate design.

  14. Informational mismatches: a neglected threat of climate change to interspecific interactions

    Directory of Open Access Journals (Sweden)

    Deseada eParejo

    2016-04-01

    Full Text Available Interspecific interactions are deeply affected by the current scenario of climate change. This is because interactions are sensitive to many traits of interacting species as phenology, distribution, behaviour and relative abundances which may be differently influenced by climate change in each species. In this scenario, positive interactions, which require temporal coordination of events of life history of interacting species, could be particularly altered due to differential effects of climate change on phenology, apart from by the effects on abundance and distribution. Hitherto, studies focusing on the effects of climate change on positive biotic interactions are scarce and mainly focused on plant-pollinator interactions. Here I propose that, by inducing informational mismatches, climate change may lead to individuals from competing species relying on heterospecific social information to making mis- or un-informed decisions. The idea is that competing species are valuable sources of social information to each other provided overlap of their activities occurs. However, whenever coordination of events fails, competing species will co-occur at the wrong moment, co-occur only in small numbers or even not co-occur at all and thus they will not be able to access useful or any social information from heterospecifics. In that scenario, interacting species would be mis- or un- informed, and, consequently, decision taking will be impaired, leading to disequilibrium in the community. Throughout the manuscript, I will develop the idea of mismatches of information and illustrate it with some case studies.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. 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...

  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. 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...

  3. 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

  4. Emotional Intelligence and Mismatching Expressive and Verbal Messages: A Contribution to Detection of Deception

    Science.gov (United States)

    Wojciechowski, Jerzy; Stolarski, Maciej; Matthews, Gerald

    2014-01-01

    Processing facial emotion, especially mismatches between facial and verbal messages, is believed to be important in the detection of deception. For example, emotional leakage may accompany lying. Individuals with superior emotion perception abilities may then be more adept in detecting deception by identifying mismatch between facial and verbal messages. Two personal factors that may predict such abilities are female gender and high emotional intelligence (EI). However, evidence on the role of gender and EI in detection of deception is mixed. A key issue is that the facial processing skills required to detect deception may not be the same as those required to identify facial emotion. To test this possibility, we developed a novel facial processing task, the FDT (Face Decoding Test) that requires detection of inconsistencies between facial and verbal cues to emotion. We hypothesized that gender and ability EI would be related to performance when cues were inconsistent. We also hypothesized that gender effects would be mediated by EI, because women tend to score as more emotionally intelligent on ability tests. Data were collected from 210 participants. Analyses of the FDT suggested that EI was correlated with superior face decoding in all conditions. We also confirmed the expected gender difference, the superiority of high EI individuals, and the mediation hypothesis. Also, EI was more strongly associated with facial decoding performance in women than in men, implying there may be gender differences in strategies for processing affective cues. It is concluded that integration of emotional and cognitive cues may be a core attribute of EI that contributes to the detection of deception. PMID:24658500

  5. Emotional intelligence and mismatching expressive and verbal messages: a contribution to detection of deception.

    Directory of Open Access Journals (Sweden)

    Jerzy Wojciechowski

    Full Text Available Processing facial emotion, especially mismatches between facial and verbal messages, is believed to be important in the detection of deception. For example, emotional leakage may accompany lying. Individuals with superior emotion perception abilities may then be more adept in detecting deception by identifying mismatch between facial and verbal messages. Two personal factors that may predict such abilities are female gender and high emotional intelligence (EI. However, evidence on the role of gender and EI in detection of deception is mixed. A key issue is that the facial processing skills required to detect deception may not be the same as those required to identify facial emotion. To test this possibility, we developed a novel facial processing task, the FDT (Face Decoding Test that requires detection of inconsistencies between facial and verbal cues to emotion. We hypothesized that gender and ability EI would be related to performance when cues were inconsistent. We also hypothesized that gender effects would be mediated by EI, because women tend to score as more emotionally intelligent on ability tests. Data were collected from 210 participants. Analyses of the FDT suggested that EI was correlated with superior face decoding in all conditions. We also confirmed the expected gender difference, the superiority of high EI individuals, and the mediation hypothesis. Also, EI was more strongly associated with facial decoding performance in women than in men, implying there may be gender differences in strategies for processing affective cues. It is concluded that integration of emotional and cognitive cues may be a core attribute of EI that contributes to the detection of deception.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. Correlation and agreement between eplet mismatches calculated using serological, low-intermediate and high resolution molecular human leukocyte antigen typing methods.

    Science.gov (United States)

    Fidler, Samantha; D'Orsogna, Lloyd; Irish, Ashley B; Lewis, Joshua R; Wong, Germaine; Lim, Wai H

    2018-03-02

    Structural human leukocyte antigen (HLA) matching at the eplet level can be identified by HLAMatchmaker, which requires the entry of four-digit alleles. The aim of this study was to evaluate the agreement between eplet mismatches calculated by serological and two-digit typing methods compared to high-resolution four-digit typing. In a cohort of 264 donor/recipient pairs, the evaluation of measurement error was assessed using intra-class correlation to confirm the absolute agreement between the number of eplet mismatches at class I (HLA-A, -B, C) and II loci (HLA-DQ and -DR) calculated using serological or two-digit molecular typing compared to four-digit molecular typing methods. The proportion of donor/recipient pairs with a difference of >5 eplet mismatches between the HLA typing methods was also determined. Intra-class correlation coefficients between serological and four-digit molecular typing methods were 0.969 (95% confidence intervals [95% CI] 0.960-0.975) and 0.926 (95% CI 0.899-0.944), respectively; and 0.995 (95% CI 0.994-0.996) and 0.993 (95% CI 0.991-0.995), respectively between two-digit and four-digit molecular typing methods. The proportion of donor/recipient pairs with a difference of >5 eplet mismatches at class I and II loci was 4% and 16% for serological versus four-digit molecular typing methods, and 0% and 2% for two-digit versus four-digit molecular typing methods, respectively. In this small predominantly Caucasian population, compared with serology, there is a high level of agreement in the number of eplet mismatches calculated using two-compared to four-digit molecular HLA-typing methods, suggesting that two-digit typing may be sufficient in determining eplet mismatch load in kidney transplantation.

  14. 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.

  15. Attention-dependent allocation of auditory processing resources as measured by mismatch negativity.

    Science.gov (United States)

    Dittmann-Balcar, A; Thienel, R; Schall, U

    1999-12-16

    Mismatch negativity (MMN) is a pre-attentive event-related potential measure of echoic memory. However, recent studies suggest attention-related modulation of MMN. This study investigates duration-elicited MMN in healthy subjects (n = 12) who were performing a visual discrimination task and, subsequently, an auditory discrimination task in a series of increasing task difficulty. MMN amplitude was found to be maximal at centro-frontal electrode sites without hemispheric differences. Comparison of both attend conditions (visual vs. auditory), revealed larger MMN amplitudes at Fz in the visual task without differences across task difficulty. However, significantly smaller MMN in the most demanding auditory condition supports the notion of limited processing capacity whose resources are modulated by attention in response to task requirements.

  16. 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...

  17. 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.

  18. 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

  19. 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...

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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...

  8. 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

  9. Gender differences in specialty preference and mismatch with real needs in Japanese medical students

    Directory of Open Access Journals (Sweden)

    Harada Tadanari

    2010-02-01

    Full Text Available Abstract Background The shortage of doctors and maldistribution among specialties are of great concern in the Japanese health care system. This study investigated specialty preference in medical students of one university, and examined gender differences and compared their preference with real needs. Methods We conducted a self-administered questionnaire including specialty preference in all students of one medical university. Preference was assessed by the five-level probability of their future choice: 1 = very low, 2 = low, 3 = moderate, 4 = high, and 5 = very high. The proportion of 4 or 5 was calculated as the preference rate. The real needs (magnitude of doctor shortage in the prefecture were drawn from two different surveys. The relationship between the sex-specific preference rate by specialty and real needs was assessed by Spearman's correlation coefficient. Results Internal medicine showed the highest preference rate, followed by general surgery, pediatrics, and emergency medicine. There was no significant correlation between the preference rates of men and women (r = 0.27, p = 0.34. The preference rates for general surgery, orthopedics, neurosurgery, and emergency medicine were significantly higher in men than in women, while those of obstetrics & gynecology, pediatrics, and dermatology were significantly higher in women. The magnitude of doctor shortage by specialty from two surveys were significantly correlated with the total preference rate and men's preference rate (r = 0.54 to 0.74, but not with women's preference rate (r = 0.06 and 0.32. Conclusions This study elucidated not only gender differences in specialty preference but also the relationship to real needs. Critical gender differences and mismatch with real needs were found in women. In addition to traditional gender roles and insufficient support for women's participation in Japan, gender differences and mismatch influence the current and future maldistribution of

  10. 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

  11. 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

  12. 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

  13. 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. ...

  14. 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...

  15. 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...

  16. A Modified Protocol with Improved Detection Rate for Mis-Matched Donor HLA from Low Quantities of DNA in Urine Samples from Kidney Graft Recipients.

    Directory of Open Access Journals (Sweden)

    Janette Kwok

    Full Text Available Urine from kidney transplant recipient has proven to be a viable source for donor DNA. However, an optimized protocol would be required to determine mis-matched donor HLA specificities in view of the scarcity of DNA obtained in some cases.In this study, fresh early morning urine specimens were obtained from 155 kidney transplant recipients with known donor HLA phenotype. DNA was extracted and typing of HLA-A, B and DRB1 loci by polymerase chain reaction-specific sequence primers was performed using tailor-made condition according to the concentration of extracted DNA.HLA typing of DNA extracted from urine revealed both recipient and donor HLA phenotypes, allowing the deduction of the unknown donor HLA and hence the degree of HLA mis-match. By adopting the modified procedures, mis-matched donor HLA phenotypes were successfully deduced in all of 35 tested urine samples at DNA quantities spanning the range of 620-24,000 ng.This urine-based method offers a promising and reliable non-invasive means for the identification of mis-matched donor HLA antigens in kidney transplant recipients with unknown donor HLA phenotype or otherwise inadequate donor information.

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. Activation of Saccharomyces cerevisiae Mlh1-Pms1 Endonuclease in a Reconstituted Mismatch Repair System*

    Science.gov (United States)

    Smith, Catherine E.; Bowen, Nikki; Graham, William J.; Goellner, Eva M.; Srivatsan, Anjana; Kolodner, Richard D.

    2015-01-01

    Previous studies reported the reconstitution of an Mlh1-Pms1-independent 5′ nick-directed mismatch repair (MMR) reaction using Saccharomyces cerevisiae proteins. Here we describe the reconstitution of a mispair-dependent Mlh1-Pms1 endonuclease activation reaction requiring Msh2-Msh6 (or Msh2-Msh3), proliferating cell nuclear antigen (PCNA), and replication factor C (RFC) and a reconstituted Mlh1-Pms1-dependent 3′ nick-directed MMR reaction requiring Msh2-Msh6 (or Msh2-Msh3), exonuclease 1 (Exo1), replication protein A (RPA), RFC, PCNA, and DNA polymerase δ. Both reactions required Mg2+ and Mn2+ for optimal activity. The MMR reaction also required two reaction stages in which the first stage required incubation of Mlh1-Pms1 with substrate DNA, with or without Msh2-Msh6 (or Msh2-Msh3), PCNA, and RFC but did not require nicking of the substrate, followed by a second stage in which other proteins were added. Analysis of different mutant proteins demonstrated that both reactions required a functional Mlh1-Pms1 endonuclease active site, as well as mispair recognition and Mlh1-Pms1 recruitment by Msh2-Msh6 but not sliding clamp formation. Mutant Mlh1-Pms1 and PCNA proteins that were defective for Exo1-independent but not Exo1-dependent MMR in vivo were partially defective in the Mlh1-Pms1 endonuclease and MMR reactions, suggesting that both reactions reflect the activation of Mlh1-Pms1 seen in Exo1-independent MMR in vivo. The availability of this reconstituted MMR reaction should now make it possible to better study both Exo1-independent and Exo1-dependent MMR. PMID:26170454

  3. Activation of Saccharomyces cerevisiae Mlh1-Pms1 Endonuclease in a Reconstituted Mismatch Repair System.

    Science.gov (United States)

    Smith, Catherine E; Bowen, Nikki; Graham, William J; Goellner, Eva M; Srivatsan, Anjana; Kolodner, Richard D

    2015-08-28

    Previous studies reported the reconstitution of an Mlh1-Pms1-independent 5' nick-directed mismatch repair (MMR) reaction using Saccharomyces cerevisiae proteins. Here we describe the reconstitution of a mispair-dependent Mlh1-Pms1 endonuclease activation reaction requiring Msh2-Msh6 (or Msh2-Msh3), proliferating cell nuclear antigen (PCNA), and replication factor C (RFC) and a reconstituted Mlh1-Pms1-dependent 3' nick-directed MMR reaction requiring Msh2-Msh6 (or Msh2-Msh3), exonuclease 1 (Exo1), replication protein A (RPA), RFC, PCNA, and DNA polymerase δ. Both reactions required Mg(2+) and Mn(2+) for optimal activity. The MMR reaction also required two reaction stages in which the first stage required incubation of Mlh1-Pms1 with substrate DNA, with or without Msh2-Msh6 (or Msh2-Msh3), PCNA, and RFC but did not require nicking of the substrate, followed by a second stage in which other proteins were added. Analysis of different mutant proteins demonstrated that both reactions required a functional Mlh1-Pms1 endonuclease active site, as well as mispair recognition and Mlh1-Pms1 recruitment by Msh2-Msh6 but not sliding clamp formation. Mutant Mlh1-Pms1 and PCNA proteins that were defective for Exo1-independent but not Exo1-dependent MMR in vivo were partially defective in the Mlh1-Pms1 endonuclease and MMR reactions, suggesting that both reactions reflect the activation of Mlh1-Pms1 seen in Exo1-independent MMR in vivo. The availability of this reconstituted MMR reaction should now make it possible to better study both Exo1-independent and Exo1-dependent MMR. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  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. 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

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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...

  15. 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

  16. 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

  17. Optical CT imaging of solid radiochromic dosimeters in mismatched refractive index solutions using a scanning laser and large area detector.

    Science.gov (United States)

    Dekker, Kurtis H; Battista, Jerry J; Jordan, Kevin J

    2016-08-01

    either a uniform dose or a 2-level "step-dose" pattern. With 6% refractive index mismatching, a circular field of view of 85% of the diameter of a cylindrical sample can be reconstructed accurately. Reconstructed images of the test solution phantom were uniform (within 3%) inside this radius. However, the dose responses of the PRESAGE® samples were not spatially uniform, with variations of at least 5% in sensitivity. The variation appears as a "cupping" artifact with less sensitivity in the middle than at the periphery of the PRESAGE® cylinder. Polarization effects were also detected for these samples. The fiducial-based ray path measurement scheme, coupled with an iterative reconstruction algorithm, enabled optical CT scanning of PRESAGE® dosimeters immersed in mismatched refractive index solutions. However, improvements to PRESAGE® dose response uniformity are required.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

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

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    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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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...

  14. 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

  15. 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.

  16. 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...

  17. 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...

  18. 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.

  19. 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.

  20. 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.

  1. A Calibration Method for Nonlinear Mismatches in M-Channel Time-Interleaved Analog-to-Digital Converters Based on Hadamard Sequences

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    Husheng Liu

    2016-11-01

    Full Text Available The time-interleaved analog-to-digital converter (TIADC is an architecture used to achieve a high sampling rate and high dynamic performance. However, estimation and compensation methods are required to maintain the dynamic performance of the constituent analog-to-digital converters (ADCs due to channel mismatches. This paper proposes a blind adaptive method to calibrate the nonlinear mismatches in M-channel TIADCs (M-TIADCs. The nonlinearity-induced error signal is reconstructed by the proposed multiplier Hadamard transform (MHT structure, and the nonlinear parameters are estimated by the filtered-X least-mean square (FxLMS algorithm. The performance of cascade calibration is also analyzed. The numerical simulation results show that the proposed method consumes much less hardware resources while maintaining the calibration performance.

  2. 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

  3. 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

  4. A reversible histone H3 acetylation cooperates with mismatch repair and replicative polymerases in maintaining genome stability.

    Directory of Open Access Journals (Sweden)

    Lyudmila Y Kadyrova

    2013-10-01

    Full Text Available Mutations are a major driving force of evolution and genetic disease. In eukaryotes, mutations are produced in the chromatin environment, but the impact of chromatin on mutagenesis is poorly understood. Previous studies have determined that in yeast Saccharomyces cerevisiae, Rtt109-dependent acetylation of histone H3 on K56 is an abundant modification that is introduced in chromatin in S phase and removed by Hst3 and Hst4 in G2/M. We show here that the chromatin deacetylation on histone H3 K56 by Hst3 and Hst4 is required for the suppression of spontaneous gross chromosomal rearrangements, base substitutions, 1-bp insertions/deletions, and complex mutations. The rate of base substitutions in hst3Δ hst4Δ is similar to that in isogenic mismatch repair-deficient msh2Δ mutant. We also provide evidence that H3 K56 acetylation by Rtt109 is important for safeguarding DNA from small insertions/deletions and complex mutations. Furthermore, we reveal that both the deacetylation and acetylation on histone H3 K56 are involved in mutation avoidance mechanisms that cooperate with mismatch repair and the proofreading activities of replicative DNA polymerases in suppressing spontaneous mutagenesis. Our results suggest that cyclic acetylation and deacetylation of chromatin contribute to replication fidelity and play important roles in the protection of nuclear DNA from diverse spontaneous mutations.

  5. 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

  6. 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.

  7. Mlh2 is an accessory factor for DNA mismatch repair in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Christopher S Campbell

    2014-05-01

    Full Text Available In Saccharomyces cerevisiae, the essential mismatch repair (MMR endonuclease Mlh1-Pms1 forms foci promoted by Msh2-Msh6 or Msh2-Msh3 in response to mispaired bases. Here we analyzed the Mlh1-Mlh2 complex, whose role in MMR has been unclear. Mlh1-Mlh2 formed foci that often colocalized with and had a longer lifetime than Mlh1-Pms1 foci. Mlh1-Mlh2 foci were similar to Mlh1-Pms1 foci: they required mispair recognition by Msh2-Msh6, increased in response to increased mispairs or downstream defects in MMR, and formed after induction of DNA damage by phleomycin but not double-stranded breaks by I-SceI. Mlh1-Mlh2 could be recruited to mispair-containing DNA in vitro by either Msh2-Msh6 or Msh2-Msh3. Deletion of MLH2 caused a synergistic increase in mutation rate in combination with deletion of MSH6 or reduced expression of Pms1. Phylogenetic analysis demonstrated that the S. cerevisiae Mlh2 protein and the mammalian PMS1 protein are homologs. These results support a hypothesis that Mlh1-Mlh2 is a non-essential accessory factor that acts to enhance the activity of Mlh1-Pms1.

  8. A meta-analysis of mismatch negativity in children with attention deficit-hyperactivity disorders.

    Science.gov (United States)

    Cheng, Chia-Hsiung; Chan, Pei-Ying S; Hsieh, Yu-Wei; Chen, Kuan-Fu

    2016-01-26

    Mismatch negativity (MMN) is an optimal neurophysiological signal to assess the integrity of auditory sensory memory and involuntary attention switch. The generation of MMN is independent of overt behavioral requirements, concentration or motivation, and thus serves as a suitable tool to study the perceptual function in children with attention deficit-hyperactivity disorders (ADHD). It remains unclear whether ADHD children showed altered MMN responses. Therefore we performed a meta-analysis of peer-reviewed MMN studies that had targeted both typically developed and ADHD children to examine the pooled effect size. The published articles between 1990 and 2014 were searched in PubMed, Medline, Cochrane, and CINAHL. The mean effect size and a 95% confidence interval (CI) were estimated. Six studies, consisting of 10 individual investigations, were included in the final analysis. A significant effect size of 0.28 was found (p=0.028, 95% CI at 0.03-0.53). These results were also free from publication bias or heterogeneity. In conclusion, our meta-analysis results suggest ADHD children demonstrated a reduced MMN amplitude compared to healthy controls. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. The dual nature of mismatch repair as antimutator and mutator: for better or for worse

    Directory of Open Access Journals (Sweden)

    Sara Thornby Bak

    2014-08-01

    Full Text Available DNA is constantly under attack by a number of both exogenous and endogenous agents that challenge its integrity. Among the mechanisms that have evolved to counteract this deleterious action, mismatch repair (MMR has specialized in removing DNA biosynthetic errors that occur when replicating the genome. Malfunction or inactivation of this system results in an increase in spontaneous mutability and a strong predisposition to tumor development. Besides this key corrective role, MMR proteins are involved in other pathways of DNA metabolism such as mitotic and meiotic recombination and processing of oxidative damage. Surprisingly, MMR is also required for certain mutagenic processes. The mutagenic MMR has beneficial consequences contributing to the generation of a vast repertoire of antibodies through class switch recombination and somatic hypermutation processes. However, this non-canonical mutagenic MMR also has detrimental effects; it promotes repeat expansions associated with neuromuscular and neurodegenerative diseases and may contribute to cancer/disease-related aberrant mutations and translocations. The reaction responsible for replication error correction has been the most thoroughly studied and it is the subject to numerous reviews. This review describes briefly the biochemistry of MMR and focuses primarily on the non-canonical MMR activities described in mammals as well as emerging research implicating interplay of MMR and chromatin.

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. 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)

  20. 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

  1. 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...

  2. 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 ...

  3. 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.

  4. 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.

  5. 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.

  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. 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.

  9. 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.

  10. Development of infant mismatch responses to auditory pattern changes between 2 and 4 months old.

    Science.gov (United States)

    He, Chao; Hotson, Lisa; Trainor, Laurel J

    2009-02-01

    In order to process speech and music, the auditory cortex must learn to process patterns of sounds. Our previous studies showed that with a stream consisting of a repeating (standard) sound, younger infants show an increase in the amplitude of a positive slow wave in response to occasional changes (deviants) in pitch or duration, whereas older infants show a faster negative response that resembles mismatch negativity (MMN) in adults (Trainor et al., 2001, 2003; He et al., 2007). MMN reflects an automatic change-detection process that does not require attention, conscious awareness or behavioural response for its elicitation (Picton et al., 2000; Näätänen et al., 2007). It is an important tool for understanding auditory perception because MMN reflects a change-detection mechanism, and not simply that repetition of a stimulus results in a refractory state of sensory neural circuits while occasional changes to a new sound activate new non-refractory neural circuits (Näätänen et al., 2005). For example, MMN is elicited by a change in the pattern of a repeating note sequence, even when no new notes are introduced that could activate new sensory circuits (Alain et al., 1994, 1999;Schröger et al., 1996). In the present study, we show that in response to a change in the pattern of two repeating tones, MMN in 4-month-olds remains robust whereas the 2-month-old response does not. This indicates that the MMN response to a change in pattern at 4 months reflects the activation of a change-detection mechanism similarly as in adults.

  11. A mismatch between population health literacy and the complexity of health information: an observational study.

    Science.gov (United States)

    Rowlands, Gillian; Protheroe, Joanne; Winkley, John; Richardson, Marty; Seed, Paul T; Rudd, Rima

    2015-06-01

    Low health literacy is associated with poorer health and higher mortality. Complex health materials are a barrier to health. To assess the literacy and numeracy skills required to understand and use commonly used English health information materials, and to describe population skills in relation to these. An English observational study comparing health materials with national working-age population skills. Health materials were sampled using a health literacy framework. Competency thresholds to understand and use the materials were identified. The proportion of the population above and below these thresholds, and the sociodemographic variables associated with a greater risk of being below the thresholds, were described. Sixty-four health materials were sampled. Two competency thresholds were identified: text (literacy) only, and text + numeracy; 2515/5795 participants (43%) were below the text-only threshold, while 2905/4767 (61%) were below the text + numeracy threshold. Univariable analyses of social determinants of health showed that those groups more at risk of socioeconomic deprivation had higher odds of being below the health literacy competency threshold than those at lower risk of deprivation. Multivariable analysis resulted in some variables becoming non-significant or reduced in effect. Levels of low health literacy mirror those found in other industrialised countries, with a mismatch between the complexity of health materials and the skills of the English adult working-age population. Those most in need of health information have the least access to it. Efficacious strategies are building population skills, improving health professionals' communication, and improving written health information. © British Journal of General Practice 2015.

  12. DNA Mismatch Repair Deficiency Promotes Genomic Instability in a Subset of Papillary Thyroid Cancers.

    Science.gov (United States)

    Javid, Mahsa; Sasanakietkul, Thanyawat; Nicolson, Norman G; Gibson, Courtney E; Callender, Glenda G; Korah, Reju; Carling, Tobias

    2018-02-01

    Efficient DNA damage repair by MutL-homolog DNA mismatch repair (MMR) enzymes, MLH1, MLH3, PMS1 and PMS2, are required to maintain thyrocyte genomic integrity. We hypothesized that persistent oxidative stress and consequent transcriptional dysregulation observed in thyroid follicles will lead to MMR deficiency and potentiate papillary thyroid tumorigenesis. MMR gene expression was analyzed by targeted microarray in 18 papillary thyroid cancer (PTC), 9 paracarcinoma normal thyroid (PCNT) and 10 normal thyroid (NT) samples. The findings were validated by qRT-PCR, and in follicular thyroid cancers (FTC) and follicular thyroid adenomas (FTA) for comparison. FOXO transcription factor expression was also analyzed. Protein expression was assessed by immunohistochemistry. Genomic integrity was evaluated by whole-exome sequencing-derived read-depth analysis and Mann-Whitney U test. Clinical correlations were assessed using Fisher's exact and t tests. Microarray and qRT-PCR revealed reduced expression of all four MMR genes in PTC compared with PCNT and of PMS2 compared with NT. FTC and FTA showed upregulation in MLH1, MLH3 and PMS2. PMS2 protein expression correlated with the mRNA expression pattern. FOXO1 showed lower expression in PMS2-deficient PTCs (log2-fold change -1.72 vs. -0.55, U = 11, p clinical characteristics. MMR deficiency, potentially promoted by FOXO1 suppression, may explain the etiology for PTC development in some patients. FTC and FTA retain MMR activity and are likely caused by a different tumorigenic pathway.

  13. 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

  14. 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

  15. 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.)

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. Chimerism and tolerance without GVHD or engraftment syndrome in HLA-mismatched combined kidney and hematopoietic stem cell transplantation.

    Science.gov (United States)

    Leventhal, Joseph; Abecassis, Michael; Miller, Joshua; Gallon, Lorenzo; Ravindra, Kadiyala; Tollerud, David J; King, Bradley; Elliott, Mary Jane; Herzig, Geoffrey; Herzig, Roger; Ildstad, Suzanne T

    2012-03-07

    The toxicity of chronic immunosuppressive agents required for organ transplant maintenance has prompted investigators to pursue approaches to induce immune tolerance. We developed an approach using a bioengineered mobilized cellular product enriched for hematopoietic stem cells (HSCs) and tolerogenic graft facilitating cells (FCs) combined with nonmyeloablative conditioning; this approach resulted in engraftment, durable chimerism, and tolerance induction in recipients with highly mismatched related and unrelated donors. Eight recipients of human leukocyte antigen (HLA)-mismatched kidney and FC/HSC transplants underwent conditioning with fludarabine, 200-centigray total body irradiation, and cyclophosphamide followed by posttransplant immunosuppression with tacrolimus and mycophenolate mofetil. Subjects ranged in age from 29 to 56 years. HLA match ranged from five of six loci with related donors to one of six loci with unrelated donors. The absolute neutrophil counts reached a nadir about 1 week after transplant, with recovery by 2 weeks. Multilineage chimerism at 1 month ranged from 6 to 100%. The conditioning was well tolerated, with outpatient management after postoperative day 2. Two subjects exhibited transient chimerism and were maintained on low-dose tacrolimus monotherapy. One subject developed viral sepsis 2 months after transplant and experienced renal artery thrombosis. Five subjects experienced durable chimerism, demonstrated immunocompetence and donor-specific tolerance by in vitro proliferative assays, and were successfully weaned off all immunosuppression 1 year after transplant. None of the recipients produced anti-donor antibody or exhibited engraftment syndrome or graft-versus-host disease. These results suggest that manipulation of a mobilized stem cell graft and nonmyeloablative conditioning represents a safe, practical, and reproducible means of inducing durable chimerism and donor-specific tolerance in solid organ transplant recipients.

  1. Is patient-prosthesis mismatch a predictor of survival or a surrogate marker of co-morbidities in cardiac surgery?

    Science.gov (United States)

    Dayan, Victor; Soca, Gerardo; Stanham, Roberto; Lorenzo, Alvaro; Ferreiro, Alejandro

    2015-01-01

    Patient-prosthesis mismatch (PPM) has ignited much debate and no definite conclusions have been drawn on the outcome of these patients. Therefore, additional large studies with long-term follow-up are required to help the cardiologist and surgeon outline the best therapeutic strategy for patients with high risk for PPM. Patients who underwent aortic valve replacement (AVR) from 2000 to 2013 were identified. Baseline and operative data was extracted and indexed effective orifice area calculated for each patient. The presence of PPM was defined in those patients with an iEOA ≤ 0.85 cm(2)/m(2). Regression analyses were performed to determine the association of PPM with operative mortality, post-operative complications and survival. Predictors for PPM were evaluated based on clinical and operative data. From 2023 patients who underwent AVR, PPM was present in 64.6%. These patients had increased age, more coronary artery bypass procedures, increased risk of diabetes, hypertension, higher creatinine values and higher Euroscore. Age, body surface area, prosthesis type and size were found to be predictors of mismatch. Operative mortality (8.1% vs 5.7%, p = 0.05), stroke (3.9% vs 2.4, p = 0.02) and acute kidney injury (47.6% vs 35.1%, p =< 0 .001) were more frequent in patients with PPM and mean 10-year survival was reduced (6.6 years, 95% CI: 6.3-6.8 vs 7.3, 95% CI: 6.9-7.2, p < 0.001). After adjusting for confounders, PPM was not found to be associated to either adverse outcome or survival. Patients with PPM have worse operative mortality, post-operative complications and survival mainly due to the fact that they represent a higher risk population based on age and co-morbidities. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. 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…

  3. 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...

  4. 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:

  5. 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…

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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

  11. 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…

  12. 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.

  13. 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...

  14. 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...

  15. 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

  16. 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

  17. 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,

  18. 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

  19. 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.

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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…

  10. Educational Mismatches and Earnings: Extensions of Occupational Mobility Theory and Evidence of Human Capital Depreciation

    Science.gov (United States)

    Rubb, Stephen

    2006-01-01

    Using a human capital theory framework, this study examines the impact of educational mismatches on earnings and occupational mobility. Occupational mobility theory suggests that overeducated workers observe greater upward occupational mobility and undereducated workers observe lower upward occupational mobility. By extension, this leads to…

  11. Interaural Place-Mismatch Estimation With Two-Formant Vowels in Unilateral Cochlear- Implant Users

    DEFF Research Database (Denmark)

    Guérit, François; Santurette, Sébastien; Chalupper, Josef

    stimulation, with listeners showing either basal or apical shifts, or generally-poor vowel discrimination. Conclusion The two-formant-vowel method is a fast and clinic-friendly candidate to derive interaural place mismatches from a simple vowel-recognition task. However, it remains unclear whether...

  12. Determining the functional significance of mismatch repair gene missense variants using biochemical and cellular assays

    DEFF Research Database (Denmark)

    Heinen, Christopher D; Juel Rasmussen, Lene

    2012-01-01

    ABSTRACT: With the discovery that the hereditary cancer susceptibility disease Lynch syndrome (LS) is caused by deleterious germline mutations in the DNA mismatch repair (MMR) genes nearly 20 years ago, genetic testing can now be used to diagnose this disorder in patients. A definitive diagnosis...

  13. The Impact of Educational Mismatch on Firm Productivity: Evidence from Linked Panel Data

    Science.gov (United States)

    Kampelmann, Stephan; Rycx, Francois

    2012-01-01

    We provide first evidence regarding the direct impact of educational mismatch on firm productivity. To do so, we rely on representative linked employer-employee panel data for Belgium covering the period 1999-2006. Controlling for simultaneity issues, time-invariant unobserved workplace characteristics, cohort effects and dynamics in the…

  14. 76 FR 33780 - Assessments for Mismatched Payments or Inadequate Payment Information for Geothermal, Solid...

    Science.gov (United States)

    2011-06-09

    ...] Assessments for Mismatched Payments or Inadequate Payment Information for Geothermal, Solid Minerals, and...: Regulations for geothermal, solid minerals, and Indian oil and gas leases authorize the Office of Natural..., Office of Natural Resources Revenue, P.O. Box 25165, MS 61211B, Denver, Colorado 80225-0165...

  15. Mental Ability and Mismatch Negativity: Pre-Attentive Discrimination of Abstract Feature Conjunctions in Auditory Sequences

    Science.gov (United States)

    Houlihan, Michael; Stelmack, Robert M.

