Self-Selection of Frequency Tables with Bilateral Mismatches in an Acoustic Simulation of a Cochlear Implant

PubMed Central

Fitzgerald, Matthew B.; Prosolovich, Ksenia; Tan, Chin-Tuan; Glassman, E. Katelyn; Svirsky, Mario A.

2017-01-01

Background Many recipients of bilateral cochlear implants (CIs) may have differences in electrode insertion depth. Previous reports indicate that when a bilateral mismatch is imposed, performance on tests of speech understanding or sound localization becomes worse. If recipients of bilateral CIs cannot adjust to a difference in insertion depth, adjustments to the frequency table may be necessary to maximize bilateral performance. Purpose The purpose of this study was to examine the feasibility of using real-time manipulations of the frequency table to offset any decrements in performance resulting from a bilateral mismatch. Research Design A simulation of a CI was used because it allows for explicit control of the size of a bilateral mismatch. Such control is not available with users of CIs. Study Sample A total of 31 normal-hearing young adults participated in this study. Data Collection and Analysis Using a CI simulation, four bilateral mismatch conditions (0, 0.75, 1.5, and 3 mm) were created. In the left ear, the analysis filters and noise bands of the CI simulation were the same. In the right ear, the noise bands were shifted higher in frequency to simulate a bilateral mismatch. Then, listeners selected a frequency table in the right ear that was perceived as maximizing bilateral speech intelligibility. Word-recognition scores were then assessed for each bilateral mismatch condition. Listeners were tested with both a standard frequency table, which preserved a bilateral mismatch, or with their self-selected frequency table. Results Consistent with previous reports, bilateral mismatches of 1.5 and 3 mm yielded decrements in word recognition when the standard table was used in both ears. However, when listeners used the self-selected frequency table, performance was the same regardless of the size of the bilateral mismatch. Conclusions Self-selection of a frequency table appears to be a feasible method for ameliorating the negative effects of a bilateral mismatch. These data may have implications for recipients of bilateral CIs who cannot adapt to a bilateral mismatch, because they suggest that (1) such individuals may benefit from modification of the frequency table in one ear and (2) self-selection of a “most intelligible” frequency table may be a useful tool for determining how the frequency table should be altered to optimize speech recognition. PMID:28534729

Mismatch Negativity and P3a in Adolescents and Young Adults with Autism Spectrum Disorders: Behavioral Correlates and Clinical Implications

ERIC Educational Resources Information Center

Chien, Yi-Ling; Hsieh, Ming Hsien; Gau, Susan Shur-Fen

2018-01-01

In a sample of 37 adolescents and young adults with autism spectrum disorder (ASD) and 35 typically-developing controls (TDC), we investigated sensory symptoms by clinical measures, and Mismatch Negativity and P3a component at Fz with the frequency and duration oddball paradigms of event-related potentials. Results showed that compared to TDC, ASD…

Recent sequence variation in probe binding site affected detection of respiratory syncytial virus group B by real-time RT-PCR.

PubMed

Kamau, Everlyn; Agoti, Charles N; Lewa, Clement S; Oketch, John; Owor, Betty E; Otieno, Grieven P; Bett, Anne; Cane, Patricia A; Nokes, D James

2017-03-01

Direct immuno-fluorescence test (IFAT) and multiplex real-time RT-PCR have been central to RSV diagnosis in Kilifi, Kenya. Recently, these two methods showed discrepancies with an increasing number of PCR undetectable RSV-B viruses. Establish if mismatches in the primer and probe binding sites could have reduced real-time RT-PCR sensitivity. Nucleoprotein (N) and glycoprotein (G) genes were sequenced for real-time RT-PCR positive and negative samples. Primer and probe binding regions in N gene were checked for mismatches and phylogenetic analyses done to determine molecular epidemiology of these viruses. New primers and probe were designed and tested on the previously real-time RT-PCR negative samples. N gene sequences revealed 3 different mismatches in the probe target site of PCR negative, IFAT positive viruses. The primers target sites had no mismatches. Phylogenetic analysis of N and G genes showed that real-time RT-PCR positive and negative samples fell into distinct clades. Newly designed primers-probe pair improved detection and recovered previous PCR undetectable viruses. An emerging RSV-B variant is undetectable by a quite widely used real-time RT-PCR assay due to polymorphisms that influence probe hybridization affecting PCR accuracy. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

The separate and combined effects of monoamine oxidase A inhibition and nicotine on the mismatch negativity event related potential.

PubMed

Smith, Dylan M; Fisher, Derek; Blier, Pierre; Ilivitsky, Vadim; Knott, Verner

2015-10-01

The mismatch negativity (MMN) auditory event-related potential (ERP) has been extensively studied as a potential biomarker for abnormal auditory processing in schizophrenia (SZ), a population which exhibits abnormally high smoking rates. The relationship between nicotinic activation and cognition in SZ may be related to underlying nicotinic and NMDA receptor dysfunction within the disease. However, transient cognitive improvements via smoking in patients may also result from monoamine oxidase (MAO) inhibition, achieved through tobacco smoke. In 24 healthy non-smoking males, we investigated the separate and combined effects of nicotine and MAO-A inhibition via moclobemide (75mg) on the optimal-5 variation of the MMN paradigm. No significant drug effects were observed in our total sample, however, stratification of individuals into low (N=12) and high (N=12) baseline MMN amplitude groups revealed increases in duration MMN amplitude relative to placebo by nicotine, as well as moclobemide, but not after the combination of the two. Because previous research has shown there was no effect of monoamine modulation on MMN, this study shows an unexpected effect of moclobemide on duration MMN. Copyright © 2015 Elsevier Inc. All rights reserved.

Stem cell collection in unmanipulated HLA-haploidentical/mismatched related transplantation with combined granulocyte-colony stimulating factor-mobilised blood and bone marrow for patients with haematologic malignancies: the impact of donor characteristics and procedural settings.

PubMed

Zhang, C; Chen, X-H; Zhang, X; Gao, L; Gao, L; Kong, P-Y; Peng, X-G; Sun, A-H; Gong, Y; Zeng, D-F; Wang, Q-Y

2010-06-01

Unmanipulated haploidentical/mismatched related transplantation with combined granulocyte-colony stimulating factor-mobilised peripheral blood stem cells (G-PBSCs) and granulocyte-colony stimulating factor-mobilised bone marrow (G-BM) has been developed as an alternative transplantation strategy for patients with haematologic malignancies. However, little information is available about the factors predicting the outcome of peripheral blood stem cell (PBSC) collection and bone marrow (BM) harvest in this transplantation. The effects of donor characteristics and procedure factors on CD34(+) cell yield were investigated. A total of 104 related healthy donors received granulocyte-colony stimulating factor (G-CSF) followed by PBSC collection and BM harvest. Male donors had significantly higher yields compared with female donors. In multiple regression analysis for peripheral blood collection, age and flow rate were negatively correlated with cell yield, whereas body mass index, pre-aphaeresis white blood cell (WBC) and circulating immature cell (CIC) counts were positively correlated with cell yields. For BM harvest, age was negatively correlated with cell yields, whereas pre-BM collection CIC counts were positively correlated with cell yield. All donors achieved the final product of >or=6 x10(6) kg(-1) recipient body weight. This transplantation strategy has been shown to be a feasible approach with acceptable outcomes in stem cell collection for patients who received HLA-haploidentical/mismatched transplantation with combined G-PBSCs and G-BM. In donors with multiple high-risk characteristics for poor aphaeresis CD34(+) cell yield, BM was an alternative source.

Immediate integration of prosodic information from speech and visual information from pictures in the absence of focused attention: a mismatch negativity study.

PubMed

Li, X; Yang, Y; Ren, G

2009-06-16

Language is often perceived together with visual information. Recent experimental evidences indicated that, during spoken language comprehension, the brain can immediately integrate visual information with semantic or syntactic information from speech. Here we used the mismatch negativity to further investigate whether prosodic information from speech could be immediately integrated into a visual scene context or not, and especially the time course and automaticity of this integration process. Sixteen Chinese native speakers participated in the study. The materials included Chinese spoken sentences and picture pairs. In the audiovisual situation, relative to the concomitant pictures, the spoken sentence was appropriately accented in the standard stimuli, but inappropriately accented in the two kinds of deviant stimuli. In the purely auditory situation, the speech sentences were presented without pictures. It was found that the deviants evoked mismatch responses in both audiovisual and purely auditory situations; the mismatch negativity in the purely auditory situation peaked at the same time as, but was weaker than that evoked by the same deviant speech sounds in the audiovisual situation. This pattern of results suggested immediate integration of prosodic information from speech and visual information from pictures in the absence of focused attention.

Total variation-based method for radar coincidence imaging with model mismatch for extended target

NASA Astrophysics Data System (ADS)

Cao, Kaicheng; Zhou, Xiaoli; Cheng, Yongqiang; Fan, Bo; Qin, Yuliang

2017-11-01

Originating from traditional optical coincidence imaging, radar coincidence imaging (RCI) is a staring/forward-looking imaging technique. In RCI, the reference matrix must be computed precisely to reconstruct the image as preferred; unfortunately, such precision is almost impossible due to the existence of model mismatch in practical applications. Although some conventional sparse recovery algorithms are proposed to solve the model-mismatch problem, they are inapplicable to nonsparse targets. We therefore sought to derive the signal model of RCI with model mismatch by replacing the sparsity constraint item with total variation (TV) regularization in the sparse total least squares optimization problem; in this manner, we obtain the objective function of RCI with model mismatch for an extended target. A more robust and efficient algorithm called TV-TLS is proposed, in which the objective function is divided into two parts and the perturbation matrix and scattering coefficients are updated alternately. Moreover, due to the ability of TV regularization to recover sparse signal or image with sparse gradient, TV-TLS method is also applicable to sparse recovering. Results of numerical experiments demonstrate that, for uniform extended targets, sparse targets, and real extended targets, the algorithm can achieve preferred imaging performance both in suppressing noise and in adapting to model mismatch.

The Context Matters: Outcome Probability and Expectation Mismatch Modulate the Feedback Negativity When Self-Evaluation of Response Correctness Is Possible

PubMed Central

Leue, Anja; Cano Rodilla, Carmen; Beauducel, André

2015-01-01

Individuals typically evaluate whether their performance and the obtained feedback match. Previous research has shown that feedback negativity (FN) depends on outcome probability and feedback valence. It is, however, less clear to what extent previous effects of outcome probability on FN depend on self-evaluations of response correctness. Therefore, we investigated the effects of outcome probability on FN amplitude in a simple go/no-go task that allowed for the self-evaluation of response correctness. We also investigated effects of performance incompatibility and feedback valence. In a sample of N = 22 participants, outcome probability was manipulated by means of precues, feedback valence by means of monetary feedback, and performance incompatibility by means of feedback that induced a match versus mismatch with individuals' performance. We found that the 100% outcome probability condition induced a more negative FN following no-loss than the 50% outcome probability condition. The FN following loss was more negative in the 50% compared to the 100% outcome probability condition. Performance-incompatible loss resulted in a more negative FN than performance-compatible loss. Our results indicate that the self-evaluation of the correctness of responses should be taken into account when the effects of outcome probability and expectation mismatch on FN are investigated. PMID:26783525

The Context Matters: Outcome Probability and Expectation Mismatch Modulate the Feedback Negativity When Self-Evaluation of Response Correctness Is Possible.

PubMed

Leue, Anja; Cano Rodilla, Carmen; Beauducel, André

2015-01-01

Individuals typically evaluate whether their performance and the obtained feedback match. Previous research has shown that feedback negativity (FN) depends on outcome probability and feedback valence. It is, however, less clear to what extent previous effects of outcome probability on FN depend on self-evaluations of response correctness. Therefore, we investigated the effects of outcome probability on FN amplitude in a simple go/no-go task that allowed for the self-evaluation of response correctness. We also investigated effects of performance incompatibility and feedback valence. In a sample of N = 22 participants, outcome probability was manipulated by means of precues, feedback valence by means of monetary feedback, and performance incompatibility by means of feedback that induced a match versus mismatch with individuals' performance. We found that the 100% outcome probability condition induced a more negative FN following no-loss than the 50% outcome probability condition. The FN following loss was more negative in the 50% compared to the 100% outcome probability condition. Performance-incompatible loss resulted in a more negative FN than performance-compatible loss. Our results indicate that the self-evaluation of the correctness of responses should be taken into account when the effects of outcome probability and expectation mismatch on FN are investigated.

Physical Origin of Transient Negative Capacitance in a Ferroelectric Capacitor

NASA Astrophysics Data System (ADS)

Chang, Sou-Chi; Avci, Uygar E.; Nikonov, Dmitri E.; Manipatruni, Sasikanth; Young, Ian A.

2018-01-01

Transient negative differential capacitance, the dynamic reversal of transient capacitance in an electrical circuit, is of highly technological and scientific interest since it probes the foundation of ferroelectricity. We study a resistor-ferroelectric capacitor (R -FEC) network through a series of coupled equations based on Kirchhoff's law, electrostatics, and Landau theory. We show that transient negative capacitance (NC) in a R -FEC circuit originates from the mismatch in switching rate between the free charge on the metal plate and the bound charge in a ferroelectric (FE) capacitor during the polarization switching. This transient free charge-polarization mismatch is driven by the negative curvature of the FE free-energy landscape, and it is also analytically shown that a free-energy profile with a negative curvature is the only physical system that can describe transient NC in a R -FEC circuit. Furthermore, transient NC induced by the free charge-polarization mismatch is justified by its dependence on both external resistance and the intrinsic FE viscosity coefficient. The depolarization effect on FE capacitors emphasizes the importance of negative curvature to transient NC and also implies that transient and steady-state NC cannot be observed in a FE capacitor simultaneously. Finally, using the transient NC measurements, a procedure to experimentally determine the viscosity coefficient is presented to provide more insight into the relation between transient NC and the FE free-energy profile.

Worktime control access, need and use in relation to work-home interference, fatigue, and job motivation.

PubMed

Nijp, Hylco H; Beckers, Debby G J; Kompier, Michiel A J; van den Bossche, Seth N J; Geurts, Sabine A E

2015-07-01

Worktime control (WTC) has been suggested as a tool to reduce employees' work-home interference and fatigue and improve job motivation. The purpose of this study was twofold: (i) to examine the prevalence of employees' need for, access to, and use of WTC, as well as the incongruence between need for and access to WTC (ie, mismatch); and (ii) to examine the associations of this mismatch and the use of WTC with employees' work-home interference (WHI), fatigue and job motivation. Questionnaire data were collected among a large (N=2420) quasi-representative sample of Dutch employees. The prevalence of WTC need, access, use, and mismatch was assessed by means of descriptive statistics. Associations with employees' outcomes were assessed by analyses of covariance. The need for WTC was highly prevalent. For many employees, we observed a negative mismatch between access to and need for WTC (ie, access

Equine bone marrow-derived mesenchymal stromal cells are heterogeneous in MHC class II expression and capable of inciting an immune response in vitro

PubMed Central

2014-01-01

Introduction The horse is a valuable species to assess the effect of allogeneic mesenchymal stromal cells (MSCs) in regenerative treatments. No studies to date have examined recipient response to major histocompatibility complex (MHC)-mismatched equine MSCs. The purposes of this study were to immunophenotype MSCs from horses of known MHC haplotype and to compare the immunogenicity of MSCs with differing MHC class II expression. Methods MSCs and peripheral blood leukocytes (PBLs) were obtained from Thoroughbred horses (n = 10) of known MHC haplotype (ELA-A2, -A3, and -A9 homozygotes). MSCs were cultured through P8; cells from each passage (P2 to P8) were cryopreserved until used. Immunophenotyping of MHC class I and II, CD44, CD29, CD90, LFA-1, and CD45RB was performed by using flow cytometry. Tri-lineage differentiation assays were performed to confirm MSC multipotency. Recombinant equine IFN-γ was used to stimulate MHC class II negative MSCs in culture, after which expression of MHC class II was re-examined. To assess the ability of MHC class II negative or positive MSCs to stimulate an immune response, modified one-way mixed leukocyte reactions (MLRs) were performed by using MHC-matched and mismatched responder PBLs and stimulator PBLs or MSCs. Proliferation of gated CFSE-labeled CD3+ responder T cells was evaluated via CFSE attenuation by using flow cytometry and reported as the number of cells in the proliferating T-cell gate. Results MSCs varied widely in MHC class II expression despite being homogenous in terms of “stemness” marker expression and ability to undergo trilineage differentiation. Stimulation of MHC class II negative MSCs with IFN-γ resulted in markedly increased expression of MHC class II. MLR results revealed that MHC-mismatched MHC class II-positive MSCs caused significantly increased responder T-cell proliferation compared with MHC-mismatched MHC class II-negative and MHC-matched MSCs, and equivalent to that of the positive control of MHC-mismatched leukocytes. Conclusions The results of this study suggest that MSCs should be confirmed as MHC class II negative before allogeneic application. Additionally, it must be considered that even MHC class II-negative MSCs could upregulate MHC class II expression if implanted into an area of active inflammation, as demonstrated with in vitro stimulation with IFN-γ. PMID:24461709

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

PubMed

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.

Is Auditory Discrimination Mature by Middle Childhood? A Study Using Time-Frequency Analysis of Mismatch Responses from 7 Years to Adulthood

ERIC Educational Resources Information Center

Bishop, Dorothy V. M.; Hardiman, Mervyn J.; Barry, Johanna G.

2011-01-01

Behavioural and electrophysiological studies give differing impressions of when auditory discrimination is mature. Ability to discriminate frequency and speech contrasts reaches adult levels only around 12 years of age, yet an electrophysiological index of auditory discrimination, the mismatch negativity (MMN), is reported to be as large in…

Reactivity of cytosine and thymine in single-base-pair mismatches with hydroxylamine and osmium tetroxide and its application to the study of mutations.

PubMed Central

Cotton, R G; Rodrigues, N R; Campbell, R D

1988-01-01

The chemical reactivity of thymine (T), when mismatched with the bases cytosine, guanine, and thymine, and of cytosine (C), when mismatched with thymine, adenine, and cytosine, has been examined. Heteroduplex DNAs containing such mismatched base pairs were first incubated with osmium tetroxide (for T and C mismatches) or hydroxylamine (for C mismatches) and then incubated with piperidine to cleave the DNA at the modified mismatched base. This cleavage was studied with an internally labeled strand containing the mismatched T or C, such that DNA cleavage and thus reactivity could be detected by gel electrophoresis. Cleavage at a total of 13 T and 21 C mismatches isolated (by at least three properly paired bases on both sides) single-base-pair mismatches was identified. All T or C mismatches studied were cleaved. By using end-labeled DNA probes containing T or C single-base-pair mismatches and conditions for limited cleavage, we were able to show that cleavage was at the base predicted by sequence analysis and that mismatches in a length of DNA could be readily detected by such an approach. This procedure may enable detection of all single-base-pair mismatches by use of sense and antisense probes and thus may be used to identify the mutated base and its position in a heteroduplex. Images PMID:3260032

Automatic auditory processing deficits in schizophrenia and clinical high-risk patients: forecasting psychosis risk with mismatch negativity.

PubMed

Perez, Veronica B; Woods, Scott W; Roach, Brian J; Ford, Judith M; McGlashan, Thomas H; Srihari, Vinod H; Mathalon, Daniel H

2014-03-15

Only about one third of patients at high risk for psychosis based on current clinical criteria convert to a psychotic disorder within a 2.5-year follow-up period. Targeting clinical high-risk (CHR) individuals for preventive interventions could expose many to unnecessary treatments, underscoring the need to enhance predictive accuracy with nonclinical measures. Candidate measures include event-related potential components with established sensitivity to schizophrenia. Here, we examined the mismatch negativity (MMN) component of the event-related potential elicited automatically by auditory deviance in CHR and early illness schizophrenia (ESZ) patients. We also examined whether MMN predicted subsequent conversion to psychosis in CHR patients. Mismatch negativity to auditory deviants (duration, frequency, and duration + frequency double deviant) was assessed in 44 healthy control subjects, 19 ESZ, and 38 CHR patients. Within CHR patients, 15 converters to psychosis were compared with 16 nonconverters with at least 12 months of clinical follow-up. Hierarchical Cox regression examined the ability of MMN to predict time to psychosis onset in CHR patients. Irrespective of deviant type, MMN was significantly reduced in ESZ and CHR patients relative to healthy control subjects and in CHR converters relative to nonconverters. Mismatch negativity did not significantly differentiate ESZ and CHR patients. The duration + frequency double deviant MMN, but not the single deviant MMNs, significantly predicted the time to psychosis onset in CHR patients. Neurophysiological mechanisms underlying automatic processing of auditory deviance, as reflected by the duration + frequency double deviant MMN, are compromised before psychosis onset and can enhance the prediction of psychosis risk among CHR patients. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2001-03-01

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

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

PubMed

Miyanishi, Tomohiro; Sumiyoshi, Tomiki; Higuchi, Yuko; Seo, Tomonori; Suzuki, Michio

2013-01-01

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

Higher Rate of Revision in PFC Sigma Primary Total Knee Arthroplasty With Mismatch of Femoro-Tibial Component Sizes.

PubMed

Young, Simon W; Clarke, Henry D; Graves, Stephen E; Liu, Yen-Liang; de Steiger, Richard N

2015-05-01

Total knee arthroplasty (TKA) systems permit a degree of femoro-tibial component size mismatch. The effect of mismatched components on revision rates has not been evaluated in a large study. We reviewed 21,906 fixed-bearing PFC Sigma primary TKAs using the Australian Orthopaedic Association National Joint Replacement Registry, dividing patients into three groups: no femoro-tibial size mismatch, tibial component size > femoral component size, and femoral component > tibial component. Revision rates were higher when the femoral size was greater than the tibia, compared to both equal size (HR = 1.20 (1.00, 1.45), P = 0.047) and to tibial size greater than femoral (HR = 1.60 (1.08, 2.37), P = 0.019). Potential mechanisms to explain these findings include edge loading of polyethylene and increased tibial component stresses. Copyright © 2014 Elsevier Inc. All rights reserved.

Incidence of a single subsegmental mismatched perfusion defect in single-photon emission computed tomography and planar ventilation/perfusion scans.

PubMed

Stubbs, Matthew; Chan, Kenneth; McMeekin, Helena; Navalkissoor, Shaunak; Wagner, Thomas

2017-02-01

This study aims to compare the incidence of ventilation/perfusion (V/Q) scans interpreted as indeterminate for the diagnosis of pulmonary embolism (PE) using single-photon emission computed tomography (SPECT) versus planar scintigraphy and to consider the effect of variable interpretation of single subsegmental V/Q mismatch (SSM). A total of 1300 consecutive V/Q scans were retrospectively reviewed. After exclusion and matching for age and sex, 542 SPECT and 589 planar scans were included in the analysis. European Association of Nuclear Medicine guidelines were used to interpret the V/Q scans, initially interpreting SSM as negative scans. Patients with SSM were followed up for 3 months and further imaging for PE was collected. Indeterminate scans were significantly fewer in the SPECT than the planar group on the basis of the initial report (7.7 vs. 12.2%, P<0.05). This is irrespective of classification of SSM as a negative scan (4.6 vs. 12.1%, P<0.0001) or an indeterminate scan (8.3 vs. 12.2%, P<0.05). Of the 21 patients who had SSM, 19 underwent computer tomography pulmonary angiogram and embolism was found in one patient. None of these patients died at the 3-month follow-up. V/Q SPECT has greater diagnostic certainty of PE, with a 41% reduction in an indeterminate scan compared with planar scintigraphy. This is irrespective of the clinician's interpretation of SSM as negative or intermediate probability. Patients with SSM would not require further computer tomography pulmonary angiogram imaging.

Supply-demand mismatch transients in susceptible peri-infarct hot zones explain the origins of spreading injury depolarizations.

PubMed

von Bornstädt, Daniel; Houben, Thijs; Seidel, Jessica L; Zheng, Yi; Dilekoz, Ergin; Qin, Tao; Sandow, Nora; Kura, Sreekanth; Eikermann-Haerter, Katharina; Endres, Matthias; Boas, David A; Moskowitz, Michael A; Lo, Eng H; Dreier, Jens P; Woitzik, Johannes; Sakadžić, Sava; Ayata, Cenk

2015-03-04

Peri-infarct depolarizations (PIDs) are seemingly spontaneous spreading depression-like waves that negatively impact tissue outcome in both experimental and human stroke. Factors triggering PIDs are unknown. Here, we show that somatosensory activation of peri-infarct cortex triggers PIDs when the activated cortex is within a critical range of ischemia. We show that the mechanism involves increased oxygen utilization within the activated cortex, worsening the supply-demand mismatch. We support the concept by clinical data showing that mismatch predisposes stroke patients to PIDs as well. Conversely, transient worsening of mismatch by episodic hypoxemia or hypotension also reproducibly triggers PIDs. Therefore, PIDs are triggered upon supply-demand mismatch transients in metastable peri-infarct hot zones due to increased demand or reduced supply. Based on the data, we propose that minimizing sensory stimulation and hypoxic or hypotensive transients in stroke and brain injury would reduce PID incidence and their adverse impact on outcome. Copyright © 2015 Elsevier Inc. All rights reserved.

Supply-demand mismatch transients in susceptible peri-infarct hot zones explain the origin of spreading injury depolarizations

PubMed Central

von Bornstädt, Daniel; Houben, Thijs; Seidel, Jessica; Zheng, Yi; Dilekoz, Ergin; Qin, Tao; Sandow, Nora; Kura, Sreekanth; Eikermann-Haerter, Katharina; Endres, Matthias; Boas, David A.; Moskowitz, Michael A.; Lo, Eng H.; Dreier, Jens P.; Woitzik, Johannes; Sakadžić, Sava; Ayata, Cenk

2015-01-01

SUMMARY Peri-infarct depolarizations (PIDs) are seemingly spontaneous spreading depression-like waves that negatively impact tissue outcome in both experimental and human stroke. Factors triggering PIDs are unknown. Here, we show that somatosensory activation of peri-infarct cortex triggers PIDs when the activated cortex is within a critical range of ischemia. We show that the mechanism involves increased oxygen utilization within the activated cortex, worsening the supply-demand mismatch. We support the concept by clinical data showing that mismatch predisposes to PIDs in human stroke as well. Conversely, transient worsening of mismatch by episodic hypoxemia or hypotension also reproducibly triggers PIDs. Therefore, PIDs are triggered upon supply-demand mismatch transients in metastable peri-infarct hot zones due to increased demand or reduced supply. Based on the data, we propose that minimizing sensory stimulation and hypoxic or hypotensive transients in stroke and brain injury would reduce PID incidence and their adverse impact on outcome. PMID:25741731

Energetic basis for selective recognition of T*G mismatched base pairs in DNA by imidazole-rich polyamides.

PubMed

Lacy, Eilyn R; Nguyen, Binh; Le, Minh; Cox, Kari K; OHare, Caroline; Hartley, John A; Lee, Moses; Wilson, W David

2004-01-01

To complement available structure and binding results and to develop a detailed understanding of the basis for selective molecular recognition of T.G mismatches in DNA by imidazole containing polyamides, a full thermodynamic profile for formation of the T.G-polyamide complex has been determined. The amide-linked heterocycles f-ImImIm and f-PyImIm (where f is formamido group, Im is imidazole and Py is pyrrole) were studied by using biosensor-surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC) with a T.G mismatch containing DNA hairpin duplex and a similar DNA with only Watson-Crick base pairs. Large negative binding enthalpies for all of the polyamide-DNA complexes indicate that the interactions are enthalpically driven. SPR results show slower complex formation and stronger binding of f-ImImIm to the T.G than to the match site. The thermodynamic analysis indicates that the enhanced binding to the T.G site is the result of better entropic contributions. Negative heat capacity changes for the complex are correlated with calculated solvent accessible surface area changes and indicate hydrophobic contributions to complex formation. DNase I footprinting analysis in a long DNA sequence provided supporting evidence that f-ImImIm binds selectively to T.G mismatch sites.

Energetic basis for selective recognition of T·G mismatched base pairs in DNA by imidazole-rich polyamides

PubMed Central

Lacy, Eilyn R.; Nguyen, Binh; Le, Minh; Cox, Kari K.; O'Hare, Caroline; Hartley, John A.; Lee, Moses; Wilson, W. David

2004-01-01

To complement available structure and binding results and to develop a detailed understanding of the basis for selective molecular recognition of T·G mismatches in DNA by imidazole containing polyamides, a full thermodynamic profile for formation of the T·G–polyamide complex has been determined. The amide-linked heterocycles f-ImImIm and f-PyImIm (where f is formamido group, Im is imidazole and Py is pyrrole) were studied by using biosensor-surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC) with a T·G mismatch containing DNA hairpin duplex and a similar DNA with only Watson–Crick base pairs. Large negative binding enthalpies for all of the polyamide–DNA complexes indicate that the interactions are enthalpically driven. SPR results show slower complex formation and stronger binding of f-ImImIm to the T·G than to the match site. The thermodynamic analysis indicates that the enhanced binding to the T·G site is the result of better entropic contributions. Negative heat capacity changes for the complex are correlated with calculated solvent accessible surface area changes and indicate hydrophobic contributions to complex formation. DNase I footprinting analysis in a long DNA sequence provided supporting evidence that f-ImImIm binds selectively to T·G mismatch sites. PMID:15064359

Atypical pattern of discriminating sound features in adults with Asperger syndrome as reflected by the mismatch negativity.

PubMed

Kujala, T; Aho, E; Lepistö, T; Jansson-Verkasalo, E; Nieminen-von Wendt, T; von Wendt, L; Näätänen, R

2007-04-01

Asperger syndrome, which belongs to the autistic spectrum of disorders, is characterized by deficits of social interaction and abnormal perception, like hypo- or hypersensitivity in reacting to sounds and discriminating certain sound features. We determined auditory feature discrimination in adults with Asperger syndrome with the mismatch negativity (MMN), a neural response which is an index of cortical change detection. We recorded MMN for five different sound features (duration, frequency, intensity, location, and gap). Our results suggest hypersensitive auditory change detection in Asperger syndrome, as reflected in the enhanced MMN for deviant sounds with a gap or shorter duration, and speeded MMN elicitation for frequency changes.

I Like Them…Will They Like Me? Evidence for the Role of the Ventrolateral Prefrontal Cortex During Mismatched Social Appraisals in Anxious Youth.

PubMed

Smith, Ashley R; Nelson, Eric E; Rappaport, Brent I; Pine, Daniel S; Leibenluft, Ellen; Jarcho, Johanna M

2018-05-24

Socially anxious adolescents report distress during social decision-making, wherein their favorable view of peers directly conflicts with their expectation to be viewed negatively by peers; a phenomenon we refer to as "mismatch bias." The present study utilizes a novel paradigm with dynamic social stimuli to explore the correlates of mismatch biases in anxious and healthy youth. The behavioral and neural correlates of mismatch biases were assessed in healthy (N = 17) and anxious (N = 14) youth during functional MRI. Participants completed a novel task where they viewed silent videos of unknown peers. After viewing each video, participants appraised the social desirability of the peer ("How much do you think you would like them [if you met them]") or predicted how socially desirable the peer would find them ("How much do you think they would like you [if you met them]"). Each participant's mismatch bias was calculated as the difference between their appraisal of peers and their prediction of peers' appraisal of them. We found that anxious youth exhibited mismatch bias: they rated unknown peers as more desirable than they predicted peers would rate them. This effect was not present in the healthy group. Mismatch biases were associated with increased engagement of the ventrolateral prefrontal cortex (vlPFC), a region broadly involved in flexible cognitions and behavioral selection. In addition, greater mismatch biases and vlPFC activation during mismatch biases were associated with more severe anxiety symptoms. The findings highlight the importance of understanding mismatch biases to inform treatments that target distress elicited by discrepant social appraisals in anxious youth.

Mismatch and lexical retrieval gestures are associated with visual information processing, verbal production, and symptomatology in youth at high risk for psychosis.

PubMed

Millman, Zachary B; Goss, James; Schiffman, Jason; Mejias, Johana; Gupta, Tina; Mittal, Vijay A

2014-09-01

Gesture is integrally linked with language and cognitive systems, and recent years have seen a growing attention to these movements in patients with schizophrenia. To date, however, there have been no investigations of gesture in youth at ultra high risk (UHR) for psychosis. Examining gesture in UHR individuals may help to elucidate other widely recognized communicative and cognitive deficits in this population and yield new clues for treatment development. In this study, mismatch (indicating semantic incongruency between the content of speech and a given gesture) and retrieval (used during pauses in speech while a person appears to be searching for a word or idea) gestures were evaluated in 42 UHR individuals and 36 matched healthy controls. Cognitive functions relevant to gesture production (i.e., speed of visual information processing and verbal production) as well as positive and negative symptomatologies were assessed. Although the overall frequency of cases exhibiting these behaviors was low, UHR individuals produced substantially more mismatch and retrieval gestures than controls. The UHR group also exhibited significantly poorer verbal production performance when compared with controls. In the patient group, mismatch gestures were associated with poorer visual processing speed and elevated negative symptoms, while retrieval gestures were associated with higher speed of visual information-processing and verbal production, but not symptoms. Taken together these findings indicate that gesture abnormalities are present in individuals at high risk for psychosis. While mismatch gestures may be closely related to disease processes, retrieval gestures may be employed as a compensatory mechanism. Copyright © 2014 Elsevier B.V. All rights reserved.

LORETA Current Source Density for Duration Mismatch Negativity and Neuropsychological Assessment in Early Schizophrenia

PubMed Central

Miyanishi, Tomohiro; Sumiyoshi, Tomiki; Higuchi, Yuko; Seo, Tomonori; Suzuki, Michio

2013-01-01

Introduction Patients with schizophrenia elicit cognitive decline from the early phase of the illness. Mismatch negativity (MMN) has been shown to be associated with cognitive function. We investigated the current source density of duration mismatch negativity (dMMN), by using low-resolution brain electromagnetic tomography (LORETA), and neuropsychological performance in subjects with early schizophrenia. Methods Data were obtained from 20 patients meeting DSM-IV criteria for schizophrenia or schizophreniform disorder, and 20 healthy control (HC) subjects. An auditory odd-ball paradigm was used to measure dMMN. Neuropsychological performance was evaluated by the brief assessment of cognition in schizophrenia Japanese version (BACS-J). Results Patients showed smaller dMMN amplitudes than those in the HC subjects. LORETA current density for dMMN was significantly lower in patients compared to HC subjects, especially in the temporal lobes. dMMN current density in the frontal lobe was positively correlated with working memory performance in patients. Conclusions This is the first study to identify brain regions showing smaller dMMN current density in early schizophrenia. Further, poor working memory was associated with decreased dMMN current density in patients. These results are likely to help understand the neural basis for cognitive impairment of schizophrenia. PMID:23577204

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

PubMed

Chang, Ming; Iizuka, Hiroyuki; Kashioka, Hideki; Naruse, Yasushi; Furukawa, Masahiro; Ando, Hideyuki; Maeda, Taro

2017-01-01

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

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

PubMed Central

Iizuka, Hiroyuki; Kashioka, Hideki; Naruse, Yasushi; Furukawa, Masahiro; Ando, Hideyuki; Maeda, Taro

2017-01-01

When people learn foreign languages, they find it difficult to perceive speech sounds that are nonexistent in their native language, and extensive training is consequently necessary. Our previous studies have shown that by using neurofeedback based on the mismatch negativity event-related brain potential, participants could unconsciously achieve learning in the auditory discrimination of pure tones that could not be consciously discriminated without the neurofeedback. Here, we examined whether mismatch negativity neurofeedback is effective for helping someone to perceive new speech sounds in foreign language learning. We developed a task for training native Japanese speakers to discriminate between ‘l’ and ‘r’ sounds in English, as they usually cannot discriminate between these two sounds. Without participants attending to auditory stimuli or being aware of the nature of the experiment, neurofeedback training helped them to achieve significant improvement in unconscious auditory discrimination and recognition of the target words ‘light’ and ‘right’. There was also improvement in the recognition of other words containing ‘l’ and ‘r’ (e.g., ‘blight’ and ‘bright’), even though these words had not been presented during training. This method could be used to facilitate foreign language learning and can be extended to other fields of auditory and clinical research and even other senses. PMID:28617861

Discrimination of stress in speech and music: a mismatch negativity (MMN) study.

PubMed

Peter, Varghese; McArthur, Genevieve; Thompson, William Forde

2012-12-01

The aim of this study was to determine if duration-related stress in speech and music is processed in a similar way in the brain. To this end, we tested 20 adults for their abstract mismatch negativity (MMN) event-related potentials to two duration-related stress patterns: stress on the first syllable or note (long-short), and stress on the second syllable or note (short-long). A significant MMN was elicited for both speech and music except for the short-long speech stimulus. The long-short stimuli elicited larger MMN amplitudes for speech and music compared to short-long stimuli. An extra negativity-the late discriminative negativity (LDN)-was observed only for music. The larger MMN amplitude for long-short stimuli might be due to the familiarity of the stress pattern in speech and music. The presence of LDN for music may reflect greater long-term memory transfer for music stimuli. Copyright © 2012 Society for Psychophysiological Research.

The behavior of commensurate-incommensurate transitions using the phase field crystal model

NASA Astrophysics Data System (ADS)

Zhang, Tinghui; Lu, Yanli; Chen, Zheng

2018-02-01

We study the behavior of the commensurate-incommensurate (CI) transitions by using a phase field crystal model. The model is capable of modeling both elastic and plastic deformation and can simulate the evolution of the microstructure of the material at the atomic scale and the diffusive time scale, such as for adsorbed monolayer. Specifically, we study the behavior of the CI transitions as a function of lattice mismatch and the amplitude of substrate pinning potential. The behavior of CI phase transitions is revealed with the increase of the amplitude of pinning potential in some certain lattice mismatches. We find that for the negative lattice mismatch absorbed monolayer undergoes division, reorganization and displacement as increasing the amplitude of substrate pinning potential. In addition, for the positive mismatch absorbed monolayer undergoes a progress of phase transformation after a complete grain is split. Our results accord with simulations for atomic models of absorbed monolayer on a substrate surface.

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

PubMed

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.

Molecular simulation of the effect of cholesterol on lipid-mediated protein-protein interactions.

PubMed

de Meyer, Frédérick J-M; Rodgers, Jocelyn M; Willems, Thomas F; Smit, Berend

2010-12-01

Experiments and molecular simulations have shown that the hydrophobic mismatch between proteins and membranes contributes significantly to lipid-mediated protein-protein interactions. In this article, we discuss the effect of cholesterol on lipid-mediated protein-protein interactions as function of hydrophobic mismatch, protein diameter and protein cluster size, lipid tail length, and temperature. To do so, we study a mesoscopic model of a hydrated bilayer containing lipids and cholesterol in which proteins are embedded, with a hybrid dissipative particle dynamics-Monte Carlo method. We propose a mechanism by which cholesterol affects protein interactions: protein-induced, cholesterol-enriched, or cholesterol-depleted lipid shells surrounding the proteins affect the lipid-mediated protein-protein interactions. Our calculations of the potential of mean force between proteins and protein clusters show that the addition of cholesterol dramatically reduces repulsive lipid-mediated interactions between proteins (protein clusters) with positive mismatch, but does not affect attractive interactions between proteins with negative mismatch. Cholesterol has only a modest effect on the repulsive interactions between proteins with different mismatch. Copyright © 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Bacteriology testing of cardiovascular tissues: comparison of transport solution versus tissue testing.

PubMed

Díaz Rodríguez, R; Van Hoeck, B; Mujaj, B; Ngakam, R; Fan, Y; Bogaerts, K; Jashari, R

2016-06-01

Bacteriology testing is mandatory for quality control of recovered cardiovascular allografts (CVA). In this paper, two different bacteriology examinations (A tests) performed before tissue antibiotic decontamination were compared: transport solution filtration analysis (A1) and tissue fragment direct incubation (A2). For this purpose, 521 CVA (326 heart and 195 artery tissues) from 280 donors were collected and analyzed by the European Homograft Bank (EHB). Transport solution (A1) tested positive in 43.25 % of hearts and in 48.21 % of arteries, whereas the tissue samples (A2) tested positive in 38.34 % of hearts and 33.85 % of arteries. The main species identified in both A1 and A2 were Staphylococcus spp. in 55 and 26 % of cases, and Propionibacterium spp. in 8 and 19 %, respectively. Mismatches in bacteriology results between both initial tests A1 and A2 were found. 18.40 % of the heart valves were identified as positive by A1 whilst 13.50 % were considered positive by A2. For arteries, 20.51 % of cases were positive in A1 and negative in A2, and just 6.15 % of artery allografts presented contamination in the A2 test but were considered negative for the A1 test. Comparison between each A test with the B and C tests after antibiotic treatment of the allograft was also performed. A total decontamination rate of 70.8 % of initial positive A tests was obtained. Due to the described mismatches and different bacteria identification percentage, utilization of both A tests should be implemented in tissue banks in order to avoid false negatives.

Endometrial tumour BRAF mutations and MLH1 promoter methylation as predictors of germline mismatch repair gene mutation status: a literature review.

PubMed

Metcalf, Alexander M; Spurdle, Amanda B

2014-03-01

Colorectal cancer (CRC) that displays high microsatellite instability (MSI-H) can be caused by either germline mutations in mismatch repair (MMR) genes, or non-inherited transcriptional silencing of the MLH1 promoter. A correlation between MLH1 promoter methylation, specifically the 'C' region, and BRAF V600E status has been reported in CRC studies. Germline MMR mutations also greatly increase risk of endometrial cancer (EC), but no systematic review has been undertaken to determine if these tumour markers may be useful predictors of MMR mutation status in EC patients. Endometrial cancer cohorts meeting review inclusion criteria encompassed 2675 tumours from 20 studies for BRAF V600E, and 447 tumours from 11 studies for MLH1 methylation testing. BRAF V600E mutations were reported in 4/2675 (0.1%) endometrial tumours of unknown MMR mutation status, and there were 7/823 (0.9%) total sequence variants in exon 11 and 27/1012 (2.7%) in exon 15. Promoter MLH1 methylation was not observed in tumours from 32 MLH1 mutation carriers, or for 13 MSH2 or MSH6 mutation carriers. MMR mutation-negative individuals with tumour MLH1 and PMS2 IHC loss displayed MLH1 methylation in 48/51 (94%) of tumours. We have also detailed specific examples that show the importance of MLH1 promoter region, assay design, and quantification of methylation. This review shows that BRAF mutations occurs so infrequently in endometrial tumours they can be discounted as a useful marker for predicting MMR-negative mutation status, and further studies of endometrial cohorts with known MMR mutation status are necessary to quantify the utility of tumour MLH1 promoter methylation as a marker of negative germline MMR mutation status in EC patients.

Selective attention and mismatch negativity in antipsychotic-naïve, first-episode schizophrenia patients before and after 6 months of antipsychotic monotherapy.

PubMed

Oranje, B; Aggernaes, B; Rasmussen, H; Ebdrup, B H; Glenthøj, B Y

2017-09-01

Attention deficits have been frequently reported in schizophrenia. It has been suggested that treatment with second-generation antipsychotics can ameliorate these deficits. In this study, the influence of 6 months treatment with quetiapine, a compound with less affinity for dopamine D2 receptors than for serotonergic 5-HT2A receptors, on electrophysiological parameters of attention was investigated in a group of antipsychotic-naïve, first-episode schizophrenia patients compared with a group of age- and gender-matched healthy controls. A total of 34 first-episode, antipsychotic-naïve patients with schizophrenia and an equal number of healthy controls were tested in a selective attention and a typical mismatch negativity (MMN) paradigm at baseline and after 6 months. The patients were treated with quetiapine according to their clinical needs during the period between baseline and follow-up, whereas controls received no treatment. Patients showed lower MMN and P200 amplitude than healthy controls in the selective attention paradigm at baseline, while this was not the case for MMN of the typical MMN paradigm. Interestingly, after 6 months treatment, this MMN deficit was only ameliorated in patients treated with above median dosages of quetiapine. Patients had lower P3B amplitude, yet showed similar levels of processing negativity and N100 amplitude compared with healthy controls, both at baseline and follow-up. The results indicate that deficits in MMN, P200 and P3B amplitude are present at early stages of schizophrenia, although depending on the paradigm used. Furthermore, the results indicate that 6 months quetiapine treatment ameliorates MMN but not P3B deficits, and only in those subjects on higher dosages.

Living-donor liver transplantation at the University of Tokyo, 1996-2011: the impact of HLA matching and a positive crossmatch on long-term survival and tolerance.

PubMed

Waki, K; Sugawara, Y; Mizuta, K; Fujita, H; Kadowaki, T; Kokudo, N

2011-01-01

We analyzed a single center's experience during 16 years of living-donor liver transplantation (LDLT). The impacts of HLA mismatches and positive crossmatches on long term outcomes and tolerance were evaluated. This study was of primary LDLTs of consecutive patients from January 1996 to December 2011; re-transplants were not included. Long-term survival was compared by primary disease, number of HLA mismatches, and crossmatches. Demographics and complications after transplantation between pediatric recipients who achieved clinical operational tolerance and those who did not were compared. One-year liver graft survival rates for adult and pediatric cases were 90.4% and 91.9%, respectively; the 5-year rates were 83.1% and 89.2%, respectively; the 10-year rates were 79.7% and 89.2%, respectively; and 15-year rates were 65.9% and 83.8%, respectively. For the grafts that survived more than one year, the 10-year rates for adult and pediatric cases were 88.2% and 97.0%, respectively. The 10-year rates for adult LDLT in 0 mismatches, 1-2 mismatches, 3-4 mismatches, and 5-6 mismatches were 79.2%, 86.8%, 77.4%, and 69.4%, respectively. Although the survival rates were not significantly different, the survival rates were lowest in LDLT recipients with 5-6 HLA mismatches. Ten-year liver graft survival rates for adult LDLT with negative T-cell crossmatch, and positive T-cell crossmatch were 80.0% and 71.1%, respectively. The 1-year liver graft survival rates for adult LDLT with negative B-cell crossmatch, and positive B-cell crossmatch were 90.6% and 88.2%, respectively. None of the factors--age of recipients and donors, primary disease, donor gender, relationship of donors to recipients, positive crossmatches, or number of HLA mismatches--was significantly different between COT and non-COT recipients, except for recipient gender (p = 0.01); in COT cases, there were more female recipients (88.9%) than male (11.1%). Post-transplant complications--acute rejection rate in one year post-transplant, biliary complications rate, and vascular complication rate--were not significantly different between COT and non-COT recipients. High long-term survival was achieved by both adult and pediatric recipients. Even higher survival can be achieved by improving early graft loss. Further studies are necessary to determine the impact of HLA mismatches and positive crossmatches on long-term outcomes and tolerance.

Memory traces for spoken words in the brain as revealed by the hemodynamic correlate of the mismatch negativity.

PubMed

Shtyrov, Yury; Osswald, Katja; Pulvermüller, Friedemann

2008-01-01

The mismatch negativity response, considered a brain correlate of automatic preattentive auditory processing, is enhanced for word stimuli as compared with acoustically matched pseudowords. This lexical enhancement, taken as a signature of activation of language-specific long-term memory traces, was investigated here using functional magnetic resonance imaging to complement the previous electrophysiological studies. In passive oddball paradigm, word stimuli were randomly presented as rare deviants among frequent pseudowords; the reverse conditions employed infrequent pseudowords among word stimuli. Random-effect analysis indicated clearly distinct patterns for the different lexical types. Whereas the hemodynamic mismatch response was significant for the word deviants, it did not reach significance for the pseudoword conditions. This difference, more pronounced in the left than right hemisphere, was also assessed by analyzing average parameter estimates in regions of interests within both temporal lobes. A significant hemisphere-by-lexicality interaction confirmed stronger blood oxygenation level-dependent mismatch responses to words than pseudowords in the left but not in the right superior temporal cortex. The increased left superior temporal activation and the laterality of cortical sources elicited by spoken words compared with pseudowords may indicate the activation of cortical circuits for lexical material even in passive oddball conditions and suggest involvement of the left superior temporal areas in housing such word-processing neuronal circuits.

Septal and Anterior Reverse Mismatch of Myocardial Perfusion and Metabolism in Patients With Coronary Artery Disease and Left Bundle Branch Block

PubMed Central

Wang, Jian-Guang; Fang, Wei; Yang, Min-Fu; Tian, Yue-Qin; Zhang, Xiao-Li; Shen, Rui; Sun, Xiao-Xin; Guo, Feng; Wang, Dao-Yu; He, Zuo-Xiang

2015-01-01

Abstract The effects of left bundle branch block (LBBB) on left ventricular myocardial metabolism have not been well investigated. This study evaluated these effects in patients with coronary artery disease (CAD). Sixty-five CAD patients with complete LBBB (mean age, 61.8 ± 9.7 years) and 65 without LBBB (mean age, 59.9 ± 8.4 years) underwent single photon emission computed tomography, positron emission tomography, and contrast coronary angiography. The relationship between myocardial perfusion and metabolism and reverse mismatch score, and that between QRS length and reverse mismatch score and wall motion score were evaluated. The incidence of left ventricular septum and anterior wall reverse mismatching between the two groups was significantly different (P < 0.001 and P = 0.002, respectively). The incidences of normal myocardial perfusion and metabolism in the left ventricular lateral and inferior walls were also significantly different between the two groups (P < 0.001 and P < 0.001, respectively). The incidence of septal reverse mismatching in patients with mild to moderate perfusion was significantly higher among those with LBBB than among those without LBBB (P < 0.001). In CAD patients with LBBB, septal reverse mismatching was significantly more common among those with mild to moderate perfusion than among those with severe perfusion defects (P = 0.002). The correlation between the septal reverse mismatch score and QRS length was significant (P = 0.026). In patients with CAD and LBBB, septal and anterior reverse mismatching of myocardial perfusion and metabolism was frequently present; the septal reverse mismatch score negatively correlated with the QRS interval. PMID:25997045

Effects of physiological aging on mismatch negativity: a meta-analysis.

PubMed

Cheng, Chia-Hsiung; Hsu, Wan-Yu; Lin, Yung-Yang

2013-11-01

Mismatch negativity (MMN) is a promising window on how the functional integrity of auditory sensory memory and change discrimination is modulated by age and relevant clinical conditions. However, the effects of aging on MMN have remained somewhat elusive, particularly at short interstimulus intervals (ISIs). We performed a meta-analysis of peer-reviewed MMN studies that had targeted both young and elderly adults to estimate the mean effect size. Nine studies, consisting of 29 individual investigations, were included and the final total study population consisted of 182 young and 165 elderly subjects. The effects of different deviant types and duration of ISIs on the effect size were assessed. The overall mean effect size was 0.63 (95% CI at 0.43-0.82). The effect sizes for long ISI (>2s, effect size 0.68, 95% CI at 0.31-1.06) and short ISI (<2s, effect size 0.61, 95% CI at 0.39-0.84) were both considered moderate. A further analysis showed a prominent aging-related decrease in MMN responses to duration and frequency changes at short ISIs. It was also interesting to note that the effect size was about 25% larger for duration deviant condition compared to the frequency deviant condition. In conclusion, a reduced MMN response to duration and frequency deviants is a robust feature among the aged adults, which suggests that there has been a decline in the functional integrity of central auditory processing in this population. © 2013.

Genetic instability caused by loss of MutS homolog 3 in human colorectal cancer

PubMed Central

Haugen, Astrid C.; Goel, Ajay; Yamada, Kanae; Marra, Giancarlo; Nguyen, Thuy-Phuong; Nagasaka, Takeshi; Kanazawa, Shinsaku; Koike, Junichi; Kikuchi, Yoshinori; Zhong, Xiaoling; Arita, Michitsune; Shibuya, Kazutoshi; Oshimura, Mitsuo; Hemmi, Hiromichi; Boland, Clement Richard; Koi, Minoru

2008-01-01

Microsatellite instability (MSI) is a hallmark of mismatch repair deficiency. High levels of MSI at mono- and dinucleotide repeats in colorectal cancer (CRC) are attributed to inactivation of the mismatch repair genes, hMLH1 and hMSH2. CRC with low levels of MSI (MSI-L) exists; however its molecular basis is unclear. There is another type of MSI - “elevated microsatellite alterations at selected tetranucleotide repeats” - (EMAST) where loci containing [AAAG]n or [ATAG]n repeats are unstable. EMAST is frequent in non-colorectal cancers; however the incidence of EMAST and its cause in CRC is not known. Here, we report that MSH3-knock-down or MSH3-deficient cells exhibit the EMAST phenotype and low levels of mutations at dinucleotide repeats. About 60% of 117 sporadic CRC cases exhibit EMAST. All of the cases defined as MSI-H (16 cases) exhibited high levels of EMAST. Among 101 non-MSI-H cases, all 19 cases of MSI-L and 35 of 82 cases of MSS exhibited EMAST. Although non-MSI-H CRC tissues contained MSH3-negative tumor cells ranging from 2-50% of the total tumor cell population, the tissues exhibiting EMAST contained more MSH3-negative cells (average 31.5%) than did the tissues not exhibiting EMAST (8.4%). Taken together, our results support the idea that MSH3-deficiency causes EMAST or EMAST with low levels of MSI at the loci with dinucleotide repeats in CRC. PMID:18922920

77 FR 59739 - Revision to Form No. 6

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-01

... mismatch on page 700, which is being remedied by this proceeding. Valero argues that burden on pipelines of...-submit 2009 page 700 data. AOPL and Magellan assert that there is no compelling regulatory need for the..., which are being corrected by this order, created a ``mismatch between the page 700 total cost-of-service...

