Treatment-Continuity of ADHD Compared Using Immediate-Release and Extended-Release MPH

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J Gordon Millichap

2005-07-01

Full Text Available The continuity of methylphenidate (MPH therapy for ADHD in young Medicaid beneficiaries (ages 6 to 17 years treated with immediate-release (IR or extended-release (ER MPH formulations was compared in an analysis of statewide California Medicaid claims (2000-2003 conducted at Columbia University, New York; University of Pennsylvania, Philadelphia; and McNeil Pharmaceuticals, Fort Washington, PA.

[The utility of a continuous performance test embedded in virtual reality in measuring the effectiveness of MPH treatment in boys with ADHD].

Science.gov (United States)

Shriki, Liron; Weizer, Merav; Pollak, Yehuda; Weiss, Patricia L; Rizzo, Albert A; Gross-Tsur, Varda

2010-01-01

Continuous performance tasks (CPT) are popular in the diagnostic process of attention deficit hyperactivity disorder (ADHD), providing an objective measure of attention for a disorder with otherwise subjective criteria. The study aimed to: 1) examine whether the VR-CPT is sensitive to methylphenidate (MPH); 2) assess how the virtual reality (VR) environment is experienced. Twenty boys, 9-17 years, with ADHD underwent 3 CPTs: VR-CPT, the same CPT without VR (no VR-CPT) and the Test of Variables of Attention (T.O.V.A.). Subsequently, those with ADHD repeated the tests 1 hour following MPH ingestion. Immediately following the CPT, the subjects described their subjective experiences on the Short Feedback Questionnaire. Results were analyzed using ANOVA with repeated measures. MPH reduced the omission and commission errors on all tests to a similar degree. Subjective feelings of enjoyment were most positive for VR-CPT. The VR-CPT is a sensitive and user-friendly assessment tool for evaluating the effectiveness of MPH treatment in boys with ADHD.

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

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

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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

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

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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.

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

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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

Leadership training for radiologists: a survey of opportunities and participants in MBA and MPH programs by medical students, residents, and current chairpersons.

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Baker, Stephen; Daginawala, Naznin

2011-08-01

The aim of this study was to determine opportunities for students and trainees to obtain an MPH or MBA degree during either medical school or radiology residency and to determine the prevalence of such degree possession by chairpersons in radiology. All allopathic medical schools in the United States were surveyed to chart the number of MD/MPH and MD/MBA degree programs available to students. Program directors were contacted to assess the number of MPH or MBA courses of study administratively related to their residencies. Also, an e-mail survey was sent to all members of the Society of Chairs of Academic Radiology Departments inquiring whether each chairperson had earned an additional degree. Currently, 81 allopathic medical schools in the United States offer MD/MPH degrees, and 52 offer MD/MBA degrees. Six residencies provide access to MPH programs, and 3 residencies provide the opportunity to pursue an MBA in conjunction with residency. Of these, only 1 MPH program and no MBA programs had trainees enrolled at present. Twenty-six percent of the chairpersons surveyed possessed advanced degrees other than MDs. There has been rapid growth in the number of MD/MPH and MD/MBA programs available to medical students. However, there is a scarcity of similar programs accessible to trainees during or just after residency training. To assist motivated radiologists interested in leading our profession, opportunities should expand both in formal degree-granting programs and through certificate-sanctioned course series to address relevant issues of leadership and management pertinent to our specialty. Copyright © 2011 American College of Radiology. Published by Elsevier Inc. All rights reserved.

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...

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

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

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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.

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

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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.

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

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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.

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...

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

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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

Teaching Note--Educating Public Health Social Work Professionals: Results from an MSW/MPH Program Outcomes Study

Science.gov (United States)

Ruth, Betty J.; Marshall, Jamie Wyatt; Velásquez, Esther E. M.; Bachman, Sara S.

2015-01-01

Dual-degree programs in public health and social work continue to proliferate, yet there has been little research on master's of social work (MSW)/master's of public health (MPH) graduates. The purpose of this study was to describe and better understand the self-reported professional experiences, identities, roles, and outcomes associated with 1…

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

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/

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...

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

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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.

Methylphenidate enhances NMDA-receptor response in medial prefrontal cortex via sigma-1 receptor: a novel mechanism for methylphenidate action.

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Chun-Lei Zhang

Full Text Available Methylphenidate (MPH, commercially called Ritalin or Concerta, has been widely used as a drug for Attention Deficit Hyperactivity Disorder (ADHD. Noteworthily, growing numbers of young people using prescribed MPH improperly for pleasurable enhancement, take high risk of addiction. Thus, understanding the mechanism underlying high level of MPH action in the brain becomes an important goal nowadays. As a blocker of catecholamine transporters, its therapeutic effect is explained as being due to proper modulation of D1 and α2A receptor. Here we showed that higher dose of MPH facilitates NMDA-receptor mediated synaptic transmission via a catecholamine-independent mechanism, in layer V∼VI pyramidal cells of the rat medial prefrontal cortex (PFC. To indicate its postsynaptic action, we next found that MPH facilitates NMDA-induced current and such facilitation could be blocked by σ1 but not D1/5 and α2 receptor antagonists. And this MPH eliciting enhancement of NMDA-receptor activity involves PLC, PKC and IP3 receptor mediated intracellular Ca(2+ increase, but does not require PKA and extracellular Ca(2+ influx. Our additional pharmacological studies confirmed that higher dose of MPH increases locomotor activity via interacting with σ1 receptor. Together, the present study demonstrates for the first time that MPH facilitates NMDA-receptor mediated synaptic transmission via σ1 receptor, and such facilitation requires PLC/IP3/PKC signaling pathway. This novel mechanism possibly explains the underlying mechanism for MPH induced addictive potential and other psychiatric side effects.

Unaccusative Mismatches in Japanese.

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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.…

SKILLS MISMATCH OF THE YOUNG PEOPLE AT THE EUROPEAN LEVEL

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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

Snowshoe hares display limited phenotypic plasticity to mismatch in seasonal camouflage

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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.

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.

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

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)

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)

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

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

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.

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

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…

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

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.

45 MPH 6,000-Pound and 10,000-Pound Rough Terrain Fork Lift Truck Feasibility Study.

Science.gov (United States)

1986-06-24

Airport Post Office Box 66911 Chicago, IL 60666 NPN Security Classification of This Page REPORT DOCUMENTATION PAGE la . Report Security Classification...HOP Unausended Duadin., 20 - I: - 1 1.8 Inch RMS Road 14 la -3 * Clam C (0.93 Inch RMS) Rod w 12 10 10 Per~cent 9 P 7 U. 3 Percent 3 2 0 20 40 SPM...elm 10 67- * * 3 o *" - .2 0 20 40 W (mph) 4/2/ SOJA Figure 75. Rear Wheel Hop on Four Road Surfaces (10K RTFLT Unsuspended Baseline) " Page 93 Adding

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.

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.

Innovating in health care management education: development of an accelerated MBA and MPH degree program at Yale.

Science.gov (United States)

Pettigrew, Melinda M; Forman, Howard P; Pistell, Anne F; Nembhard, Ingrid M

2015-03-01

Increasingly, there is recognition of the need for individuals with expertise in both management and public health to help health care organizations deliver high-quality and cost-effective care. The Yale School of Public Health and Yale School of Management began offering an accelerated Master of Business Administration (MBA) and Master of Public Health (MPH) joint degree program in the summer of 2014. This new program enables students to earn MBA and MPH degrees simultaneously from 2 fully accredited schools in 22 months. Students will graduate with the knowledge and skills needed to become innovative leaders of health care organizations. We discuss the rationale for the program, the developmental process, the curriculum, benefits of the program, and potential challenges.

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

Materials at 200 mph: Making NASCAR Faster and Safer

Science.gov (United States)

Leslie-Pelecky, Diandra

2008-03-01

You cannot win a NASCAR race without understanding science.ootnotetextDiandra Leslie-Pelecky, The Physics of NASCAR (Dutton, New York City, 2008). Materials play important roles in improving performance, as well as ensuring safety. On the performance side, NASCAR limits the materials race car scientists and engineers can use to limit ownership costs. `Exotic metals' are not allowed, so controlling microstructure and nanostructure are important tools. Compacted Graphite Iron, a cast iron in which magnesium additions produce interlocking microscale graphite reinforcements, makes engine blocks stronger and lighter. NASCAR's new car design employs a composite called Tegris^TM that has 70 percent of the strength of carbon fiber composites at about 10 percent of the cost. The most important role of materials in racing is safety. Drivers wear firesuits made of polymers that carbonize (providing thermal protection) and expand (reducing oxygen access) when heated. Catalytic materials originally developed for space-based CO2 lasers filter air for drivers during races. Although materials help cars go fast, they also help cars slow down safely---important because the kinetic energy of a race car going 180 mph is nine times greater than that of a passenger car going 60 mph. Energy-absorbing foams in the cars and on the tracks control energy dissipation during accidents. To say that most NASCAR fans (and there are estimated to be 75 million of them) are passionate about their sport is an understatement. NASCAR fans understand that science and engineering are integral to keeping their drivers safe and helping their teams win. Their passion for racing gives us a great opportunity to share our passion for science with them. NASCAR^ is a registered trademark of the National Association for Stock Car Auto Racing, Inc. Tegris^TM is a trademark of Milliken & Company.

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

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

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.

Innovating in Health Care Management Education: Development of an Accelerated MBA and MPH Degree Program at Yale

Science.gov (United States)

Forman, Howard P.; Pistell, Anne F.; Nembhard, Ingrid M.

2015-01-01

Increasingly, there is recognition of the need for individuals with expertise in both management and public health to help health care organizations deliver high-quality and cost-effective care. The Yale School of Public Health and Yale School of Management began offering an accelerated Master of Business Administration (MBA) and Master of Public Health (MPH) joint degree program in the summer of 2014. This new program enables students to earn MBA and MPH degrees simultaneously from 2 fully accredited schools in 22 months. Students will graduate with the knowledge and skills needed to become innovative leaders of health care organizations. We discuss the rationale for the program, the developmental process, the curriculum, benefits of the program, and potential challenges. PMID:25706023

Improved functionality, health related quality of life and decreased burden of disease in patients with ADHD treated with OROS® MPH: is treatment response different between children and adolescents?

Directory of Open Access Journals (Sweden)

Rettig Klaus

2011-07-01

Full Text Available Abstract Background To compare clinical and health-related quality of life (HRQoL outcomes between children and adolescents with ADHD treated with OROS® MPH, using data from two large similarly-designed multicenter, prospective, open-label, single-arm, non-interventional studies. Methods Pooled analysis (42603ATT4037, 42603 - ATT - 4001 including patients (6 to 18 years with a confirmed diagnosis of ADHD. Patients were treated with OROS® MPH for 12 weeks; ADHD symptoms, functioning, HRQoL, safety and tolerability parameters were assessed. Results 822 patients (583 children [6-12 years], 239 adolescents [13-18 years] were included in the pooled analysis. Mean daily OROS® MPH starting doses in the child and adolescent subgroups were 29.0 ± 11.7 and 37.6 ± 15.6 mg, respectively (p ® MPH in 76.9%, 86.0% and 79.3% of children, adolescents and the total population, respectively, at study end (p = 0.029 between-age subgroups. 195 of 822 patients (23.7% experienced at least one treatment-emergent adverse event; most commonly reported AEs in the total group (≥4% were insomnia (7.2%, anorexia (4.3% and involuntary muscle contractions (4.1%. No clinically relevant changes in body weight or vital signs were observed. Conclusions Clinically relevant differences between children and adolescents with ADHD are present. Adolescents appeared to have a lower health related quality of life and functioning compared to children at baseline, however, they were able to reach comparable ratings at endpoint for most items. Similarly, burden of disease decreased in patients and their carers. OROS MPH was generally safe and well tolerated.

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.

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

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)

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.

[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

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....

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.

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.

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

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

The unstructured linker arms of Mlh1-Pms1 are important for interactions with DNA during mismatch repair

Science.gov (United States)

Plys, Aaron J.; Rogacheva, Maria V.; Greene, Eric C.; Alani, Eric

2012-01-01

DNA mismatch repair (MMR) models have proposed that MSH proteins identify DNA polymerase errors while interacting with the DNA replication fork. MLH proteins (primarily Mlh1-Pms1 in baker’s yeast) then survey the genome for lesion-bound MSH proteins. The resulting MSH-MLH complex formed at a DNA lesion initiates downstream steps in repair. MLH proteins act as dimers and contain long (20 – 30 nanometers) unstructured arms that connect two terminal globular domains. These arms can vary between 100 to 300 amino acids in length, are highly divergent between organisms, and are resistant to amino acid substitutions. To test the roles of the linker arms in MMR, we engineered a protease cleavage site into the Mlh1 linker arm domain of baker’s yeast Mlh1-Pms1. Cleavage of the Mlh1 linker arm in vitro resulted in a defect in Mlh1-Pms1 DNA binding activity, and in vivo proteolytic cleavage resulted in a complete defect in MMR. We then generated a series of truncation mutants bearing Mlh1 and Pms1 linker arms of varying lengths. This work revealed that MMR is greatly compromised when portions of the Mlh1 linker are removed, whereas repair is less sensitive to truncation of the Pms1 linker arm. Purified complexes containing truncations in Mlh1 and Pms1 linker arms were analyzed and found to have differential defects in DNA binding that also correlated with the ability to form a ternary complex with Msh2-Msh6 and mismatch DNA. These observations are consistent with the unstructured linker domains of MLH proteins providing distinct interactions with DNA during MMR. PMID:22659005

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

Effects of MPH-OROS on the Organizational, Time Management, and Planning Behaviors of Children with ADHD

Science.gov (United States)

Abikoff, Howard; Nissley-Tsiopinis, Jenelle; Gallagher, Richard; Zambenedetti, Maurizio; Seyffert, Michael; Boorady, Roy; McCarthy, John

2009-01-01

A double-blind, placebo-controlled, crossover design study was done to evaluate the effects of methylphenidate-osmotic-release oral systems (MPH-OROS) on the organization, time management, and planning (OTMP) of children with attention deficit hyperactivity disorder (ADHD). Results show significant improvements on the OTMP of children with ADHD in…

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

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)

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...

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.

Biallelic PMS2 Mutation and Heterozygous DICER1 Mutation Presenting as Constitutional Mismatch Repair Deficiency With Corpus Callosum Agenesis: Case Report and Review of Literature.

Science.gov (United States)

Cheyuo, Cletus; Radwan, Walid; Ahn, Janice; Gyure, Kymberly; Qaiser, Rabia; Tomboc, Patrick

2017-10-01

Constitutional mismatch repair deficiency syndrome is a cancer predisposition syndrome caused by autosomal recessive biallelic (homozygous) germline mutations in the mismatch repair genes (MLH1, MSH2, MSH6, and PMS2). The clinical spectrum includes neoplastic and non-neoplastic manifestations. We present the case of a 7-year-old boy who presented with T-lymphoblastic lymphoma and glioblastoma, together with non-neoplastic manifestations including corpus callosum agenesis, arachnoid cyst, developmental venous anomaly, and hydrocephalus. Gene mutation analysis revealed pathogenic biallelic mutations of PMS2 and heterozygous DICER1 variant predicted to be pathogenic. This report is the first to allude to a possible interaction of the mismatch repair system with DICER1 to cause corpus callosum agenesis.

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.

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.

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.

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…

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.

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.

Optic pathway glioma as part of a constitutional mismatch-repair deficiency syndrome in a patient meeting the criteria for neurofibromatosis type 1.