    2012-01-01

    The relation between mental ability and the ability to detect violations of an abstract, third-order conjunction rule was examined using event-related potential measures, specifically mismatch negativity (MMN). The primary objective was to determine whether the extraction of invariant relations based on abstract conjunctions between two…

  16. Major Histocompatibility Mismatch and Donor Choice for Second Allogeneic Bone Marrow Transplantation.

    Science.gov (United States)

    Imus, Philip H; Blackford, Amanda L; Bettinotti, Maria; Iglehart, Brian; Dietrich, August; Tucker, Noah; Symons, Heather; Cooke, Kenneth R; Luznik, Leo; Fuchs, Ephraim J; Brodsky, Robert A; Matsui, William H; Huff, Carol Ann; Gladstone, Douglas; Ambinder, Richard F; Borrello, Ivan M; Swinnen, Lode J; Jones, Richard J; Bolaños-Meade, Javier

    2017-11-01

    Large alternative donor pools provide the potential for selecting a different donor for a second allogeneic (allo) bone or marrow transplant (BMT). As HLA disparity may contribute to the graft-versus-tumor effect, utilizing new mismatched haplotype donors may potentially improve the antitumor activity for relapsed hematologic malignancies despite a previous alloBMT. Data from patients who received a second alloBMT for relapsed hematologic malignancies at Johns Hopkins were analyzed. Outcomes were compared between patients who received a second allograft with the same MHC composition and those who received an allograft with a new mismatched haplotype. Loss of heterozygosity analysis was performed for patients with acute myeloid leukemia (AML) whose first allograft was haploidentical. Between 2005 and 2015, 40 patients received a second BMT for a relapsed hematologic malignancy. The median follow-up is 750 (range, 26 to 2950) days. The median overall survival (OS) in the cohort is 928 days (95% confidence interval [CI], 602 to not reached [NR]); median event-free survival (EFS) for the cohort is 500 days (95% CI, 355 to NR). The 4-year OS is 40% (95% CI, 25% to 64%), and the 4-year EFS is 36% (95% CI, 24% to 55%). The cumulative incidence of nonrelapsed mortality by 2 years was 27% (95% CI, 13% to 42%). The cumulative incidence of grade 3 to 4 acute graft-versus-host disease (GVHD) at 100 days was 15% (95% CI, 4% to 26%); the cumulative incidence of extensive chronic GVHD at 2 years was 22% (95% CI, 9% to 36%). The median survival was 552 days (95% CI, 376 to 2950+) in the group who underwent transplantation with a second allograft that did not harbor a new mismatched haplotype, while it was not reached in the group whose allograft contained a new mismatched haplotype (hazard ratio [HR], .36; 95% CI, .14 to .9; P = .02). EFS was also longer in the group who received an allograft containing a new mismatched haplotype, (NR versus 401 days; HR, .50; 95% CI, .22 to 1

  17. Explosive mutation accumulation triggered by heterozygous human Pol ε proofreading-deficiency is driven by suppression of mismatch repair

    Science.gov (United States)

    Campbell, Brittany B; Ungerleider, Nathan; Light, Nicholas; Wu, Tong; LeCompte, Kimberly G; Goksenin, A Yasemin; Bunnell, Bruce A; Tabori, Uri; Shlien, Adam

    2018-01-01

    Tumors defective for DNA polymerase (Pol) ε proofreading have the highest tumor mutation burden identified. A major unanswered question is whether loss of Pol ε proofreading by itself is sufficient to drive this mutagenesis, or whether additional factors are necessary. To address this, we used a combination of next generation sequencing and in vitro biochemistry on human cell lines engineered to have defects in Pol ε proofreading and mismatch repair. Absent mismatch repair, monoallelic Pol ε proofreading deficiency caused a rapid increase in a unique mutation signature, similar to that observed in tumors from patients with biallelic mismatch repair deficiency and heterozygous Pol ε mutations. Restoring mismatch repair was sufficient to suppress the explosive mutation accumulation. These results strongly suggest that concomitant suppression of mismatch repair, a hallmark of colorectal and other aggressive cancers, is a critical force for driving the explosive mutagenesis seen in tumors expressing exonuclease-deficient Pol ε. PMID:29488881

  18. Insights into finding a mismatch through the structure of a mispaired DNA bound by a rhodium intercalator

    Science.gov (United States)

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

    2007-01-01

    We report the 1.1-Å resolution crystal structure of a bulky rhodium complex bound to two different DNA sites, mismatched and matched in the oligonucleotide 5′-(dCGGAAATTCCCG)2-3′. At the AC mismatch site, the structure reveals ligand insertion from the minor groove with ejection of both mismatched bases and elucidates how destabilized mispairs in DNA may be recognized. This unique binding mode contrasts with major groove intercalation, observed at a matched site, where doubling of the base pair rise accommodates stacking of the intercalator. Mass spectral analysis reveals different photocleavage products associated with the two binding modes in the crystal, with only products characteristic of mismatch binding in solution. This structure, illustrating two clearly distinct binding modes for a molecule with DNA, provides a rationale for the interrogation and detection of mismatches. PMID:17194756

  19. The effect of sociodemographic (mis)match between interviewers and respondents on unit and item nonresponse in Belgium.

    Science.gov (United States)

    Vercruyssen, Anina; Wuyts, Celine; Loosveldt, Geert

    2017-09-01

    Interviewer characteristics affect nonresponse and measurement errors in face-to-face surveys. Some studies have shown that mismatched sociodemographic characteristics - for example gender - affect people's behavior when interacting with an interviewer at the door and during the survey interview, resulting in more nonresponse. We investigate the effect of sociodemographic (mis)matching on nonresponse in two successive rounds of the European Social Survey in Belgium. As such, we replicate the analyses of the effect of (mis)matching gender and age on unit nonresponse on the one hand, and of gender, age and education level (mis)matching on item nonresponse on the other hand. Recurring effects of sociodemographic (mis)match are found for both unit and item nonresponse. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Understanding the Consequences of Property Rights Mismatches: a Case Study of New Zealand's Marine Resources

    Directory of Open Access Journals (Sweden)

    Tracy Yandle

    2007-12-01

    Full Text Available Within fisheries and natural resource management literature, there is considerable discussion about the key roles that property rights can play in building biologically and socially sustainable resource management regimes. A key point of agreement is that secure long-term property rights provide an incentive for resource users to manage the resource sustainably. However, property rights mismatches create ambiguity and conflict in resource use. Though the term mismatches is usually associated with problems in matching temporal and spatial resource characteristics with institutional characteristics, I expand it here to include problems that can arise when property rights are incompletely defined or incompletely distributed. Property rights mismatches are particularly likely to occur over marine resources, for which multiple types of resource and resource user can be engaged and managed under a variety of regulatory regimes. I used New Zealand's marine resources to examine the causes and consequences of these property rights mismatches. New Zealand is particularly interesting because its property-rights-based commercial fishing regime, in the form of individual transferable quotas, has attracted considerable positive attention. However, my review of the marine natural resource management regime from a broader property rights perspective highlights a series of problems caused by property rights mismatches, including competition for resources among commercial, customary, and recreational fishers; spatial conflict among many marine resource users; and conflicting incentives and objectives for the management of resources over time. The use of a property rights perspective also highlights some potential solutions such as the layering of institutional arrangements and the improvement of how property rights are defined to encourage long-term sustainability.

  1. Optical CT imaging of solid radiochromic dosimeters in mismatched refractive index solutions using a scanning laser and large area detector

    Energy Technology Data Exchange (ETDEWEB)

    Dekker, Kurtis H., E-mail: kdekker2@uwo.ca [Department of Medical Biophysics, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario N6A 5C1 (Canada); Battista, Jerry J.; Jordan, Kevin J. [Departments of Medical Biophysics and Oncology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario N6A 5C1, Canada and Department of Physics and Engineering, London Regional Cancer Program, London Health Sciences Centre, 790 Commissioners Road East, London, Ontario N6A 4L6 (Canada)

    2016-08-15

    irradiator to achieve either a uniform dose or a 2-level “step-dose” pattern. Results: With 6% refractive index mismatching, a circular field of view of 85% of the diameter of a cylindrical sample can be reconstructed accurately. Reconstructed images of the test solution phantom were uniform (within 3%) inside this radius. However, the dose responses of the PRESAGE® samples were not spatially uniform, with variations of at least 5% in sensitivity. The variation appears as a “cupping” artifact with less sensitivity in the middle than at the periphery of the PRESAGE® cylinder. Polarization effects were also detected for these samples. Conclusions: The fiducial-based ray path measurement scheme, coupled with an iterative reconstruction algorithm, enabled optical CT scanning of PRESAGE® dosimeters immersed in mismatched refractive index solutions. However, improvements to PRESAGE® dose response uniformity are required.

  2. 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

  3. 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

  4. Femoral head retroposition as a potential compensatory mechanism in patients with a severe mismatch between pelvic incidence and lumbar lordosis.

    Science.gov (United States)

    Cheng, Xiaofei; Zhang, Kai; Sun, Xiaojiang; Zhao, Changqing; Li, Hua; Zhao, Jie

    2017-12-01

    Severe mismatch between pelvic incidence (PI) and lumbar lordosis (LL) leads to extra anterior displacement of the gravity line. The objective of this study is to investigate whether femoral head retroposition is a separate compensatory mechanism responsible for the extra anterior displacement. Based on the values of PI and LL, 94 patients were divided into the PI-LL match group (PI-LL ≤ 0°), the mild PI-LL mismatch group (20°> PI-LL >0°), and the severe PI-LL mismatch group (PI-LL ≥ 20°). A series of parameters including PI, LL, PI-LL, thoracic kyphosis (TK), pelvic tilt (PT), sacral slope (SS), knee flexion angle (KFA), tibial obliquity angle (TOA), sagittal vertical axis (SVA), S1 overhang, femoral head shift (FHS), and pelvic shift (PS) were measured and compared among the three groups. The severe PI-LL mismatch group exhibited significantly greater PI, PI-LL, PT, KFA, SVA, PS, and FHS, and less LL and TK, compared with the control and mild PI-LL mismatch group. The mild PI-LL mismatch group had significantly greater PI-LL, PT, KFA, TOA, and S1 overhang, and less LL and SS than the control group. SS, TOA, and S1 overhang in the severe PI-LL mismatch group differed significantly from that in the control group, but did not differ significantly from that in the mild PI-LL mismatch group. Femoral head retroposition is an entirely separate compensatory mechanism and, in this study, participated in the compensation for the anterior displacement of the gravity line induced by extra-sagittal spinal malalignment in patients with severe PI-LL mismatch.

  5. Spontaneous Improvement of Compensatory Knee Flexion After Surgical Correction of Mismatch Between Pelvic Incidence and Lumbar Lordosis.

    Science.gov (United States)

    Cheng, Xiaofei; Zhang, Feng; Wu, Jigong; Zhu, Zhenan; Dai, Kerong; Zhao, Jie

    2016-08-15

    A retrospective study. The aim of this study was to investigate the correlation between pelvic incidence (PI) and lumbar lordosis (LL) mismatch and knee flexion during standing in patients with lumbar degenerative diseases and to examine the effects of surgical correction of the PI-LL mismatch on knee flexion. Only several studies focused on knee flexion as a compensatory mechanism of the PI-LL mismatch. Little information is currently available on the effects of lumbar correction on knee flexion in patients with the PI-LL mismatch. A group of patients with lumbar degenerative diseases were divided into PI-LL match group (PI-LL ≤ 10°) and PI-LL mismatch group (PI-LL > 10°). A series of radiographic parameters and knee flexion angle (KFA) were compared between the two groups. The PI-LL mismatch group was further subdivided into operative and nonoperative group. The changes in KFA with PI-LL were examined. The PI-LL mismatch group exhibited significantly greater sagittal vertical axis (SVA), pelvic tilt (PT) and KFA, and smaller LL, thoracic kyphosis (TK), and sacral slope than the PI-LL match group. PI-LL, LL, PI, SVA, and PT were significantly correlated with KFA in the PI-LL mismatch group. From baseline to 6-month follow-up, all variables were significantly different in the operative group with the exception of PI, although there was no significant difference in any variable in the nonoperative group. The magnitude of surgical correction in the PI-LL mismatch was significantly correlated with the degree of spontaneous changes in KFA, PT, and TK. The PI-LL mismatch would contribute to compensatory knee flexion during standing in patients with lumbar degenerative disease. Surgical correction of the PI-LL mismatch could lead to a spontaneous improvement of compensatory knee flexion. The degree of improvement in knee flexion depends in part on the amount of correction in the PI-LL mismatch. 3.

  6. A Newborn Case of “c” Subgroup Mismatch Presenting with Severe Hemolysis and Anemia

    Directory of Open Access Journals (Sweden)

    Ezgi Yangın Ergon

    2017-12-01

    Full Text Available Hemolysis and jaundice related to Rh incompatibility in the neonatal period has decreased substantially due to the widespread use of anti-D gammaglobulin in recent years. Nevertheless, the rate of subgroup mismatch in the etiology of hemolytic diseases of the newborn has increased significantly. In this article an 8-day-old newborn infant with “c” subgroup incompatibility and presenting with severe anemia, in whom hemolysis could be controlled with intravenous immunoglobulin infusion and subgroup appropriate blood transfusion, has been presented. Scientific studies have demonstrated that the hemolytic disease of patients who don’t have major blood group incompatibility but carry anti-C antibodies can be rather serious. Therefore, subgroup mismatch should always be kept in mind for newborns presenting with severe hemolytic anemia, and transfusion or if necessary exchange transfusion should be provided with subgroup matched blood products.

  7. HLA-mismatched hematopoietic stem cell tranplantation for pediatric solid tumors

    Directory of Open Access Journals (Sweden)

    Andrea Pession

    2011-06-01

    Full Text Available Even if the overall survival of children with cancer is significantly improved over these decades, the cure rate of high-risk pediatric solid tumors such as neuroblastoma, Ewing’s sarcoma family tumors or rhabdomiosarcoma remain challenging. Autologous hematopoietic stem cell transplantation (HSCT allows chemotherapy dose intensification beyond marrow tolerance and has become a fundamental tool in the multimodal therapeutical approach of these patients. Anyway this procedure does not allow to these children an eventfree survival approaching more than 50% at 5 years. New concepts of allogeneic HSCT and in particular HLA-mismatched HSCT for high risk solid tumors do not rely on escalation of chemo therapy intensity and tumor load reduction but rather on a graft-versus-tumor effect. We here report an experimental study design of HLA-mismatched HSCT for the treatment of pediatric solid tumors and the inherent preliminary results.

  8. Collective pedagogical teacher culture, teacher-student ethno-racial mismatch, and teacher job satisfaction.

    Science.gov (United States)

    Stearns, Elizabeth; Banerjee, Neena; Mickelson, Roslyn; Moller, Stephanie

    2014-05-01

    Teacher job satisfaction is critical to schools' successful functioning. Using a representative sample of kindergarten teachers from the Early Childhood Longitudinal Study, we investigate the association among professional learning community and teacher collaboration, teacher ethno-racial group, teacher-student ethno-racial mismatch, and teacher job satisfaction. We find that White teachers are significantly less satisfied than African-American and Latino teachers, especially when they teach in majority non-White classrooms. However, the existence of a professional community moderates the negative influence of teacher-student ethno-racial mismatch on White teachers' job satisfaction. In effect, strong professional communities serve as a cushion to bolster teacher job satisfaction. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. 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

  10. Design Impedance Mismatch Physical Unclonable Functions for IoT Security

    Directory of Open Access Journals (Sweden)

    Xiaomin Zheng

    2017-01-01

    Full Text Available We propose a new design, Physical Unclonable Function (PUF scheme, for the Internet of Things (IoT, which has been suffering from multiple-level security threats. As more and more objects interconnect on IoT networks, the identity of each thing is very important. To authenticate each object, we design an impedance mismatch PUF, which exploits random physical factors of the transmission line to generate a security unique private key. The characteristic impedance of the transmission line and signal transmission theory of the printed circuit board (PCB are also analyzed in detail. To improve the reliability, current feedback amplifier (CFA method is applied on the PUF. Finally, the proposed scheme is implemented and tested. The measure results show that impedance mismatch PUF provides better unpredictability and randomness.

  11. Chaos synchronization in time-delayed systems with parameter mismatches and variable delay times

    International Nuclear Information System (INIS)

    Shahverdiev, E.M.; Nuriev, R.A.; Hashimov, R.H.; Shore, K.A.

    2004-06-01

    We investigate synchronization between two undirectionally linearly coupled chaotic nonidentical time-delayed systems and show that parameter mismatches are of crucial importance to achieve synchronization. We establish that independent of the relation between the delay time in the coupled systems and the coupling delay time, only retarded synchronization with the coupling delay time is obtained. We show that with parameter mismatch or without it neither complete nor anticipating synchronization occurs. We derive existence and stability conditions for the retarded synchronization manifold. We demonstrate our approach using examples of the Ikeda and Mackey Glass models. Also for the first time we investigate chaos synchronization in time-delayed systems with variable delay time and find both existence and sufficient stability conditions for the retarded synchronization manifold with the coupling-delay lag time. (author)

  12. A graphene solution to conductivity mismatch: spin injection from ferromagnetic metal/graphene tunnel contacts into silicon

    Science.gov (United States)

    van't Erve, Olaf

    2014-03-01

    New paradigms for spin-based devices, such as spin-FETs and reconfigurable logic, have been proposed and modeled. These devices rely on electron spin being injected, transported, manipulated and detected in a semiconductor channel. This work is the first demonstration on how a single layer of graphene can be used as a low resistance tunnel barrier solution for electrical spin injection into Silicon at room temperature. We will show that a FM metal / monolayer graphene contact serves as a spin-polarized tunnel barrier which successfully circumvents the classic metal / semiconductor conductivity mismatch issue for electrical spin injection. We demonstrate electrical injection and detection of spin accumulation in Si above room temperature, and show that the corresponding spin lifetimes correlate with the Si carrier concentration, confirming that the spin accumulation measured occurs in the Si and not in interface trap states. An ideal tunnel barrier should exhibit several key material characteristics: a uniform and planar habit with well-controlled thickness, minimal defect / trapped charge density, a low resistance-area product for minimal power consumption, and compatibility with both the FM metal and semiconductor, insuring minimal diffusion to/from the surrounding materials at temperatures required for device processing. Graphene, offers all of the above, while preserving spin injection properties, making it a compelling solution to the conductivity mismatch for spin injection into Si. Although Graphene is very conductive in plane, it exhibits poor conductivity perpendicular to the plane. Its sp2 bonding results in a highly uniform, defect free layer, which is chemically inert, thermally robust, and essentially impervious to diffusion. The use of a single monolayer of graphene at the Si interface provides a much lower RA product than any film of an oxide thick enough to prevent pinholes (1 nm). Our results identify a new route to low resistance-area product spin

  13. Scalable solution-phase epitaxial growth of symmetry-mismatched heterostructures on two-dimensional crystal soft template.

    Science.gov (United States)

    Lin, Zhaoyang; Yin, Anxiang; Mao, Jun; Xia, Yi; Kempf, Nicholas; He, Qiyuan; Wang, Yiliu; Chen, Chih-Yen; Zhang, Yanliang; Ozolins, Vidvuds; Ren, Zhifeng; Huang, Yu; Duan, Xiangfeng

    2016-10-01

    Epitaxial heterostructures with precisely controlled composition and electronic modulation are of central importance for electronics, optoelectronics, thermoelectrics, and catalysis. In general, epitaxial material growth requires identical or nearly identical crystal structures with small misfit in lattice symmetry and parameters and is typically achieved by vapor-phase depositions in vacuum. We report a scalable solution-phase growth of symmetry-mismatched PbSe/Bi 2 Se 3 epitaxial heterostructures by using two-dimensional (2D) Bi 2 Se 3 nanoplates as soft templates. The dangling bond-free surface of 2D Bi 2 Se 3 nanoplates guides the growth of PbSe crystal without requiring a one-to-one match in the atomic structure, which exerts minimal restriction on the epitaxial layer. With a layered structure and weak van der Waals interlayer interaction, the interface layer in the 2D Bi 2 Se 3 nanoplates can deform to accommodate incoming layer, thus functioning as a soft template for symmetry-mismatched epitaxial growth of cubic PbSe crystal on rhombohedral Bi 2 Se 3 nanoplates. We show that a solution chemistry approach can be readily used for the synthesis of gram-scale PbSe/Bi 2 Se 3 epitaxial heterostructures, in which the square PbSe (001) layer forms on the trigonal/hexagonal (0001) plane of Bi 2 Se 3 nanoplates. We further show that the resulted PbSe/Bi 2 Se 3 heterostructures can be readily processed into bulk pellet with considerably suppressed thermal conductivity (0.30 W/m·K at room temperature) while retaining respectable electrical conductivity, together delivering a thermoelectric figure of merit ZT three times higher than that of the pristine Bi 2 Se 3 nanoplates at 575 K. Our study demonstrates a unique epitaxy mode enabled by the 2D nanocrystal soft template via an affordable and scalable solution chemistry approach. It opens up new opportunities for the creation of diverse epitaxial heterostructures with highly disparate structures and functions.

  14. The spontaneous replication error and the mismatch discrimination mechanisms of human DNA polymerase β

    Science.gov (United States)

    Koag, Myong-Chul; Nam, Kwangho; Lee, Seongmin

    2014-01-01

    To provide molecular-level insights into the spontaneous replication error and the mismatch discrimination mechanisms of human DNA polymerase β (polβ), we report four crystal structures of polβ complexed with dG•dTTP and dA•dCTP mismatches in the presence of Mg2+ or Mn2+. The Mg2+-bound ground-state structures show that the dA•dCTP-Mg2+ complex adopts an ‘intermediate’ protein conformation while the dG•dTTP-Mg2+ complex adopts an open protein conformation. The Mn2+-bound ‘pre-chemistry-state’ structures show that the dA•dCTP-Mn2+ complex is structurally very similar to the dA•dCTP-Mg2+ complex, whereas the dG•dTTP-Mn2+ complex undergoes a large-scale conformational change to adopt a Watson–Crick-like dG•dTTP base pair and a closed protein conformation. These structural differences, together with our molecular dynamics simulation studies, suggest that polβ increases replication fidelity via a two-stage mismatch discrimination mechanism, where one is in the ground state and the other in the closed conformation state. In the closed conformation state, polβ appears to allow only a Watson–Crick-like conformation for purine•pyrimidine base pairs, thereby discriminating the mismatched base pairs based on their ability to form the Watson–Crick-like conformation. Overall, the present studies provide new insights into the spontaneous replication error and the replication fidelity mechanisms of polβ. PMID:25200079

  15. Processes influencing model-data mismatch in drought-stressed, fire-disturbed eddy flux sites

    Science.gov (United States)

    Mitchell, Stephen; Beven, Keith; Freer, Jim; Law, Beverly

    2011-06-01

    Semiarid forests are very sensitive to climatic change and among the most difficult ecosystems to accurately model. We tested the performance of the Biome-BGC model against eddy flux data taken from young (years 2004-2008), mature (years 2002-2008), and old-growth (year 2000) ponderosa pine stands at Metolius, Oregon, and subsequently examined several potential causes for model-data mismatch. We used the Generalized Likelihood Uncertainty Estimation methodology, which involved 500,000 model runs for each stand (1,500,000 total). Each simulation was run with randomly generated parameter values from a uniform distribution based on published parameter ranges, resulting in modeled estimates of net ecosystem CO2 exchange (NEE) that were compared to measured eddy flux data. Simulations for the young stand exhibited the highest level of performance, though they overestimated ecosystem C accumulation (-NEE) 99% of the time. Among the simulations for the mature and old-growth stands, 100% and 99% of the simulations underestimated ecosystem C accumulation. One obvious area of model-data mismatch is soil moisture, which was overestimated by the model in the young and old-growth stands yet underestimated in the mature stand. However, modeled estimates of soil water content and associated water deficits did not appear to be the primary cause of model-data mismatch; our analysis indicated that gross primary production can be accurately modeled even if soil moisture content is not. Instead, difficulties in adequately modeling ecosystem respiration, mainly autotrophic respiration, appeared to be the fundamental cause of model-data mismatch.

  16. Constitutional mismatch repair deficiency presenting in childhood as three simultaneous malignancies.

    Science.gov (United States)

    Walter, Andrew W; Ennis, Sara; Best, Hunter; Vaughn, Cecily P; Swensen, Jeffrey J; Openshaw, Amanda; Gripp, Karen W

    2013-11-01

    A 13-year-old child presented with three simultaneous malignancies: glioblastoma multiforme, Burkitt lymphoma, and colonic adenocarcinoma. She was treated for her diseases without success and died 8 months after presentation. Genetic analysis revealed a homozygous mutation in the PMS2 gene, consistent with constitutional mismatch repair deficiency. Her siblings and parents were screened: three of four siblings and both parents were heterozygous for this mutation; the fourth sibling did not have the mutation. Copyright © 2013 Wiley Periodicals, Inc.

  17. Phenological mismatch in coastal western Alaska may increase summer season greenhouse gas uptake

    Science.gov (United States)

    Kelsey, Katharine C.; Leffler, A. Joshua; Beard, Karen H.; Choi, Ryan T.; Schmutz, Joel A.; Welker, Jeffery M.

    2018-04-01

    High latitude ecosystems are prone to phenological mismatches due to climate change- driven advances in the growing season and changing arrival times of migratory herbivores. These changes have the potential to alter biogeochemical cycling and contribute to feedbacks on climate change by altering greenhouse gas (GHG) emissions of carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O) through large regions of the Arctic. Yet the effects of phenological mismatches on gas fluxes are currently unexplored. We used a three-year field experiment that altered the start of the growing season and timing of grazing to investigate how phenological mismatch affects GHG exchange. We found early grazing increased mean GHG emission to the atmosphere despite lower CH4 emissions due to grazing-induced changes in vegetation structure that increased uptake of CO2. In contrast, late grazing reduced GHG emissions because greater plant productivity led to an increase in CO2 uptake that overcame the increase in CH4 emission. Timing of grazing was an important control on both CO2 and CH4 emissions, and net GHG exchange was the result of opposing fluxes of CO2 and CH4. N2O played a negligible role in GHG flux. Advancing the growing season had a smaller effect on GHG emissions than changes to timing of grazing in this study. Our results suggest that a phenological mismatch that delays timing of grazing relative to the growing season, a change which is already developing along in western coastal Alaska, will reduce GHG emissions to the atmosphere through increased CO2 uptake despite greater CH4 emissions.

  18. A Newborn Case of “c” Subgroup Mismatch Presenting with Severe Hemolysis and Anemia

    OpenAIRE

    Ezgi Yangın Ergon; Senem Alkan Özdemir; Rüya Çolak; Kıymet Çelik; Özgür Olukman; Şebnem Çalkavur

    2017-01-01

    Hemolysis and jaundice related to Rh incompatibility in the neonatal period has decreased substantially due to the widespread use of anti-D gammaglobulin in recent years. Nevertheless, the rate of subgroup mismatch in the etiology of hemolytic diseases of the newborn has increased significantly. In this article an 8-day-old newborn infant with “c” subgroup incompatibility and presenting with severe anemia, in whom hemolysis could be controlled with intravenous immunoglobulin infusion and subg...

  19. Phenological mismatch in coastal western Alaska may increase summer season greenhouse gas uptake

    Science.gov (United States)

    Kelsey, Katharine C.; Leffler, A. Joshua; Beard, Karen H.; Choi, Ryan T.; Schmutz, Joel A.; Welker, Jeffery M.

    2018-01-01

    High latitude ecosystems are prone to phenological mismatches due to climate change- driven advances in the growing season and changing arrival times of migratory herbivores. These changes have the potential to alter biogeochemical cycling and contribute to feedbacks on climate change by altering greenhouse gas (GHG) emissions of carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O) through large regions of the Arctic. Yet the effects of phenological mismatches on gas fluxes are currently unexplored. We used a three-year field experiment that altered the start of the growing season and timing of grazing to investigate how phenological mismatch affects GHG exchange. We found early grazing increased mean GHG emission to the atmosphere despite lower CH4 emissions due to grazing-induced changes in vegetation structure that increased uptake of CO2. In contrast, late grazing reduced GHG emissions because greater plant productivity led to an increase in CO2 uptake that overcame the increase in CH4 emission. Timing of grazing was an important control on both CO2 and CH4 emissions, and net GHG exchange was the result of opposing fluxes of CO2 and CH4. N2O played a negligible role in GHG flux. Advancing the growing season had a smaller effect on GHG emissions than changes to timing of grazing in this study. Our results suggest that a phenological mismatch that delays timing of grazing relative to the growing season, a change which is already developing along in western coastal Alaska, will reduce GHG emissions to the atmosphere through increased CO2 uptake despite greater CH4 emissions.

  20. Decadal declines in avian herbivore reproduction: density-dependent nutrition and phenological mismatch in the Arctic.

    Science.gov (United States)

    Ross, Megan V; Alisauskas, Ray T; Douglas, David C; Kellett, Dana K

    2017-07-01

    A full understanding of population dynamics depends not only on estimation of mechanistic contributions of recruitment and survival, but also knowledge about the ecological processes that drive each of these vital rates. The process of recruitment in particular may be protracted over several years, and can depend on numerous ecological complexities until sexually mature adulthood is attained. We addressed long-term declines (23 breeding seasons, 1992-2014) in the per capita production of young by both Ross's Geese (Chen rossii) and Lesser Snow Geese (Chen caerulescens caerulescens) nesting at Karrak Lake in Canada's central Arctic. During this period, there was a contemporaneous increase from 0.4 to 1.1 million adults nesting at this colony. We evaluated whether (1) density-dependent nutritional deficiencies of pre-breeding females or (2) phenological mismatch between peak gosling hatch and peak forage quality, inferred from NDVI on the brood-rearing areas, may have been behind decadal declines in the per capita production of goslings. We found that, in years when pre-breeding females arrived to the nesting grounds with diminished nutrient reserves, the proportional composition of young during brood-rearing was reduced for both species. Furthermore, increased mismatch between peak gosling hatch and peak forage quality contributed additively to further declines in gosling production, in addition to declines caused by delayed nesting with associated subsequent negative effects on clutch size and nest success. The degree of mismatch increased over the course of our study because of advanced vegetation phenology without a corresponding advance in Goose nesting phenology. Vegetation phenology was significantly earlier in years with warm surface air temperatures measured in spring (i.e., 25 May-30 June). We suggest that both increased phenological mismatch and reduced nutritional condition of arriving females were behind declines in population-level recruitment, leading

  1. A global mismatch in the protection of multiple marine biodiversity components and ecosystem services

    DEFF Research Database (Denmark)

    Lindegren, Martin; Holt, Ben G.; MacKenzie, Brian R.

    2018-01-01

    spatial scale. We demonstrate a pronounced spatial mismatch between the existing degree of protection and all the conservation priorities above, highlighting that neither the world's most diverse, nor the most productive ecosystems are currently the most protected ecosystems. Furthermore, we show...... more effectively than the existing degree of protection, which at best is only marginally better than a random expectation. Therefore, a holistic perspective is needed when designating an appropriate degree of protection of marine conservation priorities worldwide....

  2. Diffusion Tensor Imaging for the Differentiation of Microangiopathy, Infarction and Perfusion-Diffusion Mismatch Lesions

    International Nuclear Information System (INIS)

    Ha, Dong Ho; Choi, Sun Seob; Kang, Myong Jin; Lee, Jin Hwa; Yoon, Seong Kuk; Nam, Kyung Jin

    2009-01-01

    This study was designed to evaluate the usefulness of diffusion tensor imaging (DTI) and the DTI indices for differentiating between microangiopathy lesions, acute infarction lesions and perfusion-diffusion mismatch areas. DTI was performed in 35 patients with the use of a 1.5 Tesla MRI system. The MRI parameters were as follows: a spin echo EPI sequence with a bvalue = 1000 s/mm 2 , 25 diffusion directions, a repetition time of 8400 msec, an echo time of 75 msec, a matrix size of 128 x 128, a FOV of 22 cm and a 4 mm slice thickness. From the diffusion tensor images, the apparent diffusion coefficient (ADC), fractional anisotropy (FA), volume ratio (VR), relative anisotropy (RA), anisotropy index (AI), exponential ADC (eADC) and magnitude diffusion coefficient (MDC) were measured for the contra-lateral normal area (28 cases), the microangiopathy lesions (10 cases), the infarction lesions (17 cases) and the perfusion-diffusion mismatch area (8 cases). As compared to the normal area, the microangiopathy lesions showed increased ADC and MDC values and decreased FA, VR, RA, AI and eADC values. The infarction lesions showed increased VR, RA and eADC values, a normal FA, a decreased AI and decreased ADC and MDC values. The mismatch area showed a similar pattern as that for the microangiopathy lesions; however, the differences were not prominent, with an increase of the ADC and MDC values and a decrease of FA, VR, RA, AI and eADC values. The DTI indices could have a role in making the differential diagnosis of microangiopathy, acute infarction and perfusion-diffusion mismatch lesions

  3. "Clinical-CT mismatch" and the response to systemic thrombolytic therapy in acute ischemic stroke.

    Science.gov (United States)

    Kent, David M; Hill, Michael D; Ruthazer, Robin; Coutts, Shelagh B; Demchuk, Andrew M; Dzialowski, Imanuel; Wunderlich, Olaf; von Kummer, Rudiger

    2005-08-01

    Mismatch between clinical deficits and imaging lesions in acute stroke has been proposed as a method of identifying patients who have hypoperfused but still have viable brain, and may be especially apt to respond to reperfusion therapy. We explored this hypothesis using a combined database including 4 major clinical trials of intravenous (IV) thrombolytic therapy. To determine what the radiological correlates of a "matched" functional deficit are, we calculated the relationship between the ASPECT score of the 24-hour (follow-up) CT scan and the 24-hour National Institutes of Health Stroke Scale (NIHSS) score on the subsample with ASPECT scores performed at this time (n=820). Based on this empirical relationship, we computed the absolute difference between the observed baseline ASPECT score and the "expected" score (ie, matched) based on baseline NIHSS for all patients (n=2131). We tested whether patients with better than expected baseline ASPECTS were more likely to benefit from IV recombinant tissue plasminogen activation (rtPA). At 24 hours, there was a strong, linear, negative correlation between NIHSS and ASPECTS (r2=0.33, P<0.0001); on average, an increase of 10 points on NIHSS corresponded to a decrease of approximately 3 points on ASPECTS. At baseline, the average degree of mismatch between the observed and "expected" ASPECTS was 2.1 points (interquartile range, 1.0 to 3.4). However, multiple analyses failed to reveal a consistent relationship between the degree of clinical-CT mismatch at baseline and a patient's likelihood of benefiting from IV rtPA. Clinical-CT mismatch using ASPECT scoring does not reliably identify patients more or less likely to benefit from IV rtPA.