Using a multi-feature paradigm to measure mismatch responses to minimal sound contrasts in children with cochlear implants and hearing aids.

PubMed

Uhlén, Inger; Engström, Elisabet; Kallioinen, Petter; Nakeva von Mentzer, Cecilia; Lyxell, Björn; Sahlén, Birgitta; Lindgren, Magnus; Ors, Marianne

2017-10-01

Our aim was to explore whether a multi-feature paradigm (Optimum-1) for eliciting mismatch negativity (MMN) would objectively capture difficulties in perceiving small sound contrasts in children with hearing impairment (HI) listening through their hearing aids (HAs) and/or cochlear implants (CIs). Children aged 5-7 years with HAs, CIs and children with normal hearing (NH) were tested in a free-field setting using a multi-feature paradigm with deviations in pitch, intensity, gap, duration, and location. There were significant mismatch responses across all subjects that were positive (p-MMR) for the gap and pitch deviants (F(1,43) = 5.17, p = 0.028 and F(1,43) = 6.56, p = 0.014, respectively) and negative (MMN) for the duration deviant (F(1,43) = 4.74, p = 0.035). Only the intensity deviant showed a significant group interaction with MMN in the HA group and p-MMR in the CI group (F(2,43) = 3.40, p = 0.043). The p-MMR correlated negatively with age, with the strongest correlation in the NH subjects. In the CI group, the late discriminative negativity (LDN) was replaced by a late positivity with a significant group interaction for the location deviant. Children with severe HI can be assessed through their hearing device with a fast multi-feature paradigm. For further studies a multi-feature paradigm including more complex speech sounds may better capture variation in auditory processing in these children. © 2017 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

Topography of Syllable Change-Detection Electrophysiological Indices in Children and Adults with Reading Disabilities

ERIC Educational Resources Information Center

Hommet, Caroline; Vidal, Julie; Roux, Sylvie; Blanc, Romuald; Barthez, Marie Anne; De Becque, Brigitte; Barthelemy, Catherine; Bruneau, Nicole; Gomot, Marie

2009-01-01

Introduction: Developmental dyslexia (DD) is a frequent language-based learning disorder. The predominant etiological view postulates that reading problems originate from a phonological impairment. Method: We studied mismatch negativity (MMN) and Late Discriminative Negativity (LDN) to syllables change in both children (n = 12; 8-12 years) and…

Microarray-Based Comparative Genomic Hybridization Using Sex-Matched Reference DNA Provides Greater Sensitivity for Detection of Sex Chromosome Imbalances than Array-Comparative Genomic Hybridization with Sex-Mismatched Reference DNA

PubMed Central

Yatsenko, Svetlana A.; Shaw, Chad A.; Ou, Zhishuo; Pursley, Amber N.; Patel, Ankita; Bi, Weimin; Cheung, Sau Wai; Lupski, James R.; Chinault, A. Craig; Beaudet, Arthur L.

2009-01-01

In array-comparative genomic hybridization (array-CGH) experiments, the measurement of DNA copy number of sex chromosomal regions depends on the sex of the patient and the reference DNAs used. We evaluated the ability of bacterial artificial chromosomes/P1-derived artificial and oligonucleotide array-CGH analyses to detect constitutional sex chromosome imbalances using sex-mismatched reference DNAs. Twenty-two samples with imbalances involving either the X or Y chromosome, including deletions, duplications, triplications, derivative or isodicentric chromosomes, and aneuploidy, were analyzed. Although concordant results were obtained for approximately one-half of the samples when using sex-mismatched and sex-matched reference DNAs, array-CGH analyses with sex-mismatched reference DNAs did not detect genomic imbalances that were detected using sex-matched reference DNAs in 6 of 22 patients. Small duplications and deletions of the X chromosome were most difficult to detect in female and male patients, respectively, when sex-mismatched reference DNAs were used. Sex-matched reference DNAs in array-CGH analyses provides optimal sensitivity and enables an automated statistical evaluation for the detection of sex chromosome imbalances when compared with an experimental design using sex-mismatched reference DNAs. Using sex-mismatched reference DNAs in array-CGH analyses may generate false-negative, false-positive, and ambiguous results for sex chromosome-specific probes, thus masking potential pathogenic genomic imbalances. Therefore, to optimize both detection of clinically relevant sex chromosome imbalances and ensure proper experimental performance, we suggest that alternative internal controls be developed and used instead of using sex-mismatched reference DNAs. PMID:19324990

Design of Amphoteric Refraction Models Using WAVICA and RAYICA

NASA Technical Reports Server (NTRS)

Su, Richard

2004-01-01

The phenomenon of refraction of light is due to refractive index mismatches in two different media. However, to achieve this effect, a finite reflection loss is inevitable. A recent finding presented a unique type of interface, ferroelastic materials, that enables refraction without any reflection for either an electron or a light beam. This property is called total refraction. The same type of interface that yields total refraction can also yield amphoteric refraction, where the index of refraction can be either positive or negative depending on the incident angle. This interface could potentially be used to steer light without reflections which could have major applications in high power optics. My goal this summer is to first familiarize myself with the Mathematica software, especially the Wavica and Rayica packages. I will then model the amphoteric refraction by either modifying the Wavica and Rayica packages or using the built-in functions in these packages.

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

PubMed

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.

'Right Now, Sophie (∗)Swims in the Pool?!': Brain Potentials of Grammatical Aspect Processing.

PubMed

Flecken, Monique; Walbert, Kelly; Dijkstra, Ton

2015-01-01

We investigated whether brain potentials of grammatical aspect processing resemble semantic or morpho-syntactic processing, or whether they instead are characterized by an entirely distinct pattern in the same individuals. We studied aspect from the perspective of agreement between the temporal information in the context (temporal adverbials, e.g., Right now) and a morpho-syntactic marker of grammatical aspect (e.g., progressive is swimming). Participants read questions providing a temporal context that was progressive (What is Sophie doing in the pool right now?) or habitual (What does Sophie do in the pool every Monday?). Following a lead-in sentence context such as Right now, Sophie…, we measured event-related brain potentials (ERPs) time-locked to verb phrases in four different conditions, e.g., (a) is swimming (control); (b) (∗)is cooking (semantic violation); (c) (∗)are swimming (morpho-syntactic violation); or (d)?swims (aspect mismatch); …in the pool." The collected ERPs show typical N400 and P600 effects for semantics and morpho-syntax, while aspect processing elicited an Early Negativity (250-350 ms). The aspect-related Negativity was short-lived and had a central scalp distribution with an anterior onset. This differentiates it not only from the semantic N400 effect, but also from the typical LAN (Left Anterior Negativity), that is frequently reported for various types of agreement processing. Moreover, aspect processing did not show a clear P600 modulation. We argue that the specific context for each item in this experiment provided a trigger for agreement checking with temporal information encoded on the verb, i.e., morphological aspect marking. The aspect-related Negativity obtained for aspect agreement mismatches reflects a violated expectation concerning verbal inflection (in the example above, the expected verb phrase was Sophie is X-ing rather than Sophie X-s in condition d). The absence of an additional P600 for aspect processing suggests that the mismatch did not require additional reintegration or processing costs. This is consistent with participants' post hoc grammaticality judgements of the same sentences, which overall show a high acceptability of aspect mismatch sentences.

UGT2B17 minor histocompatibility mismatch and clinical outcome after HLA-identical sibling donor stem cell transplantation.

PubMed

Santos, N; Rodríguez-Romanos, R; Nieto, J B; Buño, I; Vallejo, C; Jiménez-Velasco, A; Brunet, S; Buces, E; López-Jiménez, J; González, M; Ferrá, C; Sampol, A; de la Cámara, R; Martínez, C; Gallardo, D

2016-01-01

Minor histocompatibility Ags (mHags) have been implicated in the pathogenesis of GVHD after allogeneic hematopoietic stem cell transplantation (HSCT). Uridine diphospho-glucuronosyltransferase 2B17 (UGT2B17) gene deletion may act as a mHag and its association with acute GVHD (aGVHD) has been described. We retrospectively studied the clinical impact of a UGT2B17 mismatch in a cohort of 1127 patients receiving a HSCT from an HLA-identical sibling donor. UGT2B17 mismatch was present in 69 cases (6.1%). Incidence of severe aGVHD was higher in the UGT2B17 mismatched pairs (22.7% vs 14.6%), but this difference was not statistically significant (P: 0.098). We did not detect differences in chronic GVHD, overall survival, relapse-free survival, transplant-related mortality or relapse. Nevertheless, when we analyzed only those patients receiving grafts from a male donor (616 cases), aGVHD was significantly higher in the UGT2B17 mismatched group (25.1% vs 12.8%; P: 0.005) and this association was confirmed by the multivariate analysis (P: 0.043; hazard ratio: 2.16, 95% confidence interval: 1.03-4.57). Overall survival was worse for patients mismatched for UGT2B17 (P: 0.005). We conclude that UGT2B17 mismatch has a negative clinical impact in allogeneic HSCT from HLA-identical sibling donors only when a male donor is used. These results should be confirmed by other studies.

Rethinking the acculturation gap-distress theory among asian americans: Testing bidirectional indirect relations.

PubMed

Lui, P Priscilla

2018-02-19

The acculturation gap-distress theory postulates that parent-offspring acculturation mismatch precipitates greater intergenerational conflict in immigrant families, which in turn increases the risk for psychological problems among offspring. Whereas cross-sectional studies have shown support for these theory-informed relations, comparatively little is known about whether acculturation mismatch negatively affects psychological functioning, or whether offspring's psychological problems precipitate greater perceived acculturation mismatch via intergenerational cultural conflict. Furthermore, more research is needed to investigate how acculturation and family conflict affect Asian Americans transitioning into college and emerging adulthood. Across two measurement occasions, two cohorts of Asian American first-year college students (N = 555, Mage = 17.99, 56.0% women) completed survey questionnaires assessing their perception of parent-offspring acculturation discrepancies, acculturation-related intergenerational conflict, and internalizing and externalizing symptoms. For both sets of psychological functioning, gender invariant structural equation models testing the bidirectional relations demonstrated adequate fit for the data. In the case of externalizing symptoms, acculturation mismatch marginally significantly predicted subsequent intergenerational conflict, but acculturation mismatch did not predict externalizing symptoms via intergenerational cultural conflict. By contrast, offspring's internalizing and externalizing symptoms respectively predicted greater self-reported intergenerational cultural conflict, which in turn predicted perceived parent-offspring acculturation mismatch over time. These indirect relations suggested that both internalizing and externalizing symptoms indirectly contributed to greater acculturation mismatch through the presence of intergenerational cultural conflict, but data did not support the acculturation gap-distress theory. Theoretical and clinical implications as they pertain to Asian American emerging adults are discussed. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

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

PubMed

Chung, Kyungmi; Park, Jin Young

2018-04-11

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

Memantine Effects On Sensorimotor Gating and Mismatch Negativity in Patients with Chronic Psychosis.

PubMed

Swerdlow, Neal R; Bhakta, Savita; Chou, Hsun-Hua; Talledo, Jo A; Balvaneda, Bryan; Light, Gregory A

2016-01-01

Patients with chronic psychotic disorders (CPD) exhibit deficient sensorimotor gating (measured by prepulse inhibition (PPI) of startle) and mismatch negativity (MMN). In healthy subjects (HS), N-methyl-D-aspartate (NMDA) antagonists like memantine and ketamine increase PPI, and under some conditions, memantine enhances MMN; these findings present a challenge to understanding the basis for deficient PPI and MMN in psychotic disorders, as reduced NMDA activity is implicated in the pathogenesis of these disorders. Here we assessed for the first time the effects of memantine on PPI and MMN in CPD subjects. Baseline PPI was measured in HS and patients with a diagnosis of schizophrenia or schizoaffective disorder, depressed type. Subjects (total n=84) were then tested twice, in a double-blind crossover design, comparing either: (1) placebo vs 10 mg of memantine or (2) placebo vs 20 mg memantine. Tests included measures of acoustic startle magnitude and habituation, PPI, MMN, autonomic indices, and subjective self-rating scales. Memantine (20 mg) significantly enhanced PPI in CPD subjects, and enhanced MMN across subject groups. These effects on PPI were age dependent and most evident in older CPD patients, whereas those on MMN were most evident in younger subjects. The lower dose (10 mg) either had no detectable effect or tended to degrade these measures. The NMDA antagonist, memantine, has dose-dependent effects on preconscious, automatic measures of sensorimotor gating and auditory sensory processing that are associated with enhanced cognition and function in CPD patients. Ongoing studies will determine whether these memantine-induced changes predict acute pro-cognitive or otherwise clinically beneficial effects in CPD patients.

Residential Segregation,Spatial Mismatch and Economic Growth across US Metropolitan Area

DOE Office of Scientific and Technical Information (OSTI.GOV)

Campbell, Dr Harrison; Li, Huiping

2013-01-01

Numerous studies have demonstrated the detrimental influence of residential segregation on poor inner-city residents. This study examines the impact of residential segregation on the welfare of populations in US metropolitan areas using economic growth as the indicator. Panel data of US metropolitan areas spanning 25 years, 1980 2005, are used to analyze the effect of segregation on economic growth. The results show that both racial and skill segregation have a negative impact on short and long-term economic growth, which have increased over time. Further, the negative impact of the variables associated with spatial mismatch is also revealed. The results clearlymore » point to the need for mobility policies that favor non-White households and comprehensive strategies that promote economic opportunities in low-resource communities in the US.« less

Visual mismatch negativity and categorization.

PubMed

Czigler, István

2014-07-01

Visual mismatch negativity (vMMN) component of event-related potentials is elicited by stimuli violating the category rule of stimulus sequences, even if such stimuli are outside the focus of attention. Category-related vMMN emerges to colors, and color-related vMMN is sensitive to language-related effects. A higher-order perceptual category, bilateral symmetry is also represented in the memory processes underlying vMMN. As a relatively large body of research shows, violating the emotional category of human faces elicits vMMN. Another face-related category sensitive to the violation of regular presentation is gender. Finally, vMMN was elicited to the laterality of hands. As results on category-related vMMN show, stimulus representation in the non-conscious change detection system is fairly complex, and it is not restricted to the registration of elementary perceptual regularities.

Job burnout and engagement among teachers - Worklife areas and personality traits as predictors of relationships with work.

PubMed

Mojsa-Kaja, Justyna; Golonka, Krystyna; Marek, Tadeusz

2015-01-01

The main goal of the present study was to analyze the burnout syndrome due to selected personality traits (based on the Cloninger's psychobiological personality model and positive and negative affectivity) and the degree of mismatch between teachers and their work environment (described in terms of the Model of Worklife Areas). The 2nd goal was to determine if the participants could be classified into different burnout profile groups (clusters) based on their burnout dimension (exhaustion, cynicism and efficacy) scores and whether those groups differed significantly with regard to their personality traits and levels of mismatch between them and the workplace. Individual and contextual factors responsible for burnout were analyzed in a group of 205 Polish teachers who completed a set of questionnaires: Maslach Burnout Inventory - General Scale, Areas of Worklife Scale, Temperament and Character Inventory, and Positive and Negative Affect Schedule. The hierarchical regression analysis revealed that teachers' efficacy is determined only by personality factors, while exhaustion and cynicism are determined by both individual and organizational variables. The cluster analysis revealed 3 groups (burnout, engaged, ineffective) that varied in the level of all burnout dimensions. Teachers experiencing burnout perceived a higher level of mismatch between themselves and the work environment, compared to the engaged teachers demonstrating better alignment. The engaged teachers were lower on negative affectivity and higher on self-directedness as compared to the burnout group. The study provided insight into the role of individual factors in the development of teacher burnout and engagement. Negative affectivity could be considered as a predisposing risk factor and self-directedness as a protective factor for burnout. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Effects of Prosthetic Mismatch and Subscapularis Tear on Glenohumeral Contact Patterns in Total Shoulder Arthroplasty: A Numerical Musculoskeletal Analysis.

PubMed

Sins, Lauranne; Tétreault, Patrice; Nuño, Natalia; Hagemeister, Nicola

2016-12-01

Prosthetic components' mismatch and subscapularis (SC) tear are determining factors for glenoid failure complication in nonconforming total shoulder arthroplasty (NC-TSA). Risk factors are linked to glenoid prosthetic loading. However, the mechanisms underlying the clinical observations remain unclear. This study assessed the combined impact of mismatch and subscapularis tear on glenoid loading. It was assumed that adequate glenoid loading was associated with minimal, but non-null, humeral head translations and contact pressure, as well as with maximal glenoid contact area, and that the center of pressure (COP) on the glenoid would have a centered displacement pattern. A numerical model was used to achieve two objectives. The first was to verify whether an optimum mismatch existed, for which failure risk would be minimal. The second was to explore the effect of subscapularis tear on the position of applied forces on the glenoid. A shoulder AnyBody musculoskeletal model was adapted to the arthroplasty context by introducing humeral head translations and contact between implants. Ten simulations were computed to compare combinations of varying mismatches (1.4 mm, 3.4 mm, 6.4 mm, 8.6 mm, and 9 mm) with two shoulder conditions (intact-muscle or subscapularis tear). Humeral head translations, center-of-pressure, contact area, contact pressure, and glenohumeral joint contact forces were numerically estimated. Mismatches between 3.4 mm and 6.4 mm were associated with the most minimal humeral translations and contact pressure, as well as with maximal contact area. Center of pressure displacement pattern differed according to shoulder condition, with an outward anterior tendency in presence of tear.

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

PubMed

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 deficiency syndrome should be considered in patients who present with early onset cancer, a strong family history of cancer, and cutaneous features resembling neurofibromatosis type I. Immunohistochemistry analysis of tumour and normal tissue is sensitive and specific for identifying patients with mismatch repair deficiency and should direct DNA sequencing of lymphocytic tissue to establish a diagnosis. Microsatellite instability status appears to be of little value in identifying patients who may have constitutional mismatch repair deficiency syndrome.

MRI based thrombolysis for FLAIR-negative stroke patients within 4.5-6h after symptom onset.

PubMed

Wei, Xiao-Er; Zhou, Jia; Li, Wen-Bin; Zhao, Yu-Wu; Li, Ming-Hua; Li, Yue-Hua

2017-01-15

To investigate the feasibility of DWI-FLAIR mismatch in identifying patients who might benefit from thrombolytic therapy within 4.5-6h, we analyzed the data of 105 ischemic stroke patients with known time of symptom onset who underwent MRI within 6h of stroke and thrombolysis between December 2006 and December 2013. They were divided into three groups: symptom onset within 4.5h (n=66); 4.5-6h and FLAIR images negative (n=9); and 4.5-6h and FLAIR images positive (n=30). Outcome of thrombolysis was assessed for each group by recanalization rate, National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores. The results showed that mismatch between positive DWI and negative FLAIR images identified patients within 4.5h of symptom onset with sensitivity, specificity, positive predictive value and negative predictive value of 40.9%, 76.9%, and 75% and 43.5%. Recanalization rate, NIHSS score and mRS score were all better in both the 0-4.5h and 4.5-6h FLAIR-negative groups than in the 4.5-6h FLAIR-positive group (p<0.05). These data demonstrate that within 4.5-6h of symptom onset, patients with negative FLAIR images may benefit from thrombolysis therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Mismatch Negativity with Visual-only and Audiovisual Speech

PubMed Central

Ponton, Curtis W.; Bernstein, Lynne E.; Auer, Edward T.

2009-01-01

The functional organization of cortical speech processing is thought to be hierarchical, increasing in complexity and proceeding from primary sensory areas centrifugally. The current study used the mismatch negativity (MMN) obtained with electrophysiology (EEG) to investigate the early latency period of visual speech processing under both visual-only (VO) and audiovisual (AV) conditions. Current density reconstruction (CDR) methods were used to model the cortical MMN generator locations. MMNs were obtained with VO and AV speech stimuli at early latencies (approximately 82-87 ms peak in time waveforms relative to the acoustic onset) and in regions of the right lateral temporal and parietal cortices. Latencies were consistent with bottom-up processing of the visible stimuli. We suggest that a visual pathway extracts phonetic cues from visible speech, and that previously reported effects of AV speech in classical early auditory areas, given later reported latencies, could be attributable to modulatory feedback from visual phonetic processing. PMID:19404730

Independent processing of changes in auditory single features and feature conjunctions in humans as indexed by the mismatch negativity.

PubMed

Takegata, R; Paavilainen, P; Näätänen, R; Winkler, I

1999-05-07

The mismatch negativity (MMN), an event-related potential component of the EEG, is elicited by violations of auditory regularities In the present study, the stimulus blocks contained two types of standard tones, differing from each other in frequency and intensity. MMNs were recorded to three different types of deviant stimuli: (a) feature deviants, differing from standards in their perceived locus of origin; (b) conjunction deviants, having the frequency of one of the standards and the intensity of the other; (c) double deviants, differing from standards in both (a) and (b). The MMN to double deviants was similar to the sum of the MMNs to feature and conjunction deviants. This result indicates that changes in simple stimulus features and conjunction of features are processed independently by the automatic sound change detection system indexed by MMN.

Effects of spectral complexity and sound duration on automatic complex-sound pitch processing in humans - a mismatch negativity study.

PubMed

Tervaniemi, M; Schröger, E; Saher, M; Näätänen, R

2000-08-18

The pitch of a spectrally rich sound is known to be more easily perceived than that of a sinusoidal tone. The present study compared the importance of spectral complexity and sound duration in facilitated pitch discrimination. The mismatch negativity (MMN), which reflects automatic neural discrimination, was recorded to a 2. 5% pitch change in pure tones with only one sinusoidal frequency component (500 Hz) and in spectrally rich tones with three (500-1500 Hz) and five (500-2500 Hz) harmonic partials. During the recordings, subjects concentrated on watching a silent movie. In separate blocks, stimuli were of 100 and 250 ms in duration. The MMN amplitude was enhanced with both spectrally rich sounds when compared with pure tones. The prolonged sound duration did not significantly enhance the MMN. This suggests that increased spectral rather than temporal information facilitates pitch processing of spectrally rich sounds.

The mismatch negativity: A review of underlying mechanisms

PubMed Central

Garrido, Marta I.; Kilner, James M.; Stephan, Klaas E.; Friston, Karl J.

2009-01-01

The mismatch negativity (MMN) is a brain response to violations of a rule, established by a sequence of sensory stimuli (typically in the auditory domain) [Näätänen R. Attention and brain function. Hillsdale, NJ: Lawrence Erlbaum; 1992]. The MMN reflects the brain’s ability to perform automatic comparisons between consecutive stimuli and provides an electrophysiological index of sensory learning and perceptual accuracy. Although the MMN has been studied extensively, the neurophysiological mechanisms underlying the MMN are not well understood. Several hypotheses have been put forward to explain the generation of the MMN; amongst these accounts, the “adaptation hypothesis” and the “model adjustment hypothesis” have received the most attention. This paper presents a review of studies that focus on neuronal mechanisms underlying the MMN generation, discusses the two major explanatory hypotheses, and proposes predictive coding as a general framework that attempts to unify both. PMID:19181570

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

PubMed

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

2010-09-01

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

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

PubMed

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

2015-02-01

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

Student's Body Dimensions in Relation to Classroom Furniture.

PubMed

Baharampour, Samira; Nazari, Jalil; Dianat, Iman; Asgharijafarabadi, Mohamad

2013-01-01

This study was carried out to investigate the fit between university student's anthropometry and classroom furniture dimensions. In this cross-sectional and descriptive-analyzing study conducted in 2012, a total of 194 students (aged 18 through 30 years), were recruited randomly from Tabriz University of Medical Science community. The body size of each student was assessed using anthropometric measurements including shoulder height, elbow height, popliteal height, buttock-popliteal length, hip breadth and distance between elbows. Combinational equations defined the acceptable furni-ture dimensions according to anthropometry and match percentages were computed, according to either the existing situations assuming that they could use the most appropriate of the sizes available. Desk and seat height were higher than the accepted limits for most students (92.5% and 98.4%, respectively), while seat depth was appropriate for only 84.6% of students. The data indicate a mismatch between the students' bodily dimensions and the classroom furniture available to them. The chairs are too high and too deep and desks are also too high for the pupils. This situation may have negative effects on the sitting posture of the students especially when reading and writing. High mismatch percentages were found between furniture and stu-dents' anthropometry. The results confirm that furniture for university students should be selected and designed busied on their anthropometric dimensions.

Preoperative diagnosis of Lynch syndrome with DNA mismatch repair immunohistochemistry on a diagnostic biopsy.

PubMed

Warrier, S K; Trainer, A H; Lynch, A C; Mitchell, C; Hiscock, R; Sawyer, S; Boussioutas, A; Heriot, A G

2011-12-01

DNA mismatch repair immunohistochemistry on tumor tissue is a simple, readily available, and cost-effective method of identifying patients with Lynch syndrome in the postoperative setting. The aim of the study was to assess whether the mismatch repair status of a colorectal cancer can be confirmed by mismatch repair immunohistochemistry on preoperative biopsy. Germline positive patients with Lynch syndrome were identified from a prospectively collected Familial Cancer Clinic database. Preoperative colorectal cancer biopsy specimens were obtained from the source pathology provider to generate a cohort of matched preoperative and postoperative specimens. The specimens were sectioned and stained for 4 mismatch repair proteins (MLH1, MSH2, MSH6, PMS2). An age-matched cohort to compare specimens was selected from Bethesda positive but mismatch repair immunohistochemistry negative patients. All slides were reviewed by a single blinded pathologist. The Wilson method was used to calculate a true underlying proportion of patients for whom the preoperative result matched the postoperative test result with a 95% confidence interval. Of 128 germline positive mutation carriers, 40 patients (mean age 41, SD 11.3) had colorectal resections. Thirty-three preoperative specimens were retrievable and were matched with biopsies from 33 controls. The germline mutations included in the study were 8 MLH1, 19 MSH2, 3 MSH6, and 2 PMS2. In patients where germline positive status was known, sensitivity was 100% (95% CI 89.2-100) and specificity was 100% (95% CI 89.2-100). Identical sensitivity and specificity were observed in 33 age-matched patients. The sensitivity of the endoscopic biopsy in predicting germline status was 94.9% (95% CI 80.4-98.3). The mismatch repair disease status of a colorectal cancer can be reliably confirmed by mismatch repair immunohistochemistry on a diagnostic colorectal cancer biopsy sample before definitive surgery. Ascertaining a diagnosis of Lynch syndrome before definitive surgery can influence surgical planning.

Comparative reactivity of mismatched and unpaired bases in relation to their type and surroundings. Chemical cleavage of DNA mismatches in mutation detection analysis.

PubMed

Yakubovskaya, Marianna G; Belyakova, Anna A; Gasanova, Viktoria K; Belitsky, Gennady A; Dolinnaya, Nina G

2010-07-01

Systematic study of chemical reactivity of non-Watson-Crick base pairs depending on their type and microenvironment was performed on a model system that represents two sets of synthetic DNA duplexes with all types of mismatched and unmatched bases flanked by T.A or G.C pairs. Using comparative cleavage pattern analysis, we identified the main and additional target bases and performed quantitative study of the time course and efficacy of DNA modification caused by potassium permanganate or hydroxylamine. Potassium permanganate in combination with tetraethylammonium chloride was shown to induce DNA cleavage at all mismatched or bulged T residues, as well as at thymines of neighboring canonical pairs. Other mispaired (bulged) bases and thymine residues located on the second position from the mismatch site were not the targets for KMnO(4) attack. In contrast, hydroxylamine cleaved only heteroduplexes containing mismatched or unmatched C residues, and did not modify adjacent cytosines. However when G.C pairs flank bulged C residue, neighboring cytosines are also attacked by hydroxylamine due to defect migration. Chemical reactivity of target bases was shown to correlate strongly with the local disturbance of DNA double helix at mismatch or bulge site. With our model system, we were able to prove the absence of false-negative and false-positive results. Portion of heteroduplex reliably revealed in a mixture with corresponding homoduplex consists of 5% for bulge bases and "open" non-canonical pairs, and 10% for wobble base pairs giving minimal violations in DNA structure. This study provides a complete understanding of the principles of mutation detection methodology based on chemical cleavage of mismatches and clarifies the advantages and limitations of this approach in various biological and conformational studies of DNA. Copyright 2010 Elsevier Masson SAS. All rights reserved.

Finding the missing stimulus mismatch negativity (MMN): Emitted MMN to violations of an auditory gestalt

PubMed Central

Salisbury, Dean F

2011-01-01

Deviations from repetitive auditory stimuli evoke a mismatch negativity (MMN). Counter-intuitively, omissions of repetitive stimuli do not. Violations of patterns reflecting complex rules also evoke MMN. To detect a MMN to missing stimuli, we developed an auditory gestalt task using one stimulus. Groups of 6 pips (50 msec duration, 330 msec stimulus onset asynchrony (SOA), 400 trials), were presented with an inter-trial interval (ITI) of 750 msec while subjects (n=16) watched a silent video. Occasional deviant groups had missing 4th or 6th tones (50 trials each). Missing stimuli evoked a MMN (p<.05). The missing 4th (−0.8 uV, p <.01) and the missing 6th stimuli (−1.1 uV, p <.05) were more negative than standard 6th stimuli (0.3 uV). MMN can be elicited by a missing stimulus at long SOAs by violation of a gestalt grouping rule. Homogenous stimulus streams appear to differ in the relative weighting of omissions than strongly patterned streams. PMID:22221004

Research in China on event-related potentials in patients with schizophrenia

PubMed Central

Wang, Jijun; Guo, Qian

2012-01-01

Abstract Event-related potentials (ERPs) are objective electrophysiological indicators that can be used to assess cognitive processes in the human brain. Psychiatric researchers in China have applied this method to study schizophrenia since the early 1980s. ERP measures used in the study of schizophrenia include contingent negative variation (CNV), P300, mismatch negativity (MMN), error-related negativity (ERN) and auditory P50 inhibition. This review summarizes the main findings of ERP research in patients with schizophrenia reported by Chinese investigators. PMID:25324605

Upper tract urothelial carcinomas: frequency of association with mismatch repair protein loss and lynch syndrome.

PubMed

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 carcinoma; however, mismatch repair protein loss of MSH2 and/or MSH6 by immunohistochemistry seems relatively sensitive and specific for identifying patients with potential Lynch syndrome.

Solution structure and stability of the DNA undecamer duplexes containing oxanine mismatch

PubMed Central

Pack, Seung Pil; Morimoto, Hirohisa; Makino, Keisuke; Tajima, Kunihiko; Kanaori, Kenji

2012-01-01

Solution structures of DNA duplexes containing oxanine (Oxa, O) opposite a cytosine (O:C duplex) and opposite a thymine (O:T duplex) have been solved by the combined use of 1H NMR and restrained molecular dynamics calculation. One mismatch pair was introduced into the center of the 11-mer duplex of [d(GTGACO6CACTG)/d(CAGTGX17GTCAC), X = C or T]. 1H NMR chemical shifts and nuclear Overhauser enhancement (NOE) intensities indicate that both the duplexes adopt an overall right-handed B-type conformation. Exchangeable resonances of C17 4-amino proton of the O:C duplex and of T17 imino proton of O:T duplex showed unusual chemical shifts, and disappeared with temperature increasing up to 30°C, although the melting temperatures were >50°C. The O:C mismatch takes a wobble geometry with positive shear parameter where the Oxa ring shifted toward the major groove and the paired C17 toward the minor groove, while, in the O:T mismatch pair with the negative shear, the Oxa ring slightly shifted toward the minor groove and the paired T17 toward the major groove. The Oxa mismatch pairs can be wobbled largely because of no hydrogen bond to the O1 position of the Oxa base, and may occupy positions in the strands that optimize the stacking with adjacent bases. PMID:22039100

N400 brain responses to spoken phrases paired with photographs of scenes: implications for visual scene displays in AAC systems.

PubMed

Wilkinson, Krista M; Stutzman, Allyson; Seisler, Andrea

2015-03-01

Augmentative and alternative communication (AAC) systems are often implemented for individuals whose speech cannot meet their full communication needs. One type of aided display is called a Visual Scene Display (VSD). VSDs consist of integrated scenes (such as photographs) in which language concepts are embedded. Often, the representations of concepts on VSDs are perceptually similar to their referents. Given this physical resemblance, one may ask how well VSDs support development of symbolic functioning. We used brain imaging techniques to examine whether matches and mismatches between the content of spoken messages and photographic images of scenes evoke neural activity similar to activity that occurs to spoken or written words. Electroencephalography (EEG) was recorded from 15 college students who were shown photographs paired with spoken phrases that were either matched or mismatched to the concepts embedded within each photograph. Of interest was the N400 component, a negative deflecting wave 400 ms post-stimulus that is considered to be an index of semantic functioning. An N400 response in the mismatched condition (but not the matched) would replicate brain responses to traditional linguistic symbols. An N400 was found, exclusively in the mismatched condition, suggesting that mismatches between spoken messages and VSD-type representations set the stage for the N400 in ways similar to traditional linguistic symbols.

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

PubMed

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.

Assessment of primer/template mismatch effects on real-time PCR amplification of target taxa for GMO quantification.

PubMed

Ghedira, Rim; Papazova, Nina; Vuylsteke, Marnik; Ruttink, Tom; Taverniers, Isabel; De Loose, Marc

2009-10-28

GMO quantification, based on real-time PCR, relies on the amplification of an event-specific transgene assay and a species-specific reference assay. The uniformity of the nucleotide sequences targeted by both assays across various transgenic varieties is an important prerequisite for correct quantification. Single nucleotide polymorphisms (SNPs) frequently occur in the maize genome and might lead to nucleotide variation in regions used to design primers and probes for reference assays. Further, they may affect the annealing of the primer to the template and reduce the efficiency of DNA amplification. We assessed the effect of a minor DNA template modification, such as a single base pair mismatch in the primer attachment site, on real-time PCR quantification. A model system was used based on the introduction of artificial mismatches between the forward primer and the DNA template in the reference assay targeting the maize starch synthase (SSIIb) gene. The results show that the presence of a mismatch between the primer and the DNA template causes partial to complete failure of the amplification of the initial DNA template depending on the type and location of the nucleotide mismatch. With this study, we show that the presence of a primer/template mismatch affects the estimated total DNA quantity to a varying degree.

Memantine Effects On Sensorimotor Gating and Mismatch Negativity in Patients with Chronic Psychosis

PubMed Central

Swerdlow, Neal R; Bhakta, Savita; Chou, Hsun-Hua; Talledo, Jo A; Balvaneda, Bryan; Light, Gregory A

2016-01-01

Patients with chronic psychotic disorders (CPD) exhibit deficient sensorimotor gating (measured by prepulse inhibition (PPI) of startle) and mismatch negativity (MMN). In healthy subjects (HS), N-methyl-D-aspartate (NMDA) antagonists like memantine and ketamine increase PPI, and under some conditions, memantine enhances MMN; these findings present a challenge to understanding the basis for deficient PPI and MMN in psychotic disorders, as reduced NMDA activity is implicated in the pathogenesis of these disorders. Here we assessed for the first time the effects of memantine on PPI and MMN in CPD subjects. Baseline PPI was measured in HS and patients with a diagnosis of schizophrenia or schizoaffective disorder, depressed type. Subjects (total n=84) were then tested twice, in a double-blind crossover design, comparing either: (1) placebo vs 10 mg of memantine or (2) placebo vs 20 mg memantine. Tests included measures of acoustic startle magnitude and habituation, PPI, MMN, autonomic indices, and subjective self-rating scales. Memantine (20 mg) significantly enhanced PPI in CPD subjects, and enhanced MMN across subject groups. These effects on PPI were age dependent and most evident in older CPD patients, whereas those on MMN were most evident in younger subjects. The lower dose (10 mg) either had no detectable effect or tended to degrade these measures. The NMDA antagonist, memantine, has dose-dependent effects on preconscious, automatic measures of sensorimotor gating and auditory sensory processing that are associated with enhanced cognition and function in CPD patients. Ongoing studies will determine whether these memantine-induced changes predict acute pro-cognitive or otherwise clinically beneficial effects in CPD patients. PMID:26062785

The role of musical aptitude and language skills in preattentive duration processing in school-aged children.

PubMed

Milovanov, Riia; Huotilainen, Minna; Esquef, Paulo A A; Alku, Paavo; Välimäki, Vesa; Tervaniemi, Mari

2009-08-28

We examined 10-12-year old elementary school children's ability to preattentively process sound durations in music and speech stimuli. In total, 40 children had either advanced foreign language production skills and higher musical aptitude or less advanced results in both musicality and linguistic tests. Event-related potential (ERP) recordings of the mismatch negativity (MMN) show that the duration changes in musical sounds are more prominently and accurately processed than changes in speech sounds. Moreover, children with advanced pronunciation and musicality skills displayed enhanced MMNs to duration changes in both speech and musical sounds. Thus, our study provides further evidence for the claim that musical aptitude and linguistic skills are interconnected and the musical features of the stimuli could have a preponderant role in preattentive duration processing.

Method for enhancing the solubility of dopants in silicon

DOEpatents

Sadigh, Babak; Lenosky, Thomas J.; De La Rubia, Tomas Diaz

2003-09-30

A method for enhancing the equilibrium solid solubility of dopants in silicon, germanium and silicon-germanium alloys. The method involves subjecting silicon-based substrate to biaxial or compression strain. It has been determined that boron solubility was largely enhanced (more than 100%) by a compressive bi-axial strain, based on a size-mismatch theory since the boron atoms are smaller than the silicon atoms. It has been found that the large enhancement or mixing properties of dopants in silicon and germanium substrates is primarily governed by their, and to second order by their size-mismatch with the substrate. Further, it has been determined that the dopant solubility enhancement with strain is most effective when the charge and the size-mismatch of the impurity favor the same type of strain. Thus, the solid solubility of small p-type (e.g., boron) as well as large n-type (e.g., arsenic) dopants can be raised most dramatically by appropriate bi-axial (compressive) strain, and that solubility of a large p-type dopant (e.g, indium) in silicon will be raised due to size-mismatch with silicon, which favors tensile strain, while its negative charge prefers compressive strain, and thus the two effects counteract each other.

Affective Monitoring: A Generic Mechanism for Affect Elicitation

PubMed Central

Phaf, R. Hans; Rotteveel, Mark

2012-01-01

In this paper we sketch a new framework for affect elicitation, which is based on previous evolutionary and connectionist modeling and experimental work from our group. Affective monitoring is considered a local match–mismatch process within a module of the neural network. Negative affect is raised instantly by mismatches, incongruency, disfluency, novelty, incoherence, and dissonance, whereas positive affect follows from matches, congruency, fluency, familiarity, coherence, and resonance, at least when an initial mismatch can be solved quickly. Affective monitoring is considered an evolutionary-early conflict and change detection process operating at the same level as, for instance, attentional selection. It runs in parallel and imparts affective flavor to emotional behavior systems, which involve evolutionary-prepared stimuli and action tendencies related to for instance defensive, exploratory, attachment, or appetitive behavior. Positive affect is represented in the networks by high-frequency oscillations, presumably in the gamma band. Negative affect corresponds to more incoherent lower-frequency oscillations, presumably in the theta band. For affect to become conscious, large-scale synchronization of the oscillations over the network and the construction of emotional experiences are required. These constructions involve perceptions of bodily states and action tendencies, but also appraisals as well as efforts to regulate the emotion. Importantly, affective monitoring accompanies every kind of information processing, but conscious emotions, which result from the later integration of affect in a cognitive context, are much rarer events. PMID:22403557

Atypical central auditory speech-sound discrimination in children who stutter as indexed by the mismatch negativity.

PubMed

Jansson-Verkasalo, Eira; Eggers, Kurt; Järvenpää, Anu; Suominen, Kalervo; Van den Bergh, Bea; De Nil, Luc; Kujala, Teija

2014-09-01

Recent theoretical conceptualizations suggest that disfluencies in stuttering may arise from several factors, one of them being atypical auditory processing. The main purpose of the present study was to investigate whether speech sound encoding and central auditory discrimination, are affected in children who stutter (CWS). Participants were 10 CWS, and 12 typically developing children with fluent speech (TDC). Event-related potentials (ERPs) for syllables and syllable changes [consonant, vowel, vowel-duration, frequency (F0), and intensity changes], critical in speech perception and language development of CWS were compared to those of TDC. There were no significant group differences in the amplitudes or latencies of the P1 or N2 responses elicited by the standard stimuli. However, the Mismatch Negativity (MMN) amplitude was significantly smaller in CWS than in TDC. For TDC all deviants of the linguistic multifeature paradigm elicited significant MMN amplitudes, comparable with the results found earlier with the same paradigm in 6-year-old children. In contrast, only the duration change elicited a significant MMN in CWS. The results showed that central auditory speech-sound processing was typical at the level of sound encoding in CWS. In contrast, central speech-sound discrimination, as indexed by the MMN for multiple sound features (both phonetic and prosodic), was atypical in the group of CWS. Findings were linked to existing conceptualizations on stuttering etiology. The reader will be able (a) to describe recent findings on central auditory speech-sound processing in individuals who stutter, (b) to describe the measurement of auditory reception and central auditory speech-sound discrimination, (c) to describe the findings of central auditory speech-sound discrimination, as indexed by the mismatch negativity (MMN), in children who stutter. Copyright © 2014 Elsevier Inc. All rights reserved.

HLA Association with hematopoietic stem cell transplantation outcome: the number of mismatches at HLA-A, -B, -C, -DRB1, or -DQB1 is strongly associated with overall survival.

PubMed

Loiseau, Pascale; Busson, Marc; Balere, Marie-Lorraine; Dormoy, Anne; Bignon, Jean-Denis; Gagne, Katia; Gebuhrer, Lucette; Dubois, Valérie; Jollet, Isabelle; Bois, Monique; Perrier, Pascale; Masson, Dominique; Moine, Agnès; Absi, Léna; Reviron, Denis; Lepage, Virginia; Tamouza, Ryad; Toubert, Antoine; Marry, Evelyne; Chir, Zina; Jouet, Jean-Pierre; Blaise, Didier; Charron, Dominique; Raffoux, Colette

2007-08-01

HLA matching between the donor and recipient improves the success of unrelated hematopoietic stem cell transplantation (HSCT). Because many patients in need of an unrelated transplant have only donors with mismatch, information is needed to evaluate the limits of HLA mismatching. We examined the association of survival, acute graft-versus-host disease (aGVHD) and relapse with HLA-A, -B, -C, -DRB, -DQB1, and -DPB1 mismatching in 334 patients coming from 12 French transplant centers and who received a non-T cell-depleted bone marrow graft from an unrelated donor. All patients were prepared with the use of myeloablative conditioning regimens. Our analyses demonstrate negative effects of HLA mismatching for either HLA-A, -B, -C, -DRB1, or -DQB1 loci on survival. Multivariate Cox analyses showed that a single mismatch was associated with a significant decrement in survival (P=.046, hazard ratio [HR]=1.41, confidence interval [CI] 95% 1.1-1.98). The presence of multiple mismatches was worse for survival (P=.003, HR=1.91, CI 95% 1.26-2.91) and severe aGVHD (grade III-IV) (P=.002, HR=2.51, CI95% 1.41-4.46). The cumulative incidences of aGVHD and relapse in those HLA-A, -B, -C, -DRB1, and -DQB1 identical pairs with 2, 1, or 0 DPB1 incompatibilities were 63%, 50%, and 51%, and 12%, 27%, and 20%, respectively, but these differences were not statistically significant. Similar differences of aGVHD and relapse, but not statistically significant, were observed in those HLA-A, -B, -C, -DRB1, and -DQB1 identical pairs with DPB1 disparities classified into permissive or nonpermissive mismatches according to Zino's classification based on a hierarchy of the immunogenicity of the HLA-DP molecules. "Missing killer cell immunoglobulin-like receptor (KIR) ligand" evaluated on the presence of HLA-C1, -C2, and Bw4 groups in the recipients was not associated with aGVHD, survival, and relapse in this cohort of non-T cell-depleted HSCT.

Visual mismatch negativity indicates automatic, task-independent detection of artistic image composition in abstract artworks.

PubMed

Menzel, Claudia; Kovács, Gyula; Amado, Catarina; Hayn-Leichsenring, Gregor U; Redies, Christoph

2018-05-06

In complex abstract art, image composition (i.e., the artist's deliberate arrangement of pictorial elements) is an important aesthetic feature. We investigated whether the human brain detects image composition in abstract artworks automatically (i.e., independently of the experimental task). To this aim, we studied whether a group of 20 original artworks elicited a visual mismatch negativity when contrasted with a group of 20 images that were composed of the same pictorial elements as the originals, but in shuffled arrangements, which destroy artistic composition. We used a passive oddball paradigm with parallel electroencephalogram recordings to investigate the detection of image type-specific properties. We observed significant deviant-standard differences for the shuffled and original images, respectively. Furthermore, for both types of images, differences in amplitudes correlated with the behavioral ratings of the images. In conclusion, we show that the human brain can detect composition-related image properties in visual artworks in an automatic fashion. Copyright © 2018 Elsevier B.V. All rights reserved.

Arithmetic mismatch negativity and numerical magnitude processing in number matching.

PubMed

Hsu, Yi-Fang; Szücs, Dénes

2011-08-11

This study examined the relationship of the arithmetic mismatch negativity (AMN) and the semantic evaluation of numerical magnitude. The first question was whether the AMN was sensitive to the incongruity in numerical information per se, or rather, to the violation of strategic expectations. The second question was whether the numerical distance effect could appear independently of the AMN. Event-related potentials (ERPs) were recorded while participants decided whether two digits were matching or non-matching in terms of physical similarity. The AMN was enhanced in matching trials presented infrequently relative to non-matching trials presented frequently. The numerical distance effect was found over posterior sites during a 92 ms long interval (236-328 ms) but appeared independently of the AMN. It was not the incongruity in numerical information per se, but rather, the violation of strategic expectations that elicited the AMN. The numerical distance effect might only temporally coincide with the AMN and did not form an inherent part of it.

Automatic processing of pragmatic information in the human brain: a mismatch negativity study.

PubMed

Zhao, Ming; Liu, Tao; Chen, Feiyan

2018-05-23

Language comprehension involves pragmatic information processing, which allows world knowledge to influence the interpretation of a sentence. This study explored whether pragmatic information can be automatically processed during spoken sentence comprehension. The experiment adopted the mismatch negativity (MMN) paradigm to capture the neurophysiological indicators of automatic processing of spoken sentences. Pragmatically incorrect ('Foxes have wings') and correct ('Butterflies have wings') sentences were used as the experimental stimuli. In condition 1, the pragmatically correct sentence was the deviant and the pragmatically incorrect sentence was the standard stimulus, whereas the opposite case was presented in condition 2. The experimental results showed that, compared with the condition that the pragmatically correct sentence is the deviant stimulus, when the condition that the pragmatically incorrect sentence is the deviant stimulus MMN effects were induced within 60-120 and 220-260 ms. The results indicated that the human brain can monitor for incorrect pragmatic information in the inattentive state and can automatically process pragmatic information at the beginning of spoken sentence comprehension.

Equivalent mismatch negativity deficits across deviant types in early illness schizophrenia-spectrum patients.

PubMed

Hay, Rachel A; Roach, Brian J; Srihari, Vinod H; Woods, Scott W; Ford, Judith M; Mathalon, Daniel H

2015-02-01

Neurophysiological abnormalities in auditory deviance processing, as reflected by the mismatch negativity (MMN), have been observed across the course of schizophrenia. Studies in early schizophrenia patients have typically shown varying degrees of MMN amplitude reduction for different deviant types, suggesting that different auditory deviants are uniquely processed and may be differentially affected by duration of illness. To explore this further, we examined the MMN response to 4 auditory deviants (duration, frequency, duration+frequency "double deviant", and intensity) in 24 schizophrenia-spectrum patients early in the illness (ESZ) and 21 healthy controls. ESZ showed significantly reduced MMN relative to healthy controls for all deviant types (p<0.05), with no significant interaction with deviant type. No correlations with clinical symptoms were present (all ps>0.05). These findings support the conclusion that neurophysiological mechanisms underlying processing of auditory deviants are compromised early in illness, and these deficiencies are not specific to the type of deviant presented. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed

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

2001-05-25

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

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

PubMed

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.

Effect of moderate learning style-teaching mode mismatch on academic performance among 2nd year medical students in Pakistan.

PubMed

Hamza, Muhammad; Inam-Ul-Haq; Hamid, Sidra; Nadir, Maha; Mehmood, Nadir

2018-01-01

The vagueness surrounding "learning style-teaching mode mismatch" makes its effects uncertain. This study tried to tackle that controversy by comparing and assessing the effect of different learning styles on performance in physiology examination when teaching mode was somewhat different than learning preferences of the 2 nd year medical students. A total of 102 2 nd year medical students participated in this study. Honey and Mumford learning style questionnaire was used to categorize the participants into one of the four learning styles (activist, reflector, theorist, and pragmatist). Many teaching modes were used in the medical college. The first professional theory and practical physiology scores of these 102 students of University of Health Sciences were obtained online. Learning styles were compared with physiology scores and age using one-way analysis of variance and post hoc statistical analysis and between males and females by using Chi-square test. Pragmatists had the lowest total physiology score ( P < 0.001), while theorists had the highest total physiology scores ( P < 0.001). Activists and reflectors had scores in between pragmatists and theorists, and there was no statistical difference between these two styles of learning ( P = 0.9). No student scored below 60%. This study demonstrated that the effect of moderate teaching-learning mismatch is different for different learners. Theorists excelled as they had the highest physiology score, while pragmatists lagged in comparison. Reflectors and activists performed better than pragmatists but were worse than theorists. Despite this, none of the students scored below 60%. This shows that a moderate learning style-teaching mode mismatch is not harmful for learning.

A Computational Model for Biomechanical Effects of Arterial Compliance Mismatch

PubMed Central

He, Fan; Hua, Lu; Gao, Li-jian

2015-01-01

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. PMID:27019580

Influence of cognitive control and mismatch on the N2 component of the ERP: A review

PubMed Central

Folstein, Jonathan R.; Van Petten, Cyma

2008-01-01

Recent years have seen an explosion of research on the N2 component of the event-related potential, a negative wave peaking between 200 and 350 ms after stimulus onset. This research has focused on the influence of “cognitive control,” a concept that covers strategic monitoring and control of motor responses. However, rich research traditions focus on attention and novelty or mismatch as determinants of N2 amplitude. We focus on paradigms that elicit N2 components with an anterior scalp distribution, namely, cognitive control, novelty, and sequential matching, and argue that the anterior N2 should be divided into separate control- and mismatch-related subcomponents. We also argue that the oddball N2 belongs in the family of attention-related N2 components that, in the visual modality, have a posterior scalp distribution. We focus on the visual modality for which components with frontocentral and more posterior scalp distributions can be readily distinguished. PMID:17850238

Successful Blood Transfusion Management of a Living Donor Liver Transplant Recipient in the Presence of Anti-Jra: A Case Report.

PubMed

Kurata, N; Onishi, Y; Kamei, H; Hori, T; Komagome, M; Kato, C; Matsushita, T; Ogura, Y

2017-09-01

A 48-year-old Japanese woman was diagnosed with Budd-Chiari syndrome and transferred for possible living donor liver transplantation (LDLT). Examinations before LDLT revealed that the recipient had anti-Jr a and preformed donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA). Rituximab was administrated at 16 days prior to the patient's scheduled LDLT for the prophylaxis of antibody-mediated rejection by DSA. The clinical significance of anti-Jr a has not been clearly established because of the rarity of this antibody, so we discussed blood transfusion strategy with the Department of Blood Transfusion Service and prepared for Jr a -negative packed red blood cells (RBCs). Intraoperative blood salvage was used during LDLT procedures to reduce the use of packed RBCs. Although post-transplantation graft function was excellent, a total of 44 U of Jr a -negative RBCs were transfused during the entire perioperative period. Because sufficient amounts of Jr a -negative packed RBCs were supplied, Jr a mismatched blood transfusion was avoided. The patient was discharged from our hospital on postoperative day 102 without clinical evidence of any blood transfusion-related adverse events. Although there are some controversies of blood transfusion related to anti-Jr a antibodies, the current strategies of blood transfusion for liver transplantation with anti-Jr a are as follows: (1) sufficient supply and transfusion of Jr a -negative matched packed RBCs and (2) application of intraoperative blood salvage to reduce the total amount of rare blood type RBCs. These strategies may be changed when the mechanism of anti-Jr a alloimmunization is fully understood in the future. Copyright © 2017 Elsevier Inc. All rights reserved.