Science.gov (United States)

Yeung, Jacky T; Pollack, Ian F; Shah, Sapana; Jaffe, Ronald; Nikiforova, Marina; Jakacki, Regina I

2013-01-01

Patients with constitutional mismatch repair-deficiency (CMMR-D) caused by the biallelic deletions of mismatch repair (MMR) genes have a high likelihood of developing malignancies of the bone marrow, bowel, and brain. Affected individuals often have phenotypic features of neurofibromatosis type 1 (NF-1), including café-au-lait spots. Optic pathway gliomas (OPGs), a common manifestation of NF-1, have not been reported. We report the case of a 3-year-old male with an extensive OPG who met the diagnostic criteria for NF-1. He was subsequently found to have multiple colonic polyps and bi-allelic loss of PMS2. Testing for NF-1 was negative. Copyright © 2012 Wiley Periodicals, Inc.

DNA mismatch repair deficiency accelerates lung neoplasm development in K-rasLA1/+ mice: a brief report

International Nuclear Information System (INIS)

Downey, Charlene M; Jirik, Frank R

2015-01-01

Inherited as well as acquired deficiencies in specific DNA mismatch repair (MMR) components are associated with the development of a wide range of benign and malignant neoplasms. Loss of key members such as MSH2 and MLH1 severely cripples the ability of the cell to recognize and correct such lesions as base:base mismatches and replicative DNA polymerase errors such as slippages at repetitive sequences. Genomic instability resulting from MMR deficiency not only predisposes cells to malignant transformation but may also promote tumor progression. To test the latter, we interbred Msh2 −/− mice with the K-ras LA1/+ transgenic line that spontaneously develops a range of premalignant and malignant lung lesions. Compared to K-ras LA1/+ mice, K-ras LA1/+ ; Msh2 −/− mice developed lung adenomas and adenocarcinomas at an increased frequency and also demonstrated evidence of accelerated adenocarcinoma growth. Since MMR defects have been identified in some human lung cancers, the mutant mice may not only be of preclinical utility but they will also be useful in identifying gene alterations able to act in concert with Kras mutants to promote tumor progression

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.

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...

Interdependence of DNA mismatch repair proteins MLH1 and MSH2 in apoptosis in human colorectal carcinoma cell lines.

Science.gov (United States)

Hassen, Samar; Ali, Akhtar A; Kilaparty, Surya P; Al-Anbaky, Qudes A; Majeed, Waqar; Boman, Bruce M; Fields, Jeremy Z; Ali, Nawab

2016-01-01

The mammalian DNA mismatch repair (MMR) system consists of a number of proteins that play important roles in repair of base pair mismatch mutations and in maintenance of genomic integrity. A defect in this system can cause genetic instability, which can lead to carcinogenesis. For instance, a germline mutation in one of the mismatch repair proteins, especially MLH1 or MSH2, is responsible for hereditary non-polyposis colorectal cancer. These MMR proteins also play an important role in the induction of apoptosis. Accordingly, altered expression of or a defect in MLH1 or MSH2 may confer resistance to anti-cancer drugs used in chemotherapy. We hypothesized that the ability of these two MMR proteins to regulate apoptosis are interdependent. Moreover, a defect in either one may confer resistance to chemotherapy by an inability to trigger apoptosis. To this end, we studied three cell lines-SW480, LoVo, and HTC116. These cell lines were selected based on their differential expression of MLH1 and MSH2 proteins. SW480 expresses both MLH1 and MSH2; LoVo expresses only MLH1 but not MSH2; HCT116 expresses only MSH2 but not MLH1 protein. MTT assays, a measure of cytotoxicity, showed that there were different cytotoxic effects of an anti-cancer drug, etoposide, on these cell lines, effects that were correlated with the MMR status of the cells. Cells that are deficient in MLH1 protein (HCT116 cells) were resistant to the drug. Cells that express both MLH1 and MSH2 proteins (SW480 cells) showed caspase-3 cleavage, an indicator of apoptosis. Cells that lack MLH1 (HCT116 cells) did not show any caspase-3 cleavage. Expression of full-length MLH1 protein was decreased in MMR proficient (SW480) cells during apoptosis; it remained unchanged in cells that lack MSH2 (LoVo cells). The expression of MSH2 protein remained unchanged during apoptosis both in MMR proficient (SW480) and deficient (HCT116) cells. Studies on translocation of MLH1 protein from nucleus to cytosolic fraction, an

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.

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

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.

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.

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...

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.

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...

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....

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

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

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.

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...

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...

IN VITRO INTERACTION OF INFLUENZA VIRUS A(H1N1pdm09 WITH MONOCYTIC MACROPHAGES: INDIVIDUAL RESPONSES OF TLR7 AND RIG1 RECEPTOR GENES

Directory of Open Access Journals (Sweden)

T. M. Sokolova

2017-01-01

Full Text Available In vitro differentiation of donor blood monocytes to macrophages (Mph following GM-CSF treatment was accompanied by a significant increase in the levels of gene transcription signaling receptors TLR7 or RIG1. The levels of intracellular viral RNA (M1 gene in Mph remained high upon infection by influenza virus A H1N1pdm (Moscow 2009 for 24-96 hours. The innate immunity reactions caused by influenza virus show individual features: they are decreased in Mph from donor 1 which had initially high level of endosomal TLR7 gene activity, and it increased by influenza virus in MPh from donor 2 who had a very low level of TLR7 gene expression. The influenza H1N1pdm virus weakly stimulated expression of gene RIG1 and production of inflammatory cytokines in Mf in donor 1. The differences may be connected with individual sensitivity of the donors to influenza infection.

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

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.

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

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.

A chloroplast thylakoid lumen protein is required for proper photosynthetic acclimation of plants under fluctuating light environments.

Science.gov (United States)

Liu, Jun; Last, Robert L

2017-09-19

Despite our increasingly sophisticated understanding of mechanisms ensuring efficient photosynthesis under laboratory-controlled light conditions, less is known about the regulation of photosynthesis under fluctuating light. This is important because-in nature-photosynthetic organisms experience rapid and extreme changes in sunlight, potentially causing deleterious effects on photosynthetic efficiency and productivity. Here we report that the chloroplast thylakoid lumenal protein MAINTENANCE OF PHOTOSYSTEM II UNDER HIGH LIGHT 2 (MPH2; encoded by At4g02530 ) is required for growth acclimation of Arabidopsis thaliana plants under controlled photoinhibitory light and fluctuating light environments. Evidence is presented that mph2 mutant light stress susceptibility results from a defect in photosystem II (PSII) repair, and our results are consistent with the hypothesis that MPH2 is involved in disassembling monomeric complexes during regeneration of dimeric functional PSII supercomplexes. Moreover, mph2 -and previously characterized PSII repair-defective mutants-exhibited reduced growth under fluctuating light conditions, while PSII photoprotection-impaired mutants did not. These findings suggest that repair is not only required for PSII maintenance under static high-irradiance light conditions but is also a regulatory mechanism facilitating photosynthetic adaptation under fluctuating light environments. This work has implications for improvement of agricultural plant productivity through engineering PSII repair.

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.

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.

Programmed Death Ligand 1 Expression Among 700 Consecutive Endometrial Cancers: Strong Association With Mismatch Repair Protein Deficiency.

Science.gov (United States)

Li, Zaibo; Joehlin-Price, Amy S; Rhoades, Jennifer; Ayoola-Adeola, Martins; Miller, Karin; Parwani, Anil V; Backes, Floor J; Felix, Ashley S; Suarez, Adrian A

2018-01-01

This study aims to determine the prevalence of programmed death ligand 1 (PD-L1) expression in endometrial carcinoma (EC) and determine clinical and pathological associations. Immunohistochemistry for PD-L1 was performed on sections of a triple-core tissue microarray of 700 ECs. Positive PD-L1 expression, defined as 1% of cells staining positive, was evaluated in tumor and stromal compartments. Using age-adjusted logistic regression, we estimated odds ratios and 95% confidence intervals for associations between PD-L1 expression (overall and by staining compartment) with clinical and tumor characteristics. Kaplan-Meier plots and log-rank tests were used to evaluate associations between PD-L1 expression and EC-specific survival. PD-L1 expression was observed in 100 cases (14.3%), including 27 (3.9%) with expression in tumor cells only, 35 (5.0%) with expression in both tumor cells and stroma, and 38 (5.4%) with expression in stroma only. Expression was observed in ECs of different histologic types. Tumors characterized by loss of mismatch repair proteins were significantly associated with tumoral PD-L1 expression (P < 0.0001), but not with stromal PD-L1 expression. Both tumoral and stromal PD-L1 expressions were associated with high-grade endometrioid histology, nonendometrioid histology, and lymphovascular space invasion. We observed no significant associations between PD-L1 expression and EC-specific survival. PD-L1 is expressed in a significant proportion of EC and is associated with mismatch repair deficiency, potentially representing a mechanism of tumor immune evasion and a therapeutic target in EC.

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.

Connections between constitutional mismatch repair deficiency syndrome and neurofibromatosis type 1.

Science.gov (United States)

Wimmer, K; Rosenbaum, T; Messiaen, L

2017-04-01

Constitutional mismatch repair (MMR) deficiency (CMMRD) is a rare childhood cancer susceptibility syndrome resulting from biallelic germline loss-of-function mutations in one of the MMR genes. Individuals with CMMRD have high risk to develop a broad spectrum of malignancies and frequently display features reminiscent of neurofibromatosis type 1 (NF1). Evaluation of the clinical findings of genetically proven CMMRD patients shows that not only multiple café-au-lait macules but also any of the diagnostic features of NF1 may be present in a CMMRD patient. This phenotypic overlap may lead to misdiagnosis of CMMRD patients as having NF1, which impedes adequate management of the patients and their families. The spectrum of CMMRD-associated childhood malignancies includes high-grade glioma, acute myeloid leukaemia or rhabdomyosarcoma, also reported as associated with NF1. Reported associations between NF1 and these malignancies are to a large extent based on studies that neither proved the presence of an NF1 germline mutation nor ruled-out CMMRD in the affected. Hence, these associations are challenged by our current knowledge of the phenotypic overlap between NF1 and CMMRD and should be re-evaluated in future studies. Recent advances in the diagnostics of CMMRD should render it possible to definitely state or refute this diagnosis in these individuals. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

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

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.

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.

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

Science.gov (United States)

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

2014-01-01

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

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.

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.

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...

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

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

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.

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

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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

Two-year-olds' sensitivity to subphonemic mismatch during online spoken word recognition.

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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.

Convergent transmission of RNAi guide-target mismatch information across Argonaute internal allosteric network.

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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

DNA mismatch repair gene MLH1 induces apoptosis in prostate cancer cells.

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Fukuhara, Shinichiro; Chang, Inik; Mitsui, Yozo; Chiyomaru, Takeshi; Yamamura, Soichiro; Majid, Shahana; Saini, Sharanjot; Hirata, Hiroshi; Deng, Guoren; Gill, Ankurpreet; Wong, Darryn K; Shiina, Hiroaki; Nonomura, Norio; Dahiya, Rajvir; Tanaka, Yuichiro

2014-11-30

Mismatch repair (MMR) enzymes have been shown to be deficient in prostate cancer (PCa). MMR can influence the regulation of tumor development in various cancers but their role on PCa has not been investigated. The aim of the present study was to determine the functional effects of the mutL-homolog 1 (MLH1) gene on growth of PCa cells. The DU145 cell line has been established as MLH1-deficient and thus, this cell line was utilized to determine effects of MLH1 by gene expression. Lack of MLH1 protein expression was confirmed by Western blotting in DU145 cells whereas levels were high in normal PWR-1E and RWPE-1 prostatic cells. MLH1-expressing stable transfectant DU145 cells were then created to characterize the effects this MMR gene has on various growth properties. Expression of MLH1 resulted in decreased cell proliferation, migration and invasion properties. Lack of cell growth in vivo also indicated a tumor suppressive effect by MLH1. Interestingly, MLH1 caused an increase in apoptosis along with phosphorylated c-Abl, and treatment with MLH1 siRNAs countered this effect. Furthermore, inhibition of c-Abl with STI571 also abrogated the effect on apoptosis caused by MLH1. These results demonstrate MLH1 protects against PCa development by inducing c-Abl-mediated apoptosis.

Identification of Lynch syndrome mutations in the MLH1-PMS2 interface that disturb dimerization and mismatch repair.

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Kosinski, Jan; Hinrichsen, Inga; Bujnicki, Janusz M; Friedhoff, Peter; Plotz, Guido

2010-08-01

Missense alterations of the mismatch repair gene MLH1 have been identified in a significant proportion of individuals suspected of having Lynch syndrome, a hereditary syndrome that predisposes for cancer of colon and endometrium. The pathogenicity of many of these alterations, however, is unclear. A number of MLH1 alterations are located in the C-terminal domain (CTD) of MLH1, which is responsible for constitutive dimerization with PMS2. We analyzed which alterations may result in pathogenic effects due to interference with dimerization. We used a structural model of CTD of MLH1-PMS2 heterodimer to select 19 MLH1 alterations located inside and outside two candidate dimerization interfaces in the MLH1-CTD. Three alterations (p.Gln542Leu, p.Leu749Pro, p.Tyr750X) caused decreased coexpression of PMS2, which is unstable in the absence of interaction with MLH1, suggesting that these alterations interfere with dimerization. All three alterations are located within the dimerization interface suggested by our model. They also compromised mismatch repair, suggesting that defects in dimerization abrogate repair and confirming that all three alterations are pathogenic. Additionally, we provided biochemical evidence that four alterations with uncertain pathogenicity (p.Ala586Pro, p.Leu636Pro, p.Thr662Pro, and p.Arg755Trp) are deleterious because of poor expression or poor repair efficiency, and confirm the deleterious effect of eight further alterations.

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

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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

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

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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.

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

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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.

The Effect of Codon Mismatch on the Protein Translation System.

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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.

The Effect of Codon Mismatch on the Protein Translation System.

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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.

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

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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.

Impact of aortic prosthesis-patient mismatch on left ventricular mass regression.

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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.

Immunohistochemical and DNA sequencing analysis on human mismatch repair gene MLH1 in cervical squamous cell carcinoma with LOH of this gene

NARCIS (Netherlands)

Hu, X.; Guo, Z.; Pang, T.; Li, Q.; Afink, G.; Pontén, J.

2000-01-01

BACKGROUND: The human MLH1 gene (hMLH1) is one of the DNA mismatch repair genes. Defects in these genes are believed to be the underlying cause of microsatellite instability (MSI). MSI has been demonstrated in many human cancers such as colon cancer and some female-specific tumors. The hMLH1 gene

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

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

2013-10-01

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

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

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Ricardo Mouro Pinto

2013-10-01

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

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...

BRCA2, EGFR, and NTRK mutations in mismatch repair-deficient colorectal cancers with MSH2 or MLH1 mutations.