  4. Do polymorphisms and haplotypes of mismatch repair genes modulate risk of sporadic colorectal cancer?

    Czech Academy of Sciences Publication Activity Database

    Tulupová, Elena; Kumar, R.; Hánová, Monika; Slyšková, Jana; Pardini, Barbara; Poláková, Veronika; Naccarati, Alessio; Vodičková, Ludmila; Novotný, J.; Halamková, J.; Hemminki, K.; Vodička, Pavel

    2008-01-01

    Roč. 648, 1-2 (2008), s. 40-45 ISSN 0027-5107 R&D Projects: GA ČR GA310/07/1430 Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z50390703 Keywords : DNA mismatch repair * Genetic polymorphism * Haplotype analysis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.198, year: 2008

  5. Decadal declines in avian herbivore reproduction: density-dependent nutrition and phenological mismatch in the Arctic

    Science.gov (United States)

    Ross, Megan V.; Alisaukas, Ray T.; Douglas, David C.; Kellett, Dana K.

    2017-01-01

    A full understanding of population dynamics depends not only on estimation of mechanistic contributions of recruitment and survival, but also knowledge about the ecological processes that drive each of these vital rates. The process of recruitment in particular may be protracted over several years, and can depend on numerous ecological complexities until sexually mature adulthood is attained. We addressed long-term declines (23 breeding seasons, 1992–2014) in the per capita production of young by both Ross's Geese (Chen rossii) and Lesser Snow Geese (Chen caerulescens caerulescens) nesting at Karrak Lake in Canada's central Arctic. During this period, there was a contemporaneous increase from 0.4 to 1.1 million adults nesting at this colony. We evaluated whether (1) density-dependent nutritional deficiencies of pre-breeding females or (2) phenological mismatch between peak gosling hatch and peak forage quality, inferred from NDVI on the brood-rearing areas, may have been behind decadal declines in the per capita production of goslings. We found that, in years when pre-breeding females arrived to the nesting grounds with diminished nutrient reserves, the proportional composition of young during brood-rearing was reduced for both species. Furthermore, increased mismatch between peak gosling hatch and peak forage quality contributed additively to further declines in gosling production, in addition to declines caused by delayed nesting with associated subsequent negative effects on clutch size and nest success. The degree of mismatch increased over the course of our study because of advanced vegetation phenology without a corresponding advance in Goose nesting phenology. Vegetation phenology was significantly earlier in years with warm surface air temperatures measured in spring (i.e., 25 May–30 June). We suggest that both increased phenological mismatch and reduced nutritional condition of arriving females were behind declines in population-level recruitment

  6. Aspectual mismatches in the interpretation of idioms: the view from AspP

    Directory of Open Access Journals (Sweden)

    Imola-Ágnes Farkas

    2016-11-01

    Full Text Available The present paper is an attempt to uncover some of the (syntactic properties of idioms that present aspectual mismatches between their literal and idiomatic interpretation. The novelty value of the proposal lies in its syntactic rather than semantic or cognitive approach: whereas most accounts in the literature deal with this conundrum from a semantic and cognitive point of view, the present analysis provides a syntactic aspectual account by relying on AspP.

  7. An Underreported Consequence of Obesity in Pregnancy: Patient-Prosthesis Mismatch

    OpenAIRE

    Hartman, William R.; Arendt, Katherine W.; Rehfeldt, Kent H.

    2012-01-01

    As the rate of obesity increases in childbearing-aged women, so too will the complications of obesity in pregnancy. An uncommon and likely underreported complication occurs in obese women who have received prepregnancy cardiac valve replacement with a prosthesis that is inadequately sized for body habitus, a condition referred to as patient-prosthesis mismatch (PPM). The physiologic changes of pregnancy as well as the increased weight gain combine to exacerbate PPM. We report a case of PPM th...

  8. The importance of heterogeneity when examining immigrant education-occupation mismatch: evidence from New Zealand

    OpenAIRE

    Jacques Poot; Steven Stillman

    2010-01-01

    Many immigrants are overqualified in their first job after arrival in the host country. Education-occupation mismatch can affect the economic integration of immigrants and the returns to education and experience. The extent of this problem has been measured in recent years by means of micro level data in Australia, North America and Europe. However, these papers have typically ignored the importance of allowing for heterogeneity, in particular by qualification level and years in the destinati...

  9. Variations in mismatch repair genes and colorectal cancer risk and clinical outcome

    Czech Academy of Sciences Publication Activity Database

    Vymetálková, Veronika; Pardini, B.; Rosa, F.; Di Gaetano, C.; Novotný, J.; Levý, M.; Buchler, T.; Slyšková, Jana; Vodičková, Ludmila; Naccarati, Alessio; Vodička, Pavel

    2014-01-01

    Roč. 29, č. 4 (2014), s. 259-265 ISSN 0267-8357 R&D Projects: GA ČR GPP304/11/P715; GA ČR GAP304/10/1286; GA MZd NT12025 Institutional support: RVO:68378041 Keywords : colorectal cancer , , * mismatch repair genes * miRNA Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.793, year: 2014

  10. Molecular characteristics of mismatch repair genes in sporadic colorectal tumors in Czech patients

    Czech Academy of Sciences Publication Activity Database

    Vymetálková, Veronika; Slyšková, Jana; Korenková, Vlasta; Bielik, Ludovít; Langerová, Lucie; Procházka, Pavel; Rejhová, Alexandra; Schwarzová, L.; Pardini, B.; Naccarati, Alessio; Vodička, Pavel

    2014-01-01

    Roč. 15, č. 1 (2014), s. 17 ISSN 1471-2350 R&D Projects: GA AV ČR IAA500200917; GA ČR(CZ) GPP304/11/P715 Grant - others:GA MŠk(CZ) Prvouk-P27/LF1/1 Institutional support: RVO:68378041 ; RVO:86652036 Keywords : colorectal cancer * mismatch repair genes * expression levels Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.083, year: 2014

  11. Effect of group velocity mismatch on acousto-optic interaction of ultrashort laser pulses

    International Nuclear Information System (INIS)

    Yushkov, K B; Molchanov, V Ya

    2011-01-01

    Equations describing acousto-optic diffraction of ultrashort laser pulses in an anisotropic medium are derived, taking into account the group velocity mismatch of optical eigenmodes. It is shown that the solution of the modified coupled-mode equations taking into account the group delay is characterised by an increase in the pulse duration, a decrease in diffraction efficiency, a change in the shape of the wave packet envelope, as well as by an increase in the width of the transmission function.

  12. A mismatch in the human realism of face and voice produces an uncanny valley

    Science.gov (United States)

    Mitchell, Wade J; Szerszen, Kevin A; Lu, Amy Shirong; Schermerhorn, Paul W; Scheutz, Matthias; MacDorman, Karl F

    2011-01-01

    The uncanny valley has become synonymous with the uneasy feeling of viewing an animated character or robot that looks imperfectly human. Although previous uncanny valley experiments have focused on relations among a character's visual elements, the current experiment examines whether a mismatch in the human realism of a character's face and voice causes it to be evaluated as eerie. The results support this hypothesis. PMID:23145223

  13. Constitutional mismatch repair deficiency and Lynch syndrome among consecutive Arab Bedouins with colorectal cancer in Israel.

    Science.gov (United States)

    Abu Freha, Naim; Leibovici Weissman, Yaara; Fich, Alexander; Barnes Kedar, Inbal; Halpern, Marisa; Sztarkier, Ignacio; Behar, Doron M; Arbib Sneh, Orly; Vilkin, Alex; Baris, Hagit N; Gingold, Rachel; Lejbkowicz, Flavio; Niv, Yaron; Goldberg, Yael; Levi, Zohar

    2018-01-01

    We assessed the molecular characteristics and the frequency of mutations in mismatch-repair genes among Bedouin patients with colorectal cancer (CRC) in Israel. Bedouin patients with a diagnosis of CRC at a major hospital in the southern part of Israel were deemed eligible for this study. The primary screening method was immunohistochemical staining for mismatch-repair proteins (MLH1, MSH2, MSH6, and PMS2). For subjects with abnormal immunohistochemical staining, we performed microsatellite instability (MSI) analyses, and for tumors with a loss of MLH1 expression we also performed BRAF testing. In MSI high cases we searched further for germline mutations. Of the 24 patients enrolled, four subjects (16.7%) had MSI high tumors: one subject was found to harbor a biallelic PMS2 mutation, one subject had Lynch syndrome (LS) with MSH6 mutation and two subjects had a loss of MLH1/PMS2 proteins/BRAF wild type /normal MLH1 sequence. Ten patients (41.7%) were younger than 50 at the time of diagnosis and none had first degree relatives with CRC. In conclusion, in this cohort of 24 consecutive Arab Bedouins with CRC, one patient was found to harbor a constitutional mismatch repair deficiency, one patient had LS with MSH6 mutation, and two patients had unresolved loss of MLH1/PMS2 proteins/BRAF wild type phenotype.

  14. 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

  15. Estrogen enhances mismatch repair by induction of MLH1 expression via estrogen receptor-β.

    Science.gov (United States)

    Lu, Jun-Yu; Jin, Peng; Gao, Wei; Wang, De-Zhi; Sheng, Jian-Qiu

    2017-06-13

    Epidemiological data demonstrated that hormone replace treatment has protective effect against colorectal cancer (CRC). Our previous studies showed that this effect may be associated with DNA mismatch repair. This study aims to investigate the mechanism of estrogen induction of MLH1, and whether colorectal tumor proliferation can be inhibited through induction of MLH1 by estrogen signal pathway. Human CRC cell lines were used to examine the regulation of MLH1 expression by over-expression and depletion of estrogen receptor-α (ERα) and estrogen receptor-β (ERβ), under the treatment with 17β-estradiol or β-Estradiol 6-(O-carboxy-methyl)oxime:BSA, followed by a real-time Q-PCR and Western blotting analysis. Luciferase reporter and chromatin immunoprecipitation assays were used to identify the estrogen response elements in the proximal promoter of MLH1 gene. Then, the influence of estrogen-induced MLH1 on CRC tumor growth were determined in vitro and in vivo. We found that mismatch repair ability and microsatellite stability of cells were enhanced by estrogen via induction of MLH1 expression, which was mediated by ERβ, through a transcriptional activation process. Furthermore, we identified that ERβ exerted an inhibitory effect on CRC tumor proliferation in vitro and in vivo, combined with 5-FU, through up-regulation of MLH1 expression. Finally, we concluded that estrogen enhances mismatch repair ability and tumor inhibition effect in vitro and in vivo, via induction of MLH1 expression mediated by ERβ.

  16. 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.

  17. Selective alkylation of T–T mismatched DNA using vinyldiaminotriazine–acridine conjugate

    Science.gov (United States)

    Onizuka, Kazumitsu; Usami, Akira; Yamaoki, Yudai; Kobayashi, Tomohito; Hazemi, Madoka E; Chikuni, Tomoko; Sato, Norihiro; Sasaki, Kaname; Katahira, Masato

    2018-01-01

    Abstract The alkylation of the specific higher-order nucleic acid structures is of great significance in order to control its function and gene expression. In this report, we have described the T–T mismatch selective alkylation with a vinyldiaminotriazine (VDAT)–acridine conjugate. The alkylation selectively proceeded at the N3 position of thymidine on the T–T mismatch. Interestingly, the alkylated thymidine induced base flipping of the complementary base in the duplex. In a model experiment for the alkylation of the CTG repeats DNA which causes myotonic dystrophy type 1 (DM1), the observed reaction rate for one alkylation increased in proportion to the number of T–T mismatches. In addition, we showed that primer extension reactions with DNA polymerase and transcription with RNA polymerase were stopped by the alkylation. The alkylation of the repeat DNA will efficiently work for the inhibition of replication and transcription reactions. These functions of the VDAT–acridine conjugate would be useful as a new biochemical tool for the study of CTG repeats and may provide a new strategy for the molecular therapy of DM1. PMID:29309639

  18. Selective alkylation of T-T mismatched DNA using vinyldiaminotriazine-acridine conjugate.

    Science.gov (United States)

    Onizuka, Kazumitsu; Usami, Akira; Yamaoki, Yudai; Kobayashi, Tomohito; Hazemi, Madoka E; Chikuni, Tomoko; Sato, Norihiro; Sasaki, Kaname; Katahira, Masato; Nagatsugi, Fumi

    2018-02-16

    The alkylation of the specific higher-order nucleic acid structures is of great significance in order to control its function and gene expression. In this report, we have described the T-T mismatch selective alkylation with a vinyldiaminotriazine (VDAT)-acridine conjugate. The alkylation selectively proceeded at the N3 position of thymidine on the T-T mismatch. Interestingly, the alkylated thymidine induced base flipping of the complementary base in the duplex. In a model experiment for the alkylation of the CTG repeats DNA which causes myotonic dystrophy type 1 (DM1), the observed reaction rate for one alkylation increased in proportion to the number of T-T mismatches. In addition, we showed that primer extension reactions with DNA polymerase and transcription with RNA polymerase were stopped by the alkylation. The alkylation of the repeat DNA will efficiently work for the inhibition of replication and transcription reactions. These functions of the VDAT-acridine conjugate would be useful as a new biochemical tool for the study of CTG repeats and may provide a new strategy for the molecular therapy of DM1.

  19. Auditory cortical and hippocampal-system mismatch responses to duration deviants in urethane-anesthetized rats.

    Directory of Open Access Journals (Sweden)

    Timo Ruusuvirta

    Full Text Available Any change in the invariant aspects of the auditory environment is of potential importance. The human brain preattentively or automatically detects such changes. The mismatch negativity (MMN of event-related potentials (ERPs reflects this initial stage of auditory change detection. The origin of MMN is held to be cortical. The hippocampus is associated with a later generated P3a of ERPs reflecting involuntarily attention switches towards auditory changes that are high in magnitude. The evidence for this cortico-hippocampal dichotomy is scarce, however. To shed further light on this issue, auditory cortical and hippocampal-system (CA1, dentate gyrus, subiculum local-field potentials were recorded in urethane-anesthetized rats. A rare tone in duration (deviant was interspersed with a repeated tone (standard. Two standard-to-standard (SSI and standard-to-deviant (SDI intervals (200 ms vs. 500 ms were applied in different combinations to vary the observability of responses resembling MMN (mismatch responses. Mismatch responses were observed at 51.5-89 ms with the 500-ms SSI coupled with the 200-ms SDI but not with the three remaining combinations. Most importantly, the responses appeared in both the auditory-cortical and hippocampal locations. The findings suggest that the hippocampus may play a role in (cortical manifestation of MMN.

  20. The development of estimated methodology for interfacial adhesion of semiconductor coatings having an enormous mismatch extent

    Science.gov (United States)

    Lee, Chang-Chun; Huang, Pei-Chen

    2018-05-01

    The long-term reliability of multi-stacked coatings suffering the bending or rolling load was a severe challenge to extend the lifespan of foregoing structure. In addition, the adhesive strength of dissimilar materials was regarded as the major mechanical reliability concerns among multi-stacked films. However, the significant scale-mismatch from several nano-meter to micro-meter among the multi-stacked coatings causing the numerical accuracy and converged capability issues on fracture-based simulation approach. For those reasons, this study proposed the FEA-based multi-level submodeling and multi-point constraint (MPC) technique to conquer the foregoing scale-mismatch issue. The results indicated that the decent region of first and second-order submodeling can achieve the small error of 1.27% compared with the experimental result and significantly reduced the mesh density and computing time. Moreover, the MPC method adopted in FEA simulation also shown only 0.54% error when the boundary of selected local region was away the concerned critical region following the Saint-Venant principle. In this investigation, two FEA-based approaches were used to conquer the evidently scale mismatch issue when the adhesive strengths of micro and nano-scale multi-stacked coating were taken into account.

  1. Environmental determinants and spatial mismatch of mammal diversity measures in Colombia

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez-Maya, J.F.; Arias-Alzate, A.; Granados-Peña, R.; Mancera-Rodriguez, N.J.; Ceballos, G.

    2016-07-01

    Including complementary diversity measures into ecological and conservation studies should improve our ability to link species assemblages to ecosystems. Recent measures such as phylogenetic and functional diversity have furthered our understanding of assemblage patterns of ecosystems and species, allowing improved inference of ecosystem function and conservation. We evaluated spatial patterns of taxonomic, phylogenetic and functional diversity of mammals in Colombia and identified their main environmental determinants, as well as interrelationships and spatial mismatch between the three measures. We found significant effects of elevation and precipitation on species richness, slope and species richness on phylogenetic diversity, and slope and phylogenetic diversity on functional diversity. We also identified a spatial mismatch of the three measures in some areas of the country: 12% of the country for species richness and 14% for phylogenetic and functional diversity. Our results highlight the importance of including species relationships within environmental drivers with biogeographical and distribution analyses and could facilitate selection of priority areas for conservation, especially when mismatch occurs between measures. (Author)

  2. Environmental determinants and spatial mismatch of mammal diversity measures in Colombia

    Directory of Open Access Journals (Sweden)

    González–Maya, J. F.

    2016-02-01

    Full Text Available Including complementary diversity measures into ecological and conservation studies should improve our ability to link species assemblages to ecosystems. Recent measures such as phylogenetic and functional diversity have furthered our understanding of assemblage patterns of ecosystems and species, allowing improved inference of ecosystem function and conservation. We evaluated spatial patterns of taxonomic, phylogenetic and functional diversity of mammals in Colombia and identified their main environmental determinants, as well as interrelationships and spatial mismatch between the three measures. We found significant effects of elevation and precipitation on species richness, slope and species richness on phylogenetic diversity, and slope and phylogenetic diversity on functional diversity. We also identified a spatial mismatch of the three measures in some areas of the country: 12% of the country for species richness and 14% for phylogenetic and functional diversity. Our results highlight the importance of including species relationships within environmental drivers with biogeographical and distribution analyses and could facilitate selection of priority areas for conservation, especially when mismatch occurs between measures.

  3. Rhodium metalloinsertor binding generates a lesion with selective cytotoxicity for mismatch repair-deficient cells.

    Science.gov (United States)

    Bailis, Julie M; Weidmann, Alyson G; Mariano, Natalie F; Barton, Jacqueline K

    2017-07-03

    The DNA mismatch repair (MMR) pathway recognizes and repairs errors in base pairing and acts to maintain genome stability. Cancers that have lost MMR function are common and comprise an important clinical subtype that is resistant to many standard of care chemotherapeutics such as cisplatin. We have identified a family of rhodium metalloinsertors that bind DNA mismatches with high specificity and are preferentially cytotoxic to MMR-deficient cells. Here, we characterize the cellular mechanism of action of the most potent and selective complex in this family, [Rh(chrysi)(phen)(PPO)] 2+ (Rh-PPO). We find that Rh-PPO binding induces a lesion that triggers the DNA damage response (DDR). DDR activation results in cell-cycle blockade and inhibition of DNA replication and transcription. Significantly, the lesion induced by Rh-PPO is not repaired in MMR-deficient cells, resulting in selective cytotoxicity. The Rh-PPO mechanism is reminiscent of DNA repair enzymes that displace mismatched bases, and is differentiated from other DNA-targeted chemotherapeutics such as cisplatin by its potency, cellular mechanism, and selectivity for MMR-deficient cells.

  4. Self-organization and mismatch tolerance in protein folding: General theory and an application

    Science.gov (United States)

    Fernández, Ariel; Berry, R. Stephen

    2000-03-01

    The folding of a protein is a process both expeditious and robust. The analysis of this process presented here uses a coarse, discretized representation of the evolving form of the backbone chain, based on its torsional states. This coarse description consists of discretizing the torsional coordinates modulo the Ramachandran basins in the local softmode dynamics. Whenever the representation exhibits "contact patterns" that correspond to topological compatibilities with particular structural forms, secondary and then tertiary, the elements constituting the pattern are effectively entrained by a reduction of their rates of exploration of their discretized configuration space. The properties "expeditious and robust" imply that the folding protein must have some tolerance to both torsional "frustrated" and side-chain contact mismatches which may occur during the folding process. The energy-entropy consequences of the staircase or funnel topography of the potential surface should allow the folding protein to correct these mismatches, eventually. This tolerance lends itself to an iterative pattern-recognition-and-feedback description of the folding process that reflects mismatched local torsional states and hydrophobic/polar contacts. The predictive potential of our algorithm is tested by application to the folding of bovine pancreatic trypsin inhibitor (BPTI), a protein whose ability to form its active structure is contingent upon its frustration tolerance.

  5. 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.

  6. Compensation strategy to reduce geometry and mechanics mismatches in porous biomaterials built with Selective Laser Melting.

    Science.gov (United States)

    Bagheri, Zahra S; Melancon, David; Liu, Lu; Johnston, R Burnett; Pasini, Damiano

    2017-06-01

    The accuracy of Additive Manufacturing processes in fabricating porous biomaterials is currently limited by their capacity to render pore morphology that precisely matches its design. In a porous biomaterial, a geometric mismatch can result in pore occlusion and strut thinning, drawbacks that can inherently compromise bone ingrowth and severely impact mechanical performance. This paper focuses on Selective Laser Melting of porous microarchitecture and proposes a compensation scheme that reduces the morphology mismatch between as-designed and as-manufactured geometry, in particular that of the pore. A spider web analog is introduced, built out of Ti-6Al-4V powder via SLM, and morphologically characterized. Results from error analysis of strut thickness are used to generate thickness compensation relations expressed as a function of the angle each strut formed with the build plane. The scheme is applied to fabricate a set of three-dimensional porous biomaterials, which are morphologically and mechanically characterized via micro Computed Tomography, mechanically tested and numerically analyzed. For strut thickness, the results show the largest mismatch (60% from the design) occurring for horizontal members, reduces to 3.1% upon application of the compensation. Similar improvement is observed also for the mechanical properties, a factor that further corroborates the merit of the design-oriented scheme here introduced. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Impact of mismatched and misaligned laser light sheet profiles on PIV performance

    Science.gov (United States)

    Grayson, K.; de Silva, C. M.; Hutchins, N.; Marusic, I.

    2018-01-01

    The effect of mismatched or misaligned laser light sheet profiles on the quality of particle image velocimetry (PIV) results is considered in this study. Light sheet profiles with differing widths, shapes, or alignment can reduce the correlation between PIV images and increase experimental errors. Systematic PIV simulations isolate these behaviours to assess the sensitivity and implications of light sheet mismatch on measurements. The simulations in this work use flow fields from a turbulent boundary layer; however, the behaviours and impacts of laser profile mismatch are highly relevant to any fluid flow or PIV application. Experimental measurements from a turbulent boundary layer facility are incorporated, as well as additional simulations matched to experimental image characteristics, to validate the synthetic image analysis. Experimental laser profiles are captured using a modular laser profiling camera, designed to quantify the distribution of laser light sheet intensities and inform any corrective adjustments to an experimental configuration. Results suggest that an offset of just 1.35 standard deviations in the Gaussian light sheet intensity distributions can cause a 40% reduction in the average correlation coefficient and a 45% increase in spurious vectors. Errors in measured flow statistics are also amplified when two successive laser profiles are no longer well matched in alignment or intensity distribution. Consequently, an awareness of how laser light sheet overlap influences PIV results can guide faster setup of an experiment, as well as achieve superior experimental measurements.

  8. Relationship among mismatch repair deficiency, CDX2 loss, p53 and E-cadherin in colon carcinoma and suitability of using a double panel of mismatch repair proteins by immunohistochemistry.

    Science.gov (United States)

    Sayar, Ilyas; Akbas, Emin Murat; Isik, Arda; Gokce, Aysun; Peker, Kemal; Demirtas, Levent; Gürbüzel, Mehmet

    2015-09-01

    Biomarkers such as mismatch repair proteins, CDX2, p53, and E-cadherin are blamed for colon cancers, but the relationships of these biomarkers with each other and with pathological risk factors in colon carcinoma are still not clear. The aim of this study was to evaluate the association of these biomarkers with each other by using immunohistochemical staining and to compare their expression with pathological risk factors for colonic adenocarcinoma. We also aimed to study the usability of a double panel of mismatch repair proteins. One hundred and eleven cases with colonic adenocarcinoma were examined. There was a statistically significant relationship between tumor histological differentiation and perineural invasion, vascular invasion, mismatch repair deficiency, p53, CDX2, and E-cadherin (p < 0.05). PMS2 and MSH6 loss covered 100% of cases with mismatch repair deficiency. Mismatch repair deficiency was correlated with CDX2 loss and E-cadherin expression (p < 0.05). It was also observed that cases with PMS2 loss covered all the cases with CDX2 loss. In conclusion, this double panel may be used instead of a quadruple panel for detecting mismatch repair deficiency. Association of CDX2 and PMS2 in the present study is necessary to conduct further genetic and pathological studies focusing on these two markers together.

  9. Role of Cell Cycle Regulation and MLH1, A Key DNA Mismatch Repair Protein, In Adaptive Survival Responses. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    David A. Boothman

    1999-08-11

    Due to several interesting findings on both adaptive survival responses (ASRs) and DNA mismatch repair (MMR), this grant was separated into two discrete Specific Aim sets (each with their own discrete hypotheses). The described experiments were simultaneously performed.

  10. A monofunctional platinum complex coordinated to a rhodium metalloinsertor selectively binds mismatched DNA in the minor groove.

    Science.gov (United States)

    Weidmann, Alyson G; Barton, Jacqueline K

    2015-10-05

    We report the synthesis and characterization of a bimetallic complex derived from a new family of potent and selective metalloinsertors containing an unusual Rh-O axial coordination. This complex incorporates a monofunctional platinum center containing only one labile site for coordination to DNA, rather than two, and coordinates DNA nonclassically through adduct formation in the minor groove. This conjugate displays bifunctional, interdependent binding of mismatched DNA via metalloinsertion at a mismatch as well as covalent platinum binding. DNA sequencing experiments revealed that the preferred site of platinum coordination is not the traditional N7-guanine site in the major groove, but rather N3-adenine in the minor groove. The complex also displays enhanced cytotoxicity in mismatch repair-deficient and mismatch repair-proficient human colorectal carcinoma cell lines compared to the chemotherapeutic cisplatin, and it triggers cell death via an apoptotic pathway, rather than the necrotic pathway induced by rhodium metalloinsertors.

  11. Increasing donor-recipient weight mismatch in pediatric orthotopic heart transplantation does not adversely affect outcome.

    Science.gov (United States)

    Kanani, Mazyar; Hoskote, Aparna; Carter, Catherine; Burch, Michael; Tsang, Victor; Kostolny, Martin

    2012-02-01

    The aim of the study was to show the effect of heart transplant donor-recipient weight mismatch on mortality, right-ventricular (RV) failure, and medium-term control of systemic blood pressure. From 2000 to 2008 inclusive, 161 patients undergoing orthotopic heart transplantation at our unit were retrospectively analyzed. The cohort was divided into three groups of similar size depending on the tertile ranges of the donor-recipient weight ratio. Median follow-up was 4.81 years. Donor-recipient body weight ratio was analyzed with respect to intubation time, time in intensive care unit (ITU), development of RV failure, medium-term survival, and freedom from medium-term hypertension. The median age was 115 months (23 days to 18 years), at a median weight of 26.9 kg (3-88 kg) at transplant. Median donor-recipient weight ratio was 1.61 (0.62-3.25). Mean intubation time was 448 h (SD 749.2), mean time in the ITU 302.7 h (SD 617.8). On linear regression, these were not related to donor-recipient weight ratio. A total of 38 patients (23.6%) developed postoperative RV failure. Nearly one-fifth (18.9) of patients in the lowest tertile group developed RV failure. In the middle tertile group, 24.5% developed RV failure and 28.8% in the upper tertile of weight mismatch, although this was not statistically significant (p = 0.48). On survival analysis, there was a higher mortality among those with the lowest tertile of mismatch (log-rank p = 0.04), but there was no difference in midterm survival on condition of survival to discharge (log-rank p = 0.14). There was also no association between weight ratio and freedom from medium-term hypertension as measured on serial 24-h ambulatory blood pressure monitoring (log-rank p = 0.39). There were nine patients in whom the weight mismatch was 3 or greater. There was no association between this 'extreme' mismatch group and either midterm mortality (p = 0.76) or freedom from hypertension (p = 0.62), but this was associated with the need for

  12. Alteration of cellular radiation response as a consequence of defective DNA mismatch repair

    International Nuclear Information System (INIS)

    Weese, Theodore L. de; Bucci, Jennifer M.; Larrier, Nicole A.; Cutler, Richard G.; Riele, Hein te; Nelson, William G.

    1997-01-01

    Purpose/Objective: A number of genes have been implicated in the response of mammalian cells to ionizing radiation. Among these include the genes P53 and P21. Disruption of these genes can alter the predicted cellular behavior following radiation-induced DNA damage. Similarly, cells defective in mismatch repair are known to be tolerant to the lethal effects of alkylating agents. We hypothesized that mammalian cells which are defective in mismatch repair and tolerant to alkylating DNA damage might also be tolerant to the effects of oxidative DNA damage inflicted by ionizing radiation. Materials and Methods: Mouse embryonic stem cells homozygous for disrupted Msh2 alleles (Msh2-/-), heterozygous for a disrupted Msh2 allele (Msh2+/-) or intact cells (Msh2+/+) were exposed to both acute dose (1 Gy/min) and low dose rate (LDR) radiation (0.004 Gy/min) and cell survival was determined by clonogenic assay. Apoptosis induced by LDR was assessed by a terminal transferase assay. Immunoblot analysis was performed in order to evaluate induction of the polypeptides p53 and p21. Another measure of radiation damage tolerance may be accumulation of oxidative DNA species. Therefore, we monitored levels of 8-hydroxyguanine (8-OHG) and 8-hydroxyadenine (8-OHA) by gas chromatography - mass spectrometry with selected ion monitoring (GC-MS/SIM). Results: Cells containing either one or two disrupted Msh2 alleles (Msh2+/-, Msh2-/-) were found to be less sensitive to LDR than cells containing a complete complement of Msh2 alleles (Msh2+/+). Interestingly, all three cell lines had a nearly identical radiosensitivity to acute dose ionizing radiation despite differences in mismatch repair capacity. Apoptosis after LDR also varied between cells, with the Msh2+/+ cells exhibiting higher levels of apoptosis as compared to either the Msh2+/- or Msh2-/- cell lines. In addition, GC-MS/SIM revealed the Msh2+/- and Msh2-/- cell lines to have an approximately ten fold greater accumulation of the

  13. Early CT perfusion mismatch in acute stroke is not time-dependent but relies on collateralization grade

    Energy Technology Data Exchange (ETDEWEB)

    Baumgarten, Louisa von; Straube, Andreas [University of Munich Hospitals, Department of Neurology, Munich (Germany); Thierfelder, Kolja M.; Beyer, Sebastian E.; Baumann, Alena B.; Bollwein, Christine; Reiser, Maximilian F.; Sommer, Wieland H. [Ludwig-Maximilians-University Hospital Munich, Institute for Clinical Radiology, Munich (Germany); Janssen, Hendrik [Ludwig-Maximilians-University Hospital Munich, Department of Neuroradiology, Munich (Germany)

    2016-04-15

    Factors that determine the extent of the penumbra in the initial diagnostic workup using whole brain CT Perfusion (WB-CTP) remain unclear. The purpose of the current study was to determine a possible dependency of the initial mismatch size between cerebral blood flow (CBF) and cerebral blood volume (CBV) from time after symptom onset, leptomeningeal collateralization, and occlusion localization in acute middle cerebral artery (MCA) infarctions. Out of an existing cohort of 992 consecutive patients receiving multiparametric CT scans including WB-CTP due to suspected stroke, we included patients who had (1) a witnessed time of symptom onset, (2) an infarction of the MCA territory as documented by follow-up imaging, and (3) an initial CBF volume of >10 ml. CBF and CBV lesion sizes, collateralization grade, and the site of occlusion were determined. We included 103 patients. Univariate analysis showed that time from symptom onset (168 +/- 91.2 min) did not correlate with relative or absolute mismatch volumes (p = 0.458 and p = 0.921). Higher collateralization gradings were associated with small absolute mismatch volumes (p = 0.004 and p < 0.001). Internal carotid artery (ICA) occlusions were associated with large absolute mismatch volumes (p = 0.004). Multivariate analysis confirmed that ICA occlusion was associated with large absolute mismatch volumes (p = 0.005), and high collateral grade was associated with small absolute mismatch volumes (p = 0.017). There is no significant correlation between initial CTP mismatch and time after symptom onset. Predictors of mismatch size include the extent of the collaterals and a proximal location of the occlusion. (orig.)

  14. Standard Test Method for Determination of the Spectral Mismatch Parameter Between a Photovoltaic Device and a Photovoltaic Reference Cell

    CERN Document Server

    American Society for Testing and Materials. Philadelphia

    2010-01-01

    1.1 This test method covers a procedure for the determination of a spectral mismatch parameter used in performance testing of photovoltaic devices. 1.2 The spectral mismatch parameter is a measure of the error, introduced in the testing of a photovoltaic device, caused by mismatch between the spectral responses of the photovoltaic device and the photovoltaic reference cell, as well as mismatch between the test light source and the reference spectral irradiance distribution to which the photovoltaic reference cell was calibrated. Examples of reference spectral irradiance distributions are Tables E490 or G173. 1.3 The spectral mismatch parameter can be used to correct photovoltaic performance data for spectral mismatch error. 1.4 This test method is intended for use with linear photovoltaic devices. 1.5 The values stated in SI units are to be regarded as standard. No other units of measurement are included in this standard. 1.6 This standard does not purport to address all of the safety concerns, if any, a...

  15. The Risk of Transplant Failure With HLA Mismatch in First Adult Kidney Allografts 2: Living Donors, Summary, Guide.

    Science.gov (United States)

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

    2017-05-01

    Allografts from living donors survive longer than those from deceased donors but the role of HLA mismatching in living kidney donation is still in question. We examined the effect of HLA compatibility on kidney allograft survival from living donors by studying all first adult kidney transplants performed in the United States over 25 years. Using the United Network for Organ Sharing data, we identified first kidney transplants between October 1, 1987, and December 31, 2013. Recipients were classified by their number of HLA mismatches and stratified by donor origin. Cox multivariate regression analyses adjusting for recipient and donor transplant characteristics were performed to determine impact of HLA compatibility on kidney allograft survival for all living donors and for living related and living unrelated subsets. There were 66 596 first adult transplants from living donors with 348 960 years of follow-up. We found a linear relationship between HLA mismatch and allograft survival. In adjusted analyses, among all living donors, 1 mismatch conferred a 44% higher risk, whereas 6 mismatches conferred a twofold higher risk of allograft failure. When using 0-mismatched full siblings as a reference, living-donor kidneys reduce the hazard of failure by approximately 34% when compared with deceased donors. Twenty-five years of transplant experience, stratified by donor source, was summarized and presented as a guide for allocation. These data reinforce the importance of optimizing HLA matching to further improve survival in first adult kidney allografts in the future, especially in living unrelated donations, when possible.