The acceleration of spoken-word processing in children's native-language acquisition: an ERP cohort study.

PubMed

Ojima, Shiro; Matsuba-Kurita, Hiroko; Nakamura, Naoko; Hagiwara, Hiroko

2011-04-01

Healthy adults can identify spoken words at a remarkable speed, by incrementally analyzing word-onset information. It is currently unknown how this adult-level speed of spoken-word processing emerges during children's native-language acquisition. In a picture-word mismatch paradigm, we manipulated the semantic congruency between picture contexts and spoken words, and recorded event-related potential (ERP) responses to the words. Previous similar studies focused on the N400 response, but we focused instead on the onsets of semantic congruency effects (N200 or Phonological Mismatch Negativity), which contain critical information for incremental spoken-word processing. We analyzed ERPs obtained longitudinally from two age cohorts of 40 primary-school children (total n=80) in a 3-year period. Children first tested at 7 years of age showed earlier onsets of congruency effects (by approximately 70ms) when tested 2 years later (i.e., at age 9). Children first tested at 9 years of age did not show such shortening of onset latencies 2 years later (i.e., at age 11). Overall, children's onset latencies at age 9 appeared similar to those of adults. These data challenge the previous hypothesis that word processing is well established at age 7. Instead they support the view that the acceleration of spoken-word processing continues beyond age 7. Copyright © 2011 Elsevier Ltd. All rights reserved.

High risk of graft failure in patients with anti-HLA antibodies undergoing haploidentical stem-cell transplantation.

PubMed

Ciurea, Stefan O; de Lima, Marcos; Cano, Pedro; Korbling, Martin; Giralt, Sergio; Shpall, Elizabeth J; Wang, Xuemei; Thall, Peter F; Champlin, Richard E; Fernandez-Vina, Marcelo

2009-10-27

BACKGROUND.: Although donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) have been implicated in graft rejection in solid organ transplantation, their role in hematopoietic stem-cell transplantation remains unclear. METHODS.: To address the hypothesis that the presence of DSA contributes to the development graft failure, we tested 24 consecutive patients for the presence of anti-HLA antibodies determined by a sensitive and specific solid-phase/single-antigen assay. The study included a total of 28 haploidentical transplants, each with 2 to 5 HLA allele mismatches, at a single institution, from September 2005 to August 2008. RESULTS.: DSA were detected in five patients (21%). Three of four (75%) patients with DSA before the first transplant failed to engraft, compared with 1 of 20 (5%) without DSA (P=0.008). All four patients who experienced primary graft failure had second haploidentical transplants. One patient developed a second graft failure with persistent high DSA levels, whereas three engrafted, two of them in the absence of DSA. No other known factors that could negatively influence engraftment were associated with the development of graft failure in these patients. CONCLUSIONS.: These results suggest that donor-specific anti-HLA antibodies are associated with a high rate of graft rejection in patients undergoing haploidentical stem-cell transplantation. Anti-HLA sensitization should be evaluated routinely in hematopoietic stem-cell transplantation with HLA mismatched donors.

Applying different equations to evaluate the level of mismatch between students and school furniture.

PubMed

Castellucci, H I; Arezes, P M; Molenbroek, J F M

2014-07-01

The mismatch between students and school furniture is likely to result in a number of negative effects, such as uncomfortable body posture, pain, and ultimately, it may also affect the learning process. This study's main aim is to review the literature describing the criteria equations for defining the mismatch between students and school furniture, to apply these equations to a specific sample and, based on the results, to propose a methodology to evaluate school furniture suitability. The literature review comprises one publications database, which was used to identify the studies carried out in the field of the abovementioned mismatch. The sample used for testing the different equations was composed of 2261 volunteer subjects from 14 schools. Fifteen studies were found to meet the criteria of this review and 21 equations to test 6 furniture dimensions were identified. Regarding seat height, there are considerable differences between the two most frequently used equations. Although seat to desk clearance was evaluated by knee height, this condition seems to be based on the false assumption that students are sitting on a chair with a proper seat height. Finally, the proposed methodology for suitability evaluation of school furniture should allow for a more reliable analysis of school furniture. Copyright © 2014 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Impact of the phase-mismatch in the SHG crystal and consequential self-action of the fundamental wave by cascaded second-order effects on the THG efficiency of a Q-switched 1342 nm Nd:YVO₄ laser.

PubMed

Koch, Peter; Bartschke, Juergen; L'huillier, Johannes A

2015-05-18

We report on the influence of self-focusing and self-defocusing in the phase-mismatched frequency doubling crystal on the third harmonic generation (THG) efficiency in a two crystal frequency tripling scheme. By detuning the temperature of the doubling crystal, the impact of a phase-mismatch in second harmonic generation (SHG) on the subsequent sum frequency mixing process was investigated. It was found that adjusting the temperature not only affected the power ratio of the second harmonic to the fundamental but also the beam diameter of the fundamental beam in the THG crystal, which was caused by self-focusing and self-defocusing of the fundamental beam, respectively. This self-action was induced by a cascaded χ(2) : χ(2) process in the phase-mismatched SHG crystal. Self-defocusing was observable for positive detuning and self-focusing for negative detuning of the phase-matching temperature. Hence, the THG efficiency was not symmetric with respect to the point of optimum phase-matching. Optimum THG was obtained for positive detuning and the resulting self-defocusing in combination with the focusing lens in front of the THG stage was also beneficial for the beam quality of the third harmonic.

Changes in room acoustics elicit a Mismatch Negativity in the absence of overall interaural intensity differences.

PubMed

Frey, Johannes Daniel; Wendt, Mike; Löw, Andreas; Möller, Stephan; Zölzer, Udo; Jacobsen, Thomas

2017-02-15

Changes in room acoustics provide important clues about the environment of sound source-perceiver systems, for example, by indicating changes in the reflecting characteristics of surrounding objects. To study the detection of auditory irregularities brought about by a change in room acoustics, a passive oddball protocol with participants watching a movie was applied in this study. Acoustic stimuli were presented via headphones. Standards and deviants were created by modelling rooms of different sizes, keeping the values of the basic acoustic dimensions (e.g., frequency, duration, sound pressure, and sound source location) as constant as possible. In the first experiment, each standard and deviant stimulus consisted of sequences of three short sounds derived from sinusoidal tones, resulting in three onsets during each stimulus. Deviant stimuli elicited a Mismatch Negativity (MMN) as well as two additional negative deflections corresponding to the three onset peaks. In the second experiment, only one sound was used; the stimuli were otherwise identical to the ones used in the first experiment. Again, an MMN was observed, followed by an additional negative deflection. These results provide further support for the hypothesis of automatic detection of unattended changes in room acoustics, extending previous work by demonstrating the elicitation of an MMN by changes in room acoustics. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Inequality across Consonantal Contrasts in Speech Perception: Evidence from Mismatch Negativity

ERIC Educational Resources Information Center

Cornell, Sonia A.; Lahiri, Aditi; Eulitz, Carsten

2013-01-01

The precise structure of speech sound representations is still a matter of debate. In the present neurobiological study, we compared predictions about differential sensitivity to speech contrasts between models that assume full specification of all phonological information in the mental lexicon with those assuming sparse representations (only…

Electrophysiological Correlates of Automatic Visual Change Detection in School-Age Children

ERIC Educational Resources Information Center

Clery, Helen; Roux, Sylvie; Besle, Julien; Giard, Marie-Helene; Bruneau, Nicole; Gomot, Marie

2012-01-01

Automatic stimulus-change detection is usually investigated in the auditory modality by studying Mismatch Negativity (MMN). Although the change-detection process occurs in all sensory modalities, little is known about visual deviance detection, particularly regarding the development of this brain function throughout childhood. The aim of the…

Auditory Phoneme Discrimination in Illiterates: Mismatch Negativity--A Question of Literacy?

ERIC Educational Resources Information Center

Schaadt, Gesa; Pannekamp, Ann; van der Meer, Elke

2013-01-01

These days, illiteracy is still a major problem. There is empirical evidence that auditory phoneme discrimination is one of the factors contributing to written language acquisition. The current study investigated auditory phoneme discrimination in participants who did not acquire written language sufficiently. Auditory phoneme discrimination was…

ERP Study of Pre-Attentive Auditory Processing in Treatment-Refractory Schizophrenia

ERIC Educational Resources Information Center

Milovan, Denise L.; Baribeau, Jacinthe; Roth, Robert M.; Stip, Emmanuel

2004-01-01

Event-related potential (ERP) studies have demonstrated impaired auditory sensory processing in patients with schizophrenia, as reflected in abnormal mismatch negativity (MMN). We sought to extend this finding by evaluating MMN in 13 treatment-refractory patients with schizophrenia, and 14 age- and gender-matched healthy controls. Subjects…

Overestimation of femoral tunnel length during anterior cruciate ligament reconstruction using the retrograde outside-in drilling technique.

PubMed

Okazaki, Ken; Osaki, Kanji; Nishikawa, Kazutaka; Matsubara, Hirokazu; Tashiro, Yasutaka; Iwamoto, Yukihide

2016-08-01

When the femoral tunnel socket is reamed in an oblique direction from the wall of inter-condylar notch in anterior cruciate ligament (ACL) reconstruction, the tunnel length can be shorter at the periphery than at the centre. Because surgeons can manipulate the direction of tunnel in the outside-in femoral tunnel drilling technique, this length mismatch would vary depending on the direction of the tunnel. The purpose of this study was to investigate this length mismatch when reamed in various directions. In total of thirteen points were defined as femoral drilling entry points on concentric lines with 0, 1, 2, and 3 cm radius from the lateral epicondyle of a three-dimensional bone model from 40 subjects. Femoral tunnel drilling was simulated on the models by connecting the centre of the ACL footprint with each defined point on the lateral femoral surface. The mismatch length was measured between the centre and the shortest peripheral side of the tunnel socket. When the distance between the drilling entry point on the lateral femoral surface and the lateral epicondyle was increased to anterior proximal direction, there was a significant increase in the mismatch length. The mismatch length became more than 2 mm when the entry point was located more than 2 cm away from the lateral epicondyle. When the drilling entry point is set far away from the lateral epicondyle, a significant increase was observed in tunnel length mismatch between the centre of the tunnel and its shortest peripheral side. Because the tunnel length is measured with a guide pin introduced at the centre of the tunnel before reaming in retrograde outside-in technique, this length mismatch could cause an overestimation of the tunnel length. Surgeons should recognise this mismatch when preparing the length of graft and socket to optimise the graft insertion length into the socket.

Effects of Microstructural Parameters on Creep of Nickel-Base Superalloy Single Crystals

NASA Technical Reports Server (NTRS)

MacKay, Rebecca A.; Gabb, Timothy P.; Nathal, Michael V.

2013-01-01

Microstructure-sensitive creep models have been developed for Ni-base superalloy single crystals. Creep rupture testing was conducted on fourteen single crystal alloys at two applied stress levels at each of two temperatures, 982 and 1093 C. The variation in creep lives among the different alloys could be explained with regression models containing relatively few microstructural parameters. At 982 C, gamma-gamma prime lattice mismatch, gamma prime volume fraction, and initial gamma prime size were statistically significant in explaining the creep rupture lives. At 1093 C, only lattice mismatch and gamma prime volume fraction were significant. These models could explain from 84 to 94 percent of the variation in creep lives, depending on test condition. Longer creep lives were associated with alloys having more negative lattice mismatch, lower gamma prime volume fractions, and finer gamma prime sizes. The gamma-gamma prime lattice mismatch exhibited the strongest influence of all the microstructural parameters at both temperatures. Although a majority of the alloys in this study were stable with respect to topologically close packed (TCP) phases, it appeared that up to approximately 2 vol% TCP phase did not affect the 1093 C creep lives under applied stresses that produced lives of approximately 200 to 300 h. In contrast, TCP phase contents of approximately 2 vol% were detrimental at lower applied stresses where creep lives were longer. A regression model was also developed for the as-heat treated initial gamma prime size; this model showed that gamma prime solvus temperature, gamma-gamma prime lattice mismatch, and bulk Re content were all statistically significant.

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

PubMed

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

2016-08-17

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

Influenza-related health care utilization and productivity losses during seasons with and without a match between the seasonal and vaccine virus B lineage.

PubMed

Karve, Sudeep; Meier, Genevieve; Davis, Keith L; Misurski, Derek A; Wang, Chi-Chuan Emma

2013-07-18

To assess and compare direct medical costs (incurred by payers) and indirect productivity losses (incurred by employers) associated with influenza seasons with matched or mismatched circulating and vaccine containing influenza B lineages. A retrospective analysis, using two MarketScan databases, for the years 2000-2009. Each influenza season was categorized as matched or mismatched after comparing that season's circulating influenza B lineage and the vaccine influenza B lineage. Patients selected had at least one diagnosis claim for influenza (ICD-9-CM code 487.xx [influenza] or 488.1 [H1N1]) during an influenza season. We assessed the incidence of influenza (overall and influenza B), influenza-related medical utilization and associated costs, and productivity losses for each season. The four matched seasons had lower average influenza incidence (overall incidence per 100,000 plan members: 509; 95% confidence interval [CI]: 505-512) than the five mismatched seasons (748; 95% CI: 745-751). The mismatched seasons had lower influenza B incidence (average incidence per 100,000 plan members: 126; 95% CI: 125-128) than the matched seasons (165; 95% CI: 163-167). The average, per-patient, total influenza-related medical costs in the mismatched seasons ($300.83; range: $245.38-$371.58) were approximately $61.00 higher than in the matched seasons ($239.43; range: $201.49-$264.01). The mismatched seasons had greater average per-patient, influenza-related productivity-loss costs than the matched seasons (mean: $237.31 vs. $175.10). CDC data showed that influenza A was the predominant circulating strain during seasons in which the circulating influenza B lineage did not match the vaccine influenza B lineage. This resulted in lower influenza B incidence during the mismatched seasons. However, the average, per-patient, influenza-related direct medical costs and indirect productivity losses were higher during the mismatched seasons. Additional research is required to determine if these higher costs can be attributed to influenza B infections and if the influenza severity varies during mismatched seasons. Copyright © 2013 Elsevier Ltd. All rights reserved.

Phase-locked loop design with fast-digital-calibration charge pump

NASA Astrophysics Data System (ADS)

Wang, San-Fu; Hwang, Tsuen-Shiau; Wang, Jhen-Ji

2016-02-01

A fast-digital-calibration technique is proposed for reducing current mismatch in the charge pump (CP) of a phase-locked loop (PLL). The current mismatch in the CP generates fluctuations, which is transferred to the input of voltage-controlled oscillator (VCO). Therefore, the current mismatch increases the reference spur in the PLL. Improving current match of CP will reduce the reference spur and decrease the static phase offset of PLLs. Moreover, the settling time, ripple and power consumption of the PLL are also improved by the proposed technique. This study evaluated a 2.27-2.88 GHz frequency synthesiser fabricated in TSMC 0.18 μm CMOS 1.8 V process. The tuning range of proposed VCO is about 26%. By using the fast-digital-calibration technique, current mismatch is reduced to lower than 0.97%, and the operation range of the proposed CP is between 0.2 and 1.6 V. The proposed PLL has a total power consumption of 22.57 mW and a settling time of 10 μs or less.

Mexican American adolescent couples' vulnerability for observed negativity and physical violence: Pregnancy and acculturation mismatch.

PubMed

Williams, Lela Rankin; Rueda, Heidi Adams

2016-10-01

Stress and vulnerability for dating violence may be heightened among acculturating Mexican American (MA) adolescents, and MA adolescent parents, because of differing cultural values and norms within romantic relationships. We hypothesized, in a sample of MA heterosexual couples (N = 30, 15-17 years), that: 1) within-couple level acculturation discrepancies, and pregnancy/parenting, would predict physical violence perpetration, and 2) that this association would have an indirect effect through couple-level negativity during an observed dyadic video-taped discussion of conflict. Using a path model we found that pregnant/parenting adolescents (B = .37, SE = .16, p = .002), and couples with greater acculturation mismatch resulted in greater couple negativity (B = .16, SE = .06, p = .01), which was associated with self-reported physical violence perpetration (B = .41, SE = .22, p = .02; indirect effect, B = .15, SE = .07, p = .03). Within-couple acculturation discrepancies and pregnancy/parenting may be a pathway to dating violence through poor communication skills around conflict for MA youth. Support services that strengthen communication skills, particularly for pregnant/parenting couples, are recommended. Copyright © 2016 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

The Mismatch Negativity: An Indicator of Perception of Regularities in Music.

PubMed

Yu, Xide; Liu, Tao; Gao, Dingguo

2015-01-01

This paper reviews music research using Mismatch Negativity (MMN). MMN is a deviation-specific component of auditory event-related potential (EPR), which detects a deviation between a sound and an internal representation (e.g., memory trace). Recent studies have expanded the notion and the paradigms of MMN to higher-order music processing such as those involving short melodies, harmony chord, and music syntax. In this vein, we firstly reviewed the evolution of MMN from sound to music and then mainly compared the differences of MMN features between musicians and nonmusicians, followed by the discussion of the potential roles of the training effect and the natural exposure in MMN. Since MMN can serve as an index of neural plasticity, it thus can be widely used in clinical and other applied areas, such as detecting music preference in newborns or assessing wholeness of central auditory system of hearing illness. Finally, we pointed out some open questions and further directions. Current music perception research using MMN has mainly focused on relatively low hierarchical structure of music perception. To fully understand the neural substrates underlying processing of regularities in music, it is important and beneficial to combine MMN with other experimental paradigms such as early right-anterior negativity (ERAN).

Mismatch negativity evoked by the McGurk-MacDonald effect: a phonetic representation within short-term memory.

PubMed

Colin, C; Radeau, M; Soquet, A; Demolin, D; Colin, F; Deltenre, P

2002-04-01

The McGurk-MacDonald illusory percept is obtained by dubbing an incongruent articulatory movement on an auditory phoneme. This type of audiovisual speech perception contributes to the assessment of theories of speech perception. The mismatch negativity (MMN) reflects the detection of a deviant stimulus within the auditory short-term memory and besides an acoustic component, possesses, under certain conditions, a phonetic one. The present study assessed the existence of an MMN evoked by McGurk-MacDonald percepts elicited by audiovisual stimuli with constant auditory components. Cortical evoked potentials were recorded using the oddball paradigm on 8 adults in 3 experimental conditions: auditory alone, visual alone and audiovisual stimulation. Obtaining illusory percepts was confirmed in an additional psychophysical condition. The auditory deviant syllables and the audiovisual incongruent syllables elicited a significant MMN at Fz. In the visual condition, no negativity was observed either at Fz, or at O(z). An MMN can be evoked by visual articulatory deviants, provided they are presented in a suitable auditory context leading to a phonetically significant interaction. The recording of an MMN elicited by illusory McGurk percepts suggests that audiovisual integration mechanisms in speech take place rather early during the perceptual processes.

The Mismatch Negativity: An Indicator of Perception of Regularities in Music

PubMed Central

Yu, Xide; Liu, Tao; Gao, Dingguo

2015-01-01

This paper reviews music research using Mismatch Negativity (MMN). MMN is a deviation-specific component of auditory event-related potential (EPR), which detects a deviation between a sound and an internal representation (e.g., memory trace). Recent studies have expanded the notion and the paradigms of MMN to higher-order music processing such as those involving short melodies, harmony chord, and music syntax. In this vein, we firstly reviewed the evolution of MMN from sound to music and then mainly compared the differences of MMN features between musicians and nonmusicians, followed by the discussion of the potential roles of the training effect and the natural exposure in MMN. Since MMN can serve as an index of neural plasticity, it thus can be widely used in clinical and other applied areas, such as detecting music preference in newborns or assessing wholeness of central auditory system of hearing illness. Finally, we pointed out some open questions and further directions. Current music perception research using MMN has mainly focused on relatively low hierarchical structure of music perception. To fully understand the neural substrates underlying processing of regularities in music, it is important and beneficial to combine MMN with other experimental paradigms such as early right-anterior negativity (ERAN). PMID:26504352

Recombination energy for negatively charged excitons inside type-II core/shell spherical quantum dots

NASA Astrophysics Data System (ADS)

Chafai, A.; Essaoudi, I.; Ainane, A.; Dujardin, F.; Ahuja, R.

2018-07-01

The recombination energy of isolated neutral exciton and that of isolated negatively charged exciton inside a type-II core/shell spherical quantum dot are studied. Our investigation considers the charge-carriers effective mass discontinuity at the surface contact between the core and shell materials. Although our model omits the effect of the surface polarization, the dielectric-constant mismatch at the nanodot boundaries was taken into account. In order to achieve the exciton and negative trion energies, we proceed by a variational calculation in the framework of the envelope approximation. Our results reveal a strong correlation between the nanodot morphology and the energy spectrum of the neutral and negatively charged exciton.

Stoichiometric Mismatch between Consumers and Resources Mediates the Growth of Rocky Intertidal Suspension Feeders

PubMed Central

Bracken, Matthew E. S.

2017-01-01

The concept of ecological stoichiometry—the balancing of elemental ratios in ecological interactions—has transformed our thinking about processes in natural systems. Here, this perspective is applied to rocky shore ecosystems to explore the consequences of variation in internal nutrient ratios across two trophic levels. Specifically, I measured the internal concentrations of carbon (C) and nitrogen (N) in mussels (Mytilus spp.) and particulate organic matter (POM) to evaluate the effects of stoichiometric mismatch—the difference in the carbon-to-nitrogen ratio (C:N) between a consumer and its resources—on mussel growth at sites on the coasts of Oregon, USA, and the South Island of New Zealand. As POM quality (i.e., Chl a, a proxy for phytoplankton availability in the POM) increased, C:N of the POM declined, but C:N of mussels increased. This resulted in a greater mismatch in C:N between mussels and their food source at low Chl a. Mussel growth across sites was positively associated with Chl a, particulate organic carbon (POC), and particulate organic nitrogen (PON) but negatively associated with stoichiometric mismatch. Overall, as the elemental ratios of consumers became more different from those of their resources, growth declined, likely due to the energetic cost associated with processing lower quality food. Furthermore, the effect of food quantity on growth depended on stoichiometric mismatch. In New Zealand, where mismatch was high—i.e., consumer C:N differed substantially from resource C:N—consumer growth was strongly affected by resource quantity (Chl a or POC). However, in Oregon, where mismatch was low, the relationship between resource quantity and growth was considerably weaker. This interaction between resource quantity and mismatch was not apparent for PON, which is consistent with variation in PON underlying variation in POM C:N and highlights the role of N in limiting growth. Previous research has neglected the importance of ecological stoichiometry as a mediator of consumer-resource interactions in rocky intertidal communities. I show that resource quality and quantity interact to determine consumer growth, highlighting the utility of ecological stoichiometry in understanding spatial subsidies in benthic marine systems. PMID:28747903

Mother-Infant Emotion Regulation at Three Months: The Role of Maternal Anxiety, Depression and Parenting Stress.

PubMed

Riva Crugnola, Cristina; Ierardi, Elena; Ferro, Valentino; Gallucci, Marcello; Parodi, Cinzia; Astengo, Marina

While the association between anxiety and postpartum depression is well known, few studies have investigated the relationship between these two states and parenting stress. Furthermore, a number of studies have found that postpartum depression affects mother-infant emotion regulation, but there has been only one study on anxiety and emotion regulation and no studies at all on parenting stress and emotion regulation. Therefore, the primary aim of our study is to identify, in a community sample of 71 mothers, the relationship between maternal depression, anxiety, and parenting stress. The second aim is to examine the relationship between anxiety, postpartum depression, and parenting stress and mother-infant emotion regulation assessed at 3 months. Mother-infant interaction was coded with a modified version of the Infant Caregiver and Engagement Phases (ICEP) using a microanalytic approach. The Edinburgh Postnatal Depression Scale (EPDS), State-Trait Anxiety Inventory (STAI), and Parenting Stress Index-Short Form (PSI-SF) were administered to the mothers to assess depression, anxiety, and parenting stress, respectively. Analysis revealed correlations between anxiety and depression, showing that parenting stress is associated with both states. In a laboratory observation, depression was correlated with both negative maternal states and negative dyadic matches as well as infant positive/mother negative mismatches; anxiety was correlated with both negative maternal states and infant negative states as well as mismatches involving one of the partners having a negative state. Multiple regression analysis showed that anxiety is a greater predictor than depression of less adequate styles of mother-infant emotion regulation. Parenting stress was not shown to predict such regulation. © 2016 S. Karger AG, Basel.

HLA-DQ Mismatching and Kidney Transplant Outcomes.

PubMed

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 <0.01), but not in deceased kidney donor recipients (HR, 1.05; 95% CI, 0.98 to 1.12; P =0.18) ( P value for interaction <0.01). When taking cold ischemic time into account, 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 <0.01). Recipients with one or two 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 <0.01) in deceased donor and 1.14 (95% CI, 1.03 to 1.27; P =0.02) in living donor kidney 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 Society of Nephrology.

Atypical Mismatch Negativity to Distressful Voices Associated with Conduct Disorder Symptoms

ERIC Educational Resources Information Center

Hung, An-Yi; Ahveninen, Jyrki; Cheng, Yawei

2013-01-01

Background: Although a general consensus holds that emotional reactivity in youth with conduct disorder (CD) symptoms arises as one of the main causes of successive aggression, it remains to be determined whether automatic emotional processing is altered in this population. Methods: We measured auditory event-related potentials (ERP) in 20 young…

Is the Feeling Mutual? Examining Parent-Teacher Relationships in Low-Income, Predominantly Latino Schools

ERIC Educational Resources Information Center

Miller, Hannah; Robinson, Michelle; Valentine, Jessa Lewis; Fish, Rachel

2016-01-01

Strong parent-teacher relationships are critical to students' academic success. Mismatches in parents' and teachers' perceptions of each other may negatively affect children's outcomes. Using survey data collected from parents and teachers in 52 low-income, predominantly Latino schools, we explore subgroup variation in parents' and teachers'…

Effects of aging on neuromagnetic mismatch responses to pitch changes.

PubMed

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.

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

PubMed

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

2009-08-23

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

Processing of acoustic and phonological information of lexical tones in Mandarin Chinese revealed by mismatch negativity.

PubMed

Yu, Keke; Wang, Ruiming; Li, Li; Li, Ping

2014-01-01

The accurate perception of lexical tones in tonal languages involves the processing of both acoustic information and phonological information carried by the tonal signal. In this study we evaluated the relative role of the two types of information in native Chinese speaker's processing of tones at a preattentive stage with event-related potentials (ERPs), particularly the mismatch negativity (MNN). Specifically, we distinguished the acoustic from the phonological information by manipulating phonological category and acoustic interval of the stimulus materials. We found a significant main effect of phonological category for the peak latency of MMN, but a main effect of both phonological category and acoustic interval for the mean amplitude of MMN. The results indicated that the two types of information, acoustic and phonological, play different roles in the processing of Chinese lexical tones: acoustic information only impacts the extent of tonal processing, while phonological information affects both the extent and the time course of tonal processing. Implications of these findings are discussed in light of neurocognitive processes of phonological processing.

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

PubMed

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

2012-03-01

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

Electrophysiological evidence for the left-lateralized effect of language on preattentive categorical perception of color

PubMed Central

Mo, Lei; Xu, Guiping; Kay, Paul; Tan, Li-Hai

2011-01-01

Previous studies have shown that the effect of language on categorical perception of color is stronger when stimuli are presented in the right visual field than in the left. To examine whether this lateralized effect occurs preattentively at an early stage of processing, we monitored the visual mismatch negativity, which is a component of the event-related potential of the brain to an unfamiliar stimulus among a temporally presented series of stimuli. In the oddball paradigm we used, the deviant stimuli were unrelated to the explicit task. A significant interaction between color-pair type (within-category vs. between-category) and visual field (left vs. right) was found. The amplitude of the visual mismatch negativity component evoked by the within-category deviant was significantly smaller than that evoked by the between-category deviant when displayed in the right visual field, but no such difference was observed for the left visual field. This result constitutes electroencephalographic evidence that the lateralized Whorf effect per se occurs out of awareness and at an early stage of processing. PMID:21844340

Abnormal frequency discrimination in children with SLI as indexed by mismatch negativity (MMN).

PubMed

Rinker, Tanja; Kohls, Gregor; Richter, Cathrin; Maas, Verena; Schulz, Eberhard; Schecker, Michael

2007-02-14

For several decades, the aetiology of specific language impairment (SLI) has been associated with a central auditory processing deficit disrupting the normal language development of affected children. One important aspect for language acquisition is the discrimination of different acoustic features, such as frequency information. Concerning SLI, studies to date that examined frequency discrimination abilities have been contradictory. We hypothesized that an auditory processing deficit in children with SLI depends on the frequency range and the difference between the tones used. Using a passive mismatch negativity (MMN)-design, 13 boys with SLI and 13 age- and IQ-matched controls (7-11 years) were tested with two sine tones of different frequency (700Hz versus 750Hz). Reversed hemispheric activity between groups indicated abnormal processing in SLI. In a second time window, MMN2 was absent for the children with SLI. It can therefore be assumed that a frequency discrimination deficit in children with SLI becomes particularly apparent for tones below 750Hz and for a frequency difference of 50Hz. This finding may have important implications for future research and integration of various research approaches.

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

PubMed

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

2016-01-26

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

Clinicopathological characteristics of patients with upper urinary tract urothelial cancer with loss of immunohistochemical expression of the DNA mismatch repair proteins in universal screening.

PubMed

Urakami, Shinji; Inoshita, Naoko; Oka, Suguru; Miyama, Yu; Nomura, Sachio; Arai, Masami; Sakaguchi, Kazushige; Kurosawa, Kazuhiro; Okaneya, Toshikazu

2018-02-01

To assess the detection rate of putative Lynch syndrome-associated upper urinary tract urothelial cancer among all upper urinary tract urothelial cancers and to examine its clinicopathological characteristics. A total of 143 patients with upper urinary tract urothelial cancer who had received total nephroureterectomy were immunohistochemically stained for the expression of mismatch repair proteins MLH1, PMS2, MSH2 and MSH6. For all suspected mismatch repair-deficient cases, MMR genetic testing was recommended and clinicopathological features were examined. Loss of mismatch repair proteins was found in seven patients (5%) who were thus categorized as putative Lynch syndrome-associated upper urinary tract urothelial cancer. Five of these patients showed dual loss of MSH2/MSH6. Two patients were confirmed to be MSH2 germline mutation carriers. Histologically, all seven tumors were low-grade atypical urothelial carcinoma and showed its unique histological features, such as an inverted papilloma-like growth pattern and a villous to papillary structure with mild stratification of tumor cells. Six tumors had no invasion of the muscularis propria. No recurrence or cancer-related deaths were reported in these seven patients. Just three patients met the revised Amsterdam criteria. This is the first report that universally examined mismatch repair immunohistochemical screening for upper urinary tract urothelial cancers. The prevalence (5%) of putative Lynch syndrome-associated upper urinary tract urothelial cancers is much higher than we had expected. We ascertained that putative Lynch syndrome-associated upper urinary tract urothelial cancers were clinically in the early stage and histologically classified into low-grade malignancy with its characteristic pathological features. The clinicopathological characteristics that we found in the present study could become additional possible markers in the diagnosis of Lynch syndrome-associated upper urinary tract urothelial cancers. © 2017 The Japanese Urological Association.

Mind the Gap: Mismatches Between Clinicians and Patients in Heart Failure Medication Management.

PubMed

Chin, Ken Lee; Skiba, Marina; Reid, Christopher M; Tonkin, Andrew; Hopper, Ingrid; Mariani, Justin A; Liew, Danny

2018-02-01

Previous studies on the 'treatment gap' in patients with heart failure (HF) have focused either on prescribing or patients' adherence to prescribed treatment. This study sought to determine whether or not recent initiatives to close the gap have also minimised any mismatches between physicians' expectation of their patients' medications, medications in the patients' possession and their actual medication use. A cross-sectional observational survey was conducted from December 2015 to June 2016 in The Alfred Hospital HF clinic in Melbourne, Australia. Patients were invited to participate if they had chronic HF (NYHA class II to IV), were aged ≥ 60 years, had no history of HF related hospitalisation within the past 6 months and were prescribed at least two HF medications. Of 123 eligible patients, 102 were recruited into the study. Beta-blockers, mineralocorticoid receptor antagonists, loop diuretics and statins were associated with the highest rates of mismatches of drugs and doses, ranging from 10 to 17%. Discrepancy of total daily doses was the most common type of mismatch. Overall, only 23.5% of the patients were taking the right drugs at the right doses as expected by their cardiologists/HF specialists. Despite improved prescribers' adherence to guideline-directed medical therapy, there remain considerable mismatches between prescribers' expectation of patients' HF medications, medications in patients' possession and their actual medication use. Initiatives to improve this situation are urgently needed.

A dynamic system analysis of dyadic flexibility and stability across the Face-to-Face Still-Face procedure: application of the State Space Grid.

PubMed

Provenzi, Livio; Borgatti, Renato; Menozzi, Giorgia; Montirosso, Rosario

2015-02-01

The Face-to-Face Still-Face (FFSF) paradigm allows to study the mother-infant dyad as a dynamic system coping with social stress perturbations. The State Space Grid (SSG) method is thought to depict both flexibility and stability of the dyad across perturbations, but previous SSG evidence for the FFSF is limited. The main aims were: (1) to investigate mother-infant dyadic flexibility and stability across the FFSF using the SSG; (2) to evaluate the influence of dyadic functioning during Play on infant Still-Face response and of infant stress response in affecting dyadic functioning during Reunion. Forty 4-month-old infants and their mothers were micro-analytically coded during a FFSF and eight SSG dyadic states were obtained. Dyadic flexibility and attractor states were assessed during Play and Reunion. Infants' stress response was coded as negative engagement during the Still-Face episode. Two dyadic states, "maternal hetero-regulation" and "affective mismatch", showed significant changes in the number of visits from Play to Reunion. During Play "maternal positive support to infant play" emerged as attractor state, whereas during Reunion a second attractor emerged, namely "affective mismatch". Dyadic affective mismatch during Play correlated with infants' negative engagement during Still-Face, whereas infants' response to Still-Face resulted in minor social matching during Reunion. Findings provide new insights into the flexible, yet stable, functioning of the mother-infant dyad as a dynamic system. Evidence of a reciprocal influence between dyadic functioning and infant social stress response are discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

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

PubMed

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

2017-01-01

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

Lattice mismatch induced ripples and wrinkles in planar graphene/boron nitride superlattices

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nandwana, Dinkar; Ertekin, Elif, E-mail: ertekin@illinois.edu; International Institute for Carbon Neutral Energy Research

A continuum theory to describe periodic ripple formation in planar graphene/boron nitride superlattices is formulated. Due to the lattice mismatch between the two materials, it is shown that flat superlattices are unstable with respect to ripple formation of appropriate wavelengths. A competition between bending energy and transverse stretching energy gives rise to an optimal ripple wavelength that depends on the superlattice pitch. The optimal wavelengths predicted by the continuum theory are in good agreement with atomic scale total energy calculations previously reported by Nandwana and Ertekin [Nano Lett. 15, 1468 (2015)].

Speech-Sound Duration Processing in a Second Language is Specific to Phonetic Categories

ERIC Educational Resources Information Center

Nenonen, Sari; Shestakova, Anna; Huotilainen, Minna; Naatanen, Risto

2005-01-01

The mismatch negativity (MMN) component of the auditory event-related potential was used to determine the effect of native language, Russian, on the processing of speech-sound duration in a second language, Finnish, that uses duration as a cue for phonological distinction. The native-language effect was compared with Finnish vowels that either can…

Noise Equally Degrades Central Auditory Processing in 2- and 4-Year-Old Children

ERIC Educational Resources Information Center

Niemitalo-Haapola, Elina; Haapala, Sini; Kujala, Teija; Raappana, Antti; Kujala, Tiia; Jansson-Verkasalo, Eira

2017-01-01

Purpose: The aim of this study was to investigate developmental and noise-induced changes in central auditory processing indexed by event-related potentials in typically developing children. Method: P1, N2, and N4 responses as well as mismatch negativities (MMNs) were recorded for standard syllables and consonants, frequency, intensity, vowel, and…

Duration of Auditory Sensory Memory in Parents of Children with SLI: A Mismatch Negativity Study

ERIC Educational Resources Information Center

Barry, Johanna G.; Hardiman, Mervyn J.; Line, Elizabeth; White, Katherine B.; Yasin, Ifat; Bishop, Dorothy V. M.

2008-01-01

In a previous behavioral study, we showed that parents of children with SLI had a subclinical deficit in phonological short-term memory. Here, we tested the hypothesis that they also have a deficit in nonverbal auditory sensory memory. We measured auditory sensory memory using a paradigm involving an electrophysiological component called the…

Parametric Modulation of Error-Related ERP Components by the Magnitude of Visuo-Motor Mismatch

ERIC Educational Resources Information Center

Vocat, Roland; Pourtois, Gilles; Vuilleumier, Patrik

2011-01-01

Errors generate typical brain responses, characterized by two successive event-related potentials (ERP) following incorrect action: the error-related negativity (ERN) and the positivity error (Pe). However, it is unclear whether these error-related responses are sensitive to the magnitude of the error, or instead show all-or-none effects. We…

Psychophysiological Correlates of Developmental Changes in Healthy and Autistic Boys

ERIC Educational Resources Information Center

Weismüller, Benjamin; Thienel, Renate; Youlden, Anne-Marie; Fulham, Ross; Koch, Michael; Schall, Ulrich

2015-01-01

This study investigated neurodevelopmental changes in sound processing by recording mismatch negativity (MMN) in response to various degrees of sound complexity in 18 mildly to moderately autistic versus 15 healthy boys aged between 6 and 15 years. Autistic boys presented with lower IQ and poor performance on a range of executive and social…

Effect of the SOS response on the mean fitness of unicellular populations: a quasispecies approach.

PubMed

Kama, Amit; Tannenbaum, Emmanuel

2010-11-30

The goal of this paper is to develop a mathematical model that analyzes the selective advantage of the SOS response in unicellular organisms. To this end, this paper develops a quasispecies model that incorporates the SOS response. We consider a unicellular, asexually replicating population of organisms, whose genomes consist of a single, double-stranded DNA molecule, i.e. one chromosome. We assume that repair of post-replication mismatched base-pairs occurs with probability , and that the SOS response is triggered when the total number of mismatched base-pairs is at least . We further assume that the per-mismatch SOS elimination rate is characterized by a first-order rate constant . For a single fitness peak landscape where the master genome can sustain up to mismatches and remain viable, this model is analytically solvable in the limit of infinite sequence length. The results, which are confirmed by stochastic simulations, indicate that the SOS response does indeed confer a fitness advantage to a population, provided that it is only activated when DNA damage is so extensive that a cell will die if it does not attempt to repair its DNA.

Mid-IR femtosecond frequency conversion by soliton-probe collision in phase-mismatched quadratic nonlinear crystals.

PubMed

Liu, Xing; Zhou, Binbin; Guo, Hairun; Bache, Morten

2015-08-15

We show numerically that ultrashort self-defocusing temporal solitons colliding with a weak pulsed probe in the near-IR can convert the probe to the mid-IR. A near-perfect conversion efficiency is possible for a high effective soliton order. The near-IR self-defocusing soliton can form in a quadratic nonlinear crystal (beta-barium borate) in the normal dispersion regime due to cascaded (phase-mismatched) second-harmonic generation, and the mid-IR converted wave is formed in the anomalous dispersion regime between λ=2.2-2.4  μm as a resonant dispersive wave. This process relies on nondegenerate four-wave mixing mediated by an effective negative cross-phase modulation term caused by cascaded soliton-probe sum-frequency generation.

Effect of atomic size on undercoolability of binary solid solution alloy liquids with Zr, Ti, and Hf using electrostatic levitation

NASA Astrophysics Data System (ADS)

Jeon, S.; Kang, D.-H.; Lee, Y. H.; Lee, S.; Lee, G. W.

2016-11-01

We investigate the relationship between the excess volume and undercoolability of Zr-Ti and Zr-Hf alloy liquids by using electrostatic levitation. Unlike in the case of Zr-Hf alloy liquids in which sizes of the constituent atoms are matched, a remarkable increase of undercoolability and negative excess volumes are observed in Zr-Ti alloy liquids as a function of their compositional ratios. In this work, size mismatch entropies for the liquids were obtained by calculating their hard sphere diameters, number densities, and packing fractions. We also show that the size mismatch entropy, which arises from the differences in atomic sizes of the constituent elements, plays an important role in determining the stabilities of metallic liquids.

Marrow Ablative and Immunosuppressive Effects of I-131-anti-CD45 Antibody in Congenic and H2-Mismatched Murine Transplant Models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matthews, D. C.; Martin, P J.; Nourigat, C.

1998-12-01

Targeted hematopoietic irradiation delivered by I-131-anti-CD45 antibody has been combined with conventional marrow transplant preparative regimens in an effort to decrease relapse. Before increasing the proportion of therapy delivered by radiolabeled antibody, the myeloablative and immunosuppressive effects of such low dose rate irradiation must be quantitated. We have examined the ability of I-131-anti-CD45 antibody to facilitate engraftment in Ly5-congenic and H2-mismatched murine marrow transplant models. Recipient B6-Ly5-a mice were treated with 30F11 antibody labeled with 0.1 to 1.5 mCi I-131 and/or total body irradiation (TBI), followed by T-cell-depleted marrow from Ly5-b-congenic (C57BL/6) or H2-mismatched (BALB/c) donors. Engraftment was achieved readilymore » in the Ly5-congenic setting, with greater than 80% donor granulocytes and T cells after 0.5 mCi I-131 (estimated 17 Gy to marrow) or 8 Gy TBI. A higher TBI dose (14 Gy) was required to achieve engraftment of H2-mismatched mar row, and engraftment occurred in only 3 of 11 mice receiving 1.5 mCi I-131 delivered by anti-CD45 antibody. Engraftment of H2-mismatched marrow was achieved in 22 of 23 animals receiving 0.75 mCi I-131 delivered by anti-CD45 antibody combined with 8 Gy TBI. Thus, targeted radiation delivered via I-131-anti-CD45 antibody can enable engraftment of congenic marrow and can partially replace TBI when transplanting T-cell-depleted H2-mismatched marrow.« less

Under the hood of statistical learning: A statistical MMN reflects the magnitude of transitional probabilities in auditory sequences.

PubMed

Koelsch, Stefan; Busch, Tobias; Jentschke, Sebastian; Rohrmeier, Martin

2016-02-02

Within the framework of statistical learning, many behavioural studies investigated the processing of unpredicted events. However, surprisingly few neurophysiological studies are available on this topic, and no statistical learning experiment has investigated electroencephalographic (EEG) correlates of processing events with different transition probabilities. We carried out an EEG study with a novel variant of the established statistical learning paradigm. Timbres were presented in isochronous sequences of triplets. The first two sounds of all triplets were equiprobable, while the third sound occurred with either low (10%), intermediate (30%), or high (60%) probability. Thus, the occurrence probability of the third item of each triplet (given the first two items) was varied. Compared to high-probability triplet endings, endings with low and intermediate probability elicited an early anterior negativity that had an onset around 100 ms and was maximal at around 180 ms. This effect was larger for events with low than for events with intermediate probability. Our results reveal that, when predictions are based on statistical learning, events that do not match a prediction evoke an early anterior negativity, with the amplitude of this mismatch response being inversely related to the probability of such events. Thus, we report a statistical mismatch negativity (sMMN) that reflects statistical learning of transitional probability distributions that go beyond auditory sensory memory capabilities.

Do Participants’ Preferences for Mode of Delivery (Text, Video, or Both) Influence the Effectiveness of a Web-Based Physical Activity Intervention?

PubMed Central

Duncan, Mitch J; Plotnikoff, Ronald C; Mummery, W Kerry

2012-01-01

Background In randomized controlled trials, participants cannot choose their preferred intervention delivery mode and thus might refuse to participate or not engage fully if assigned to a nonpreferred group. This might underestimate the true effectiveness of behavior-change interventions. Objective To examine whether receiving interventions either matched or mismatched with participants’ preferred delivery mode would influence effectiveness of a Web-based physical activity intervention. Methods Adults (n = 863), recruited via email, were randomly assigned to one of three intervention delivery modes (text based, video based, or combined) and received fully automated, Internet-delivered personal advice about physical activity. Personalized intervention content, based on the theory of planned behavior and stages of change concept, was identical across groups. Online, self-assessed questionnaires measuring physical activity were completed at baseline, 1 week, and 1 month. Physical activity advice acceptability and website usability were assessed at 1 week. Before randomization, participants were asked which delivery mode they preferred, to categorize them as matched or mismatched. Time spent on the website was measured throughout the intervention. We applied intention-to-treat, repeated-measures analyses of covariance to assess group differences. Results Attrition was high (575/863, 66.6%), though equal between groups (t 86 3 =1.31, P =.19). At 1-month follow-up, 93 participants were categorized as matched and 195 as mismatched. They preferred text mode (493/803, 61.4%) over combined (216/803, 26.9%) and video modes (94/803, 11.7%). After the intervention, 20% (26/132) of matched-group participants and 34% (96/282) in the mismatched group changed their delivery mode preference. Time effects were significant for all physical activity outcomes (total physical activity: F 2,801 = 5.07, P = .009; number of activity sessions: F 2,801 = 7.52, P < .001; walking: F 2,801 = 8.32, P < .001; moderate physical activity: F 2,801 = 9.53, P < .001; and vigorous physical activity: F 2,801 = 6.04, P = .002), indicating that physical activity increased over time for both matched and mismatched groups. Matched-group participants improved physical activity outcomes slightly more than those in the mismatched group, but interaction effects were not significant. Physical activity advice acceptability (content scale: t 368 = .10, P = .92; layout scale: t 368 = 1.53, P = .12) and website usability (layout scale: t 426 = .05, P = .96; ease of use scale: t 426 = .21, P = .83) were generally high and did not differ between the matched and mismatched groups. The only significant difference (t 621 = 2.16, P = .03) was in relation to total time spent on the website: the mismatched group spent significantly more time on the website (14.4 minutes) than the matched group (12.1 minutes). Conclusion Participants’ preference regarding delivery mode may not significantly influence intervention outcomes. Consequently, allowing participants to choose their preferred delivery mode may not increase effectiveness of Web-based interventions. PMID:22377834

Do participants' preferences for mode of delivery (text, video, or both) influence the effectiveness of a Web-based physical activity intervention?

PubMed

Vandelanotte, Corneel; Duncan, Mitch J; Plotnikoff, Ronald C; Mummery, W Kerry

2012-02-29

In randomized controlled trials, participants cannot choose their preferred intervention delivery mode and thus might refuse to participate or not engage fully if assigned to a nonpreferred group. This might underestimate the true effectiveness of behavior-change interventions. To examine whether receiving interventions either matched or mismatched with participants' preferred delivery mode would influence effectiveness of a Web-based physical activity intervention. Adults (n = 863), recruited via email, were randomly assigned to one of three intervention delivery modes (text based, video based, or combined) and received fully automated, Internet-delivered personal advice about physical activity. Personalized intervention content, based on the theory of planned behavior and stages of change concept, was identical across groups. Online, self-assessed questionnaires measuring physical activity were completed at baseline, 1 week, and 1 month. Physical activity advice acceptability and website usability were assessed at 1 week. Before randomization, participants were asked which delivery mode they preferred, to categorize them as matched or mismatched. Time spent on the website was measured throughout the intervention. We applied intention-to-treat, repeated-measures analyses of covariance to assess group differences. Attrition was high (575/863, 66.6%), though equal between groups (t(86) (3) =1.31, P =.19). At 1-month follow-up, 93 participants were categorized as matched and 195 as mismatched. They preferred text mode (493/803, 61.4%) over combined (216/803, 26.9%) and video modes (94/803, 11.7%). After the intervention, 20% (26/132) of matched-group participants and 34% (96/282) in the mismatched group changed their delivery mode preference. Time effects were significant for all physical activity outcomes (total physical activity: F(2,801) = 5.07, P = .009; number of activity sessions: F(2,801) = 7.52, P < .001; walking: F(2,801) = 8.32, P < .001; moderate physical activity: F(2,801) = 9.53, P < .001; and vigorous physical activity: F(2,801) = 6.04, P = .002), indicating that physical activity increased over time for both matched and mismatched groups. Matched-group participants improved physical activity outcomes slightly more than those in the mismatched group, but interaction effects were not significant. Physical activity advice acceptability (content scale: t(368) = .10, P = .92; layout scale: t(368) = 1.53, P = .12) and website usability (layout scale: t(426) = .05, P = .96; ease of use scale: t(426) = .21, P = .83) were generally high and did not differ between the matched and mismatched groups. The only significant difference (t(621) = 2.16, P = .03) was in relation to total time spent on the website: the mismatched group spent significantly more time on the website (14.4 minutes) than the matched group (12.1 minutes). Participants' preference regarding delivery mode may not significantly influence intervention outcomes. Consequently, allowing participants to choose their preferred delivery mode may not increase effectiveness of Web-based interventions.

Color-coded fluid-attenuated inversion recovery images improve inter-rater reliability of fluid-attenuated inversion recovery signal changes within acute diffusion-weighted image lesions.

PubMed

Kim, Bum Joon; Kim, Yong-Hwan; Kim, Yeon-Jung; Ahn, Sung Ho; Lee, Deok Hee; Kwon, Sun U; Kim, Sang Joon; Kim, Jong S; Kang, Dong-Wha

2014-09-01

Diffusion-weighted image fluid-attenuated inversion recovery (FLAIR) mismatch has been considered to represent ischemic lesion age. However, the inter-rater agreement of diffusion-weighted image FLAIR mismatch is low. We hypothesized that color-coded images would increase its inter-rater agreement. Patients with ischemic stroke <24 hours of a clear onset were retrospectively studied. FLAIR signal change was rated as negative, subtle, or obvious on conventional and color-coded FLAIR images based on visual inspection. Inter-rater agreement was evaluated using κ and percent agreement. The predictive value of diffusion-weighted image FLAIR mismatch for identification of patients <4.5 hours of symptom onset was evaluated. One hundred and thirteen patients were enrolled. The inter-rater agreement of FLAIR signal change improved from 69.9% (k=0.538) with conventional images to 85.8% (k=0.754) with color-coded images (P=0.004). Discrepantly rated patients on conventional, but not on color-coded images, had a higher prevalence of cardioembolic stroke (P=0.02) and cortical infarction (P=0.04). The positive predictive value for patients <4.5 hours of onset was 85.3% and 71.9% with conventional and 95.7% and 82.1% with color-coded images, by each rater. Color-coded FLAIR images increased the inter-rater agreement of diffusion-weighted image FLAIR recovery mismatch and may ultimately help identify unknown-onset stroke patients appropriate for thrombolysis. © 2014 American Heart Association, Inc.

Ray trace visualization of negative refraction of light in two-dimensional air-bridged silicon photonic crystal slabs at 1.55 microm.

PubMed

Gan, Lin; Liu, Ya-Zhao; Li, Jiang-Yan; Zhang, Ze-Bo; Zhang, Dao-Zhong; Li, Zhi-Yuan

2009-06-08

We demonstrate design, fabrication, and ray trace observation of negative refraction of near-infrared light in a two-dimensional square lattice of air holes etched into an air-bridged silicon slab. Special surface morphologies are designed to reduce the impedance mismatch when light refracts from a homogeneous silicon slab into the photonic crystal slab. We clearly observed negative refraction of infrared light for TE-like modes in a broad wavelength range by using scanning near-field optical microscopy technology. The experimental results are in good agreement with finite-difference time-domain simulations. The results indicate the designed photonic crystal structure can serve as polarization beam splitter.