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Deihimi, Safoora; Lev, Avital; Slifker, Michael; Shagisultanova, Elena; Xu, Qifang; Jung, Kyungsuk; Vijayvergia, Namrata; Ross, Eric A; Xiu, Joanne; Swensen, Jeffrey; Gatalica, Zoran; Andrake, Mark; Dunbrack, Roland L; El-Deiry, Wafik S

2017-06-20

Deficient mismatch repair (MMR) and microsatellite instability (MSI) contribute to ~15% of colorectal cancer (CRCs). We hypothesized MSI leads to mutations in DNA repair proteins including BRCA2 and cancer drivers including EGFR. We analyzed mutations among a discovery cohort of 26 MSI-High (MSI-H) and 558 non-MSI-H CRCs profiled at Caris Life Sciences. Caris-profiled MSI-H CRCs had high mutation rates (50% vs 14% in non-MSI-H, P MLH1-mutant CRCs showed higher mutation rates in BRCA2 compared to non-MSH2/MLH1-mutant tumors (38% vs 6%, P MLH1-mutant CRCs included 75 unique mutations not known to occur in breast or pancreatic cancer per COSMIC v73. Only 5 deleterious BRCA2 mutations in CRC were previously reported in the BIC database as germ-line mutations in breast cancer. Some BRCA2 mutations were predicted to disrupt interactions with partner proteins DSS1 and RAD51. Some CRCs harbored multiple BRCA2 mutations. EGFR was mutated in 45.5% of MSH2/MLH1-mutant and 6.5% of non-MSH2/MLH1-mutant tumors (P MLH1-mutant CRC including NTRK1 I699V, NTRK2 P716S, and NTRK3 R745L. Our findings have clinical relevance regarding therapeutic targeting of BRCA2 vulnerabilities, EGFR mutations or other identified oncogenic drivers such as NTRK in MSH2/MLH1-mutant CRCs or other tumors with mismatch repair deficiency.

Galectin-1 is required for the regulatory function of B cells.

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Alhabbab, R; Blair, P; Smyth, L A; Ratnasothy, K; Peng, Q; Moreau, A; Lechler, R; Elgueta, R; Lombardi, G

2018-02-09

Galectin-1 (Gal-1) is required for the development of B cells in the bone marrow (BM), however very little is known about the contribution of Gal-1 to the development of B cell regulatory function. Here, we report an important role for Gal-1 in the induction of B cells regulatory function. Mice deficient of Gal-1 (Gal-1 -/- ) showed significant loss of Transitional-2 (T2) B cells, previously reported to include IL-10 + regulatory B cells. Gal-1 -/- B cells stimulated in vitro via CD40 molecules have impaired IL-10 and Tim-1 expression, the latter reported to be required for IL-10 production in regulatory B cells, and increased TNF-α expression compared to wild type (WT) B cells. Unlike their WT counterparts, T2 and T1 Gal-1 -/- B cells did not suppress TNF-α expression by CD4 + T cells activated in vitro with allogenic DCs (allo-DCs), nor were they suppressive in vivo, being unable to delay MHC-class I mismatched skin allograft rejection following adoptive transfer. Moreover, T cells stimulated with allo-DCs show an increase in their survival when co-cultured with Gal-1 -/- T2 and MZ B cells compared to WT T2 and MZ B cells. Collectively, these data suggest that Gal-1 contributes to the induction of B cells regulatory function.

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

[Constitutional mismatch repair deficiency syndrome].

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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.

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

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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.

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

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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.

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

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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.

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

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…

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…

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.)

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....

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.

Advancing the match-mismatch framework for large herbivores in the Arctic: Evaluating the evidence for a trophic mismatch in caribou.

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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.

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

Structure Transformation and Coherent Interface in Large Lattice-Mismatched Nanoscale Multilayers

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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.

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

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.

A multicenter, open-label trial to evaluate the quality of life in adults with ADHD treated with long-acting methylphenidate (OROS MPH): Concerta Quality of Life (CONQoL) study.

Science.gov (United States)

Mattos, Paulo; Louzã, Mário Rodrigues; Palmini, André Luís Fernandes; de Oliveira, Irismar Reis; Rocha, Fábio Lopes

2013-07-01

The available literature provides few studies on the effectiveness of methylphenidate in improving quality of life in individuals with ADHD. To assess the effectiveness of methylphenidate OROS formulation (OROS MPH) through QoL in adults with ADHD. A 12-week, multicenter, open-label trial involving 60 patients was used. The measures used were Adult Self-Rating Scale, Adult ADHD Quality of Life Scale (AAQoL), State and Trait Anxiety Inventory (STAI), Hamilton Depression Rating Scale (HAM-D), Clinical Global Impression (CGI), and safety measures. A significance statistic level of 5% was adopted. Analyses included 60 patients (66.7% male; M age = 31.1 years) for safety and 58 patients for effectiveness. All AAQoL subscales improved from baseline to Week 12 (p < .0001), as well as the Total AAQoL (p < .0001). A significant reduction on Clinical Global Impression-Improvement (CGI-I), HAM-D, STAI, and ASRS scores was observed (p < .0001). No serious adverse event was reported. Treatment of adult ADHD patients with OROS MPH improves QoL.

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.

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

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...

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)

The galaxy major merger fraction to {z} 1

Science.gov (United States)

López-Sanjuan, C.; Balcells, M.; Pérez-González, P. G.; Barro, G.; García-Dabó, C. E.; Gallego, J.; Zamorano, J.

2009-07-01

Aims: The importance of disc-disc major mergers in galaxy evolution remains uncertain. We study the major merger fraction in a SPITZER/IRAC-selected catalogue in the GOODS-S field up to z 1 for luminosity- and mass-limited samples. Methods: We select disc-disc merger remnants on the basis of morphological asymmetries/distortions, and address three main sources of systematic errors: (i) we explicitly apply morphological K-corrections; (ii) we measure asymmetries in galaxies artificially redshifted to zd = 1.0 to deal with loss of morphological information with redshift; and (iii) we take into account the observational errors in z and A, which tend to overestimate the merger fraction, though use of maximum likelihood techniques. Results: We obtain morphological merger fractions (f_m^mph) below 0.06 up to z 1. Parameterizing the merger fraction evolution with redshift as f_m^mph(z) = f_m^mph(0) (1+z)^m, we find that m = 1.8 ± 0.5 for MB ≤ -20 galaxies, while m = 5.4 ± 0.4 for Mstar ≥ 1010 M⊙ galaxies. When we translate our merger fractions to merger rates (Re_m^mph), their evolution, parameterized as Re_m^mph(z) = Re_m^mph(0) (1+z)^n, is quite similar in both cases: n = 3.3 ± 0.8 for MB ≤ -20 galaxies, and n = 3.5 ± 0.4 for Mstar ≥ 1010 M⊙ galaxies. Conclusions: Our results imply that only 8% of today's Mstar ≥ 1010 M⊙ galaxies have undergone a disc-disc major merger since z 1. In addition, 21% of Mstar ≥ 1010 M⊙ galaxies at z 1 have undergone one of these mergers since z 1.5. This suggests that disc-disc major mergers are not the dominant process in the evolution of Mstar ≥ 1010 M⊙ galaxies since z 1, with only 0.2 disc-disc major mergers per galaxy, but may be an important process at z > 1, with ˜1 merger per galaxy at 1 < z < 3.

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

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...

The relationship between the PD-1/PD-L1 pathway and DNA mismatch repair in cervical cancer and its clinical significance

Directory of Open Access Journals (Sweden)

Feng YC

2018-01-01

Full Text Available Yang-chun Feng,1,2 Wen-li Ji,3 Na Yue,3 Yan-chun Huang,2 Xiu-min Ma1 1Clinical Laboratory Center, The First Affiliated Hospital of Xinjiang Medical University, 2Clinical Laboratory Center, 3Clinical Pathology Center, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, People’s Republic of China Background: According to recent clinical observations, deficient DNA mismatch repair (dMMR is capable of improving antitumor effects of the PD-1/PD-L1 pathway, suggesting that dMMR may act as a prognostic indicator of PD-1/PD-L1 antibody drugs. In this study, we examined the dMMR and PD-1/PD-L1 expression, as well as explored the correlation of dMMR status with PD-1/PD-L1 expression in cervical cancer patients, in order to optimize cervical cancer patient selection for PD-1/PD-L1 antibody drug treatment, which is helpful to avoid adverse effects and keep costs manageable. Methods: Sixty-six tissue samples from patients with squamous cell carcinoma were collected, and data of their clinical characteristics were also gathered. Based on these samples, the expression levels of MLH1, MSH2, and PD-L1 in cancer cells were tested by immunohistochemical assay (IHC. Moreover, PD-1/PD-L1 expression in tumor-invading lymphocytes (TILs was detected by IHC as well. Six single-nucleotide-repeat markers of microsatellite instability (MSI, including NR-27, MONO-27, BAT-25, NR-24, NR-21, and BAT-26, were tested by capillary electrophoresis sequencer analysis. According to expression of MLH1, MSH2 and the MSI test, all 66 cases were divided into dMMR or proficient DNA mismatch repair (pMMR groups. The comparisons of dMMR and PD-L1 in cancer cells and of PD-1/PD-L1 in TILs were conducted categorized by age, childbearing history, history of abortion, ethnicity, and cancer cell differentiation subgroup. Furthermore, PD-L1 levels in cancer cells and PD-1/PD-L1 in TILs were analyzed and compared in both dMMR and pMMR subgroups. Results: Of the patient samples, 25

Impact of valve prosthesis-patient mismatch estimated by echocardiographic-determined effective orifice area on long-term outcome after aortic valve replacement.

Science.gov (United States)

Florath, Ines; Albert, Alexander; Rosendahl, Ulrich; Ennker, Ina Carolin; Ennker, Jrgen

2008-06-01

The impact of valve prosthesis-patient mismatch on long-term outcome after aortic valve replacement estimated by various variables such as projected indexed effective orifice area and internal geometric orifice area obtained from in vivo or in vitro published data is still controversial. The effective orifice area was measured by echocardiography in 533 patients. The mean age of the patients was 71 +/- 9 years; mean follow-up time was 4.7 +/- 2.2 years. The impact of severe (indexed effective orifice area regression. Severe mismatch (hazard ratio: 1.9 [1.08-3.21]) was a significant predictor of survival time after adjustment for age, left ventricular ejection fraction, atrial fibrillation, New York Heart Association class, serum creatinine, and hemoglobin level. The 5- and 7-year survival rates were 71% +/- 4% and 54% +/- 8% for patients with severe mismatch and 83% +/- 4% and 80% +/- 8% for patients with mild mismatch, respectively. The correlation between projected and measured indexed effective orifice area was of medium strength (r = 0.49), and the frequency of observed mismatch depended linearly on the projected indexed effective orifice area. Although projected indexed effective orifice area and indexed internal geometric orifice area were significant predictors of severe mismatch, the sensitivity and specificity for severe prosthesis-patient mismatch were only 75% and 52%, using an optimal threshold of projected indexed effective orifice area defined by the Youden index. Severe prosthesis-patient mismatch estimated by effective orifice area measured within 10 days was an independent risk factor of survival time. Projected indexed effective orifice area determined at surgery does not sufficiently predict mismatch.

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

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

Photovoltaic yield: correction method for the mismatch between the solar spectrum and the reference ASTMG AM1.5G spectrum

Directory of Open Access Journals (Sweden)

Mambrini Thomas

2015-01-01

Full Text Available We propose a method for a spectral correction of the predicted PV yield and we show the importance of the spectral mismatch on the solar cell. Indeed, currently predicted PV yield are made considering solar irradiation, ambient temperature, incidence angle and partially (or not the solar spectrum. However, the solar spectrum is not always the same. It varies depending on the site location, atmospheric conditions, time of the day...This may impact the photovoltaic solar cells differently according to their technology (crystalline Silicon, thin film, multi-junctions... This paper presents a method for calculating the correction of the short-circuit current of a photovoltaic cell due to the mismatch of the solar spectrum with the reference ASTM AM1.5G spectrum, for a specific site, throughout the year, using monthly data of AERONET (AErosol RObotic NETwork established by NASA and CNRS and the model SMARTS (simple model for atmospheric transmission of sunshine developed by the NREL. We applied this correction method on the site of Palaiseau (France, 48.7°N, 2.2°E, 156 m, close to our laboratory, just for comparison and the example of Blida (Algeria, 36°N, 2°E, 230 m is given for one year. This example illustrates the importance of this spectral correction to better estimate the photovoltaic yield. To be more precise, instead of modeling the solar spectral distribution, one can measure it with a spectro-radiometer, and then, derive the spectral mismatch correction. Some of our typical measurements are presented in this paper.

Donor/recipient sex mismatch and survival after heart transplantation: only an issue in male recipients? An analysis of the Spanish Heart Transplantation Registry.

Science.gov (United States)

Martinez-Selles, Manuel; Almenar, Luis; Paniagua-Martin, Maria J; Segovia, Javier; Delgado, Juan F; Arizón, Jose M; Ayesta, Ana; Lage, Ernesto; Brossa, Vicens; Manito, Nicolás; Pérez-Villa, Félix; Diaz-Molina, Beatriz; Rábago, Gregorio; Blasco-Peiró, Teresa; De La Fuente Galán, Luis; Pascual-Figal, Domingo; Gonzalez-Vilchez, Francisco

2015-03-01

The results of studies on the association between sex mismatch and survival after heart transplantation are conflicting. Data from the Spanish Heart Transplantation Registry. From 4625 recipients, 3707 (80%) were men. The donor was female in 943 male recipients (25%) and male in 481 female recipients (52%). Recipients of male hearts had a higher body mass index (25.9 ± 4.1 vs. 24.3 ± 3.7; P gender (P = 0.02). In the multivariate analysis, sex mismatch was associated with long-term mortality (HR, 1.14; 95% CI 1.01-1.29; P = 0.04), and there was a tendency toward significance for the interaction between sex mismatch and recipient gender (P = 0.08). In male recipients, mismatch increased mortality mainly during the first month and in patients with pulmonary gradient >13 mmHg. Sex mismatch seems to be associated with mortality after heart transplantation in men but not in women. © 2014 Steunstichting ESOT.

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.

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

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.

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...

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

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

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

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.

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.

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

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.

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

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.

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.

Sex differences, learning flexibility, and striatal dopamine D1 and D2 following adolescent drug exposure in rats

Science.gov (United States)

Izquierdo, Alicia; Pozos, Hilda; De La Torre, Adrianna; DeShields, Simone; Cevallos, James; Rodriguez, Jonathan; Stolyarova, Alexandra

2016-01-01

Corticostriatal circuitry supports flexible reward learning and emotional behavior from the critical neurodevelopmental stage of adolescence through adulthood. It is still poorly understood how prescription drug exposure in adolescence may impact these outcomes in the long-term. We studied adolescent methylphenidate (MPH) and fluoxetine (FLX) exposure in rats and their impact on learning and emotion in adulthood. In Experiment 1, male and female rats were administered MPH, FLX, or saline (SAL), and compared with methamphetamine (mAMPH) treatment beginning in postnatal day (PND) 37. The rats were then tested on discrimination and reversal learning in adulthood. In Experiment 2, animals were administered MPH or SAL also beginning in PND 37 and later tested in adulthood for anxiety levels. In Experiment 3, we analyzed striatal dopamine D1 and D2 receptor expression in adulthood following either extensive learning (after Experiment 1) or more brief emotional measures (after Experiment 2). We found sex differences in discrimination learning and attenuated reversal learning after MPH and only sex differences in adulthood anxiety. In learners, there was enhanced striatal D1, but not D2, after either adolescent MPH or mAMPH. Lastly, also in learners, there was a sex x treatment group interaction for D2, but not D1, driven by the MPH-pretreated females, who expressed significantly higher D2 levels compared to SAL. These results show enduring effects of adolescent MPH on reversal learning in rats. Developmental psychostimulant exposure may interact with learning to enhance D1 expression in adulthood, and affect D2 expression in a sex-dependent manner. PMID:27091300

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

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.

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

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.