  16. NMR and molecular modeling evidence for a G·A mismatch base pair in a purine-rich DNA duplex

    International Nuclear Information System (INIS)

    Li, Ying; Wilson, W.D.; Zon, G.

    1991-01-01

    1 H NMR experiments indicate that the oligomer 5'-d(ATGAGCGAATA) forms an unusual 10-base-pair duplex with 4 G·A base pairs and a 3' unpaired adenosine. NMR results indicate that guanoxine imino protons of the F·A mismatches are not hydrogen bonded but are stacked in the helix. A G→ I substitution in either G·A base pair causes a dramatic decrtease in duplex stability and indicates that hydrogen bonding of the guanosine amino group is critical. Nuclear Overhauser effect spectroscopy (NOESY) and two-dimensional correlated spectroscopy (COSY) results indicate that the overall duplex conformation is in the B-family. Cross-strand NOEs in two-dimensional NOESY spectra between a mismatched AH2 and an AH1' of the other mismatched base pair and between a mismatched GH8 and GNH1 of the other mismatch establish a purine-purine stacking pattern, adenosine over adenosine and guanosine over guanosine, which strongly stabilizes the duplex. A computer graphics molecular model of the ususual duplex was constructed with G·A base pairs containing A-NH 2 to GN3 and G-NH 2 to AN7 hydrogen bonds and B-form base pairs on both sides of the G·A pairs [5'-d(ATGAGC)]. The energy-minimized duplex satisfies all experimental constraints from NOESY and COSY results. A hydrogen bond from G-NH 2 of the mismatch to a phosphate oxygen is predicted

  17. Dominant mutations in S. cerevisiae PMS1 identify the Mlh1-Pms1 endonuclease active site and an exonuclease 1-independent mismatch repair pathway.

    Directory of Open Access Journals (Sweden)

    Catherine E Smith

    2013-10-01

    Full Text Available Lynch syndrome (hereditary nonpolypsis colorectal cancer or HNPCC is a common cancer predisposition syndrome. Predisposition to cancer in this syndrome results from increased accumulation of mutations due to defective mismatch repair (MMR caused by a mutation in one of the mismatch repair genes MLH1, MSH2, MSH6 or PMS2/scPMS1. To better understand the function of Mlh1-Pms1 in MMR, we used Saccharomyces cerevisiae to identify six pms1 mutations (pms1-G683E, pms1-C817R, pms1-C848S, pms1-H850R, pms1-H703A and pms1-E707A that were weakly dominant in wild-type cells, which surprisingly caused a strong MMR defect when present on low copy plasmids in an exo1Δ mutant. Molecular modeling showed these mutations caused amino acid substitutions in the metal coordination pocket of the Pms1 endonuclease active site and biochemical studies showed that they inactivated the endonuclease activity. This model of Mlh1-Pms1 suggested that the Mlh1-FERC motif contributes to the endonuclease active site. Consistent with this, the mlh1-E767stp mutation caused both MMR and endonuclease defects similar to those caused by the dominant pms1 mutations whereas mutations affecting the predicted metal coordinating residue Mlh1-C769 had no effect. These studies establish that the Mlh1-Pms1 endonuclease is required for MMR in a previously uncharacterized Exo1-independent MMR pathway.

  18. Dominant mutations in S. cerevisiae PMS1 identify the Mlh1-Pms1 endonuclease active site and an exonuclease 1-independent mismatch repair pathway.

    Science.gov (United States)

    Smith, Catherine E; Mendillo, Marc L; Bowen, Nikki; Hombauer, Hans; Campbell, Christopher S; Desai, Arshad; Putnam, Christopher D; Kolodner, Richard D

    2013-10-01

    Lynch syndrome (hereditary nonpolypsis colorectal cancer or HNPCC) is a common cancer predisposition syndrome. Predisposition to cancer in this syndrome results from increased accumulation of mutations due to defective mismatch repair (MMR) caused by a mutation in one of the mismatch repair genes MLH1, MSH2, MSH6 or PMS2/scPMS1. To better understand the function of Mlh1-Pms1 in MMR, we used Saccharomyces cerevisiae to identify six pms1 mutations (pms1-G683E, pms1-C817R, pms1-C848S, pms1-H850R, pms1-H703A and pms1-E707A) that were weakly dominant in wild-type cells, which surprisingly caused a strong MMR defect when present on low copy plasmids in an exo1Δ mutant. Molecular modeling showed these mutations caused amino acid substitutions in the metal coordination pocket of the Pms1 endonuclease active site and biochemical studies showed that they inactivated the endonuclease activity. This model of Mlh1-Pms1 suggested that the Mlh1-FERC motif contributes to the endonuclease active site. Consistent with this, the mlh1-E767stp mutation caused both MMR and endonuclease defects similar to those caused by the dominant pms1 mutations whereas mutations affecting the predicted metal coordinating residue Mlh1-C769 had no effect. These studies establish that the Mlh1-Pms1 endonuclease is required for MMR in a previously uncharacterized Exo1-independent MMR pathway.

  19. Mechanism of the Glycosidic Bond Cleavage of Mismatched Thymine in Human Thymine DNA Glycosylase Revealed by Classical Molecular Dynamics and Quantum Mechanical/Molecular Mechanical Calculations.

    Science.gov (United States)

    Kanaan, Natalia; Crehuet, Ramon; Imhof, Petra

    2015-09-24

    Base excision of mismatched or damaged nucleotides catalyzed by glycosylase enzymes is the first step of the base excision repair system, a machinery preserving the integrity of DNA. Thymine DNA glycosylase recognizes and removes mismatched thymine by cleaving the C1'-N1 bond between the base and the sugar ring. Our quantum mechanical/molecular mechanical calculations of this reaction in human thymine DNA glycosylase reveal a requirement for a positive charge in the active site to facilitate C1'-N1 bond scission: protonation of His151 significantly lowers the free energy barrier for C1'-N1 bond dissociation compared to the situation with neutral His151. Shuttling a proton from His151 to the thymine base further reduces the activation free energy for glycosidic bond cleavage. Classical molecular dynamics simulations of the H151A mutant suggest that the mutation to the smaller, neutral, residue increases the water accessibility of the thymine base, rendering direct proton transfer from the bulk feasible. Quantum mechanical/molecular mechanical calculations of the glycosidic bond cleavage reaction in the H151A mutant show that the activation free energy is slightly lower than in the wild-type enzyme, explaining the experimentally observed higher reaction rates in this mutant.

  20. Expectations of Competency: The Mismatch between Employers' and Graduates' Views of End-User Computing Skills Requirements in the Workplace

    Science.gov (United States)

    Gibbs, Shirley; Steel, Gary; Kuiper, Alison

    2011-01-01

    The use of computers has become part of everyday life. The high prevalence of computer use appears to lead employers to assume that university graduates will have the good computing skills necessary in many graduate level jobs. This study investigates how well the expectations of employers match the perceptions of near-graduate students about the…

  1. The effect of S-substitution at the O6-guanine site on the structure and dynamics of a DNA oligomer containing a G:T mismatch.

    Directory of Open Access Journals (Sweden)

    Elaine Ann Moore

    Full Text Available The effect of S-substitution on the O6 guanine site of a 13-mer DNA duplex containing a G:T mismatch is studied using molecular dynamics. The structure, dynamic evolution and hydration of the S-substituted duplex are compared with those of a normal duplex, a duplex with S-substitution on guanine, but no mismatch and a duplex with just a G:T mismatch. The S-substituted mismatch leads to cell death rather than repair. One suggestion is that the G:T mismatch recognition protein recognises the S-substituted mismatch (GS:T as G:T. This leads to a cycle of futile repair ending in DNA breakage and cell death. We find that some structural features of the helix are similar for the duplex with the G:T mismatch and that with the S-substituted mismatch, but differ from the normal duplex, notably the helical twist. These differences arise from the change in the hydrogen-bonding pattern of the base pair. However a marked feature of the S-substituted G:T mismatch duplex is a very large opening. This showed considerable variability. It is suggested that this enlarged opening would lend support to an alternative model of cell death in which the mismatch protein attaches to thioguanine and activates downstream damage-response pathways. Attack on the sulphur by reactive oxygen species, also leading to cell death, would also be aided by the large, variable opening.

  2. Graft Growth and Podocyte Dedifferentiation in Donor-Recipient Size Mismatch Kidney Transplants.

    Science.gov (United States)

    Müller-Deile, Janina; Bräsen, Jan Hinrich; Pollheimer, Marion; Ratschek, Manfred; Haller, Hermann; Pape, Lars; Schiffer, Mario

    2017-10-01

    Kidney transplantation is the treatment choice for patients with end-stage renal diseases. Because of good long-term outcome, pediatric kidney grafts are also accepted for transplantation in adult recipients despite a significant mismatch in body size and age between donor and recipient. These grafts show a remarkable ability of adaptation to the recipient body and increase in size in a very short period, presumably as an adaptation to hyperfiltration. We investigated renal graft growth as well as glomerular proliferation and differentiation markers Kiel-67, paired box gene 2 and Wilms tumor protein (WT1) expression in control biopsies from different transplant constellations: infant donor for infant recipient, infant donor for child recipient, infant donor for adult recipient, child donor for child recipient, child donor for adult recipient, and adult donor for an adult recipient. We detected a significant increase in kidney graft size after transplantation in all conditions with a body size mismatch, which was most prominent when an infant donated for a child. Podocyte WT1 expression was comparable in different transplant conditions, whereas a significant increase in WT1 expression could be detected in parietal epithelial cells, when a kidney graft from a child was transplanted into an adult. In kidney grafts that were relatively small for the recipients, we could detect reexpression of podocyte paired box gene 2. Moreover, the proliferation marker Kiel-67 was expressed in glomerular cells in grafts that increased in size after transplantation. Kidney grafts rapidly adapt to the recipient size after transplantation if they are transplanted in a body size mismatch constellation. The increase in transplant size is accompanied by an upregulation of proliferation and dedifferentiation markers in podocytes. The different examined conditions exclude hormonal factors as the key trigger for this growth so that most likely hyperfiltration is the key trigger inducing the

  3. Graft Growth and Podocyte Dedifferentiation in Donor-Recipient Size Mismatch Kidney Transplants

    Directory of Open Access Journals (Sweden)

    Janina Müller-Deile, MD

    2017-10-01

    Full Text Available Background. Kidney transplantation is the treatment choice for patients with end-stage renal diseases. Because of good long-term outcome, pediatric kidney grafts are also accepted for transplantation in adult recipients despite a significant mismatch in body size and age between donor and recipient. These grafts show a remarkable ability of adaptation to the recipient body and increase in size in a very short period, presumably as an adaptation to hyperfiltration. Methods. We investigated renal graft growth as well as glomerular proliferation and differentiation markers Kiel-67, paired box gene 2 and Wilms tumor protein (WT1 expression in control biopsies from different transplant constellations: infant donor for infant recipient, infant donor for child recipient, infant donor for adult recipient, child donor for child recipient, child donor for adult recipient, and adult donor for an adult recipient. Results. We detected a significant increase in kidney graft size after transplantation in all conditions with a body size mismatch, which was most prominent when an infant donated for a child. Podocyte WT1 expression was comparable in different transplant conditions, whereas a significant increase in WT1 expression could be detected in parietal epithelial cells, when a kidney graft from a child was transplanted into an adult. In kidney grafts that were relatively small for the recipients, we could detect reexpression of podocyte paired box gene 2. Moreover, the proliferation marker Kiel-67 was expressed in glomerular cells in grafts that increased in size after transplantation. Conclusions. Kidney grafts rapidly adapt to the recipient size after transplantation if they are transplanted in a body size mismatch constellation. The increase in transplant size is accompanied by an upregulation of proliferation and dedifferentiation markers in podocytes. The different examined conditions exclude hormonal factors as the key trigger for this growth so that

  4. Mismatch oligonucleotides in human and yeast: guidelines for probe design on tiling microarrays

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    Jee Justin

    2008-12-01

    Full Text Available Abstract Background Mismatched oligonucleotides are widely used on microarrays to differentiate specific from nonspecific hybridization. While many experiments rely on such oligos, the hybridization behavior of various degrees of mismatch (MM structure has not been extensively studied. Here, we present the results of two large-scale microarray experiments on S. cerevisiae and H. sapiens genomic DNA, to explore MM oligonucleotide behavior with real sample mixtures under tiling-array conditions. Results We examined all possible nucleotide substitutions at the central position of 36-nucleotide probes, and found that nonspecific binding by MM oligos depends upon the individual nucleotide substitutions they incorporate: C→A, C→G and T→A (yielding purine-purine mispairs are most disruptive, whereas A→X were least disruptive. We also quantify a marked GC skew effect: substitutions raising probe GC content exhibit higher intensity (and vice versa. This skew is small in highly-expressed regions (± 0.5% of total intensity range and large (± 2% or more elsewhere. Multiple mismatches per oligo are largely additive in effect: each MM added in a distributed fashion causes an additional 21% intensity drop relative to PM, three-fold more disruptive than adding adjacent mispairs (7% drop per MM. Conclusion We investigate several parameters for oligonucleotide design, including the effects of each central nucleotide substitution on array signal intensity and of multiple MM per oligo. To avoid GC skew, individual substitutions should not alter probe GC content. RNA sample mixture complexity may increase the amount of nonspecific hybridization, magnify GC skew and boost the intensity of MM oligos at all levels.

  5. AN INTEGRATED RANSAC AND GRAPH BASED MISMATCH ELIMINATION APPROACH FOR WIDE-BASELINE IMAGE MATCHING

    Directory of Open Access Journals (Sweden)

    M. Hasheminasab

    2015-12-01

    Full Text Available In this paper we propose an integrated approach in order to increase the precision of feature point matching. Many different algorithms have been developed as to optimizing the short-baseline image matching while because of illumination differences and viewpoints changes, wide-baseline image matching is so difficult to handle. Fortunately, the recent developments in the automatic extraction of local invariant features make wide-baseline image matching possible. The matching algorithms which are based on local feature similarity principle, using feature descriptor as to establish correspondence between feature point sets. To date, the most remarkable descriptor is the scale-invariant feature transform (SIFT descriptor , which is invariant to image rotation and scale, and it remains robust across a substantial range of affine distortion, presence of noise, and changes in illumination. The epipolar constraint based on RANSAC (random sample consensus method is a conventional model for mismatch elimination, particularly in computer vision. Because only the distance from the epipolar line is considered, there are a few false matches in the selected matching results based on epipolar geometry and RANSAC. Aguilariu et al. proposed Graph Transformation Matching (GTM algorithm to remove outliers which has some difficulties when the mismatched points surrounded by the same local neighbor structure. In this study to overcome these limitations, which mentioned above, a new three step matching scheme is presented where the SIFT algorithm is used to obtain initial corresponding point sets. In the second step, in order to reduce the outliers, RANSAC algorithm is applied. Finally, to remove the remained mismatches, based on the adjacent K-NN graph, the GTM is implemented. Four different close range image datasets with changes in viewpoint are utilized to evaluate the performance of the proposed method and the experimental results indicate its robustness and

  6. Understanding mismatches in body size, speed and power among adolescent rugby union players.

    Science.gov (United States)

    Krause, Lyndon M; Naughton, Geraldine A; Denny, Greg; Patton, Declan; Hartwig, Tim; Gabbett, Tim J

    2015-05-01

    With adolescent sport increasingly challenged by mismatches in size, new strategies are important to maximize participation. The objectives were to (1) improve the understanding of mismatches in physical size, speed and power in adolescent rugby union players, (2) explore associations between size and performance with demographic, playing-history, and injury profiles, and (3) explore the applicability of existing criteria for age/body mass-based dispensation (playing-down) strategies. Cross-sectional study. Four hundred and eighty-five male community rugby union players were recruited from three Australian states selected to represent community-based U12, U13, U14 and U15 players. Body mass, stature, speed (10, 30, and 40 m sprints) and lower-leg power (relative peak power and relative peak force) were measured. Independent student t-tests, linear regressions and Chi square analyses were undertaken. Mean values in age groups for size, speed and power masked considerable overlap in the ranges within specific age groups of adolescent rugby players. Only a small proportion of players (approximately 5%) shared the highest and lowest tertiles for speed, relative peak power and body mass. Physical size was not related to injury. The mean body mass of current community rugby union players was above the 75th percentile on normative growth-charts. The notion that bigger, faster, and more powerful characteristics occur simultaneously in adolescent rugby players was not supported in the present study. Current practices in body mass-based criteria for playing down an age group lack a sufficient evidence for decision-making. Dispensation solely based on body mass may not address mismatch in junior rugby union. Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  7. Contractility-afterload mismatch in patients with protein-losing enteropathy after the Fontan operation.

    Science.gov (United States)

    Ozawa, Hideto; Ueno, Takayoshi; Iwai, Shigemitsu; Kawata, Hiroaki; Nishigaki, Kyouichi; Kishimoto, Hidefumi; Sawa, Yoshiki

    2014-10-01

    This study aimed to clarify the relationship between onset of protein-losing enteropathy (PLE) and Fontan circulation, with special reference to the development of contractility-afterload mismatch. The PLE group comprised 9 patients who experienced PLE after undergoing the Fontan operation, and the control group consisted of 32 patients had did not experienced PLE more than 10 years after the Fontan operation. The study compared the pre- and postoperative values of arterial elastance (Ea), end-systolic elastance (Ees), and contractility-afterload mismatch (Ea/Ees). Furthermore, the variations in the values were examined during the preoperative, postoperative, and midterm postoperative periods in seven PLE patients who underwent cardiac catheterization at the onset of PLE and during the pre- and postintervention periods in three PLE patients who underwent surgical intervention to improve the Fontan circulation after the onset of PLE. Comparison of the values obtained before and after Fontan operations showed that the Ea values increased significantly in the PLE group. However, the pre- and postoperative Ees values did not differ in the two groups. During the postoperative period, Ea/Ees increased significantly, and the Ea and Ea/Ees values increased continuously until the onset of PLE in the PLE group. In the patients who underwent surgical intervention to improve the Fontan circulation after the onset of PLE, the Ea/Ees decreased significantly, and the serum albumin levels improved after the intervention. Contractility-afterload mismatch, mainly caused by the increase in the afterload of the systemic ventricle, may have an important role in the development of PLE after the Fontan operation.

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

    Science.gov (United States)

    Koefoed-Nielsen, P; Weinreich, I; Bengtsson, M; Lauronen, J; Naper, C; Gäbel, M; Sørensen, S S; Wennberg, L; Reisaeter, A V; Møller, B K

    2017-07-01

    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 (STAMP), a de-centralized approach has been implemented in 2009. The program has been improved during the years from utilizing HLA-A, -B, -DR matching only to include typing of all deceased donors for HLA-A, -B, -C, -DRB1 and -DQB1. The calculation of a transplantability score (TS) has been introduced in order to take both HLA and AB0 into consideration resulting in a more realistic picture of the transplantability chance. Patients were selected for eligibility and results of immunisation status were prepared in each of the 9 tissue typing laboratories, while access to the program is finally governed by a common steering group of immunologists and clinicians. In the period from March 2009 until February 2015, 96 patients were transplanted within this program. The mean recipient age was 49 years and 57% were females, 30% of the patients were first transplants and of these 93% were females. The majority of the patients had 2-5 HLA-A, -B. -DR mismatches. The allograft survival at 60 months was 79.1%. Applying the TS to the cohort confirmed that patients with a low TS score had longer waiting times. The program has matured during the years and now proves to be a valid approach for transplanting highly immunized patients. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. The Steppengrille (Gryllus spec./assimilis: selective filters and signal mismatch on two time scales.

    Directory of Open Access Journals (Sweden)

    Matti Michael Rothbart

    Full Text Available In Europe, several species of crickets are available commercially as pet food. Here we investigated the calling song and phonotactic selectivity for sound patterns on the short and long time scales for one such a cricket, Gryllus spec., available as "Gryllus assimilis", the Steppengrille, originally from Ecuador. The calling song consisted of short chirps (2-3 pulses, carrier frequency: 5.0 kHz emitted with a pulse period of 30.2 ms and chirp rate of 0.43 per second. Females exhibited high selectivity on both time scales. The preference for pulse period peaked at 33 ms which was higher then the pulse period produced by males. Two consecutive pulses per chirp at the correct pulse period were already sufficient for positive phonotaxis. The preference for the chirp pattern was limited by selectivity for small chirp duty cycles and for chirp periods between 200 ms and 500 ms. The long chirp period of the songs of males was unattractive to females. On both time scales a mismatch between the song signal of the males and the preference of females was observed. The variability of song parameters as quantified by the coefficient of variation was below 50% for all temporal measures. Hence, there was not a strong indication for directional selection on song parameters by females which could account for the observed mismatch. The divergence of the chirp period and female preference may originate from a founder effect, when the Steppengrille was cultured. Alternatively the mismatch was a result of selection pressures exerted by commercial breeders on low singing activity, to satisfy customers with softly singing crickets. In the latter case the prominent divergence between male song and female preference was the result of domestication and may serve as an example of rapid evolution of song traits in acoustic communication systems.

  10. Measuring DNA hybridization using fluorescent DNA-stabilized silver clusters to investigate mismatch effects on therapeutic oligonucleotides.

    Science.gov (United States)

    de Bruin, Donny; Bossert, Nelli; Aartsma-Rus, Annemieke; Bouwmeester, Dirk

    2018-04-06

    Short nucleic acid oligomers have found a wide range of applications in experimental physics, biology and medicine, and show potential for the treatment of acquired and genetic diseases. These applications rely heavily on the predictability of hybridization through Watson-Crick base pairing to allow positioning on a nanometer scale, as well as binding to the target transcripts, but also off-target binding to transcripts with partial homology. These effects are of particular importance in the development of therapeutic oligonucleotides, where off-target effects caused by the binding of mismatched sequences need to be avoided. We employ a novel method of probing DNA hybridization using optically active DNA-stabilized silver clusters (Ag-DNA) to measure binding efficiencies through a change in fluorescence intensity. In this way we can determine their location-specific sensitivity to individual mismatches in the sequence. The results reveal a strong dependence of the hybridization on the location of the mismatch, whereby mismatches close to the edges and center show a relatively minor impact. In parallel, we propose a simple model for calculating the annealing ratios of mismatched DNA sequences, which supports our experimental results. The primary result shown in this work is a demonstration of a novel technique to measure DNA hybridization using fluorescent Ag-DNA. With this technique, we investigated the effect of mismatches on the hybridization efficiency, and found a significant dependence on the location of individual mismatches. These effects are strongly influenced by the length of the used oligonucleotides. The novel probe method based on fluorescent Ag-DNA functions as a reliable tool in measuring this behavior. As a secondary result, we formulated a simple model that is consistent with the experimental data.

  11. Software development processes and analysis software: a mismatch and a novel framework

    International Nuclear Information System (INIS)

    Kelly, D.; Harauz, J.

    2011-01-01

    This paper discusses the salient characteristics of analysis software and the impact of those characteristics on its development. From this discussion, it can be seen that mainstream software development processes, usually characterized as Plan Driven or Agile, are built upon assumptions that are mismatched to the development and maintenance of analysis software. We propose a novel software development framework that would match the process normally observed in the development of analysis software. In the discussion of this framework, we suggest areas of research and directions for future work. (author)

  12. 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.

  13. Inactivation of DNA mismatch repair by variants of uncertain significance in the PMS2 gene.

    Science.gov (United States)

    Drost, Mark; Koppejan, Hester; de Wind, Niels

    2013-11-01

    Lynch syndrome (LS) is a common cancer predisposition caused by an inactivating mutation in one of four DNA mismatch repair (MMR) genes. Frequently a variant of uncertain significance (VUS), rather than an obviously pathogenic mutation, is identified in one of these genes. The inability to define pathogenicity of such variants precludes targeted healthcare. Here, we have modified a cell-free assay to test VUS in the MMR gene PMS2 for functional activity. We have analyzed nearly all VUS in PMS2 found thus far and describe loss of MMR activity for five, suggesting the applicability of the assay for diagnosis of LS. © 2013 WILEY PERIODICALS, INC.

  14. Regional ventilation/perfusion mismatch pattern in patient with Swyer James (MacLeod′s syndrome

    Directory of Open Access Journals (Sweden)

    Sait Sager

    2014-01-01

    Full Text Available Swyer James (McLeod′s syndrome (SJMS is an uncommon disease, which occurs as a result of childhood bronchiolitis obliterans. Patients may not be diagnosed until later in their life. A 46-year-old man underwent ventilation/perfusion scintigraphy for acute onset of dyspnea. The scan showed markedly diminished ventilation and perfusion unilaterally on the right middle and inferior lobes. However, mismatched ventilation-perfusion pattern was shown on the upper right lobe, which was consistent with pulmonary embolism. Unilaterally matched ventilation/perfusion defect can see in SJMS in lung scintigraphy; however, when pulmoner embolism may accompany, scintigraphy should be carefully examined.

  15. Mouth reversal extinguishes mismatch negativity induced by the McGurk illusion

    DEFF Research Database (Denmark)

    Eskelund, Kasper; Andersen, Tobias

    2013-01-01

    The sight of articulatory mouth movements (visual speech) influences auditory speech perception. This is demonstrated by the McGurk illusion in which incongruent visual speech alters the auditory phonetic percept. In behavioral studies, reversal of the vertical mouth direction has been reported...... by visual speech with either upright (unaltered) or vertically reversed mouth area. In a preliminary analysis, we found a Mismatch Negativity component induced by the McGurk illusion for 6 of 17 participants at electrode Cz when the mouth area was upright. In comparison, these participants produced...

  16. A rare case of Crohn's ileitis in a patient with constitutional mismatch repair deficiency.

    Science.gov (United States)

    Kaimakliotis, Pavlos; Giardiello, Francis; Eze, Ogechukwu; Truta, Brindusa

    2017-01-01

    Constitutional mismatch repair deficiency (CMMRD), a variant of Lynch syndrome, is a rare disease characterized by café-au-lait spots, oligopolyposis, glioblastoma and lymphoma. A 24-year-old male, under surveillance for CMMRD, developed Crohn's ileitis after total colectomy with end ileostomy for colorectal cancer and failed to respond to oral corticosteroids. The patient underwent induction and maintenance of remission with vedolizumab infusions. We report the first patient with CMMRD developing Crohn's disease. The choice of immunosuppressive therapy in these patients is challenging and needs to be made according to their risk for malignancy.

  17. Involvement of the DNA mismatch repair system in cisplatin sensitivity of testicular germ cell tumours

    DEFF Research Database (Denmark)

    Rudolph, Christiane; Melau, Cecilie; Nielsen, John E.

    2017-01-01

    in the majority of tumours, although the underlying mechanism largely remains to be elucidated. The aim of this study was to investigate the role of the DNA mismatch repair (MMR) system in the cisplatin sensitivity of TGCT. MethodsThe expression pattern of key MMR proteins, including MSH2, MSH6, MLH1 and PMS2...... proteins, in particular MSH2 and MLH1, which are involved in the recognition of cisplatin adducts and in activation of the DNA damage response pathway to initiate apoptosis....

  18. Heat Mismatch of future Net Zero Energy Buildings within district heating areas in Denmark

    DEFF Research Database (Denmark)

    Nielsen, Steffen; Möller, Bernd

    The long-term goal for Denmark is to develop an energy system solely based on renewable energy sources (RES) in 2050. To reach this goal energy savings in buildings are essential. Therefore, a focus on energy efficient measures in buildings and net zero energy buildings (NZEBs) have increased...... systems enables them to send or receive energy from these systems. This is beneficial for NZEBs because even though they have an annual net exchange of zero, there is a temporal mismatch in regard to the energy consumption of buildings and the production from the renewable energy units added to them...

  19. Errors in short circuit measurements due to spectral mismatch between sunlight and solar simulators

    Science.gov (United States)

    Curtis, H. B.

    1976-01-01

    Errors in short circuit current measurement were calculated for a variety of spectral mismatch conditions. The differences in spectral irradiance between terrestrial sunlight and three types of solar simulator were studied, as well as the differences in spectral response between three types of reference solar cells and various test cells. The simulators considered were a short arc xenon lamp AMO sunlight simulator, an ordinary quartz halogen lamp, and an ELH-type quartz halogen lamp. Three types of solar cells studied were a silicon cell, a cadmium sulfide cell and a gallium arsenide cell.

  20. 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.)

  1. Performance Analysis of Spectral Amplitude Coding Based OCDMA System with Gain and Splitter Mismatch

    Science.gov (United States)

    Umrani, Fahim A.; Umrani, A. Waheed; Umrani, Naveed A.; Memon, Kehkashan A.; Kalwar, Imtiaz Hussain

    2013-09-01

    This paper presents the practical analysis of the optical code-division multiple-access (O-CDMA) systems based on perfect difference codes. The work carried out use SNR criterion to select the optimal value of avalanche photodiodes (APD) gain and shows how the mismatch in the splitters and gains of the APD used in the transmitters and receivers of network can degrade the BER performance of the system. The investigations also reveal that higher APD gains are not suitable for such systems even at higher powers. The system performance, with consideration of shot noise, thermal noise, bulk and surface leakage currents is also investigated.

  2. Selecting patients with young-onset colorectal cancer for mismatch repair gene analysis

    DEFF Research Database (Denmark)

    Walker, M; O'Sullivan, B; Perakath, B

    2007-01-01

    BACKGROUND: Young patients with colorectal cancer are at increased risk of carrying a germline mutation in mismatch repair (MMR) genes. This study investigated the role of clinical criteria and immunohistochemistry for MMR proteins in selecting young patients for mutation testing. METHODS: A cohort...... of 56 consecutive patients with colorectal cancer aged less than 45 years were stratified into three groups based on clinical criteria: 'Amsterdam criteria', 'high risk' and 'young onset only'. Immunohistochemistry for four MMR proteins was carried out and the rate of compliance with clinical guidelines...

  3. The role of mismatch repair in small-cell lung cancer cells

    DEFF Research Database (Denmark)

    Hansen, L T; Thykjaer, T; Ørntoft, T F

    2003-01-01

    The role of mismatch repair (MMR) in small-cell lung cancer (SCLC) is controversial, as the phenotype of a MMR-deficiency, microsatellite instability (MSI), has been reported to range from 0 to 76%. We studied the MMR pathway in a panel of 21 SCLC cell lines and observed a highly heterogeneous...... pattern of MMR gene expression. A significant correlation between the mRNA and protein levels was found. We demonstrate that low hMLH1 gene expression was not linked to promoter CpG methylation. One cell line (86MI) was found to be deficient in MMR and exhibited resistance to the alkylating agent MNNG...

  4. The transition to modernity and chronic disease: mismatch and natural selection.

    Science.gov (United States)

    Corbett, Stephen; Courtiol, Alexandre; Lummaa, Virpi; Moorad, Jacob; Stearns, Stephen

    2018-05-09

    The Industrial Revolution and the accompanying nutritional, epidemiological and demographic transitions have profoundly changed human ecology and biology, leading to major shifts in life history traits, which include age and size at maturity, age-specific fertility and lifespan. Mismatch between past adaptations and the current environment means that gene variants linked to higher fitness in the past may now, through antagonistic pleiotropic effects, predispose post-transition populations to non-communicable diseases, such as Alzheimer disease, cancer and coronary artery disease. Increasing evidence suggests that the transition to modernity has also altered the direction and intensity of natural selection acting on many traits, with important implications for public and global health.

  5. 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

  6. Behavior of a nine-rod PWR bundle under power-cooling-mismatch conditions

    International Nuclear Information System (INIS)

    Gunnerson, F.S.; Sparks, D.T.

    1979-01-01

    An experiment to characterize the behavior of a nine-rod pressurized water reactor (PWR) fuel bundle operating during power-cooling-mismatch (PCM) conditions has been conducted in the Power Burst Facility (PBF) at the Idaho National Engineering Laboratory (INEL). The experiment, designated Test PCM-5, is part of a series of PCM experiments designed to evaluate light water reactor (LWR) fuel rod response under postulated accident conditions. Test PCM-5 was the first nine-rod bundle experiment in the PCM test series. The primary objectives and the results of the experiment are described

  7. Preattentive extraction of abstract feature conjunctions from auditory stimulation as reflected by the mismatch negativity (MMN).

    Science.gov (United States)

    Paavilainen, P; Simola, J; Jaramillo, M; Näätänen, R; Winkler, I

    2001-03-01

    Brain mechanisms extracting invariant information from varying auditory inputs were studied using the mismatch-negativity (MMN) brain response. We wished to determine whether the preattentive sound-analysis mechanisms, reflected by MMN, are capable of extracting invariant relationships based on abstract conjunctions between two sound features. The standard stimuli varied over a large range in frequency and intensity dimensions following the rule that the higher the frequency, the louder the intensity. The occasional deviant stimuli violated this frequency-intensity relationship and elicited an MMN. The results demonstrate that preattentive processing of auditory stimuli extends to unexpectedly complex relationships between the stimulus features.

  8. T-cell depleted haploidentical three loci mismatched bone-marrow and peripheral blood stem cell transplantation in acute leukaemia patients

    International Nuclear Information System (INIS)

    Aristei, C.; Aversa, F.; Panizza, B.M.; Perrucci, E.; Barone, V.; Marafioti, L.; Raymondi, C.; Terenzi, A.; Martelli, M.F.; Latini, P.