Mental Representations of Weekdays

PubMed Central

Ellis, David A.; Wiseman, Richard; Jenkins, Rob

2015-01-01

Keeping social appointments involves keeping track of what day it is. In practice, mismatches between apparent day and actual day are common. For example, a person might think the current day is Wednesday when in fact it is Thursday. Here we show that such mismatches are highly systematic, and can be traced to specific properties of their mental representations. In Study 1, mismatches between apparent day and actual day occurred more frequently on midweek days (Tuesday, Wednesday, and Thursday) than on other days, and were mainly due to intrusions from immediately neighboring days. In Study 2, reaction times to report the current day were fastest on Monday and Friday, and slowest midweek. In Study 3, participants generated fewer semantic associations for “Tuesday”, “Wednesday” and “Thursday” than for other weekday names. Similarly, Google searches found fewer occurrences of midweek days in webpages and books. Analysis of affective norms revealed that participants’ associations were strongly negative for Monday, strongly positive for Friday, and graded over the intervening days. Midweek days are confusable because their mental representations are sparse and similar. Mondays and Fridays are less confusable because their mental representations are rich and distinctive, forming two extremes along a continuum of change. PMID:26288194

Weighting of Amplitude and Formant Rise Time Cues by School-Aged Children: A Mismatch Negativity Study

ERIC Educational Resources Information Center

Varghese, Peter; Kalashnikova, Marina; Burnham, Denis

2018-01-01

Purpose: An important skill in the development of speech perception is to apply optimal weights to acoustic cues so that phonemic information is recovered from speech with minimum effort. Here, we investigated the development of acoustic cue weighting of amplitude rise time (ART) and formant rise time (FRT) cues in children as measured by mismatch…

Mismatch Negativity Responses in Children with a Diagnosis of Childhood Apraxia of Speech (CAS)

ERIC Educational Resources Information Center

Froud, Karen; Khamis-Dakwar, Reem

2012-01-01

Purpose: To evaluate whether a hypothesis suggesting that apraxia of speech results from phonological overspecification could be relevant for childhood apraxia of speech (CAS). Method: High-density EEG was recorded from 5 children with CAS and 5 matched controls, ages 5-8 years, with and without CAS, as they listened to randomized sequences of CV…

Temporal Processing Ability Is Related to Ear-Asymmetry for Detecting Time Cues in Sound: A Mismatch Negativity (MMN) Study

ERIC Educational Resources Information Center

Todd, Juanita; Finch, Brayden; Smith, Ellen; Budd, Timothy W.; Schall, Ulrich

2011-01-01

Temporal and spectral sound information is processed asymmetrically in the brain with the left-hemisphere showing an advantage for processing the former and the right-hemisphere for the latter. Using monaural sound presentation we demonstrate a context and ability dependent ear-asymmetry in brain measures of temporal change detection. Our measure…

Professional Identity Formation and Development of Imagined Communities in an English Language Major in Mexico

ERIC Educational Resources Information Center

Villarreal Ballesteros, Ana Cecilia

2010-01-01

Recent work has shown the importance of identity in language learning and how the desire to belong to an imagined community drives individuals to invest in their learning (Norton, 2000). This work has documented that a mismatch between students' imagined community and the community envisioned by the teacher can have negative outcomes on students'…

Direct Evidence for Differential Roles of Temporal and Frontal Components of Auditory Change Detection

ERIC Educational Resources Information Center

Shalgi, Shani; Deouell, Leon Y.

2007-01-01

Automatic change detection is a fundamental capacity of the human brain. In audition, this capacity is indexed by the mismatch negativity (MMN) event-related potential, which is putatively supported by a network consisting of superior temporal and frontal nodes. The aim of this study was to elucidate the roles of these nodes within the neural…

Children's Performance on Pseudoword Repetition Depends on Auditory Trace Quality: Evidence from Event-Related Potentials.

ERIC Educational Resources Information Center

Ceponiene, Rita; Service, Elisabet; Kurjenluoma, Sanna; Cheour, Marie; Naatanen, Risto

1999-01-01

Compared the mismatch-negativity (MMN) component of auditory event-related brain potentials to explore the relationship between phonological short-term memory and auditory-sensory processing in 7- to 9-year olds scoring the highest and lowest on a pseudoword repetition test. Found that high and low repeaters differed in MMN amplitude to speech…

Combined ICA-LORETA analysis of mismatch negativity.

PubMed

Marco-Pallarés, J; Grau, C; Ruffini, G

2005-04-01

A major challenge for neuroscience is to map accurately the spatiotemporal patterns of activity of the large neuronal populations that are believed to underlie computing in the human brain. To study a specific example, we selected the mismatch negativity (MMN) brain wave (an event-related potential, ERP) because it gives an electrophysiological index of a "primitive intelligence" capable of detecting changes, even abstract ones, in a regular auditory pattern. ERPs have a temporal resolution of milliseconds but appear to result from mixed neuronal contributions whose spatial location is not fully understood. Thus, it is important to separate these sources in space and time. To tackle this problem, a two-step approach was designed combining the independent component analysis (ICA) and low-resolution tomography (LORETA) algorithms. Here we implement this approach to analyze the subsecond spatiotemporal dynamics of MMN cerebral sources using trial-by-trial experimental data. We show evidence that a cerebral computation mechanism underlies MMN. This mechanism is mediated by the orchestrated activity of several spatially distributed brain sources located in the temporal, frontal, and parietal areas, which activate at distinct time intervals and are grouped in six main statistically independent components.

Context shapes social judgments of positive emotion suppression and expression.

PubMed

Kalokerinos, Elise K; Greenaway, Katharine H; Casey, James P

2017-02-01

It is generally considered socially undesirable to suppress the expression of positive emotion. However, previous research has not considered the role that social context plays in governing appropriate emotion regulation. We investigated a context in which it may be more appropriate to suppress than express positive emotion, hypothesizing that positive emotion expressions would be considered inappropriate when the valence of the expressed emotion (i.e., positive) did not match the valence of the context (i.e., negative). Six experiments (N = 1,621) supported this hypothesis: when there was a positive emotion-context mismatch, participants rated targets who suppressed positive emotion as more appropriate, and evaluated them more positively than targets who expressed positive emotion. This effect occurred even when participants were explicitly made aware that suppressing targets were experiencing mismatched emotion for the context (e.g., feeling positive in a negative context), suggesting that appropriate emotional expression is key to these effects. These studies are among the first to provide empirical evidence that social costs to suppression are not inevitable, but instead are dependent on context. Expressive suppression can be a socially useful emotion regulation strategy in situations that call for it. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Mismatch negativity to the patient's own name in chronic disorders of consciousness.

PubMed

Qin, Pengmin; Di, Haibo; Yan, Xiaodan; Yu, Senming; Yu, Dan; Laureys, Steven; Weng, Xuchu

2008-12-19

Previous studies implicated potential value of mismatch negativity (MMN) in predicting recovery of consciousness in patients with disorders of consciousness (DOC). We have adopted a novel MMN evoked by subject's own name (SON), a self-referential stimulus thought to be powerful in evoking residual brain activity, and examined the correlation between the MMN and recovery of consciousness in patients with chronic (>1 month) DOC. Twelve patients and 12 age-matched healthy controls were investigated. The patients were diagnosed as coma (n=4), vegetative state (VS, n=6), and minimally conscious state (MCS, n=2), mainly based on the JFK Coma Recovery Scale-Revised. The SON-evoked MMN (SON-MMN) was present in seven patients. Critically, the presence of SON-MMN was significantly correlated with recovery of consciousness. While four of the five patients (three VS and two coma) showing SON-MMN changed to MCS 3 months later, the rest of the patients (three VS and two coma) without SON-MMN failed to show any clinical improvement. Our study thus illustrates that the subject's own name is effective in evoking MMN in patients with DOC, and that SON-MMN has potential prognostic values in predicting recovery of consciousness.

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

PubMed

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

2012-01-01

Mild cognitive impairment (MCI) refers to a transitory state between healthy aging and dementia. Biomarkers are needed to facilitate early identification of MCI and predict progression to dementia. One potential neurophysiological biomarker, mismatch negativity (MMN), is an event-related potential reflecting fundamental, pre-attentive cognitive processes. MMN is reduced in normal aging and dementia and in neuropsychiatric samples and is associated with verbal memory deficits and poor executive functioning. This study aimed to investigate auditory MMN and its relationship to neuropsychological performance in MCI. Twenty-eight MCI participants and fourteen controls, aged ≥50 years, underwent neurophysiological and neuropsychological assessment, and completed questionnaires pertaining to disability. Relative to controls, the MCI group demonstrated reduced temporal MMN amplitude (p < 0.01). Reduced right temporal MMN was significantly associated with poorer verbal learning (r = 0.496; p < 0.01) and reduced left temporal MMN was significantly associated with increased self-reported disability (r = -0.419; p < 0.05). These results indicate that patients with MCI exhibit altered pre-attentive information processing, which in turn is associated with memory and psychosocial deficits. These findings overall suggest that MMN may be a viable neurophysiological biomarker of underlying disease in this 'at risk' group.

The brain ages optimally to model its environment: evidence from sensory learning over the adult lifespan.

PubMed

Moran, Rosalyn J; Symmonds, Mkael; Dolan, Raymond J; Friston, Karl J

2014-01-01

The aging brain shows a progressive loss of neuropil, which is accompanied by subtle changes in neuronal plasticity, sensory learning and memory. Neurophysiologically, aging attenuates evoked responses--including the mismatch negativity (MMN). This is accompanied by a shift in cortical responsivity from sensory (posterior) regions to executive (anterior) regions, which has been interpreted as a compensatory response for cognitive decline. Theoretical neurobiology offers a simpler explanation for all of these effects--from a Bayesian perspective, as the brain is progressively optimized to model its world, its complexity will decrease. A corollary of this complexity reduction is an attenuation of Bayesian updating or sensory learning. Here we confirmed this hypothesis using magnetoencephalographic recordings of the mismatch negativity elicited in a large cohort of human subjects, in their third to ninth decade. Employing dynamic causal modeling to assay the synaptic mechanisms underlying these non-invasive recordings, we found a selective age-related attenuation of synaptic connectivity changes that underpin rapid sensory learning. In contrast, baseline synaptic connectivity strengths were consistently strong over the decades. Our findings suggest that the lifetime accrual of sensory experience optimizes functional brain architectures to enable efficient and generalizable predictions of the world.

The Education-Occupation Mismatch of International and Internal Migrants in Mexico, 2005-2012.

PubMed

Villarreal, Andrés

2016-06-01

Recent studies have found international migrants from developing countries such as Mexico to be negatively selected by education; that is, they are less educated than those who stay behind. Moving beyond the question of whether migrants are negatively selected by education overall, I examine how migrants are selected compared with others in similar jobs. Using data from a nationally representative panel survey of Mexican households, I find that men who migrate abroad have significantly higher levels of education than nonmigrants in the same occupation. Because men who are overeducated for their occupation tend to receive lower wages than those employed in occupations commensurate with their education, and are also more dissatisfied with their jobs, overeducation may encourage men to emigrate. Results from the regression models, which account for differential selectivity into employment, indicate that internal migrants within Mexico also have higher educational levels than nonmigrants in the same occupation prior to migrating but comparable levels of education afterward. Migrating internally, therefore, appears to allow men to improve their occupational placement. Finally, I examine changes in migrants' education over time and find evidence that the education-occupation mismatch has increased among Mexican emigrants in the years following the 2008 U.S. recession.

Low-level neural auditory discrimination dysfunctions in specific language impairment-A review on mismatch negativity findings.

PubMed

Kujala, Teija; Leminen, Miika

2017-12-01

In specific language impairment (SLI), there is a delay in the child's oral language skills when compared with nonverbal cognitive abilities. The problems typically relate to phonological and morphological processing and word learning. This article reviews studies which have used mismatch negativity (MMN) in investigating low-level neural auditory dysfunctions in this disorder. With MMN, it is possible to tap the accuracy of neural sound discrimination and sensory memory functions. These studies have found smaller response amplitudes and longer latencies for speech and non-speech sound changes in children with SLI than in typically developing children, suggesting impaired and slow auditory discrimination in SLI. Furthermore, they suggest shortened sensory memory duration and vulnerability of the sensory memory to masking effects. Importantly, some studies reported associations between MMN parameters and language test measures. In addition, it was found that language intervention can influence the abnormal MMN in children with SLI, enhancing its amplitude. These results suggest that the MMN can shed light on the neural basis of various auditory and memory impairments in SLI, which are likely to influence speech perception. Copyright © 2017. Published by Elsevier Ltd.

Laryngeal Features Are Phonetically Abstract: Mismatch Negativity Evidence from Arabic, English, and Russian

PubMed Central

Schluter, Kevin T.; Politzer-Ahles, Stephen; Al Kaabi, Meera; Almeida, Diogo

2017-01-01

Many theories of phonology assume that the sound structure of language is made up of distinctive features, but there is considerable debate about how much articulatory detail distinctive features encode in long-term memory. Laryngeal features such as voicing provide a unique window into this question: while many languages have two-way contrasts that can be given a simple binary feature account [±VOICE], the precise articulatory details underlying these contrasts can vary significantly across languages. Here, we investigate a series of two-way voicing contrasts in English, Arabic, and Russian, three languages that implement their voicing contrasts very differently at the articulatory-phonetic level. In three event-related potential experiments contrasting English, Arabic, and Russian fricatives along with Russian stops, we observe a consistent pattern of asymmetric mismatch negativity (MMN) effects that is compatible with an articulatorily abstract and cross-linguistically uniform way of marking two-way voicing contrasts, as opposed to an articulatorily precise and cross-linguistically diverse way of encoding them. Regardless of whether a language is theorized to encode [VOICE] over [SPREAD GLOTTIS], the data is consistent with a universal marking of the [SPREAD GLOTTIS] feature. PMID:28555118

Mismatch Negativity (MMN) as an Index of Cognitive Dysfunction

PubMed Central

Näätänen, Risto; Sussman, Elyse S.; Salisbury, Dean; Shafer, Valerie L.

2014-01-01

Cognition is often affected in a variety of neuropsychiatric, neurological, and neurodevelopmental disorders. The neural discriminative response, reflected in mismatch negativity (MMN) and its magnetoencephalographic equivalent (MMNm), has been used as a tool to study a variety of disorders involving auditory cognition. MMN/MMNm is an involuntary brain response to auditory change or, more generally, to pattern regularity violation. For a number of disorders, MMN/MMNm amplitude to sound deviance has been shown to be attenuated or the peak-latency of the component prolonged compared to controls. This general finding suggests that while not serving as a specific marker to any particular disorder, MMN may be useful for understanding factors of cognition in various disorders, and has potential to serve as an indicator of risk. This review presents a brief history of the MMN, followed by a description of how MMN has been used to index auditory processing capability in a range of neuropsychiatric, neurological, and neurodevelopmental disorders. Finally, we suggest future directions for research to further enhance our understanding of the neural substrate of deviance detection that could lead to improvements in the use of MMN as a clinical tool. PMID:24838819

Early integration of vowel and pitch processing: a mismatch negativity study.

PubMed

Lidji, Pascale; Jolicoeur, Pierre; Kolinsky, Régine; Moreau, Patricia; Connolly, John F; Peretz, Isabelle

2010-04-01

Several studies have explored the processing specificity of music and speech, but only a few have addressed the processing autonomy of their fundamental components: pitch and phonemes. Here, we examined the additivity of the mismatch negativity (MMN) indexing the early interactions between vowels and pitch when sung. Event-related potentials (ERPs) were recorded while participants heard frequent sung vowels and rare stimuli deviating in pitch only, in vowel only, or in both pitch and vowel. The task was to watch a silent movie while ignoring the sounds. All three types of deviants elicited both an MMN and a P3a ERP component. The observed MMNs were of similar amplitude for the three types of deviants and the P3a was larger for double deviants. The MMNs to deviance in vowel and deviance in pitch were not additive. The underadditivity of the MMN responses suggests that vowel and pitch differences are processed by interacting neural networks. The results indicate that vowel and pitch are processed as integrated units, even at a pre-attentive level. Music-processing specificity thus rests on more complex dimensions of music and speech. 2009 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Successful measurement of the mismatch negativity despite a concurrent movie soundtrack: reduced amplitude but normal component morphology.

PubMed

Moreau, Patricia; Jolicœur, Pierre; Lidji, Pascale; Peretz, Isabelle

2013-12-01

To examine the mechanisms responsible for the reduction of the mismatch negativity (MMN) ERP component observed in response to pitch changes when the soundtrack of a movie is presented while recording the MMN. In three experiments we measured the MMN to tones that differed in pitch from a repeated standard tone presented with a silent subtitled movie, with the soundtrack played forward or backward, or with soundtracks set at different intensity levels. MMN amplitude was reduced when the soundtrack was presented either forward or backward compared to the silent subtitled movie. With the soundtrack, MMN amplitude increased proportionally to the increments in the sound-to-noise intensity ratio. MMN was reduced in amplitude but had normal morphology with a concurrent soundtrack, most likely because of basic acoustical interference from the soundtrack with MMN-critical tones rather than from attentional effects. A normal MMN can be recorded with a concurrent movie soundtrack, but signal amplitudes need to be set with caution to ensure a sufficiently high sound-to-noise ratio between MMN stimuli and the soundtrack. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Elimination of initial stress-induced curvature in a micromachined bi-material composite-layered cantilever

NASA Astrophysics Data System (ADS)

Liu, Ruiwen; Jiao, Binbin; Kong, Yanmei; Li, Zhigang; Shang, Haiping; Lu, Dike; Gao, Chaoqun; Chen, Dapeng

2013-09-01

Micro-devices with a bi-material-cantilever (BMC) commonly suffer initial curvature due to the mismatch of residual stress. Traditional corrective methods to reduce the residual stress mismatch generally involve the development of different material deposition recipes. In this paper, a new method for reducing residual stress mismatch in a BMC is proposed based on various previously developed deposition recipes. An initial material film is deposited using two or more developed deposition recipes. This first film is designed to introduce a stepped stress gradient, which is then balanced by overlapping a second material film on the first and using appropriate deposition recipes to form a nearly stress-balanced structure. A theoretical model is proposed based on both the moment balance principle and total equal strain at the interface of two adjacent layers. Experimental results and analytical models suggest that the proposed method is effective in producing multi-layer micro cantilevers that display balanced residual stresses. The method provides a generic solution to the problem of mismatched initial stresses which universally exists in micro-electro-mechanical systems (MEMS) devices based on a BMC. Moreover, the method can be incorporated into a MEMS design automation package for efficient design of various multiple material layer devices from MEMS material library and developed deposition recipes.

CD4-veCD8-ve CD30+ve T cells are detectable in human lung transplant patients and their proportion of the lymphocyte population after in vitro stimulation with donor spleen cells correlates with preservation of lung physiology.

PubMed

Polster, K; Walker, A; Fildes, J; Entwistle, G; Yonan, N; Hutchinson, I V; Leonard, C T

2005-06-01

Survival following lung transplantation is less than 50% at 5 years, mainly due to immune-mediated chronic rejection. Recently a novel subset of T cells, CD4-veCD8-ve CD30+ve, so-called double negative (DN) CD30+ve T cells, has been described and shown to be responsible for tolerance in an animal model of skin transplantation. We investigated 18 lung transplant recipients for the presence of DN CD30+ve T cells in resting peripheral blood and also following in vitro stimulation of recipient peripheral blood mononuclear cells (PBMCs) with donor spleen cells. Small percentages (0.2% to 6%) of DN T cells are detectable in resting PBMCs of human transplant patients (n = 18), but these did not correlate with allograft function, acute rejection episodes, HLA mismatch, or CMV status. On repeated stimulation of recipient PBMCs (two exposures) in vitro by donor spleen cells (2:1 ratio stimulators to responders) the percentage of DN CD30+ve T cells within the lymphocyte pool correlated with preservation of allograft lung function (both for FEV(1), P = .009, and FEF(25-75), P = .036) and was inversely correlated with grade of chronic rejection. On repeated exposure of recipient PBMCs to donor spleen cells with a 1:1 ratio the percentage of DN CD30+ve T cells correlated with the number of acute rejection episodes of grade 2 or greater. The total number of HLA mismatches correlated with the percentage DN CD30+ve T cells present after primary stimulation of recipient PBMCs with donor spleen cells (1:1 ratio). The number of mismatches at the B locus inversely correlated with the percentage of DN CD30+ve T cells after primary stimulation of recipient PBMCs with donor spleen cells (1:1 ratio; P = .031, n = 18). Percentages of DN CD30+ve T cells present following repeated stimulation of recipient PBMCs by donor spleen cells correlated with preservation of graft function following lung transplantation.

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

NASA Astrophysics Data System (ADS)

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.

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

NASA Astrophysics Data System (ADS)

Mitchell, S. R.; Beven, K.; Freer, J. E.; Law, B. E.

2010-12-01

Semi-arid 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 (GLUE) 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 over-estimated ecosystem C accumulation (-NEE) 99% of the time. Among the simulations for the mature and old-growth stands, 100% and 99% of the simulations under-estimated 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, both autotrophic and heterotrophic, appeared to be fundamental causes of model-data mismatch.

Dielectric tunability of vertically aligned ferroelectric-metal oxide nanocomposite films controlled by out-of-plane misfit strain

NASA Astrophysics Data System (ADS)

Wu, Huaping; Ma, Xuefu; Zhang, Zheng; Zhu, Jun; Wang, Jie; Chai, Guozhong

2016-04-01

A nonlinear thermodynamic model based on the vertically aligned nanocomposite (VAN) thin films of ferroelectric-metal oxide system has been developed to investigate the physical properties of the epitaxial Ba0.6Sr0.4TiO3 (BST) films containing vertical Sm2O3 (SmO) nanopillar arrays on the SrTiO3 substrate. The phase diagrams of out-of-plane lattice mismatch vs. volume fraction of SmO are calculated by minimizing the total free energy. It is found that the phase transformation and dielectric response of BST-SmO VAN systems are extremely dependent on the in-plane misfit strain, the out-of-plane lattice mismatch, the volume fraction of SmO phase, and the external electric field applied to the nanocomposite films at room temperature. In particular, the BST-SmO VAN systems exhibit higher dielectric properties than pure BST films. Giant dielectric response and maximum tunability are obtained near the lattice mismatch where the phase transition occurs. Under the in-plane misfit strain of umf=0.3 % and the out-of-plane lattice mismatch of u3=0.002 , the dielectric tunability can be dramatically enhanced to 90% with the increase of SmO volume fraction, which is well consistent with previous experimental results. This work represents an approach to further understand the dependence of physical properties on the lattice mismatch (in-plane and out-of-plane) and volume fraction, and to manipulate or optimize functionalities in the nanocomposite oxide thin films.

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

USGS Publications Warehouse

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, leading to the recent attenuation in population growth of Snow Geese.

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

PubMed

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 to the recent attenuation in population growth of Snow Geese. © 2017 by the Ecological Society of America.

Comparison of Pre-Attentive Auditory Discrimination at Gross and Fine Difference between Auditory Stimuli.

PubMed

Sanju, Himanshu Kumar; Kumar, Prawin

2016-10-01

Introduction  Mismatch Negativity is a negative component of the event-related potential (ERP) elicited by any discriminable changes in auditory stimulation. Objective  The present study aimed to assess pre-attentive auditory discrimination skill with fine and gross difference between auditory stimuli. Method  Seventeen normal hearing individual participated in the study. To assess pre-attentive auditory discrimination skill with fine difference between auditory stimuli, we recorded mismatch negativity (MMN) with pair of stimuli (pure tones), using /1000 Hz/ and /1010 Hz/ with /1000 Hz/ as frequent stimulus and /1010 Hz/ as infrequent stimulus. Similarly, we used /1000 Hz/ and /1100 Hz/ with /1000 Hz/ as frequent stimulus and /1100 Hz/ as infrequent stimulus to assess pre-attentive auditory discrimination skill with gross difference between auditory stimuli. The study included 17 subjects with informed consent. We analyzed MMN for onset latency, offset latency, peak latency, peak amplitude, and area under the curve parameters. Result  Results revealed that MMN was present only in 64% of the individuals in both conditions. Further Multivariate Analysis of Variance (MANOVA) showed no significant difference in all measures of MMN (onset latency, offset latency, peak latency, peak amplitude, and area under the curve) in both conditions. Conclusion  The present study showed similar pre-attentive skills for both conditions: fine (1000 Hz and 1010 Hz) and gross (1000 Hz and 1100 Hz) difference in auditory stimuli at a higher level (endogenous) of the auditory system.

Abnormal Complex Auditory Pattern Analysis in Schizophrenia Reflected in an Absent Missing Stimulus Mismatch Negativity.

PubMed

Salisbury, Dean F; McCathern, Alexis G

2016-11-01

The simple mismatch negativity (MMN) to tones deviating physically (in pitch, loudness, duration, etc.) from repeated standard tones is robustly reduced in schizophrenia. Although generally interpreted to reflect memory or cognitive processes, simple MMN likely contains some activity from non-adapted sensory cells, clouding what process is affected in schizophrenia. Research in healthy participants has demonstrated that MMN can be elicited by deviations from abstract auditory patterns and complex rules that do not cause sensory adaptation. Whether persons with schizophrenia show abnormalities in the complex MMN is unknown. Fourteen schizophrenia participants and 16 matched healthy underwent EEG recording while listening to 400 groups of 6 tones 330 ms apart, separated by 800 ms. Occasional deviant groups were missing the 4th or 6th tone (50 groups each). Healthy participants generated a robust response to a missing but expected tone. The schizophrenia group was significantly impaired in activating the missing stimulus MMN, generating no significant activity at all. Schizophrenia affects the ability of "primitive sensory intelligence" and pre-attentive perceptual mechanisms to form implicit groups in the auditory environment. Importantly, this deficit must relate to abnormalities in abstract complex pattern analysis rather than sensory problems in the disorder. The results indicate a deficit in parsing of the complex auditory scene which likely impacts negatively on successful social navigation in schizophrenia. Knowledge of the location and circuit architecture underlying the true novelty-related MMN and its pathophysiology in schizophrenia will help target future interventions.

Developmental programming of happiness.

PubMed

Schmidt, Louis A; Fortier, Paz; Lahat, Ayelet; Tang, Alva; Mathewson, Karen J; Saigal, Saroj; Boyle, Michael H; Van Lieshout, Ryan J

2017-09-01

Being born at an extremely low birth weight (ELBW; <1,000 grams) is presumed to reflect a suboptimal intrauterine environment and thus presents an opportunity for examining developmental programming hypotheses. Interfacing prenatal programming and differential susceptibility hypotheses, we tested whether individuals with ELBW in different childhood rearing environments showed different attention biases to positive and negative facial emotions in adulthood. Using the oldest known, prospectively followed cohort of ELBW survivors, we found that relative to normal birth weight controls (NBW; >2,500 grams), ELBW survivors displayed the highest and lowest attention bias to happy faces at age 30-35, depending on whether their total family income at age 8 was relatively low (environmental match) or high (environmental mismatch), respectively. This bias to happy faces was associated with a reduced likelihood of emotional problems. Findings suggest that differential susceptibility to positive emotions may be prenatally programmed, with effects lasting into adulthood. We discuss implications for integrating prenatal programming and differential susceptibility hypotheses, and the developmental origins of postnatal plasticity and resilience. © 2017 Wiley Periodicals, Inc.

Effects of Visual Game Experience on Auditory Processing Speed.

PubMed

Shin, Kyung Soon; Yim, Yoon Kyoung; Kim, Yuwon; Park, Soowon; Lee, Jun-Young

2017-03-01

Games are one of the fastest growing and most exciting forms of entertainment. Whether casual mobile game playing has a cognitive, physiological, or behavioral effect on players whose game use is not pathological is unknown. Here we explored whether preattentive auditory processing is linked to the behavioral inhibition system (BIS) in frequent and infrequent game players. A total of 74 subjects who were enrolled in our study were divided into two groups, 40 subjects were frequent gamers and 34 subjects were age-, gender-, IQ-, and education-matched infrequent gamers. All participants underwent a passive auditory oddball paradigm and completed the behavioral inhibition/behavioral activation system scales. The mismatch negativity (MMN) latency was shorter for the frequent gamers relative to the infrequent gamers, whereas no difference in MMN amplitude was found between groups. MMN amplitude was negatively associated with the degree of behavioral inhibition in the frequent and infrequent gaming group. We also found that those who frequently play games show an enhanced processing speed, which could be an effect of game practice. Greater behavioral inhibition induces increased vigilance, and this may have enhanced the MMN amplitude in the infrequent gamers. This differential pattern of correlations suggests that differences in the BIS could lead to different approaches to auditory information processing.

Molecular changes preceding endometrial and ovarian cancer: a study of consecutive endometrial specimens from Lynch syndrome surveillance.

PubMed

Niskakoski, Anni; Pasanen, Annukka; Lassus, Heini; Renkonen-Sinisalo, Laura; Kaur, Sippy; Mecklin, Jukka-Pekka; Bützow, Ralf; Peltomäki, Päivi

2018-03-27

Molecular alterations preceding endometrial and ovarian cancer and the sequence of events are unknown. Consecutive specimens from lifelong surveillance for Lynch syndrome provides a natural setting to address such questions. To molecularly define the multistep gynecological tumorigenesis, DNA mismatch repair gene mutation carriers with endometrial or ovarian carcinoma or endometrial hyperplasia were identified from a nation-wide registry and endometrial biopsy specimens taken from these individuals during 20 years of screening were collected. A total of 213 endometrial and ovarian specimens from Lynch syndrome individuals and 197 histology-matched (non-serous) samples from sporadic cases were available for this investigation. The specimens were profiled for markers linked to endometrial and ovarian tumorigenesis, including ARID1A protein expression, mismatch repair status, and tumor suppressor gene promoter methylation. In Lynch syndrome-associated endometrial and ovarian carcinomas, ARID1A protein was lost in 61-100% and mismatch repair was deficient in 97-100%, compared to 0-17% and 14-44% in sporadic cases (P = 0.000). ARID1A loss appeared in complex hyperplasia and deficient mismatch repair and tumor suppressor gene promoter methylation in histologically normal endometrium. Despite quantitative differences between Lynch syndrome and sporadic cases, ARID1A expression, mismatch repair, and tumor suppressor gene promoter methylation divided endometrial samples from both patient groups into three categories of increasing abnormality, comprising normal endometrium and simple hyperplasia (I), complex hyperplasia with or without atypia (II), and endometrial cancer (III). Complex hyperplasias without vs. with atypia were molecularly indistinguishable. In conclusion, surveillance specimens from Lynch syndrome identify mismatch repair deficiency, tumor suppressor gene promoter methylation, and ARID1A loss as early changes in tumor development. Our findings are clinically relevant for the classification of endometrial hyperplasias and have potential implications in cancer prevention in Lynch syndrome and beyond.

Arctic-nesting birds find physiological relief in the face of trophic constraints.

PubMed

McKinnon, Laura; Nol, Erica; Juillet, Cédric

2013-01-01

A climate-induced phenological mismatch between the timing of reproduction and the timing of food resource peaks is one of the key hypothesized effects of climate change on wildlife. Though supported as a mechanism of population decline in birds, few studies have investigated whether the same temperature increases that drive this mismatch have the potential to decrease energetic costs of growth and compensate for the potential negative effects of reduced food availability. We generated independent indices of climate and resource availability and quantified their effects on growth of Dunlin (Calidris alpina) chicks, in the sub-arctic tundra of Churchill, Manitoba during the summers of 2010-2011 and found that when resource availability was below average, above average growth could be maintained in the presence of increasing temperatures. These results provide evidence that chicks may find physiological relief from the trophic constraints hypothesized by climate change studies.

Auditory mismatch impairments are characterized by core neural dysfunctions in schizophrenia

PubMed Central

Gaebler, Arnim Johannes; Mathiak, Klaus; Koten, Jan Willem; König, Andrea Anna; Koush, Yury; Weyer, David; Depner, Conny; Matentzoglu, Simeon; Edgar, James Christopher; Willmes, Klaus; Zvyagintsev, Mikhail

2015-01-01

Major theories on the neural basis of schizophrenic core symptoms highlight aberrant salience network activity (insula and anterior cingulate cortex), prefrontal hypoactivation, sensory processing deficits as well as an impaired connectivity between temporal and prefrontal cortices. The mismatch negativity is a potential biomarker of schizophrenia and its reduction might be a consequence of each of these mechanisms. In contrast to the previous electroencephalographic studies, functional magnetic resonance imaging may disentangle the involved brain networks at high spatial resolution and determine contributions from localized brain responses and functional connectivity to the schizophrenic impairments. Twenty-four patients and 24 matched control subjects underwent functional magnetic resonance imaging during an optimized auditory mismatch task. Haemodynamic responses and functional connectivity were compared between groups. These data sets further entered a diagnostic classification analysis to assess impairments on the individual patient level. In the control group, mismatch responses were detected in the auditory cortex, prefrontal cortex and the salience network (insula and anterior cingulate cortex). Furthermore, mismatch processing was associated with a deactivation of the visual system and the dorsal attention network indicating a shift of resources from the visual to the auditory domain. The patients exhibited reduced activation in all of the respective systems (right auditory cortex, prefrontal cortex, and the salience network) as well as reduced deactivation of the visual system and the dorsal attention network. Group differences were most prominent in the anterior cingulate cortex and adjacent prefrontal areas. The latter regions also exhibited a reduced functional connectivity with the auditory cortex in the patients. In the classification analysis, haemodynamic responses yielded a maximal accuracy of 83% based on four features; functional connectivity data performed similarly or worse for up to about 10 features. However, connectivity data yielded a better performance when including more than 10 features yielding up to 90% accuracy. Among others, the most discriminating features represented functional connections between the auditory cortex and the anterior cingulate cortex as well as adjacent prefrontal areas. Auditory mismatch impairments incorporate major neural dysfunctions in schizophrenia. Our data suggest synergistic effects of sensory processing deficits, aberrant salience attribution, prefrontal hypoactivation as well as a disrupted connectivity between temporal and prefrontal cortices. These deficits are associated with subsequent disturbances in modality-specific resource allocation. Capturing different schizophrenic core dysfunctions, functional magnetic resonance imaging during this optimized mismatch paradigm reveals processing impairments on the individual patient level, rendering it a potential biomarker of schizophrenia. PMID:25743635

Effect of moderate learning style–teaching mode mismatch on academic performance among 2nd year medical students in Pakistan

PubMed Central

Hamza, Muhammad; Inam-Ul-Haq; Hamid, Sidra; Nadir, Maha; Mehmood, Nadir

2018-01-01

Introduction: The vagueness surrounding “learning style–teaching mode mismatch” makes its effects uncertain. This study tried to tackle that controversy by comparing and assessing the effect of different learning styles on performance in physiology examination when teaching mode was somewhat different than learning preferences of the 2nd year medical students. Methods: A total of 102 2nd year medical students participated in this study. Honey and Mumford learning style questionnaire was used to categorize the participants into one of the four learning styles (activist, reflector, theorist, and pragmatist). Many teaching modes were used in the medical college. The first professional theory and practical physiology scores of these 102 students of University of Health Sciences were obtained online. Learning styles were compared with physiology scores and age using one-way analysis of variance and post hoc statistical analysis and between males and females by using Chi-square test. Results: Pragmatists had the lowest total physiology score (P < 0.001), while theorists had the highest total physiology scores (P < 0.001). Activists and reflectors had scores in between pragmatists and theorists, and there was no statistical difference between these two styles of learning (P = 0.9). No student scored below 60%. Conclusion: This study demonstrated that the effect of moderate teaching–learning mismatch is different for different learners. Theorists excelled as they had the highest physiology score, while pragmatists lagged in comparison. Reflectors and activists performed better than pragmatists but were worse than theorists. Despite this, none of the students scored below 60%. This shows that a moderate learning style–teaching mode mismatch is not harmful for learning. PMID:29736072

The pre-Argo ocean reanalyses may be seriously affected by the spatial coverage of moored buoys

PubMed Central

Sivareddy, S.; Paul, Arya; Sluka, Travis; Ravichandran, M.; Kalnay, Eugenia

2017-01-01

Assimilation methods, meant to constrain divergence of model trajectory from reality using observations, do not exactly satisfy the physical laws governing the model state variables. This allows mismatches in the analysis in the vicinity of observation locations where the effect of assimilation is most prominent. These mismatches are usually mitigated either by the model dynamics in between the analysis cycles and/or by assimilation at the next analysis cycle. However, if the observations coverage is limited in space, as it was in the ocean before the Argo era, these mechanisms may be insufficient to dampen the mismatches, which we call shocks, and they may remain and grow. Here we show through controlled experiments, using real and simulated observations in two different ocean models and assimilation systems, that such shocks are generated in the ocean at the lateral boundaries of the moored buoy network. They thrive and propagate westward as Rossby waves along these boundaries. However, these shocks are essentially eliminated by the assimilation of near-homogenous global Argo distribution. These findings question the fidelity of ocean reanalysis products in the pre-Argo era. For example, a reanalysis that ignores Argo floats and assimilates only moored buoys, wrongly represents 2008 as a negative Indian Ocean Dipole year. PMID:28429748

The mismatch negativity as a measure of auditory stream segregation in a simulated "cocktail-party" scenario: effect of age.

PubMed

Getzmann, Stephan; Näätänen, Risto

2015-11-01

With age the ability to understand speech in multitalker environments usually deteriorates. The central auditory system has to perceptually segregate and group the acoustic input into sequences of distinct auditory objects. The present study used electrophysiological measures to study effects of age on auditory stream segregation in a multitalker scenario. Younger and older adults were presented with streams of short speech stimuli. When a single target stream was presented, the occurrence of a rare (deviant) syllable among a frequent (standard) syllable elicited the mismatch negativity (MMN), an electrophysiological correlate of automatic deviance detection. The presence of a second, concurrent stream consisting of the deviant syllable of the target stream reduced the MMN amplitude, especially when located nearby the target stream. The decrease in MMN amplitude indicates that the rare syllable of the target stream was less perceived as deviant, suggesting reduced stream segregation with decreasing stream distance. Moreover, the presence of a concurrent stream increased the MMN peak latency of the older group but not that of the younger group. The results provide neurophysiological evidence for the effects of concurrent speech on auditory processing in older adults, suggesting that older adults need more time for stream segregation in the presence of concurrent speech. Copyright © 2015 Elsevier Inc. All rights reserved.

Mismatch negativity (MMN) amplitude as a biomarker of sensory memory deficit in amnestic mild cognitive impairment

PubMed Central

Lindín, Mónica; Correa, Kenia; Zurrón, Montserrat; Díaz, Fernando

2013-01-01

It has been suggested that changes in some event-related potential (ERP) parameters associated with controlled processing of stimuli could be used as biomarkers of amnestic mild cognitive impairment (aMCI). However, data regarding the suitability of ERP components associated with automatic and involuntary processing of stimuli for this purpose are not conclusive. In the present study, we studied the Mismatch Negativity (MMN) component, a correlate of the automatic detection of changes in the acoustic environment, in healthy adults and adults with aMCI (age range: 50–87 years). An auditory-visual attention-distraction task, in two evaluations separated by an interval of between 18 and 24 months, was used. In both evaluations, the MMN amplitude was significantly smaller in the aMCI adults than in the control adults. In the first evaluation, such differences were observed for the subgroup of adults between 50 and 64 years of age, but not for the subgroup of 65 years and over. In the aMCI adults, the MMN amplitude was significantly smaller in the second evaluation than in the first evaluation, but no significant changes were observed in the control adult group. The MMN amplitude was found to be a sensitive and specific biomarker of aMCI, in both the first and second evaluation. PMID:24312051

Speech-feature discrimination in children with Asperger syndrome as determined with the multi-feature mismatch negativity paradigm.

PubMed

Kujala, T; Kuuluvainen, S; Saalasti, S; Jansson-Verkasalo, E; von Wendt, L; Lepistö, T

2010-09-01

Asperger syndrome, belonging to the autistic spectrum of disorders, involves deficits in social interaction and prosodic use of language but normal development of formal language abilities. Auditory processing involves both hyper- and hypoactive reactivity to acoustic changes. Responses composed of mismatch negativity (MMN) and obligatory components were recorded for five types of deviations in syllables (vowel, vowel duration, consonant, syllable frequency, syllable intensity) with the multi-feature paradigm from 8-12-year old children with Asperger syndrome. Children with Asperger syndrome had larger MMNs for intensity and smaller MMNs for frequency changes than typically developing children, whereas no MMN group differences were found for the other deviant stimuli. Furthermore, children with Asperger syndrome performed more poorly than controls in Comprehension of Instructions subtest of a language test battery. Cortical speech-sound discrimination is aberrant in children with Asperger syndrome. This is evident both as hypersensitive and depressed neural reactions to speech-sound changes, and is associated with features (frequency, intensity) which are relevant for prosodic processing. The multi-feature MMN paradigm, which includes variation and thereby resembles natural speech hearing circumstances, suggests abnormal pattern of speech discrimination in Asperger syndrome, including both hypo- and hypersensitive responses for speech features. 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Mismatch Negativity and P50 Sensory Gating in Abstinent Former Cannabis Users

PubMed Central

Broyd, Samantha J.; Greenwood, Lisa-marie; van Hell, Hendrika H.; Croft, Rodney J.; Coyle, Hannah; Lee-Bates, Ben; Todd, Juanita; Johnstone, Stuart J.; Michie, Patricia T.; Solowij, Nadia

2016-01-01

Prolonged heavy exposure to cannabis is associated with impaired cognition and brain functional and structural alterations. We recently reported attenuated mismatch negativity (MMN) and altered P50 sensory gating in chronic cannabis users. This study investigated the extent of brain functional recovery (indexed by MMN and P50) in chronic users after cessation of use. Eighteen ex-users (median 13.5 years prior regular use; median 3.5 years abstinence) and 18 nonusers completed (1) a multifeature oddball task with duration, frequency, and intensity deviants and (2) a P50 paired-click paradigm. Trend level smaller duration MMN amplitude and larger P50 ratios (indicative of poorer sensory gating) were observed in ex-users compared to controls. Poorer P50 gating correlated with prior duration of cannabis use. Duration of abstinence was positively correlated with duration MMN amplitude, even after controlling for age and duration of cannabis use. Impaired sensory gating and attenuated MMN amplitude tended to persist in ex-users after prolonged cessation of use, suggesting a lack of full recovery. An association with prolonged duration of prior cannabis use may indicate persistent cannabis-related alterations to P50 sensory gating. Greater reductions in MMN amplitude with increasing abstinence (positive correlation) may be related to either self-medication or an accelerated aging process. PMID:27019754

The Education-Occupation Mismatch of International and Internal Migrants in Mexico, 2005–2012

PubMed Central

Villarreal, Andrés

2016-01-01

Recent studies have found international migrants from developing countries such as Mexico to be negatively selected by education; that is, they are less educated than those who stay behind. Moving beyond the question of whether migrants are negatively selected by education overall, I examine how migrants are selected compared with others in similar jobs. Using data from a nationally representative panel survey of Mexican households, I find that men who migrate abroad have significantly higher levels of education than nonmigrants in the same occupation. Because men who are overeducated for their occupation tend to receive lower wages than those employed in occupations commensurate with their education, and are also more dissatisfied with their jobs, overeducation may encourage men to emigrate. Results from the regression models, which account for differential selectivity into employment, indicate that internal migrants within Mexico also have higher educational levels than nonmigrants in the same occupation prior to migrating but comparable levels of education afterward. Migrating internally, therefore, appears to allow men to improve their occupational placement. Finally, I examine changes in migrants’ education over time and find evidence that the education-occupation mismatch has increased among Mexican emigrants in the years following the 2008 U.S. recession. PMID:27083195

Aberrant temporal behavior of mismatch negativity generators in schizophrenia patients and subjects at clinical high risk for psychosis.

PubMed

Kim, Minah; Cho, Kang Ik Kevin; Yoon, Youngwoo Bryan; Lee, Tae Young; Kwon, Jun Soo

2017-02-01

Although disconnection syndrome has been considered a core pathophysiologic mechanism of schizophrenia, little is known about the temporal behavior of mismatch negativity (MMN) generators in individuals with schizophrenia or clinical high risk (CHR) for psychosis. MMN was assessed in 29 schizophrenia patients, 40 CHR subjects, and 47 healthy controls (HCs). Individual realistic head models and the minimum L2 norm algorithm were used to generate a current source density (CSD) model of MMN. The strength and time course of MMN CSD activity were calculated separately for the frontal and temporal cortices and were compared across brain regions and groups. Schizophrenia patients and CHR subjects displayed lower MMN CSD strength than HCs in both the temporal and frontal cortices. We found a significant time delay in MMN generator activity in the frontal cortex relative to that in the temporal cortex in HCs. However, the sequential temporo-frontal activities of MMN generators were disrupted in both the schizophrenia and CHR groups. Impairments and altered temporal behavior of MMN multiple generators were observed even in individuals at risk for psychosis. These findings suggest that aberrant MMN generator activity might be helpful in revealing the pathophysiology of schizophrenia. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Extent of field change in colorectal cancers with BRAF mutation

PubMed Central

Poh, Aaron; Chang, Heidi Sian Ying; Tan, Kok Yang; Sam, Xin Xiu; Khoo, Avery; Choo, Shoa Nian; Nga, Min En; Wan, Wei Keat

2018-01-01

INTRODUCTION Sporadic colorectal cancers with BRAF mutations constitute two distinct subgroups of colorectal cancers. Recent studies have linked the presence of the BRAF mutation to a familial inheritance pattern. This was a proof-of-concept study that aimed to examine: (a) the extent of field change in sporadic colorectal cancers with BRAF mutation; and (b) the extent of resection margins required and the pattern of DNA mismatch repair protein loss in these tumours. METHODS Eight microsatellite instability-high tumours with positive BRAF mutation from an existing histopathological database were selected for BRAF mutation and mismatch repair protein analysis. RESULTS All the resection margins were negative for BRAF mutation. Three tumours had loss of MLH1 and PMS2 expressions, and five tumours had no protein loss. Six peritumoral tissues were negative and one was positive for BRAF mutation. CONCLUSION The results suggest that any early field change effect is restricted to the immediate vicinity of the tumour and is not a pan-colonic phenomenon. Current guidelines on resection margins are adequate for BRAF mutation-positive colorectal cancers. Any suggestion of a hereditary link to these tumours is likely not related to germline BRAF gene mutations. The pattern of protein loss reinforces previous findings for the two subgroups of BRAF mutation-positive colorectal cancers. PMID:28210747

A neuronal model of predictive coding accounting for the mismatch negativity.

PubMed

Wacongne, Catherine; Changeux, Jean-Pierre; Dehaene, Stanislas

2012-03-14

The mismatch negativity (MMN) is thought to index the activation of specialized neural networks for active prediction and deviance detection. However, a detailed neuronal model of the neurobiological mechanisms underlying the MMN is still lacking, and its computational foundations remain debated. We propose here a detailed neuronal model of auditory cortex, based on predictive coding, that accounts for the critical features of MMN. The model is entirely composed of spiking excitatory and inhibitory neurons interconnected in a layered cortical architecture with distinct input, predictive, and prediction error units. A spike-timing dependent learning rule, relying upon NMDA receptor synaptic transmission, allows the network to adjust its internal predictions and use a memory of the recent past inputs to anticipate on future stimuli based on transition statistics. We demonstrate that this simple architecture can account for the major empirical properties of the MMN. These include a frequency-dependent response to rare deviants, a response to unexpected repeats in alternating sequences (ABABAA…), a lack of consideration of the global sequence context, a response to sound omission, and a sensitivity of the MMN to NMDA receptor antagonists. Novel predictions are presented, and a new magnetoencephalography experiment in healthy human subjects is presented that validates our key hypothesis: the MMN results from active cortical prediction rather than passive synaptic habituation.

Auditory mismatch negativity deficits in long-term heavy cannabis users.

PubMed

Roser, Patrik; Della, Beate; Norra, Christine; Uhl, Idun; Brüne, Martin; Juckel, Georg

2010-09-01

Mismatch negativity (MMN) is an auditory event-related potential indicating auditory sensory memory and information processing. The present study tested the hypothesis that chronic cannabis use is associated with deficient MMN generation. MMN was investigated in age- and gender-matched chronic cannabis users (n = 30) and nonuser controls (n = 30). The cannabis users were divided into two groups according to duration and quantity of cannabis consumption. The MMNs resulting from a pseudorandomized sequence of 2 × 900 auditory stimuli were recorded by 32-channel EEG. The standard stimuli were 1,000 Hz, 80 dB SPL and 90 ms duration. The deviant stimuli differed in duration (50 ms) or frequency (1,200 Hz). There were no significant differences in MMN values between cannabis users and nonuser controls in both deviance conditions. With regard to subgroups, reduced amplitudes of frequency MMN at frontal electrodes were found in long-term (≥8 years of use) and heavy (≥15 joints/week) users compared to short-term and light users. The results indicate that chronic cannabis use may cause a specific impairment of auditory information processing. In particular, duration and quantity of cannabis use could be identified as important factors of deficient MMN generation.

Expression of mismatch repair gene PMS2 in nasopharyngeal carcinoma and regulation by glycogen synthase kinase-3β in vivo and in vitro.

PubMed

Fang, Jugao; Lei, Wenbin; Huang, Xiaoming; Li, Pingdong; Chen, Xiaohong; Zhu, Xiaolin; Wen, Weiping; Li, Huabin

2012-02-01

To evaluate the expression of mismatch repair gene PMS2 in human nasopharyngeal carcinoma (NPC) tissues and evaluate the effect of glycogen synthase kinase (GSK)-3β on PMS2 production in vivo and in vitro. The expression of PMS2 and inactivated phosphorylated GSK-3β(s9) was examined by immunohistochemical staining in 25 NPC tissues and the relation was determined by correlation analysis. The effect of GSK-3β transfection in CNE-2 cells on PMS2 production as well as cell apoptosis and chemosensitization were evaluated using small interference RNA (siRNA), immunoblotting and flow cytometric analysis in vitro. The expression of inactivated phosphorylated GSK-3β(s9) was found to negative correlated with PMS2 in vivo. And transfected GSK-3β was found to be able to enhance PMS2 production, and increase cell apoptosis in CNE-2 cells in combination with cisplatin administration in vitro. Inactivation of GSK-3β might be important for NPC tumorgenesis through negatively regulating PMS2 production, and enhanced PMS2 production by GSK-3β is beneficial for understanding the NPC tumorgenesis and developing potential strategy for future therapy. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Mismatch negativity is a stronger indicator of functional outcomes than neurocognition or theory of mind in patients with schizophrenia.

PubMed

Lee, Seung-Hwan; Sung, Kyongae; Lee, Kyong-Sang; Moon, Eunok; Kim, Chang-Gyu

2014-01-03

Mismatch negativity (MMN) is known to be associated with neurocognition, social cognition, and functional outcomes. The present study explored the relationships of MMN with neurocognition, theory of mind, and functional outcomes in patients with schizophrenia, first-degree relatives of patients with schizophrenia, and healthy controls. Twenty-five patients with schizophrenia, 21 first-degree relatives of patients with schizophrenia, and 29 healthy controls were recruited. We examined symptom severity, neurocognition, theory of mind, functional outcomes, and MMN. MMN amplitudes decreased in order of patients with schizophrenia, then first-degree relatives, then healthy controls. MMN amplitude was significantly correlated with measures of neurocognition, theory of mind, and functional outcome measurements in patients with schizophrenia. However, the most powerful correlations were those between MMN in the frontal region and measures of functional outcomes. The power and frequency of the correlations were weaker in first-degree relatives and healthy controls than in patients with schizophrenia. Hierarchical regression analysis revealed that functional outcomes (relative to measures of neurocognition and theory of mind) constituted the most powerful predictor of MMN. Our results suggest that MMN reflects functional outcomes more efficiently than do measures of neurocognition and theory of mind in patients with schizophrenia. © 2013.

Enhancement of MSH2-MSH3-mediated mismatch recognition by the yeast MLH1-PMS1 complex.

PubMed

Habraken, Y; Sung, P; Prakash, L; Prakash, S

1997-10-01

DNA mismatch repair has a key role in maintaining genomic stability. Defects in mismatch repair cause elevated spontaneous mutation rates and increased instability of simple repetitive sequences, while mutations in human mismatch repair genes result in hereditary nonpolyposis colorectal cancers. Mismatch recognition represents the first critical step of mismatch repair. Genetic and biochemical studies in yeast and humans have indicated a requirement for MSH2-MSH3 and MSH2-MSH6 heterodimers in mismatch recognition. These complexes have, to some extent, overlapping mismatch binding specificities. MLH1 and PMS1 are the other essential components of mismatch repair, but how they function in this process is not known. We have purified the yeast MLH1-PMS1 heterodimer to near homogeneity, and examined its effect on MSH2-MSH3 binding to DNA mismatches. By itself, the MLH1-PMS1 complex shows no affinity for mismatched DNA, but it greatly enhances the mismatch binding ability of MSH2-MSH3.

Cortical Responses to Chinese Phonemes in Preschoolers Predict Their Literacy Skills at School Age.

PubMed

Hong, Tian; Shuai, Lan; Frost, Stephen J; Landi, Nicole; Pugh, Kenneth R; Shu, Hua

2018-01-01

We investigated whether preschoolers with poor phonological awareness (PA) skills had impaired cortical basis for detecting speech feature, and whether speech perception influences future literacy outcomes in preschoolers. We recorded ERP responses to speech in 52 Chinese preschoolers. The results showed that the poor PA group processed speech changes differentially compared to control group in mismatch negativity (MMN) and late discriminative negativity (LDN). Furthermore, speech perception in kindergarten could predict literacy outcomes after literacy acquisition. These suggest that impairment in detecting speech features occurs before formal reading instruction, and that speech perception plays an important role in reading development.

Optimizing empiric therapy for Gram-negative bloodstream infections in children.