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

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...

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.

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)

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.

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.

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...

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

IPP-rich milk protein hydrolysate lowers blood pressure in subjects with stage 1 hypertension, a randomized controlled trial

Directory of Open Access Journals (Sweden)

Kloek Joris

2010-11-01

Full Text Available Abstract Background Milk derived peptides have been identified as potential antihypertensive agents. The primary objective was to investigate the effectiveness of IPP-rich milk protein hydrolysates (MPH on reducing blood pressure (BP as well as to investigate safety parameters and tolerability. The secondary objective was to confirm or falsify ACE inhibition as the mechanism underlying BP reductions by measuring plasma renin activity and angiotensin I and II. Methods We conducted a randomized, placebo-controlled, double blind, crossover study including 70 Caucasian subjects with prehypertension or stage 1 hypertension. Study treatments consisted of daily consumption of two capsules MPH1 (each containing 7.5 mg Isoleucine-Proline-Proline; IPP, MPH2 (each containing 6.6 mg Methionine-Alanine-Proline, 2.3 mg Leucine-Proline-Proline, 1.8 mg IPP, or placebo (containing cellulose for 4 weeks. Results In subjects with stage 1 hypertension, MPH1 lowered systolic BP by 3.8 mm Hg (P = 0.0080 and diastolic BP by 2.3 mm Hg (P = 0.0065 compared with placebo. In prehypertensive subjects, the differences in BP between MPH1 and placebo were not significant. MPH2 did not change BP significantly compared with placebo in stage I hypertensive or prehypertensive subjects. Intake of MPHs was well tolerated and safe. No treatment differences in hematology, clinical laboratory parameters or adverse effects were observed. No significant differences between MPHs and placebo were found in plasma renin activity, or angiotensin I and II. Conclusions MPH1, containing IPP and no minerals, exerts clinically relevant BP lowering effects in subjects with stage 1 hypertension. It may be included in lifestyle changes aiming to prevent or reduce high BP. Trial registration ClinicalTrials.gov NCT00471263

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...

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.

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.

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.

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

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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

The role of Homer 1a in increasing locomotor activity and non-selective attention, and impairing learning and memory abilities.

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Yang, Lei; Hong, Qin; Zhang, Min; Liu, Xiao; Pan, Xiao-Qin; Guo, Mei; Fei, Li; Guo, Xi-Rong; Tong, Mei-Ling; Chi, Xia

2013-06-17

The current study aimed to investigate the possible role of Homer 1a in the etiology and pathogenesis of attention deficit hyperactivity disorder (ADHD). We divided 32 rats into four groups. The rats in the RNAi-MPH group were given the lentiviral vector containing Homer 1a-specific miRNA (Homer 1a-RNAi-LV) by intracerebroventricular injection, and 7 days later they were given three daily doses of methylphenidate (MPH) by intragastric gavage. The RNAi-SAL group was given Homer 1a-RNAi-LV and saline later. The NC-MPH group was given the negative control lentiviral vector (NC-LV) and MPH later. The NC-SAL group was given NC-LV and saline later. Rats that were given Homer 1a RNAi exhibited increased locomotor activity and non-selective attention, and impaired learning and memory abilities, which is in line with the behavioral findings of animal models of ADHD. However, MPH ameliorated these abnormal behaviors. All findings indicated that Homer 1a may play an important role in the etiology and pathogenesis of ADHD. Copyright © 2013 Elsevier B.V. All rights reserved.

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

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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.

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

Patient - implant dimension mismatch in total knee arthroplasty: Is it worth worrying? An Indian scenario

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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.

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

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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.

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.

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

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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.

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

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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.

Germ line mutations of mismatch repair genes in hereditary nonpolyposis colorectal cancer patients with small bowel cancer: International Society for Gastrointestinal Hereditary Tumours Collaborative Study

DEFF Research Database (Denmark)

Park, Jae-Gahb; Kim, Duck-Woo; Hong, Chang Won

2006-01-01

PURPOSE: The aim of study was to determine the clinical characteristics and mutational profiles of the mismatch repair genes in hereditary nonpolyposis colorectal cancer (HNPCC) patients with small bowel cancer (SBC). EXPERIMENTAL DESIGN: A questionnaire was mailed to 55 members of the Internatio......PURPOSE: The aim of study was to determine the clinical characteristics and mutational profiles of the mismatch repair genes in hereditary nonpolyposis colorectal cancer (HNPCC) patients with small bowel cancer (SBC). EXPERIMENTAL DESIGN: A questionnaire was mailed to 55 members...... of the International Society for Gastrointestinal Hereditary Tumours, requesting information regarding patients with HNPCC-associated SBC and germ line mismatch repair gene mutations. RESULTS: The study population consisted of 85 HNPCC patients with identified mismatch repair gene mutations and SBCs. SBC was the first...... HNPCC-associated malignancy in 14 of 41 (34.1%) patients for whom a personal history of HNPCC-associated cancers was available. The study population harbored 69 different germ line mismatch repair gene mutations, including 31 mutations in MLH1, 34 in MSH2, 3 in MSH6, and 1 in PMS2. We compared...

Challenges in the identification of MSH6-associated colorectal cancer: rectal location, less typical histology, and a subset with retained mismatch repair function

DEFF Research Database (Denmark)

Klarskov, Louise; Holck, Susanne; Bernstein, Inge

2011-01-01

with MLH1/MSH2-mutant tumors and sporadic mismatch repair-deficient cancers. In the MSH6 subset, we confirmed a higher age (median, 56 y) at diagnosis and found a significantly larger proportion (25%) of rectal cancers. Presence of dirty necrosis was the sole histologic component that significantly...... differed between MSH6 and MLH1/MSH2 tumors. Compared with the sporadic mismatch repair-defective cohort, MSH6 cases had a lower prevalence of tumor-infiltrating lymphocytes and Crohn-like reactions. Mismatch repair defects were identified in 92% of MSH6 tumors, with high concordance between microsatellite...

Challenges in the Identification of MSH6-Associated Colorectal Cancer: Rectal Location, Less Typical Histology, and a Subset With Retained Mismatch Repair Function

DEFF Research Database (Denmark)

Klarskov, Louise Laurberg; Holck, Susanne; Bernstein, Inge Thomsen

2011-01-01

with MLH1/MSH2-mutant tumors and sporadic mismatch repair-deficient cancers. In the MSH6 subset, we confirmed a higher age (median, 56 y) at diagnosis and found a significantly larger proportion (25%) of rectal cancers. Presence of dirty necrosis was the sole histologic component that significantly...... differed between MSH6 and MLH1/MSH2 tumors. Compared with the sporadic mismatch repair-defective cohort, MSH6 cases had a lower prevalence of tumor-infiltrating lymphocytes and Crohn-like reactions. Mismatch repair defects were identified in 92% of MSH6 tumors, with high concordance between microsatellite...

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.

Ductile Crack Initiation Criterion with Mismatched Weld Joints Under Dynamic Loading Conditions.

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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.

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.

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

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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

Meiotic gene conversion mutants in Saccharomyces cerevisiae. I. Isolation and characterization of PMS1-1 and PMS1-2

International Nuclear Information System (INIS)

Williamson, M.S.; Game, J.C.; Fogel, S.

1985-01-01

The PMS1 mutants, isolated on the basis of sharply elevated meiotic prototroph frequencies for two closely linked HIS4 alleles, display pleiotropic phenotypes in meiotic and mitotic cells. Two isolates carrying recessive mutations in PMS1 were characterized. They identify a function required to maintain low postmeiotic segregation (PMS) frequencies at many heterozygous sites. In addition, they are mitotic mutators. In mutant diploids, spore viability is reduced, and among survivors, gene conversion and postmeiotic segregation frequencies are increased, but reciprocal exchange frequencies are not affected. The conversion event pattern is also dramatically changed in multiply marked regions in PMS1 homozygotes. The PMS1 locus maps near MET4 on chromosome XIV. The PMS1 gene may identify an excision-resynthesis long patch mismatch correction function or a function that facilitates correction tract elongation. The PMS1 gene product may also play an important role in spontaneous mitotic mutation avoidance and correction of mismatches in heteroduplex DNA formed during spontaneous and UV-induced mitotic recombination. Based on meiotic recombination models emphasizing mismatch correction in heteroduplex DNA intermediates, this interpretation is favored, but alternative interpretations involving longer recombination intermediates in the mutants are also considered

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.

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.

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)

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

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

Directory of Open Access Journals (Sweden)

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.

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.

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...

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.

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.

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.

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

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

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

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

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.

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

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.

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

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

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.

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.

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.

Structural studies of the 5'-phenazinium-tethered matched and G-A-mismatched DNA duplexes by NMR spectroscopy.

Science.gov (United States)

Maltseva, T; Sandström, A; Ivanova, I M; Sergeyev, D S; Zarytova, V F; Chattopadhyaya, J

1993-05-01

The mechanism through which modified oligo-DNA analogues act as antisense repressors at the transcriptional and translational level of gene expression is based on the information content in the nucleotide sequence which is determined by the specific base pairing. The efficiency of such action is largely determined by the stability of the duplex formed between the oligonucleotide reagent and the target sequence and also by the mismatched base pairing, such as G-A, that occurs during replication or recombination. We herein report that the phenazinium (Pzn)-tethered matched duplex p(d(TGTTTGGC)):(Pzn)-p(d(CCAAACA)) (III) (Tm = 50 degrees C) has a much larger stability than the parent matched duplex p(d(TGTTTGGC)):p(d(CCAAACA)) (I) (Tm = 30 degrees C). On the other hand, the Pzn-tethered G-A-mismatched duplex p(d(TGTTTGGC)):(Pzn)-p(d(ACAAACA)) (IV) (Tm = 34 degrees C) is only slightly more stable than its parent mismatched duplex p(d(TGTTTGGC)):p(d(ACAAACA)) (Tm = 25 degrees C). A detailed 500 MHz NMR study and constrained MD refinements of NMR-derived structures have been undertaken for the DNA duplexes (I), (II), (III) and (IV) in order to understand the structural basis of stabilization of Pzn-tethered matched DNA duplex (delta Tm = 20 degrees C) compared to mismatched duplex (delta Tm = 9 degrees C). Assignment of the 1H-NMR (500 MHz) spectra of the duplexes has been carried out by 2D NOESY, HOHAHA and DQF-COSY experiments. The torsion angles have been extracted from the J-coupling constants obtained by simulation of most of the DQF-COSY cross-peaks using program SMART. The solution structure of the duplexes were assessed by an iterative hybride relaxation matrix method (MORASS) combined with NOESY distances and torsion angles restrained molecular dynamics (MD) using program Amber 4.0. The standard Amber 4.0 force-field parameters were used for the oligonucleotide in conjunction with the new parameters for Pzn residue which was obtained by full geometry

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...

Immunohistochemistry for PMS2 and MSH6 alone can replace a four antibody panel for mismatch repair deficiency screening in colorectal adenocarcinoma.

Science.gov (United States)

Hall, Geoffrey; Clarkson, Adele; Shi, Amanda; Langford, Eileen; Leung, Helen; Eckstein, Robert P; Gill, Anthony J

2010-01-01

Currently, testing for mismatch repair deficiency in colorectal cancers is initiated by performing immunohistochemistry with four antibodies (MLH1, PMS2, MSH2 and MSH6). If any one of these stains is negative the tumour is considered microsatellite unstable and, if clinical circumstances warrant it, the patient is offered genetic testing for Lynch's syndrome. Due to the binding properties of the mismatch repair heterodimer complexes, gene mutation and loss of MLH1 and MSH2 invariably result in the degradation of PMS2 and MSH6, respectively, but the converse is not true. We propose that staining for PMS2 and MSH6 alone will be sufficient to detect all cases of mismatch repair deficiency and should replace routine screening with all four antibodies. The electronic database of the department of Anatomical Pathology, Royal North Shore Hospital, Sydney, Australia, was searched for all colorectal carcinomas on which a four panel immunohistochemical microsatellite instability screen was performed. An audit of the slides for concordant loss of MLH1-PMS2 and MSH2-MSH6 was then undertaken. Unusual or discordant cases were reviewed and, in some cases, re-stained to confirm the staining pattern. Of 344 cases of colorectal cancer which underwent four antibody immunohistochemistry, 104 displayed loss of at least one mismatch repair protein. Of these, 100 showed concordant mismatch repair loss (i.e., loss of MLH1 and PMS2 or loss of MSH2 and MSH6). The four discordant cases comprised two single negative cases (1 MSH6 negative/MSH2 positive case, 1 PMS2 negative/MLH1 positive) and two triple negative (both MLH1/PMS2/MSH6 negative). The microsatellite instability (MSI) group showed a relatively high median age (69.3 years) due to the departmental policy of testing all cases with possible MSI morphology regardless of age. The sensitivity and specificity of a two panel test comprised of PMS2 and MSH6, compared to a four panel test, is 100%. No false negatives or positives were

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

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.

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)

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.

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.

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

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

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.

The human cyclin B1 protein modulates sensitivity of DNA mismatch repair deficient prostate cancer cell lines to alkylating agents.

Science.gov (United States)

Rasmussen, L J; Rasmussen, M; Lützen, A; Bisgaard, H C; Singh, K K

2000-05-25

DNA damage caused by alkylating agents results in a G2 checkpoint arrest. DNA mismatch repair (MMR) deficient cells are resistant to killing by alkylating agents and are unable to arrest the cell cycle in G2 phase after alkylation damage. We investigated the response of two MMR-deficient prostate cancer cell lines DU145 and LNCaP to the alkylating agent MNNG. Our studies reveal that DU145 cancer cells are more sensitive to killing by MNNG than LNCaP. Investigation of the underlying reasons for lower resistance revealed that the DU145 cells contain low endogenous levels of cyclin B1. We provide direct evidence that the endogenous level of cyclin B1 modulates the sensitivity of MMR-deficient prostate cancer cells to alkylating agents.

Si Complies with GaN to Overcome Thermal Mismatches for the Heteroepitaxy of Thick GaN on Si.

Science.gov (United States)

Tanaka, Atsunori; Choi, Woojin; Chen, Renjie; Dayeh, Shadi A

2017-10-01

Heteroepitaxial growth of lattice mismatched materials has advanced through the epitaxy of thin coherently strained layers, the strain sharing in virtual and nanoscale substrates, and the growth of thick films with intermediate strain-relaxed buffer layers. However, the thermal mismatch is not completely resolved in highly mismatched systems such as in GaN-on-Si. Here, geometrical effects and surface faceting to dilate thermal stresses at the surface of selectively grown epitaxial GaN layers on Si are exploited. The growth of thick (19 µm), crack-free, and pure GaN layers on Si with the lowest threading dislocation density of 1.1 × 10 7 cm -2 achieved to date in GaN-on-Si is demonstrated. With these advances, the first vertical GaN metal-insulator-semiconductor field-effect transistors on Si substrates with low leakage currents and high on/off ratios paving the way for a cost-effective high power device paradigm on an Si CMOS platform are demonstrated. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

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

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

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.

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

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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

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.

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.

Nuclear import of human MLH1, PMS2, and MutLalpha: redundancy is the key.