    1996-01-01

    Objectives: Allogeneic bone-marrow transplantation (BMT) is an established treatment for many haematological malignancies. Unfortunately, most patients lack an HLA geno typically identical sibling and require an alternative donor, such as an HLA-haploidentical mismatched related donor, an HLA phenotypically matched or partially mismatched unrelated donor or an HLA-similar cord blood stem cell donor. However, these types of BMT increase the risk of graft-versus-host disease (GvHD), graft failure, delayed immuno reconstitution and fatal infection that observed after a sibling matched donor. Many centers are exploring the possibility of using donors other than matched sibling. Our approach has been to employ T-cell depleted mismatched haploidentical familial donor BMT to solve the problem of GvHD, a highly immuno- and myelo-suppressive conditioning regimen to reduce the incidence of graft failure and relapse, a graft inoculum plus G-CSF donor mobilized peripheral blood stem cells (PBSC) to overcome the host-versus-graft barrier. Patients and methods: Thirty-six patients (25 male, 11 female; median age 22 years, range 2-51) were treated with an allogeneic T-depleted haploidentical three loci mismatched bone-marrow and G-CSF mobilized PBSC transplantation from a familiar donor (18 siblings, 17 parents and 1 cousin) between March 1993 and June 1995. All had high-risk or advanced stage acute myeloid (12) or acute lymphoid (24) leukaemia; 18 were in haematological complete remission (CR) and 18 in chemo resistant relapse. Patients were conditioned with 8 Gy single dose TBI administered on day -5 at an instantaneous dose-rate of 13.4-31.7 cGy/min/midplane and average of 6.7-12.12 cGy/min/midplane. Shields were used to reduce the lung dose to 7 Gy in the first 23 cases and to 6 Gy in the last 13. 10 mg/Kg thiotepa were administered on day -4, 5 mg/Kg rabbit ATG from day -4 to day -1, 60 or 50 mg/Kg/cyclophosphamide on days -3 and -2. Bone-marrow and PBSC were infused on day

  9. Structural, molecular and cellular functions of MSH2 and MSH6 during DNA mismatch repair, damage signaling and other noncanonical activities

    Energy Technology Data Exchange (ETDEWEB)

    Edelbrock, Michael A., E-mail: Edelbrock@findlay.edu [The University of Findlay, 1000 North Main Street, Findlay, OH 45840 (United States); Kaliyaperumal, Saravanan, E-mail: Saravanan.Kaliyaperumal@hms.harvard.edu [Division of Comparative Medicine and Pathology, New England Primate Research Center, One Pine Hill Drive, Southborough, MA 01772 (United States); Williams, Kandace J., E-mail: Kandace.williams@utoledo.edu [University of Toledo College of Medicine and Life Sciences, Department of Biochemistry and Cancer Biology, 3000 Transverse Dr., Toledo, OH 43614 (United States)

    2013-03-15

    The field of DNA mismatch repair (MMR) has rapidly expanded after the discovery of the MutHLS repair system in bacteria. By the mid 1990s yeast and human homologues to bacterial MutL and MutS had been identified and their contribution to hereditary non-polyposis colorectal cancer (HNPCC; Lynch syndrome) was under intense investigation. The human MutS homologue 6 protein (hMSH6), was first reported in 1995 as a G:T binding partner (GTBP) of hMSH2, forming the hMutSα mismatch-binding complex. Signal transduction from each DNA-bound hMutSα complex is accomplished by the hMutLα heterodimer (hMLH1 and hPMS2). Molecular mechanisms and cellular regulation of individual MMR proteins are now areas of intensive research. This review will focus on molecular mechanisms associated with mismatch binding, as well as emerging evidence that MutSα, and in particular, MSH6, is a key protein in MMR-dependent DNA damage response and communication with other DNA repair pathways within the cell. MSH6 is unstable in the absence of MSH2, however it is the DNA lesion-binding partner of this heterodimer. MSH6, but not MSH2, has a conserved Phe-X-Glu motif that recognizes and binds several different DNA structural distortions, initiating different cellular responses. hMSH6 also contains the nuclear localization sequences required to shuttle hMutSα into the nucleus. For example, upon binding to O{sup 6}meG:T, MSH6 triggers a DNA damage response that involves altered phosphorylation within the N-terminal disordered domain of this unique protein. While many investigations have focused on MMR as a post-replication DNA repair mechanism, MMR proteins are expressed and active in all phases of the cell cycle. There is much more to be discovered about regulatory cellular roles that require the presence of MutSα and, in particular, MSH6.

  10. Structural, molecular and cellular functions of MSH2 and MSH6 during DNA mismatch repair, damage signaling and other noncanonical activities

    International Nuclear Information System (INIS)

    Edelbrock, Michael A.; Kaliyaperumal, Saravanan; Williams, Kandace J.

    2013-01-01

    The field of DNA mismatch repair (MMR) has rapidly expanded after the discovery of the MutHLS repair system in bacteria. By the mid 1990s yeast and human homologues to bacterial MutL and MutS had been identified and their contribution to hereditary non-polyposis colorectal cancer (HNPCC; Lynch syndrome) was under intense investigation. The human MutS homologue 6 protein (hMSH6), was first reported in 1995 as a G:T binding partner (GTBP) of hMSH2, forming the hMutSα mismatch-binding complex. Signal transduction from each DNA-bound hMutSα complex is accomplished by the hMutLα heterodimer (hMLH1 and hPMS2). Molecular mechanisms and cellular regulation of individual MMR proteins are now areas of intensive research. This review will focus on molecular mechanisms associated with mismatch binding, as well as emerging evidence that MutSα, and in particular, MSH6, is a key protein in MMR-dependent DNA damage response and communication with other DNA repair pathways within the cell. MSH6 is unstable in the absence of MSH2, however it is the DNA lesion-binding partner of this heterodimer. MSH6, but not MSH2, has a conserved Phe-X-Glu motif that recognizes and binds several different DNA structural distortions, initiating different cellular responses. hMSH6 also contains the nuclear localization sequences required to shuttle hMutSα into the nucleus. For example, upon binding to O 6 meG:T, MSH6 triggers a DNA damage response that involves altered phosphorylation within the N-terminal disordered domain of this unique protein. While many investigations have focused on MMR as a post-replication DNA repair mechanism, MMR proteins are expressed and active in all phases of the cell cycle. There is much more to be discovered about regulatory cellular roles that require the presence of MutSα and, in particular, MSH6

  11. Interpreting and Correcting Cross-scale Mismatches in Resilience Analysis: a Procedure and Examples from Australia's Rangelands

    Directory of Open Access Journals (Sweden)

    John A. Ludwig

    2005-12-01

    Full Text Available Many rangelands around the globe are degraded because of mismatches between the goals and actions of managers operating at different spatial scales. In this paper, we focus on identifying, interpreting, and correcting cross-scale mismatches in rangeland management by building on an existing four-step resilience analysis procedure. Resilience analysis is an evaluation of the capacity of a system to persist in the face of disturbances. We provide three examples of cross-scale resilience analysis using a rangeland system located in northern Australia. The system was summarized in a diagram showing key interactions between three attributes (water quality, regional biodiversity, and beef quality, which can be used to indicate the degree of resilience of the system, and other components that affect these attributes at different scales. The strengths of cross-scale interactions were rated as strong or weak, and the likely causes of mismatches in strength were interpreted. Possible actions to correct cross-scale mismatches were suggested and evaluated. We found this four-step, cross-scale resilience analysis procedure very helpful because it reduced a complex problem down to manageable parts without losing sight of the larger-scale whole. To build rangeland resilience, many such cross-scale mismatches in management will need to be corrected, especially as the global use of rangelands increases over the coming decades.

  12. Thickness dependent properties of CMR Manganite thin films on lattice mismatched substrates: Distinguishing Strain and Interface Effects

    Science.gov (United States)

    Davidson, Anthony, III; Kolagani, Rajeswari; Bacharova, Ellisaveta; Yong, Grace; Smolyaninova, Vera; Schaefer, David; Mundle, Rajeh

    2007-03-01

    Epitaxial thin films of CMR manganite materials have been known to show thickness dependent electrical and magnetic properties on lattice mismatched substrates. Below a critical thickness, insulator-metal transition is suppressed. These effects have been largely attributed to the role of bi-axial lattice mismatch strain. Our recent results of epitaxial thin films of La0.67Ca0.33MnO3 (LCMO) on two substrates with varying degrees of compressive lattice mismatch indicate that, in addition to the effect of lattice mismatch strain, the thickness dependence of the properties are influenced by other factors possibly related to the nature of the film substrate interface and defects such as twin boundaries. We have compared the properties of LCMO films on (100) oriented LaAlO3 and (001) oriented NdCaAlO4 both of which induce compressive bi-axial strain. Interestingly, the suppression of the insulator-metal transition is less in films on NCAO which has a larger lattice mismatch. We will present results correlating the electrical and magneto transport properties with the structure and morphology of the films.

  13. Circumpolar analysis of the Adélie Penguin reveals the importance of environmental variability in phenological mismatch

    Science.gov (United States)

    Youngflesh, Casey; Jenouvrier, Stephanie; Li, Yun; Ji, Rubao; Ainley, David G.; Ballard, Grant; Barbraud, Christophe; Delord, Karine; Dugger, Catherine; Emmerson, Loiuse M.; Fraser, William R.; Hinke, Jefferson T.; Lyver, Phil O'B.; Olmastroni, Silvia; Southwell, Colin J.; Trivelpiece, Susan G.; Trivelpiece, Wayne Z.; Lynch, Heather J.

    2017-01-01

    Evidence of climate-change-driven shifts in plant and animal phenology have raised concerns that certain trophic interactions may be increasingly mismatched in time, resulting in declines in reproductive success. Given the constraints imposed by extreme seasonality at high latitudes and the rapid shifts in phenology seen in the Arctic, we would also expect Antarctic species to be highly vulnerable to climate-change-driven phenological mismatches with their environment. However, few studies have assessed the impacts of phenological change in Antarctica. Using the largest database of phytoplankton phenology, sea-ice phenology, and Adélie Penguin breeding phenology and breeding success assembled to date, we find that, while a temporal match between Penguin breeding phenology and optimal environmental conditions sets an upper limit on breeding success, only a weak relationship to the mean exists. Despite previous work suggesting that divergent trends in Adélie Penguin breeding phenology are apparent across the Antarctic continent, we find no such trends. Furthermore, we find no trend in the magnitude of phenological mismatch, suggesting that mismatch is driven by interannual variability in environmental conditions rather than climate-change-driven trends, as observed in other systems. We propose several criteria necessary for a species to experience a strong climate-change-driven phenological mismatch, of which several may be violated by this system.

  14. Propagation dynamics and X-pulse formation in phase-mismatched second-harmonic generation

    International Nuclear Information System (INIS)

    Valiulis, G.; Jukna, V.; Jedrkiewicz, O.; Clerici, M.; Rubino, E.; DiTrapani, P.

    2011-01-01

    This paper concerns the theoretical, numerical, and experimental study of the second-harmonic-generation (SHG) process under conditions of phase and group-velocity mismatch and aims to demonstrate the dimensionality transition of the SHG process caused by the change of the fundamental wave diameter. We show that SHG from a narrow fundamental beam leads to the spontaneous self-phase-matching process with, in addition, the appearance of angular dispersion for the off-axis frequency components generated. The angular dispersion sustains the formation of the short X pulse in the second harmonic (SH) and is recognized as three-dimensional (3D) dynamics. On the contrary, the large-diameter fundamental beam reduces the number of the degrees of freedom, does not allow the generation of the angular dispersion, and maintains the so-called one-dimensional (1D) SHG dynamics, where the self-phase-matching appears just for axial components and is accompanied by the shrinking of the SH temporal bandwidth, and sustains a long SH pulse formation. The transition from long SH pulse generation typical of the 1D dynamics to the short 3D X pulse is illustrated numerically and experimentally by changing the conditions from the self-defocusing to the self-focusing regime by simply tuning the phase mismatch. The numerical and experimental verification of the analytical results are also presented.

  15. 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

  16. Universality for the parameter-mismatching effect on weak synchronization in coupled chaotic systems

    International Nuclear Information System (INIS)

    Lim, Woochang; Kim, Sang-Yoon

    2004-01-01

    To examine the universality for the parameter-mismatching effect on weak chaotic synchronization, we study coupled multidimensional invertible systems such as the coupled Henon maps and coupled pendula. By generalizing the method proposed in coupled one-dimensional (1D) noninvertible maps, we introduce the parameter sensitivity exponent δ to measure the degree of the parameter sensitivity of a weakly stable synchronous chaotic attractor. In terms of the parameter sensitivity exponents, we characterize the effect of the parameter mismatch on the intermittent bursting and the basin riddling occurring in the regime of weak synchronization. It is thus found that the scaling exponent μ for the average characteristic time (i.e., the average interburst time and the average chaotic transient lifetime) for both the bubbling and riddling cases is given by the reciprocal of the parameter sensitivity exponent, as in the simple system of coupled 1D maps. Hence, the reciprocal relation (i.e., μ = 1/δ) seems to be 'universal', in the sense that it holds in typical coupled chaotic systems of different nature

  17. Characterization of cell mismatch in a multi-crystalline silicon photovoltaic module

    International Nuclear Information System (INIS)

    Crozier, J.L.; Dyk, E.E. van; Vorster, F.J.

    2012-01-01

    In this study the causes and effects of cell mismatch were identified in a multi-crystalline silicon photovoltaic module. Different techniques were used to identify the causes of the mismatch, including Electroluminescence (EL) imaging, Infrared (IR) imaging, current–voltage (I–V) characteristics, worst-case cell determination and Large Area Laser Beam Induced Current (LA-LBIC) scans. In EL images the cracked cells, broken fingers and material defects are visible. The presence of poorly contacted cells results in the formation of hot-spots. LA-LBIC line scans give the relative photoresponse of the cells in the module. However, this technique is limited due to the penetration depth of the laser beam. The worst case cell determination compares the I–V curves of the whole module with the I–V curve of the module with one cell covered, allowing the evaluation of the performance of each cell in a series-connected string. These methods allowed detection of the poorly performing cells in the module. Using all these techniques an overall view of the photoresponse in the cells and their performance is obtained.

  18. Characterization of cell mismatch in a multi-crystalline silicon photovoltaic module

    Energy Technology Data Exchange (ETDEWEB)

    Crozier, J.L., E-mail: s207094248@live.nmmu.ac.za [Department of Physics, P.O. Box 77000, Nelson Mandela Metropolitan University, Port Elizabeth 6031 (South Africa); Dyk, E.E. van; Vorster, F.J. [Department of Physics, P.O. Box 77000, Nelson Mandela Metropolitan University, Port Elizabeth 6031 (South Africa)

    2012-05-15

    In this study the causes and effects of cell mismatch were identified in a multi-crystalline silicon photovoltaic module. Different techniques were used to identify the causes of the mismatch, including Electroluminescence (EL) imaging, Infrared (IR) imaging, current-voltage (I-V) characteristics, worst-case cell determination and Large Area Laser Beam Induced Current (LA-LBIC) scans. In EL images the cracked cells, broken fingers and material defects are visible. The presence of poorly contacted cells results in the formation of hot-spots. LA-LBIC line scans give the relative photoresponse of the cells in the module. However, this technique is limited due to the penetration depth of the laser beam. The worst case cell determination compares the I-V curves of the whole module with the I-V curve of the module with one cell covered, allowing the evaluation of the performance of each cell in a series-connected string. These methods allowed detection of the poorly performing cells in the module. Using all these techniques an overall view of the photoresponse in the cells and their performance is obtained.

  19. Simple detection of germline microsatellite instability for diagnosis of constitutional mismatch repair cancer syndrome.

    Science.gov (United States)

    Ingham, Danielle; Diggle, Christine P; Berry, Ian; Bristow, Claire A; Hayward, Bruce E; Rahman, Nazneen; Markham, Alexander F; Sheridan, Eamonn G; Bonthron, David T; Carr, Ian M

    2013-06-01

    Heterozygous mutations in DNA mismatch repair (MMR) genes result in predisposition to colorectal cancer (hereditary nonpolyposis colorectal cancer or Lynch syndrome). Patients with biallelic mutations in these genes, however, present earlier, with constitutional mismatch repair deficiency cancer syndrome (CMMRD), which is characterized by a spectrum of rare childhood malignancies and café-au-lait skin patches. The hallmark of MMR deficiency, microsatellite instability (MSI), is readily detectable in tumor DNA in Lynch syndrome, but is also present in constitutional DNA of CMMRD patients. However, detection of constitutional or germline MSI (gMSI) has hitherto relied on technically difficult assays that are not routinely applicable for clinical diagnosis. Consequently, we have developed a simple high-throughput screening methodology to detect gMSI in CMMRD patients based on the presence of stutter peaks flanking a dinucleotide repeat allele when amplified from patient blood DNA samples. Using the three different microsatellite markers, the gMSI ratio was determined in a cohort of normal individuals and 10 CMMRD patients, with biallelic germline mutations in PMS2 (seven patients), MSH2 (one patient), or MSH6 (two patients). Subjects with either PMS2 or MSH2 mutations were easily identified; however, this measure was not altered in patients with CMMRD due to MSH6 mutation. © 2013 Wiley Periodicals, Inc.

  20. Acute lymphoblastic leukemia and lymphoma in the context of constitutional mismatch repair deficiency syndrome.

    Science.gov (United States)

    Ripperger, Tim; Schlegelberger, Brigitte

    2016-03-01

    Constitutional mismatch repair deficiency (CMMRD) syndrome is one of the rare diseases associated with a high risk of cancer. Causative mutations are found in DNA mismatch repair genes PMS2, MSH6, MSH2 or MLH1 that are well known in the context of Lynch syndrome. CMMRD follows an autosomal recessive inheritance trait and is characterized by childhood brain tumors and hematological malignancies as well as gastrointestinal cancer in the second and third decades of life. There is a high risk of multiple cancers, occurring synchronously and metachronously. In general, the prognosis is poor. About one third of CMMRD patients develop hematological malignancies as primary (sometimes the only) malignancy or as secondary neoplasm. T-cell non-Hodgkin lymphomas, mainly of mediastinal origin, are the most frequent hematological malignancies. Besides malignant diseases, non-neoplastic features are frequently observed, e.g. café-au-lait spots sometimes resembling neurofibromatosis type I, hypopigmented skin lesions, numerous adenomatous polyps, multiple pilomatricomas, or impaired immunoglobulin class switch recombination. Within the present review, we summarize previously published CMMRD patients with at least one hematological malignancy, provide an overview of steps necessary to substantiate the diagnosis of CMMRD, and refer to the recent most relevant literature. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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

    Science.gov (United States)

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

    2017-09-10

    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 in MMR genes. This syndrome is characterized by the development of childhood cancer. Patients with CMMRD are at extremely high risk of developing multiple cancers including hematological, brain and intestinal tumors. Mutations in MMR genes impair DNA repair and therefore most tumors of patients with CMMRD are hypermutated. These mutations lead to changes in the translational reading frame, which consequently result in neoantigen formation. Neoantigens are recognized as foreign by the immune system and can induce specific immune responses. The growing evidence on the clinical efficacy of immunotherapies, such as immune checkpoint inhibitors, offers the prospect for treatment of patients with CMMRD. Combining neoantigen-based vaccination strategies and immune checkpoint inhibitors could be an effective way to conquer CMMRD-related tumors. Neoantigen-based vaccines might also be a preventive treatment option in healthy biallelic MMR mutation carriers. Future studies need to reveal the safety and efficacy of immunotherapies for patients with CMMRD. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  2. Predictive genetic testing in children: constitutional mismatch repair deficiency cancer predisposing syndrome.

    Science.gov (United States)

    Bruwer, Zandrè; Algar, Ursula; Vorster, Alvera; Fieggen, Karen; Davidson, Alan; Goldberg, Paul; Wainwright, Helen; Ramesar, Rajkumar

    2014-04-01

    Biallelic germline mutations in mismatch repair genes predispose to constitutional mismatch repair deficiency syndrome (CMMR-D). The condition is characterized by a broad spectrum of early-onset tumors, including hematological, brain and bowel and is frequently associated with features of Neurofibromatosis type 1. Few definitive screening recommendations have been suggested and no published reports have described predictive testing. We report on the first case of predictive testing for CMMR-D following the identification of two non-consanguineous parents, with the same heterozygous mutation in MLH1: c.1528C > T. The genetic counseling offered to the family, for their two at-risk daughters, is discussed with a focus on the ethical considerations of testing children for known cancer-causing variants. The challenges that are encountered when reporting on heterozygosity in a child younger than 18 years (disclosure of carrier status and risk for Lynch syndrome), when discovered during testing for homozygosity, are addressed. In addition, the identification of CMMR-D in a three year old, and the recommended clinical surveillance that was proposed for this individual is discussed. Despite predictive testing and presymptomatic screening, the sudden death of the child with CMMR-D syndrome occurred 6 months after her last surveillance MRI. This report further highlights the difficulty of developing guidelines, as a result of the rarity of cases and diversity of presentation.

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

    Science.gov (United States)

    Suerink, M; Potjer, T P; Versluijs, A B; Ten Broeke, S W; Tops, C 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 multiple café-au-lait macules (CALM) and other NF1 signs, but no germline NF1 mutations. We report of a case of a healthy 6-year-old girl who fulfilled the diagnostic criteria of NF1 with >6 CALM and freckling. Since molecular genetic testing was unable to confirm the diagnosis of NF1 or Legius syndrome and the patient was a child of consanguineous parents, we suspected CMMRD and found a homozygous PMS2 mutation that impairs MMR function. Current guidelines advise testing for CMMRD only in cancer patients. However, this case illustrates that including CMMRD in the differential diagnosis in suspected sporadic NF1 without causative NF1 or SPRED1 mutations may facilitate identification of CMMRD prior to cancer development. We discuss the advantages and potential risks of this CMMRD testing scenario. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. 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.

  5. Impact of DNA mismatch repair system alterations on human fertility and related treatments.

    Science.gov (United States)

    Hu, Min-hao; Liu, Shu-yuan; Wang, Ning; Wu, Yan; Jin, Fan

    2016-01-01

    DNA mismatch repair (MMR) is one of the biological pathways, which plays a critical role in DNA homeostasis, primarily by repairing base-pair mismatches and insertion/deletion loops that occur during DNA replication. MMR also takes part in other metabolic pathways and regulates cell cycle arrest. Defects in MMR are associated with genomic instability, predisposition to certain types of cancers and resistance to certain therapeutic drugs. Moreover, genetic and epigenetic alterations in the MMR system demonstrate a significant relationship with human fertility and related treatments, which helps us to understand the etiology and susceptibility of human infertility. Alterations in the MMR system may also influence the health of offspring conceived by assisted reproductive technology in humans. However, further studies are needed to explore the specific mechanisms by which the MMR system may affect human infertility. This review addresses the physiological mechanisms of the MMR system and associations between alterations of the MMR system and human fertility and related treatments, and potential effects on the next generation.

  6. 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.

  7. Conflict and metacognitive control: The mismatch-monitoring hypothesis of how others’ knowledge states affect recall

    Science.gov (United States)

    Fraundorf, Scott H.; Benjamin, Aaron S.

    2015-01-01

    Information about others’ success in remembering is frequently available. For example, students taking an exam may assess its difficulty by monitoring when others turn in their exams. In two experiments, we investigated how rememberers use this information to guide recall. Participants studied paired associates, some semantically related (and thus easier to retrieve) and some unrelated (and thus harder). During a subsequent cued recall test, participants viewed fictive information about an opponent’s accuracy on each item. In Experiment 1, participants responded to each cue once before seeing the opponent’s performance and once afterwards. Participants reconsidered their responses least often when the opponent’s accuracy matched the item difficulty (easy items the opponent recalled, hard items the opponent forgot) and most often when the opponent’s accuracy and the item difficulty mismatched. When participants responded only after seeing the opponent’s performance (Experiment 2), the same mismatch conditions that led to reconsideration even produced superior recall. These results suggest that rememberers monitor whether others’ knowledge states accord or conflict with their own experience, and that this information shifts how they interrogate their memory and what they recall. PMID:26247369

  8. Conflict and metacognitive control: the mismatch-monitoring hypothesis of how others' knowledge states affect recall.

    Science.gov (United States)

    Fraundorf, Scott H; Benjamin, Aaron S

    2016-09-01

    Information about others' success in remembering is frequently available. For example, students taking an exam may assess its difficulty by monitoring when others turn in their exams. In two experiments, we investigated how rememberers use this information to guide recall. Participants studied paired associates, some semantically related (and thus easier to retrieve) and some unrelated (and thus harder). During a subsequent cued recall test, participants viewed fictive information about an opponent's accuracy on each item. In Experiment 1, participants responded to each cue once before seeing the opponent's performance and once afterwards. Participants reconsidered their responses least often when the opponent's accuracy matched the item difficulty (easy items the opponent recalled, hard items the opponent forgot) and most often when the opponent's accuracy and the item difficulty mismatched. When participants responded only after seeing the opponent's performance (Experiment 2), the same mismatch conditions that led to reconsideration even produced superior recall. These results suggest that rememberers monitor whether others' knowledge states accord or conflict with their own experience, and that this information shifts how they interrogate their memory and what they recall.

  9. Cultural mismatch and the education of Aboriginal youths: the interplay of cultural identities and teacher ratings.

    Science.gov (United States)

    Fryberg, Stephanie A; Troop-Gordon, Wendy; D'Arrisso, Alexandra; Flores, Heidi; Ponizovskiy, Vladimir; Ranney, John D; Mandour, Tarek; Tootoosis, Curtis; Robinson, Sandy; Russo, Natalie; Burack, Jacob A

    2013-01-01

    In response to the enduring "deficit" approach to the educational attainment of Aboriginal students in North America, we hypothesized that academic underperformance is related to a cultural mismatch between Aboriginal students' cultural background, which emphasizes connectedness and interdependence, and the mainstream White model of education, which focuses on independence and assertiveness. The participants included virtually all the secondary students (N = 115) in the Naskapi community of Kawawachikamach, Quebec, Canada. We obtained self-reports of identification with Aboriginal and White culture, teacher reports of assertiveness, and official grades. We found that high identification with either Aboriginal or White culture was related to higher grades, regardless of whether the students were perceived as assertive by their teacher. Conversely, at low levels of cultural identification toward Aboriginal or White culture, being perceived as low in assertiveness by one's teacher predicted lower grades. This suggests that both high cultural identification and assertiveness can contribute to enhancing the educational outcomes of Aboriginal students, but that Aboriginal students with low levels of both cultural identification and assertiveness are at particular risk as they are mismatched with the culture of mainstream schools and do not benefit from the protective effects of identity. The relationships among identity, cultural values, and academic performance point to the need to reject the notion of an inherent deficit in education among Aboriginal youths in favor of a different framework in which success can be attained when alternative ways of being are fostered and nurtured in schools.

  10. Unconscious improvement in foreign language learning using mismatch negativity neurofeedback: A preliminary study.

    Directory of Open Access Journals (Sweden)

    Ming Chang

    Full Text Available When people learn foreign languages, they find it difficult to perceive speech sounds that are nonexistent in their native language, and extensive training is consequently necessary. Our previous studies have shown that by using neurofeedback based on the mismatch negativity event-related brain potential, participants could unconsciously achieve learning in the auditory discrimination of pure tones that could not be consciously discriminated without the neurofeedback. Here, we examined whether mismatch negativity neurofeedback is effective for helping someone to perceive new speech sounds in foreign language learning. We developed a task for training native Japanese speakers to discriminate between 'l' and 'r' sounds in English, as they usually cannot discriminate between these two sounds. Without participants attending to auditory stimuli or being aware of the nature of the experiment, neurofeedback training helped them to achieve significant improvement in unconscious auditory discrimination and recognition of the target words 'light' and 'right'. There was also improvement in the recognition of other words containing 'l' and 'r' (e.g., 'blight' and 'bright', even though these words had not been presented during training. This method could be used to facilitate foreign language learning and can be extended to other fields of auditory and clinical research and even other senses.

  11. Mismatch repair proteins, meiosis, and mice: understanding the complexities of mammalian meiosis.

    Science.gov (United States)

    Svetlanov, Anton; Cohen, Paula E

    2004-05-15

    Mammalian meiosis differs from that seen in lower eukaryotes in several respects, not least of which is the added complexity of dealing with chromosomal interactions across a much larger genome (12 MB over 16 chromosome pairs in Saccharomyces cerevisiae compared to 2500 MB over 19 autosome pairs in Mus musculus). Thus, the recombination machinery, while being highly conserved through eukaryotes, has evolved to accommodate such issues to preserve genome integrity and to ensure propagation of the species. One group of highly conserved meiotic regulators is the DNA mismatch repair protein family that, as their name implies, were first identified as proteins that act to repair DNA mismatches that arise primarily during DNA replication. Their function in ensuring chromosomal integrity has also translated into a critical role for this family in meiotic recombination in most sexually reproducing organisms. In mice, targeted deletion of certain family members results in severe consequences for meiotic progression and infertility. This review will focus on the studies involving these mutant mouse models, with occasional comparison to the function of these proteins in other organisms.

  12. Climate change effects on migration phenology may mismatch brood parasitic cuckoos and their hosts.

    Science.gov (United States)

    Saino, Nicola; Rubolini, Diego; Lehikoinen, Esa; Sokolov, Leonid V; Bonisoli-Alquati, Andrea; Ambrosini, Roberto; Boncoraglio, Giuseppe; Møller, Anders P

    2009-08-23

    Phenological responses to climate change vary among taxa and across trophic levels. This can lead to a mismatch between the life cycles of ecologically interrelated populations (e.g. predators and prey), with negative consequences for population dynamics of some of the interacting species. Here we provide, to our knowledge, the first evidence that climate change might disrupt the association between the life cycles of the common cuckoo (Cuculus canorus), a migratory brood parasitic bird, and its hosts. We investigated changes in timing of spring arrival of the cuckoo and its hosts throughout Europe over six decades, and found that short-distance, but not long-distance, migratory hosts have advanced their arrival more than the cuckoo. Hence, cuckoos may keep track of phenological changes of long-distance, but not short-distance migrant hosts, with potential consequences for breeding of both cuckoo and hosts. The mismatch to some of the important hosts may contribute to the decline of cuckoo populations and explain some of the observed local changes in parasitism rates of migratory hosts.

  13. Recommendations for J and CTOD testing of strength mismatched. GKSS and EDF view

    Energy Technology Data Exchange (ETDEWEB)

    Kocak, M.; Kim, Y.J.; Hornet, P

    1998-03-01

    Recommendations for toughness testing and evaluation procedures for weldments are given in this paper. For testing aspects, two testing methods are outlined, micro-flat tensile tests and the {delta}{sub 5} testing technique. The micro-flat tensile tests are extremely useful to measure tensile properties for the Heat Affected Zone (HAZ) of multipass welds and very thin weld regions such as laser beam or electron beam and it is rather universal. It can be applied to any type of test pieces as well as to structural components with surface breaking cracks. These two test methods can provide efficient tools for tensile and fracture testing of metallic materials joined by fusion welding technology including high power beam welding processes. For toughness evaluation aspects, the J estimation procedures for mismatched specimens are reviewed, including a summary of a new proposal for best estimates of the mismatch on the J integral. The new procedure covers not only weld metal cracks but also HAZ cracks. Finally some recommendations are given for further development. (author) 29 refs.

  14. Tunable band structures of polycrystalline graphene by external and mismatch strains

    Institute of Scientific and Technical Information of China (English)

    Jiang-Tao Wu; Xing-Hua Shi; Yu-Jie Wei

    2012-01-01

    Lacking a band gap largely limits the application of graphene in electronic devices.Previous study shows that grain boundaries (GBs) in polycrystalline graphene can dramatically alter the electrical properties of graphene.Here,we investigate the band structure of polycrystalline graphene tuned by externally imposed strains and intrinsic mismatch strains at the GB by density functional theory (DFT) calculations.We found that graphene with symmetrical GBs typically has zero band gap even with large uniaxial and biaxial strain.However,some particular asymmetrical GBs can open a band gap in graphene and their band structures can be substantially tuned by external strains.A maximum band gap about 0.19 eV was observed in matched-armchair GB (5,5) | (3,7) with a misorientation of θ =13° when the applied uniaxial strain increases to 9%.Although mismatch strain is inevitable in asymmetrical GBs,it has a small influence on the band gap of polycrystalline graphene.

  15. From coherent to incoherent mismatched interfaces: A generalized continuum formulation of surface stresses

    Science.gov (United States)

    Dingreville, Rémi; Hallil, Abdelmalek; Berbenni, Stéphane

    2014-12-01

    The equilibrium of coherent and incoherent mismatched interfaces is reformulated in the context of continuum mechanics based on the Gibbs dividing surface concept. Two surface stresses are introduced: a coherent surface stress and an incoherent surface stress, as well as a transverse excess strain. The coherent surface stress and the transverse excess strain represent the thermodynamic driving forces of stretching the interface while the incoherent surface stress represents the driving force of stretching one crystal while holding the other fixed and thereby altering the structure of the interface. These three quantities fully characterize the elastic behavior of coherent and incoherent interfaces as a function of the in-plane strain, the transverse stress and the mismatch strain. The isotropic case is developed in detail and particular attention is paid to the case of interfacial thermo-elasticity. This exercise provides an insight on the physical significance of the interfacial elastic constants introduced in the formulation and illustrates the obvious coupling between the interface structure and its associated thermodynamics quantities. Finally, an example based on atomistic simulations of Cu/Cu2O interfaces is given to demonstrate the relevance of the generalized interfacial formulation and to emphasize the dependence of the interfacial thermodynamic quantities on the incoherency strain with an actual material system.