PubMed

Chao, Y; Reuter, C; Kociolek, L K; Patel, R; Zheng, X; Patel, S J

2018-06-01

Antimicrobial stewardship can be challenging in children with bloodstream infections (BSIs) caused by Gram-negative bacilli (GNB). This retrospective cohort study explored how data elements in the electronic health record could potentially optimize empiric antibiotic therapy for BSIs caused by GNB, via the construction of customized antibiograms for categorical GNB infections and identification of opportunities to minimize organism-drug mismatch and decrease time to effective therapy. Our results suggest potential strategies that could be implemented at key decision points in prescribing at initiation, modification, and targeting of therapy. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Independent Control of the Magnetization in Ferromagnetic La2/3Sr1/3MnO3/SrTiO3/LaCoO3 Heterostructures Achieved by Epitaxial Lattice Mismatch.

PubMed

Rivas-Murias, Beatriz; Lucas, Irene; Jiménez-Cavero, Pilar; Magén, César; Morellón, Luis; Rivadulla, Francisco

2016-03-09

We report the effect of interface symmetry-mismatch on the magnetic properties of LaCoO3 (LCO) thin films. Growing epitaxial LCO under tensile strain on top of cubic SrTiO3 (STO) produces a contraction along the c axis and a characteristic ferromagnetic response. However, we report here that ferromagnetism in LCO is completely suppressed when grown on top of a buffer layer of rhombohedral La2/3Sr1/3MnO3 (LSMO), in spite of identical in-plane and out-of-plane lattice deformation. This confirms that it is the lattice symmetry mismatch and not just the total strain, which determines the magnetism of LCO. On the basis of this control over the magnetic properties of LCO, we designed a multilayered structure to achieve independent rotation of the magnetization in ferromagnetic insulating LCO and half-metallic ferromagnet LSMO. This is an important step forward for the design of spin-filtering tunnel barriers based on LCO.

The Association Between Broad Antigen HLA Mismatches, Eplet HLA Mismatches and Acute Rejection After Kidney Transplantation.

PubMed

Do Nguyen, Hung Thanh; Wong, Germaine; Chapman, Jeremy R; McDonald, Stephen P; Coates, Patrick T; Watson, Narelle; Russ, Graeme R; D'Orsogna, Lloyd; Lim, Wai Hon

2016-12-01

Epitope matching, which evaluates mismatched amino acids within antigen-antibody interaction sites (eplets), may better predict acute rejection than broad antigen matching alone. We aimed to determine the association between eplet mismatches and acute rejection in kidney transplant recipients. The association between eplet mismatches, broad antigen mismatches and acute rejection was assessed using adjusted Cox proportional hazard regression. Model discrimination for acute rejection was evaluated using the area under receiver operating characteristic curves. Of the 3,499 kidney transplant recipients from 2006 to 2011, the average (SD) number of broad antigen and eplet mismatches were 3.4 (1.7) and 22.8 (12.2), respectively. Compared with 0 to 2 eplet mismatches, the adjusted hazard ratio (HR) for acute rejection among those with 20 or greater eplet mismatches was 2.16 (95% confidence interval [CI], 1.33-3.52; P = 0.001). The adjusted area under the curve for broad antigen mismatches was 0.58 (95% CI, 0.56-0.61), similar to that for eplet mismatches (HR, 0.59; 95% CI, 0.56-0.61; P = 0.365). In recipients who were considered as low immunological risk (0-2 broad antigen HLA-ABDR mismatch), those with 20 or greater eplet mismatches experienced an increased risk of rejection compared to those with less than 20 mismatches (adjusted HR, 1.85; 95% CI, 1.11-3.08; P = 0.019). Increasing number of eplet mismatches is associated with acute rejection in kidney transplant recipients. Consideration of eplet HLA mismatches may improve risk stratification for acute rejection in a selected group of kidney transplant candidates.

Impact of Life History on Fear Memory and Extinction

PubMed Central

Remmes, Jasmin; Bodden, Carina; Richter, S. Helene; Lesting, Jörg; Sachser, Norbert; Pape, Hans-Christian; Seidenbecher, Thomas

2016-01-01

Behavioral profiles are strongly shaped by an individual's whole life experience. The accumulation of negative experiences over lifetime is thought to promote anxiety-like behavior in adulthood (“allostatic load hypothesis”). In contrast, the “mismatch hypothesis” of psychiatric disease suggests that high levels of anxiety-like behavior are the result of a discrepancy between early and late environment. The aim of the present study was to investigate how different life histories shape the expression of anxiety-like behavior and modulate fear memory. In addition, we aimed to clarify which of the two hypotheses can better explain the modulation of anxiety and fear. For this purpose, male mice grew up under either adverse or beneficial conditions during early phase of life. In adulthood they were further subdivided in groups that either matched or mismatched the condition experienced before, resulting in four different life histories. The main results were: (i) Early life benefit followed by late life adversity caused decreased levels of anxiety-like behavior. (ii) Accumulation of adversity throughout life history led to impaired fear extinction learning. Late life adversity as compared to late life benefit mainly affected extinction training, while early life adversity as compared to early life benefit interfered with extinction recall. Concerning anxiety-like behavior, the results do neither support the allostatic load nor the mismatch hypothesis, but rather indicate an anxiolytic effect of a mismatched early beneficial and later adverse life history. In contrast, fear memory was strongly affected by the accumulation of adverse experiences over the lifetime, therefore supporting allostatic load hypothesis. In summary, this study highlights that anxiety-like behavior and fear memory are differently affected by specific combinations of adverse or beneficial events experienced throughout life. PMID:27757077

MHC-mismatched mixed chimerism augments thymic regulatory T-cell production and prevents relapse of EAE in mice

PubMed Central

Wu, Limin; Li, Nainong; Zhang, Mingfeng; Xue, Sheng-Li; Cassady, Kaniel; Lin, Qing; Riggs, Arthur D.; Zeng, Defu

2015-01-01

Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system with demyelination, axon damage, and paralysis. Induction of mixed chimerism with allogeneic donors has been shown to not cause graft-versus-host disease (GVHD) in animal models and humans. We have reported that induction of MHC-mismatched mixed chimerism can cure autoimmunity in autoimmune NOD mice, but this approach has not yet been tested in animal models of MS, such as experimental autoimmune encephalomyelitis (EAE). Here, we report that MHC-mismatched mixed chimerism with C57BL/6 (H-2b) donor in SJL/J (H-2s) EAE recipients eliminates clinical symptoms and prevents relapse. This cure is demonstrated by not only disappearance of clinical signs but also reversal of autoimmunity; elimination of infiltrating T, B, and macrophage cells in the spinal cord; and regeneration of myelin sheath. The reversal of autoimmunity is associated with a marked reduction of autoreactivity of CD4+ T cells and significant increase in the percentage of Foxp3+ Treg among host-type CD4+ T cells in the spleen and lymph nodes. The latter is associated with a marked reduction of the percentage of host-type CD4+CD8+ thymocytes and an increase of Treg percentage among the CD4+CD8+ and CD4+CD8− thymocytes. Thymectomy leads to loss of prevention of EAE relapse by induction of mixed chimerism, although there is a dramatic expansion of host-type Treg cells in the lymph nodes. These results indicate that induction of MHC-mismatched mixed chimerism can restore thymic negative selection of autoreactive CD4+ T cells, augment production of Foxp3+ Treg, and cure EAE. PMID:26647186

Density dependence and phenological mismatch: consequences for growth and survival of sub-arctic nesting Canada Geese

USGS Publications Warehouse

Brook, Rodney W.; Leafloor, James O.; Douglas, David C.; Abraham, Kenneth F.

2015-01-01

The extent to which species are plastic in the timing of their reproductive events relative to phenology suggests how change might affect their demography. An ecological mismatch between the timing of hatch for avian species and the peak availability in quality and quantity of forage for rapidly growing offspring might ultimately affect recruitment to the breeding population unless individuals can adjust the timing of breeding to adapt to changing phenology. We evaluated effects of goose density, hatch timing relative to forage plant phenology, and weather indices on annual growth of pre-fledging Canada geese (Branta canadensis) from 1993-2010 at Akimiski Island, Nunavut. We found effects of both density and hatch timing relative to forage plant phenology; the earlier that eggs hatched relative to forage plant phenology, the larger the mean gosling size near fledging. Goslings were smallest in years when hatch was latest relative to forage plant phenology, and when local abundance of breeding adults was highest. We found no evidence for a trend in relative hatch timing, but it was apparent that in early springs, Canada geese tended to hatch later relative to vegetation phenology, suggesting that geese were not always able to adjust the timing of nesting as rapidly as vegetation phenology was advanced. Analyses using forage biomass information revealed a positive relationship between gosling size and per capita biomass availability, suggesting a causal mechanism for the density effect. The effects of weather parameters explained additional variation in mean annual gosling size, although total June and July rainfall had a small additive effect on gosling size. Modelling of annual first year survival probability using mean annual gosling size as an annual covariate revealed a positive relationship, suggesting that reduced gosling growth negatively impacts recruitment.

Single-molecule multiparameter fluorescence spectroscopy reveals directional MutS binding to mismatched bases in DNA

PubMed Central

Cristóvão, Michele; Sisamakis, Evangelos; Hingorani, Manju M.; Marx, Andreas D.; Jung, Caroline P.; Rothwell, Paul J.; Seidel, Claus A. M.; Friedhoff, Peter

2012-01-01

Mismatch repair (MMR) corrects replication errors such as mismatched bases and loops in DNA. The evolutionarily conserved dimeric MMR protein MutS recognizes mismatches by stacking a phenylalanine of one subunit against one base of the mismatched pair. In all crystal structures of G:T mismatch-bound MutS, phenylalanine is stacked against thymine. To explore whether these structures reflect directional mismatch recognition by MutS, we monitored the orientation of Escherichia coli MutS binding to mismatches by FRET and anisotropy with steady state, pre-steady state and single-molecule multiparameter fluorescence measurements in a solution. The results confirm that specifically bound MutS bends DNA at the mismatch. We found additional MutS–mismatch complexes with distinct conformations that may have functional relevance in MMR. The analysis of individual binding events reveal significant bias in MutS orientation on asymmetric mismatches (G:T versus T:G, A:C versus C:A), but not on symmetric mismatches (G:G). When MutS is blocked from binding a mismatch in the preferred orientation by positioning asymmetric mismatches near the ends of linear DNA substrates, its ability to authorize subsequent steps of MMR, such as MutH endonuclease activation, is almost abolished. These findings shed light on prerequisites for MutS interactions with other MMR proteins for repairing the appropriate DNA strand. PMID:22367846

Robust Detection of Rare Species Using Environmental DNA: The Importance of Primer Specificity

PubMed Central

Wilcox, Taylor M.; McKelvey, Kevin S.; Young, Michael K.; Jane, Stephen F.; Lowe, Winsor H.; Whiteley, Andrew R.; Schwartz, Michael K.

2013-01-01

Environmental DNA (eDNA) is being rapidly adopted as a tool to detect rare animals. Quantitative PCR (qPCR) using probe-based chemistries may represent a particularly powerful tool because of the method’s sensitivity, specificity, and potential to quantify target DNA. However, there has been little work understanding the performance of these assays in the presence of closely related, sympatric taxa. If related species cause any cross-amplification or interference, false positives and negatives may be generated. These errors can be disastrous if false positives lead to overestimate the abundance of an endangered species or if false negatives prevent detection of an invasive species. In this study we test factors that influence the specificity and sensitivity of TaqMan MGB assays using co-occurring, closely related brook trout (Salvelinus fontinalis) and bull trout (S. confluentus) as a case study. We found qPCR to be substantially more sensitive than traditional PCR, with a high probability of detection at concentrations as low as 0.5 target copies/µl. We also found that number and placement of base pair mismatches between the Taqman MGB assay and non-target templates was important to target specificity, and that specificity was most influenced by base pair mismatches in the primers, rather than in the probe. We found that insufficient specificity can result in both false positive and false negative results, particularly in the presence of abundant related species. Our results highlight the utility of qPCR as a highly sensitive eDNA tool, and underscore the importance of careful assay design. PMID:23555689

Robust detection of rare species using environmental DNA: the importance of primer specificity.

PubMed

Wilcox, Taylor M; McKelvey, Kevin S; Young, Michael K; Jane, Stephen F; Lowe, Winsor H; Whiteley, Andrew R; Schwartz, Michael K

2013-01-01

Environmental DNA (eDNA) is being rapidly adopted as a tool to detect rare animals. Quantitative PCR (qPCR) using probe-based chemistries may represent a particularly powerful tool because of the method's sensitivity, specificity, and potential to quantify target DNA. However, there has been little work understanding the performance of these assays in the presence of closely related, sympatric taxa. If related species cause any cross-amplification or interference, false positives and negatives may be generated. These errors can be disastrous if false positives lead to overestimate the abundance of an endangered species or if false negatives prevent detection of an invasive species. In this study we test factors that influence the specificity and sensitivity of TaqMan MGB assays using co-occurring, closely related brook trout (Salvelinus fontinalis) and bull trout (S. confluentus) as a case study. We found qPCR to be substantially more sensitive than traditional PCR, with a high probability of detection at concentrations as low as 0.5 target copies/µl. We also found that number and placement of base pair mismatches between the Taqman MGB assay and non-target templates was important to target specificity, and that specificity was most influenced by base pair mismatches in the primers, rather than in the probe. We found that insufficient specificity can result in both false positive and false negative results, particularly in the presence of abundant related species. Our results highlight the utility of qPCR as a highly sensitive eDNA tool, and underscore the importance of careful assay design.

The Value of Being Imitated

ERIC Educational Resources Information Center

Parton, David A.; Priefert, Maria J.

1975-01-01

This study examines the possibility that the relational stimulus arising from being imitated serves a reinforcing function. A total of 48 preschool children performed a task in which some neutral stimuli were repeatedly associated either with an adult's matching the subject's behavior or the adult's mismatching the subject's behavior. (Author/GO)

An Asymmetry in the Automatic Detection of the Presence or Absence of a Frequency Modulation within a Tone: A Mismatch Negativity Study

PubMed Central

Timm, Jana; Weise, Annekathrin; Grimm, Sabine; Schröger, Erich

2011-01-01

The infrequent occurrence of a transient feature (deviance; e.g., frequency modulation, FM) in one of the regular occurring sinusoidal tones (standards) elicits the deviance related mismatch negativity (MMN) component of the event-related brain potential. Based on a memory-based comparison, MMN reflects the mismatch between the representations of incoming and standard sounds. The present study investigated to what extent the infrequent exclusion of an FM is detected by the MMN system. For that purpose we measured MMN to deviances that either consisted of the exclusion or inclusion of an FM at an early or late position within the sound that was present or absent, respectively, in the standard. According to the information-content hypothesis, deviance detection relies on the difference in informational content of the deviant relative to that of the standard. As this difference between deviants with FM and standards without FM is the same as in the reversed case, comparable MMNs should be elicited to FM inclusions and exclusions. According to the feature-detector hypothesis, however, the deviance detection depends on the increased activation of feature detectors to additional sound features. Thus, rare exclusions of the FM should elicit no or smaller MMN than FM inclusions. In passive listening condition, MMN was obtained only for the early inclusion, but not for the exclusions nor for the late inclusion of an FM. This asymmetry in automatic deviance detection seems to partly reflect the contribution of feature detectors even though it cannot fully account for the missing MMN to late FM inclusions. Importantly, the behavioral deviance detection performance in the active listening condition did not reveal such an asymmetry, suggesting that the intentional detection of the deviants is based on the difference in informational content. On a more general level, the results partly support the “fresh-afferent” account or an extended memory-comparison based account of MMN. PMID:21852979

Surgical treatment of pathological loss of lumbar lordosis (flatback) in patients with normal sagittal vertical axis achieves similar clinical improvement as surgical treatment of elevated sagittal vertical axis: clinical article.

PubMed

Smith, Justin S; Singh, Manish; Klineberg, Eric; Shaffrey, Christopher I; Lafage, Virginie; Schwab, Frank J; Protopsaltis, Themistocles; Ibrahimi, David; Scheer, Justin K; Mundis, Gregory; Gupta, Munish C; Hostin, Richard; Deviren, Vedat; Kebaish, Khaled; Hart, Robert; Burton, Douglas C; Bess, Shay; Ames, Christopher P

2014-08-01

Increased sagittal vertical axis (SVA) correlates strongly with pain and disability for adults with spinal deformity. A subset of patients with sagittal spinopelvic malalignment (SSM) have flatback deformity (pelvic incidence-lumbar lordosis [PI-LL] mismatch > 10°) but remain sagittally compensated with normal SVA. Few data exist for SSM patients with flatback deformity and normal SVA. The authors' objective was to compare baseline disability and treatment outcomes for patients with compensated (SVA < 5 cm and PI-LL mismatch > 10°) and decompensated (SVA > 5 cm) SSM. The study was a multicenter, prospective analysis of adults with spinal deformity who consecutively underwent surgical treatment for SSM. Inclusion criteria included age older than 18 years, presence of adult spinal deformity with SSM, plan for surgical treatment, and minimum 1-year follow-up data. Patients with SSM were divided into 2 groups: those with compensated SSM (SVA < 5 cm and PI-LL mismatch > 10°) and those with decompensated SSM (SVA ≥ 5 cm). Baseline and 1-year follow-up radiographic and health-related quality of life (HRQOL) outcomes included Oswestry Disability Index, Short Form-36 scores, and Scoliosis Research Society-22 scores. Percentages of patients achieving minimal clinically important difference (MCID) were also assessed. A total of 125 patients (27 compensated and 98 decompensated) met inclusion criteria. Compared with patients in the compensated group, patients in the decompensated group were older (62.9 vs. 55.1 years; p = 0.004) and had less scoliosis (43° vs 54°; p = 0.002), greater SVA (12.0 cm vs. 1.7 cm; p < 0.001), greater PI-LL mismatch (26° vs. 20°; p = 0.013), and poorer HRQOL scores (Oswestry Disability Index, Short Form-36 physical component score, Scoliosis Research Society-22 total; p ≤ 0.016). Although these baseline HRQOL differences between the groups reached statistical significance, only the mean difference in Short Form-36 physical component score reached threshold for MCID. Compared with baseline assessment, at 1 year after surgery improvement was noted for patients in both groups for mean SVA (compensated -1.1 cm, decompensated +4.8 cm; p ≤ 0.009), mean PI-LL mismatch (compensated 6°, decompensated 5°; p < 0.001), and all HRQOL measures assessed (p ≤ 0.005). No significant differences were found between the compensated and decompensated groups in the magnitude of HRQOL score improvement or in the percentages of patients achieving MCID for each of the outcome measures assessed. Decompensated SSM patients with elevated SVA experience significant disability; however, the amount of disability in compensated SSM patients with flatback deformity caused by PI-LL mismatch but normal SVA is underappreciated. Surgical correction of SSM demonstrated similar radiographic and HRQOL score improvements for patients in both groups. Evaluation of SSM should extend beyond measuring SVA. Among patients with concordant pain and disability, PI-LL mismatch must be evaluated for SSM patients and can be considered a primary indication for surgery.

Thermodynamic characterization of tandem mismatches found in naturally occurring RNA

PubMed Central

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

A practical assessment of magnetic resonance diffusion-perfusion mismatch in acute stroke: observer variation and outcome.

PubMed

Kane, I; Hand, P J; Rivers, C; Armitage, P; Bastin, M E; Lindley, R; Dennis, M; Wardlaw, J M

2009-11-01

MR diffusion/perfusion mismatch may help identify patients for acute stroke treatment, but mixed results from clinical trials suggest that further evaluation of the mismatch concept is required. To work effectively, mismatch should predict prognosis on arrival at hospital. We assessed mismatch duration and associations with functional outcome in acute stroke. We recruited consecutive patients with acute stroke, recorded baseline clinical variables, performed MR diffusion and perfusion imaging and assessed 3-month functional outcome. We assessed practicalities, agreement between mismatch on mean transit time (MTT) or cerebral blood flow (CBF) maps, visually and with lesion volume, and the relationship of each to functional outcome. Of 82 patients starting imaging, 14 (17%) failed perfusion imaging. Overall, 42% had mismatch (56% at <6 h; 41% at 12-24 h; 23% at 24-48 h). Agreement for mismatch by visual versus volume assessment was fair using MTT (kappa 0.59, 95% CI 0.34-0.84) but poor using CBF (kappa 0.24, 95% CI 0.01-0.48). Mismatch by either definition was not associated with functional outcome, even when the analysis was restricted to just those with mismatch. Visual estimation is a reasonable proxy for mismatch volume on MTT but not CBF. Perfusion is more difficult for acute stroke patients than diffusion imaging. Mismatch is present in many patients beyond 12 h after stroke. Mismatch alone does not distinguish patients with good and poor prognosis; both can do well or poorly. Other factors, e.g. reperfusion, may influence outcome more strongly, even in patients without mismatch.

A review of empirical evidence on different uncanny valley hypotheses: support for perceptual mismatch as one road to the valley of eeriness

PubMed Central

Kätsyri, Jari; Förger, Klaus; Mäkäräinen, Meeri; Takala, Tapio

2015-01-01

The uncanny valley hypothesis, proposed already in the 1970s, suggests that almost but not fully humanlike artificial characters will trigger a profound sense of unease. This hypothesis has become widely acknowledged both in the popular media and scientific research. Surprisingly, empirical evidence for the hypothesis has remained inconsistent. In the present article, we reinterpret the original uncanny valley hypothesis and review empirical evidence for different theoretically motivated uncanny valley hypotheses. The uncanny valley could be understood as the naïve claim that any kind of human-likeness manipulation will lead to experienced negative affinity at close-to-realistic levels. More recent hypotheses have suggested that the uncanny valley would be caused by artificial–human categorization difficulty or by a perceptual mismatch between artificial and human features. Original formulation also suggested that movement would modulate the uncanny valley. The reviewed empirical literature failed to provide consistent support for the naïve uncanny valley hypothesis or the modulatory effects of movement. Results on the categorization difficulty hypothesis were still too scarce to allow drawing firm conclusions. In contrast, good support was found for the perceptual mismatch hypothesis. Taken together, the present review findings suggest that the uncanny valley exists only under specific conditions. More research is still needed to pinpoint the exact conditions under which the uncanny valley phenomenon manifests itself. PMID:25914661

Postmortem CT versus forensic autopsy: frequent discrepancies of tracheobronchial content findings.

PubMed

Zech, Wolf-Dieter; Jackowski, Christian; Schwendener, Nicole; Brencicova, Eva; Schuster, Frederick; Lombardo, Paolo

2016-01-01

In their daily forensic casework, the authors experienced discrepancies of tracheobronchial content findings between postmortem computed tomography (PMCT) and autopsy to an extent previously unnoticed in the literature. The goal of this study was to evaluate such discrepancies in routine forensic cases. A total of 327 cases that underwent PMCT prior to routine forensic autopsy were retrospectively evaluated for tracheal and bronchial contents according to PMCT and autopsy findings. Hounsfield unit (HU) values of tracheobronchial contents, causes of death, and presence of pulmonary edema were assessed in mismatching and matching cases. Comparing contents in PMCT and autopsy in each of the separately evaluated compartments of the respiratory tract low positive predictive values were assessed (trachea, 38.2%; main bronchi, 40%; peripheral bronchi, 69.1%) indicating high discrepancy rates. The majority of tracheobronchial contents were viscous stomach contents in matching cases and low radiodensity materials (i.e., HU < 30) in mismatching cases. The majority of causes of death were cardiac related in the matching cases and skull/brain trauma in the mismatching cases. In mismatching cases, frequency of pulmonary edema was significantly higher than in matching cases. It can be concluded that discrepancies in tracheobronchial contents observed between PMCT and routine forensic autopsy occur in a considerable number of cases. Discrepancies may be explained by the runoff of contents via nose and mouth during external examination and the flow back of tracheal and main bronchial contents into the lungs caused by upright movement of the respiratory tract at autopsy.

Identification of miR-31-5p, miR-141-3p, miR-200c-3p, and GLT1 as human liver aging markers sensitive to donor-recipient age-mismatch in transplants.

PubMed

Capri, Miriam; Olivieri, Fabiola; Lanzarini, Catia; Remondini, Daniel; Borelli, Vincenzo; Lazzarini, Raffaella; Graciotti, Laura; Albertini, Maria Cristina; Bellavista, Elena; Santoro, Aurelia; Biondi, Fiammetta; Tagliafico, Enrico; Tenedini, Elena; Morsiani, Cristina; Pizza, Grazia; Vasuri, Francesco; D'Errico, Antonietta; Dazzi, Alessandro; Pellegrini, Sara; Magenta, Alessandra; D'Agostino, Marco; Capogrossi, Maurizio C; Cescon, Matteo; Rippo, Maria Rita; Procopio, Antonio Domenico; Franceschi, Claudio; Grazi, Gian Luca

2017-04-01

To understand why livers from aged donors are successfully used for transplants, we looked for markers of liver aging in 71 biopsies from donors aged 12-92 years before transplants and in 11 biopsies after transplants with high donor-recipient age-mismatch. We also assessed liver function in 36 age-mismatched recipients. The major findings were the following: (i) miR-31-5p, miR-141-3p, and miR-200c-3p increased with age, as assessed by microRNAs (miRs) and mRNA transcript profiling in 12 biopsies and results were validated by RT-qPCR in a total of 58 biopsies; (ii) telomere length measured by qPCR in 45 samples showed a significant age-dependent shortage; (iii) a bioinformatic approach combining transcriptome and miRs data identified putative miRs targets, the most informative being GLT1, a glutamate transporter expressed in hepatocytes. GLT1 was demonstrated by luciferase assay to be a target of miR-31-5p and miR-200c-3p, and both its mRNA (RT-qPCR) and protein (immunohistochemistry) significantly decreased with age in liver biopsies and in hepatic centrilobular zone, respectively; (iv) miR-31-5p, miR-141-3p and miR-200c-3p expression was significantly affected by recipient age (older environment) as assessed in eleven cases of donor-recipient extreme age-mismatch; (v) the analysis of recipients plasma by N-glycans profiling, capable of assessing liver functions and biological age, showed that liver function recovered after transplants, independently of age-mismatch, and recipients apparently 'rejuvenated' according to their glycomic age. In conclusion, we identified new markers of aging in human liver, their relevance in donor-recipient age-mismatches in transplantation, and offered positive evidence for the use of organs from old donors. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Frontal Glutamate and γ-Aminobutyric Acid Levels and Their Associations With Mismatch Negativity and Digit Sequencing Task Performance in Schizophrenia.

PubMed

Rowland, Laura M; Summerfelt, Ann; Wijtenburg, S Andrea; Du, Xiaoming; Chiappelli, Joshua J; Krishna, Nithin; West, Jeffrey; Muellerklein, Florian; Kochunov, Peter; Hong, L Elliot

2016-02-01

Auditory mismatch negativity (MMN) is a biomarker for schizophrenia thought to reflect glutamatergic N-methyl-d-aspartate receptor function and excitatory-inhibitory neurotransmission balance. However, the association of glutamate level with MMN has not been directly examined in patients with schizophrenia, to our knowledge. To investigate the contributions of glutamate and γ-aminobutyric acid (GABA) to MMN and digit sequencing task (DST) performance, an assessment of verbal working memory, in schizophrenia. Fifty-three control participants from the community and 45 persons with schizophrenia from outpatient clinics completed an electroencephalographic session for MMN, magnetic resonance spectroscopy for glutamate and GABA, and a DST. The study dates were July 2011 to May 2014, and the dates of our analysis were May 2014 to August 2015. Glutamate, GABA, the ratio of glutamine to glutamate, MMN amplitude, and DST. Structural equation modeling was used to test the effects of neurochemistry and MMN amplitude on DST performance. The 45 persons with schizophrenia were a mean (SD) of 37.7 (12.8) years and the control participants were 37.1 (13.1) years. The schizophrenia group had a mean (SD) of 14.7 (12.1) years of illness. Mismatch negativity amplitude (F = 4.39, P = .04) and glutamate (F = 9.69, P = .002) were reduced in the schizophrenia group. Smaller MMN amplitude was significantly associated with lower GABA level (P = .008), lower glutamate level (P = .05), and higher ratio of glutamine to glutamate (P = .003). Reduced MMN amplitude was linked to poor verbal working memory in schizophrenia (P = .002). Modeling revealed that a proxy of glutamatergic function, indexed by the ratio of glutamine to glutamate, influenced a path from the ratio of glutamine to glutamate to MMN to verbal working memory (P = .38 [root-mean-square error of approximation, P < .001] by χ2 test), supporting the contention that MMN serves as an intermediate biomarker linking glutamatergic function to DST performance in schizophrenia. The role of glutamate and GABA in MMN and verbal working memory deficits in schizophrenia has been frequently debated. These data provide in vivo evidence that support glutamatergic and GABAergic regulation of MMN and verbal working memory function in schizophrenia.

Frontal Glutamate and γ-Aminobutyric Acid Levels and Their Associations With Mismatch Negativity and Digit Sequencing Task Performance in Schizophrenia

PubMed Central

Rowland, Laura M.; Summerfelt, Ann; Wijtenburg, S. Andrea; Du, Xiaoming; Chiappelli, Joshua J.; Krishna, Nithin; West, Jeffrey; Muellerklein, Florian; Kochunov, Peter; Hong, L. Elliot

2016-01-01

IMPORTANCE Auditory mismatch negativity (MMN) is a biomarker for schizophrenia thought to reflect glutamatergic N-methyl-d-aspartate receptor function and excitatory-inhibitory neurotransmission balance. However, the association of glutamate level with MMN has not been directly examined in patients with schizophrenia, to our knowledge. OBJECTIVE To investigate the contributions of glutamate and γ-aminobutyric acid (GABA) to MMN and digit sequencing task (DST) performance, an assessment of verbal working memory, in schizophrenia. DESIGN, SETTING, AND PARTICIPANTS Fifty-three control participants from the community and 45 persons with schizophrenia from outpatient clinics completed an electroencephalographic session for MMN, magnetic resonance spectroscopy for glutamate and GABA, and a DST. The study dates were July 2011 to May 2014, and the dates of our analysis were May 2014 to August 2015. MAIN OUTCOMES AND MEASURES Glutamate, GABA, the ratio of glutamine to glutamate, MMN amplitude, and DST. Structural equation modeling was used to test the effects of neurochemistry and MMN amplitude on DST performance. RESULTS The 45 persons with schizophrenia were a mean (SD) of 37.7 (12.8) years and the control participants were 37.1 (13.1) years. The schizophrenia group had a mean (SD) of 14.7 (12.1) years of illness. Mismatch negativity amplitude (F = 4.39, P = .04) and glutamate (F = 9.69, P = .002) were reduced in the schizophrenia group. Smaller MMN amplitude was significantly associated with lower GABA level (P = .008), lower glutamate level (P = .05), and higher ratio of glutamine to glutamate (P = .003). Reduced MMN amplitude was linked to poor verbal working memory in schizophrenia (P = .002). Modeling revealed that a proxy of glutamatergic function, indexed by the ratio of glutamine to glutamate, influenced a path from the ratio of glutamine to glutamate to MMN to verbal working memory (P = .38 [root-mean-square error of approximation, P < .001] by χ2 test), supporting the contention that MMN serves as an intermediate biomarker linking glutamatergic function to DST performance in schizophrenia. CONCLUSIONS AND RELEVANCE The role of glutamate and GABA in MMN and verbal working memory deficits in schizophrenia has been frequently debated. These data provide in vivo evidence that support glutamatergic and GABAergic regulation of MMN and verbal working memory function in schizophrenia. PMID:26720179

Effects of zolpidem and zopiclone on cognitive and attentional function in young healthy volunteers: an event-related potential study.

PubMed

Nakajima, T; Takazawa, S; Hayashida, S; Nakagome, K; Sasaki, T; Kanno, O

2000-02-01

The effects of zolpidem and zopiclone, non-benzodiazepine ultra-short-acting hypnotics, on cognitive function and vigilance level were investigated in the morning following nocturnal administration using event-related potentials (ERP) and a sleep latency test (SLT). Zopiclone significantly shortened the sleep latency the following morning, whereas zolpidem did not, perhaps due to the difference in the elimination half-lives between the compounds. No significant effect was observed for either drug on the ERP indices, including the P3, mismatch negativity and negative difference components. At a clinically prescribed dosage these sleep inducers have no remarkable effect on cognitive or attentional functions but increase sleepiness of the subjects.

Feasibility of Real-Time Selection of Frequency Tables in an Acoustic Simulation of a Cochlear Implant

PubMed Central

Fitzgerald, Matthew; Sagi, Elad; Morbiwala, Tasnim A.; Tan, Chin-Tuan; Svirsky, Mario A.

2013-01-01

Objectives Perception of spectrally degraded speech is particularly difficult when the signal is also distorted along the frequency axis. This might be particularly important for post-lingually deafened recipients of cochlear implants (CI), who must adapt to a signal where there may be a mismatch between the frequencies of an input signal and the characteristic frequencies of the neurons stimulated by the CI. However, there is a lack of tools that can be used to identify whether an individual has adapted fully to a mismatch in the frequency-to-place relationship and if so, to find a frequency table that ameliorates any negative effects of an unadapted mismatch. The goal of the proposed investigation is to test the feasibility of whether real-time selection of frequency tables can be used to identify cases in which listeners have not fully adapted to a frequency mismatch. The assumption underlying this approach is that listeners who have not adapted to a frequency mismatch will select a frequency table that minimizes any such mismatches, even at the expense of reducing the information provided by this frequency table. Design 34 normal-hearing adults listened to a noise-vocoded acoustic simulation of a cochlear implant and adjusted the frequency table in real time until they obtained a frequency table that sounded “most intelligible” to them. The use of an acoustic simulation was essential to this study because it allowed us to explicitly control the degree of frequency mismatch present in the simulation. None of the listeners had any previous experience with vocoded speech, in order to test the hypothesis that the real-time selection procedure could be used to identify cases in which a listener has not adapted to a frequency mismatch. After obtaining a self-selected table, we measured CNC word-recognition scores with that self-selected table and two other frequency tables: a “frequency-matched” table that matched the analysis filters with the noisebands of the noise-vocoder simulation, and a “right information” table that is similar to that used in most cochlear implant speech processors, but in this simulation results in a frequency shift equivalent to 6.5 mm of cochlear space. Results Listeners tended to select a table that was very close to, but shifted slightly lower in frequency from the frequency-matched table. The real-time selection process took on average 2–3 minutes for each trial, and the between-trial variability was comparable to that previously observed with closely-related procedures. The word-recognition scores with the self-selected table were clearly higher than with the right-information table and slightly higher than with the frequency-matched table. Conclusions Real-time self-selection of frequency tables may be a viable tool for identifying listeners who have not adapted to a mismatch in the frequency-to-place relationship, and to find a frequency table that is more appropriate for them. Moreover, the small but significant improvements in word-recognition ability observed with the self-selected table suggest that these listeners based their selections on intelligibility rather than some other factor. The within-subject variability in the real-time selection procedure was comparable to that of a genetic algorithm, and the speed of the real-time procedure appeared to be faster than either a genetic algorithm or a simplex procedure. PMID:23807089

Mismatch negativity results from bilateral asymmetric dipole sources in the frontal and temporal lobes.

PubMed

Jemel, Boutheina; Achenbach, Christiane; Müller, Bernhard W; Röpcke, Bernd; Oades, Robert D

2002-01-01

The event-related potential (ERP) reflecting auditory change detection (mismatch negativity, MMN) registers automatic selective processing of a deviant sound with respect to a working memory template resulting from a series of standard sounds. Controversy remains whether MMN can be generated in the frontal as well as the temporal cortex. Our aim was to see if frontal as well as temporal lobe dipoles could explain MMN recorded after pitch-deviants (Pd-MMN) and duration deviants (Dd-MMN). EEG recordings were taken from 32 sites in 14 healthy subjects during a passive 3-tone oddball presented during a simple visual discrimination and an active auditory discrimination condition. Both conditions were repeated after one month. The Pd-MMN was larger, peaked earlier and correlated better between sessions than the Dd-MMN. Two dipoles in the auditory cortex and two in the frontal lobe (left cingulate and right inferior frontal cortex) were found to be similarly placed for Pd- and Dd-MMN, and were well replicated on retest. This study confirms interactions between activity generated in the frontal and auditory temporal cortices in automatic attention-like processes that resemble initial brain imaging reports of unconscious visual change detection. The lack of interference between sessions shows that the situation is likely to be sensitive to treatment or illness effects on fronto-temporal interactions involving repeated measures.

Modelling Trial-by-Trial Changes in the Mismatch Negativity

PubMed Central

Lieder, Falk; Daunizeau, Jean; Garrido, Marta I.; Friston, Karl J.; Stephan, Klaas E.

2013-01-01

The mismatch negativity (MMN) is a differential brain response to violations of learned regularities. It has been used to demonstrate that the brain learns the statistical structure of its environment and predicts future sensory inputs. However, the algorithmic nature of these computations and the underlying neurobiological implementation remain controversial. This article introduces a mathematical framework with which competing ideas about the computational quantities indexed by MMN responses can be formalized and tested against single-trial EEG data. This framework was applied to five major theories of the MMN, comparing their ability to explain trial-by-trial changes in MMN amplitude. Three of these theories (predictive coding, model adjustment, and novelty detection) were formalized by linking the MMN to different manifestations of the same computational mechanism: approximate Bayesian inference according to the free-energy principle. We thereby propose a unifying view on three distinct theories of the MMN. The relative plausibility of each theory was assessed against empirical single-trial MMN amplitudes acquired from eight healthy volunteers in a roving oddball experiment. Models based on the free-energy principle provided more plausible explanations of trial-by-trial changes in MMN amplitude than models representing the two more traditional theories (change detection and adaptation). Our results suggest that the MMN reflects approximate Bayesian learning of sensory regularities, and that the MMN-generating process adjusts a probabilistic model of the environment according to prediction errors. PMID:23436989

The effect of deviance predictability on mismatch negativity in schizophrenia patients.

PubMed

Horacek, Magdalena; Kärgel, Christian; Scherbaum, Norbert; Müller, Bernhard W

2016-03-23

Mismatch negativity (MMN) is an electrophysiological index of prediction error processing and recently has been considered an endophenotype marker in schizophrenia. While the prediction error is a core concept in the MMN generation, predictability of deviance occurrence has rarely been assessed in MMN research and in schizophrenia patients. We investigated the MMN to 12% temporally predictable or unpredictable duration decrement deviant stimuli in two runs in 29 healthy controls and 31 schizophrenia patients. We analyzed MMN amplitudes and latencies and its associations with clinical symptoms at electrode Fz. With a stimulus onset asynchronicity of 500 ms in the regular predictable condition, a deviant occurred every 4s while it varied randomly in the unpredictable condition. In the random condition we found diminished MMN amplitudes in patients which normalized in the regular deviance condition, resulting in an analysis of variance main effect of predictability and a predictability x group interaction. Deviance predictability did not affect the MMN of control subjects and we found no relevant results with regard to MMN latencies. Our results indicate that MMN amplitudes in patients normalize to the level of the control subjects in the case of a temporally fixed regular deviant. In schizophrenia patients the detection of deviance is basically intact. However, the temporal uncertainty of deviance occurrence may be of substantial relevance to the highly replicated MMN deficit in schizophrenia patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Rethinking the advantage of zero-HLA mismatches in unrelated living donor kidney transplantation: implications on kidney paired donation.

PubMed

Casey, Michael Jin; Wen, Xuerong; Rehman, Shehzad; Santos, Alfonso H; Andreoni, Kenneth A

2015-04-01

The OPTN/UNOS Kidney Paired Donation (KPD) Pilot Program allocates priority to zero-HLA mismatches. However, in unrelated living donor kidney transplants (LDKT)-the same donor source in KPD-no study has shown whether zero-HLA mismatches provide any advantage over >0 HLA mismatches. We hypothesize that zero-HLA mismatches among unrelated LDKT do not benefit graft survival. This retrospective SRTR database study analyzed LDKT recipients from 1987 to 2012. Among unrelated LDKT, subjects with zero-HLA mismatches were compared to a 1:1-5 matched (by donor age ±1 year and year of transplantation) control cohort with >0 HLA mismatches. The primary endpoint was death-censored graft survival. Among 32,654 unrelated LDKT recipients, 83 had zero-HLA mismatches and were matched to 407 controls with >0 HLA mismatches. Kaplan-Meier analyses for death-censored graft and patient survival showed no difference between study and control cohorts. In multivariate marginal Cox models, zero-HLA mismatches saw no benefit with death-censored graft survival (HR = 1.46, 95% CI 0.78-2.73) or patient survival (HR = 1.43, 95% CI 0.68-3.01). Our data suggest that in unrelated LDKT, zero-HLA mismatches may not offer any survival advantage. Therefore, particular study of zero-HLA mismatching is needed to validate its place in the OPTN/UNOS KPD Pilot Program allocation algorithm. © 2014 Steunstichting ESOT.

Temperature nonuniformity occurring during the cooling process of a KDP crystal and its effects on second-harmonic generation.

PubMed

Liang, Yingchun; Su, Ruifeng; Lu, Lihua; Liu, Haitao

2014-08-10

The temperature nonuniformity occurring during the cooling process of a KDP crystal is studied, along with its effects on the second-harmonic generation (SHG) of a high-average-power laser. A comprehensive model is proposed incorporating principles of thermodynamics, mechanics, and optics, and it is applied to investigate the temperature nonuniformity and its effects. The temperature rise caused by linear absorption is calculated, while the temperature nonuniformity occurring during the cooling process is analyzed using the finite-element method (FEM). The stress induced by the nonuniformity is then studied using the FEM, and the trend of its change is determined. Moreover, the changes in refractive index caused by the stress are calculated, the results of which are used to determine the variations in the induced phase mismatch. The SHG efficiency considering the phase mismatch is eventually obtained by solving the coupling wave equations. The results demonstrate that the temperature nonuniformity has negative effects on the SHG efficiency.

Dissociation of tone and vowel processing in Mandarin idioms.

PubMed

Hu, Jiehui; Gao, Shan; Ma, Weiyi; Yao, Dezhong

2012-09-01

Using event-related potentials, this study measured the access of suprasegmental (tone) and segmental (vowel) information in spoken word recognition with Mandarin idioms. Participants performed a delayed-response acceptability task, in which they judged the correctness of the last word of each idiom, which might deviate from the correct word in either tone or vowel. Results showed that, compared with the correct idioms, a larger early negativity appeared only for vowel violation. Additionally, a larger N400 effect was observed for vowel mismatch than tone mismatch. A control experiment revealed that these differences were not due to low-level physical differences across conditions; instead, they represented the greater constraining power of vowels than tones in the lexical selection and semantic integration of the spoken words. Furthermore, tone violation elicited a more robust late positive component than vowel violation, suggesting different reanalyses of the two types of information. In summary, the current results support a functional dissociation of tone and vowel processing in spoken word recognition. Copyright © 2012 Society for Psychophysiological Research.

Positive Gene Regulation by a Natural Protective miRNA Enables Arbuscular Mycorrhizal Symbiosis.

PubMed

Couzigou, Jean-Malo; Lauressergues, Dominique; André, Olivier; Gutjahr, Caroline; Guillotin, Bruno; Bécard, Guillaume; Combier, Jean-Philippe

2017-01-11

Arbuscular mycorrhizal (AM) symbiosis associates most plants with fungi of the phylum Glomeromycota. The fungus penetrates into roots and forms within cortical cell branched structures called arbuscules for nutrient exchange. We discovered that miR171b has a mismatched cleavage site and is unable to downregulate the miR171 family target gene, LOM1 (LOST MERISTEMS 1). This mismatched cleavage site is conserved among plants that establish AM symbiosis, but not in non-mycotrophic plants. Unlike other members of the miR171 family, miR171b stimulates AM symbiosis and is expressed specifically in root cells that contain arbuscules. MiR171b protects LOM1 from negative regulation by other miR171 family members. These findings uncover a unique mechanism of positive post-transcriptional regulation of gene expression by miRNAs and demonstrate its relevance for the establishment of AM symbiosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Severe acute radiation syndrome: treatment of a lethally 60Co-source irradiated accident victim in China with HLA-mismatched peripheral blood stem cell transplantation and mesenchymal stem cells.

PubMed

Guo, Mei; Dong, Zheng; Qiao, Jianhui; Yu, Changlin; Sun, Qiyun; Hu, Kaixun; Liu, Guangxian; Wei, Li; Yao, Bo; Man, Qiuhong; Sun, Xuedong; Liu, Zhiqing; Song, Zhiwu; Yu, Chengze; Chen, Ying; Luo, Qingliang; Liu, Sugang; Ai, Hui-Sheng

2014-03-01

This is a case report of a 32-year-old man exposed to a total body dose of 14.5 Gy γ-radiation in a lethal (60)Co-source irradiation accident in 2008 in China. Frequent nausea, vomiting and marked neutropenia and lymphopenia were observed from 30 min to 45 h after exposure. HLA-mismatched peripheral blood stem cell transplantation combined with infusion of mesenchymal stem cells was used at Day 7. Rapid hematopoietic recovery, stable donor engraftment and healing of radioactive skin ulceration were achieved during Days 18-36. The patient finally developed intestinal obstruction and died of multi-organ failure on Day 62, although intestinal obstruction was successfully released by emergency bowel resection.

Competencies for Young European Higher Education Graduates: Labor Market Mismatches and Their Payoffs

ERIC Educational Resources Information Center

Garcia-Aracil, Adela; Van der Velden, Rolf

2008-01-01

Labor market rewards based on competencies are analyzed using a sample of young European higher education (HE) graduates. Estimates of monetary rewards are obtained from conventional earnings regressions, while estimates total rewards are based on job satisfaction and derived through ordered probit regressions. Results for income show that jobs…

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

PubMed Central

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

Identification of a permissible HLA mismatch in hematopoietic stem cell transplantation

PubMed Central

Fernandez-Viña, Marcelo A.; Wang, Tao; Lee, Stephanie J.; Haagenson, Michael; Aljurf, Mahmoud; Askar, Medhat; Battiwalla, Minoo; Baxter-Lowe, Lee-Ann; Gajewski, James; Jakubowski, Ann A.; Marino, Susana; Oudshoorn, Machteld; Marsh, Steven G. E.; Petersdorf, Effie W.; Schultz, Kirk; Turner, E. Victoria; Waller, Edmund K.; Woolfrey, Ann; Umejiego, John; Spellman, Stephen R.; Setterholm, Michelle

2014-01-01

In subjects mismatched in the HLA alleles C*03:03/C*03:04 no allogeneic cytotoxic T-lymphocyte responses are detected in vitro. Hematopoietic stem cell transplantation (HSCT) with unrelated donors (UDs) showed no association between the HLA-C allele mismatches (CAMMs) and adverse outcomes; antigen mismatches at this and mismatches other HLA loci are deleterious. The absence of effect of the CAMM may have resulted from the predominance of the mismatch C*03:03/C*03:04. Patients with hematologic malignancies receiving UD HSCT matched in 8/8 and 7/8 HLA alleles were examined. Transplants mismatched in HLA-C antigens or mismatched in HLA-A, -B, or -DRB1 presented significant differences (P < .0001) in mortality (hazard ratio [HR] = 1.37, 1.30), disease-free survival (HR = 1.33, 1.27), treatment-related mortality (HR = 1.54, 1.54), and grade 3-4 acute graft-versus-host disease (HR = 1.49, 1.77) compared with the 8/8 group; transplants mismatched in other CAMMs had similar outcomes with HR ranging from 1.34 to 172 for these endpoints. The C*03:03/C*03:04 mismatched and the 8/8 matched groups had identical outcomes (HR ranging from 0.96-1.05). The previous finding that CAMMs do not associate with adverse outcomes is explained by the predominance (69%) of the mismatch C*03:03/03:04 in this group that is better tolerated than other HLA mismatches. PMID:24408320

Psilocybin disrupts sensory and higher order cognitive processing but not pre-attentive cognitive processing-study on P300 and mismatch negativity in healthy volunteers.

PubMed

Bravermanová, Anna; Viktorinová, Michaela; Tylš, Filip; Novák, Tomáš; Androvičová, Renáta; Korčák, Jakub; Horáček, Jiří; Balíková, Marie; Griškova-Bulanova, Inga; Danielová, Dominika; Vlček, Přemysl; Mohr, Pavel; Brunovský, Martin; Koudelka, Vlastimil; Páleníček, Tomáš

2018-02-01

Disruption of auditory event-related evoked potentials (ERPs) P300 and mismatch negativity (MMN), electrophysiological markers of attentive and pre-attentive cognitive processing, is repeatedly described in psychosis and schizophrenia. Similar findings were observed in a glutamatergic model of psychosis, but the role of serotonergic 5-HT 2A receptors in information processing is less clear. We studied ERPs in a serotonergic model of psychosis, induced by psilocybin, a psychedelic with 5-HT 2A/C agonistic properties, in healthy volunteers. Twenty subjects (10M/10F) were given 0.26 mg/kg of psilocybin orally in a placebo-controlled, double-blind, cross-over design. ERPs (P300, MMN) were registered during the peak of intoxication. Correlations between measured electrophysiological variables and psilocin serum levels and neuropsychological effects were also analyzed. Psilocybin induced robust psychedelic effects and psychotic-like symptoms, decreased P300 amplitude (p = 0.009) but did not affect the MMN. Psilocybin's disruptive effect on P300 correlated with the intensity of the psychedelic state, which was dependent on the psilocin serum levels. We also observed a decrease in N100 amplitude (p = 0.039) in the P300 paradigm and a negative correlation between P300 and MMN amplitude (p = 0.014). Even though pre-attentive cognition (MMN) was not affected, processing at the early perceptual level (N100) and in higher-order cognition (P300) was significantly disrupted by psilocybin. Our results have implications for the role of 5-HT 2A receptors in altered information processing in psychosis and schizophrenia.

Statistical Learning, Syllable Processing, and Speech Production in Healthy Hearing and Hearing-Impaired Preschool Children: A Mismatch Negativity Study.

PubMed

Studer-Eichenberger, Esther; Studer-Eichenberger, Felix; Koenig, Thomas

2016-01-01

The objectives of the present study were to investigate temporal/spectral sound-feature processing in preschool children (4 to 7 years old) with peripheral hearing loss compared with age-matched controls. The results verified the presence of statistical learning, which was diminished in children with hearing impairments (HIs), and elucidated possible perceptual mediators of speech production. Perception and production of the syllables /ba/, /da/, /ta/, and /na/ were recorded in 13 children with normal hearing and 13 children with HI. Perception was assessed physiologically through event-related potentials (ERPs) recorded by EEG in a multifeature mismatch negativity paradigm and behaviorally through a discrimination task. Temporal and spectral features of the ERPs during speech perception were analyzed, and speech production was quantitatively evaluated using speech motor maximum performance tasks. Proximal to stimulus onset, children with HI displayed a difference in map topography, indicating diminished statistical learning. In later ERP components, children with HI exhibited reduced amplitudes in the N2 and early parts of the late disciminative negativity components specifically, which are associated with temporal and spectral control mechanisms. Abnormalities of speech perception were only subtly reflected in speech production, as the lone difference found in speech production studies was a mild delay in regulating speech intensity. In addition to previously reported deficits of sound-feature discriminations, the present study results reflect diminished statistical learning in children with HI, which plays an early and important, but so far neglected, role in phonological processing. Furthermore, the lack of corresponding behavioral abnormalities in speech production implies that impaired perceptual capacities do not necessarily translate into productive deficits.

Universal screening for Lynch syndrome in endometrial cancers: frequency of germline mutations and identification of patients with Lynch-like syndrome.

PubMed

Dillon, Jessica L; Gonzalez, Jorge L; DeMars, Leslie; Bloch, Katarzyna J; Tafe, Laura J

2017-12-01

Lynch syndrome (LS) is an inherited clinical syndrome characterized by a high risk of colorectal, endometrial (lifetime risk of up to 60%), ovarian, and urinary tract cancers. The diagnosis is confirmed by identification of germline mutations in the DNA mismatch repair genes MLH1, PMS2, MSH2, MSH6, or EPCAM. In 2015, our institution implemented universal screening of endometrial cancer (EC) hysterectomy specimens by mismatch repair immunohistochemistry (IHC) with reflex MLH1 promoter hypermethylation analysis for tumors with loss of MLH1/PMS2 expression. Patients with tumors negative for MLH1 methylation and those with a loss of the heterodimer pair MSH2 and MSH6, or isolated loss of either PMS2 or MSH6 were referred to the Familial Cancer Program for genetic counseling and consideration of germline testing. Between May 2015 to Dec 2016, 233 EC patients were screened by IHC for LS with a median age of 63 years. Sixty tumors (27%) had abnormal IHC staining results. Fifty-one (22%) harbored heterodimeric loss of MLH1 and PMS2, 49 of which showed MLH1 promoter methylation (1 failure, 1 negative). One showed loss of MLH1/PMS2 and MSH6, 2 showed loss of MSH2/MSH6, and 6 had isolated loss of MSH6 only. Ten patients underwent genetic counseling, and germline testing was performed in 8; LS was confirmed in 5 patients (2.1%). In addition, 3 patients with negative germline testing and presumed Lynch-like syndrome were identified and offered additional somatic testing. Universal screening for LS in EC patients has yielded positive results for identification of patients at risk for this inherited syndrome. Copyright © 2017 Elsevier Inc. All rights reserved.