Science.gov (United States)

Leong, Vivian; Lorenowicz, Jessica; Kozij, Natalie; Guarné, Alba

2009-08-01

DNA mismatch repair maintains genomic stability by correcting errors that have escaped polymerase proofreading. Defects on mismatch repair genes lead to an increased mutation rate, microsatellite instability and predisposition to human non-polyposis colorectal cancer (HNPCC). Human MutLalpha is a heterodimer formed by the interaction of MLH1 and PMS2 that coordinates a series of key events in mismatch repair. It has been proposed that nuclear import of MutLalpha may be the first regulatory step on the activation of the mismatch repair pathway. Using confocal microscopy and mismatch repair deficient cells, we have identified the sequence determinants that drive nuclear import of human MLH1, PMS2, and MutLalpha. Transient transfection of the individual proteins reveals that MLH1 has a bipartite and PMS2 has a single monopartite nuclear localization signal. Although dimerization is not required for nuclear localization, the MutLalpha heterodimer is imported more efficiently than the MLH1 or PMS2 monomers. Interestingly, the bipartite localization signal of MLH1 can direct import of MutLalpha even when PMS2 encompasses a mutated localization signal. Hence we conclude that the presence of redundant nuclear localization signals guarantees nuclear transport of MutLalpha and, consequently, efficient mismatch repair.

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

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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.

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

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

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.

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.

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.

Mismatched single stranded antisense oligonucleotides can induce efficient dystrophin splice switching

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Kole Ryszard

2011-10-01

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

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

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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.

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…

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

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.

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

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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.

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...

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

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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.

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

The mismatch repair and meiotic recombination endonuclease Mlh1-Mlh3 is activated by polymer formation and can cleave DNA substrates in trans.

Science.gov (United States)

Manhart, Carol M; Ni, Xiaodan; White, Martin A; Ortega, Joaquin; Surtees, Jennifer A; Alani, Eric

2017-04-01

Crossing over between homologs is initiated in meiotic prophase by the formation of DNA double-strand breaks that occur throughout the genome. In the major interference-responsive crossover pathway in baker's yeast, these breaks are resected to form 3' single-strand tails that participate in a homology search, ultimately forming double Holliday junctions (dHJs) that primarily include both homologs. These dHJs are resolved by endonuclease activity to form exclusively crossovers, which are critical for proper homolog segregation in Meiosis I. Recent genetic, biochemical, and molecular studies in yeast are consistent with the hypothesis of Mlh1-Mlh3 DNA mismatch repair complex acting as the major endonuclease activity that resolves dHJs into crossovers. However, the mechanism by which the Mlh1-Mlh3 endonuclease is activated is unknown. Here, we provide evidence that Mlh1-Mlh3 does not behave like a structure-specific endonuclease but forms polymers required to generate nicks in DNA. This conclusion is supported by DNA binding studies performed with different-sized substrates that contain or lack polymerization barriers and endonuclease assays performed with varying ratios of endonuclease-deficient and endonuclease-proficient Mlh1-Mlh3. In addition, Mlh1-Mlh3 can generate religatable double-strand breaks and form an active nucleoprotein complex that can nick DNA substrates in trans. Together these observations argue that Mlh1-Mlh3 may not act like a canonical, RuvC-like Holliday junction resolvase and support a novel model in which Mlh1-Mlh3 is loaded onto DNA to form an activated polymer that cleaves DNA.

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.

Environmental determinants and spatial mismatch of mammal diversity measures in Colombia

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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.

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...

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.

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

International Nuclear Information System (INIS)

David A. Boothman

1999-01-01

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

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.

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

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

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.

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...

GLI1 interferes with the DNA mismatch repair system in pancreatic cancer through BHLHE41-mediated suppression of MLH1.

Science.gov (United States)

Inaguma, Shingo; Riku, Miho; Hashimoto, Mitsuyoshi; Murakami, Hideki; Saga, Shinsuke; Ikeda, Hiroshi; Kasai, Kenji

2013-12-15

The mismatch repair (MMR) system is indispensable for the fidelity of DNA replication, the impairment of which predisposes to the development and progression of many types of cancers. To date, GLI1 transcription factor, a key molecule of the Hedgehog signaling pathway, has been shown to regulate the expression of several genes crucial for a variety of cancer cell properties in many types of cancers, including pancreatic ductal adenocarcinoma (PDAC), but whether GLI1 could control the MMR system was not known. Here, we showed that GLI1 and GLI2 indirectly suppressed the expression of MLH1 in PDAC cells. Through GLI1 target gene screening, we found that GLI1 and GLI2 activated the expression of a basic helix-loop-helix type suppressor BHLHE41/DEC2/SHARP1 through a GLI-binding site in the promoter. Consistent with a previous report that BHLHE41 suppresses the MLH1 promoter activity, we found that the activation of GLI1 led to the BHLHE41-dependent suppression of MLH1, and a double knockdown of GLI1 and GLI2 conversely increased the MLH1 protein in PDAC cells. Using TALEN-based modification of the MLH1 gene, we further showed that GLI1 expression was indeed associated with an increased tolerance to a methylating agent, methylnitrosourea cooperatively with a lower copy number status of MLH1. Finally, GLI1 expression was immunohistochemically related positively with BHLHE41 and inversely with MLH1 in PDAC cells and precancerous lesions of the pancreas. On the basis of these results, we propose that GLI1 depresses the MMR activity and might contribute to the development and progression of PDAC. ©2013 AACR.

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 ...

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

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

Methylphenidate DAT binding in adolescents with Attention-Deficit/ Hyperactivity Disorder comorbid with Substance Use Disorder--a single photon emission computed tomography with [Tc(99m)]TRODAT-1 study.

Science.gov (United States)

Szobot, Claudia M; Shih, Ming Chi; Schaefer, Thais; Júnior, Neivo; Hoexter, Marcelo Q; Fu, Ying Kai; Pechansky, Flávio; Bressan, Rodrigo A; Rohde, Luis A P

2008-04-15

Attention-Deficit/Hyperactivity Disorder (ADHD) is highly prevalent among adolescents with Substance Use Disorders (SUD). Effects of methylphenidate (MPH) on ADHD are attributed to its properties of blocking the dopamine transporter (DAT) in the striatum. However, it has been demonstrated that drug addiction is associated with dopaminergic system changes that may affect MPH brain effects, emphasizing the need to better understand MPH actions in subjects with ADHD+SUD. To evaluate the effect of an extended release formulation of MPH (MPH-SODAS) on DAT availability in 17 stimulant-naive ADHD adolescents with comorbid SUD (cannabis and cocaine). Subjects underwent two single photon emission computed tomography (SPECT) scans with [Tc(99m)]TRODAT-1, at baseline and after 3 weeks on MPH-SODAS. Clinical assessment for ADHD relied on the Swanson, Nolan and Pelham Scale - version IV (SNAP-IV). Caudate and putamen DAT binding potential (BP) was calculated. After 3 weeks on MPH-SODAS, there was a significant reduction of SNAP-IV total scores (pADHD patients without SUD comorbidity, providing neurobiological support for trials with stimulants in adolescents with ADHD+SUD, an important population excluded from studies.

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

Comparative treatment patterns, healthcare resource utilization and costs of atomoxetine and long-acting methylphenidate among children and adolescents with attention-deficit/hyperactivity disorder in Germany.

Science.gov (United States)

Greven, Peter; Sikirica, Vanja; Chen, Yaozhu J; Curtice, Tammy G; Makin, Charles

2017-09-01

Attention-deficit/hyperactivity disorder (ADHD) imposes a substantial burden on patients and their families. A retrospective, propensity score-matched cohort study compared treatment patterns, healthcare resource utilization (HRU) and costs among children/adolescents with ADHD aged 6-17 years at treatment initiation (index) in Germany who received atomoxetine (ATX) or long-acting methylphenidate (LA-MPH) monotherapy. Patients received at least one prescription for their index medication (ATX/LA-MPH) during 2006-2010; the first prescription marked the index date. ATX- and LA-MPH-indexed cohorts were matched 1:1 (n = 737); a patient subset was identified that had not received ADHD-indicated medications in 12 months prior to index (novel initiators: ATX, n = 486; LA-MPH, n = 488). Treatment patterns were evaluated among novel initiators, and HRU and costs among the matched cohorts in the 12 months after index. No significant differences in baseline characteristics were found between the novel initiator patient subsets. ATX-indexed novel initiators had significantly longer persistence to index medication [mean (standard deviation; SD) days: 222.0 (133.9) vs 203.2 (135.0), P = 0.029) but higher switching rates (8.8 vs 5.5 %, P = 0.045) than LA-MPH-indexed novel initiators. The total ATX-indexed cohort required more prescriptions [any medication; mean (SD): 20.9 (11.5) vs 15.7 (9.0), P < 0.001] and outpatient visits [mean (SD): 10.1 (6.3) vs 8.3 (5.3), P < 0.001], and incurred significantly higher total median healthcare costs (€1144 vs €541, P < 0.001) versus matched LA-MPH patients. These real-world data indicate that, among children/adolescents with ADHD in Germany, ATX-indexed patients may require more prescriptions and physician visits, and incur higher total healthcare costs, than matched LA-MPH patients.

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.

Using consensus methods to develop a country-specific Master of Public Health curriculum for the Republic of Maldives

Directory of Open Access Journals (Sweden)

Robotin MC

2016-02-01

Full Text Available Monica C Robotin,1,2 Muthau Shaheem,3 Aishath S Ismail3 1Faculty of Medicine, School of Public Health, University of Sydney, 2Cancer Programs Division, Cancer Council New South Wales, Sydney, Australia; 3Faculty of Health Sciences, Maldives National University, Male, Maldives Background: Over the last four decades, the health status of Maldivian people improved considerably, as reflected in child and maternal mortality indicators and the eradication or control of many communicable diseases. However, changing disease patterns are now undermining these successes, so the local public health practitioners need new skills to perform effectively in this changing environment. To address these needs, in 2013 the Faculty of Health Sciences of the Maldives National University developed the country's first Master of Public Health (MPH program.Methods: The process commenced with a wide scoping exercise and an analysis of the curricular structure of MPH programs of high-ranking universities. Thereafter, a stakeholder consultation using consensus methods reached agreement on overall course structure and the competencies required for local MPH graduates. Subsequently, a working group developed course descriptors and identified local public health research priorities, which could be addressed by MPH students.Results: Ten semistructured interviews explored specific training needs of prospective MPH students, key public health competencies required by local employers and preferred MPH training models. The recommendations informed a nominal group meeting, where participants agreed on MPH core competencies, overall curricular structure and core subjects. The 17 public health electives put forward by the group were prioritized using an online Delphi process. Participants ranked them by their propensity to address local public health needs and the locally available teaching expertise. The first student cohort commenced their MPH studies in January 2014.Conclusion

Expression of DNA mismatch repair proteins MLH1, MSH2, and MSH6 in recurrent glioblastoma.

Science.gov (United States)

Stark, Andreas M; Doukas, Alexander; Hugo, Heinz-Herrmann; Hedderich, Jürgen; Hattermann, Kirsten; Maximilian Mehdorn, H; Held-Feindt, Janka

2015-02-01

Methylated O6-methylguanin-DNA-methytransferase (MGMT) promoter methylation is associated with survival in patients with glioblastoma. Current evidence suggests that further mismatch repair genes play a pivotal role in the tumor response to treatment. Candidate genes are MLH1, MSH2, and MSH6. Formerly, we found evidence of prognostic impact of MLH1 and MSH6 immunohistochemical expression in a small series of patients with initial glioblastoma. Two hundred and eleven patients were included who underwent macroscopically total removal of primary glioblastoma and at least one re-craniotomy for recurrence. Immunohistochemical staining was performed on paraffin-embedded specimens of initial tumors with specific antibodies against MLH1, MSH2, and MSH6. RESULTS were compared to the Ki67 proliferation index and patient survival. Additionally, fresh frozen samples from 16 paired initial and recurrent specimens were examined using real-time reverse transcription polymerase chain reaction (RT-PCR) with specific primers against MLH1, MSH2, and MSH6. RESULTS were compared to MGMT status and survival. (1) Immunohistochemical expression of MSH6 was significantly associated with the Ki67 proliferation index (PMLH1, MLH2, and MSH6 over treatment combined with lacking MGMT methylation. In another two patients, decreased MLH1, MSH2, and MSH6 expression was observed in combination with MGMT promoter methylation. Our data indicate that there may be glioblastoma patient subgroups characterized by MMR-expression changes beyond MGMT promoter methylation. The immunohistochemical expression of MLH1, MSH2, and MSH6 in initial glioblastoma is not associated with patient survival.

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.

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.

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.

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

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

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.

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.

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 ...

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

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...

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. ...

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 CFR 10.1 - Publication required.

Science.gov (United States)

2010-01-01

... 1 General Provisions 1 2010-01-01 2010-01-01 false Publication required. 10.1 Section 10.1 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER SPECIAL EDITIONS OF THE FEDERAL REGISTER PRESIDENTIAL PAPERS Regular Publication § 10.1 Publication required. The Director publishes a special edition...

NRP-1 Receptor Expression Mismatch in Skin of Subjects with Experimental and Diabetic Small Fiber Neuropathy.

Directory of Open Access Journals (Sweden)

Nathalie Van Acker

Full Text Available The in vivo cutaneous nerve regeneration model using capsaicin is applied extensively to study the regenerative mechanisms and therapeutic efficacy of disease modifying molecules for small fiber neuropathy (SFN. Since mismatches between functional and morphological nerve fiber recovery are described for this model, we aimed at determining the capability of the capsaicin model to truly mimic the morphological manifestations of SFN in diabetes. As nerve and blood vessel growth and regenerative capacities are defective in diabetes, we focused on studying the key regulator of these processes, the neuropilin-1 (NRP-1/semaphorin pathway. This led us to the evaluation of NRP-1 receptor expression in epidermis and dermis of subjects presenting experimentally induced small fiber neuropathy, diabetic polyneuropathy and of diabetic subjects without clinical signs of small fiber neuropathy. The NRP-1 receptor was co-stained with CD31 vessel-marker using immunofluorescence and analyzed with Definiens® technology. This study indicates that capsaicin application results in significant loss of epidermal NRP-1 receptor expression, whereas diabetic subjects presenting small fiber neuropathy show full epidermal NRP-1 expression in contrast to the basal expression pattern seen in healthy controls. Capsaicin induced a decrease in dermal non-vascular NRP-1 receptor expression which did not appear in diabetic polyneuropathy. We can conclude that the capsaicin model does not mimic diabetic neuropathy related changes for cutaneous NRP-1 receptor expression. In addition, our data suggest that NRP-1 might play an important role in epidermal nerve fiber loss and/or defective regeneration and that NRP-1 receptor could change the epidermal environment to a nerve fiber repellant bed possibly through Sem3A in diabetes.

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

1 CFR 9.1 - Publication required.

Science.gov (United States)

2010-01-01

... 1 General Provisions 1 2010-01-01 2010-01-01 false Publication required. 9.1 Section 9.1 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER SPECIAL EDITIONS OF THE FEDERAL REGISTER THE UNITED STATES GOVERNMENT MANUAL § 9.1 Publication required. The Director of the Federal Register shall...

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

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

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...

The effect of methylphenidate on postural stability under single and dual task conditions in children with attention deficit hyperactivity disorder - a double blind randomized control trial.

Science.gov (United States)

Jacobi-Polishook, Talia; Shorer, Zamir; Melzer, Itshak

2009-05-15

To investigate the effects of Methylphenidate (MPH) on postural stability in attention deficit hyperactivity disorder (ADHD) children in single and dual task conditions. A randomized controlled double-blind study analyzing postural stability in 24 ADHD children before and after MPH vs. placebo treatments, in three task conditions: (1) Single task, standing still; (2) dual task, standing still performing a memory-attention demanding task; (3) standing still listening to music. MPH resulted in a significant improvement in postural stability during the dual task condition and while listening to music, with no equivalent improvement in placebo controls. MPH improves postural stability in ADHD, especially when an additional task is performed. This is probably due to enhanced attention abilities, thus contributing to improved balance control during performance of tasks that require attention. MPH remains to be studied as a potential drug treatment to improve balance control and physical functioning in other clinical populations.