  16. Crack arrest within teeth at the dentinoenamel junction caused by elastic modulus mismatch.

    Science.gov (United States)

    Bechtle, Sabine; Fett, Theo; Rizzi, Gabriele; Habelitz, Stefan; Klocke, Arndt; Schneider, Gerold A

    2010-05-01

    Enamel and dentin compose the crowns of human teeth. They are joined at the dentinoenamel junction (DEJ) which is a very strong and well-bonded interface unlikely to fail within healthy teeth despite the formation of multiple cracks within enamel during a lifetime of exposure to masticatory forces. These cracks commonly are arrested when reaching the DEJ. The phenomenon of crack arrest at the DEJ is described in many publications but there is little consensus on the underlying cause and mechanism. Explanations range from the DEJ having a larger toughness than both enamel and dentin up to the assumption that not the DEJ itself causes crack arrest but the so-called mantle dentin, a thin material layer close to the DEJ that is somewhat softer than the bulk dentin. In this study we conducted 3-point bending experiments with bending bars consisting of the DEJ and surrounding enamel and dentin to investigate crack propagation and arrest within the DEJ region. Calculated stress intensities around crack tips were found to be highly influenced by the elastic modulus mismatch between enamel and dentin and hence, the phenomenon of crack arrest at the DEJ could be explained accordingly via this elastic modulus mismatch. Copyright 2010 Elsevier Ltd. All rights reserved.

  17. Practical impulsive synchronization of chaotic systems with parametric uncertainty and mismatch

    International Nuclear Information System (INIS)

    Wen, C.Y.; Ji, Y.; Li, Z.G.

    2007-01-01

    Recently, there has been increasing interest in the synchronization of two chaotic systems and some significant results have been reported. In these results, a strong assumption that the two chaotic systems should be identical, i.e., without any mismatch, is imposed. Furthermore, system parameters are also assumed known exactly. Clearly, these are impractical. In this Letter, pure impulsive synchronization is considered. We quantitatively establish a relationship between a pre-specified bound of the synchronization error and the length of impulsive intervals in the presence of both parametric uncertainties and mismatch between the two systems. This is the first available result in the area, to the knowledge of the authors. With such a relationship as a guideline to choose impulsive intervals, a practical impulsive synchronization scheme is obtained. With the proposed scheme, the magnitude of the synchronization error is theoretically ensured to approach to and stay within the pre-specified bound which can be arbitrarily small. Simulation studies on the Lorenz system also verify the effectiveness of the proposed scheme

  18. Climate change is affecting mortality of weasels due to camouflage mismatch.

    Science.gov (United States)

    Atmeh, Kamal; Andruszkiewicz, Anna; Zub, Karol

    2018-05-24

    Direct phenological mismatch caused by climate change can occur in mammals that moult seasonally. Two colour morphs of the weasel Mustela nivalis (M. n.) occur sympatrically in Białowieża Forest (NE Poland) and differ in their winter pelage colour: white in M. n. nivalis and brown in M. n. vulgaris. Due to their small body size, weasels are vulnerable to attacks by a range of different predators; thus cryptic coat colour may increase their winter survival. By analysing trapping data, we found that the share of white subspecies in the weasel population inhabiting Białowieża Forest decreases with decreasing numbers of days with snow cover. This led us to hypothesise that selective predation pressure should favour one of the two phenotypes, according to the prevailing weather conditions in winter. A simple field experiment with weasel models (white and brown), exposed against different background colours, revealed that contrasting models faced significantly higher detection by predators. Our observations also confirmed earlier findings that the plasticity of moult in M. n. nivalis is very limited. This means that climate change will strongly influence the mortality of the nivalis-type due to prolonged camouflage mismatch, which will directly affect the abundance and geographical distribution of this subspecies.

  19. Duplex Healing of Selectively Thiolated Guanosine Mismatches through a Cd2+ Chemical Stimulus.

    Science.gov (United States)

    Lunn, Samantha M L; Hribesh, Samira; Whitfield, Colette J; Hall, Michael J; Houlton, Andrew; Bronowska, Agnieszka K; Tuite, Eimer M; Pike, Andrew R

    2018-03-25

    The on-column selective conversion of guanosine to thioguanosine (tG) yields modified oligomers that exhibit destabilisation over the fully complementary duplex. Restoration to a stabilised duplex is induced through thio-directed Cd 2+ coordination; a route for healing DNA damage. Short oligomers are G-specifically thiolated through a modified on-column protocol without the need for costly thioguanosine phosphoramidites. Addition of Cd 2+ ions to a duplex containing a highly disrupted tG central mismatch sequence, 3'-A 6 tG 4 T 6 -5', suggests a (tG) 8 Cd 2 central coordination regime, resulting in increased base stacking and duplex stability. Equilibrium molecular dynamic calculations support the hypothesis of metal-induced healing of the thiolated duplex. The 2 nm displacement of the central tG mismatched region is dramatically reduced after the addition of a chemical stimuli, Cd 2+ ions, returning to a minimized fluctuational state comparable to the unmodified fully complementary oligomer. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Effect of parameter mismatch on the dynamics of strongly coupled self sustained oscillators.

    Science.gov (United States)

    Chakrabarty, Nilaj; Jain, Aditya; Lal, Nijil; Das Gupta, Kantimay; Parmananda, Punit

    2017-01-01

    In this paper, we present an experimental setup and an associated mathematical model to study the synchronization of two self-sustained, strongly coupled, mechanical oscillators (metronomes). The effects of a small detuning in the internal parameters, namely, damping and frequency, have been studied. Our experimental system is a pair of spring wound mechanical metronomes; coupled by placing them on a common base, free to move along a horizontal direction. We designed a photodiode array based non-contact, non-magnetic position detection system driven by a microcontroller to record the instantaneous angular displacement of each oscillator and the small linear displacement of the base, coupling the two. In our system, the mass of the oscillating pendula forms a significant fraction of the total mass of the system, leading to strong coupling of the oscillators. We modified the internal mechanism of the spring-wound "clockwork" slightly, such that the natural frequency and the internal damping could be independently tuned. Stable synchronized and anti-synchronized states were observed as the difference in the parameters was varied in the experiments. The simulation results showed a rapid increase in the phase difference between the two oscillators beyond a certain threshold of parameter mismatch. Our simple model of the escapement mechanism did not reproduce a complete 180° out of phase state. However, the numerical simulations show that increased mismatch in parameters leads to a synchronized state with a large phase difference.

  1. LORETA current source density for duration mismatch negativity and neuropsychological assessment in early schizophrenia.

    Directory of Open Access Journals (Sweden)

    Tomohiro Miyanishi

    Full Text Available INTRODUCTION: Patients with schizophrenia elicit cognitive decline from the early phase of the illness. Mismatch negativity (MMN has been shown to be associated with cognitive function. We investigated the current source density of duration mismatch negativity (dMMN, by using low-resolution brain electromagnetic tomography (LORETA, and neuropsychological performance in subjects with early schizophrenia. METHODS: Data were obtained from 20 patients meeting DSM-IV criteria for schizophrenia or schizophreniform disorder, and 20 healthy control (HC subjects. An auditory odd-ball paradigm was used to measure dMMN. Neuropsychological performance was evaluated by the brief assessment of cognition in schizophrenia Japanese version (BACS-J. RESULTS: Patients showed smaller dMMN amplitudes than those in the HC subjects. LORETA current density for dMMN was significantly lower in patients compared to HC subjects, especially in the temporal lobes. dMMN current density in the frontal lobe was positively correlated with working memory performance in patients. CONCLUSIONS: This is the first study to identify brain regions showing smaller dMMN current density in early schizophrenia. Further, poor working memory was associated with decreased dMMN current density in patients. These results are likely to help understand the neural basis for cognitive impairment of schizophrenia.

  2. Multirate Formulation for Mismatch Sensitivity Analysis of Analog-to-Digital Converters That Utilize Parallel ΣΔ-Modulators

    Directory of Open Access Journals (Sweden)

    Per Löwenborg

    2008-02-01

    Full Text Available A general formulation based on multirate filterbank theory for analog-to-digital converters using parallel sigmadelta modulators in conjunction with modulation sequences is presented. The time-interleaved modulators (TIMs, Hadamard modulators (HMs, and frequency-band decomposition modulators (FBDMs can be viewed as special cases of the proposed description. The usefulness of the formulation stems from its ability to analyze a system's sensitivity to aliasing due to channel mismatch and modulation sequence level errors. Both Nyquist-rate and oversampled systems are considered, and it is shown how the matching requirements between channels can be reduced for oversampled systems. The new formulation is useful also for the derivation of new modulation schemes, and an example is given of how it can be used in this context.

  3. Anomeric 2'-Deoxycytidines and Silver Ions: Hybrid Base Pairs with Greatly Enhanced Stability and Efficient DNA Mismatch Detection with α-dC.

    Science.gov (United States)

    Guo, Xiurong; Seela, Frank

    2017-09-04

    α-d-Nucleosides are rare in nature but can develop fascinating properties when incorporated into DNA. This work reports on the first silver-mediated base pair constructed from two anomeric nucleosides: α-dC and β-dC. The hybrid base pair was integrated into the DNA and DNA/RNA double helix. A 12-mer duplex with α-dC and β-dC pair exhibits a higher thermal stability (T m =43 °C) than that incorporating the β-dC-Ag + -β-dC homo pair (T m =34 °C). Furthermore, α-dC shows excellent mismatch discrimination for DNA single nucleotide polymorphism (SNP). All four SNPs were identified on the basis of large T m value differences measured in the presence of silver ions. High resolution melting was not required. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Enhanced Engraftment of a Very Low-Dose Cord Blood Unit in an Adult Haemopoietic Transplant by Addition of Six Mismatched Viable Cord Units

    Directory of Open Access Journals (Sweden)

    Stephen J. Proctor

    2010-01-01

    , supported by six mismatched cord blood units (one unit per 10 kg recipient weight. No adverse reaction occurred following the infusion of mismatched units and engraftment of the suboptimal-dose matched unit occurred rapidly, with no molecular evidence of engraftment of mismatched cords. Early molecular remission of ALL was demonstrated using a novel PCR for a mitochondrial DNA mutation in the leukaemic clone. The cell dose of the matched cord was well below that recommended to engraft a 70 kg recipient. We suggest that a factor or factors in the mismatched cords enhanced/supported engraftment of the matched cord.

  5. Occupational stratification, job-mismatches, and child poverty: understanding the disadvantage of Black immigrants in the US.

    Science.gov (United States)

    Thomas, Kevin J A

    2015-03-01

    This study examines the implications of occupational stratification and job mismatches for the welfare of children, using data from the 2005-2009 American Community Survey. The results show that Black children of immigrants have household heads that are more likely to have occupations with low SEI scores than children in US-born households. More importantly, they demonstrate that intersections between parental job-mismatches and employment in the bottom rather than upper levels of the occupational distribution have important implications for understanding poverty differences among children. Job mismatches within occupations with low SEI scores are associated with greater poverty risks among Black than White, Asian, or Hispanic children of immigrants. However, racial poverty disparities are considerably lower among children with household heads in the highest occupational strata. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Contingency blindness: location-identity binding mismatches obscure awareness of spatial contingencies and produce profound interference in visual working memory.

    Science.gov (United States)

    Fiacconi, Chris M; Milliken, Bruce

    2012-08-01

    The purpose of the present study was to highlight the role of location-identity binding mismatches in obscuring explicit awareness of a strong contingency. In a spatial-priming procedure, we introduced a high likelihood of location-repeat trials. Experiments 1, 2a, and 2b demonstrated that participants' explicit awareness of this contingency was heavily influenced by the local match in location-identity bindings. In Experiment 3, we sought to determine why location-identity binding mismatches produce such low levels of contingency awareness. Our results suggest that binding mismatches can interfere substantially with visual-memory performance. We attribute the low levels of contingency awareness to participants' inability to remember the critical location-identity binding in the prime on a trial-to-trial basis. These results imply a close interplay between object files and visual working memory.

  7. Log-layer mismatch and modeling of the fluctuating wall stress in wall-modeled large-eddy simulations

    Science.gov (United States)

    Yang, Xiang I. A.; Park, George Ilhwan; Moin, Parviz

    2017-10-01

    Log-layer mismatch refers to a chronic problem found in wall-modeled large-eddy simulation (WMLES) or detached-eddy simulation, where the modeled wall-shear stress deviates from the true one by approximately 15 % . Many efforts have been made to resolve this mismatch. The often-used fixes, which are generally ad hoc, include modifying subgrid-scale stress models, adding a stochastic forcing, and moving the LES-wall-model matching location away from the wall. An analysis motivated by the integral wall-model formalism suggests that log-layer mismatch is resolved by the built-in physics-based temporal filtering. In this work we investigate in detail the effects of local filtering on log-layer mismatch. We show that both local temporal filtering and local wall-parallel filtering resolve log-layer mismatch without moving the LES-wall-model matching location away from the wall. Additionally, we look into the momentum balance in the near-wall region to provide an alternative explanation of how LLM occurs, which does not necessarily rely on the numerical-error argument. While filtering resolves log-layer mismatch, the quality of the wall-shear stress fluctuations predicted by WMLES does not improve with our remedy. The wall-shear stress fluctuations are highly underpredicted due to the implied use of LES filtering. However, good agreement can be found when the WMLES data are compared to the direct numerical simulation data filtered at the corresponding WMLES resolutions.

  8. 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.

  9. Peritumoral granulomatous reaction in endometrial carcinoma: association with DNA mismatch repair protein deficiency, particularly loss of PMS2 expression.

    Science.gov (United States)

    Stewart, Colin J R; Pearn, Amy; Pachter, Nicholas; Tan, Adeline

    2018-04-30

    The observation of peritumoral granulomatous reactions (PGRs) in two endometrial carcinomas (ECs) with a PMS2-deficient/MLH1-intact expression pattern led us to investigate whether PGRs in EC were specifically associated with DNA mismatch repair (MMR) protein deficiency, particularly PMS2 loss. Hysterectomy specimens from 22 MMR protein-intact and 54 MMR protein-deficient ECs were reviewed with specific attention to the presence of a PGR and a tumour-associated lymphoid reaction [including tumour-infiltrating lymphocytes (TILs) and stromal lymphoid infiltrates]. The MMR protein-deficient ECs included 22 cases with combined MLH1/PMS2 loss, 11 with combined MSH2/MSH6 loss, 11 with isolated MSH6 loss, and 10 with PMS2 loss but intact MLH1 staining (including the two 'index' cases). Overall, PGRs were identified in seven of 54 (13%) MMR protein-deficient ECs, five of which showed a PMS2-deficient/MLH1-intact immunophenotype; three of these patients had germline PMS2 mutations and one additional patient had a germline MSH6 mutation. None of the MMR protein-intact tumours showed a PGR. Although five of the seven PGR-positive ECs had a high-grade histological component, six were stage I. Most ECs with PGRs also showed TILs and stromal lymphoid reactions, similarly to MMR protein-deficient ECs in general. MMR protein-deficient ECs, particularly those with PMS2 loss, occasionally show PGRs in addition to stromal lymphoid infiltrates and TILs. Therefore, PGRs could be considered to constitute a histological prompt for consideration of Lynch syndrome. The potential prognostic significance of PGRs in EC requires further study. © 2018 John Wiley & Sons Ltd.

  10. Policy recommendations on tacing and reducing program mismatch and perverse incentives present in earmarking sin tax to tobacco growing areas

    Directory of Open Access Journals (Sweden)

    Madeiline Joy Aloria

    2018-03-01

    Full Text Available Background Recognizing that the Philippine 1991 tobacco tax sharing law favoured the development of tobacco, the Sin Tax Law, a separate law on restructuring cigarette tax, expanded the use of such to also cover shifting farmers to viable alternative livelihood. Aside from health-driven supply reduction objectives, this is crucial as evidence shows that tobacco production is continuously declining starting decades ago, requiring to actively shift farmers. Methods Data on tobacco excise tax earmarking and utilization, farmers´ production and shifting behaviours, labor improvement and poverty alleviation indicators, and LGU capacity were analysed to determine potential program mismatches and perverse incentives. Supporting qualitative data were used to identify policy and structural gaps to address these. Results Financing livelihood projects becomes the least priority (only 6% average share i funds, as a result of LGU´s final allocation being determined by their share in total tobacco leaf production, which actually put pressure on their farmers to increase production volume. Meanwhile, infrastructure continue to get bulk of sin tax earmarking and are linked to its political benefits. Last, the provision of cooperative and agro-industrial projects in selected areas were shifting behaviour is heavy can still be improved. Conclusions As the two tobacco tax sharing laws fund both programs to develop tobacco and to shift tobacco farmers to other livelihood, a schizophrenic management exists. Key structural and policy ingredients have to be present to reverse this. First is the need to establish institutional support to manage alternative livelihood funds, in order to balance the powers of National Tobacco Administration over tobacco growing areas. Allocation should not be based on production volume but rather on a systemic or comprehensive welfare assessment of shifted farmers. As livelihood programs are most commonly coursed through civil society

  11. EpHLA software: a timesaving and accurate tool for improving identification of acceptable mismatches for clinical purposes.

    Science.gov (United States)

    Filho, Herton Luiz Alves Sales; da Mata Sousa, Luiz Claudio Demes; von Glehn, Cristina de Queiroz Carrascosa; da Silva, Adalberto Socorro; dos Santos Neto, Pedro de Alcântara; do Nascimento, Ferraz; de Castro, Adail Fonseca; do Nascimento, Liliane Machado; Kneib, Carolina; Bianchi Cazarote, Helena; Mayumi Kitamura, Daniele; Torres, Juliane Roberta Dias; da Cruz Lopes, Laiane; Barros, Aryela Loureiro; da Silva Edlin, Evelin Nildiane; de Moura, Fernanda Sá Leal; Watanabe, Janine Midori Figueiredo; do Monte, Semiramis Jamil Hadad

    2012-06-01

    The HLAMatchmaker algorithm, which allows the identification of “safe” acceptable mismatches (AMMs) for recipients of solid organ and cell allografts, is rarely used in part due to the difficulty in using it in the current Excel format. The automation of this algorithm may universalize its use to benefit the allocation of allografts. Recently, we have developed a new software called EpHLA, which is the first computer program automating the use of the HLAMatchmaker algorithm. Herein, we present the experimental validation of the EpHLA program by showing the time efficiency and the quality of operation. The same results, obtained by a single antigen bead assay with sera from 10 sensitized patients waiting for kidney transplants, were analyzed either by conventional HLAMatchmaker or by automated EpHLA method. Users testing these two methods were asked to record: (i) time required for completion of the analysis (in minutes); (ii) number of eplets obtained for class I and class II HLA molecules; (iii) categorization of eplets as reactive or non-reactive based on the MFI cutoff value; and (iv) determination of AMMs based on eplets' reactivities. We showed that although both methods had similar accuracy, the automated EpHLA method was over 8 times faster in comparison to the conventional HLAMatchmaker method. In particular the EpHLA software was faster and more reliable but equally accurate as the conventional method to define AMMs for allografts. The EpHLA software is an accurate and quick method for the identification of AMMs and thus it may be a very useful tool in the decision-making process of organ allocation for highly sensitized patients as well as in many other applications.

  12. Effects of Emotional Intelligence on the Impression of Irony Created by the Mismatch between Verbal and Nonverbal Cues.

    Science.gov (United States)

    Jacob, Heike; Kreifelts, Benjamin; Nizielski, Sophia; Schütz, Astrid; Wildgruber, Dirk

    2016-01-01

    Emotional information is conveyed through verbal and nonverbal signals, with nonverbal cues often being considered the decisive factor in the judgment of others' emotional states. The aim of the present study was to examine how verbal and nonverbal cues are integrated by perceivers. More specifically, we tested whether the mismatch between verbal and nonverbal information was perceived as an expression of irony. Moreover, we investigated the effects of emotional intelligence on the impression of irony. The findings revealed that the mismatch between verbal and nonverbal information created the impression of irony. Furthermore, participants higher in emotional intelligence were faster at rating such stimuli as ironic expressions.

  13. Influence of very short patch mismatch repair on SOS inducing lesions after aminoglycoside treatment in Escherichia coli.

    Science.gov (United States)

    Baharoglu, Zeynep; Mazel, Didier

    2014-01-01

    Low concentrations of aminoglycosides induce the SOS response in Vibrio cholerae but not in Escherichia coli. In order to determine whether a specific factor present in E. coli prevents this induction, we developed a genetic screen where only SOS inducing mutants are viable. We identified the vsr gene coding for the Vsr protein of the very short patch mismatch repair (VSPR) pathway. The effect of mismatch repair (MMR) mutants was also studied. We propose that lesions formed upon aminoglycoside treatment are preferentially repaired by VSPR without SOS induction in E. coli and by MMR when VSPR is impaired. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  14. Effects of Emotional Intelligence on the Impression of Irony Created by the Mismatch between Verbal and Nonverbal Cues

    Science.gov (United States)

    Jacob, Heike; Kreifelts, Benjamin; Nizielski, Sophia; Schütz, Astrid; Wildgruber, Dirk

    2016-01-01

    Emotional information is conveyed through verbal and nonverbal signals, with nonverbal cues often being considered the decisive factor in the judgment of others’ emotional states. The aim of the present study was to examine how verbal and nonverbal cues are integrated by perceivers. More specifically, we tested whether the mismatch between verbal and nonverbal information was perceived as an expression of irony. Moreover, we investigated the effects of emotional intelligence on the impression of irony. The findings revealed that the mismatch between verbal and nonverbal information created the impression of irony. Furthermore, participants higher in emotional intelligence were faster at rating such stimuli as ironic expressions. PMID:27716831

  15. Reduced mismatch negativity in mild cognitive impairment: associations with neuropsychological performance.

    Science.gov (United States)

    Mowszowski, Loren; Hermens, Daniel F; Diamond, Keri; Norrie, Louisa; Hickie, Ian B; Lewis, Simon J G; Naismith, Sharon L

    2012-01-01

    Mild cognitive impairment (MCI) refers to a transitory state between healthy aging and dementia. Biomarkers are needed to facilitate early identification of MCI and predict progression to dementia. One potential neurophysiological biomarker, mismatch negativity (MMN), is an event-related potential reflecting fundamental, pre-attentive cognitive processes. MMN is reduced in normal aging and dementia and in neuropsychiatric samples and is associated with verbal memory deficits and poor executive functioning. This study aimed to investigate auditory MMN and its relationship to neuropsychological performance in MCI. Twenty-eight MCI participants and fourteen controls, aged ≥50 years, underwent neurophysiological and neuropsychological assessment, and completed questionnaires pertaining to disability. Relative to controls, the MCI group demonstrated reduced temporal MMN amplitude (p patients with MCI exhibit altered pre-attentive information processing, which in turn is associated with memory and psychosocial deficits. These findings overall suggest that MMN may be a viable neurophysiological biomarker of underlying disease in this 'at risk' group.

  16. Role of APC and DNA mismatch repair genes in the development of colorectal cancers

    Directory of Open Access Journals (Sweden)

    Roy Deodutta

    2003-12-01

    Full Text Available Abstract Colorectal cancer is the third most common cause of cancer-related death in both men and women in the western hemisphere. According to the American Cancer Society, an estimated 105,500 new cases of colon cancer with 57,100 deaths will occur in the U.S. in 2003, accounting for about 10% of cancer deaths. Among the colon cancer patients, hereditary risk contributes approximately 20%. The main inherited colorectal cancers are the familial adenomatous polyposis (FAP and the hereditary nonpolyposis colorectal cancers (HNPCC. The FAP and HNPCC are caused due to mutations in the adenomatous polyposis coli (APC and DNA mismatch repair (MMR genes. The focus of this review is to summarize the functions of APC and MMR gene products in the development of colorectal cancers.

  17. Kinetic characterisation of primer mismatches in allele-specific PCR: a quantitative assessment.

    Science.gov (United States)

    Waterfall, Christy M; Eisenthal, Robert; Cobb, Benjamin D

    2002-12-20

    A novel method of estimating the kinetic parameters of Taq DNA polymerase during rapid cycle PCR is presented. A model was constructed using a simplified sigmoid function to represent substrate accumulation during PCR in combination with the general equation describing high substrate inhibition for Michaelis-Menten enzymes. The PCR progress curve was viewed as a series of independent reactions where initial rates were accurately measured for each cycle. Kinetic parameters were obtained for allele-specific PCR (AS-PCR) amplification to examine the effect of mismatches on amplification. A high degree of correlation was obtained providing evidence of substrate inhibition as a major cause of the plateau phase that occurs in the later cycles of PCR.

  18. Auditory sensory memory and language abilities in former late talkers: a mismatch negativity study.

    Science.gov (United States)

    Grossheinrich, Nicola; Kademann, Stefanie; Bruder, Jennifer; Bartling, Juergen; Von Suchodoletz, Waldemar

    2010-09-01

    The present study investigated whether (a) a reduced duration of auditory sensory memory is found in late talking children and (b) whether deficits of sensory memory are linked to persistent difficulties in language acquisition. Former late talkers and children without delayed language development were examined at the age of 4 years and 7 months using mismatch negativity (MMN) with interstimulus intervals (ISIs) of 500 ms and 2000 ms. Additionally, short-term memory, language skills, and nonverbal intelligence were assessed. MMN mean amplitude was reduced for the ISI of 2000 ms in former late talking children both with and without persistent language deficits. In summary, our findings suggest that late talkers are characterized by a reduced duration of auditory sensory memory. However, deficits in auditory sensory memory are not sufficient for persistent language difficulties and may be compensated for by some children.

  19. Evolution and Adaptation in Pseudomonas aeruginosa Biofilms Driven by Mismatch Repair System-Deficient Mutators

    DEFF Research Database (Denmark)

    Luján, Adela M.; Maciá, María D.; Yang, Liang

    2011-01-01

    , which are rarely eradicated despite intensive antibiotic therapy. Current knowledge indicates that three major adaptive strategies, biofilm development, phenotypic diversification, and mutator phenotypes [driven by a defective mismatch repair system (MRS)], play important roles in P. aeruginosa chronic...... infections, but the relationship between these strategies is still poorly understood. We have used the flow-cell biofilm model system to investigate the impact of the mutS associated mutator phenotype on development, dynamics, diversification and adaptation of P. aeruginosa biofilms. Through competition...... diversification, evidenced by biofilm architecture features and by a wider range and proportion of morphotypic colony variants, respectively. Additionally, morphotypic variants generated in mutator biofilms showed increased competitiveness, providing further evidence for mutator-driven adaptive evolution...

  20. Constitutional mismatch repair-deficiency syndrome presenting as colonic adenomatous polyposis: clues from the skin.

    Science.gov (United States)

    Jasperson, K W; Samowitz, W S; Burt, R W

    2011-10-01

    Constitutional mismatch repair-deficiency (CMMR-D) syndrome is an autosomal recessive condition characterized by hematologic malignancies, brain tumors, Lynch syndrome-associated cancers and skin manifestations reminiscent of neurofibromatosis type 1 (NF1). In contrast to Lynch syndrome, CMMR-D syndrome is exceptionally rare, onset typically occurs in infancy or early childhood and, as described in this report, may also present with colonic polyposis suggestive of attenuated familial adenomatous polyposis (AFAP) or MUTYH associated polyposis (MAP). Here we describe two sisters with CMMR-D syndrome due to germline bi-allelic MSH6 mutations. Both sisters are without cancer, are older than typical for this condition, have NF1 associated features and a colonic phenotype suspicious for an attenuated polyposis syndrome. This report highlights the role of skin examinations in leading to an underlying genetic diagnosis in individuals with colonic adenomatous polyposis, but without mutations associated with AFAP or MAP. © 2010 John Wiley & Sons A/S.

  1. Expression of DNA mismatch repair proteins in transformed non-Hodgkin's lymphoma: relationship to smoking

    DEFF Research Database (Denmark)

    Nandi, S; Yu, J; Reinert, Line

    2006-01-01

    leukemia (CLL/SLL), that have transformed to diffuse-large B-cell lymphoma (DLBCL). We correlated the presence or absence of DNA-mismatch repair enzymes by immunostaining as well as the p53 status to smoking history. Of all patients (n = 30), 37% showed negative immunostaining of MLH1, 16% showed negative...... for either MLH1 or MSH2 was 2.2 times higher in smokers than non-smokers (relative risk = 2.2041, 95% confidence interval: 0.89714, 5.41491). No direct correlation was found between smoking and the mutations in the p53 gene. These results suggest that cigarette smoking may play a role in the development...

  2. Matches, Mismatches, and Methods: Multiple-View Workflows for Energy Portfolio Analysis.

    Science.gov (United States)

    Brehmer, Matthew; Ng, Jocelyn; Tate, Kevin; Munzner, Tamara

    2016-01-01

    The energy performance of large building portfolios is challenging to analyze and monitor, as current analysis tools are not scalable or they present derived and aggregated data at too coarse of a level. We conducted a visualization design study, beginning with a thorough work domain analysis and a characterization of data and task abstractions. We describe generalizable visual encoding design choices for time-oriented data framed in terms of matches and mismatches, as well as considerations for workflow design. Our designs address several research questions pertaining to scalability, view coordination, and the inappropriateness of line charts for derived and aggregated data due to a combination of data semantics and domain convention. We also present guidelines relating to familiarity and trust, as well as methodological considerations for visualization design studies. Our designs were adopted by our collaborators and incorporated into the design of an energy analysis software application that will be deployed to tens of thousands of energy workers in their client base.

  3. Robust control of nonlinear MAGLEV suspension system with mismatched uncertainties via DOBC approach.

    Science.gov (United States)

    Yang, Jun; Zolotas, Argyrios; Chen, Wen-Hua; Michail, Konstantinos; Li, Shihua

    2011-07-01

    Robust control of a class of uncertain systems that have disturbances and uncertainties not satisfying "matching" condition is investigated in this paper via a disturbance observer based control (DOBC) approach. In the context of this paper, "matched" disturbances/uncertainties stand for the disturbances/uncertainties entering the system through the same channels as control inputs. By properly designing a disturbance compensation gain, a novel composite controller is proposed to counteract the "mismatched" lumped disturbances from the output channels. The proposed method significantly extends the applicability of the DOBC methods. Rigorous stability analysis of the closed-loop system with the proposed method is established under mild assumptions. The proposed method is applied to a nonlinear MAGnetic LEViation (MAGLEV) suspension system. Simulation shows that compared to the widely used integral control method, the proposed method provides significantly improved disturbance rejection and robustness against load variation. Copyright © 2011 ISA. Published by Elsevier Ltd. All rights reserved.

  4. Fast vigilance decrement in closed head injury patients as reflected by the mismatch negativity (MMN).

    Science.gov (United States)

    Kaipio, M L; Novitski, N; Tervaniemi, M; Alho, K; Ohman, J; Salonen, O; Näätänen, R

    2001-05-25

    Event-related potentials (ERPs) were measured from 24 chronic closed head injury (CHI) patients and 18 age- and education-matched controls. The oddball paradigm was applied while subjects were watching a silent movie. The standard (p=0.8) sound of 75 ms duration had a basic frequency of 500 Hz with harmonic partials of 1000 Hz and 1500 Hz, whereas these frequencies for the pitch deviant were each 10% higher. The frequencies of the duration deviant matched with those of the standard but was 25 ms in duration. The MMN (mismatch negativity), generated by the brain's automatic auditory change-detector mechanism, was elicited by both deviants. No significant differences in the MMN latency or amplitude for either pitch or duration deviants were found between the groups. However, the MMN amplitude for the pitch deviant decreased in the patient group during the experiment considerably faster than in controls, suggesting a faster vigilance decrement in the patients.

  5. Mode-mismatched confocal thermal-lens microscope with collimated probe beam

    Energy Technology Data Exchange (ETDEWEB)

    Cabrera, Humberto, E-mail: hcabrera@ictp.it [SPIE-ICTP Anchor Research Laboratory, International Centre for Theoretical Physics (ICTP), Strada Costiera 11, Trieste (Italy); Centro Multidisciplinartio de Ciencias, Instituto Venezolano de Investigaciones Científicas (IVIC), Mérida 5101 (Venezuela, Bolivarian Republic of); Korte, Dorota; Franko, Mladen [Laboratory for Environmental Research, University of Nova Gorica, Vipavska 13, 5000 Nova Gorica (Slovenia)

    2015-05-15

    We report a thermal lens microscope (TLM) based on an optimized mode-mismatched configuration. It takes advantage of the coaxial counter propagating tightly focused excitation and collimated probe beams, instead of both focused at the sample, as it is in currently known TLM setups. A simple mathematical model that takes into account the main features of the instrument is presented. The confocal detection scheme and the introduction of highly collimated probe beam allow enhancing the versatility, limit of detection (LOD), and sensitivity of the instrument. The theory is experimentally verified measuring ethanol’s absorption coefficient at 532.8 nm. Additionally, the presented technique is applied for detection of ultra-trace amounts of Cr(III) in liquid solution. The achieved LOD is 1.3 ppb, which represents 20-fold enhancement compared to transmission mode spectrometric techniques and a 7.5-fold improvement compared to previously reported methods for Cr(III) based on thermal lens effect.

  6. Mismatch negativity and P3a amplitude in young adolescents with first-episode psychosis

    DEFF Research Database (Denmark)

    Rydkjær, J.; Møllegaard Jepsen, J. R.; Pagsberg, A. K.

    2017-01-01

    Background Deficient mismatch negativity (MMN) has been proposed as a candidate biomarker in schizophrenia and may therefore be potentially useful in early identification and intervention in early onset psychosis. In this study we explored whether deficits in the automatic orienting and reorienting...... responses, measured as MMN and P3a amplitude, are present in young adolescents with first-episode psychosis (FEP) and whether findings are specific to psychosis compared to young adolescents with attention deficit hyperactivity disorder (ADHD). Method MMN and P3a amplitude were assessed in young adolescents...... (age 12-17 years) with either FEP (N = 27) or ADHD (N = 28) and age- and gender-matched healthy controls (N = 43). The MMN paradigm consisted of a four-tone auditory oddball task with deviant stimuli based on frequency, duration and their combination. Results Significantly less MMN was found...