A neuroanatomically grounded Hebbian-learning model of attention–language interactions in the human brain

PubMed Central

Garagnani, Max; Wennekers, Thomas; Pulvermüller, Friedemann

2008-01-01

Meaningful familiar stimuli and senseless unknown materials lead to different patterns of brain activation. A late major neurophysiological response indexing ‘sense’ is the negative component of event-related potential peaking at around 400 ms (N400), an event-related potential that emerges in attention-demanding tasks and is larger for senseless materials (e.g. meaningless pseudowords) than for matched meaningful stimuli (words). However, the mismatch negativity (latency 100–250 ms), an early automatic brain response elicited under distraction, is larger to words than to pseudowords, thus exhibiting the opposite pattern to that seen for the N400. So far, no theoretical account has been able to reconcile and explain these findings by means of a single, mechanistic neural model. We implemented a neuroanatomically grounded neural network model of the left perisylvian language cortex and simulated: (i) brain processes of early language acquisition and (ii) cortical responses to familiar word and senseless pseudoword stimuli. We found that variation of the area-specific inhibition (the model correlate of attention) modulated the simulated brain response to words and pseudowords, producing either an N400- or a mismatch negativity-like response depending on the amount of inhibition (i.e. available attentional resources). Our model: (i) provides a unifying explanatory account, at cortical level, of experimental observations that, so far, had not been given a coherent interpretation within a single framework; (ii) demonstrates the viability of purely Hebbian, associative learning in a multilayered neural network architecture; and (iii) makes clear predictions on the effects of attention on latency and magnitude of event-related potentials to lexical items. Such predictions have been confirmed by recent experimental evidence. PMID:18215243

Treatment of acute leukemia with unmanipulated HLA-mismatched/haploidentical blood and bone marrow transplantation.

PubMed

Huang, Xiao-Jun; Liu, Dai-Hong; Liu, Kai-Yan; Xu, Lan-Ping; Chen, Huan; Han, Wei; Chen, Yu-Hong; Zhang, Xiao-Hui; Lu, Dao-Pei

2009-02-01

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains one of the best therapeutic options to cure acute leukemia (AL). However, many patients have no human leukocyte antigen (HLA)-matched donor. Recently, we developed a new method for HLA-mismatched/haploidentical transplantation without in vitro T cell depletion (TCD). This method combined granulocyte-colony stimulating factor (G-CSF)-primed bone marrow and peripheral blood with intensive immunosuppression. We analyzed the outcome of 250 consecutive patients with AL who underwent HLA-mismatched/haploidentical transplantation with 1-3 mismatched loci of HLA-A, B, and DR from family donors via our new transplant protocol. Two hundred forty-nine patients achieved sustained, full donor chimerism. The incidence of grade 2-4 acute graft-versus-host disease (aGVHD) was 45.8%, and that of grades 3 and 4 was 13.4%, which was not associated with the extent of HLA disparity. The cumulative incidence of total chronic GVHD (cGVHD) was 53.9% and that of extensive cGVHD was 22.6% in 217 evaluable patients. One hundred forty-one of the 250 patients survived free of disease recurrence at a median of 1092 days (range: 442-2437 days) of follow-up. Seventeen patients received DLI as a treatment for relapse after transplantation and 7 patients achieved leukemia-free survival (LFS). The 3-year probability of LFS for acute myelogenous leukemia (AML) was 70.7% and 55.9%, and for acute lymphoblastic leukemia (ALL) it was 59.7% and 24.8% in standard-risk and high-risk groups, respectively. Lower LFS were associated with diagnosis of acute leukemia in the high-risk group (P= .001, relative risk [RR], 95% confidence interval [CI]: 2.94[1.535-5.631]) and the occurrence of aGVHD of grades 3 and 4 (P= .004). HLA-mismatched/haploidentical HSCT was feasible with unmanipulated blood and bone marrow harvest.

The structural impact of DNA mismatches

PubMed Central

Rossetti, Giulia; Dans, Pablo D.; Gomez-Pinto, Irene; Ivani, Ivan; Gonzalez, Carlos; Orozco, Modesto

2015-01-01

The structure and dynamics of all the transversion and transition mismatches in three different DNA environments have been characterized by molecular dynamics simulations and NMR spectroscopy. We found that the presence of mismatches produced significant local structural alterations, especially in the case of purine transversions. Mismatched pairs often show promiscuous hydrogen bonding patterns, which interchange among each other in the nanosecond time scale. This therefore defines flexible base pairs, where breathing is frequent, and where distortions in helical parameters are strong, resulting in significant alterations in groove dimension. Even if the DNA structure is plastic enough to absorb the structural impact of the mismatch, local structural changes can be propagated far from the mismatch site, following the expected through-backbone and a previously unknown through-space mechanism. The structural changes related to the presence of mismatches help to understand the different susceptibility of mismatches to the action of repairing proteins. PMID:25820425

Define the Twist-ATX-LPAR1 Signaling Axis in Promoting Obesity Associated Triple Negative Breast Cancer

DTIC Science & Technology

2017-05-01

contain His tags for purification and streptavidin binding peptide tag for detection (Figure 1). In addition, we have applied recently developed CRISPR ...breast cancer cells MDA-MB-578 and SUM-1315, and selected single cell colony with Twist knockout. We chose CRISPR -gRNA over the shRNA system which was...originally proposed, as CRISPR provides higher specificity and fewer off-target effects. To verify knockout of Twist, we first performed mismatch

HLA-DQ Mismatches and Rejection in Kidney Transplant Recipients

PubMed Central

Chapman, Jeremy R.; Coates, Patrick T.; Lewis, Joshua R.; Russ, Graeme R.; Watson, Narelle; Holdsworth, Rhonda; Wong, Germaine

2016-01-01

Background and objectives The current allocation algorithm for deceased donor kidney transplantation takes into consideration HLA mismatches at the ABDR loci but not HLA mismatches at other loci, including HLA-DQ. However, the independent effects of incompatibilities for the closely linked HLA-DQ antigens in the context of HLA-DR antigen matched and mismatched allografts are uncertain. We aimed to determine the effect of HLA-DQ mismatches on renal allograft outcomes. Design, setting, participants, & measurements Using data from the Australia and New Zealand Dialysis and Transplant Registry, we examined the association between HLA-DQ mismatches and acute rejections in primary live and deceased donor kidney transplant recipients between 2004 and 2012 using adjusted Cox regression models. Results Of the 788 recipients followed for a median of 2.8 years (resulting in 2891 person-years), 321 (40.7%) and 467 (59.3%) received zero and one or two HLA-DQ mismatched kidneys, respectively. Compared with recipients who have received zero HLA-DQ mismatched kidneys, those who have received one or two HLA-DQ mismatched kidneys experienced greater numbers of any rejection (50 of 321 versus 117 of 467; P<0.01), late rejections (occurring >6 months post-transplant; 8 of 321 versus 27 of 467; P=0.03), and antibody-mediated rejections (AMRs; 12 of 321 versus 38 of 467; P=0.01). Compared with recipients of zero HLA-DQ mismatched kidneys, the adjusted hazard ratios for any and late rejections in recipients who had received one or two HLA-DQ mismatched kidneys were 1.54 (95% confidence interval [95% CI], 1.08 to 2.19) and 2.85 (95% CI, 1.05 to 7.75), respectively. HLA-DR was an effect modifier between HLA-DQ mismatches and AMR (P value for interaction =0.02), such that the association between HLA-DQ mismatches and AMR was statistically significant in those who have received one or two HLA-DR mismatched kidneys, with adjusted hazard ratio of 2.50 (95% CI, 1.05 to 5.94). Conclusions HLA-DQ mismatches are associated with acute rejection, independent of HLA-ABDR mismatches and initial immunosuppression. Clinicians should be aware of the potential importance of HLA-DQ matching in the assessment of immunologic risk in kidney transplant recipients. PMID:27034399

Match between classroom dimensions and students' anthropometry: re-equipment according to European educational furniture standard.

PubMed

Macedo, Angela C; Morais, André V; Martins, Henriqueta F; Martins, João C; Pais, Silvina M; Mayan, Olga S

2015-02-01

The aim of this study was to investigate mismatch between students and classroom furniture dimensions and evaluate the improvement in implementing the European furniture standard. In Portugal, school furniture does not meet any national ergonomic criteria, so it cannot fit students' anthropometric measures. A total of 893 students belonging to third (7th through 9th grades) and secondary (10th through 12th grades) cycles participated in the study. Anthropometric measurements of the students were gathered in several physical education classes. The furniture dimensions were measured for two models of tables and seats. Several two-way equations for match criteria based on published studies were applied to data. The percentage of students who match with classroom furniture dimensions is low (24% and 44% between table and students, 4% and 9% between seat and students at 7th and 12th grades, respectively). Table is high for the third cycle, seat is high for both cycles, and seat depth fits well to students. No significant relationship was found between ergonomic mismatch and prevalence of pain. For each cycle, at least two different sizes indicated in the European standard should be available to students, considering the large variability in body dimensions within each cycle. The match criteria used gives a large percentage of students without pain in a mismatch situation. Future measures applying to secondary schools should revise the decision of selecting a single size of classroom furniture and improve the implementation of the European standard. New criteria for ergonomic mismatch are needed that more closely model the responses about discomfort/pain.

Negative-pressure-induced enhancement in a freestanding ferroelectric

NASA Astrophysics Data System (ADS)

Wang, Jin; Wylie-van Eerd, Ben; Sluka, Tomas; Sandu, Cosmin; Cantoni, Marco; Wei, Xian-Kui; Kvasov, Alexander; McGilly, Leo John; Gemeiner, Pascale; Dkhil, Brahim; Tagantsev, Alexander; Trodahl, Joe; Setter, Nava

2015-10-01

Ferroelectrics are widespread in technology, being used in electronics and communications, medical diagnostics and industrial automation. However, extension of their operational temperature range and useful properties is desired. Recent developments have exploited ultrathin epitaxial films on lattice-mismatched substrates, imposing tensile or compressive biaxial strain, to enhance ferroelectric properties. Much larger hydrostatic compression can be achieved by diamond anvil cells, but hydrostatic tensile stress is regarded as unachievable. Theory and ab initio treatments predict enhanced properties for perovskite ferroelectrics under hydrostatic tensile stress. Here we report negative-pressure-driven enhancement of the tetragonality, Curie temperature and spontaneous polarization in freestanding PbTiO3 nanowires, driven by stress that develops during transformation of the material from a lower-density crystal structure to the perovskite phase. This study suggests a simple route to obtain negative pressure in other materials, potentially extending their exploitable properties beyond their present levels.

Measuring strand discontinuity-directed mismatch repair in yeast Saccharomyces cerevisiae by cell-free nuclear extracts.

PubMed

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.

The Spatial Relationship between Apparent Diffusion Coefficient and Standardized Uptake Value of 18F-Fluorodeoxyglucose Has a Crucial Influence on the Numeric Correlation of Both Parameters in PET/MRI of Lung Tumors

PubMed Central

Stieltjes, Bram; Weikert, Thomas; Gatidis, Sergios; Wiese, Mark; Wild, Damian; Lardinois, Didier

2017-01-01

The minimum apparent diffusion coefficient (ADCmin) derived from diffusion-weighted MRI (DW-MRI) and the maximum standardized uptake value (SUVmax) of FDG-PET are markers of aggressiveness in lung cancer. The numeric correlation of the two parameters has been extensively studied, but their spatial interplay is not well understood. After FDG-PET and DW-MRI coregistration, values and location of ADCmin- and SUVmax-voxels were analyzed. The upper limit of the 95% confidence interval for registration accuracy of sequential PET/MRI was 12 mm, and the mean distance (D) between ADCmin- and SUVmax-voxels was 14.0 mm (average of two readers). Spatial mismatch (D > 12 mm) between ADCmin and SUVmax was found in 9/25 patients. A considerable number of mismatch cases (65%) was also seen in a control group that underwent simultaneous PET/MRI. In the entire patient cohort, no statistically significant correlation between SUVmax and ADCmin was seen, while a moderate negative linear relationship (r = −0.5) between SUVmax and ADCmin was observed in tumors with a spatial match (D ≤ 12 mm). In conclusion, spatial mismatch between ADCmin and SUVmax is found in a considerable percentage of patients. The spatial connection of the two parameters SUVmax and ADCmin has a crucial influence on their numeric correlation. PMID:29391862

Innovative look at dairy heifer rearing: Effect of prenatal and post-natal environment on later performance.

PubMed

Van Eetvelde, M; Opsomer, G

2017-08-01

As heifer rearing is a costly investment, dairy farmers have been stimulated to maximize early growth of their calves, mainly by enhanced liquid feeding. However, the long-term effects of this "accelerated growth" are largely unknown. Studies recently performed at Ghent University indicate that in dairy cattle, certain maternal factors (such as young age and high milk yield) and environmental factors (such as high ambient temperatures) create a suboptimal environment for the developing foetus, altering the phenotype of the newborn calf. According to the "thrifty phenotype hypothesis," these metabolic alterations prepare the newborn for similar ("matching") conditions after birth, enhancing its survival during periods of limited feeding. Yet, when an abundance of nutrients is available in post-natal life (e.g., during periods of enhanced feeding), the "mismatch" between pre- and post-natal environment results in an early catch-up growth, with potential negative consequences. The aim of the article was to discuss this mismatch between pre- and post-natal environment in dairy calves. Previous studies, especially in human medicine, have shown catch-up growth to be associated with obesity, fertility problems, metabolic diseases and a reduced lifespan. Hence, we hypothesize that, by applying programs of accelerated growth, our current management system accentuates the mismatch between the pre- and post-natal environment in dairy calves. We can conclude that, although more research is necessary, the current findings point towards a more individual approach when rearing dairy heifers. © 2017 Blackwell Verlag GmbH.

Gold nanoparticle enhanced fluorescence anisotropy for the assay of single nucleotide polymorphisms (SNPs) based on toehold-mediated strand-displacement reaction.

PubMed

Wang, Xinyi; Zou, Mingjian; Huang, Hongduan; Ren, Yuqian; Li, Limei; Yang, Xiaoda; Li, Na

2013-03-15

We developed a highly differentiating, homogeneous gold nanoparticle (AuNP) enhanced fluorescence anisotropic method for single nucleotide polymorphism (SNP) detection at nanomolar level using toehold-mediated strand-displacement reaction. The template strand, containing a toehold domain with an allele-specific site, was immobilized on the surface of AuNPs, and the solution fluorescence anisotropy was markedly enhanced when the fluorescein-labeled blocking DNA was attached to the AuNP via hybridization. Strand-displacement by the target ssDNA strand resulted in detachment of fluorescein-labeled DNA from AuNPs, and thus decreased fluorescence anisotropy. The drastic kinetic difference in strand-displacement from toehold design was used to distinguish between the perfectly matched and the single-base mismatched strands. Free energy changes were calculated to elucidate the dependence of the differentiation ability on the mutation site in the toehold region. A solid negative signal change can be obtained for single-base mismatched strand in the dynamic range of the calibration curve, and a more than 10-fold signal difference can still be observed in a mixed solution containing 100 times the single-base mismatched strand, indicating the good specificity of the method. This proposed method can be performed with a standard spectrofluorimeter in a homogeneous and cost-effective manner, and has the potential to be extended to the application of fluorescence anisotropy method of SNP detection. Copyright © 2012 Elsevier B.V. All rights reserved.

The Spatial Relationship between Apparent Diffusion Coefficient and Standardized Uptake Value of 18F-Fluorodeoxyglucose Has a Crucial Influence on the Numeric Correlation of Both Parameters in PET/MRI of Lung Tumors.

PubMed

Sauter, Alexander W; Stieltjes, Bram; Weikert, Thomas; Gatidis, Sergios; Wiese, Mark; Klarhöfer, Markus; Wild, Damian; Lardinois, Didier; Bremerich, Jens; Sommer, Gregor

2017-01-01

The minimum apparent diffusion coefficient (ADC min ) derived from diffusion-weighted MRI (DW-MRI) and the maximum standardized uptake value (SUV max ) of FDG-PET are markers of aggressiveness in lung cancer. The numeric correlation of the two parameters has been extensively studied, but their spatial interplay is not well understood. After FDG-PET and DW-MRI coregistration, values and location of ADC min - and SUV max -voxels were analyzed. The upper limit of the 95% confidence interval for registration accuracy of sequential PET/MRI was 12 mm, and the mean distance ( D ) between ADC min - and SUV max -voxels was 14.0 mm (average of two readers). Spatial mismatch ( D > 12 mm) between ADC min and SUV max was found in 9/25 patients. A considerable number of mismatch cases (65%) was also seen in a control group that underwent simultaneous PET/MRI. In the entire patient cohort, no statistically significant correlation between SUV max and ADC min was seen, while a moderate negative linear relationship ( r = -0.5) between SUV max and ADC min was observed in tumors with a spatial match ( D ≤ 12 mm). In conclusion, spatial mismatch between ADC min and SUV max is found in a considerable percentage of patients. The spatial connection of the two parameters SUV max and ADC min has a crucial influence on their numeric correlation.

Involvement of the human midbrain and thalamus in auditory deviance detection.

PubMed

Cacciaglia, Raffaele; Escera, Carles; Slabu, Lavinia; Grimm, Sabine; Sanjuán, Ana; Ventura-Campos, Noelia; Ávila, César

2015-02-01

Prompt detection of unexpected changes in the sensory environment is critical for survival. In the auditory domain, the occurrence of a rare stimulus triggers a cascade of neurophysiological events spanning over multiple time-scales. Besides the role of the mismatch negativity (MMN), whose cortical generators are located in supratemporal areas, cumulative evidence suggests that violations of auditory regularities can be detected earlier and lower in the auditory hierarchy. Recent human scalp recordings have shown signatures of auditory mismatch responses at shorter latencies than those of the MMN. Moreover, animal single-unit recordings have demonstrated that rare stimulus changes cause a release from stimulus-specific adaptation in neurons of the primary auditory cortex, the medial geniculate body (MGB), and the inferior colliculus (IC). Although these data suggest that change detection is a pervasive property of the auditory system which may reside upstream cortical sites, direct evidence for the involvement of subcortical stages in the human auditory novelty system is lacking. Using event-related functional magnetic resonance imaging during a frequency oddball paradigm, we here report that auditory deviance detection occurs in the MGB and the IC of healthy human participants. By implementing a random condition controlling for neural refractoriness effects, we show that auditory change detection in these subcortical stations involves the encoding of statistical regularities from the acoustic input. These results provide the first direct evidence of the existence of multiple mismatch detectors nested at different levels along the human ascending auditory pathway. Copyright © 2015 Elsevier Ltd. 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

PubMed Central

2017-01-01

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. PMID:28910418

Saccharomyces cerevisiae MSH2-MSH3 and MSH2-MSH6 complexes display distinct requirements for DNA binding Domain I in mismatch recognition.

PubMed Central

Lee, Susan D.; Surtees, Jennifer A.; Alani, Eric

2007-01-01

In eukaryotic mismatch repair (MMR) MSH2-MSH6 initiates the repair of base-base and small insertion/deletion mismatches while MSH2-MSH3 repairs larger insertion/deletion mismatches. In this study we showed that the msh2Δ1 mutation, containing a complete deletion of the conserved mismatch recognition Domain I of MSH2, conferred a separation of function phenotype with respect to MSH2-MSH3 and MSH2-MSH6 functions. Strains bearing the msh2Δ1 mutation were nearly wild-type in MSH2-MSH6-mediated MMR and in suppressing recombination between DNA sequences predicted to form mismatches recognized by MSH2-MSH6. However, these strains were completely defective in MSH2-MSH3-mediated MMR and recombination functions. This information encouraged us to analyze the contributions of Domain I to the mismatch binding specificity of MSH2-MSH3 in genetic and biochemical assays. We found that Domain I in MSH2 contributed a non-specific DNA binding activity while Domain I of MSH3 appeared important for mismatch binding specificity and for suppressing non-specific DNA-binding. These observations reveal distinct requirements for the MSH2 DNA binding Domain I in the repair of DNA mismatches and suggest that the binding of MSH2-MSH3 to mismatch DNA involves protein-DNA contacts that appear very different from those required for MSH2-MSH6 mismatch binding. PMID:17157869

Saccharomyces cerevisiae MSH2-MSH3 and MSH2-MSH6 complexes display distinct requirements for DNA binding domain I in mismatch recognition.

PubMed

Lee, Susan D; Surtees, Jennifer A; Alani, Eric

2007-02-09

In eukaryotic mismatch repair (MMR) MSH2-MSH6 initiates the repair of base-base and small insertion/deletion mismatches while MSH2-MSH3 repairs larger insertion/deletion mismatches. Here, we show that the msh2Delta1 mutation, containing a complete deletion of the conserved mismatch recognition domain I of MSH2, conferred a separation of function phenotype with respect to MSH2-MSH3 and MSH2-MSH6 functions. Strains bearing the msh2Delta1 mutation were nearly wild-type in MSH2-MSH6-mediated MMR and in suppressing recombination between DNA sequences predicted to form mismatches recognized by MSH2-MSH6. However, these strains were completely defective in MSH2-MSH3-mediated MMR and recombination functions. This information encouraged us to analyze the contributions of domain I to the mismatch binding specificity of MSH2-MSH3 in genetic and biochemical assays. We found that domain I in MSH2 contributed a non-specific DNA binding activity while domain I of MSH3 appeared important for mismatch binding specificity and for suppressing non-specific DNA binding. These observations reveal distinct requirements for the MSH2 DNA binding domain I in the repair of DNA mismatches and suggest that the binding of MSH2-MSH3 to mismatch DNA involves protein-DNA contacts that appear very different from those required for MSH2-MSH6 mismatch binding.

Binding of insertion/deletion DNA mismatches by the heterodimer of yeast mismatch repair proteins MSH2 and MSH3.

PubMed

Habraken, Y; Sung, P; Prakash, L; Prakash, S

1996-09-01

DNA-mismatch repair removes mismatches from the newly replicated DNA strand. In humans, mutations in the mismatch repair genes hMSH2, hMLH1, hPMS1 and hPMS2 result in hereditary non-polyposis colorectal cancer (HNPCC) [1-8]. The hMSH2 (MSH for MutS homologue) protein forms a complex with a 160 kDa protein, and this heterodimer, hMutSalpha, has high affinity for a G/T mismatch [9,10]. Cell lines in which the 160 kDa subunit of hMutSalpha is mutated are specifically defective in the repair of base-base and single-nucleotide insertion/deletion mismatches [9,11]. Genetic studies in S. cerevisiae have suggested that MSH2 functions with either MSH3 or MSH6 in mismatch repair, and, in the absence of the latter two genes, MSH2 is inactive [12,13]. MSH6 encodes the yeast counterpart of the 160 kDa subunit of hMutSalpha [12,13]. As in humans, yeast MSH6 forms a complex with MSH2, and the MSH2-MSH6 heterodimer binds a G/T mismatch [14]. Here, we find that MSH2 and MSH3 form another stable heterodimer, and we purify this heterodimer to near homogeneity. We show that MSH2-MSH3 has low affinity for a G/T mismatch but binds to insertion/deletion mismatches with high specificity, unlike MSH2-MSH6.

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

PubMed

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

2017-04-01

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

[Impact of HLA mismatch on transplant outcomes].

PubMed

Kanda, Junya

Human leukocyte antigen (HLA) mismatch increases the risk of severe graft-versus-host disease (GVHD) and transplant-related mortality. However, the variety of stem cell sources such as cord blood units or the improvements in GVHD prophylaxis makes the interpretation of HLA mismatch more complex. In unrelated transplantation, the locus of HLA mismatch has a great impact on the donor candidate selection, whereas in related transplantation, it has an impact on the intensity of GVHD prophylaxis because donor availability is limited. Anti-thymocyte globulin and post-transplant cyclophosphamide are attractive GVHD prophylactic agents to reduce the risk of immune-associated complications in HLA-mismatched transplantations. HLA mismatch has a reduced impact in adult cord blood transplantation. In this review article, the impact of HLA mismatch based on graft sources is discussed.

Gender Matches in Liver Transplant Allocation: Matched and Mismatched Male-Female Donor-Recipient Combinations; Long-term Follow-up of More Than 2000 Patients at a Single Center.

PubMed

Schoening, Wenzel N; Helbig, Michael; Buescher, Niklas; Andreou, Andreas; Bahra, Marcus; Schmitz, Volker; Pascher, Andreas; Pratschke, Johann; Seehofer, Daniel

2016-04-01

The influence of donor-recipient sex mismatches on long-term graft survival after liver transplant is controversial. In this study, our aim was to characterize the differences in long-term graft outcome after liver transplant in more than 2000 cases with special regard to sex match and mismatch. In this retrospective, single center study of 2144 adult primary liver transplant recipients (median follow-up of 92 months), we analyzed specific long-term graft survival and the effect of different donor and recipient sex combinations (Kaplan-Meier, multivariate regression). In the 15-year follow-up, female recipients (58.6%) had significantly better graft survival than male recipients did (51.6%, P = .031). Matched and mismatched male-female combinations revealed significant differences (P = .003): a male donor-female recipient combination showed the best 15-year graft survival (61.1%), and a female donor-male recipient combination showed the worst graft survival (48.6%), whereas male-male (53.3%) and female-female combinations (55.6%) were not significantly different (P = .967). Donor age (P ≤ .0001), body mass index (P = .021), female sex (P = .015), Eurotransplant Donor Risk Index > 1.4 (P ≤ .001), recipients' age (P < .0001), indication for liver transplant (P < .0001), and kidney function (P = .003) significantly affected graft survival. In the multivariate analysis model, a Eurotransplant Donor Risk Index > 1.4 and impaired kidney function at liver transplant again emerged as significant negative predictors. Female donors and male recipients showed significantly more unfavorable characteristics concerning long-term graft survival. The impressive long-term graft survival benefit of male donor-female recipient versus female donor-male recipient and of male donor-female recipient versus matched groups (male-male, female-female) in liver transplant may be caused by significant differences in donor quality and recipient characteristics and may not be related to sex itself.

Single-base-pair discrimination of terminal mismatches by using oligonucleotide microarrays and neural network analyses

NASA Technical Reports Server (NTRS)

Urakawa, Hidetoshi; Noble, Peter A.; El Fantroussi, Said; Kelly, John J.; Stahl, David A.

2002-01-01

The effects of single-base-pair near-terminal and terminal mismatches on the dissociation temperature (T(d)) and signal intensity of short DNA duplexes were determined by using oligonucleotide microarrays and neural network (NN) analyses. Two perfect-match probes and 29 probes having a single-base-pair mismatch at positions 1 to 5 from the 5' terminus of the probe were designed to target one of two short sequences representing 16S rRNA. Nonequilibrium dissociation rates (i.e., melting profiles) of all probe-target duplexes were determined simultaneously. Analysis of variance revealed that position of the mismatch, type of mismatch, and formamide concentration significantly affected the T(d) and signal intensity. Increasing the concentration of formamide in the washing buffer decreased the T(d) and signal intensity, and it decreased the variability of the signal. Although T(d)s of probe-target duplexes with mismatches in the first or second position were not significantly different from one another, duplexes with mismatches in the third to fifth positions had significantly lower T(d)s than those with mismatches in the first or second position. The trained NNs predicted the T(d) with high accuracies (R(2) = 0.93). However, the NNs predicted the signal intensity only moderately accurately (R(2) = 0.67), presumably due to increased noise in the signal intensity at low formamide concentrations. Sensitivity analysis revealed that the concentration of formamide explained most (75%) of the variability in T(d)s, followed by position of the mismatch (19%) and type of mismatch (6%). The results suggest that position of the mismatch at or near the 5' terminus plays a greater role in determining the T(d) and signal intensity of duplexes than the type of mismatch.

The capacity to cope with climate warming declines from temperate to tropical latitudes in two widely distributed Eucalyptus species.

PubMed

Drake, John E; Aspinwall, Michael J; Pfautsch, Sebastian; Rymer, Paul D; Reich, Peter B; Smith, Renee A; Crous, Kristine Y; Tissue, David T; Ghannoum, Oula; Tjoelker, Mark G

2015-01-01

As rapid climate warming creates a mismatch between forest trees and their home environment, the ability of trees to cope with warming depends on their capacity to physiologically adjust to higher temperatures. In widespread species, individual trees in cooler home climates are hypothesized to more successfully acclimate to warming than their counterparts in warmer climates that may approach thermal limits. We tested this prediction with a climate-shift experiment in widely distributed Eucalyptus tereticornis and E. grandis using provenances originating along a ~2500 km latitudinal transect (15.5-38.0°S) in eastern Australia. We grew 21 provenances in conditions approximating summer temperatures at seed origin and warmed temperatures (+3.5 °C) using a series of climate-controlled glasshouse bays. The effects of +3.5 °C warming strongly depended on home climate. Cool-origin provenances responded to warming through an increase in photosynthetic capacity and total leaf area, leading to enhanced growth of 20-60%. Warm-origin provenances, however, responded to warming through a reduction in photosynthetic capacity and total leaf area, leading to reduced growth of approximately 10%. These results suggest that there is predictable intraspecific variation in the capacity of trees to respond to warming; cool-origin taxa are likely to benefit from warming, while warm-origin taxa may be negatively affected. © 2014 John Wiley & Sons Ltd.

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

PubMed

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.

Rapid Extraction of Lexical Tone Phonology in Chinese Characters: A Visual Mismatch Negativity Study

PubMed Central

Wang, Xiao-Dong; Liu, A-Ping; Wu, Yin-Yuan; Wang, Peng

2013-01-01

Background In alphabetic languages, emerging evidence from behavioral and neuroimaging studies shows the rapid and automatic activation of phonological information in visual word recognition. In the mapping from orthography to phonology, unlike most alphabetic languages in which there is a natural correspondence between the visual and phonological forms, in logographic Chinese, the mapping between visual and phonological forms is rather arbitrary and depends on learning and experience. The issue of whether the phonological information is rapidly and automatically extracted in Chinese characters by the brain has not yet been thoroughly addressed. Methodology/Principal Findings We continuously presented Chinese characters differing in orthography and meaning to adult native Mandarin Chinese speakers to construct a constant varying visual stream. In the stream, most stimuli were homophones of Chinese characters: The phonological features embedded in these visual characters were the same, including consonants, vowels and the lexical tone. Occasionally, the rule of phonology was randomly violated by characters whose phonological features differed in the lexical tone. Conclusions/Significance We showed that the violation of the lexical tone phonology evoked an early, robust visual response, as revealed by whole-head electrical recordings of the visual mismatch negativity (vMMN), indicating the rapid extraction of phonological information embedded in Chinese characters. Source analysis revealed that the vMMN was involved in neural activations of the visual cortex, suggesting that the visual sensory memory is sensitive to phonological information embedded in visual words at an early processing stage. PMID:23437235

Alteration of Duration Mismatch Negativity Induced by Transcranial Magnetic Stimulation Over the Left Parietal Lobe.

PubMed

Oshima, Hirokazu; Shiga, Tetsuya; Niwa, Shin-Ichi; Enomoto, Hiroyuki; Ugawa, Yoshikazu; Yabe, Hirooki

2017-01-01

Mismatch negativity (MMN) is generated by a comparison between an incoming sound and the memory trace of preceding sounds stored in sensory memory without any attention to the sound. N100 (N1) is associated with the afferent response to sound onset and reflects early analysis of stimulus characteristics. MMN generators are present in the temporal and frontal lobe, and N1 generators are present in the temporal lobe. The parietal lobe is involved in MMN generation elicited by a change in duration. The anatomical network connecting these areas, lateralization, and the effect of the side of ear stimulation on MMN remain unknown. Thus, we studied the effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) over the left parietal lobe on MMN and N1 in 10 healthy subjects. Low-frequency rTMS over the left parietal lobe decreased the amplitude of MMN following right ear sound stimulation, but the amplitude was unaffected with left ear sound stimulation. We observed no significant changes in the amplitude of N1 or the latency of MMN or N1. These results suggest that low-frequency rTMS over the left parietal lobe modulates the detection of early auditory changes in duration in healthy subjects. Stimulation that is contralateral to the side of the ear experiencing sound may affect the generation of duration MMN more than ipsilateral stimulation. © EEG and Clinical Neuroscience Society (ECNS) 2016.

Mismatch negativity as a potential neurobiological marker of early-stage Alzheimer disease and vascular dementia.

PubMed

Jiang, Shixiang; Yan, Chang; Qiao, Zhengxue; Yao, Haiqian; Jiang, Shiquan; Qiu, Xiaohui; Yang, Xiuxian; Fang, Deyu; Yang, Yanjie; Zhang, Limei; Wang, Lina; Zhang, Liming

2017-04-24

Alzheimer's disease (AD) and vascular dementia (VD) are serious, irreversible forms of cognitive impairment, which means that an early diagnosis is essential to slow down their progression. One potential neurophysiological biomarker of these diseases is the mismatch negativity (MMN) event-related potentials (ERP) component, which reflects an automatic detection mechanism at the pre-attentive stages of information processing. We evaluated the auditory MMN response in individuals from two patient groups: those in the prodromal stages of AD (P-AD) and those in the prodromal stages of VD (P-VD). Thirty patients (15 P-AD patients and 15 P-VD patients) and 30 age-matched controls were recruited to undergo electrophysiological recordings during the presentation of an auditory deviant-standard-reverse oddball paradigm that was used to elicit genuine MMN responses. We show that over the frontal-central area, the mean amplitude of the MMN was significantly reduced in both the P-AD (p=0.017) and P-VD groups (p=0.013) compared with controls. The MMN peak latency in P-VD patients was significantly shorter than in controls (p=0.027). No MMN response differences between the P-AD and P-VD were found in either the frontal-central or the temporal areas. These results indicate that P-AD and P-VD patients exhibit impaired pre-attentive information processing mechanisms as revealed by the frontal-central area MMN response, which is associated with sensory memory and cognitive deficits. Copyright © 2017 Elsevier B.V. All rights reserved.

Multisensory integration of speech sounds with letters vs. visual speech: only visual speech induces the mismatch negativity.

PubMed

Stekelenburg, Jeroen J; Keetels, Mirjam; Vroomen, Jean

2018-05-01

Numerous studies have demonstrated that the vision of lip movements can alter the perception of auditory speech syllables (McGurk effect). While there is ample evidence for integration of text and auditory speech, there are only a few studies on the orthographic equivalent of the McGurk effect. Here, we examined whether written text, like visual speech, can induce an illusory change in the perception of speech sounds on both the behavioural and neural levels. In a sound categorization task, we found that both text and visual speech changed the identity of speech sounds from an /aba/-/ada/ continuum, but the size of this audiovisual effect was considerably smaller for text than visual speech. To examine at which level in the information processing hierarchy these multisensory interactions occur, we recorded electroencephalography in an audiovisual mismatch negativity (MMN, a component of the event-related potential reflecting preattentive auditory change detection) paradigm in which deviant text or visual speech was used to induce an illusory change in a sequence of ambiguous sounds halfway between /aba/ and /ada/. We found that only deviant visual speech induced an MMN, but not deviant text, which induced a late P3-like positive potential. These results demonstrate that text has much weaker effects on sound processing than visual speech does, possibly because text has different biological roots than visual speech. © 2018 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

First-impression bias effects on mismatch negativity to auditory spatial deviants.

PubMed

Fitzgerald, Kaitlin; Provost, Alexander; Todd, Juanita

2018-04-01

Internal models of regularities in the world serve to facilitate perception as redundant input can be predicted and neural resources conserved for that which is new or unexpected. In the auditory system, this is reflected in an evoked potential component known as mismatch negativity (MMN). MMN is elicited by the violation of an established regularity to signal the inaccuracy of the current model and direct resources to the unexpected event. Prevailing accounts suggest that MMN amplitude will increase with stability in regularity; however, observations of first-impression bias contradict stability effects. If tones rotate probabilities as a rare deviant (p = .125) and common standard (p = .875), MMN elicited to the initial deviant tone reaches maximal amplitude faster than MMN to the first standard when later encountered as deviant-a differential pattern that persists throughout rotations. Sensory inference is therefore biased by longer-term contextual information beyond local probability statistics. Using the same multicontext sequence structure, we examined whether this bias generalizes to MMN elicited by spatial sound cues using monaural sounds (n = 19, right first deviant and n = 22, left first deviant) and binaural sounds (n = 19, right first deviant). The characteristic differential modulation of MMN to the two tones was observed in two of three groups, providing partial support for the generalization of first-impression bias to spatially deviant sounds. We discuss possible explanations for its absence when the initial deviant was delivered monaurally to the right ear. © 2017 Society for Psychophysiological Research.

Unaccusative Mismatches in Japanese.

ERIC Educational Resources Information Center

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.…

Educational Mismatch and Self-Employment

ERIC Educational Resources Information Center

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…

Application of failure mode and effect analysis in an assisted reproduction technology laboratory.

PubMed

Intra, Giulia; Alteri, Alessandra; Corti, Laura; Rabellotti, Elisa; Papaleo, Enrico; Restelli, Liliana; Biondo, Stefania; Garancini, Maria Paola; Candiani, Massimo; Viganò, Paola

2016-08-01

Assisted reproduction technology laboratories have a very high degree of complexity. Mismatches of gametes or embryos can occur, with catastrophic consequences for patients. To minimize the risk of error, a multi-institutional working group applied failure mode and effects analysis (FMEA) to each critical activity/step as a method of risk assessment. This analysis led to the identification of the potential failure modes, together with their causes and effects, using the risk priority number (RPN) scoring system. In total, 11 individual steps and 68 different potential failure modes were identified. The highest ranked failure modes, with an RPN score of 25, encompassed 17 failures and pertained to "patient mismatch" and "biological sample mismatch". The maximum reduction in risk, with RPN reduced from 25 to 5, was mostly related to the introduction of witnessing. The critical failure modes in sample processing were improved by 50% in the RPN by focusing on staff training. Three indicators of FMEA success, based on technical skill, competence and traceability, have been evaluated after FMEA implementation. Witnessing by a second human operator should be introduced in the laboratory to avoid sample mix-ups. These findings confirm that FMEA can effectively reduce errors in assisted reproduction technology laboratories. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Viral fusion efficacy of specific H3N2 influenza virus reassortant combinations at single-particle level

NASA Astrophysics Data System (ADS)

Hsu, Hung-Lun; Millet, Jean K.; Costello, Deirdre A.; Whittaker, Gary R.; Daniel, Susan

2016-10-01

Virus pseudotyping is a useful and safe technique for studying entry of emerging strains of influenza virus. However, few studies have compared different reassortant combinations in pseudoparticle systems, or compared entry kinetics of native viruses and their pseudotyped analogs. Here, vesicular stomatitis virus (VSV)-based pseudovirions displaying distinct influenza virus envelope proteins were tested for fusion activity. We produced VSV pseudotypes containing the prototypical X-31 (H3) HA, either alone or with strain-matched or mismatched N2 NAs. We performed single-particle fusion assays using total internal reflection fluorescence microscopy to compare hemifusion kinetics among these pairings. Results illustrate that matching pseudoparticles behaved very similarly to native virus. Pseudoparticles harboring mismatched HA-NA pairings fuse at significantly slower rates than native virus, and NA-lacking pseudoparticles exhibiting the slowest fusion rates. Relative viral membrane HA density of matching pseudoparticles was higher than in mismatching or NA-lacking pseudoparticles. An equivalent trend of HA expression level on cell membranes of HA/NA co-transfected cells was observed and intracellular trafficking of HA was affected by NA co-expression. Overall, we show that specific influenza HA-NA combinations can profoundly affect the critical role played by HA during entry, which may factor into viral fitness and the emergence of new pandemic influenza viruses.

Detection of single base mismatches of thymine and cytosine residues by potassium permanganate and hydroxylamine in the presence of tetralkylammonium salts.

PubMed Central

Gogos, J A; Karayiorgou, M; Aburatani, H; Kafatos, F C

1990-01-01

In the presence of tetramethylammonium chloride, potassium permanganate specifically modifies mismatched thymines. Similarly, the modification of mismatched cytosines by hydroxylamine was enhanced by tetraethylammonium chloride. Modification followed by piperidine cleavage permits specific identification of the T and C mismatches and by extension, when the opposite DNA strand is analyzed, of A and G mismatches as well. These reactions can be performed conveniently with DNA immobilized on Hybond M-G paper. We describe conditions that exploit these reactions to detect mismatches, e.g. point mutations or genetic polymorphisms, using either synthetic oligonucleotide probes or PCR amplification of specific genomic DNA sequences. Images PMID:2263445

Natural rubber latex skin testing reagents: safety and diagnostic accuracy of nonammoniated latex, ammoniated latex, and latex rubber glove extracts.

PubMed

Hamilton, R G; Adkinson, N F

1996-11-01

Nonammoniated latex, ammoniated latex, and rubber glove extracts are the only sources of natural rubber (Hevea brasiliensis) latex that have potential for use as skin testing reagents in the diagnosis of latex allergy. Their diagnostic sensitivity and specificity as skin test reagents are unknown. We conducted a phase 1/2 clinical study to examine the safety and diagnostic accuracy (sensitivity and specificity) of nonammoniated latex, ammoniated latex, and rubber glove extracts as skin test extracts to identify the most efficacious source material for future skin test reagent development. Twenty-four adults not allergic to latex, 19 adults with hand dermatitis or pruritus, and 59 adults with a latex allergy were identified by clinical history. All provided blood and then received puncture skin tests and intradermal skin tests with nonammoniated latex, ammoniated latex, and rubber glove extracts from Malaysian H. brasiliensis latex by use of sequential titration. A glove provocation test and IgE anti-latex RAST were used to clarify positive history-negative skin test response and negative history-positive skin test response mismatches. All three extracts were biologically safe and sterile. After normalization to 1 mg/ml of total protein, all three extracts produced equivalent diagnostic sensitivity and specificity in puncture skin tests and intradermal skin tests at various extract concentrations. Optimal diagnostic accuracy was safely achieved at 100 micrograms/ml for intradermal skin tests (e.g., nonammoniated latex: puncture skin test sensitivity 96%, specificity 100%; intradermal skin test sensitivity 93%, specificity 96%). The presence of IgE antibody in skin was highly correlated with IgE anti-latex in serum (nonammoniated latex: r = 0.98, p < 0.001; ammoniated latex: r = 0.94, p < 0.001; rubber glove extract: r = 0.96, p < 0.001). All five available subjects with a positive history, negative skin test response, and absence of IgE antibody in serum had a negative glove provocation test response, indicating no clinical evidence of latex allergy. No systemic or large local allergic reactions were observed with puncture skin tests or intradermal skin tests. Equivalent diagnostic sensitivity and specificity were observed with the nonammoniated latex, ammoniated latex, and rubber glove extract skin test reagents after normalization for total protein; nonammoniated latex may be considered the reagent of choice on the basis of practical quality control and reproducibility considerations.

Technique to measure wavenumber mismatch between quadratically interacting modes

NASA Astrophysics Data System (ADS)

Hajj, M. R.; Davila, J. B.; Miksad, R. W.; Powers, E. J.

1995-02-01

Nonlinear energy cascade by means of three-wave resonant interactions is a characteristic feature of transitioning and turbulent flows. Resonant wavenumber mismatch between these interacting modes can arise from the dispersive characteristics of the interacting waves and from spectral broadening due to random effects. In this paper, a general technique is presented to estimate the average level of instantaneous wavenumber mismatch, (Delta k) = (k(sub m) - k(sub i) - k(sub j)), between components whose frequencies obey the resonant selection condition, f(sub m) - f(sub i) - f(sub j) = 0. Cross-correlation of the auto-bispectrum is used to quantify the level of mismatch. The concept of bispectrum coupling coherency is introduced to determine the confidence level in the wavenumber mismatch estimates. These techniques are then applied to measure wavenumber mismatch in the transitioning field of a plane wake. The results show that the average of the instantaneous mismatch between the actual interacting modes (k(sub m) - k(sub i) - k(sub j)) is in general not equal to the mismatch between the average wavenumbers of each interacting mode (k(sub m) - (k(sub i)) - (k(sub j)).

DNA mismatch-specific targeting and hypersensitivity of mismatch-repair-deficient cells to bulky rhodium(III) intercalators

PubMed Central

Hart, Jonathan R.; Glebov, Oleg; Ernst, Russell J.; Kirsch, Ilan R.; Barton, Jacqueline K.

2006-01-01

Mismatch repair (MMR) is critical to maintaining the integrity of the genome, and deficiencies in MMR are correlated with cancerous transformations. Bulky rhodium intercalators target DNA base mismatches with high specificity. Here we describe the application of bulky rhodium intercalators to inhibit cellular proliferation differentially in MMR-deficient cells compared with cells that are MMR-proficient. Preferential inhibition by the rhodium complexes associated with MMR deficiency is seen both in a human colon cancer cell line and in normal mouse fibroblast cells; the inhibition of cellular proliferation depends strictly on the MMR deficiency of the cell. Furthermore, our assay of cellular proliferation is found to correlate with DNA mismatch targeting by the bulky metallointercalators. It is the Δ-isomer that is active both in targeting base mismatches and in inhibiting DNA synthesis. Additionally, the rhodium intercalators promote strand cleavage at the mismatch site with photoactivation, and we observe that the cellular response is enhanced with photoactivation. Targeting DNA mismatches may therefore provide a cell-selective strategy for chemotherapeutic design. PMID:17030786

Construction and characterization of mismatch-containing circular DNA molecules competent for assessment of nick-directed human mismatch repair in vitro.

PubMed

Larson, Erik D; Nickens, David; Drummond, James T

2002-02-01

The ability of cell-free extracts to correct DNA mismatches has been demonstrated in both prokaryotes and eukaryotes. Such an assay requires a template containing both a mismatch and a strand discrimination signal, and the multi-step construction process can be technically difficult. We have developed a three-step procedure for preparing DNA heteroduplexes containing a site-specific nick. The mismatch composition, sequence context, distance to the strand signal, and the means for assessing repair in each strand are adjustable features built into a synthetic oligonucleotide. Controlled ligation events involving three of the four DNA strands incorporate the oligonucleotide into a circular template and generate the repair-directing nick. Mismatch correction in either strand of a prototype G.T mismatch was achieved by placing a nick 10-40 bp away from the targeted base. This proximity of nick and mismatch represents a setting where repair has not been well characterized, but the presence of a nick was shown to be essential, as was the MSH2/MSH6 heterodimer, although low levels of repair occurred in extract defective in each protein. All repair events were inhibited by a peptide that interacts with proliferating cell nuclear antigen and inhibits both mismatch repair and long-patch replication.

Analysis of in vivo correction of defined mismatches in the DNA mismatch repair mutants msh2, msh3 and msh6 of Saccharomyces cerevisiae.

PubMed

Lühr, B; Scheller, J; Meyer, P; Kramer, W

1998-02-01

We have analysed the correction of defined mismatches in wild-type and msh2, msh3, msh6 and msh3 msh6 mutants of Saccharomyces cerevisiae in two different yeast strain backgrounds by transformation with plasmid heteroduplex DNA constructs. Ten different base/base mismatches, two single-nucleotide loops and a 38-nucleotide loop were tested. Repair of all types of mismatches was severely impaired in msh2 and msh3 msh6 mutants. In msh6 mutants, repair efficiency of most base/base mismatches was reduced to a similar extent as in msh3 msh6 double mutants. G/T and A/C mismatches, however, displayed residual repair in msh6 mutants in one strain background, implying a role for Msh3p in recognition of base/base mismatches. Furthermore, the efficiency of repair of base/base mismatches was considerably reduced in msh3 mutants in one strain background, indicating a requirement for MSH3 for fully efficient mismatch correction. Also the efficiency of repair of the 38-nucleotide loop was reduced in msh3 mutants, and to a lesser extent in msh6 mutants. The single-nucleotide loop with an unpaired A was less efficiently repaired in msh3 mutants and that with an unpaired T was less efficiently corrected in msh6 mutants, indicating non-redundant functions for the two proteins in the recognition of single-nucleotide loops.

Impact of beacon wavelength on phase-compensation performance

NASA Astrophysics Data System (ADS)

Enterline, Allison A.; Spencer, Mark F.; Burrell, Derek J.; Brennan, Terry J.

2017-09-01

This study evaluates the effects of beacon-wavelength mismatch on phase-compensation performance. In general, beacon-wavelength mismatch occurs at the system level because the beacon-illuminator laser (BIL) and high-energy laser (HEL) are often at different wavelengths. Such is the case, for example, when using an aperture sharing element to isolate the beam-control sensor suite from the blinding nature of the HEL. With that said, this study uses the WavePlex Toolbox in MATLAB® to model ideal spherical wave propagation through various atmospheric-turbulence conditions. To quantify phase-compensation performance, we also model a nominal adaptive-optics (AO) system. We achieve correction from a Shack-Hartmann wavefront sensor and continuous-face-sheet deformable mirror using a least-squares phase reconstruction algorithm in the Fried geometry and a leaky integrator control law. To this end, we plot the power in the bucket metric as a function of BIL-HEL wavelength difference. Our initial results show that positive BIL-HEL wavelength differences achieve better phase compensation performance compared to negative BIL-HEL wavelength differences (i.e., red BILs outperform blue BILs). This outcome is consistent with past results.

Simulation of LV pacemaker lead in marginal vein: potential risk factors for acute dislodgement.

PubMed

Zhao, Xuefeng; Burger, Mike; Liu, Yi; Das, Mithilesh K; Combs, William; Wenk, Jonathan F; Guccione, Julius M; Kassab, Ghassan S

2011-03-01

Although left ventricular (LV) coronary sinus lead dislodgement remains a problem, the risk factors for dislodgement have not been clearly defined. In order to identify potential risk factors for acute lead dislodgement, we conducted dynamic finite element simulations of pacemaker lead dislodgement in marginal LV vein. We considered factors such as mismatch in lead and vein diameters, velocity of myocardial motion, branch angle between the insertion vein and the coronary sinus, degree of slack, and depth of insertion. The results show that large lead-to-vein diameter mismatch, rapid myocardial motion, and superficial insertion are potential risk factors for lead dislodgement. In addition, the degree of slack presents either a positive or negative effect on dislodgement risk depending on the branch angle. The prevention of acute lead dislodgment can be enforced by inducing as much static friction force as possible at the lead-vein interface, while reducing the external force. If the latter exceeds the former, dislodgement will occur. The present findings underscore the major risk factors for lead dislodgment, which may improve implantation criterion and future lead design.

Working Hours Mismatch, Macroeconomic Changes, and Mental Well-being in Europe.

PubMed

De Moortel, Deborah; Thévenon, Olivier; De Witte, Hans; Vanroelen, Christophe

2017-06-01

This study explores the association between involuntarily working less or more than the standard workweek and poor mental well-being, and whether this relationship is dependent upon (changing) national-level unemployment and gross domestic product growth rates. Data from the European Social Survey Round 2 (2004-2005) and Round 5 (2010) were analyzed. The sample included 16,224 male and 16,184 female employees. Mental well-being was assessed by the World Health Organization Well-being Index. Three-level linear multilevel modeling was used to account for clustering of employees within research years and countries. Working involuntary long hours was positively associated with poor mental well-being for men. For women, working voluntary long, involuntary long, and involuntary short hours were positively associated with poor mental well-being. The mental well-being of women working voluntary and involuntary long hours was negatively influenced by deteriorating economic conditions. This study suggests women are more vulnerable to the effects of long working hours and working hours mismatch on mental well-being, especially during difficult economic periods.

Beyond Gender Stereotypes in Language Comprehension: Self Sex-Role Descriptions Affect the Brain's Potentials Associated with Agreement Processing.

PubMed

Canal, Paolo; Garnham, Alan; Oakhill, Jane

2015-01-01

We recorded Event-Related Potentials to investigate differences in the use of gender information during the processing of reflexive pronouns. Pronouns either matched the gender provided by role nouns (such as "king" or "engineer") or did not. We compared two types of gender information, definitional information, which is semantic in nature (a mother is female), or stereotypical (a nurse is likely to be female). When they followed definitional role-nouns, gender-mismatching pronouns elicited a P600 effect reflecting a failure in the agreement process. When instead the gender violation occurred after stereotypical role-nouns the Event Related Potential response was biphasic, being positive in parietal electrodes and negative in anterior left electrodes. The use of a correlational approach showed that those participants with more "feminine" or "expressive" self sex-role descriptions showed a P600 response for stereotype violations, suggesting that they experienced the mismatch as an agreement violation; whereas less "expressive" participants showed an Nref effect, indicating more effort spent in linking the pronouns with the possible, although less likely, counter-stereotypical referent.