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.

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

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.

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.

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.

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.

Patient-prosthesis mismatch and left ventricular remodelling after implantation of Shelhigh SuperStentless aortic valve prostheses.

Science.gov (United States)

Germing, A; Lindstaedt, M; Holt, S; Reber, D; Mügge, A; Laczkovics, A; Fritz, M

2008-08-01

Aortic valve replacement is a standard procedure for the treatment of severe aortic valve stenosis. Due to lower flow velocities stentless valves are associated with a more effective regression of left ventricular hypertrophy in comparison to stented valves. However, mismatch between body surface area and valve size supports unfavourable hemodynamic results. The aim of the study was to analyze hemodynamic parameters by echocardiography after implantation of the Shelhigh SuperStentless bioprosthesis and to analyze the occurrence of patient-prosthesis mismatch and left ventricular remodelling in this specific valve type. A total of 20 patients with severe aortic stenosis underwent implantation of a Shelhigh Super Stentless prosthesis. Clinical and echocardiographic assessment was done prior to, immediate after and six months after surgery. All surgical procedures were successful, no surgery-related complication was documented perioperatively. One patient died after development of multiorgan failure. Echocardiography during the first eight days after surgery showed mean gradients of 16 mmHg, mean valve orifice areas of 1.8 cm(2) and indexed effective orifice areas at 0.95 cm(2)/m(2). Six-months follow-up data were obtained in 19/20 patients. There were no relevant changes in echocardiographic hemodynamic findings at the time of follow-up measurements. Significant regression of left ventricular hypertrophy was shown (P=0.0088). A patient-prosthesis mismatch occurred in one patient (0.54 cm(2)/m(2)). No recurrent symptoms were documented. Patient-prosthesis mismatch after implantation of SuperStentless Shelhigh prosthesis is rare. A significant regression of left ventricular hypertrophy could be shown after six months. Hemodynamic valve function assessed by echocardiography may be predicted early after surgery.

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...

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.

Constitutional mismatch repair-deficiency syndrome: have we so far seen only the tip of an iceberg?

Science.gov (United States)

Wimmer, Katharina; Etzler, Julia

2008-09-01

Heterozygous mutations in one of the mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2 cause the dominant adult cancer syndrome termed Lynch syndrome or hereditary non-polyposis colorectal cancer. During the past 10 years, some 35 reports have delineated the phenotype of patients with biallelic inheritance of mutations in one of these MMR genes. The patients suffer from a condition that is characterised by the development of childhood cancers, mainly haematological malignancies and/or brain tumours, as well as early-onset colorectal cancers. Almost all patients also show signs reminiscent of neurofibromatosis type 1, mainly café au lait spots. Alluding to the underlying mechanism, this condition may be termed as "constitutional mismatch repair-deficiency (CMMR-D) syndrome". To give an overview of the current knowledge and its implications of this recessively inherited cancer syndrome we summarise here the genetic, clinical and pathological findings of the so far 78 reported patients of 46 families suffering from this syndrome.

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...

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

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.

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...

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

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.

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.

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.

Dispersion of fruit flies (Diptera: Tephritidae) at high and low densities and consequences of mismatching dispersions of wild and sterile flies

International Nuclear Information System (INIS)

Meats, A.

2007-01-01

Both wild and released (sterile) Bactrocera tryoni (Froggatt) (Diptera: Tephritidae) and wild Bactrocera papayae (Drew and Hancock) in Australia had patchy distributions and comparisons with predictions of the negative binomial model indicated that the degree of clumping was sometimes very high, particularly at low densities during eradication. An increase of mean recapture rate of sterile B. tryoni on either of 2 trap arrays was not accompanied by a reduction in its coefficient of variation and when recapture rates were high, the percentage of traps catching zero decreased only slightly with increase in recapture rate, indicating that it is not practicable to decrease the heterogeneity of dispersion of sterile flies by increasing the number released. There was often a mismatch between the dispersion patterns of the wild and sterile flies, and the implications of this for the efficiency of the sterile insect technique (SIT) were investigated with a simulation study with the observed degrees of mismatch obtained from the monitoring data and assuming the overall ratio of sterile to wild flies to be 100:1. The simulation indicated that mismatches could result in the imposed rate of increase of wild flies being up to 3.5 times higher than that intended (i.e., 0.35 instead of 0.1). The effect of a mismatch always reduces the efficiency of SIT. The reason for this asymmetry is discussed and a comparison made with host-parasitoid and other systems. A release strategy to counter this effect is suggested. (author) [es

Osmotic Release Oral System Methylphenidate Versus Atomoxetine for the Treatment of Attention-Deficit/Hyperactivity Disorder in Chinese Youth: 8-Week Comparative Efficacy and 1-Year Follow-Up.

Science.gov (United States)

Su, Yi; Yang, Li; Stein, Mark A; Cao, Qingjiu; Wang, Yufeng

2016-05-01

The purpose of this study was to compare the short-term efficacy, tolerability, and 1-year adherence in Chinese children and adolescents with attention-deficit/hyperactivity disorder (ADHD) treated with either osmotic release oral system methylphenidate (OROS MPH) or atomoxetine (ATX). Children and adolescents meeting Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria for ADHD were randomly assigned to receive either OROS MPH (n = 119) or ATX (n = 118). Participants underwent a 1-4 week dose titration period to determine optimal dose, and then were maintained on that dose for 4 weeks (maintenance period). Assessment for efficacy was conducted every week over the titration period and at the end of the maintenance period. The primary efficacy measure was the investigator-rated total ADHD Rating Scale-IV (ADHD-RS-IV) score. Response was further classified as remission (ADHD-RS-IV [18 or 9 items] average score ≤1), robust improvement (ADHD-RS-IV ≥40% decrease in total score), or improvement (≥ 25% decrease in total score) at the end of maintenance period. Medication adherence (taking medication at least 5 days in 1 week) and reasons for nonadherence were evaluated every week over the titration period, at the end of maintenance period, and then at 3, 6, and 12 months. At the end of maintenance period, both OROS MPH and ATX were associated with significant and similar reductions from baseline in ADHD symptoms. Percentages achieving remission, robust improvement, and improvement were comparable for OROS MPH and ATX treatment (35.3% vs. 37.1%, 45.4% vs. 44.8%, 65.5% vs. 66.4%). Medication use decreased over time for both treatments; however, at end of maintenance period, 3 month, 6 month, and 1 year follow-ups, subjects in the OROS MPH group were more likely to be compliant with treatment (74.8%, 50.4%, 38.7%, and 21.8% for OROS MPH vs. 52.5%, 33.9%, 12.7%, and 3.4% for ATX) ( p < 0.05). The most common reasons for

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

Donor-Recipient Size Mismatch in Paediatric Renal Transplantation

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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.

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...

Screening of the DNA mismatch repair genes MLH1, MSH2 and MSH6 in a Greek cohort of Lynch syndrome suspected families

International Nuclear Information System (INIS)

Thodi, Georgia; Fountzilas, George; Yannoukakos, Drakoulis; Fostira, Florentia; Sandaltzopoulos, Raphael; Nasioulas, George; Grivas, Anastasios; Boukovinas, Ioannis; Mylonaki, Maria; Panopoulos, Christos; Magic, Mirjana Brankovic

2010-01-01

Germline mutations in the DNA mismatch repair genes predispose to Lynch syndrome, thus conferring a high relative risk of colorectal and endometrial cancer. The MLH1, MSH2 and MSH6 mutational spectrum reported so far involves minor alterations scattered throughout their coding regions as well as large genomic rearrangements. Therefore, a combination of complete sequencing and a specialized technique for the detection of genomic rearrangements should be conducted during a proper DNA-testing procedure. Our main goal was to successfully identify Lynch syndrome families and determine the spectrum of MLH1, MSH2 and MSH6 mutations in Greek Lynch families in order to develop an efficient screening protocol for the Greek colorectal cancer patients' cohort. Forty-two samples from twenty-four families, out of which twenty two of Greek, one of Cypriot and one of Serbian origin, were screened for the presence of germline mutations in the major mismatch repair genes through direct sequencing and MLPA. Families were selected upon Amsterdam criteria or revised Bethesda guidelines. Ten deleterious alterations were detected in twelve out of the twenty-four families subjected to genetic testing, thus our detection rate is 50%. Four of the pathogenic point mutations, namely two nonsense, one missense and one splice site change, are novel, whereas the detected genomic deletion encompassing exon 6 of the MLH1 gene has been described repeatedly in the LOVD database. The average age of onset for the development of both colorectal and endometrial cancer among mutation positive families is 43.2 years. The mutational spectrum of the MMR genes investigated as it has been shaped by our analysis is quite heterogeneous without any strong indication for the presence of a founder effect

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.

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

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...

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.

HLA-mismatched hematopoietic stem cell tranplantation for pediatric solid tumors

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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.

Promoter hypermethylation of mismatch repair gene hMLH1 predicts the clinical response of malignant astrocytomas to nitrosourea.

Science.gov (United States)

Fukushima, Takao; Katayama, Yoichi; Watanabe, Takao; Yoshino, Atsuo; Ogino, Akiyoshi; Ohta, Takashi; Komine, Chiaki

2005-02-15

In certain types of human cancers, transcriptional inactivation of hMLH1 by promoter hypermethylation plays a causal role in the loss of mismatch repair functions that modulate cytotoxic pathways in response to DNA-damaging agents. The aim of the present study was to investigate the role of promoter methylation of the hMLH1 gene in malignant astrocytomas. We examined the hMLH1 promoter methylation in a homogeneous cohort of patients with 41 malignant astrocytomas treated by 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-2(2-chloroethyl)-3-nitrosourea chemotherapy in combination with radiation and interferon therapy, and assessed the correlation of such methylation with clinical outcome. hMLH1 promoter methylation was found in 6 (15%) of the 41 newly diagnosed malignant astrocytomas. Hypermethylation of the hMLH1 promoter corresponded closely with a loss of immunohistochemical staining for hMLH1 protein (P = 0.0013). Patients with hMLH1-methylated tumors displayed a greater chance of responding to adjuvant therapy as compared with those with hMLH1-unmethylated tumors (P = 0.0150). The presence of hMLH1 hypermethylation was significantly associated with a longer progression-free survival on both univariate analysis (P = 0.0340) and multivariate analysis (P = 0.0161). The present study identified hMLH1 methylation status as a predictor of the clinical response of malignant astrocytomas to chloroethylnitrosourea-based adjuvant therapy. The findings obtained suggest that determination of the methylation status of hMLH1 could provide a potential basis for designing rational chemotherapeutic strategies, as well as for predicting prognosis.

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

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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.

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.

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

Science.gov (United States)

Turner, D P; Connolly, B A

2000-12-15

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

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...

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.

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...

A Computational Model for Biomechanical Effects of Arterial Compliance Mismatch

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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.

In vivo DNA mismatch repair measurement in zebrafish embryos and its use in screening of environmental carcinogens

International Nuclear Information System (INIS)

Chen, Yuanhong; Huang, Changjiang; Bai, Chenglian; Du, Changchun; Liao, Junhua; Dong, Qiaoxiang

2016-01-01

Highlights: • We developed an in vivo DNA mismatch repair (MMR) measurement assay in zebrafish embryos. • This assay involves microinjection of homo- and heteroduplex EGFP plasmids into zebrafish embryos. • This novel assay was validated with embryos from the MMR-deficient mlh1 mutant fish. • We successfully applied this assay for detecting environmental chemicals with carcinogenic effect. • This novel assay can be used for screening of environmental carcinogens. - Abstract: Impairment of DNA mismatch repair (MMR) function leads to the development and progression of certain cancers. Many environmental contaminants can target DNA MMR system. Currently, measurement of MMR activity is limited to in vitro or in vivo methods at the cell line level, and reports on measurement of MMR activity at the live organism level are lacking. Here, we report an efficient method to measure DNA MMR activity in zebrafish embryos. A G-T mismatch was introduced into enhanced green fluorescent protein (EGFP) gene. Repair of the G-T mismatch to G-C in the heteroduplex plasmid generates a functional EGFP expression. The heteroduplex plasmid and a similarly constructed homoduplex plasmid were injected in parallel into the same batch of embryos at 1-cell stage and EGFP expression in EGFP positive embryos was quantified at 24 h after injection. MMR efficiency was calculated as the total fluorescence intensity of embryos injected with the heteroduplex construct divided by that of embryos injected with the homoduplex construct. Our results showed 73% reduction of MMR activity in embryos derived from MMR-deficient mlh1 mutant fish (positive control) when compared with embryos from MMR-competent wild type AB line fish, indicating feasibility of in vivo MMR activity measurement in zebrafish embryos. We further applied this novel assay for measurement of MMR efficiency in embryos exposed to environmental chemicals such as cadmium chloride (CdCl_2), benzo[a]pyrene (BaP), and

In vivo DNA mismatch repair measurement in zebrafish embryos and its use in screening of environmental carcinogens

Energy Technology Data Exchange (ETDEWEB)

Chen, Yuanhong [Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou 325035 (China); Huang, Changjiang, E-mail: cjhuang5711@163.com [Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou 325035 (China); Bai, Chenglian; Du, Changchun; Liao, Junhua [Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou 325035 (China); Dong, Qiaoxiang, E-mail: dqxdong@163.com [Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou 325035 (China); School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325035 (China)

2016-01-25

Highlights: • We developed an in vivo DNA mismatch repair (MMR) measurement assay in zebrafish embryos. • This assay involves microinjection of homo- and heteroduplex EGFP plasmids into zebrafish embryos. • This novel assay was validated with embryos from the MMR-deficient mlh1 mutant fish. • We successfully applied this assay for detecting environmental chemicals with carcinogenic effect. • This novel assay can be used for screening of environmental carcinogens. - Abstract: Impairment of DNA mismatch repair (MMR) function leads to the development and progression of certain cancers. Many environmental contaminants can target DNA MMR system. Currently, measurement of MMR activity is limited to in vitro or in vivo methods at the cell line level, and reports on measurement of MMR activity at the live organism level are lacking. Here, we report an efficient method to measure DNA MMR activity in zebrafish embryos. A G-T mismatch was introduced into enhanced green fluorescent protein (EGFP) gene. Repair of the G-T mismatch to G-C in the heteroduplex plasmid generates a functional EGFP expression. The heteroduplex plasmid and a similarly constructed homoduplex plasmid were injected in parallel into the same batch of embryos at 1-cell stage and EGFP expression in EGFP positive embryos was quantified at 24 h after injection. MMR efficiency was calculated as the total fluorescence intensity of embryos injected with the heteroduplex construct divided by that of embryos injected with the homoduplex construct. Our results showed 73% reduction of MMR activity in embryos derived from MMR-deficient mlh1 mutant fish (positive control) when compared with embryos from MMR-competent wild type AB line fish, indicating feasibility of in vivo MMR activity measurement in zebrafish embryos. We further applied this novel assay for measurement of MMR efficiency in embryos exposed to environmental chemicals such as cadmium chloride (CdCl{sub 2}), benzo[a]pyrene (BaP), and

Association of Carboxylesterase 1 Gene (CES1) Polymorphism with Weight loss in Children with Attention Deficit Hyperactivity Disorder during Methylphenidate Treatment

DEFF Research Database (Denmark)

Oxenbøll, Maria; Kaalund-Jørgensen, Kristine; Rasmussen, Simone

2017-01-01

Children with Attention Deficit Hyperactivity Disorder (ADHD) show large variations in response to methylphenidate (MPH) treatment, which may result from genetic factors associated with MPH metabolism. We aimed at investigating a possible link between the -75 T>G polymorphism in the 5’ untranslated...