  7. Mismatch between diagnostic reports and special educational needs classification in a public educational system

    Directory of Open Access Journals (Sweden)

    Maria Cristina Triguero Veloz Teixeira

    Full Text Available ABSTRACT Objective To assess the diagnostic status, the sociodemographic and health profiles for students with special educational needs (SEN in a public educational system, and to map their use of educational/social services. Methods The sample comprised 1,202 SEN students from a total of 59,344 students. Results Only 792 students of the 1,202 had an established diagnosis. The most prevalent SEN condition was intellectual disability. There was a low percentage (29.4% of use of specialized educational services or support. It was found that, for some neurodevelopmental disorders, prevalence data suggest an under-reporting in the school system. Conclusion Results suggest that there is a mismatch between the diagnostic reports and the SEN condition legally recognized according to Brazilian law, in addition to the under-reporting and under specialized service use of students with disabilities.

  8. Global mismatch between fishing dependency and larval supply from marine reserves

    Science.gov (United States)

    Andrello, Marco; Guilhaumon, François; Albouy, Camille; Parravicini, Valeriano; Scholtens, Joeri; Verley, Philippe; Barange, Manuel; Sumaila, U. Rashid; Manel, Stéphanie; Mouillot, David

    2017-07-01

    Marine reserves are viewed as flagship tools to protect exploited species and to contribute to the effective management of coastal fisheries. Yet, the extent to which marine reserves are globally interconnected and able to effectively seed areas, where fisheries are most critical for food and livelihood security is largely unknown. Using a hydrodynamic model of larval dispersal, we predict that most marine reserves are not interconnected by currents and that their potential benefits to fishing areas are presently limited, since countries with high dependency on coastal fisheries receive very little larval supply from marine reserves. This global mismatch could be reversed, however, by placing new marine reserves in areas sufficiently remote to minimize social and economic costs but sufficiently connected through sea currents to seed the most exploited fisheries and endangered ecosystems.

  9. The sound of music: Differentiating musicians using a fast, musical multi-feature mismatch negativity paradigm

    DEFF Research Database (Denmark)

    Vuust, Peter; Brattico, Elvira; Seppänen, Miia

    2012-01-01

    to the other deviants in jazz musicians and left lateralization of the MMN to timbre in classical musicians. These findings indicate that the characteristics of the style/genre of music played by musicians influence their perceptual skills and the brain processing of sound features embedded in a musical......Musicians' skills in auditory processing depend highly on instrument, performance practice, and on level of expertise. Yet, it is not known though whether the style/genre of music might shape auditory processing in the brains of musicians. Here, we aimed at tackling the role of musical style....../genre on modulating neural and behavioral responses to changes in musical features. Using a novel, fast and musical sounding multi-feature paradigm, we measured the mismatch negativity (MMN), a pre-attentive brain response, to six types of musical feature change in musicians playing three distinct styles of music...

  10. Assessment of Mismatch at Indicated Level of the Upper Side Zone of LZC on abnormal operations

    International Nuclear Information System (INIS)

    Kim, Sung-Min; Park, Joong-Woo; Kho, Dae-Hack; Seo, Hyung-Beom; Han, Bong-Gyun; Moon, Jin-Soo

    2006-01-01

    Liquid Zone Control System of CANDU reactor provides bulk and spatial control. This system has produced abnormal operations with water level increase due to refueling since 1998. The abnormal operations of LZC system at Wolsong 2 can be divided into two periods. One is the sudden drop with continuous operation mode of LZC compressor and the other one is cycling with the on-off operation mode of the LZC compressor. It is identified through the communication with other CANDU reactors that this phenomenon is not unique to Wolsong. Whenever the upper side zone (1,8,6,13) level exceeded 80%, these abnormal operations occurred and mismatch between indicated and actual zone level was found. Counter-plan is prepared to ease these abnormal operations by physicist own efforts at Wolsong 2

  11. On Transform Domain Communication Systems under Spectrum Sensing Mismatch: A Deterministic Analysis.

    Science.gov (United States)

    Jin, Chuanxue; Hu, Su; Huang, Yixuan; Luo, Qu; Huang, Dan; Li, Yi; Gao, Yuan; Cheng, Shaochi

    2017-07-08

    Towards the era of mobile Internet and the Internet of Things (IoT), numerous sensors and devices are being introduced and interconnected. To support such an amount of data traffic, traditional wireless communication technologies are facing challenges both in terms of the increasing shortage of spectrum resources and massive multiple access. The transform-domain communication system (TDCS) is considered as an alternative multiple access system, where 5G and mobile IoT are mainly focused. However, previous studies about TDCS are under the assumption that the transceiver has the global spectrum information, without the consideration of spectrum sensing mismatch (SSM). In this paper, we present the deterministic analysis of TDCS systems under arbitrary given spectrum sensing scenarios, especially the influence of the SSM pattern to the signal to noise ratio (SNR) performance. Simulation results show that arbitrary SSM pattern can lead to inferior bit error rate (BER) performance.

  12. Mismatch between diagnostic reports and special educational needs classification in a public educational system.

    Science.gov (United States)

    Teixeira, Maria Cristina Triguero Veloz; Brunoni, Décio; Carreiro, Luiz Renato Rodrigues; Braga, Ana Claudia; Silva, Naiara Adorna da; Paula, Cristiane Silvestre

    2017-04-01

    To assess the diagnostic status, the sociodemographic and health profiles for students with special educational needs (SEN) in a public educational system, and to map their use of educational/social services. The sample comprised 1,202 SEN students from a total of 59,344 students. Only 792 students of the 1,202 had an established diagnosis. The most prevalent SEN condition was intellectual disability. There was a low percentage (29.4%) of use of specialized educational services or support. It was found that, for some neurodevelopmental disorders, prevalence data suggest an under-reporting in the school system. Results suggest that there is a mismatch between the diagnostic reports and the SEN condition legally recognized according to Brazilian law, in addition to the under-reporting and under specialized service use of students with disabilities.

  13. Influence of plasticity mismatch and porosity on mechanical behavior of nanoscale Ag/W multilayers

    International Nuclear Information System (INIS)

    Wen, S.P.; Zong, R.L.; Zeng, F.; Gao, Y.; Pan, F.

    2007-01-01

    Ag/W multilayers with periodicity ranging from 15 to 200 nm were deposited by direct current magnetron sputtering. The microstructure, hardness and elastic modulus were investigated by X-ray diffraction, Rutherford backscattering, X-ray fluorescence, scanning electron microscopy and nanoindentation. The results show that multilayers with periodicity less than 50 nm have columnar porous structure, which leads to low modulus and brittle fracture. Multilayers with periodicity larger than 50 nm have continuous laminated structure, and they are relatively ductile. All the multilayers have abnormal low hardness far less than a rule of mixture value, which has been attributed to porous structure and the deformation localization due to the plasticity mismatch between Ag and W

  14. A discrete element model of brittle damages generated by thermal expansion mismatch of heterogeneous media

    Directory of Open Access Journals (Sweden)

    André Damien

    2017-01-01

    Full Text Available At the macroscopic scale, such media as rocks or ceramics can be seen as homogeneous continuum. However, at the microscopic scale these materials involve sophisticated micro-structures that mix several phases. Generally, these micro-structures are composed by a large amount of inclusions embedded in a brittle matrix that ensures the cohesion of the structure. These materials generally exhibit complex non linear mechanical behaviors that result from the interactions between the different phases. This paper proposes to study the impact of the diffuse damages that result from the thermal expansion mismatch between the phases in presence. The Discrete Element Method (DEM that naturally take into account discontinuities is proposed to study these phenomena.

  15. Exponential synchronization of chaotic systems with time-varying delays and parameter mismatches via intermittent control.

    Science.gov (United States)

    Cai, Shuiming; Hao, Junjun; Liu, Zengrong

    2011-06-01

    This paper studies the synchronization of coupled chaotic systems with time-varying delays in the presence of parameter mismatches by means of periodically intermittent control. Some novel and useful quasisynchronization criteria are obtained by using the methods which are different from the techniques employed in the existing works, and the derived results are less conservative. Especially, a strong constraint on the control width that the control width should be larger than the time delay imposed by the current references is released in this paper. Moreover, our results show that the synchronization criteria depend on the ratio of control width to control period, but not the control width or the control period. Finally, some numerical simulations are given to show the effectiveness of the theoretical results.

  16. When the face fits: recognition of celebrities from matching and mismatching faces and voices.

    Science.gov (United States)

    Stevenage, Sarah V; Neil, Greg J; Hamlin, Iain

    2014-01-01

    The results of two experiments are presented in which participants engaged in a face-recognition or a voice-recognition task. The stimuli were face-voice pairs in which the face and voice were co-presented and were either "matched" (same person), "related" (two highly associated people), or "mismatched" (two unrelated people). Analysis in both experiments confirmed that accuracy and confidence in face recognition was consistently high regardless of the identity of the accompanying voice. However accuracy of voice recognition was increasingly affected as the relationship between voice and accompanying face declined. Moreover, when considering self-reported confidence in voice recognition, confidence remained high for correct responses despite the proportion of these responses declining across conditions. These results converged with existing evidence indicating the vulnerability of voice recognition as a relatively weak signaller of identity, and results are discussed in the context of a person-recognition framework.

  17. Synchronous glioblastoma and medulloblastoma in a child with mismatch repair mutation.

    Science.gov (United States)

    Amayiri, Nisreen; Al-Hussaini, Maysa; Swaidan, Maisa; Jaradat, Imad; Qandeel, Monther; Tabori, Uri; Hawkins, Cynthia; Musharbash, Awni; Alsaad, Khulood; Bouffet, Eric

    2016-03-01

    Synchronous primary malignant brain tumors are rare. We present a 5-year-old boy with synchronous glioblastoma and medulloblastoma. Both tumor samples had positive p53 stain and loss of PMS2 and MLH1 stains. The child had multiple café au lait spots and a significant family history of cancer. After subtotal resection of both tumors, he received craniospinal radiation with concomitant temozolomide followed by chemotherapy, alternating cycles of cisplatin/lomustine/vincristine with temozolomide. Then, he started maintenance treatment with cis-retinoic acid (100 mg/m(2)/day for 21 days). He remained asymptomatic for 34 months despite a follow-up brain MRI consistent with glioblastoma relapse 9 months before his death. Cis-retinoic acid may have contributed to prolong survival in this child with a probable biallelic mismatch repair syndrome.

  18. Gas Source Techniques for Molecular Beam Epitaxy of Highly Mismatched Ge Alloys

    Directory of Open Access Journals (Sweden)

    Chad A. Stephenson

    2016-12-01

    Full Text Available Ge and its alloys are attractive candidates for a laser compatible with silicon integrated circuits. Dilute germanium carbide (Ge1−xCx offers a particularly interesting prospect. By using a precursor gas with a Ge4C core, C can be preferentially incorporated in substitutional sites, suppressing interstitial and C cluster defects. We present a method of reproducible and upscalable gas synthesis of tetrakis(germylmethane, or (H3Ge4C, followed by the design of a hybrid gas/solid-source molecular beam epitaxy system and subsequent growth of defect-free Ge1−xCx by molecular beam epitaxy (MBE. Secondary ion mass spectroscopy, transmission electron microscopy and contactless electroreflectance confirm the presence of carbon with very high crystal quality resulting in a decrease in the direct bandgap energy. This technique has broad applicability to growth of highly mismatched alloys by MBE.

  19. Replication Stalling and Heteroduplex Formation within CAG/CTG Trinucleotide Repeats by Mismatch Repair

    KAUST Repository

    Viterbo, David

    2016-03-16

    Trinucleotide repeat expansions are responsible for at least two dozen neurological disorders. Mechanisms leading to these large expansions of repeated DNA are still poorly understood. It was proposed that transient stalling of the replication fork by the repeat tract might trigger slippage of the newly-synthesized strand over its template, leading to expansions or contractions of the triplet repeat. However, such mechanism was never formally proven. Here we show that replication fork pausing and CAG/CTG trinucleotide repeat instability are not linked, stable and unstable repeats exhibiting the same propensity to stall replication forks when integrated in a yeast natural chromosome. We found that replication fork stalling was dependent on the integrity of the mismatch-repair system, especially the Msh2p-Msh6p complex, suggesting that direct interaction of MMR proteins with secondary structures formed by trinucleotide repeats in vivo, triggers replication fork pauses. We also show by chromatin immunoprecipitation that Msh2p is enriched at trinucleotide repeat tracts, in both stable and unstable orientations, this enrichment being dependent on MSH3 and MSH6. Finally, we show that overexpressing MSH2 favors the formation of heteroduplex regions, leading to an increase in contractions and expansions of CAG/CTG repeat tracts during replication, these heteroduplexes being dependent on both MSH3 and MSH6. These heteroduplex regions were not detected when a mutant msh2-E768A gene in which the ATPase domain was mutated was overexpressed. Our results unravel two new roles for mismatch-repair proteins: stabilization of heteroduplex regions and transient blocking of replication forks passing through such repeats. Both roles may involve direct interactions between MMR proteins and secondary structures formed by trinucleotide repeat tracts, although indirect interactions may not be formally excluded.

  20. Application of the simplified J-estimation scheme Aramis to mismatching welds in CCP

    International Nuclear Information System (INIS)

    Eripret, C.; Franco, C.; Gilles, P.

    1995-01-01

    The J-based criteria give reasonable predictions of the failure behaviour of ductile cracked metallic structures, even if the material characterization may be sensitive to the size of the specimens. However in cracked welds, this phenomenon due to stress triaxiality effects could be enhanced. Furthermore, the application of conventional methods of toughness measurement (ESIS or ASTM standard) have evidenced a strong influence of the portion of the weld metal in the specimen. Several authors have shown the inadequacy of the simplified J-estimation methods developed for homogeneous materials. These heterogeneity effects mainly related to the mismatch ratio (ratio of weld metal yield strength upon base metal yield strength) as well as to the geometrical parameter h/W-a (weld width upon ligament size). In order to make decisive progress in this field, the Atomic Energy Commission (CEA), the PWR manufacturer FRAMATOME, and the French utility (EDF) have launched a large research program on cracked piping welds behaviour. As part of this program, a new J-estimation scheme, so called ARAMIS, has been developed to account for the influence of both materials, i.e. base metal and weld metal, on the structural resistance of cracked welds. It has been shown that, when the mismatch is high, and when the ligament size is small compared to the weld width, a classical J-based method using the softer material properties is very conservative. On the opposite the ARAMIS method provides a good estimate of J, because it predicts pretty well the shift of the cracked weld limit load, due to the presence of the weld. the influence of geometrical parameters such as crack size, weld width, or specimen length is property accounted for. (authors). 23 refs., 8 figs., 1 tab., 1 appendix

  1. Association of common variants in mismatch repair genes and breast cancer susceptibility: a multigene study

    International Nuclear Information System (INIS)

    Conde, João; Silva, Susana N; Azevedo, Ana P; Teixeira, Valdemar; Pina, Julieta Esperança; Rueff, José; Gaspar, Jorge F

    2009-01-01

    MMR is responsible for the repair of base-base mismatches and insertion/deletion loops. Besides this, MMR is also associated with an anti-recombination function, suppressing homologous recombination. Losses of heterozygosity and/or microsatellite instability have been detected in a large number of skin samples from breast cancer patients, suggesting a potential role of MMR in breast cancer susceptibility. We carried out a hospital-based case-control study in a Caucasian Portuguese population (287 cases and 547 controls) to estimate the susceptibility to non-familial breast cancer associated with some polymorphisms in mismatch repair genes (MSH3, MSH4, MSH6, MLH1, MLH3, PMS1 and MUTYH). Using unconditional logistic regression we found that MLH3 (L844P, G>A) polymorphism GA (Leu/Pro) and AA (Pro/Pro) genotypes were associated with a decreased risk: OR = 0.65 (0.45-0.95) (p = 0.03) and OR = 0.62 (0.41-0.94) (p = 0.03), respectively. Analysis of two-way SNP interaction effects on breast cancer revealed two potential associations to breast cancer susceptibility: MSH3 Ala1045Thr/MSH6 Gly39Glu - AA/TC [OR = 0.43 (0.21-0.83), p = 0.01] associated with a decreased risk; and MSH4 Ala97Thr/MLH3 Leu844Pro - AG/AA [OR = 2.35 (1.23-4.49), p = 0.01], GG/AA [OR = 2.11 (1.12-3,98), p = 0.02], and GG/AG [adjusted OR = 1.88 (1.12-3.15), p = 0.02] all associated with an increased risk for breast cancer. It is possible that some of these common variants in MMR genes contribute significantly to breast cancer susceptibility. However, further studies with a large sample size will be needed to support our results

  2. Impedance Mismatch study between the Microwave Generator and the PUPR Plasma Machine

    International Nuclear Information System (INIS)

    Gaudier, Jorge R.; Castellanos, Ligeia; Encarnacion, Kabir; Zavala, Natyaliz; Rivera, Ramon; Farahat, Nader; Leal, Edberto

    2006-01-01

    Impedance mismatch inside the connection from the microwave power generator to the plasma machine is studied. A magnetron power generator transmits microwaves of 2.45 GHz and variable power from 50W to 5000W, through a flexible rectangular waveguide to heat plasma inside a Mirror Cusp devise located at the Polytechnic University of Puerto Rico. Before the production of plasma, the residual gas of the devise must be extracted by a vacuum system (5Torr or better), then Argon gas is injected to the machine. The microwaves heat the Argon ions to initiate ionization and plasma is produced. A dielectric wall is used inside the rectangular waveguide to isolate the plasma machine and maintain vacuum. Even though the dielectric will not block the wave propagation, some absorption of microwaves will occur. This absorption will cause reflection, reducing the efficiency of the power transfer. Typically a thin layer of Teflon is used, but measurements using this dielectric show a significant reflection of power back to the generator. Due to the high-power nature of the generator (5KW), this mismatch is not desirable. An electromagnetic field solver based on the Finite Difference Time Domain Method(FDTD) is used to model the rectangular waveguide connection. The characteristic impedance of the simulation is compared with the analytical formula expression and a good agreement is obtain. Furthermore the Teflon-loaded guide is modeled using the above program and the input impedance is computed. The reflection coefficient is calculated based on the transmission line theory with the characteristic and input impedances. Based on the simulation results it is possible to optimize the thickness, shape and dielectric constant of the material, in order to seal the connection with a better match

  3. Replication Stalling and Heteroduplex Formation within CAG/CTG Trinucleotide Repeats by Mismatch Repair

    KAUST Repository

    Viterbo, David; Michoud, Gregoire; Mosbach, Valentine; Dujon, Bernard; Richard, Guy-Franck

    2016-01-01

    Trinucleotide repeat expansions are responsible for at least two dozen neurological disorders. Mechanisms leading to these large expansions of repeated DNA are still poorly understood. It was proposed that transient stalling of the replication fork by the repeat tract might trigger slippage of the newly-synthesized strand over its template, leading to expansions or contractions of the triplet repeat. However, such mechanism was never formally proven. Here we show that replication fork pausing and CAG/CTG trinucleotide repeat instability are not linked, stable and unstable repeats exhibiting the same propensity to stall replication forks when integrated in a yeast natural chromosome. We found that replication fork stalling was dependent on the integrity of the mismatch-repair system, especially the Msh2p-Msh6p complex, suggesting that direct interaction of MMR proteins with secondary structures formed by trinucleotide repeats in vivo, triggers replication fork pauses. We also show by chromatin immunoprecipitation that Msh2p is enriched at trinucleotide repeat tracts, in both stable and unstable orientations, this enrichment being dependent on MSH3 and MSH6. Finally, we show that overexpressing MSH2 favors the formation of heteroduplex regions, leading to an increase in contractions and expansions of CAG/CTG repeat tracts during replication, these heteroduplexes being dependent on both MSH3 and MSH6. These heteroduplex regions were not detected when a mutant msh2-E768A gene in which the ATPase domain was mutated was overexpressed. Our results unravel two new roles for mismatch-repair proteins: stabilization of heteroduplex regions and transient blocking of replication forks passing through such repeats. Both roles may involve direct interactions between MMR proteins and secondary structures formed by trinucleotide repeat tracts, although indirect interactions may not be formally excluded.

  4. A typology of time-scale mismatches and behavioral interventions to diagnose and solve conservation problems

    Science.gov (United States)

    Wilson, Robyn S.; Hardisty, David J.; Epanchin-Niell, Rebecca S.; Runge, Michael C.; Cottingham, Kathryn L.; Urban, Dean L.; Maguire, Lynn A.; Hastings, Alan; Mumby, Peter J.; Peters, Debra P.C.

    2016-01-01

    Ecological systems often operate on time scales significantly longer or shorter than the time scales typical of human decision making, which causes substantial difficulty for conservation and management in socioecological systems. For example, invasive species may move faster than humans can diagnose problems and initiate solutions, and climate systems may exhibit long-term inertia and short-term fluctuations that obscure learning about the efficacy of management efforts in many ecological systems. We adopted a management-decision framework that distinguishes decision makers within public institutions from individual actors within the social system, calls attention to the ways socioecological systems respond to decision makers’ actions, and notes institutional learning that accrues from observing these responses. We used this framework, along with insights from bedeviling conservation problems, to create a typology that identifies problematic time-scale mismatches occurring between individual decision makers in public institutions and between individual actors in the social or ecological system. We also considered solutions that involve modifying human perception and behavior at the individual level as a means of resolving these problematic mismatches. The potential solutions are derived from the behavioral economics and psychology literature on temporal challenges in decision making, such as the human tendency to discount future outcomes at irrationally high rates. These solutions range from framing environmental decisions to enhance the salience of long-term consequences, to using structured decision processes that make time scales of actions and consequences more explicit, to structural solutions aimed at altering the consequences of short-sighted behavior to make it less appealing. Additional application of these tools and long-term evaluation measures that assess not just behavioral changes but also associated changes in ecological systems are needed.

  5. A typology of time-scale mismatches and behavioral interventions to diagnose and solve conservation problems.

    Science.gov (United States)

    Wilson, Robyn S; Hardisty, David J; Epanchin-Niell, Rebecca S; Runge, Michael C; Cottingham, Kathryn L; Urban, Dean L; Maguire, Lynn A; Hastings, Alan; Mumby, Peter J; Peters, Debra P C

    2016-02-01

    Ecological systems often operate on time scales significantly longer or shorter than the time scales typical of human decision making, which causes substantial difficulty for conservation and management in socioecological systems. For example, invasive species may move faster than humans can diagnose problems and initiate solutions, and climate systems may exhibit long-term inertia and short-term fluctuations that obscure learning about the efficacy of management efforts in many ecological systems. We adopted a management-decision framework that distinguishes decision makers within public institutions from individual actors within the social system, calls attention to the ways socioecological systems respond to decision makers' actions, and notes institutional learning that accrues from observing these responses. We used this framework, along with insights from bedeviling conservation problems, to create a typology that identifies problematic time-scale mismatches occurring between individual decision makers in public institutions and between individual actors in the social or ecological system. We also considered solutions that involve modifying human perception and behavior at the individual level as a means of resolving these problematic mismatches. The potential solutions are derived from the behavioral economics and psychology literature on temporal challenges in decision making, such as the human tendency to discount future outcomes at irrationally high rates. These solutions range from framing environmental decisions to enhance the salience of long-term consequences, to using structured decision processes that make time scales of actions and consequences more explicit, to structural solutions aimed at altering the consequences of short-sighted behavior to make it less appealing. Additional application of these tools and long-term evaluation measures that assess not just behavioral changes but also associated changes in ecological systems are needed. © 2015

  6. The plant virus microscope image registration method based on mismatches removing.

    Science.gov (United States)

    Wei, Lifang; Zhou, Shucheng; Dong, Heng; Mao, Qianzhuo; Lin, Jiaxiang; Chen, Riqing

    2016-01-01

    The electron microscopy is one of the major means to observe the virus. The view of virus microscope images is limited by making specimen and the size of the camera's view field. To solve this problem, the virus sample is produced into multi-slice for information fusion and image registration techniques are applied to obtain large field and whole sections. Image registration techniques have been developed in the past decades for increasing the camera's field of view. Nevertheless, these approaches typically work in batch mode and rely on motorized microscopes. Alternatively, the methods are conceived just to provide visually pleasant registration for high overlap ratio image sequence. This work presents a method for virus microscope image registration acquired with detailed visual information and subpixel accuracy, even when overlap ratio of image sequence is 10% or less. The method proposed focus on the correspondence set and interimage transformation. A mismatch removal strategy is proposed by the spatial consistency and the components of keypoint to enrich the correspondence set. And the translation model parameter as well as tonal inhomogeneities is corrected by the hierarchical estimation and model select. In the experiments performed, we tested different registration approaches and virus images, confirming that the translation model is not always stationary, despite the fact that the images of the sample come from the same sequence. The mismatch removal strategy makes building registration of virus microscope images at subpixel accuracy easier and optional parameters for building registration according to the hierarchical estimation and model select strategies make the proposed method high precision and reliable for low overlap ratio image sequence. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Rhythmic and melodic deviations in musical sequences recruit different cortical areas for mismatch detection

    Directory of Open Access Journals (Sweden)

    Claudia eLappe

    2013-06-01

    Full Text Available The mismatch negativity (MMN, an event-related potential (ERP representing the violation of an acoustic regularity, is considered as a pre-attentive change detection mechanism at the sensory level on the one hand and as a prediction error signal on the other hand, suggesting that bottom-up as well as top-down processes are involved in its generation. Rhythmic and melodic deviations within a musical sequence elicit a mismatch negativity in musically trained subjects, indicating that acquired musical expertise leads to better discrimination accuracy of musical material and better predictions about upcoming musical events. Expectation violations to musical material could therefore recruit neural generators that reflect top-down processes that are based on musical knowledge.We describe the neural generators of the musical MMN for rhythmic and melodic material after a short-term sensorimotor-auditory training. We compare the localization of musical MMN data from two previous MEG studies by applying beamformer analysis. One study focused on the melodic harmonic progression whereas the other study focused on rhythmic progression. The MMN to melodic deviations revealed significant right hemispheric neural activation in the superior temporal gyrus (STG, inferior frontal cortex (IFC, and the superior frontal (SFG and orbitofrontal (OFG gyri. IFC and SFG activation was also observed in the left hemisphere. In contrast, beamformer analysis of the data from the rhythm study revealed bilatral activation within the vicinity of auditory cortices and in the inferior parietal lobule, an area that has recently been implied in temporal processing. We conclude that different cortical networks are activated in the analysis of the temporal and the melodic content of musical material, and discuss these networks in the context of the the dual-pathway model of auditory processing.

  8. Influence of oxidized purine processing on strand directionality of mismatch repair.

    Science.gov (United States)

    Repmann, Simone; Olivera-Harris, Maite; Jiricny, Josef

    2015-04-17

    Replicative DNA polymerases are high fidelity enzymes that misincorporate nucleotides into nascent DNA with a frequency lower than [1/10(5)], and this precision is improved to about [1/10(7)] by their proofreading activity. Because this fidelity is insufficient to replicate most genomes without error, nature evolved postreplicative mismatch repair (MMR), which improves the fidelity of DNA replication by up to 3 orders of magnitude through correcting biosynthetic errors that escaped proofreading. MMR must be able to recognize non-Watson-Crick base pairs and excise the misincorporated nucleotides from the nascent DNA strand, which carries by definition the erroneous genetic information. In eukaryotes, MMR is believed to be directed to the nascent strand by preexisting discontinuities such as gaps between Okazaki fragments in the lagging strand or breaks in the leading strand generated by the mismatch-activated endonuclease of the MutL homologs PMS1 in yeast and PMS2 in vertebrates. We recently demonstrated that the eukaryotic MMR machinery can make use also of strand breaks arising during excision of uracils or ribonucleotides from DNA. We now show that intermediates of MutY homolog-dependent excision of adenines mispaired with 8-oxoguanine (G(O)) also act as MMR initiation sites in extracts of human cells or Xenopus laevis eggs. Unexpectedly, G(O)/C pairs were not processed in these extracts and failed to affect MMR directionality, but extracts supplemented with exogenous 8-oxoguanine DNA glycosylase (OGG1) did so. Because OGG1-mediated excision of G(O) might misdirect MMR to the template strand, our findings suggest that OGG1 activity might be inhibited during MMR. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Brain responses to audiovisual speech mismatch in infants are associated with individual differences in looking behaviour.

    Science.gov (United States)

    Kushnerenko, Elena; Tomalski, Przemyslaw; Ballieux, Haiko; Ribeiro, Helena; Potton, Anita; Axelsson, Emma L; Murphy, Elizabeth; Moore, Derek G

    2013-11-01

    Research on audiovisual speech integration has reported high levels of individual variability, especially among young infants. In the present study we tested the hypothesis that this variability results from individual differences in the maturation of audiovisual speech processing during infancy. A developmental shift in selective attention to audiovisual speech has been demonstrated between 6 and 9 months with an increase in the time spent looking to articulating mouths as compared to eyes (Lewkowicz & Hansen-Tift. (2012) Proc. Natl Acad. Sci. USA, 109, 1431-1436; Tomalski et al. (2012) Eur. J. Dev. Psychol., 1-14). In the present study we tested whether these changes in behavioural maturational level are associated with differences in brain responses to audiovisual speech across this age range. We measured high-density event-related potentials (ERPs) in response to videos of audiovisually matching and mismatched syllables /ba/ and /ga/, and subsequently examined visual scanning of the same stimuli with eye-tracking. There were no clear age-specific changes in ERPs, but the amplitude of audiovisual mismatch response (AVMMR) to the combination of visual /ba/ and auditory /ga/ was strongly negatively associated with looking time to the mouth in the same condition. These results have significant implications for our understanding of individual differences in neural signatures of audiovisual speech processing in infants, suggesting that they are not strictly related to chronological age but instead associated with the maturation of looking behaviour, and develop at individual rates in the second half of the first year of life. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  10. A Kidney Graft Survival Calculator that Accounts for Mismatches in Age, Sex, HLA, and Body Size.

    Science.gov (United States)

    Ashby, Valarie B; Leichtman, Alan B; Rees, Michael A; Song, Peter X-K; Bray, Mathieu; Wang, Wen; Kalbfleisch, John D

    2017-07-07

    Outcomes for transplants from living unrelated donors are of particular interest in kidney paired donation (KPD) programs where exchanges can be arranged between incompatible donor-recipient pairs or chains created from nondirected/altruistic donors. Using Scientific Registry of Transplant Recipients data, we analyzed 232,705 recipients of kidney-alone transplants from 1998 to 2012. Graft failure rates were estimated using Cox models for recipients of kidney transplants from living unrelated, living related, and deceased donors. Models were adjusted for year of transplant and donor and recipient characteristics, with particular attention to mismatches in age, sex, human leukocyte antigens (HLA), body size, and weight. The dependence of graft failure on increasing donor age was less pronounced for living-donor than for deceased-donor transplants. Male donor-to-male recipient transplants had lower graft failure, particularly better than female to male (5%-13% lower risk). HLA mismatch was important in all donor types. Obesity of both the recipient (8%-18% higher risk) and donor (5%-11% higher risk) was associated with higher graft loss, as were donor-recipient weight ratios of transplants where both parties were of similar weight (9%-12% higher risk). These models are used to create a calculator of estimated graft survival for living donors. This calculator provides useful information to donors, candidates, and physicians of estimated outcomes and potentially in allowing candidates to choose among several living donors. It may also help inform candidates with compatible donors on the advisability of joining a KPD program. Copyright © 2017 by the American Society of Nephrology.

  11. Patient-prosthesis mismatch has no influence on in-hospital mortality after aortic valve replacement.

    Science.gov (United States)

    Yottasurodom, Chaiwut; Namthaisong, Kriengkrai; Porapakkham, Pramote; Kasemsarn, Choosak; Chotivatanapong, Taweesak; Chaiseri, Pradistchai; Wongdit, Suwannee; Yasotarin, Suwanna

    2012-08-01

    To analyze the relationship between prosthetic aortic valve orifice and body surface area (Effective Orifice Area Index, EOAI) and in-hospital mortality after aortic valve replacement. A prospective study was conducted between October 2007 to September 2010, 536 patients underwent isolated aortic valve replacement (AVR) was recorded on preoperative, operative and postoperative data. Patient Prosthesis Mismatch (PPM) was classified by Effective Orifice Area Indexed (EOAI) by prosthetic valve area divided by body surface area as mild or no significance if the EOAI is greater than 0.85 cm2/m2, moderate if between 0.65 cm2/m2 and 0.85 cm2/m2, and severe if less than 0.65 cm2/m2. Statistical differences were analyzed by Chi-square and student t-test with p-value less than 0.05 considered significant. There were 304 men, mean age was 60.98 years, mean valve orifice area 1.69 cm2, body surface area 1.60 m2, cross clamp time 1.13 hrs., bypass time 1.67 hrs. Mechanical valves were used in 274 patients (51.2%) and Bioprosthesis were used in 181 patients (48.8%). PPM was found in 33.7%, 6.7% was severe PPM, 27% was moderate PPM and 66.3% has no significant PPM Over all in-hospital mortality was 1.5%. There was no significant difference in hospital mortality between no PPM group, moderate PPM and severe PPM group (1.4% vs. 1.4% vs. 5.4%, p-value = 0.86). In a large aortic valve surgery population, moderate and severe patient prosthesis mismatch occurred in 35.6% of patients but had no influence on in-hospital mortality.