DNA Methylation-a Potential Source of Mitochondria DNA Base Mismatch in the Development of Diabetic Retinopathy.

PubMed

Mishra, Manish; Kowluru, Renu A

2018-04-21

In the development of diabetic retinopathy, retinal mitochondria are dysfunctional, and mitochondrial DNA (mtDNA) is damaged with increased base mismatches and hypermethylated cytosines. DNA methylation is also a potential source of mutation, and in diabetes, the noncoding region, the displacement loop (D-loop), experiences more methylation and base mismatches than other regions of the mtDNA. Our aim was to investigate a possible crosstalk between mtDNA methylation and base mismatches in the development of diabetic retinopathy. The effect of inhibition of Dnmts (by 5-aza-2'-deoxycytidine or Dnmt1-siRNA) on glucose-induced mtDNA base mismatches was investigated in human retinal endothelial cells by surveyor endonuclease digestion and validated by Sanger sequencing. The role of deamination factors on increased base mismatches was determined in the cells genetically modulated for mitochondrial superoxide dismutase (Sod2) or cytidine-deaminase (APOBEC3A). The results were confirmed in an in vivo model using retinal microvasculature from diabetic mice overexpressing Sod2. Inhibition of DNA methylation, or regulation of cytosine deamination, significantly inhibited an increase in base mismatches at the D-loop and prevented mitochondrial dysfunction. Overexpression of Sod2 in mice also prevented diabetes-induced D-loop hypermethylation and increase in base mismatches. The crosstalk between DNA methylation and base mismatches continued even after termination of hyperglycemia, suggesting its role in the metabolic memory phenomenon associated with the progression of diabetic retinopathy. Inhibition of DNA methylation limits the availability of methylated cytosine for deamination, suggesting a crosstalk between DNA methylation and base mismatches. Thus, regulation of DNA methylation, or its deamination, should impede the development of diabetic retinopathy by preventing formation of base mismatches and mitochondrial dysfunction.

Mismatched HLA-DRB3 Can Induce a Potent Immune Response After HLA 10/10 Matched Stem Cell Transplantation.

PubMed

van Balen, Peter; van Luxemburg-Heijs, Simone A P; van de Meent, Marian; van Bergen, Cornelis A M; Halkes, Constantijn J M; Jedema, Inge; Falkenburg, J H Frederik

2017-12-01

Donors for allogeneic stem cell transplantation are preferentially matched with patients for HLA-A, -B, -C, and -DRB1. Mismatches between donor and patient in these alleles are associated with an increased risk of graft-versus-host disease (GVHD). In contrast, HLA-DRB3, 4 and 5, HLA-DQ and HLA-DP are usually assumed to be low expression loci with limited relevance, although mismatches in HLA-DQ and HLA-DP can result in alloimmune responses. Mismatches in HLA-DRB3, 4, and 5 are usually not taken into account in donor selection. Conversion of chimerism in the presence of GVHD after CD4 donor lymphocyte infusion was observed in a patient, HLA 10/10 matched, but mismatched for HLA-DRB3 and HLA-DPB1 compared with the donor. Alloreactive CD4 T cells were isolated from peripheral blood after CD4 donor lymphocyte infusion and recognition of donor-derived target cells transduced with the mismatched patient variant HLA-DRB3 and HLA-DPB1 molecule was tested. A dominant polyclonal CD4 T cell response against patient's mismatched HLA-DRB3 molecule was found in addition to an immune response against patient's mismatched HLA-DPB1 molecule. CD4 T cells specific for these HLA class II molecules recognized both hematopoietic target cells as well as GVHD target cells. In contrast to the assumption that mismatches in HLA-DRB3, 4, and 5 are not of immunogenic significance after HLA 10/10 matched allogeneic stem cell transplantation, we show that in this matched setting not only mismatches in HLA-DPB1, but also mismatches in HLA-DRB3 may induce a polyclonal allo-immune response associated with conversion of chimerism and severe GVHD.

Impact of ABO incompatibility on patients' outcome after haploidentical hematopoietic stem cell transplantation for acute myeloid leukemia - a report from the Acute Leukemia Working Party of the EBMT.

PubMed

Canaani, Jonathan; Savani, Bipin N; Labopin, Myriam; Huang, Xiao-Jun; Ciceri, Fabio; Arcese, William; Tischer, Johanna; Koc, Yener; Bruno, Benedetto; Gülbas, Zafer; Blaise, Didier; Maertens, Johan; Ehninger, Gerhard; Mohty, Mohamad; Nagler, Arnon

2017-06-01

A significant proportion of hematopoietic stem cell transplants are performed with ABO-mismatched donors. The impact of ABO mismatch on outcome following transplantation remains controversial and there are no published data regarding the impact of ABO mismatch in acute myeloid leukemia patients receiving haploidentical transplants. Using the European Blood and Marrow Transplant Acute Leukemia Working Group registry we identified 837 patients who underwent haploidentical transplantation. Comparative analysis was performed between patients who received ABO-matched versus ABO-mismatched haploidentical transplants for common clinical outcome variables. Our cohort consisted of 522 ABO-matched patients and 315 ABO-mismatched patients including 150 with minor, 127 with major, and 38 with bi-directional ABO mismatching. There were no significant differences between ABO matched and mismatched patients in terms of baseline disease and clinical characteristics. Major ABO mismatching was associated with inferior day 100 engraftment rate whereas multivariate analysis showed that bi-directional mismatching was associated with increased risk of grade II-IV acute graft- versus -host disease [hazard ratio (HR) 2.387; 95% confidence interval (CI): 1.22-4.66; P =0.01). Non-relapse mortality, relapse incidence, leukemia-free survival, overall survival, and chronic graft- versus -host disease rates were comparable between ABO-matched and -mismatched patients. Focused analysis on stem cell source showed that patients with minor mismatching transplanted with bone marrow grafts experienced increased grade II-IV acute graft- versus -host disease rates (HR 2.03; 95% CI: 1.00-4.10; P =0.04). Patients with major ABO mismatching and bone marrow grafts had decreased survival (HR=1.82; CI 95%: 1.048 - 3.18; P =0.033). In conclusion, ABO incompatibility has a marginal but significant clinical effect in acute myeloid leukemia patients undergoing haploidentical transplantation. Copyright© Ferrata Storti Foundation.

Impact of ABO incompatibility on patients’ outcome after haploidentical hematopoietic stem cell transplantation for acute myeloid leukemia - a report from the Acute Leukemia Working Party of the EBMT

PubMed Central

Canaani, Jonathan; Savani, Bipin N; Labopin, Myriam; Huang, Xiao-jun; Ciceri, Fabio; Arcese, William; Tischer, Johanna; Koc, Yener; Bruno, Benedetto; Gülbas, Zafer; Blaise, Didier; Maertens, Johan; Ehninger, Gerhard; Mohty, Mohamad; Nagler, Arnon

2017-01-01

A significant proportion of hematopoietic stem cell transplants are performed with ABO-mismatched donors. The impact of ABO mismatch on outcome following transplantation remains controversial and there are no published data regarding the impact of ABO mismatch in acute myeloid leukemia patients receiving haploidentical transplants. Using the European Blood and Marrow Transplant Acute Leukemia Working Group registry we identified 837 patients who underwent haploidentical transplantation. Comparative analysis was performed between patients who received ABO-matched versus ABO-mismatched haploidentical transplants for common clinical outcome variables. Our cohort consisted of 522 ABO-matched patients and 315 ABO-mismatched patients including 150 with minor, 127 with major, and 38 with bi-directional ABO mismatching. There were no significant differences between ABO matched and mismatched patients in terms of baseline disease and clinical characteristics. Major ABO mismatching was associated with inferior day 100 engraftment rate whereas multivariate analysis showed that bi-directional mismatching was associated with increased risk of grade II–IV acute graft-versus-host disease [hazard ratio (HR) 2.387; 95% confidence interval (CI): 1.22–4.66; P=0.01). Non-relapse mortality, relapse incidence, leukemia-free survival, overall survival, and chronic graft-versus-host disease rates were comparable between ABO-matched and -mismatched patients. Focused analysis on stem cell source showed that patients with minor mismatching transplanted with bone marrow grafts experienced increased grade II–IV acute graft-versus-host disease rates (HR 2.03; 95% CI: 1.00–4.10; P=0.04). Patients with major ABO mismatching and bone marrow grafts had decreased survival (HR=1.82; CI 95%: 1.048 – 3.18; P=0.033). In conclusion, ABO incompatibility has a marginal but significant clinical effect in acute myeloid leukemia patients undergoing haploidentical transplantation. PMID:28255020

Removal of N-6-methyladenine by the nucleotide excision repair pathway triggers the repair of mismatches in yeast gap-repair intermediates.

PubMed

Guo, Xiaoge; Jinks-Robertson, Sue

2013-12-01

Gap-repair assays have been an important tool for studying the genetic control of homologous recombination in yeast. Sequence analysis of recombination products derived when a gapped plasmid is diverged relative to the chromosomal repair template additionally has been used to infer structures of strand-exchange intermediates. In the absence of the canonical mismatch repair pathway, mismatches present in these intermediates are expected to persist and segregate at the next round of DNA replication. In a mismatch repair defective (mlh1Δ) background, however, we have observed that recombination-generated mismatches are often corrected to generate gene conversion or restoration events. In the analyses reported here, the source of the aberrant mismatch removal during gap repair was examined. We find that most mismatch removal is linked to the methylation status of the plasmid used in the gap-repair assay. Whereas more than half of Dam-methylated plasmids had patches of gene conversion and/or restoration interspersed with unrepaired mismatches, mismatch removal was observed in less than 10% of products obtained when un-methylated plasmids were used in transformation experiments. The methylation-linked removal of mismatches in recombination intermediates was due specifically to the nucleotide excision repair pathway, with such mismatch removal being partially counteracted by glycosylases of the base excision repair pathway. These data demonstrate that nucleotide excision repair activity is not limited to bulky, helix-distorting DNA lesions, but also targets removal of very modest perturbations in DNA structure. In addition to its effects on mismatch removal, methylation reduced the overall gap-repair efficiency, but this reduction was not affected by the status of excision repair pathways. Finally, gel purification of DNA prior to transformation reduced gap-repair efficiency four-fold in a nucleotide excision repair-defective background, indicating that the collateral introduction of UV damage can potentially compromise genetic interpretations. Copyright © 2013 Elsevier B.V. All rights reserved.

Removal of N-6-methyladenine by the nucleotide excision repair pathway triggers the repair of mismatches in yeast gap-repair intermediates

PubMed Central

Guo, Xiaoge; Jinks-Robertson, Sue

2013-01-01

Gap-repair assays have been an important tool for studying the genetic control of homologous recombination in yeast. Sequence analysis of recombination products derived when a gapped plasmid is diverged relative to the chromosomal repair template additionally has been used to infer structures of strand-exchange intermediates. In the absence of the canonical mismatch repair pathway, mismatches present in these intermediates are expected to persist and segregate at the next round of DNA replication. In a mismatch repair defective (mlh1Δ) background, however, we have observed that recombination-generated mismatches are often corrected to generate gene conversion or restoration events. In the analyses reported here, the source of the aberrant mismatch removal during gap repair was examined. We find that most mismatch removal is linked to the methylation status of the plasmid used in the gap-repair assay. Whereas more than half of Dam-methylated plasmids had patches of gene conversion and/or restoration interspersed with unrepaired mismatches, mismatch removal was observed in less than 10% of products obtained when un-methylated plasmids were used in transformation experiments. The methylation-linked removal of mismatches in recombination intermediates was due specifically to the nucleotide excision repair pathway, with such mismatch removal being partially counteracted by glycosylases of the base excision repair pathway. These data demonstrate that nucleotide excision repair activity is not limited to bulky, helix-distorting DNA lesions, but also targets removal of very modest perturbations in DNA structure. In addition to its effects on mismatch removal, methylation reduced the overall gap-repair efficiency, but this reduction was not affected by the status of excision repair pathways. Finally, gel purification of DNA prior to transformation reduced gap-repair efficiency four-fold in a nucleotide excision repair-defective background, indicating that the cillateral introduction of UV damage can potentially compromise genetic interpretations. PMID:24120148

Desynchronizations in bee-plant interactions cause severe fitness losses in solitary bees.

PubMed

Schenk, Mariela; Krauss, Jochen; Holzschuh, Andrea

2018-01-01

Global warming can disrupt mutualistic interactions between solitary bees and plants when increasing temperature differentially changes the timing of interacting partners. One possible scenario is for insect phenology to advance more rapidly than plant phenology. However, empirical evidence for fitness consequences due to temporal mismatches is lacking for pollinators and it remains unknown if bees have developed strategies to mitigate fitness losses following temporal mismatches. We tested the effect of temporal mismatches on the fitness of three spring-emerging solitary bee species, including one pollen specialist. Using flight cages, we simulated (i) a perfect synchronization (from a bee perspective): bees and flowers occur simultaneously, (ii) a mismatch of 3 days and (iii) a mismatch of 6 days, with bees occurring earlier than flowers in the latter two cases. A mismatch of 6 days caused severe fitness losses in all three bee species, as few bees survived without flowers. Females showed strongly reduced activity and reproductive output compared to synchronized bees. Fitness consequences of a 3-day mismatch were species-specific. Both the early-spring species Osmia cornuta and the mid-spring species Osmia bicornis produced the same number of brood cells after a mismatch of 3 days as under perfect synchronization. However, O. cornuta decreased the number of female offspring, whereas O. bicornis spread the brood cells over fewer nests, which may increase offspring mortality, e.g. due to parasitoids. The late-spring specialist Osmia brevicornis produced fewer brood cells even after a mismatch of 3 days. Additionally, our results suggest that fitness losses after temporal mismatches are higher during warm than cold springs, as the naturally occurring temperature variability revealed that warm temperatures during starvation decreased the survival rate of O. bicornis. We conclude that short temporal mismatches can cause clear fitness losses in solitary bees. Although our results suggest that bees have evolved species-specific strategies to mitigate fitness losses after temporal mismatches, the bees were not able to completely compensate for impacts on their fitness after temporal mismatches with their food resources. © 2017 The Authors. Journal of Animal Ecology published by John Wiley & Sons Ltd on behalf of British Ecological Society.

Washout of ⁸²Rb as a marker of impaired tissue integrity, obtained by list-mode cardiac PET/CT: relationship with perfusion/metabolism patterns of myocardial viability.

PubMed

Chien, David T; Bravo, Paco; Higuchi, Takahiro; Merrill, Jennifer; Bengel, Frank M

2011-08-01

Myocardial washout of the potassium analogue (82)Rb may indicate tissue impairment. Few studies have evaluated its usefulness for viability assessment, and controversial results were reported. We revisited this topic using list-mode positron emission tomography (PET)/CT. A total of 22 patients with chronic ischemic cardiomyopathy (ICM) and 11 control subjects with normal CT coronary angiogram were studied. Rest (82)Rb PET/CT studies were acquired in list mode and resampled to static, gated, and dynamic images. Using a 17-segment model, (82)Rb washout was determined by monoexponential fitting of myocardial time-activity curves. In ICM patients, (18)F-fluorodeoxyglucose (FDG) studies were obtained in the same session and segments were classified as normally perfused, mismatch, or matched defect. (82)Rb washout was minimal and homogeneous in control subjects. Normally perfused segments of ICM did not differ (p = 0.33). ICM patients had a left ventricular ejection fraction (LVEF) of 25 ± 12%, 25/353 mismatched, and 46/353 matched defect segments. (82)Rb washout was higher in hypoperfused vs normal segments (p < 0.05), but not different between mismatch and matched defect (p = 0.18). Intraindividual analysis in nine patients showing both FDG mismatch and matched defect confirmed absence of differences. Overall, segmental (82)Rb washout correlated inversely with (82)Rb uptake (r = -0.70; p < 0.05) and less well with FDG uptake (r = -0.31; p < 0.05). Using state-of-the-art PET/CT technology for myocardial viability assessment, (82)Rb washout does not distinguish between perfusion/metabolism patterns of hibernating myocardium and scar. Tissue integrity may be at least partially impaired in hibernation.

Bone marrow produces sufficient alloreactive natural killer (NK) cells in vivo to cure mice from subcutaneously and intravascularly injected 4T1 breast cancer.

PubMed

van Gelder, Michel; Vanclée, Ariane; van Elssen, Catharina H M J; Hupperets, Pierre; Wieten, Lotte; Bos, Gerard M

2017-02-01

Administration of 5 million alloreactive natural killer (NK) cells after low-dose chemo-irradiation cured mice of 4T1 breast cancer, supposedly dose dependent. We now explored the efficacy of bone marrow as alternative in vivo source of NK cells for anti-breast cancer treatment, as methods for in vitro clinical scale NK cell expansion are still in developmental phases. Progression-free survival (PFS) after treatment with different doses of spleen-derived alloreactive NK cells to 4T1-bearing Balb/c mice was measured to determine a dose-response relation. The potential of bone marrow as source of alloreactive NK cells was explored using MHC-mismatched mice as recipients of 4T1. Chemo-irradiation consisted of 2× 2 Gy total body irradiation and 200 mg/kg cyclophosphamide. Antibody-mediated in vivo NK cell depletion was applied to demonstrate the NK cell's role. Administration of 2.5 instead of 5 million alloreactive NK cells significantly reduced PFS, evidencing dose responsiveness. Compared to MHC-matched receivers of subcutaneous 4T1, fewer MHC-mismatched mice developed tumors, which was due to NK cell alloreactivity because in vivo NK cell depletion facilitated tumor growth. Application of low-dose chemo-irradiation increased plasma levels of NK cell-activating cytokines, NK cell activity and enhanced NK cell-dependent elimination of subcutaneous tumors. Intravenously injected 4T1 was eliminated by alloreactive NK cells in MHC-mismatched recipients without the need for chemo-irradiation. Bone marrow is a suitable source of sufficient alloreactive NK cells for the cure of 4T1 breast cancer. These results prompt clinical exploration of bone marrow transplantation from NK-alloreactive MHC-mismatched donors in patients with metastasized breast cancer.

Mutation spectrum of MSH3-deficient HHUA/chr.2 cells reflects in vivo activity of the MSH3 gene product in mismatch repair.

PubMed

Tauchi, H; Komatsu, K; Ishizaki, K; Yatagai, F; Kato, T

2000-02-14

The endometrial tumor cell line HHUA carries mutations in two mismatch repair (MMR) genes MSH3 and MSH6. We have established an MSH3-deficient HHUA/chr.2 cell line by introducing human chromosome 2, which carries wild-type MSH6 and MSH2 genes, to HHUA cells. Introduction of chromosome 2 to HHUA cells partially restored G:G MMR activity to the cell extract and reduced the frequency of mutation at the hypoxanthine-guanine phosphoribosyltransferase (hprt*) locus to about 3% that of the parental HHUA cells, which is five-fold the frequency in MMR-proficient cells, indicating that the residual mutator activity in HHUA/chr.2 is due to an MSH3-deficiency in these cells. The spectrum of mutations occurring at the HPRT locus of HHUA/chr.2 was determined with 71 spontaneous 6TG(r) clones. Base substitutions and +/-1 bp frameshifts were the major mutational events constituting, respectively, 54% and 42% of the total mutations, and more than 70% of them occurred at A:T sites. A possible explanation for the apparent bias of mutations to A:T sites in HHUA/chr.2 is haploinsufficiency of the MSH6 gene on the transferred chromosome 2. Comparison of the mutation spectra of HHUA/chr.2 with that of the MSH6-deficient HCT-15 cell line [S. Ohzeki, A. Tachibana, K. Tatsumi, T. Kato, Carcinogenesis 18 (1997) 1127-1133.] suggests that in vivo the MutSalpha (MSH2:MSH6) efficiently repairs both mismatch and unpaired extrahelical bases, whereas MutSbeta (MSH2:MSH3) efficiently repairs extrahelical bases and repairs mismatch bases to a limited extent.

Immigrants' Educational Mismatch and the Penalty of Over-Education

ERIC Educational Resources Information Center

Kalfa, Eleni; Piracha, Matloob

2017-01-01

This paper analyses immigrants' educational mismatch and its impact on wages in Spain. The incidence of immigrants' education-occupation mismatch in the Spanish labour market can largely be explained by the mismatch in the last job held in the home country. The probability of having been over-educated in the home country has a higher effect on the…

The Mismatch between Student Educational Expectations and Realities: Prevalence, Causes, and Consequences

ERIC Educational Resources Information Center

Maloshonok, Natalia; Terentev, Evgeniy

2017-01-01

This article aims to answer three questions concerning (1) the prevalence of the mismatch between student expectations and real university life, (2) factors influencing this mismatch, and (3) the effect of the expectation-reality mismatch on academic performance during the first year of study at university. The results of this study suggest that a…

Social, Spatial, and Skill Mismatch among Immigrants and Native-Born Workers in Los Angeles. Working Paper.

ERIC Educational Resources Information Center

Pastor, Manuel, Jr.; Marcelli, Enrico A.

Racially different economic outcomes stem from multiple causes, including various "mismatches" between minority employees and available jobs. A skill mismatch occurs when individuals' education and job skills do not qualify them for existing jobs. A spatial mismatch means that people live far from the work for which they qualify. A…

Entanglement verification with detection efficiency mismatch

NASA Astrophysics Data System (ADS)

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.

Too Materialistic to Get Married and Have Children?

PubMed Central

Li, Norman P.; Lim, Amy J. Y.; Tsai, Ming-Hong; O, Jiaqing

2015-01-01

We developed new materials to induce a luxury mindset and activate materialistic values, and examined materialism’s relationship to attitudes toward marriage and having children in Singapore. Path analyses indicated that materialistic values led to more negative attitudes toward marriage, which led to more negative attitudes toward children, which in turn led to a decreased number of children desired. Results across two studies highlight, at the individual level, the tradeoff between materialistic values and attitudes toward marriage and procreation and suggest that a consideration of psychological variables such as materialistic values may allow for a better understanding of larger-scale socioeconomic issues including low fertility rates among developed countries. We discuss implications and describe how psychological factors relating to low fertility fit within evolutionary mismatch and life history theory frameworks. PMID:25955502

Too materialistic to get married and have children?

PubMed

Li, Norman P; Lim, Amy J Y; Tsai, Ming-Hong; O, Jiaqing

2015-01-01

We developed new materials to induce a luxury mindset and activate materialistic values, and examined materialism's relationship to attitudes toward marriage and having children in Singapore. Path analyses indicated that materialistic values led to more negative attitudes toward marriage, which led to more negative attitudes toward children, which in turn led to a decreased number of children desired. Results across two studies highlight, at the individual level, the tradeoff between materialistic values and attitudes toward marriage and procreation and suggest that a consideration of psychological variables such as materialistic values may allow for a better understanding of larger-scale socioeconomic issues including low fertility rates among developed countries. We discuss implications and describe how psychological factors relating to low fertility fit within evolutionary mismatch and life history theory frameworks.

Clinicopathologic Significance of Mismatch Repair Defects in Endometrial Cancer: An NRG Oncology/Gynecologic Oncology Group Study

PubMed Central

McMeekin, D. Scott; Tritchler, David L.; Cohn, David E.; Mutch, David G.; Lankes, Heather A.; Geller, Melissa A.; Powell, Matthew A.; Backes, Floor J.; Landrum, Lisa M.; Zaino, Richard; Broaddus, Russell D.; Ramirez, Nilsa; Gao, Feng; Ali, Shamshad; Darcy, Kathleen M.; Pearl, Michael L.; DiSilvestro, Paul A.; Lele, Shashikant B.

2016-01-01

Purpose The clinicopathologic significance of mismatch repair (MMR) defects in endometrioid endometrial cancer (EEC) has not been definitively established. We undertook tumor typing to classify MMR defects to determine if MMR status is prognostic or predictive. Methods Primary EECs from NRG/GOG0210 patients were assessed for microsatellite instability (MSI), MLH1 methylation, and MMR protein expression. Each tumor was assigned to one of four MMR classes: normal, epigenetic defect, probable mutation (MMR defect not attributable to MLH1 methylation), or MSI-low. The relationships between MMR classes and clinicopathologic variables were assessed using contingency table tests and Cox proportional hazard models. Results A total of 1,024 tumors were assigned to MMR classes. Epigenetic and probable mutations in MMR were significantly associated with higher grade and more frequent lymphovascular space invasion. Epigenetic defects were more common in patients with higher International Federation of Gynecology and Obstetrics stage. Overall, there were no differences in outcomes. Progression-free survival was, however, worse for women whose tumors had epigenetic MMR defects compared with the MMR normal group (hazard ratio, 1.37; P < .05; 95% CI, 1.00 to 1.86). An exploratory analysis of interaction between MMR status and adjuvant therapy showed a trend toward improved progression-free survival for probable MMR mutation cases. Conclusion MMR defects in EECs are associated with a number of well-established poor prognostic indicators. Women with tumors that had MMR defects were likely to have higher-grade cancers and more frequent lymphovascular space invasion. Surprisingly, outcomes in these patients were similar to patients with MMR normal tumors, suggesting that MMR defects may counteract the effects of negative prognostic factors. Altered immune surveillance of MMR-deficient tumors, and other host/tumor interactions, is likely to determine outcomes for patients with MMR-deficient tumors. PMID:27325856

Clinicopathologic Significance of Mismatch Repair Defects in Endometrial Cancer: An NRG Oncology/Gynecologic Oncology Group Study.

PubMed

McMeekin, D Scott; Tritchler, David L; Cohn, David E; Mutch, David G; Lankes, Heather A; Geller, Melissa A; Powell, Matthew A; Backes, Floor J; Landrum, Lisa M; Zaino, Richard; Broaddus, Russell D; Ramirez, Nilsa; Gao, Feng; Ali, Shamshad; Darcy, Kathleen M; Pearl, Michael L; DiSilvestro, Paul A; Lele, Shashikant B; Goodfellow, Paul J

2016-09-01

The clinicopathologic significance of mismatch repair (MMR) defects in endometrioid endometrial cancer (EEC) has not been definitively established. We undertook tumor typing to classify MMR defects to determine if MMR status is prognostic or predictive. Primary EECs from NRG/GOG0210 patients were assessed for microsatellite instability (MSI), MLH1 methylation, and MMR protein expression. Each tumor was assigned to one of four MMR classes: normal, epigenetic defect, probable mutation (MMR defect not attributable to MLH1 methylation), or MSI-low. The relationships between MMR classes and clinicopathologic variables were assessed using contingency table tests and Cox proportional hazard models. A total of 1,024 tumors were assigned to MMR classes. Epigenetic and probable mutations in MMR were significantly associated with higher grade and more frequent lymphovascular space invasion. Epigenetic defects were more common in patients with higher International Federation of Gynecology and Obstetrics stage. Overall, there were no differences in outcomes. Progression-free survival was, however, worse for women whose tumors had epigenetic MMR defects compared with the MMR normal group (hazard ratio, 1.37; P < .05; 95% CI, 1.00 to 1.86). An exploratory analysis of interaction between MMR status and adjuvant therapy showed a trend toward improved progression-free survival for probable MMR mutation cases. MMR defects in EECs are associated with a number of well-established poor prognostic indicators. Women with tumors that had MMR defects were likely to have higher-grade cancers and more frequent lymphovascular space invasion. Surprisingly, outcomes in these patients were similar to patients with MMR normal tumors, suggesting that MMR defects may counteract the effects of negative prognostic factors. Altered immune surveillance of MMR-deficient tumors, and other host/tumor interactions, is likely to determine outcomes for patients with MMR-deficient tumors. © 2016 by American Society of Clinical Oncology.

Storage of feature conjunctions in transient auditory memory.

PubMed

Gomes, H; Bernstein, R; Ritter, W; Vaughan, H G; Miller, J

1997-11-01

The purpose of this study was to determine whether feature conjunctions are stored in transient auditory memory. The mismatch negativity (MMN), an event-related potential that is elicited by stimuli that differ from a series of preceding stimuli, was used in this endeavour. A tone that differed from the preceding series of stimuli in the conjunction of two of its features, both present in preceding stimuli but in different combinations, was found to elicit the MMN. The data are interpreted to indicate that information about the conjunction of features is stored in the memory.

Snowshoe hares display limited phenotypic plasticity to mismatch in seasonal camouflage

USGS Publications Warehouse

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.

Understanding Emotions in Frontotemporal Dementia: The Explicit and Implicit Emotional Cue Mismatch.

PubMed

Balconi, Michela; Cotelli, Maria; Brambilla, Michela; Manenti, Rosa; Cosseddu, Maura; Premi, Enrico; Gasparotti, Roberto; Zanetti, Orazio; Padovani, Alessandro; Borroni, Barbara

2015-01-01

Previous studies have reported significant deficits in emotion recognition among individuals along the frontotemporal dementia (FTD) spectrum. The basis of emotional impairment is still poorly understood and explicit (emotion appraisal) and implicit (autonomic system activity) responses have not been carefully evaluated. We investigated explicit evaluation of emotions by testing valence and arousal using self-report measures and we also assessed automatic responses to emotional cues, using autonomic measures (skin conductance response and heart rate). 16 behavioral variant FTD and 12 agrammatic variants of primary progressive aphasia patients were included. The performance of these patients was compared to a group of 14 patients with Alzheimer's disease and 20 healthy controls. Each subject was required to observe and evaluate affective pictures while autonomic parameters were recorded. FTD patients preserved a functional general competency in terms of valence (correct positive versus negative attribution) and arousal (correct dichotomy between high versus low arousal category) distinction. These patients showed significant changes in autonomic implicit response compared to the other groups. The mismatch between explicit and implicit responsiveness to emotional cues was found both in behavioral variant FTD and in agrammatic variants of primary progressive aphasia. Emotional responsiveness was related to the severity of behavioral abnormalities as measured by the Frontal Behavioral Inventory and associated with atrophy of the left putamen. The present findings indicate that FTD patients are able to explicitly "appraise" the emotion, but they cannot implicitly "feel" the emotion. This mismatch between the two levels may help explain the general emotional behavior impairment found in these patients.

Factors affecting operational tolerance after pediatric living-donor liver transplantation: impact of early post-transplant events and HLA match.

PubMed

Ohe, Hidenori; Waki, Kayo; Yoshitomi, Mami; Morimoto, Takeshi; Nafady-Hego, Hanaa; Satoda, Naoki; Li, Ying; Zhao, Xiangdong; Sakaguchi, Shimon; Uemoto, Shinji; Bishop, G Alex; Koshiba, Takaaki

2012-01-01

Pediatric recipients of living-donor liver transplants (LDLT) can often discontinue immunosuppression (IS). We examined factors affecting development of operational tolerance (OT), defined as off IS for >1 year, in this population. A historic cohort analysis was conducted in 134 pediatric primary semi-allogeneic LDLT. Multivariate logistic regression analysis was used. The frequency of peripheral regulatory T cells (Tregs) was determined at >10 years post-Tx by FACS analysis. IS was successfully discontinued in 84 tolerant patients (Gr-tol), but not in 50 intolerant patients (Gr-intol). The Gr-intol consisted of 24 patients with rejection (Gr-rej) and 26 with fibrosis of grafts (Gr-fib). The absence of early rejection [odds ratio (OR) 2.79, 95% CI 1.11-7.02, P = 0.03], was a positive independent predictor, whereas HLA-A mismatch (0.18, 0.03-0.91, P = 0.04) was a negative predictor. HLA-DR mismatches did not affect OT. The Treg frequency was significantly decreased in Gr-intol (4.9%) compared with Gr-tol (7.6%) (P = 0.003). There were increased levels of tacrolimus in the first week in Gr-Tol (P = 0.02). Although HLA-B mismatch (8.73, 1.09-70.0, P = 0.04) was a positive independent predictor of OT, its clinical significance remains doubtful. In this large cohort of pediatric LDLT recipients, absence of early rejection, HLA-A match and the later predominance of Tregs are factors associated with OT. © 2011 The Authors. Transplant International © 2011 European Society for Organ Transplantation.

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

PubMed

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

2013-11-01

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

Inculcating the ergonomic culture in developing countries: national healthy schoolbag initiative in Sri Lanka.

PubMed

Jayaratne, Kapila

2012-12-01

The aim of this article is to describe a survey on ergonomic factors of classroom environments of school children, their influence on health, and use of research outcomes to launch a healthy schoolbag initiative. Ergonomics have not yet well penetrated relevant fields in industrially developing countries, such as Sri Lanka. One of the crucial parameters of the school environment is ergonomics. Available evidence suggests ergonomic mismatches in classroom settings. Good practice examples in child ergonomic interventions are few in resource-poor contexts. A school-based cross-sectional study was conducted in a district in Sri Lanka with a sample of 1,607 children in Grades 6 to 8 with the use of a stratified multistage cluster sampling method. Many children did experience discomfort related to substandard seating arrangements in the classroom. A significant proportion had to turn their necks to see the blackboard. For many children, seating locations were not changed. There were widespread incompatibilities of classroom furniture with anthropometric dimensions of children. A majority of children perceived discomfort contributed by mismatched classroom furniture. Carriage of school materials was not healthy. Deficiencies were noted in weight, model, ergonomic features, and carrying behavior of bags. Children experienced several negative effects, in part attributable to mismatched ergonomic factors. The schoolbag was considered a priority issue. Findings were disseminated to stakeholders and to media. Solutions were contemplated on bag weight reduction, healthy schoolbag introduction, and behavior change in a collaborative initiative with the Education Ministry. Political, administrative, and business stakeholders were successfully engaged to inculcate an ergonomic culture in an industrially developing country.

Asynchrony between Host Plant and Insects-Defoliator within a Tritrophic System: The Role of Herbivore Innate Immunity

PubMed Central

Martemyanov, Vyacheslav V.; Pavlushin, Sergey V.; Dubovskiy, Ivan M.; Yushkova, Yuliya V.; Morosov, Sergey V.; Chernyak, Elena I.; Efimov, Vadim M.; Ruuhola, Teija; Glupov, Victor V.

2015-01-01

The effects of asynchrony in the phenology of spring-feeding insect-defoliators and their host plants on insects’ fitness, as well as the importance of this effect for the population dynamics of outbreaking species of insects, is a widespread and well-documented phenomenon. However, the spreading of this phenomenon through the food chain, and especially those mechanisms operating this spreading, are still unclear. In this paper, we study the effect of seasonally declined leafquality (estimated in terms of phenolics and nitrogen content) on herbivore fitness, immune parameters and resistance against pathogen by using the silver birch Betula pendula—gypsy moth Lymantria dispar—nucleopolyhedrovirus as the tritrophic system. We show that a phenological mismatch induced by the delay in the emergence of gypsy moth larvae and following feeding on mature leaves has negative effects on the female pupal weight, on the rate of larval development and on the activity of phenoloxidase in the plasma of haemolymph. In addition, the larval susceptibility to exogenous nucleopolyhydrovirus infection as well as covert virus activation were both enhanced due to the phenological mismatch. The observed effects of phenological mismatch on insect-baculovirus interaction may partially explain the strong and fast fluctuations in the population dynamics of the gypsy moth that is often observed in the studied part of the defoliator area. This study also reveals some indirect mechanisms of effect related to host plant quality, which operate through the insect innate immune status and affect resistance to both exogenous and endogenous virus. PMID:26115118

Formation of Dirac point and the topological surface states inside the strained gap for mixed 3D Hg1-xCdx Te

NASA Astrophysics Data System (ADS)

Marchewka, Michał

2016-10-01

In this paper the results of the numerical calculation obtained for the three-dimensional (3D) strained Hg1-xCdx Te layers for the x-Cd composition from 0.1 to 0.155 and a different mismatch of the lattice constant are presented. For the investigated region of the Cd composition (x value) the negative energy gap (Eg =Γ8 -Γ6) in the Hg1-xCdx Te is smaller than in the case of pure HgTe which, as it turns out, has a significant influence on the topological surface states (TSS) and the position of the Dirac point. The numerical calculation based on the finite difference method applied for the 8×8 kp model with the in-plane tensile strain for (001) growth oriented structure shows that the Dirac cone inside the induced insulating band gap for non zero of the Cd composition and a bigger strain caused by the bigger lattice mismatch (than for the 3D HgTe TI) can be obtained. It was also shown how different x-Cd compounds move the Dirac cone from the valence band into the band gap. The presented results show that 75 nm wide 3D Hg1-xCdx Te structures with x ≈ 0.155 and 1.6% lattice mismatch make the system a true topological insulator with the dispersion of the topological surface states similar to those ones obtained for the strained CdTe/HgTe QW.

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

PubMed

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.

Stereotype Threat Reinterpreted as a Regulatory Mismatch

PubMed Central

Grimm, Lisa R.; Markman, Arthur B.; Maddox, W. Todd; Baldwin, Grant C.

2008-01-01

Research documents performance decrements resulting from the activation of a negative task-relevant stereotype. We combine a number of strands of work to identify causes of stereotype threat in a way that allows us to reverse the effects and improve the performance of individuals with negative task-relevant stereotypes. We draw on prior work suggesting that negative stereotypes induce a prevention focus, and other research suggesting that people exhibit greater flexibility when their regulatory focus matches the reward structure of the task. This work suggests that stereotype threat effects emerge from a prevention focus combined with tasks that have an explicit or implicit gains reward structure. We find flexible performance can be induced in individuals who have a negative task-relevant stereotype by using a losses reward structure. We demonstrate the interaction of stereotypes and the reward structure of the task using chronic stereotypes and GRE math problems (Experiment 1), and primed stereotypes and a category learning task (Experiments 2a and 2b). We discuss implications of this research for other work on stereotype threat. PMID:19159133

Signs of impaired selective attention in patients with amyotrophic lateral sclerosis.

PubMed

Pinkhardt, Elmar H; Jürgens, Reinhart; Becker, Wolfgang; Mölle, Matthias; Born, Jan; Ludolph, Albert C; Schreiber, Herbert

2008-04-01

The evidence for involvement of extramotor cortical areas in non-demented patients with amyotrophic lateral sclerosis (ALS) has been provided by recent neuropsychological and functional brain imaging studies. The aim of this study was to investigate possible alterations in selective attention, as an important constituent part of frontal brain function in ALS patients. A classical dichotic listening task paradigm was employed to assess event-related EEG potential (ERPs) indicators of selective attention as well as preattentive processing of mismatch, without interference by motor impairment.A total of 20 patients with sporadic ALS according to the revised El Escorial criteria and 20 healthy controls were studied. Additionally a neuropsychological test battery of frontotemporal functions was applied. Compared with the controls, the ALS patients showed a distinct decrease of the fronto-precentral negative difference wave (Nd), i.e., the main ERP indicator of selective attention. Analysis of the P3 component of the ERPs indicated an increased processing of non-relevant stimuli in ALS patients confirming a reduced focus of attention. We conclude impaired selective attention reflects a subtle variant of frontotemporal dementia frequently observed in ALS patients at a relatively early stage of the disease.

Measurement of mismatch loss in CPV modul

NASA Astrophysics Data System (ADS)

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.

Enhancing links between visual short term memory, visual attention and cognitive control processes through practice: An electrophysiological insight.

PubMed

Fuggetta, Giorgio; Duke, Philip A

2017-05-01

The operation of attention on visible objects involves a sequence of cognitive processes. The current study firstly aimed to elucidate the effects of practice on neural mechanisms underlying attentional processes as measured with both behavioural and electrophysiological measures. Secondly, it aimed to identify any pattern in the relationship between Event-Related Potential (ERP) components which play a role in the operation of attention in vision. Twenty-seven participants took part in two recording sessions one week apart, performing an experimental paradigm which combined a match-to-sample task with a memory-guided efficient visual-search task within one trial sequence. Overall, practice decreased behavioural response times, increased accuracy, and modulated several ERP components that represent cognitive and neural processing stages. This neuromodulation through practice was also associated with an enhanced link between behavioural measures and ERP components and with an enhanced cortico-cortical interaction of functionally interconnected ERP components. Principal component analysis (PCA) of the ERP amplitude data revealed three components, having different rostro-caudal topographic representations. The first component included both the centro-parietal and parieto-occipital mismatch triggered negativity - involved in integration of visual representations of the target with current task-relevant representations stored in visual working memory - loaded with second negative posterior-bilateral (N2pb) component, involved in categorising specific pop-out target features. The second component comprised the amplitude of bilateral anterior P2 - related to detection of a specific pop-out feature - loaded with bilateral anterior N2, related to detection of conflicting features, and fronto-central mismatch triggered negativity. The third component included the parieto-occipital N1 - related to early neural responses to the stimulus array - which loaded with the second negative posterior-contralateral (N2pc) component, mediating the process of orienting and focusing covert attention on peripheral target features. We discussed these three components as representing different neurocognitive systems modulated with practice within which the input selection process operates. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Effect of HLA mismatch on acute graft-versus-host disease.

PubMed

Kanda, Junya

2013-09-01

HLA matching between donors and recipients is the most important factor associated with acute graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation. With improvements in GVHD prophylaxis and supportive care, transplantations from HLA mismatched donors are performed increasingly frequently, drawing greater attention to the effects of HLA mismatch. In related transplantation, HLA 1-antigen mismatch at the HLA-A, HLA-B, and HLA-DR loci is considered acceptable, but the incidence of severe acute GVHD under standard prophylaxis is higher than that for matched related and unrelated transplantation, highlighting the need for a modification of GVHD prophylaxis. Development of new GVHD prophylaxes has now made HLA 2-3-antigen mismatched related transplantation feasible, and has almost overcome the HLA barrier. In unrelated bone marrow or peripheral blood stem cell transplantation, donors matched for HLA-A, HLA-B, HLA-C, and HLA-DRB1 alleles are the most preferable. The impact of allele or antigen mismatch has been evaluated in a number of studies, but the results of these have not been consistent, partly due to differences in race and HLA distribution. The effects of HLA mismatch may differ depending on the year of transplantation and the form of GVHD prophylaxis administered. In cord blood transplantation, successful transplantation can be achieved with up to two HLA mismatches. In children, compared to the use of HLA mismatched units, the use of HLA-matched units is associated with a lower risk of acute GVHD and mortality, while in adults HLA mismatches may have a lower impact on outcome. Thus, the effect of HLA matching should be evaluated separately for different stem cell sources.

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

PubMed

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.

Recognition of T·G mismatched base pairs in DNA by stacked imidazole-containing polyamides: surface plasmon resonance and circular dichroism studies

PubMed Central

Lacy, Eilyn R.; Cox, Kari K.; Wilson, W. David; Lee, Moses

2002-01-01

An imidazole-containing polyamide trimer, f-ImImIm, where f is a formamido group, was recently found using NMR methods to recognize T·G mismatched base pairs. In order to characterize in detail the T·G recognition affinity and specificity of imidazole-containing polyamides, f-ImIm, f-ImImIm and f-PyImIm were synthesized. The kinetics and thermodynamics for the polyamides binding to Watson–Crick and mismatched (containing one or two T·G, A·G or G·G mismatched base pairs) hairpin oligonucleotides were determined by surface plasmon resonance and circular dichroism (CD) methods. f-ImImIm binds significantly more strongly to the T·G mismatch-containing oligonucleotides than to the sequences with other mismatched or with Watson–Crick base pairs. Compared with the Watson–Crick CCGG sequence, f-ImImIm associates more slowly with DNAs containing T·G mismatches in place of one or two C·G base pairs and, more importantly, the dissociation rate from the T·G oligonucleotides is very slow (small kd). These results clearly demonstrate the binding selectivity and enhanced affinity of side-by-side imidazole/imidazole pairings for T·G mismatches and show that the affinity and specificity increase arise from much lower kd values with the T·G mismatched duplexes. CD titration studies of f-ImImIm complexes with T·G mismatched sequences produce strong induced bands at ∼330 nm with clear isodichroic points, in support of a single minor groove complex. CD DNA bands suggest that the complexes remain in the B conformation. PMID:11937638

Phonon cross-plane transport and thermal boundary resistance: effect of heat source size and thermal boundary resistance on phonon characteristics

NASA Astrophysics Data System (ADS)

Ali, H.; Yilbas, B. S.

2016-09-01

Phonon cross-plane transport across silicon and diamond thin films pair is considered, and thermal boundary resistance across the films pair interface is examined incorporating the cut-off mismatch and diffusive mismatch models. In the cut-off mismatch model, phonon frequency mismatch for each acoustic branch is incorporated across the interface of the silicon and diamond films pair in line with the dispersion relations of both films. The frequency-dependent and transient solution of the Boltzmann transport equation is presented, and the equilibrium phonon intensity ratios at the silicon and diamond film edges are predicted across the interface for each phonon acoustic branch. Temperature disturbance across the edges of the films pair is incorporated to assess the phonon transport characteristics due to cut-off and diffusive mismatch models across the interface. The effect of heat source size, which is allocated at high-temperature (301 K) edge of the silicon film, on the phonon transport characteristics at the films pair interface is also investigated. It is found that cut-off mismatch model predicts higher values of the thermal boundary resistance across the films pair interface as compared to that of the diffusive mismatch model. The ratio of equilibrium phonon intensity due to the cut-off mismatch over the diffusive mismatch models remains >1 at the silicon edge, while it becomes <1 at the diamond edge for all acoustic branches.

DNA Mismatch Binding and Antiproliferative Activity of Rhodium Metalloinsertors

PubMed Central

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

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

PubMed

Vuust, Peter; Brattico, Elvira; Seppänen, Miia; Näätänen, Risto; Tervaniemi, Mari

2012-06-01

Musicians' skills in auditory processing depend highly on instrument, performance practice, and on level of expertise. Yet, it is not known though whether the style/genre of music might shape auditory processing in the brains of musicians. Here, we aimed at tackling the role of musical style/genre on modulating neural and behavioral responses to changes in musical features. Using a novel, fast and musical sounding multi-feature paradigm, we measured the mismatch negativity (MMN), a pre-attentive brain response, to six types of musical feature change in musicians playing three distinct styles of music (classical, jazz, rock/pop) and in non-musicians. Jazz and classical musicians scored higher in the musical aptitude test than band musicians and non-musicians, especially with regards to tonal abilities. These results were extended by the MMN findings: jazz musicians had larger MMN-amplitude than all other experimental groups across the six different sound features, indicating a greater overall sensitivity to auditory outliers. In particular, we found enhanced processing of pith and sliding up to pitches in jazz musicians only. Furthermore, we observed a more frontal MMN to pitch and location compared to the other deviants in jazz musicians and left lateralization of the MMN to timbre in classical musicians. These findings indicate that the characteristics of the style/genre of music played by musicians influence their perceptual skills and the brain processing of sound features embedded in a musical context. Musicians' brain is hence shaped by the type of training, musical style/genre, and listening experiences. Copyright © 2012 Elsevier Ltd. All rights reserved.

Statistical parametric mapping of LORETA using high density EEG and individual MRI: application to mismatch negativities in schizophrenia.

PubMed

Park, Hae-Jeong; Kwon, Jun Soo; Youn, Tak; Pae, Ji Soo; Kim, Jae-Jin; Kim, Myung-Sun; Ha, Kyoo-Seob

2002-11-01

We describe a method for the statistical parametric mapping of low resolution electromagnetic tomography (LORETA) using high-density electroencephalography (EEG) and individual magnetic resonance images (MRI) to investigate the characteristics of the mismatch negativity (MMN) generators in schizophrenia. LORETA, using a realistic head model of the boundary element method derived from the individual anatomy, estimated the current density maps from the scalp topography of the 128-channel EEG. From the current density maps that covered the whole cortical gray matter (up to 20,000 points), volumetric current density images were reconstructed. Intensity normalization of the smoothed current density images was used to reduce the confounding effect of subject specific global activity. After transforming each image into a standard stereotaxic space, we carried out statistical parametric mapping of the normalized current density images. We applied this method to the source localization of MMN in schizophrenia. The MMN generators, produced by a deviant tone of 1,200 Hz (5% of 1,600 trials) under the standard tone of 1,000 Hz, 80 dB binaural stimuli with 300 msec of inter-stimulus interval, were measured in 14 right-handed schizophrenic subjects and 14 age-, gender-, and handedness-matched controls. We found that the schizophrenic group exhibited significant current density reductions of MMN in the left superior temporal gyrus and the left inferior parietal gyrus (P < 0. 0005). This study is the first voxel-by-voxel statistical mapping of current density using individual MRI and high-density EEG. Copyright 2002 Wiley-Liss, Inc.

The mechanisms and meaning of the mismatch negativity.

PubMed

Fishman, Yonatan I

2014-07-01

The mismatch negativity (MMN) is a pre-attentive auditory event-related potential (ERP) component that is elicited by a change in a repetitive acoustic pattern. It is obtained by subtracting responses evoked by frequent 'standard' sounds from responses evoked by infrequent 'deviant' sounds that differ from the standards along some acoustic dimension, e.g., frequency, intensity, or duration, or abstract feature. The MMN has been attributed to neural generators within the temporal and frontal lobes. The mechanisms and meaning of the MMN continue to be debated. Two dominant explanations for the MMN have been proposed. According to the "neural adaptation" hypothesis, repeated presentation of the standards results in adapted (i.e., attenuated) responses of feature-selective neurons in auditory cortex. Rare deviant sounds activate neurons that are less adapted than those stimulated by the frequent standard sounds, and thus elicit a larger 'obligatory' response, which yields the MMN following the subtraction procedure. In contrast, according to the "sensory memory" hypothesis, the MMN is a 'novel' (non-obligatory) ERP component that reflects a deviation between properties of an incoming sound and those of a neural 'memory trace' established by the preceding standard sounds. Here, we provide a selective review of studies which are relevant to the controversy between proponents of these two interpretations of the MMN. We also present preliminary neurophysiological data from monkey auditory cortex with potential implications for the debate. We conclude that the mechanisms and meaning of the MMN are still unresolved and offer remarks on how to make progress on these important issues.

Distributed feature binding in the auditory modality: experimental evidence toward reconciliation of opposing views on the basis of mismatch negativity and behavioral measures.

PubMed

Chernyshev, Boris V; Bryzgalov, Dmitri V; Lazarev, Ivan E; Chernysheva, Elena G

2016-08-03

Current understanding of feature binding remains controversial. Studies involving mismatch negativity (MMN) measurement show a low level of binding, whereas behavioral experiments suggest a higher level. We examined the possibility that the two levels of feature binding coexist and may be shown within one experiment. The electroencephalogram was recorded while participants were engaged in an auditory two-alternative choice task, which was a combination of the oddball and the condensation tasks. Two types of deviant target stimuli were used - complex stimuli, which required feature conjunction to be identified, and simple stimuli, which differed from standard stimuli in a single feature. Two behavioral outcomes - correct responses and errors - were analyzed separately. Responses to complex stimuli were slower and less accurate than responses to simple stimuli. MMN was prominent and its amplitude was similar for both simple and complex stimuli, whereas the respective stimuli differed from standards in a single feature or two features respectively. Errors in response only to complex stimuli were associated with decreased MMN amplitude. P300 amplitude was greater for complex stimuli than for simple stimuli. Our data are compatible with the explanation that feature binding in auditory modality depends on two concurrent levels of processing. We speculate that the earlier level related to MMN generation is an essential and critical stage. Yet, a later analysis is also carried out, affecting P300 amplitude and response time. The current findings provide resolution to conflicting views on the nature of feature binding and show that feature binding is a distributed multilevel process.

Neural mechanisms of mismatch negativity dysfunction in schizophrenia.

PubMed

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

2017-11-01

Schizophrenia is associated with cognitive deficits that reflect impaired cortical information processing. Mismatch negativity (MMN) indexes pre-attentive information processing dysfunction at the level of primary auditory cortex. This study investigates mechanisms underlying MMN impairments in schizophrenia using event-related potential, event-related spectral decomposition (ERSP) and resting state functional connectivity (rsfcMRI) approaches. For this study, MMN data to frequency, intensity and duration-deviants were analyzed from 69 schizophrenia patients and 38 healthy controls. rsfcMRI was obtained from a subsample of 38 patients and 23 controls. As expected, schizophrenia patients showed highly significant, large effect size (P=0.0004, d=1.0) deficits in MMN generation across deviant types. In ERSP analyses, responses to deviants occurred primarily the theta (4-7 Hz) frequency range consistent with distributed corticocortical processing, whereas responses to standards occurred primarily in alpha (8-12 Hz) range consistent with known frequencies of thalamocortical activation. Independent deficits in schizophrenia were observed in both the theta response to deviants (P=0.021) and the alpha-response to standards (P=0.003). At the single-trial level, differential patterns of response were observed for frequency vs duration/intensity deviants, along with At the network level, MMN deficits engaged canonical somatomotor, ventral attention and default networks, with a differential pattern of engagement across deviant types (P<0.0001). Findings indicate that deficits in thalamocortical, as well as corticocortical, connectivity contribute to auditory dysfunction in schizophrenia. In addition, differences in ERSP and rsfcMRI profiles across deviant types suggest potential differential engagement of underlying generator mechanisms.

Magnetoencephalographic recording of auditory mismatch negativity in response to duration and frequency deviants in a single session in patients with schizophrenia.