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.

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.

A Fixed-Point Phase Lock Loop in a Software Defined Radio

Science.gov (United States)

2002-09-01

code from a simulation model. This feature will allow easy implementation on an FPGA as C can be easily converted to VHDL , the language required...this is equivalent to the MATLAB code implementation in Appendix A. The PD takes the input signal 40 and multiplies it by the in-phase and...stop to 60 mph in 3.1 seconds (the fastest production car ever built is the Porsche Carrera twin turbo which was tested at 0-60 mph in 3.1 seconds

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.

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.

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...

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.

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.

PMS2 gene mutation results in DNA mismatch repair system failure in a case of adult granulosa cell tumor.

Science.gov (United States)

Wang, Wen-Chung; Lee, Ya-Ting; Lai, Yen-Chein

2017-03-27

Granulosa cell tumors are rare ovarian malignancies. Their characteristics include unpredictable indolent growth with malignant potential and late recurrence. Approximately 95% are of adult type. Recent molecular studies have characterized the FOXL2 402C > G mutation in adult granulosa cell tumor. Our previous case report showed that unique FOXL2 402C > G mutation and defective DNA mismatch repair system are associated with the development of adult granulosa cell tumor. In this study, the DNA sequences of four genes, MSH2, MLH1, MSH6, and PMS2, in the DNA mismatch repair system were determined via direct sequencing to elucidate the exact mechanism for the development of this granulosa cell tumor. The results showed that two missense germline mutations, T485K and N775L, inactivate the PMS2 gene. The results of this case study indicated that although FOXL2 402C > G mutation determines the development of granulosa cell tumor, PMS2 mutation may be the initial driver of carcinogenesis. Immunohistochemistry-based tumor testing for mismatch repair gene expression may be necessary for granulosa cell tumors to determine their malignant potential or if they are part of Lynch syndrome.

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.

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

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

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.

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.

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

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

Science.gov (United States)

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

2018-04-18

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

Semantic processing in deaf and hard-of-hearing children: Large N400 mismatch effects in brain responses, despite poor semantic ability

Directory of Open Access Journals (Sweden)

Petter Kallioinen

2016-08-01

Full Text Available Difficulties in auditory and phonological processing affect semantic processing in speech comprehension of deaf and hard-of-hearing (DHH children. However, little is known about brain responses of semantic processing in this group. We investigated event-related potentials (ERPs in DHH children with cochlear implants (CI and/or hearing aids (HA, and in normally hearing controls (NH. We used a semantic priming task with spoken word primes followed by picture targets. In both DHH children and controls, response differences between matching and mismatching targets revealed a typical N400-effect associated with semantic processing. Children with CI had the largest mismatch response despite poor semantic abilities overall, children with CI also had the largest ERP differentiation between mismatch types, with small effects of within-category mismatches (target from same category as prime and large effects between-category mismatches (were target is from a different category than prime. NH and HA children had similar responses to both mismatch types. While the large and differentiated ERP responses in the CI group were unexpected and should be interpreted with caution, the results could reflect less precision in semantic processing among children with CI, or a stronger reliance on predictive processing.

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…

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.)

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

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...

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.

Tumor mismatch repair immunohistochemistry and DNA MLH1 methylation testing of patients with endometrial cancer diagnosed at age younger than 60 years optimizes triage for population-level germline mismatch repair gene mutation testing.

Science.gov (United States)

Buchanan, Daniel D; Tan, Yen Y; Walsh, Michael D; Clendenning, Mark; Metcalf, Alexander M; Ferguson, Kaltin; Arnold, Sven T; Thompson, Bryony A; Lose, Felicity A; Parsons, Michael T; Walters, Rhiannon J; Pearson, Sally-Ann; Cummings, Margaret; Oehler, Martin K; Blomfield, Penelope B; Quinn, Michael A; Kirk, Judy A; Stewart, Colin J; Obermair, Andreas; Young, Joanne P; Webb, Penelope M; Spurdle, Amanda B

2014-01-10

Clinicopathologic data from a population-based endometrial cancer cohort, unselected for age or family history, were analyzed to determine the optimal scheme for identification of patients with germline mismatch repair (MMR) gene mutations. Endometrial cancers from 702 patients recruited into the Australian National Endometrial Cancer Study (ANECS) were tested for MMR protein expression using immunohistochemistry (IHC) and for MLH1 gene promoter methylation in MLH1-deficient cases. MMR mutation testing was performed on germline DNA of patients with MMR-protein deficient tumors. Prediction of germline mutation status was compared for combinations of tumor characteristics, age at diagnosis, and various clinical criteria (Amsterdam, Bethesda, Society of Gynecologic Oncology, ANECS). Tumor MMR-protein deficiency was detected in 170 (24%) of 702 cases. Germline testing of 158 MMR-deficient cases identified 22 truncating mutations (3% of all cases) and four unclassified variants. Tumor MLH1 methylation was detected in 99 (89%) of 111 cases demonstrating MLH1/PMS2 IHC loss; all were germline MLH1 mutation negative. A combination of MMR IHC plus MLH1 methylation testing in women younger than 60 years of age at diagnosis provided the highest positive predictive value for the identification of mutation carriers at 46% versus ≤ 41% for any other criteria considered. Population-level identification of patients with MMR mutation-positive endometrial cancer is optimized by stepwise testing for tumor MMR IHC loss in patients younger than 60 years, tumor MLH1 methylation in individuals with MLH1 IHC loss, and germline mutations in patients exhibiting loss of MSH6, MSH2, or PMS2 or loss of MLH1/PMS2 with absence of MLH1 methylation.

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.

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.

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.

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.

Ovarian cancer at young age: the contribution of mismatch-repair defects in a population-based series of epithelial ovarian

DEFF Research Database (Denmark)

Domanska, K; Malander, S; Måsbäck, A

2007-01-01

and endometrioid cancers were overrepresented and were diagnosed in 27% and 16% of the tumors, respectively. Immunostaining using antibodies against MLH1, PMS2, MSH2, and MSH6 was used to assess the mismatch-repair status and revealed loss of expression of MLH1/PMS2 in two cases, loss of MSH2/MSH6 in one case...

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.

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.

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 �

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....

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.

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...

Mis-Match Limit Load Analyses and Fracture Mechanics Assessment for Welded Pipe with Circumferential Crack at the Center of Weldment

Energy Technology Data Exchange (ETDEWEB)

Song, Tae Kwang; Jeon, Jun Young; Shim, Kwang Bo; Kim, Yun Jae [Korea University, Seoul (Korea, Republic of); Kim, Jong Sung [Sunchon University, Suncheon (Korea, Republic of); Jin, Tae Eun [Korea Power Engineering Company, Daejeon (Korea, Republic of)

2010-01-15

In this paper, limit load analyses and fracture mechanics analyses were conducted via finite element analyses for the welded pipe with circumferential crack at the center of the weldment. Systematic changes for strength mismatch ratio, width of weldment, crack shape and thickness ratio of the pipe were considered to provide strength mismatch limit load. And J-integral calculations based on reference stress method were conducted for two materials, stainless steel and ferritic steel. Reference stress defined by provided strength mis-match limit load gives much more accurate J-integral.

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.

Improvement of the homogeneity of protein-imprinted polymer films by orientated immobilization of the template

Energy Technology Data Exchange (ETDEWEB)

Liu Lijian; Zheng Jingjing; Fang Guijie [Key Laboratory of Fermentation Engineering (Ministry of Education), College of Bioengineering, Hubei University of Technology, Nanhu Li Jia Dun 1, Wuhan 430068 (China); Xie Weihong, E-mail: weihong.xie@yahoo.com.cn [Key Laboratory of Fermentation Engineering (Ministry of Education), College of Bioengineering, Hubei University of Technology, Nanhu Li Jia Dun 1, Wuhan 430068 (China)

2012-05-13

Highlights: Black-Right-Pointing-Pointer MPH was genetically modified at its C-terminal with (Gly-Ser){sub 5}-Cys. Black-Right-Pointing-Pointer MPH-L was immobilized with fixed orientation via disulfide chemistry. Black-Right-Pointing-Pointer The immobilized MPH-L retained the activity of MPH. Black-Right-Pointing-Pointer MPH-L formed a homogeneous template. Black-Right-Pointing-Pointer Homogeneous MIP film was obtained with orientated immobilization of the template. - Abstract: A method for preparing homogeneous protein-imprinted polymer films with orientated immobilization of template is described. The template methyl parathion hydrolase (MPH) was modified with a peptide linker (Gly-Ser){sub 5}-Cys and was immobilized on a cover glass with a fixed orientation via the linker. The activity of the fusion enzyme (MPH-L) was evaluated by determining the product's absorbance at 405 nm (A{sub 405}). Both the free and the immobilized MPH-L showed higher retention of the bioactivity than the wide type enzyme (MPH-W) as revealed by the A{sub 405} values for MPH-L{sub free}/MPH-W{sub free} (1.159/1.111) and for MPH-L{sub immobilized}/MPH-W{sub immobilized} (0.348/0.118). The immobilized MPH-L also formed a more homogeneous template stamp compared to the immobilized MPH-W. The molecularly imprinted polymer films prepared with the immobilized MPH-L exhibited high homogeneity with low Std. Deviations of 80 and 200 from the CL intensity mean volumes which were observed for batch-prepared films and an individual film, respectively. MPH-L-imprinted polymer film also had a larger template binding capacity indicated by higher CL intensity mean volume of 3900 INT over 2500 INT for MPH-W-imprinted films. The imprinted film prepared with the orientated immobilization of template showed an imprinting factor of 1.7, while the controls did not show an imprinting effect.

Improvement of the homogeneity of protein-imprinted polymer films by orientated immobilization of the template

International Nuclear Information System (INIS)

Liu Lijian; Zheng Jingjing; Fang Guijie; Xie Weihong

2012-01-01

Highlights: ► MPH was genetically modified at its C-terminal with (Gly-Ser) 5 –Cys. ► MPH-L was immobilized with fixed orientation via disulfide chemistry. ► The immobilized MPH-L retained the activity of MPH. ► MPH-L formed a homogeneous template. ► Homogeneous MIP film was obtained with orientated immobilization of the template. - Abstract: A method for preparing homogeneous protein-imprinted polymer films with orientated immobilization of template is described. The template methyl parathion hydrolase (MPH) was modified with a peptide linker (Gly-Ser) 5 –Cys and was immobilized on a cover glass with a fixed orientation via the linker. The activity of the fusion enzyme (MPH-L) was evaluated by determining the product's absorbance at 405 nm (A 405 ). Both the free and the immobilized MPH-L showed higher retention of the bioactivity than the wide type enzyme (MPH-W) as revealed by the A 405 values for MPH-L free /MPH-W free (1.159/1.111) and for MPH-L immobilized /MPH-W immobilized (0.348/0.118). The immobilized MPH-L also formed a more homogeneous template stamp compared to the immobilized MPH-W. The molecularly imprinted polymer films prepared with the immobilized MPH-L exhibited high homogeneity with low Std. Deviations of 80 and 200 from the CL intensity mean volumes which were observed for batch-prepared films and an individual film, respectively. MPH-L-imprinted polymer film also had a larger template binding capacity indicated by higher CL intensity mean volume of 3900 INT over 2500 INT for MPH-W-imprinted films. The imprinted film prepared with the orientated immobilization of template showed an imprinting factor of 1.7, while the controls did not show an imprinting effect.

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…

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.

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

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.

Fully relaxed low-mismatched InAlAs layer on an InP substrate by using a two step buffer

NARCIS (Netherlands)

Plissard, S.R.; Coinon, C.; Androussi, Y.; Wallart, X.

2010-01-01

The strain relaxation in low mismatched InxAl1-xAs layers has been studied by triple axis x-ray diffraction, transmission electron microscopy, and photoluminescence. Using a two step buffer, a fully relaxed top layer has been grown by adapting the composition and thickness of a first "strained

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…

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...

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,

Mismatch repair gene mutation spectrum in the Swedish Lynch syndrome population

DEFF Research Database (Denmark)

Lagerstedt-Robinson, Kristina; Rohlin, Anna; Aravidis, Christos

2016-01-01

Lynch syndrome caused by constitutional mismatch‑repair defects is one of the most common hereditary cancer syndromes with a high risk for colorectal, endometrial, ovarian and urothelial cancer. Lynch syndrome is caused by mutations in the mismatch repair (MMR) genes i.e., MLH1, MSH2, MSH6 and PMS2...... Lynch syndrome families. These mutations affected MLH1 in 40%, MSH2 in 36%, MSH6 in 18% and PMS2 in 6% of the families. A large variety of mutations were identified with splice site mutations being the most common mutation type in MLH1 and frameshift mutations predominating in MSH2 and MSH6. Large...... deletions of one or several exons accounted for 21% of the mutations in MLH1 and MSH2 and 22% in PMS2, but were rare (4%) in MSH6. In 66% of the Lynch syndrome families the variants identified were private and the effect from founder mutations was limited and predominantly related to a Finnish founder...

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

Interactive effects of methylphenidate and alcohol on discrimination, conditioned place preference and motor coordination in C57BL/6J mice.

Science.gov (United States)

Griffin, William C; McGovern, Robin W; Bell, Guinevere H; Randall, Patrick K; Middaugh, Lawrence D; Patrick, Kennerly S

2013-02-01

Prior research indicates methylphenidate (MPH) and alcohol (ethanol, EtOH) interact to significantly affect responses humans and mice. The present studies tested the hypothesis that MPH and EtOH interact to potentiate ethanol-related behaviors in mice. We used several behavioral tasks including: drug discrimination in MPH-trained and EtOH-trained mice, conditioned place preference (CPP), rota-rod and the parallel rod apparatus. We also used gas chromatographic methods to measure brain tissue levels of EtOH and the D- and L-isomers of MPH and the metabolite, ethylphenidate (EPH). In discrimination, EtOH (1 g/kg) produced a significant leftward shift in the MPH generalization curve (1-2 mg/kg) for MPH-trained mice, but no effects of MPH (0.625-1.25 mg/kg) on EtOH discrimination in EtOH-trained mice (0-2.5 g/kg) were observed. In CPP, the MPH (1.25 mg/kg) and EtOH (1.75 g/kg) combination significantly increased time on the drug paired side compared to vehicle (30.7 %), but this was similar to MPH (28.8 %) and EtOH (33.6 %). Footslip errors measured in a parallel rod apparatus indicated that the drug combination was very ataxic, with footslips increasing 29.5 % compared to EtOH. Finally, brain EtOH concentrations were not altered by 1.75 g/kg EtOH combined with 1.25 mg/kg MPH. However, EtOH significantly increased D-MPH and L-EPH without changing L-MPH brain concentrations. The enhanced behavioral effects when EtOH is combined with MPH are likely due to the selective increase in brain D-MPH concentrations. These studies are consistent with observations in humans of increased interoceptive awareness of the drug combination and provide new clinical perspectives regarding enhanced ataxic effects of this drug combination.