  12. Multidetector CT predictors of prosthesis-patient mismatch in transcatheter aortic valve replacement.

    Science.gov (United States)

    Freeman, Melanie; Webb, John G; Willson, Alexander B; Wheeler, Miriam; Blanke, Philipp; Moss, Robert R; Thompson, Christopher R; Munt, Brad; Norgaard, Bjarne L; Yang, Tae-Hyun; Min, James K; Poulsen, Steen; Hansson, Nicolaj C; Binder, Ronald K; Toggweiler, Stefan; Hague, Cameron; Wood, David A; Pibarot, Philippe; Leipsic, Jonathon

    2013-01-01

    Prosthesis-patient mismatch (PPM) is a predictor of mortality after aortic valve replacement (AVR). We examined whether accurate 3-dimensional annular sizing with multidetector CT (MDCT) is predictive of PPM after transcatheter AVR (TAVR). One hundred twenty-eight patients underwent MDCT then TAVR. Moderate PPM was defined as an indexed effective orifice area ≤0.85 cm²/m² and severe ≤0.65 cm²/m². MDCT annular measurements (area, short and long axis) were compared with the size of the selected transcatheter heart valve (THV) to obtain (1) the difference between prosthesis size and CT-measured mean annular diameter and (2) the percentage of undersizing or oversizing (calculated as 100 × [MDCT annular area--THV nominal area]/THV nominal area). In addition, the MDCT annular area was indexed to body surface area. These measures were evaluated as potential PPM predictors. We found that 42.2% of patients had moderate PPM and 9.4% had severe PPM. Procedural characteristics and in-hospital outcomes were similar between patients with or without PPM. THV undersizing of the mean aortic annulus diameter was not predictive of PPM (odds ratio [OR], 0.84; 95% CI, 0.65-1.07; P = .16; area under the receiver-operating characteristic curve [AUC], 0.58). THV undersizing of annular area was not predictive of PPM (OR, 0.96; 95% CI, 0.80-1.16; P = .69; AUC, 0.52). Indexed MDCT annular area was, however, predictive of PPM (OR, 0.24; 95% CI, 0.10-0.59; P < .001; AUC, 0.66). PPM is frequent after TAVR. Appropriate annular oversizing does not reduce the rate or severity of PPM. Patient annulus size mismatch, identified by indexed MDCT annular area, is a significant predictor of PPM. Copyright © 2013 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

  13. 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.

  14. Coevolution of female and male genital components to avoid genital size mismatches in sexually dimorphic spiders.

    Science.gov (United States)

    Lupše, Nik; Cheng, Ren-Chung; Kuntner, Matjaž

    2016-08-17

    In most animal groups, it is unclear how body size variation relates to genital size differences between the sexes. While most morphological features tend to scale with total somatic size, this does not necessarily hold for genitalia because divergent evolution in somatic size between the sexes would cause genital size mismatches. Theory predicts that the interplay of female-biased sexual size dimorphism (SSD) and sexual genital size dimorphism (SGD) should adhere to the 'positive genital divergence', the 'constant genital divergence', or the 'negative genital divergence' model, but these models remain largely untested. We test their validity in the spider family Nephilidae known for the highest degrees of SSD among terrestrial animals. Through comparative analyses of sex-specific somatic and genital sizes, we first demonstrate that 99 of the 351 pairs of traits are phylogenetically correlated. Through factor analyses we then group these traits for MCMCglmm analyses that test broader correlation patterns, and these reveal significant correlations in 10 out of the 36 pairwise comparisons. Both types of analyses agree that female somatic and internal genital sizes evolve independently. While sizes of non-intromittent male genital parts coevolve with male body size, the size of the intromittent male genital parts is independent of the male somatic size. Instead, male intromittent genital size coevolves with female (external and, in part, internal) genital size. All analyses also agree that SGD and SSD evolve independently. Internal dimensions of female genitalia evolve independently of female body size in nephilid spiders, and similarly, male intromittent genital size evolves independently of the male body size. The size of the male intromittent organ (the embolus) and the sizes of female internal and external genital components thus seem to respond to selection against genital size mismatches. In accord with these interpretations, we reject the validity of the

  15. Capillary/myocyte mismatch in the heart in renal failure--a role for erythropoietin?

    Science.gov (United States)

    Amann, K; Buzello, M; Simonaviciene, A; Miltenberger-Miltenyi, G; Koch, A; Nabokov, A; Gross, M L; Gless, B; Mall, G; Ritz, E

    2000-07-01

    Chronic renal failure is characterized by remodeling of the heart with left ventricular hypertrophy (increasing oxygen demand) and capillary deficit leading to capillary/myocyte mismatch (decreasing oxygen supply). Erythropoietin (Epo) has known angiogenic properties causing endothelial cell activation, migration and sprouting, mediated at least in part via the JAK/STAT (Janus kinase/signal transducers and activators of transcription) pathway. In uraemic cardiac hypertrophy the presence of diminished capillary supply implies that capillary growth does not keep pace with development of hypertrophy. To investigate whether this was due to a deficit of the angiogenic hormone Epo we examined whether Epo levels are altered and whether an increase in haematocrit by administration of rhEpo influences capillary supply, i.e. capillary/myocyte mismatch in experimental renal failure. Male Spraque-Dawley rats were either subjected to partial renal ablation or sham operation. Only modest amounts of renal tissue were removed so that the rats were not anemic. Subgroups of rats received either human (rh)Epo alone or in combination with unspecific antihypertensive treatment (dihydralazine plus furosemide) in order to control the Epo induced rise in blood pressure. Capillary supply was measured stereologically as capillary length per volume myocardium using the orientator method. Capillary length density was reduced by approximately 25% after partial renal ablation (3237+/-601 vs 4293+/-501 mm/mm(3) in controls). It was not statistically different in animals with partial renal ablation+rhEpo+antihypertensive treatment (3620+/-828 mm/mm(3)) compared to partial ablation alone. The study shows that lack of Epo does not cause, or contribute to, the deficit of capillary growth in the hypertrophied left ventricle of rats with renal failure. In addition, a rise in haematocrit is not accompanied by beneficial effects on alterations of cardiovascular structure in experimental renal failure.

  16. On the trade-off between mainlobe width and peak sidelobe level of mismatched pulse compression filters for linear chirp waveforms

    CSIR Research Space (South Africa)

    Cilliers, Jacques E

    2009-09-01

    Full Text Available that constant, extremely low sidelobe levels better than 60 dB can be achieved for minimal mismatch loss but with some broadening of the compression peak. This paper investigates the tradeoff between the sidelobe level and the mainlobe width for mismatched...

  17. Source-Sink Mismatch Causing Functional Conduction Block in Re-Entrant Ventricular Tachycardia.

    Science.gov (United States)

    Ciaccio, Edward J; Coromilas, James; Wit, Andrew L; Peters, Nicholas S; Garan, Hasan

    2018-01-01

    Ventricular tachycardia (VT) caused by a re-entrant circuit is a life-threatening arrhythmia that at present cannot always be treated adequately. A realistic model of re-entry would be helpful to accurately guide catheter ablation for interruption of the circuit. In this review, models of electrical activation wavefront propagation during onset and maintenance of re-entrant VT are discussed. In particular, the relationship between activation mapping and maps of transition in infarct border zone thickness, which results in source-sink mismatch, is considered in detail and supplemented with additional data. Based on source-sink mismatch, the re-entry isthmus can be modeled from its boundary properties. Isthmus boundary segments with large transitions in infarct border zone thickness have large source-sink mismatch, and functional block forms there during VT. These alternate with segments having lesser thickness change and therefore lesser source-sink mismatch, which act as gaps, or entrance and exit points, to the isthmus during VT. Besides post-infarction substrates, the source-sink model is likely applicable to other types of volumetric changes in the myocardial conducting medium, such as when there is presence of fibrosis or dissociation of muscle fibers. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  18. Impact of Prosthesis-Patient Mismatch on Long-term Functional Capacity After Mechanical Aortic Valve Replacement

    NARCIS (Netherlands)

    Petit-Eisenmann, H.; Epailly, E.; Velten, M.; Radojevic, J.; Eisenmann, B.; Kremer, H.; Kindo, M.

    2016-01-01

    BACKGROUND: The impact of prosthesis-patient mismatch (PPM) after aortic valve replacement (AVR) for aortic stenosis on exercise capacity remains controversial. The aim of this study was to analyze the long-term impact of PPM after mechanical AVR on maximal oxygen uptake (VO2max). METHODS: The study

  19. A 30-Year-Old Man with Three Primary Malignancies: A Case of Constitutional Mismatch Repair Deficiency

    OpenAIRE

    Rengifo-Cam, William; Jasperson, Kory; Garrido-Laguna, Ignacio; Colman, Howard; Scaife, Courtney; Samowitz, Wade; Samadder, N. Jewel

    2017-01-01

    Constitutional mismatch repair deficiency (CMMRD) is a devastating cancer predisposition syndrome for which clinical manifestations, genetic screening, and cancer prevention strategies are limited. We report a case of CMMRD presenting with metachronous colorectal cancer and brain cancer. Oncologists and gastroenterologists should be aware of the CMMRD syndrome as a rare cause of very early-onset colorectal cancer.

  20. A 30-Year-Old Man with Three Primary Malignancies: A Case of Constitutional Mismatch Repair Deficiency.

    Science.gov (United States)

    Rengifo-Cam, William; Jasperson, Kory; Garrido-Laguna, Ignacio; Colman, Howard; Scaife, Courtney; Samowitz, Wade; Samadder, N Jewel

    2017-01-01

    Constitutional mismatch repair deficiency (CMMRD) is a devastating cancer predisposition syndrome for which clinical manifestations, genetic screening, and cancer prevention strategies are limited. We report a case of CMMRD presenting with metachronous colorectal cancer and brain cancer. Oncologists and gastroenterologists should be aware of the CMMRD syndrome as a rare cause of very early-onset colorectal cancer.

  1. Completion of meiosis in male zebrafish (Danio rerio) despite lack of DNA mismatch repair gene mlh1.

    NARCIS (Netherlands)

    Leal, M.C.; Feitsma, H.; Cuppen, E.; Franca, L.R.; Schulz, R.W.

    2008-01-01

    Mlh1 is a member of DNA mismatch repair (MMR) machinery and is also essential for the stabilization of crossovers during the first meiotic division. Recently, we have shown that zebrafish mlh1 mutant males are completely infertile because of a block in metaphase I, whereas females are fertile but

  2. Functional implications of the p.Cys680Arg mutation in the MLH1 mismatch repair protein

    DEFF Research Database (Denmark)

    Dominguez-Valentin, Mev; Drost, Mark; Therkildsen, Christina

    2014-01-01

    >C missense mutation in exon 18 of the human MLH1 gene and biochemically characterization of the p.Cys680Arg mutant MLH1 protein to implicate it in the pathogenicity of the Lynch syndrome (LS). We show that the mutation is deficient in DNA mismatch repair and, therefore, contributing to LS in the carriers....

  3. Completion of meiosis in male zebrafish (Danio rerio) despite lack of DNA mismatch repair gene mlh1

    NARCIS (Netherlands)

    Leal, M.C.; Feitsma, H.; Cuppen, E.; França, L.R.; Schulz, R.W.

    2008-01-01

    Mlh1 is a member of DNA mismatch repair (MMR) machinery and is also essential for the stabilization of crossovers during the first meiotic division. Recently, we have shown that zebrafish mlh1 mutant males are completely infertile because of a block in metaphase I, whereas females are fertile

  4. Mismatch repair deficiency: a temozolomide resistance factor in medulloblastoma cell lines that is uncommon in primary medulloblastoma tumours

    NARCIS (Netherlands)

    von Bueren, A. O.; Bacolod, M. D.; Hagel, C.; Heinimann, K.; Fedier, A.; Kordes, U.; Pietsch, T.; Koster, J.; Grotzer, M. A.; Friedman, H. S.; Marra, G.; Kool, M.; Rutkowski, S.

    2012-01-01

    BACKGROUND: Tumours are responsive to temozolomide (TMZ) if they are deficient in O-6-methylguanine-DNA methyltransferase (MGMT), and mismatch repair (MMR) proficient. METHODS: The effect of TMZ on medulloblastoma (MB) cell killing was analysed with clonogenic survival assays. Expression of DNA

  5. On the effects of quantization on mismatched pulse compression filters designed using L-p norm minimization techniques

    CSIR Research Space (South Africa)

    Cilliers, Jacques E

    2007-10-01

    Full Text Available In [1] the authors introduced a technique for generating mismatched pulse compression filters for linear frequency chirp signals. The technique minimizes the sum of the pulse compression sidelobes in a p L –norm sense. It was shown that extremely...

  6. A comparative study between matched and mis-matched projection/back projection pairs used with ASIRT reconstruction method

    International Nuclear Information System (INIS)

    Guedouar, R.; Zarrad, B.

    2010-01-01

    For algebraic reconstruction techniques both forward and back projection operators are needed. The ability to perform accurate reconstruction relies fundamentally on the forward projection and back projection methods which are usually, the transpose of each other. Even though the mis-matched pairs may introduce additional errors during the iterative process, the usefulness of mis-matched projector/back projector pairs has been proved in image reconstruction. This work investigates the performance of matched and mis-matched reconstruction pairs using popular forward projectors and their transposes when used in reconstruction tasks with additive simultaneous iterative reconstruction techniques (ASIRT) in a parallel beam approach. Simulated noiseless phantoms are used to compare the performance of the investigated pairs in terms of the root mean squared errors (RMSE) which are calculated between reconstructed slices and the reference in different regions. Results show that mis-matched projection/back projection pairs can promise more accuracy of reconstructed images than matched ones. The forward projection operator performance seems independent of the choice of the back projection operator and vice versa.

  7. A comparative study between matched and mis-matched projection/back projection pairs used with ASIRT reconstruction method

    Energy Technology Data Exchange (ETDEWEB)

    Guedouar, R., E-mail: raja_guedouar@yahoo.f [Higher School of Health Sciences and Techniques of Monastir, Av. Avicenne, 5060 Monastir, B.P. 128 (Tunisia); Zarrad, B., E-mail: boubakerzarrad@yahoo.f [Higher School of Health Sciences and Techniques of Monastir, Av. Avicenne, 5060 Monastir, B.P. 128 (Tunisia)

    2010-07-21

    For algebraic reconstruction techniques both forward and back projection operators are needed. The ability to perform accurate reconstruction relies fundamentally on the forward projection and back projection methods which are usually, the transpose of each other. Even though the mis-matched pairs may introduce additional errors during the iterative process, the usefulness of mis-matched projector/back projector pairs has been proved in image reconstruction. This work investigates the performance of matched and mis-matched reconstruction pairs using popular forward projectors and their transposes when used in reconstruction tasks with additive simultaneous iterative reconstruction techniques (ASIRT) in a parallel beam approach. Simulated noiseless phantoms are used to compare the performance of the investigated pairs in terms of the root mean squared errors (RMSE) which are calculated between reconstructed slices and the reference in different regions. Results show that mis-matched projection/back projection pairs can promise more accuracy of reconstructed images than matched ones. The forward projection operator performance seems independent of the choice of the back projection operator and vice versa.

  8. The Interplay of Family Income, Campus Residency, and Student Retention (What Practitioners Should Know about Cultural Mismatch)

    Science.gov (United States)

    Schudde, Lauren

    2016-01-01

    Students from low-income families consistently trail behind their peers in retention and degree attainment. Research on college student experiences suggests that low-income students experience "cultural mismatch" at college--they feel that their backgrounds are at odds with the middle-class values dominant on campus (Armstrong &…

  9. Basic Block of Pipelined ADC Design Requirements

    Directory of Open Access Journals (Sweden)

    V. Kledrowetz

    2011-04-01

    Full Text Available The paper describes design requirements of a basic stage (called MDAC - Multiplying Digital-to- Analog Converter of a pipelined ADC. There exist error sources such as finite DC gain of opamp, capacitor mismatch, thermal noise, etc., arising when the switched capacitor (SC technique and CMOS technology are used. These non-idealities are explained and their influences on overall parameters of a pipelined ADC are studied. The pipelined ADC including non-idealities was modeled in MATLAB - Simulink simulation environment.

  10. Toward maximum transmittance into absorption layers in solar cells: investigation of lossy-film-induced mismatches between reflectance and transmittance extrema.

    Science.gov (United States)

    Chang, Yin-Jung; Lai, Chi-Sheng

    2013-09-01

    The mismatch in film thickness and incident angle between reflectance and transmittance extrema due to the presence of lossy film(s) is investigated toward the maximum transmittance design in the active region of solar cells. Using a planar air/lossy film/silicon double-interface geometry illustrates important and quite opposite mismatch behaviors associated with TE and TM waves. In a typical thin-film CIGS solar cell, mismatches contributed by TM waves in general dominate. The angular mismatch is at least 10° in about 37%-53% of the spectrum, depending on the thickness combination of all lossy interlayers. The largest thickness mismatch of a specific interlayer generally increases with the thickness of the layer itself. Antireflection coating designs for solar cells should therefore be optimized in terms of the maximum transmittance into the active region, even if the corresponding reflectance is not at its minimum.

  11. Analysis of compensatory mechanisms in the pelvis and lower extremities in patients with pelvic incidence and lumbar lordosis mismatch.

    Science.gov (United States)

    Cheng, Xiaofei; Zhang, Kai; Sun, Xiaojiang; Zhao, Changqing; Li, Hua; Zhao, Jie

    2017-07-01

    The objective was to analyze the compensatory effect of the pelvis and lower extremities on sagittal spinal malalignment in patients with pelvic incidence (PI) and lumbar lordosis (LL) mismatch. A series of parameters including PI, LL, PI-LL, thoracic kyphosis (TK), pelvic tilt (PT), sacral slope (SS), knee flexion angle (KFA), tibial obliquity angle (TOA), femoral obliquity angle (FOA), femur pelvis angle (FPA) and pelvic shift (PS) were measured. Patients with PI-LL mismatch were divided into pelvic retroversion group and pelvic retroposition group based on their PT and PS, and then the parameters were compared within the two groups and with the control group. All variables were significantly different when comparing the pelvic retroversion and retroposition group with the control group except for PI, FOA and PS in the pelvic retroversion group. The pelvic retroposition group had significantly greater value of PI-LL, PI, PT, KFA, FOA and PS and contribution ratio of FOA and PS, and smaller value of LL, TK and FPA and contribution ratio of PT, TOA and FPA compared with the pelvic retroversion group. Patients with lesser PI-LL mismatch rely more on hip extension to increase pelvic retroversion while those with greater PI-LL mismatch tend to add extra femoral obliquity. When compensating for larger PI-LL mismatch, the importance of hip extension is decreased and the effect of the knee and ankle joint becomes more important by providing greater femoral incline and relatively lesser ankle dorsiflexion respectively. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Factors of education-job mismatch among youth in Kyrgyz Republic

    Directory of Open Access Journals (Sweden)

    Burulcha B. Sulaimanova

    2018-03-01

    article which establishes the relationship between gender level of education experience economic sectors and other factors enabled to conclude that age significantly affects the opportunity to occupy a position corresponding to the level of education while age and place of residence largely determine the probability of ldquoexcessrdquo education. Scientific novelty for the first time the article examines the factors of mismatch between the education level and the labor market in Kyrgyz Republic case using empirical methods. Practical significance the main conclusions of the article can be used in scientific research and analytical studies of the mismatch between the educational services and the labor market. In addition the study results can serve as a basis for the development of employment policies by the relevant authorities.

  13. DNA mismatch repair deficiency and hereditary syndromes in Latino patients with colorectal cancer.

    Science.gov (United States)

    Ricker, Charité N; Hanna, Diana L; Peng, Cheng; Nguyen, Nathalie T; Stern, Mariana C; Schmit, Stephanie L; Idos, Greg E; Patel, Ravi; Tsai, Steven; Ramirez, Veronica; Lin, Sonia; Shamasunadara, Vinay; Barzi, Afsaneh; Lenz, Heinz-Josef; Figueiredo, Jane C

    2017-10-01

    The landscape of hereditary syndromes and clinicopathologic characteristics among US Latino/Hispanic individuals with colorectal cancer (CRC) remains poorly understood. A total of 265 patients with CRC who were enrolled in the Hispanic Colorectal Cancer Study were included in the current study. Information regarding CRC risk factors was elicited through interviews, and treatment and survival data were abstracted from clinical charts. Tumor studies and germline genetic testing results were collected from medical records or performed using standard molecular methods. The mean age of the patients at the time of diagnosis was 53.7 years (standard deviation, 10.3 years), and 48.3% were female. Overall, 21.2% of patients reported a first-degree or second-degree relative with CRC; 3.4% met Amsterdam I/II criteria. With respect to Bethesda guidelines, 38.5% of patients met at least 1 criterion. Of the 161 individuals who had immunohistochemistry and/or microsatellite instability testing performed, 21 (13.0%) had mismatch repair (MMR)-deficient (dMMR) tumors. dMMR tumors were associated with female sex (61.9%), earlier age at the time of diagnosis (50.4 ± 12.4 years), proximal location (61.9%), and first-degree (23.8%) or second-degree (9.5%) family history of CRC. Among individuals with dMMR tumors, 13 (61.9%) had a germline MMR mutation (MutL homolog 1 [MLH1] in 6 patients; MutS homolog 2 [MSH2] in 4 patients; MutS homolog 6 [MHS6] in 2 patients; and PMS1 homolog 2, mismatch repair system component [PMS2] in 1 patient). The authors identified 2 additional MLH1 mutation carriers by genetic testing who had not received immunohistochemistry/microsatellite instability testing. In total, 5.7% of the entire cohort were confirmed to have Lynch syndrome. In addition, 6 individuals (2.3%) had a polyposis phenotype. The percentage of dMMR tumors noted among Latino individuals (13%) is similar to estimates in non-Hispanic white individuals. In the current study, the majority of

  14. Numerical simulation of CTE mismatch and thermal-structural stresses in the design of interconnects

    Science.gov (United States)

    Peter, Geoffrey John M.

    With the ever-increasing chip complexity, interconnects have to be designed to meet the new challenges. Advances in optical lithography have made chip feature sizes available today at 70 nm dimensions. With advances in Extreme Ultraviolet Lithography, X-ray Lithography, and Ion Projection Lithography it is expected that the line width will further decrease to 20 nm or less. With the decrease in feature size, the number of active devices on the chip increases. With higher levels of circuit integration, the challenge is to dissipate the increased heat flux from the chip surface area. Thermal management considerations include coefficient of thermal expansion (CTE) matching to prevent failure between the chip and the board. This in turn calls for improved system performance and reliability of the electronic structural systems. Experience has shown that in most electronic systems, failures are mostly due to CTE mismatch between the chip, board, and the solder joint (solder interconnect). The resulting high thermal-structural stress and strain due to CTE mismatch produces cracks in the solder joints with eventual failure of the electronic component. In order to reduce the thermal stress between the chip, board, and the solder joint, this dissertation examines the effect of inserting wire bundle (wire interconnect) between the chip and the board. The flexibility of the wires or fibers would reduce the stress at the rigid joints. Numerical simulations of two, and three-dimensional models of the solder and wire interconnects are examined. The numerical simulation is linear in nature and is based on linear isotropic material properties. The effect of different wire material properties is examined. The effect of varying the wire diameter is studied by changing the wire diameter. A major cause of electronic equipment failure is due to fatigue failure caused by thermal cycling, and vibrations. A two-dimensional modal and harmonic analysis was simulated for the wire interconnect

  15. Pelvic incidence-lumbar lordosis mismatch predisposes to adjacent segment disease after lumbar spinal fusion.

    Science.gov (United States)

    Rothenfluh, Dominique A; Mueller, Daniel A; Rothenfluh, Esin; Min, Kan

    2015-06-01

    Several risk factors and causes of adjacent segment disease have been debated; however, no quantitative relationship to spino-pelvic parameters has been established so far. A retrospective case-control study was carried out to investigate spino-pelvic alignment in patients with adjacent segment disease compared to a control group. 45 patients (ASDis) were identified that underwent revision surgery for adjacent segment disease after on average 49 months (7-125), 39 patients were selected as control group (CTRL) similar in the distribution of the matching variables, such as age, gender, preoperative degenerative changes, and numbers of segments fused with a mean follow-up of 84 months (61-142) (total n = 84). Several radiographic parameters were measured on pre- and postoperative radiographs, including lumbar lordosis measured (LL), sacral slope, pelvic incidence (PI), and tilt. Significant differences between ASDis and CTRL groups on preoperative radiographs were seen for PI (60.9 ± 10.0° vs. 51.7 ± 10.4°, p = 0.001) and LL (48.1 ± 12.5° vs. 53.8 ± 10.8°, p = 0.012). Pelvic incidence was put into relation to lumbar lordosis by calculating the difference between pelvic incidence and lumbar lordosis (∆PILL = PI-LL, ASDis 12.5 ± 16.7° vs. CTRL 3.4 ± 12.1°, p = 0.001). A cutoff value of 9.8° was determined by logistic regression and ROC analysis and patients classified into a type A (∆PILL lordosis mismatch. In type A spino-pelvic alignment, 25.5 % of patients underwent revision surgery for adjacent segment disease, whereas 78.3 % of patients classified as type B alignment had revision surgery. Classification of patients into type A and B alignments yields a sensitivity for predicting adjacent segment disease of 71 %, a specificity of 81 % and an odds ratio of 10.6. In degenerative disease of the lumbar spine a high pelvic incidence with diminished lumbar lordosis seems to predispose to adjacent segment disease. Patients with such pelvic incidence

  16. Mismatch Negativity in Han Chinese Patients with Schizophrenia: A Meta-Analysis.

    Science.gov (United States)

    Xiong, Yanbing; Ll, Xianbin; Zhao, Lei; Wang, Chuanyue

    2017-10-25

    Previous meta-analysis revealed that mismatch negativity(MMN) amplitude decreased in patients with schizophrenia compared with healthy controls (Cohen's d, d about 1), leading to the possibility of mismatch negativity being used as a biomarker for schizophrenia. However, it is unknown whether MMN is reliably changed in Chinese patients. It is necessary to carry out a meta-analysis on MMN of Han Chinese patients with schizophrenia. To investigate whether MMN could be used as a biomarker for Han Chinese patients with schizophrenia. A literature search was conducted to identify clinical trials on MMN in Han Chinese schizophrenia patients published before May 8, 2017, by searching the Chinese language databases CNKI, WanFang Data, VIP Data and PubMed. The effects of MMN deficits were evaluated for MMN amplitude by calculating standard mean difference (SMDs) between schizophrenia patient groups and healthy control groups. A total of 11 studies were included in the analysis. The total quality of all the studies were more than 6 as evaluated by Newcastle-Ottawa Scale (NOS). Meta-analysis of data from these studies had a pooled sample of 432 patients with schizophrenia and 392 healthy controls. There exists significant MMN deficit in schizophrenia patients compared to healthy controls (Cohen's d =1.004). When studies were excluded due to heterogeneity, the pooled effect size of the MMN differences between the patient group and healthy controls dropped to 0.79 (Cohen's d =0.79). Subgroup analysis showed that MMN amplitude deficits of schizophrenia over three years had the pooled effect size of 0.95, and less than three years had the pooled effect size of 0.77. Publication bias conducted via Egger regression test ( t = 1.83; p = 0.101), suggested that there was no publication bias. The effect size of MMN amplitude between Chinese patients with schizophrenia and healthy controls is consistent with other meta-analyses published on this topic, suggesting that Han Chinese

  17. Stent valve implantation in conventional redo aortic valve surgery to prevent patient-prosthesis mismatch.

    Science.gov (United States)

    Ferrari, Enrico; Franciosi, Giorgio; Clivio, Sara; Faletra, Francesco; Moccetti, Marco; Moccetti, Tiziano; Pedrazzini, Giovanni; Demertzis, Stefanos

    2017-03-01

    The goal was to show the technical details, feasibility and clinical results of balloon-expandable stent valve implantation in the aortic position during conventional redo open-heart surgery in selected obese patients with a small aortic prosthesis and severe patient-prosthesis mismatch. Two symptomatic overweight patients (body mass index of 31 and 38), each with a small aortic prosthesis (a 4-year-old, 21-mm Hancock II biological valve and a 29-year-old, 23-mm Duromedic mechanical valve), increased transvalvular gradients (59/31 and 74/44 mmHg) and a reduced indexed effective orifice area (0.50 and 0.43 cm 2 /m 2 ) underwent implantation of two 26-mm balloon-expandable Sapien 3 valves during standard on-pump redo valve surgery. Using full re-sternotomy, cardiopulmonary bypass and cardioplegic arrest, the two balloon-expandable stent valves were implanted under direct view using a standard aortotomy, after prosthesis removal and without annulus enlargement. Aortic cross-clamp times were 162 and 126 min; cardiopulmonary bypass times were 178 and 180 min; total surgical times were 360 and 318 min. At discharge, echocardiograms showed transvalvular peak and mean gradients of 13/9 and 23/13 mmHg and indexed effective orifice areas of 0.64 and 1.08 cm 2 /m 2 . The 3-month echocardiographic follow-up showed transvalvular peak and mean gradients of 18/9 and 19/11 mmHg and indexed effective orifice areas of 0.78 cm 2 /m 2 and 0.84 cm 2 /m 2 , with improved symptoms (New York Heart Association class 1). Implantation of a balloon-expandable stent valve during redo aortic valve surgery is feasible in selected cases and prevents patient-prosthesis mismatch in obese patients without need for aortic annulus enlargement. Moreover, in the case of stent valve degeneration, this approach permits additional valve-in-valve procedures with large stent valves and prevents re-redo surgery. © The Author 2016. Published by Oxford University Press on behalf of the

  18. Patient-prosthesis mismatch after transapical aortic valve implantation: incidence and impact on survival.

    Science.gov (United States)

    Kukucka, Marian; Pasic, Miralem; Dreysse, Stephan; Mladenow, Alexander; Habazettl, Helmut; Hetzer, Roland; Unbehaun, Axel

    2013-02-01

    Transcatheter aortic valve implantation (TAVI) has become an important therapeutic option for high-risk patients with severe aortic valve stenosis. Patient-prosthesis mismatch (P-PM) is an important determinant of morbidity and mortality after open aortic valve replacement. The objective of our study was to evaluate P-PM incidence and its impact on survival in a large cohort of patients treated with TAVI. We retrospectively analyzed transesophageal echocardiographic data of 278 consecutive patients (Society of Thoracic Surgeons score 18.5 ± 15.3, age 80 ± 8 years) who underwent transapical TAVI with Edwards Sapien valves between April 2008 and March 2011. Effective orifice area was calculated using the continuity equation and indexed with body surface area (iEOA). P-PM was stratified as severe (iEOA < 0.65 cm(2)/cm(2)) and moderate (iEOA, 0.65-0.85 cm(2)/m(2)). Midterm survival (up to 30 months) was analyzed by Kaplan-Meier curves and log-rank tests. There was no P-PM in 181 (65.1%) patients; moderate P-PM was found in 76 (27.3%) patients and severe P-PM in 21 (7.6%). Thirty-day survival was 96.0%, 97.3%, and 90.5%. The 3-month survival was 91%, 90%, and 66%, respectively (P = .0013). Combination of severe P-PM with peak pressure gradients greater than 10 mm Hg further reduced the 3-month survival to 48%. Additionally, mean survival time in patients with an ejection fraction less than 50% was significantly shorter than in patients with an ejection fraction greater than 50% (20.8 ± 1.5 vs 24.1 ± 0.8 months; P = .027). P-PM is found in patients undergoing transapical TAVI. Severe mismatch is accompanied by high early mortality, especially when combined with increased pressure gradients. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  19. Association of common variants in mismatch repair genes and breast cancer susceptibility: a multigene study

    Directory of Open Access Journals (Sweden)

    Pina Julieta

    2009-09-01

    Full Text Available Abstract Background MMR is responsible for the repair of base-base mismatches and insertion/deletion loops. Besides this, MMR is also associated with an anti-recombination function, suppressing homologous recombination. Losses of heterozygosity and/or microsatellite instability have been detected in a large number of skin samples from breast cancer patients, suggesting a potential role of MMR in breast cancer susceptibility. Methods We carried out a hospital-based case-control study in a Caucasian Portuguese population (287 cases and 547 controls to estimate the susceptibility to non-familial breast cancer associated with some polymorphisms in mismatch repair genes (MSH3, MSH4, MSH6, MLH1, MLH3, PMS1 and MUTYH. Results Using unconditional logistic regression we found that MLH3 (L844P, G>A polymorphism GA (Leu/Pro and AA (Pro/Pro genotypes were associated with a decreased risk: OR = 0.65 (0.45-0.95 (p = 0.03 and OR = 0.62 (0.41-0.94 (p = 0.03, respectively. Analysis of two-way SNP interaction effects on breast cancer revealed two potential associations to breast cancer susceptibility: MSH3 Ala1045Thr/MSH6 Gly39Glu - AA/TC [OR = 0.43 (0.21-0.83, p = 0.01] associated with a decreased risk; and MSH4 Ala97Thr/MLH3 Leu844Pro - AG/AA [OR = 2.35 (1.23-4.49, p = 0.01], GG/AA [OR = 2.11 (1.12-3,98, p = 0.02], and GG/AG [adjusted OR = 1.88 (1.12-3.15, p = 0.02] all associated with an increased risk for breast cancer. Conclusion It is possible that some of these common variants in MMR genes contribute significantly to breast cancer susceptibility. However, further studies with a large sample size will be needed to support our results.

  20. The bright side of snow cover effects on PV production - How to lower the seasonal mismatch between electricity supply and demand in a fully renewable Switzerland

    Science.gov (United States)

    Kahl, Annelen; Dujardin, Jérôme; Dupuis, Sonia; Lehning, Michael

    2017-04-01

    One of the major problems with solar PV in the context of a fully renewable electricity production at mid-latitudes is the trend of higher production in summer and lower production in winter. This trend is most often exactly opposite to demand patterns, causing a seasonal mismatch that requires extensive balancing power from other production sources or large storage capacities. Which possibilities do we have to bring PV production into closer correlation with demand? This question motivated our research and in response we investigated the effects of placing PV panels at different tilt angles in regions with extensive snow cover to increase winter production from ground reflected short wave radiation. The aim of this project is therefore to quantify the effect of varying snow cover duration (SCD) and of panel tilt angle on the annual total production and on production during winter months when electricity is most needed. We chose Switzerland as ideal test site, because it has a wide range of snow cover conditions and a high potential for renewable electricity production. But methods can be applied to other regions of comparable conditions for snow cover and irradiance. Our analysis can be separated into two steps: 1. A systematic, GIS and satellite-based analysis for all of Switzerland: We use time series of satellite-derived irradiance, and snow cover characteristics together with land surface cover types and elevation information to quantify the environmental conditions and to estimate potential production and ideal tilt angles. 2. A scenario-based analysis that contrasts the production patterns of different placement scenarios for PV panels in urban, rural and mountainous areas. We invoke a model of a fully renewable electricity system (including Switzerland's large hydropower system) at national level to compute the electricity import and storage capacity that will be required to balance the remaining mismatch between production and demand to further illuminate