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

Science.gov (United States)

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

2016-07-01

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

70-year old female patient with mismatch between hematocrit and hemoglobin values: the effects of cold agglutinin on complete blood count.

Science.gov (United States)

Ercan, Serif; Calışkan, Mustafa; Koptur, Erhan

2014-01-01

There are a number of pre-analytical and analytical factors, which cause false results in the complete blood count. The present case identifies cold agglutinins as the cause for the mismatch between hematocrit and hemoglobin values. 70-year old female patient had a history of cerebrovascular diseases and rheumatoid arthritis. During routine laboratory examination, the patient had normal leukocyte and platelet counts; however, the hemoglobin (Hb: 105 g/L) and hematocrit (HCT: 0.214 L/L) results were discordant. Hemolysis, lipemia and cold agglutinin were evaluated as possible reasons for the mismatch between hematocrit and hemoglobin values. First blood sample was slightly hemolysed. Redrawn sample without hemolysis or lipemia was analyzed but the mismatch became even more distinct (Hb: 104 g/L and HCT: 0.08 L/L). In this sample, the titration of the cold agglutinin was determined and found to be positive at 1:64 dilution ratios. After an incubation of the sample at 37°C for 2 hours, reversibility of agglutination was observed. We conclude that cold agglutinins may interfere with the analysis of erythrocyte and erythrocyte-related parameters (HCT, MCV, MCH and MCHC); however, Hb, leukocyte and platelet counts are not affected.

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

Gastric Medullary Carcinoma with Sporadic Mismatch Repair Deficiency and a TP53 R273C Mutation: An Unusual Case with Wild-Type BRAF

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Brett M. Lowenthal

2017-01-01

Full Text Available Medullary carcinoma has long been recognized as a subtype of colorectal cancer associated with microsatellite instability and Lynch syndrome. Gastric medullary carcinoma is a very rare neoplasm. We report a 67-year-old male who presented with a solitary gastric mass. Total gastrectomy revealed a well-demarcated, poorly differentiated carcinoma with an organoid growth pattern, pushing borders, and abundant peritumoral lymphocytic response. The prior cytology was cellular with immunohistochemical panel consistent with upper gastrointestinal/pancreaticobiliary origin. Overall, the histopathologic findings were consistent with gastric medullary carcinoma. A mismatch repair panel revealed a mismatch repair protein deficient tumor with loss of MLH1 and PMS2 expression. BRAF V600E immunostain (VE1 and BRAF molecular testing were negative, indicating a wild-type gene. Tumor sequencing of MLH1 demonstrated a wild-type gene, while our molecular panel identified TP53 c.817C>T (p.R273C mutation. These findings were compatible with a sporadic tumor. Given that morphologically identical medullary tumors often occur in Lynch syndrome, it is possible that mismatch repair loss is an early event in sporadic tumors with p53 mutation being a late event. Despite having wild-type BRAF, this tumor is sporadic and unrelated to Lynch syndrome. This case report demonstrates that coordinate ancillary studies are needed to resolve sporadic versus hereditary rare tumors.

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.

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.

32 CFR 636.22 - Speed regulations.

Science.gov (United States)

2010-07-01

...). (d) The following special speed limits apply: (1) When passing troop formations, 10 miles per hour... vehicles and will obey the following off-road driving speeds: Day Driving: Trails, 16 MPH Cross County, 6 MPH Night Driving: Trails, 5 MPH (with headlights) Cross Country, 5 MPH Night Driving: Trails, 4 MPH...

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)

Somatic mutations in mismatch repair genes in sporadic gastric carcinomas are not a cause but a consequence of the mutator phenotype

NARCIS (Netherlands)

Pinto, Mafalda; Wub, Ying; Mensink, Rob G. J.; Cirnes, Luis; Seruca, Raquel; Hofstra, Robert M. W.

2008-01-01

In hereditary nonpolyposis colorectal cancer (HNPCC), patients' mismatch repair (MMR) gene mutations cause MMR deficiency, leading to microsatellite instability (MSI-H). MSI-H is also found in a substantial fraction of sporadic gastric carcinomas (SGC), mainly due to MLH1 promoter hypermethylation,

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.

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

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...

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.

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.

Association of a carboxylesterase 1 polymorphism with appetite reduction in children and adolescents with attention-deficit/hyperactivity disorder treated with methylphenidate.

Science.gov (United States)

Bruxel, E M; Salatino-Oliveira, A; Genro, J P; Zeni, C P; Polanczyk, G V; Chazan, R; Rohde, L A; Hutz, M H

2013-10-01

Carboxylesterase 1 is the enzyme involved in methylphenidate (MPH) metabolism. The aim of this study was to evaluate the association between a -75 T>G polymorphism and appetite reduction in children with attention-deficit/hyperactivity disorder (ADHD). A sample of 213 children with ADHD was investigated. The primary outcome was appetite reduction measured by the Barkley Stimulant Side Effect Rating Scale applied at baseline, at 1 and 3 months of treatment. MPH doses were augmented until no further clinical improvement or significant adverse events occurred. The G allele presented a trend for association with appetite reduction scores (P=0.05). A significant interaction between the G allele and treatment over time for appetite reduction scores was also observed (P=0.03). The G allele carriers presented a higher risk for appetite reduction worsening when compared with T allele homozygotes (odds ratio=3.47, P=0.01). The present results suggest an influence of carboxylesterase 1 -75 T>G polymorphism on the worsening of appetite reduction with MPH treatment in youths with ADHD.

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.

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.

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

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.

An Unusual Case of Constitutional Mismatch Repair Deficiency Syndrome With Anaplastic Ganglioglioma, Colonic Adenocarcinoma, Osteosarcoma, Acute Myeloid Leukemia, and Signs of Neurofibromatosis Type 1: Case Report.

Science.gov (United States)

Daou, Badih; Zanello, Marc; Varlet, Pascale; Brugieres, Laurence; Jabbour, Pascal; Caron, Olivier; Lavoine, Noémie; Dhermain, Frederic; Willekens, Christophe; Beuvon, Frederic; Malka, David; Lechapt-Zalcmann, Emmanuèle; Abi Lahoud, Georges

2015-07-01

Constitutional mismatch repair deficiency (CMMRD) syndrome is a disorder with recessive inheritance caused by biallelic mismatch repair gene mutations, in which mismatch repair defects are inherited from both parents. This syndrome is associated with multiple cancers occurring in childhood. The most common tumors observed with CMMRD include brain tumors, digestive tract tumors, and hematological malignancies. The aim of this study was to report new phenotypic expressions of CMMRD syndrome and add new insight to the existing knowledge about this disease. A review of the literature was conducted and recommendation for surveillance and follow-up in patients with CMMRD are proposed. We report for the first time in the literature, the case of a 22-year-old female patient who was diagnosed with CMMRD syndrome, with the development of 2 unusual tumors: an anaplastic ganglioglioma and an osteosarcoma. She presented initially with an anaplastic ganglioglioma and later developed several malignancies including colonic adenocarcinoma, osteosarcoma, and acute myeloid leukemia. The patient had an atypical course of her disease with development of the initial malignancy at an older age and a remarkably long survival period despite developing aggressive tumors. Many aspects of this disease are still unknown. We identified a case of CMMRD in a patient presenting with an anaplastic ganglioglioma, who underwent successful surgical resection, chemotherapy, and radiotherapy and has had one of the longest survival periods known with this disease. This case broadens the tumor spectrum observed with CMMRD syndrome with anaplastic ganglioglioma and osteosarcoma as new phenotypic expressions of this genetic defect.

Vitamin A deficiency Ann Burgess MPH

African Journals Online (AJOL)

Angel_D

Here we describe vitamin A deficiency, future articles will cover other ... Vitamin A occurs mainly as 'retinol' in animal foods and as 'Я-carotene' in plant foods c. .... instil chloramphenicol or tetracycline eye drops (as required 2-3 hourly for 7-10.

Enhanced growth of highly lattice-mismatched CdSe on GaAs substrates by molecular beam epitaxy

International Nuclear Information System (INIS)

Wang, Jyh-Shyang; Tsai, Yu-Hsuan; Wang, Hsiao-Hua; Ke, Han-Xiang; Tong, Shih-Chang; Yang, Chu-Shou; Wu, Chih-Hung; Shen, Ji-Lin

2013-01-01

This work demonstrates the improvement of the molecular beam epitaxial growth of zinc-blende CdSe on (0 0 1) GaAs substrate with a large lattice mismatch by introducing a small amount of Te atoms. Exposing the growing surface to Te atoms changes the reflection high-energy electron diffraction pattern from spotty to streaky together with (2 × 1) surface reconstruction, and greatly reduces the full width at half maximum of the X-ray rocking curve and increases the integral intensity of room-temperature photoluminescence by a factor of about nine.

Methylphenidate dose optimization for ADHD treatment: review of safety, efficacy, and clinical necessity

Directory of Open Access Journals (Sweden)

Huss M

2017-07-01

Full Text Available Michael Huss,1 Praveen Duhan,2 Preetam Gandhi,3 Chien-Wei Chen,4 Carsten Spannhuth,3 Vinod Kumar5 1Child and Adolescent Psychiatry, University Medicine, Mainz, Germany; 2Global Medical Affairs, Novartis Healthcare Pvt. Ltd., Hyderabad, India; 3Development Franchise, Established Medicine Neuroscience, Novartis Pharma AG, Basel, Switzerland; 4Biostatistics Cardio-Metabolic & Established Medicine, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 5Established Medicines, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA Abstract: Attention-deficit/hyperactivity disorder (ADHD is a chronic psychiatric disorder characterized by hyperactivity and/or inattention and is often associated with a substantial impact on psychosocial functioning. Methylphenidate (MPH, a central nervous system stimulant, is commonly used for pharmacological treatment of adults and children with ADHD. Current practice guidelines recommend optimizing MPH dosage to individual patient needs; however, the clinical benefits of individual dose optimization compared with fixed-dose regimens remain unclear. Here we review the available literature on MPH dose optimization from clinical trials and real-world experience on ADHD management. In addition, we report safety and efficacy data from the largest MPH modified-release long-acting Phase III clinical trial conducted to examine benefits of dose optimization in adults with ADHD. Overall, MPH is an effective ADHD treatment with a good safety profile; data suggest that dose optimization may enhance the safety and efficacy of treatment. Further research is required to establish the extent to which short-term clinical benefits of MPH dose optimization translate into improved long-term outcomes for patients with ADHD. Keywords: methylphenidate, dose optimization, attention-deficit/hyperactivity disorder, ADHD

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

Science.gov (United States)

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

2014-10-15

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

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…

Methylphenidate use and poly-substance use among undergraduate students attending a South African university

Directory of Open Access Journals (Sweden)

Francois Steyn

2016-03-01

Full Text Available Background: Methylphenidate hydrochloride (MPH is used in the treatment of attention deficit hyperactivity disorder (ADHD. The non-medical use of MPH by learners and students has been reported by numerous studies from abroad. The practice stems from beliefs about the benefits of MPH in achieving academic success. Little is known about the use of MPH in South African student populations. Objectives: The study set out to determine (1 the extent and dynamics associated with MPH use and (2 poly-substance use among undergraduate students attending a South African university. Methods: 818 students took part in a written, group-administered survey. Data analysis resulted in descriptive results regarding MPH use and tests of association identified differences in MPH and poly-substance use among respondents. Results: One in six respondents (17.2% has used MPH in the past, although only 2.9% have been diagnosed with ADHD. Nearly a third (31.7% of users obtained MPH products illegally. The majority (69.1% used MPH only during periods of academic stress. A significant association ( p < 0.001 was found between MPH use and the frequency of using alcohol, tobacco, cannabis, hard drugs (e.g. cocaine and prescription medication. Conclusion: MPH use among students appears similar to experiences abroad, especially in the absence of clinical diagnosis for ADHD. Institutions of higher education should inform parents and students about the health risks associated with the illicit use of MPH. Prescribers and dispensers of MPH products should pay close attention to practices of stockpiling medication and poly-substance use among students who use MPH.

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...

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.

Thermodynamic and structural properties of the specific binding between Ag⁺ ion and C:C mismatched base pair in duplex DNA to form C-Ag-C metal-mediated base pair.

Science.gov (United States)

Torigoe, Hidetaka; Okamoto, Itaru; Dairaku, Takenori; Tanaka, Yoshiyuki; Ono, Akira; Kozasa, Tetsuo

2012-11-01

Metal ion-nucleic acid interactions have attracted considerable interest for their involvement in structure formation and catalytic activity of nucleic acids. Although interactions between metal ion and mismatched base pair duplex are important to understand mechanism of gene mutations related to heavy metal ions, they have not been well-characterized. We recently found that the Ag(+) ion stabilized a C:C mismatched base pair duplex DNA. A C-Ag-C metal-mediated base pair was supposed to be formed by the binding between the Ag(+) ion and the C:C mismatched base pair to stabilize the duplex. Here, we examined specificity, thermodynamics and structure of possible C-Ag-C metal-mediated base pair. UV melting indicated that only the duplex with the C:C mismatched base pair, and not of the duplexes with the perfectly matched and other mismatched base pairs, was specifically stabilized on adding the Ag(+) ion. Isothermal titration calorimetry demonstrated that the Ag(+) ion specifically bound with the C:C base pair at 1:1 molar ratio with a binding constant of 10(6) M(-1), which was significantly larger than those for nonspecific metal ion-DNA interactions. Electrospray ionization mass spectrometry also supported the specific 1:1 binding between the Ag(+) ion and the C:C base pair. Circular dichroism spectroscopy and NMR revealed that the Ag(+) ion may bind with the N3 positions of the C:C base pair without distorting the higher-order structure of the duplex. We conclude that the specific formation of C-Ag-C base pair with large binding affinity would provide a binding mode of metal ion-DNA interactions, similar to that of the previously reported T-Hg-T base pair. The C-Ag-C base pair may be useful not only for understanding of molecular mechanism of gene mutations related to heavy metal ions but also for wide variety of potential applications of metal-mediated base pairs in various fields, such as material, life and environmental sciences. Copyright © 2012 Elsevier

Maturation of cortical mismatch responses to occasional pitch change in early infancy: effects of presentation rate and magnitude of change.

Science.gov (United States)

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

2009-01-01

Previous studies have reported two types of event-related potential (ERP) mismatch responses in infants to infrequent auditory changes: a broad discriminative positivity in younger infants and a negativity resembling adult mismatch negativity (MMN) in older infants. In the present study, we investigated whether the positive discriminative slow wave and the adult-like MMN are functionally distinct by examining how they are affected by presentation rate and magnitude of change. We measured ERPs from adults, 2-month-olds, and 4-month-olds to a repeating piano tone (standard) that occasionally changed in pitch (deviant). The pitch changes between standards and deviants were either small (1/12 octave) or large (1/2 octave) in magnitude, and the stimulus presentation rate was either slow (800 ms SOA) or fast (400 ms SOA). As the presentation rate increased, both adults and 4-month-olds showed an MMN response that decreased in latency, but was unaffected in amplitude. As the magnitude of the pitch change increased, MMN increased in amplitude. On the other hand, only a broad positive mismatch response was seen in 2-month-olds. As the presentation rate increased, 2-month-olds' responses to standard tones decreased in amplitude while their responses to deviant tones were unaffected. The magnitude of the pitch change did not affect 2-month-olds' responses. These results suggest that pitch is processed differently in auditory cortex by 2-month-olds and 4-month-olds, and that a cortical change-detection mechanism for pitch discrimination similar to that of adults emerges between 2 and 4 months of age.

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