PubMed

Suga, Motomu; Nishimura, Yukika; Kawakubo, Yuki; Yumoto, Masato; Kasai, Kiyoto

2016-07-01

Auditory mismatch negativity (MMN) and its magnetoencephalographic (MEG) counterpart (MMNm) are an established biological index in schizophrenia research. MMN in response to duration and frequency deviants may have differential relevance to the pathophysiology and clinical stages of schizophrenia. MEG has advantage in that it almost purely detects MMNm arising from the auditory cortex. However, few previous MEG studies on schizophrenia have simultaneously assessed MMNm in response to duration and frequency deviants or examined the effect of chronicity on the group difference. Forty-two patients with chronic schizophrenia and 74 matched control subjects participated in the study. Using a whole-head MEG, MMNm in response to duration and frequency deviants of tones was recorded while participants passively listened to an auditory sequence. Compared to healthy subjects, patients with schizophrenia exhibited significantly reduced powers of MMNm in response to duration deviant in both hemispheres, whereas MMNm in response to frequency deviant did not differ between the two groups. These results did not change according to the chronicity of the illness. These results, obtained by using a sequence-enabling simultaneous assessment of both types of MMNm, suggest that MEG recording of MMN in response to duration deviant may be a more sensitive biological marker of schizophrenia than MMN in response to frequency deviant. Our findings represent an important first step towards establishment of MMN as a biomarker for schizophrenia in real-world clinical psychiatry settings. © 2016 The Authors. Psychiatry and Clinical Neurosciences © 2016 Japanese Society of Psychiatry and Neurology.

Meta-analysis of mismatch negativity to simple versus complex deviants in schizophrenia.

PubMed

Avissar, Michael; Xie, Shanghong; Vail, Blair; Lopez-Calderon, Javier; Wang, Yuanjia; Javitt, Daniel C

2018-01-01

Mismatch negativity (MMN) deficits in schizophrenia (SCZ) have been studied extensively since the early 1990s, with the vast majority of studies using simple auditory oddball task deviants that vary in a single acoustic dimension such as pitch or duration. There has been a growing interest in using more complex deviants that violate more abstract rules to probe higher order cognitive deficits. It is still unclear how sensory processing deficits compare to and contribute to higher order cognitive dysfunction, which can be investigated with later attention-dependent auditory event-related potential (ERP) components such as a subcomponent of P300, P3b. In this meta-analysis, we compared MMN deficits in SCZ using simple deviants to more complex deviants. We also pooled studies that measured MMN and P3b in the same study sample and examined the relationship between MMN and P3b deficits within study samples. Our analysis reveals that, to date, studies using simple deviants demonstrate larger deficits than those using complex deviants, with effect sizes in the range of moderate to large. The difference in effect sizes between deviant types was reduced significantly when accounting for magnitude of MMN measured in healthy controls. P3b deficits, while large, were only modestly greater than MMN deficits (d=0.21). Taken together, our findings suggest that MMN to simple deviants may still be optimal as a biomarker for SCZ and that sensory processing dysfunction contributes significantly to MMN deficit and disease pathophysiology. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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

2009-02-01

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

Localizing pre-attentive auditory memory-based comparison: magnetic mismatch negativity to pitch change.

PubMed

Maess, Burkhard; Jacobsen, Thomas; Schröger, Erich; Friederici, Angela D

2007-08-15

Changes in the pitch of repetitive sounds elicit the mismatch negativity (MMN) of the event-related brain potential (ERP). There exist two alternative accounts for this index of automatic change detection: (1) A sensorial, non-comparator account according to which ERPs in oddball sequences are affected by differential refractory states of frequency-specific afferent cortical neurons. (2) A cognitive, comparator account stating that MMN reflects the outcome of a memory comparison between a neuronal model of the frequently presented standard sound with the sensory memory representation of the changed sound. Using a condition controlling for refractoriness effects, the two contributions to MMN can be disentangled. The present study used whole-head MEG to further elucidate the sensorial and cognitive contributions to frequency MMN. Results replicated ERP findings that MMN to pitch change is a compound of the activity of a sensorial, non-comparator mechanism and a cognitive, comparator mechanism which could be separated in time. The sensorial part of frequency MMN consisting of spatially dipolar patterns was maximal in the late N1 range (105-125 ms), while the cognitive part peaked in the late MMN-range (170-200 ms). Spatial principal component analyses revealed that the early part of the traditionally measured MMN (deviant minus standard) is mainly due to the sensorial mechanism while the later mainly due to the cognitive mechanism. Inverse modeling revealed sources for both MMN contributions in the gyrus temporales transversus, bilaterally. These MEG results suggest temporally distinct but spatially overlapping activities of non-comparator-based and comparator-based mechanisms of automatic frequency change detection in auditory cortex.

Effects of an NMDA antagonist on the auditory mismatch negativity response to transcranial direct current stimulation.

PubMed

Impey, Danielle; de la Salle, Sara; Baddeley, Ashley; Knott, Verner

2017-05-01

Transcranial direct current stimulation (tDCS) is a non-invasive form of brain stimulation which uses a weak constant current to alter cortical excitability and activity temporarily. tDCS-induced increases in neuronal excitability and performance improvements have been observed following anodal stimulation of brain regions associated with visual and motor functions, but relatively little research has been conducted with respect to auditory processing. Recently, pilot study results indicate that anodal tDCS can increase auditory deviance detection, whereas cathodal tDCS decreases auditory processing, as measured by a brain-based event-related potential (ERP), mismatch negativity (MMN). As evidence has shown that tDCS lasting effects may be dependent on N-methyl-D-aspartate (NMDA) receptor activity, the current study investigated the use of dextromethorphan (DMO), an NMDA antagonist, to assess possible modulation of tDCS's effects on both MMN and working memory performance. The study, conducted in 12 healthy volunteers, involved four laboratory test sessions within a randomised, placebo and sham-controlled crossover design that compared pre- and post-anodal tDCS over the auditory cortex (2 mA for 20 minutes to excite cortical activity temporarily and locally) and sham stimulation (i.e. device is turned off) during both DMO (50 mL) and placebo administration. Anodal tDCS increased MMN amplitudes with placebo administration. Significant increases were not seen with sham stimulation or with anodal stimulation during DMO administration. With sham stimulation (i.e. no stimulation), DMO decreased MMN amplitudes. Findings from this study contribute to the understanding of underlying neurobiological mechanisms mediating tDCS sensory and memory improvements.

Inequality across consonantal contrasts in speech perception: evidence from mismatch negativity.

PubMed

Cornell, Sonia A; Lahiri, Aditi; Eulitz, Carsten

2013-06-01

The precise structure of speech sound representations is still a matter of debate. In the present neurobiological study, we compared predictions about differential sensitivity to speech contrasts between models that assume full specification of all phonological information in the mental lexicon with those assuming sparse representations (only contrastive or otherwise not predictable information is stored). In a passive oddball paradigm, we studied the contrast sensitivity as reflected in the mismatch negativity (MMN) response to changes in the manner of articulation, as well as place of articulation of consonants in intervocalic positions of nonwords (manner of articulation: [edi ~ eni], [ezi ~ eni]; place of articulation: [edi ~ egi]). Models that assume full specification of all phonological information in the mental lexicon posit equal MMNs within each contrast (symmetric MMNs), that is, changes from standard [edi] to deviant [eni] elicit a similar MMN response as changes from standard [eni] to deviant [edi]. In contrast, models that assume sparse representations predict that only the [ezi] ~ [eni] reversals will evoke symmetric MMNs because of their conflicting fully specified manner features. Asymmetric MMNs are predicted, however, for the reversals of [edi] ~ [eni] and [edi] ~ [egi] because either a manner or place property in each pair is not fully specified in the mental lexicon. Our results show a pattern of symmetric and asymmetric MMNs that is in line with predictions of the featurally underspecified lexicon model that assumes sparse phonological representations. We conclude that the brain refers to underspecified phonological representations during speech perception. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

Mismatch Negativity in Recent-Onset and Chronic Schizophrenia: A Current Source Density Analysis

PubMed Central

Fulham, W. Ross; Michie, Patricia T.; Ward, Philip B.; Rasser, Paul E.; Todd, Juanita; Johnston, Patrick J.; Thompson, Paul M.; Schall, Ulrich

2014-01-01

Mismatch negativity (MMN) is a component of the event-related potential elicited by deviant auditory stimuli. It is presumed to index pre-attentive monitoring of changes in the auditory environment. MMN amplitude is smaller in groups of individuals with schizophrenia compared to healthy controls. We compared duration-deviant MMN in 16 recent-onset and 19 chronic schizophrenia patients versus age- and sex-matched controls. Reduced frontal MMN was found in both patient groups, involved reduced hemispheric asymmetry, and was correlated with Global Assessment of Functioning (GAF) and negative symptom ratings. A cortically-constrained LORETA analysis, incorporating anatomical data from each individual's MRI, was performed to generate a current source density model of the MMN response over time. This model suggested MMN generation within a temporal, parietal and frontal network, which was right hemisphere dominant only in controls. An exploratory analysis revealed reduced CSD in patients in superior and middle temporal cortex, inferior and superior parietal cortex, precuneus, anterior cingulate, and superior and middle frontal cortex. A region of interest (ROI) analysis was performed. For the early phase of the MMN, patients had reduced bilateral temporal and parietal response and no lateralisation in frontal ROIs. For late MMN, patients had reduced bilateral parietal response and no lateralisation in temporal ROIs. In patients, correlations revealed a link between GAF and the MMN response in parietal cortex. In controls, the frontal response onset was 17 ms later than the temporal and parietal response. In patients, onset latency of the MMN response was delayed in secondary, but not primary, auditory cortex. However amplitude reductions were observed in both primary and secondary auditory cortex. These latency delays may indicate relatively intact information processing upstream of the primary auditory cortex, but impaired primary auditory cortex or cortico-cortical or thalamo-cortical communication with higher auditory cortices as a core deficit in schizophrenia. PMID:24949859

Making Sense of Missense in the Lynch Syndrome: The Clinical Perspective

PubMed Central

Lynch, Henry T.; Jascur, Thomas; Lanspa, Stephen; Boland, C. Richard

2010-01-01

The DNA mismatch repair system provides critical genetic housekeeping, and its failure is associated with tumorigenesis. Through distinct domains on the DNA mismatch repair proteins, the system recognizes and repairs errors occurring during DNA synthesis, but signals apoptosis when the DNA damage cannot be repaired. Certain missense mutations in the mismatch repair genes can selectively alter just one of these functions. This impacts the clinical features of tumors associated with defective DNA mismatch repair activity. New work reported by Xie et al. in this issue of the journal (beginning on page XXX) adds to the understanding of DNA mismatch repair. PMID:20978117

Decentralized Adaptive Control of Systems with Uncertain Interconnections, Plant-Model Mismatch and Actuator Failures

NASA Technical Reports Server (NTRS)

Patre, Parag; Joshi, Suresh M.

2011-01-01

Decentralized adaptive control is considered for systems consisting of multiple interconnected subsystems. It is assumed that each subsystem s parameters are uncertain and the interconnection parameters are not known. In addition, mismatch can exist between each subsystem and its reference model. A strictly decentralized adaptive control scheme is developed, wherein each subsystem has access only to its own state but has the knowledge of all reference model states. The mismatch is estimated online for each subsystem and the mismatch estimates are used to adaptively modify the corresponding reference models. The adaptive control scheme is extended to the case with actuator failures in addition to mismatch.

BatMis: a fast algorithm for k-mismatch mapping.

PubMed

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/

Bacterial genes mutL, mutS, and dcm participate in repair of mismatches at 5-methylcytosine sites.

PubMed Central

Lieb, M

1987-01-01

Certain amber mutations in the cI gene of bacteriophage lambda appear to recombine very frequently with nearby mutations. The aberrant mutations included C-to-T transitions at the second cytosine in 5'CC(A/T)GG sequences (which are subject to methylation by bacterial cytosine methylase) and in 5'CCAG and 5'CAGG sequences. Excess cI+ recombinants arising in crosses that utilize these mutations are attributable to the correction of mismatches by a bacterial very-short-patch (VSP) mismatch repair system. In the present study I found that two genes required for methyladenine-directed (long-patch) mismatch repair, mutL and mutS, also functioned in VSP mismatch repair; mutH and mutU (uvrD) were dispensable. VSP mismatch repair was greatly reduced in a dcm Escherichia coli mutant, in which 5-methylcytosine was not methylated. However, mismatches in heteroduplexes prepared from lambda DNA lacking 5-methylcytosine were repaired in dcm+ bacteria. These results indicate that the product of gene dcm has a repair function in addition to its methylase activity. PMID:2959653

Viral fusion efficacy of specific H3N2 influenza virus reassortant combinations at single-particle level

PubMed Central

Hsu, Hung-Lun; Millet, Jean K.; Costello, Deirdre A.; Whittaker, Gary R.; Daniel, Susan

2016-01-01

Virus pseudotyping is a useful and safe technique for studying entry of emerging strains of influenza virus. However, few studies have compared different reassortant combinations in pseudoparticle systems, or compared entry kinetics of native viruses and their pseudotyped analogs. Here, vesicular stomatitis virus (VSV)-based pseudovirions displaying distinct influenza virus envelope proteins were tested for fusion activity. We produced VSV pseudotypes containing the prototypical X-31 (H3) HA, either alone or with strain-matched or mismatched N2 NAs. We performed single-particle fusion assays using total internal reflection fluorescence microscopy to compare hemifusion kinetics among these pairings. Results illustrate that matching pseudoparticles behaved very similarly to native virus. Pseudoparticles harboring mismatched HA-NA pairings fuse at significantly slower rates than native virus, and NA-lacking pseudoparticles exhibiting the slowest fusion rates. Relative viral membrane HA density of matching pseudoparticles was higher than in mismatching or NA-lacking pseudoparticles. An equivalent trend of HA expression level on cell membranes of HA/NA co-transfected cells was observed and intracellular trafficking of HA was affected by NA co-expression. Overall, we show that specific influenza HA-NA combinations can profoundly affect the critical role played by HA during entry, which may factor into viral fitness and the emergence of new pandemic influenza viruses. PMID:27752100

Fit between Africa and Antarctica: A Continental Drift Reconstruction.

PubMed

Dietz, R S; Sproll, W P

1970-03-20

A computerized (smallest average misfit) best fit position is obtained for the juxtaposition of Africa and Antarctica in a continental drift reconstruction. An S-shaped portion of the Weddell and Princess Martha Coast regions of western East Antarctica is fitted into a similar profile along southeastern Africa. The total amount of overlap is 36,300 square kilometers, and the underlap is 23,600 square kilometers; the total mismatch is thus of 59,900 square kilometers. The congruency along the 1000-fathom isobath is remarkably good and suggests that this reconstruction is valid within the overall framework of the Gondwana supercontinent.

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

PubMed

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.

An Msh3 ATPase domain mutation has no effect on MMR function.

PubMed

Edwards, Yasmin

2017-11-25

To demonstrate that the Msh3 ATPase domain is required for DNA mismatch repair and tumor suppression in a murine model. The DNA mismatch repair proteins are members of the ABC family of ATPases. ATP binding and hydrolysis regulates their mismatch repair function. In the current study, a mouse model was generated harboring a glycine to aspartic acid residue change in the Walker A motif of the ATPase domain of Msh3. Impaired ATP mediated release of the Msh2-Msh3 GD/GD complex from it's DNA substrate in vitro confirmed the presence of an ATPase defect. However, the mismatch repair function of the protein was not significantly affected. Therefore, mutation of a critical residue within the ATPase domain of Msh3 did not preclude mismatch repair at the genomic sequences tested. Indicating that Msh3 mediated mismatch function is retained the absence of a functional ATPase domain.

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

PubMed Central

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

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

PubMed Central

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

Stereotype Fit Effects for Golf Putting Nonexperts

PubMed Central

Grimm, Lisa R.; Lewis, Benjamin; Maddox, W. Todd; Markman, Arthur B.

2015-01-01

Research has connected stereotype threat and regulatory fit by showing improved performance for individuals with negative stereotypes when they focused on minimizing potential losses. In the current study, non-Black participants, who were non-experts at golf putting, were told that a golf-putting task was diagnostic of natural athletic ability (i.e., negative stereotype) or sports intelligence (i.e., positive stereotype). Participants tried to maximize earned points or minimize lost points assigned after every putt, which was calculated based on the distance to a target. We demonstrate better performance for participants experiencing a fit between their global task stereotype and the task goal, and argue that regulatory fit allows for increased attention on the strategies beneficial for task performance. Interestingly, we find that performance of individuals high in working memory capacity suffers greatly when those individuals experience a regulatory mismatch. PMID:27162703

Amplitude by Peak Interaction but No Evidence of Auditory Mismatch Response Deficits to Frequency Change in Preschool-Aged Children with Fetal Alcohol Spectrum Disorders.

PubMed

Kabella, Danielle M; Flynn, Lucinda; Peters, Amanda; Kodituwakku, Piyadasa; Stephen, Julia M

2018-05-24

Prior studies indicate that the auditory mismatch response is sensitive to early alterations in brain development in multiple developmental disorders. Prenatal alcohol exposure is known to impact early auditory processing. The current study hypothesized alterations in the mismatch response in young children with fetal alcohol spectrum disorders (FASD). Participants in this study were 9 children with a FASD and 17 control children (Control) aged 3 to 6 years. Participants underwent magnetoencephalography and structural magnetic resonance imaging scans separately. We compared groups on neurophysiological mismatch negativity (MMN) responses to auditory stimuli measured using the auditory oddball paradigm. Frequent (1,000 Hz) and rare (1,200 Hz) tones were presented at 72 dB. There was no significant group difference in MMN response latency or amplitude represented by the peak located ~200 ms after stimulus presentation in the difference time course between frequent and infrequent tones. Examining the time courses to the frequent and infrequent tones separately, repeated measures analysis of variance with condition (frequent vs. rare), peak (N100m and N200m), and hemisphere as within-subject factors and diagnosis and sex as the between-subject factors showed a significant interaction of peak by diagnosis (p = 0.001), with a pattern of decreased amplitude from N100m to N200m in Control children and the opposite pattern in children with FASD. However, no significant difference was found with the simple effects comparisons. No group differences were found in the response latencies of the rare auditory evoked fields. The results indicate that there was no detectable effect of alcohol exposure on the amplitude or latency of the MMNm response to simple tones modulated by frequency change in preschool-aged children with FASD. However, while discrimination abilities to simple tones may be intact, early auditory sensory processing revealed by the interaction between N100m and N200m amplitude indicates that auditory sensory processing may be altered in children with FASD. Copyright © 2018 by the Research Society on Alcoholism.

Experience-Related Changes in Place Cell Responses to New Sensory Configuration That Does Not Occur in the Natural Environment in the Rat Hippocampus

PubMed Central

Zou, Dan; Nishimaru, Hiroshi; Matsumoto, Jumpei; Takamura, Yusaku; Ono, Taketoshi; Nishijo, Hisao

2017-01-01

The hippocampal formation (HF) is implicated in a comparator that detects sensory conflict (mismatch) among convergent inputs. This suggests that new place cells encoding the new configuration with sensory mismatch develop after the HF learns to accept the new configuration as a match. To investigate this issue, HF CA1 place cell activity in rats was analyzed after the adaptation of the rats to the same sensory mismatch condition. The rats were placed on a treadmill on a stage that was translocated in a figure 8-shaped pathway. We recorded HF neuronal activities under three conditions; (1) an initial control session, in which both the stage and the treadmill moved forward, (2) a backward (mismatch) session, in which the stage was translocated backward while the rats locomoted forward on the treadmill, and (3) the second control session. Of the 161 HF neurons, 56 place-differential activities were recorded from the HF CA1 subfield. These place-differential activities were categorized into four types; forward-related, backward-related, both-translocation-related, and session-dependent. Forward-related activities showed predominant spatial firings in the forward sessions, while backward-related activities showed predominant spatial firings in the backward sessions. Both-translocation-related activities showed consistent spatial firings in both the forward and backward conditions. On the other hand, session-dependent activities showed different spatial firings across the sessions. Detailed analyses of the place fields indicated that mean place field sizes were larger in the forward-related, backward-related, and both-translocation-related activities than in the session-dependent activities. Furthermore, firing rate distributions in the place fields were negatively skewed and asymmetric, which is similar to place field changes that occur after repeated experience. These results demonstrate that the HF encodes a naturally impossible new configuration of sensory inputs after adaptation, suggesting that the HF is capable of updating its stored memory to accept a new configuration as a match by repeated experience. PMID:28878682

Phenological mismatch with abiotic conditions implications for flowering in Arctic plants.

PubMed

Wheeler, Helen C; Høye, Toke T; Schmidt, Niels Martin; Svenning, Jens-Christian; Forchhammer, Mads C

2015-03-01

Although many studies have examined the phenological mismatches between interacting organisms, few have addressed the potential for mismatches between phenology and seasonal weather conditions. In the Arctic, rapid phenological changes in many taxa are occurring in association with earlier snowmelt. The timing of snowmelt is jointly affected by the size of the late winter snowpack and the temperature during the spring thaw. Increased winter snowpack results in delayed snowmelt, whereas higher air temperatures and faster snowmelt advance the timing of snowmelt. Where interannual variation in snowpack is substantial, changes in the timing of snowmelt can be largely uncoupled from changes in air temperature. Using detailed, long-term data on the flowering phenology of four arctic plant species from Zackenberg, Greenland, we investigate whether there is a phenological component to the temperature conditions experienced prior to and during flowering. In particular, we assess the role of timing of flowering in determining pre-flowering exposure to freezing temperatures and to the temperatures-experienced prior to flowering. We then examine the implications of flowering phenology for flower abundance. Earlier snowmelt resulted in greater exposure to freezing conditions, suggesting an increased potential for a mismatch between the timing of flowering and seasonal weather conditions and an increased potential for negative consequences, such as freezing 'damage. We also found a parabolic relationship between the timing of flowering and the temperature experienced during flowering after taking interannual temperature effects into account. If timing of flowering advances to a cooler period of the growing season, this may moderate the effects of a general warming trend across years. Flower abundance was quadratically associated with the timing of flowering, such that both early and late flowering led to lower flower abundance than did intermediate flowering. Our results indicate that shifting the timing of flowering affects the temperature experienced during flower development and flowering beyond that imposed by interannual variations in climate. We also found that phenological timing may affect flower abundance, and hence, fitness. These findings suggest that plant population responses to future climate change will be shaped not only by extrinsic climate forcing, but also by species' phenological responses.

The Case for High Resolution Extended 6-Loci HLA Typing for Identifying Related Donors in the Indian Subcontinent.

PubMed

Agarwal, Rajat Kumar; Kumari, Ankita; Sedai, Amit; Parmar, Lalith; Dhanya, Rakesh; Faulkner, Lawrence

2017-09-01

Three-loci low-resolution (LR) or intermediate-resolution HLA typing is generally considered adequate in the related blood and marrow transplantation (BMT) context. However, a single high-resolution (HR) mismatch may have a similar adverse impact on BMT outcome as an LR one. We sought to determine the frequency of mismatches that may go undetected when standard typing (LR or 3-loci HR) is used compared with 6-loci HR typing for related donor compatibility testing, and to assess its impact on relevant BMT outcomes. We analyzed data from a total of 2554 6-loci (HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1) HR sequence-based typing (full typing [FT]) from 754 patients, 1011 siblings, and 789 parents done at DKMS Germany (www.DKMS.de) between January 1, 2014, and June 21, 2016. We also studied 38 cases in which the family had undergone 3-loci HLA typing (standard typing [ST]). Patients were from India (70%), Pakistan (22%), and Sri Lanka (8%). The IMGT/HLA database (www.ebi.ac.uk/ipd/imgt/hla) was used to tease out nonpermissive DPB1 mismatches. HLA disparity-related outcomes, such as rejection and graft-versus-host disease (GVHD) were assessed in a retrospective matched-pair cohort of 50 patients (25 with ST and 25 with FT) who underwent BMT for severe thalassemia from compatible related donors. We found fully matched (either 12/12 HR matches or with a single permissive DPB1 mismatch) related donors for 285 patients (38%). Of these donors, 89% were siblings and 11% were parents. The likelihood of matching on an individual locus on LR but not on HR was found to be 5%. A total of 9 donors (3%; 7 siblings and 2 parents) who would have been considered a full match by HR typing on A, B, and DRB1 alone were not a match by extended 6-loci HR typing. Five of these 9 donors had a mismatch on C or DQB1, and 4 had a nonpermissive DPB1 mismatch. In this group, 5 donors (56%) belonged to a consanguineous family, in 2 donors (22%) there was no reported consanguinity, and in 2 donors (22%) consanguinity was unknown. We identified 18 donors (6%; 13 siblings and 5 parents) who would have been considered a 12/12 match by LR HLA typing alone but were found not to match on extended HR typing. In this group, 11 donors (61%) were from consanguineous families, 3 donors (17%) had no reported consanguinity, and in 4 donors (22%) consanguinity was unknown. Outcome analysis showed that the actuarial proportion of patients with GVHD was 4% in the FT group compared with 16% in the ST group, with log-rank P = .1952. The ST group included 2 patients with grade III-IV acute GVHD and 1 patient each with moderate and severe chronic GVHD, whereas the FT group only 1 patient with grade III acute GVHD. We conclude that even in the context of related donors, the use of LR and/or 3-loci (A, B, and DRB1) HR HLA typing might result in a sizable risk of missing a clinically relevant mismatch, which may have an adverse impact on transplantation outcomes. In the Indian subcontinent, this observation is not limited to putatively compatible parents or consanguineous families; we recommend full 6-loci HR HLA typing even for matched related BMTs. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Graft versus host disease after stem cell allotransplantation with low-dose total body irradiation, fludarabine, and antithymocyte globulin.

PubMed

Grosskreutz, Celia; Scigliano, Eileen; Osman, Keren; Isola, Luis

2007-09-15

We previously showed that antithymocyte globulin (ATG) given with total body irradiation (TBI) 200 cGy and fludarabine results in high rate of donor engraftment. Its influence on acute and chronic graft versus host disease (GVHD) and on graft versus tumor effect is less known. Sixty-five patients underwent nonmyeloablative stem cell transplant with ATG, TBI 200 cGy, and fludarabine. GVHD prophylaxis was mycophenolate mofetil and cyclosporine. Forty-two patients (pts) (65%) had match related donors, 18 (27%) match unrelated, 1 (1.5%) mismatch related, and 4 (6%) mismatch unrelated donors. At a median follow-up of 862 days, 24 patients (37%) developed GVHD. The median age of the patients with and without GVHD was 56 years respectively. Acute GVHD grade II-IV developed in 19 pts (29%). Fatal GVHD of liver and/or gut occurred in nine pts (14%). Forty-one pts survived more than 100 days. Five pts (12%) had chronic GVHD, two had extensive, and three had limited involvement. Relapsed disease was observed in 22 pts (34%). Infections occurred in 15 pts (23%) and were fatal in 13 (20%). The addition of ATG to TBI 200cGy and fludarabine resulted in a modest incidence of GVHD. The best transplant outcomes were observed in pts with lymphoid malignancies.

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

PubMed

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

2016-03-04

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

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

PubMed Central

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

2016-01-01

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

Twin-mediated epitaxial growth of highly lattice-mismatched Cu/Ag core-shell nanowires.

PubMed

Weng, Wei-Lun; Hsu, Chin-Yu; Lee, Jheng-Syun; Fan, Hsin-Hsin; Liao, Chien-Neng

2018-05-31

Lattice-mismatch is an important factor for the heteroepitaxial growth of core-shell nanostructures. A large lattice-mismatch usually leads to a non-coherent interface or a polycrystalline shell layer. In this study, a conformal Ag layer is coated on Cu nanowires with dense nanoscale twin boundaries through a galvanic replacement reaction. Despite a large lattice mismatch between Ag and Cu (∼12.6%), the Ag shell replicates the twinning structure in Cu nanowires and grows epitaxially on the nanotwinned Cu nanowire. A twin-mediated growth mechanism is proposed to explain the epitaxy of high lattice-mismatch bimetallic systems in which the misfit dislocations are accommodated by coherent twin boundaries.

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.

PubMed

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.

Patient-prosthesis mismatch in aortic valve replacement: really tolerable?

PubMed

Fuster, Rafael García; Montero Argudo, José A; Albarova, Oscar Gil; Sos, Fernando Hornero; López, Sergio Cánovas; Codoñer, María Bueno; Buendía Miñano, José A; Albarran, Ignacio Rodríguez

2005-03-01

Several studies have demonstrated favorable results despite patient-prosthesis mismatch after aortic valve replacement with the use of third generation prostheses. Our aim was to determine whether this mismatch is always tolerable. A clinical-echocardiographic study has been performed in 339 consecutive patients who underwent aortic valve replacement because of aortic stenosis. In-hospital outcome and left ventricular mass index regression (1st month-1st year) were analyzed in the presence or absence of mismatch (indexed effective orifice area < or =0.85cm(2)/m(2)). The influence of high degrees of preoperative left ventricular mass on in-hospital mortality has also been evaluated. Left ventricular mass index was considered increased if the calculated value was over the superior quartile of the frequency distribution of all the values observed in both sexes. Mismatch was found in 38% of the patients. In the absence of mismatch, the absolute mass regression was proportional to the preoperative left ventricular mass. This regression was higher in patients with increased left ventricular mass indexed (vs not increased): -38.0+/-7.8 vs -8.8+/-4.7g/m(2), p<0.01 (1st month) and -67.7+/-16.9vs -23.5+/-6.7g/m(2), p<0.05 (1st year). Mass regression was impaired in the presence of mismatch, particularly, in patients with previously increased left ventricular mass: -8.2+/-11.6 vs -5.6+/-6.3g/m(2) (p=0.83) and -24.6+/-12.6 vs -11.7+/-10.5g/m(2) (p=0.54). This worse regression was reflected on a 100% incidence of residual hypertrophy at follow-up (1st month-1st year). In the presence of mismatch, increased ventricular mass was associated with higher mortality: 14.7% vs 2.1% (p<0.01). In the absence of mismatch, ventricular mass was not associated with mortality: 4.1 vs 2.5% (p=0.55). In patients with severe ventricular hypertrophy it may be important to elude patient-prosthesis mismatch to avoid a significant increase in mortality and improve ventricular mass regression. Mismatch may be tolerable in those patients with lesser degree of hypertrophy.

Mid-infrared Plasmonic Circular Dichroism Generated by Graphene Nanodisk Assemblies.

PubMed

Kong, Xiang-Tian; Zhao, Runbo; Wang, Zhiming; Govorov, Alexander O

2017-08-09

It is very interesting to bring plasmonic circular dichroism spectroscopy to the mid-infrared spectral interval, and there are two reasons for this. This spectral interval is very important for thermal bioimaging, and simultaneously, this spectral range includes vibrational lines of many chiral biomolecules. Here we demonstrate that graphene plasmons indeed offer such opportunity. In particular, we show that chiral graphene assemblies consisting of a few graphene nanodisks can generate strong circular dichroism (CD) in the mid-infrared interval. The CD signal is generated due to the plasmon-plasmon coupling between adjacent nanodisks in the specially designed chiral graphene assemblies. Because of the large dimension mismatch between the thickness of a graphene layer and the incoming light's wavelength, three-dimensional configurations with a total height of a few hundred nanometers are necessary to obtain a strong CD signal in the mid-infrared range. The mid-infrared CD strength is mainly governed by the total dimensions (total height and helix scaffold radius) of the graphene nanodisk assembly and by the plasmon-plasmon interaction strength between its constitutive nanodisks. Both positive and negative CD bands can be observed in the graphene assembly array. The frequency interval of the plasmonic CD spectra overlaps with the vibrational modes of some important biomolecules, such as DNA and many different peptides, giving rise to the possibility of enhancing the vibrational optical activity of these molecular species by attaching them to the graphene assemblies. Simultaneously the spectral range of chiral mid-infrared plasmons in our structures appears near the typical wavelength of the human-body thermal radiation, and therefore, our chiral metastructures can be potentially utilized as optical components in thermal imaging devices.

Trivalent inactivated influenza vaccine effective against influenza A(H3N2) variant viruses in children during the 2014/15 season, Japan

PubMed Central

Sugaya, Norio; Shinjoh, Masayoshi; Kawakami, Chiharu; Yamaguchi, Yoshio; Yoshida, Makoto; Baba, Hiroaki; Ishikawa, Mayumi; Kono, Mio; Sekiguchi, Shinichiro; Kimiya, Takahisa; Mitamura, Keiko; Fujino, Motoko; Komiyama, Osamu; Yoshida, Naoko; Tsunematsu, Kenichiro; Narabayashi, Atsushi; Nakata, Yuji; Sato, Akihiro; Taguchi, Nobuhiko; Fujita, Hisayo; Toki, Machiko; Myokai, Michiko; Ookawara, Ichiro; Takahashi, Takao

2016-01-01

The 2014/15 influenza season in Japan was characterised by predominant influenza A(H3N2) activity; 99% of influenza A viruses detected were A(H3N2). Subclade 3C.2a viruses were the major epidemic A(H3N2) viruses, and were genetically distinct from A/New York/39/2012(H3N2) of 2014/15 vaccine strain in Japan, which was classified as clade 3C.1. We assessed vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) in children aged 6 months to 15 years by test-negative case–control design based on influenza rapid diagnostic test. Between November 2014 and March 2015, a total of 3,752 children were enrolled: 1,633 tested positive for influenza A and 42 for influenza B, and 2,077 tested negative. Adjusted VE was 38% (95% confidence intervals (CI): 28 to 46) against influenza virus infection overall, 37% (95% CI: 27 to 45) against influenza A, and 47% (95% CI: -2 to 73) against influenza B. However, IIV was not statistically significantly effective against influenza A in infants aged 6 to 11 months or adolescents aged 13 to 15 years. VE in preventing hospitalisation for influenza A infection was 55% (95% CI: 42 to 64). Trivalent IIV that included A/New York/39/2012(H3N2) was effective against drifted influenza A(H3N2) virus, although vaccine mismatch resulted in low VE. PMID:27784529

A Discrete Event Simulation Model of Patient Flow in a General Hospital Incorporating Infection Control Policy for Methicillin-Resistant Staphylococcus Aureus (MRSA) and Vancomycin-Resistant Enterococcus (VRE).

PubMed

Shenoy, Erica S; Lee, Hang; Ryan, Erin E; Hou, Taige; Walensky, Rochelle P; Ware, Winston; Hooper, David C

2018-02-01

Hospitalized patients are assigned to available staffed beds based on patient acuity and services required. In hospitals with double-occupancy rooms, patients must be additionally matched by gender. Patients with methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) must be bedded in single-occupancy rooms or cohorted with other patients with similar MRSA/VRE flags. We developed a discrete event simulation (DES) model of patient flow through an acute care hospital. Patients are matched to beds based on acuity, service, gender, and known MRSA/VRE colonization. Outcomes included time to bed arrival, length of stay, patient-bed acuity mismatches, occupancy, idle beds, acuity-related transfers, rooms with discordant MRSA/VRE colonization, and transmission due to discordant colonization. Observed outcomes were well-approximated by model-generated outcomes for time-to-bed arrival (6.7 v. 6.2 to 6.5 h) and length of stay (3.3 v. 2.9 to 3.0 days), with overlapping 90% coverage intervals. Patient-bed acuity mismatches, where patient acuity exceeded bed acuity and where patient acuity was lower than bed acuity, ranged from 0.6 to 0.9 and 8.6 to 11.1 mismatches per h, respectively. Values for observed occupancy, total idle beds, and acuity-related transfers compared favorably to model-predicted values (91% v. 86% to 87% occupancy, 15.1 v. 14.3 to 15.7 total idle beds, and 27.2 v. 22.6 to 23.7 transfers). Rooms with discordant colonization status and transmission due to discordance were modeled without an observed value for comparison. One-way and multi-way sensitivity analyses were performed for idle beds and rooms with discordant colonization. We developed and validated a DES model of patient flow incorporating MRSA/VRE flags. The model allowed for quantification of the substantial impact of MRSA/VRE flags on hospital efficiency and potentially avoidable nosocomial transmission.

A computational parametric study on edge loading in ceramic-on-ceramic total hip joint replacements.

PubMed

Liu, Feng; Feng, Li; Wang, Junyuan

2018-07-01

Edge loading in ceramic-on-ceramic total hip joint replacement is an adverse condition that occurs as the result of a direct contact between the head and the cup rim. It has been associated with translational mismatch in the centres of rotation of the cup and head, and found to cause severe wear and early failure of the implants. Edge loading has been considered in particular in relation to dynamic separation of the cup and head centres during a gait cycle. Research has been carried out both experimentally and computationally to understand the mechanism including the influence of bearing component positioning on the occurrence and severity of edge loading. However, it is experimentally difficult to measure both the load magnitude and duration of edge loading as it occurs as a short impact within the tight space of hip joints. Computationally, a dynamic contact model, for example, developed using the MSC ADAMS software for a multi-body dynamics simulation can be particularly useful for calculating the loads and characterising the edge loading. The aim of the present study was to further develop the computational model, and improve the predictions of contact force and the understanding of mechanism in order to provide guidance on design and surgical factors to avoid or to reduce edge loading and wear. The results have shown that edge loading can be avoided for a low range of translational mismatch in the centres of rotation of the cup and head during gait at the level of approximately 1.0 mm for a cup at 45° inclination, keeping a correct cup inclination at 45° is important to reduce the edge loading severity, and edge loading can be avoided for a certain range of translational mismatch of the cup and head centres with an increased swing phase load. Copyright © 2018 Elsevier Ltd. All rights reserved.

Indoleamine 2,3-dioxygenase in endometrial cancer: a targetable mechanism of immune resistance in mismatch repair-deficient and intact endometrial carcinomas.

PubMed

Mills, Anne; Zadeh, Sara; Sloan, Emily; Chinn, Zachary; Modesitt, Susan C; Ring, Kari L

2018-03-20

Mismatch repair-deficient endometrial carcinomas are optimal candidates for immunotherapy given their high neoantigen loads, robust lymphoid infiltrates, and frequent PD-L1 expression. However, co-opting the PD-1/PD-L1 pathway is just one mechanism that tumors can utilize to evade host immunity. Another immune modulatory molecule that has been demonstrated in endometrial carcinoma is indoleamine 2,3-dioxygenase (IDO). We herein evaluate IDO expression in 60 endometrial carcinomas and assess results in relation to PD-L1 and mismatch repair status. IDO immunohistochemistry was performed on 60 endometrial carcinomas (20 Lynch syndrome (LS)-associated, 20 MLH1 promoter hypermethylated, and 20 mismatch repair-intact). Eight-five percent of endometrial carcinomas showed IDO tumor staining in >1% of cells. Twenty-five percent were positive in >25% of tumor cells and only 7% exceeded 50% staining. Mismatch repair-deficient cancers were more likely than mismatch repair-intact cancers to be >25% IDO-positive (35% vs. 5% p = 0.024). Differences were amplified when Lynch syndrome-associated cases were evaluated in isolation (50% Lynch syndrome-associated vs. 10% mismatch repair-intact and MLH1-hypermethylated, p = 0.001). Of the four cases showing >50% staining, three were Lynch syndrome-associated and one was MLH1-hypermethylated; no mismatch repair-intact cases had >50% staining. Forty-three percent of IDO-positive tumors were also positive for PD-L1, whereas only two cases showed tumoral PD-L1 in the absence of IDO. In summary, IDO expression is prevalent in endometrial carcinomas and diffuse staining is significantly more common in mismatch repair-deficient cancers, particularly Lynch syndrome-associated cases. Given that the majority of PD-L1 positive cancers also express IDO, synergistic combination therapy with anti-IDO and anti-PD1/PD-L1 may be relevant in this tumor type. Furthermore, anti-IDO therapy may be an option for a small subset of mismatch repair-intact cancers.

Photovoltaic module hot spot durability design and test methods

NASA Technical Reports Server (NTRS)

Arnett, J. C.; Gonzalez, C. C.

1981-01-01

As part of the Jet Propulsion Laboratory's Low-Cost Solar Array Project, the susceptibility of fat-plate modules to hot-spot problems is investigated. Hot-spot problems arise in modules when the cells become back-biased and operate in the negative-voltage quadrant, as a result of short-circuit current mismatch, cell cracking or shadowing. The details of a qualification test for determining the capability of modules of surviving field hot-spot problems and typical results of this test are presented. In addition, recommended circuit-design techniques for improving the module and array reliability with respect to hot-spot problems are presented.

Impact of HLA compatibility on lung transplant survival and evidence for an HLA restriction phenomenon: a collaborative transplant study report.

PubMed

Opelz, Gerhard; Süsal, Caner; Ruhenstroth, Andrea; Döhler, Bernd

2010-10-27

Data concerning the impact of human leukocyte antigen (HLA) compatibility on lung transplant survival rates are limited. Using the Collaborative Transplant Study database, 5-year graft outcome according to HLA mismatch was examined in 8020 deceased donor lung transplants performed during 1989 to 2009. Graft survival rates showed a stepwise decrease as the combined number of HLA-A+B+DR mismatches increased from one to six (P<0.001). Surprisingly, the 28 grafts with 0 mismatches at all 3 loci had a 1-year survival rate of only 49.7%, significantly lower than for 1, 2, 3, 4, 5, or 6 mismatches (P=0.002, <0.001, <0.001, <0.001, 0.002, and 0.003, respectively). Multivariate regression analysis confirmed that, paradoxically, transplantation of grafts with zero HLA-A+B+DR mismatches was associated with a 19% increase in relative risk of failure. Donor lung preservation for up to 12 hr was not associated with inferior graft survival versus shorter preservation times (P=0.60). Our data show that a high number of HLA mismatches or zero mismatches impacts unfavorably on lung transplant survival.

Evaluation of the match between anthropometric measures and school furniture dimensions in Chile.

PubMed

Castellucci, H I; Catalán, M; Arezes, P M; Molenbroek, J F M

2015-01-01

Students are exposed to the first systematic tasks or activities that a human being carries out in his/her life while at school. In this workplace situation, school furniture is a key factor for the adoption of proper body posture. The aim of this paper was to observe and determine the potential mismatch between school furniture dimensions and anthropometric characteristics of the students from the Valparaíso region of Chile. The sample consisted of 3,078 volunteer participants from 18 schools (public, semi-public, private). Eight anthropometric measures were gathered, together with six furniture dimensions. Mismatch analyses were carried out by using pre-defined mismatch criteria. Many different types of school furniture were presented at the schools. Also, a high level of mismatch was registered for seat height, desk height and seat-to-desk clearance. Finally, the analysis of all considered dimensions together showed that there was a high level of cumulative mismatch. It can be concluded that there were high levels of mismatch between the school furniture and student anthropometric characteristics and that this mismatch varied within the difference types of schools. This situation may have occurred because furniture acquisition was made without considering any ergonomic criteria.

Mood Modulates Auditory Laterality of Hemodynamic Mismatch Responses during Dichotic Listening

PubMed Central

Schock, Lisa; Dyck, Miriam; Demenescu, Liliana R.; Edgar, J. Christopher; Hertrich, Ingo; Sturm, Walter; Mathiak, Klaus

2012-01-01

Hemodynamic mismatch responses can be elicited by deviant stimuli in a sequence of standard stimuli even during cognitive demanding tasks. Emotional context is known to modulate lateralized processing. Right-hemispheric negative emotion processing may bias attention to the right and enhance processing of right-ear stimuli. The present study examined the influence of induced mood on lateralized pre-attentive auditory processing of dichotic stimuli using functional magnetic resonance imaging (fMRI). Faces expressing emotions (sad/happy/neutral) were presented in a blocked design while a dichotic oddball sequence with consonant-vowel (CV) syllables in an event-related design was simultaneously administered. Twenty healthy participants were instructed to feel the emotion perceived on the images and to ignore the syllables. Deviant sounds reliably activated bilateral auditory cortices and confirmed attention effects by modulation of visual activity. Sad mood induction activated visual, limbic and right prefrontal areas. A lateralization effect of emotion-attention interaction was reflected in a stronger response to right-ear deviants in the right auditory cortex during sad mood. This imbalance of resources may be a neurophysiological correlate of laterality in sad mood and depression. Conceivably, the compensatory right-hemispheric enhancement of resources elicits increased ipsilateral processing. PMID:22384105

Beyond Gender Stereotypes in Language Comprehension: Self Sex-Role Descriptions Affect the Brain’s Potentials Associated with Agreement Processing

PubMed Central

Canal, Paolo; Garnham, Alan; Oakhill, Jane

2015-01-01

We recorded Event-Related Potentials to investigate differences in the use of gender information during the processing of reflexive pronouns. Pronouns either matched the gender provided by role nouns (such as “king” or “engineer”) or did not. We compared two types of gender information, definitional information, which is semantic in nature (a mother is female), or stereotypical (a nurse is likely to be female). When they followed definitional role-nouns, gender-mismatching pronouns elicited a P600 effect reflecting a failure in the agreement process. When instead the gender violation occurred after stereotypical role-nouns the Event Related Potential response was biphasic, being positive in parietal electrodes and negative in anterior left electrodes. The use of a correlational approach showed that those participants with more “feminine” or “expressive” self sex-role descriptions showed a P600 response for stereotype violations, suggesting that they experienced the mismatch as an agreement violation; whereas less “expressive” participants showed an Nref effect, indicating more effort spent in linking the pronouns with the possible, although less likely, counter-stereotypical referent. PMID:26779046

Biallelic MLH1 SNP cDNA expression or constitutional promoter methylation can hide genomic rearrangements causing Lynch syndrome.

PubMed

Morak, Monika; Koehler, Udo; Schackert, Hans Konrad; Steinke, Verena; Royer-Pokora, Brigitte; Schulmann, Karsten; Kloor, Matthias; Höchter, Wilhelm; Weingart, Josef; Keiling, Cortina; Massdorf, Trisari; Holinski-Feder, Elke

2011-08-01

A positive family history, germline mutations in DNA mismatch repair genes, tumours with high microsatellite instability, and loss of mismatch repair protein expression are the hallmarks of hereditary non-polyposis colorectal cancer (Lynch syndrome). However, in ~10-15% of cases of suspected Lynch syndrome, no disease-causing mechanism can be detected. Oligo array analysis was performed to search for genomic imbalances in patients with suspected mutation-negative Lynch syndrome with MLH1 deficiency in their colorectal tumours. A deletion in the LRRFIP2 (leucine-rich repeat flightless-interacting protein 2) gene flanking the MLH1 gene was detected, which turned out to be a paracentric inversion on chromosome 3p22.2 creating two new stable fusion transcripts between MLH1 and LRRFIP2. A single-nucleotide polymorphism in MLH1 exon 8 was expressed from both alleles, initially pointing to appropriate MLH1 function at least in peripheral cells. In a second case, an inherited duplication of the MLH1 gene region resulted in constitutional MLH1 promoter methylation. Constitutional MLH1 promoter methylation may therefore in rare cases be a heritable disease mechanism and should not be overlooked in seemingly sporadic patients.

Disruption of hierarchical predictive coding during sleep

PubMed Central

Strauss, Melanie; Sitt, Jacobo D.; King, Jean-Remi; Elbaz, Maxime; Azizi, Leila; Buiatti, Marco; Naccache, Lionel; van Wassenhove, Virginie; Dehaene, Stanislas

2015-01-01

When presented with an auditory sequence, the brain acts as a predictive-coding device that extracts regularities in the transition probabilities between sounds and detects unexpected deviations from these regularities. Does such prediction require conscious vigilance, or does it continue to unfold automatically in the sleeping brain? The mismatch negativity and P300 components of the auditory event-related potential, reflecting two steps of auditory novelty detection, have been inconsistently observed in the various sleep stages. To clarify whether these steps remain during sleep, we recorded simultaneous electroencephalographic and magnetoencephalographic signals during wakefulness and during sleep in normal subjects listening to a hierarchical auditory paradigm including short-term (local) and long-term (global) regularities. The global response, reflected in the P300, vanished during sleep, in line with the hypothesis that it is a correlate of high-level conscious error detection. The local mismatch response remained across all sleep stages (N1, N2, and REM sleep), but with an incomplete structure; compared with wakefulness, a specific peak reflecting prediction error vanished during sleep. Those results indicate that sleep leaves initial auditory processing and passive sensory response adaptation intact, but specifically disrupts both short-term and long-term auditory predictive coding. PMID:25737555

Processing visual words with numbers: electrophysiological evidence for semantic activation.

PubMed

Lien, Mei-Ching; Allen, Philip; Martin, Nicole

2014-08-01

Perea, Duñabeitia, and Carreiras (Journal of Experimental Psychology: Human Perception and Performance 34:237-241, 2008) found that LEET stimuli, formed by a mixture of digits and letters (e.g., T4BL3 instead of TABLE), produced priming effects similar to those for regular words. This finding led them to conclude that LEET stimuli automatically activate lexical information. In the present study, we examined whether semantic activation occurs for LEET stimuli by using an electrophysiological measure called the N400 effect. The N400 effect, also known as the mismatch negativity, reflects detection of a mismatch between a word and the current semantic context. This N400 effect could occur only if the LEET stimulus had been identified and processed semantically. Participants determined whether a stimulus (word or LEET) was related to a given category (e.g., APPLE or 4PPL3 belongs to the category "fruit," but TABLE or T4BL3 does not). We found that LEET stimuli produced an N400 effect similar in magnitude to that for regular uppercase words, suggesting that LEET stimuli can access meaning in a manner similar to words presented in consistent uppercase letters.

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.

PubMed

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.

PD-L1 overexpression in ampulla of Vater carcinoma and its pre-invasive lesions.

PubMed

Saraggi, Deborah; Galuppini, Francesca; Remo, Andrea; Urso, Emanuele D L; Bacchin, Deborah; Salmaso, Roberta; Lanza, Cristiano; Bao, Riccardo Q; Fanelli, Giuseppe N; Guzzardo, Vincenza; Luchini, Claudio; Scarpa, Marco; Farinati, Fabio; Fassan, Matteo; Rugge, Massimo

2017-09-01

PD-1/PD-L1 checkpoint immunotherapy has been proposed recently as a promising treatment in relapsed/refractory disease, used eventually in combination with traditional chemotherapy in different cancer settings. To date, no data are available concerning PD-L1 expression in ampulla of Vater carcinoma and its pre-invasive lesions. We assessed the immunohistochemical expression of PD-L1 in a series of 26 ampullary adenocarcinomas, 50 ampullary dysplastic lesions and 10 normal duodenal mucosa samples. Moreover, in all cases DNA mismatch repair proteins status was investigated. PD-L1 was expressed in seven of 26 (26.9%) invasive carcinomas and three of 50 (6.0%) dysplastic samples. Most of the PD-L1-positive tumours (seven of 10) were intestinal-type and poorly differentiated (G3). The number of PD-L1-positive stromal lymphoid cells was significantly higher in dysplastic and invasive lesions than in the normal samples (P = 0.011). Nineteen dysplastic lesions and eight invasive carcinomas did not show any evident epithelial or stromal PD-L1 expression. Four of the carcinomas were mismatch repair-deficient and two of these were PD-L1-positive. Furthermore, mismatch repair-deficient lesions showed a significantly higher average of PD-L1-positive stromal lymphoid cells than those of neoplastic PD-L1-negative samples (62.8 versus 21.6; P < 0.001). The present results suggest a role of the PD-1/PD-L1 axis in ampullary adenocarcinomas, and therefore this may also prompt consideration of checkpoint immunotherapy as a novel promising treatment for these tumours. © 2017 John Wiley & Sons Ltd.

Relationship between PTEN, DNA mismatch repair, and tumor histotype in endometrial carcinoma: retained positive expression of PTEN preferentially identifies sporadic non-endometrioid carcinomas.

PubMed

Djordjevic, Bojana; Barkoh, Bedia A; Luthra, Rajyalakshmi; Broaddus, Russell R

2013-10-01

Loss of PTEN (phosphatase and tensin homolog) expression and microsatellite instability are two of the more common molecular alterations in endometrial carcinoma. From the published literature, it is controversial as to whether there is a relationship between these different molecular mechanisms. Therefore, a cohort of 187 pure endometrioid and non-endometrioid endometrial carcinomas, carefully characterized as to clinical and pathological features, was examined for PTEN sequence abnormalities and the immunohistochemical expression of PTEN and the DNA mismatch repair proteins MLH1, MSH2, MSH6, and PMS2. MLH1 methylation analysis was performed when tumors had loss of MLH1 protein. Mismatch repair protein loss was more frequent in endometrioid carcinomas compared with non-endometrioid carcinomas, a difference primarily attributable to the presence of MLH1 methylation in a greater proportion of endometrioid tumors. Among the non-endometrioid group, mixed endometrioid/non-endometrioid carcinomas were the histotype that most commonly had loss of a mismatch repair protein. In endometrioid tumors, the frequency of PTEN loss measured by immunohistochemistry and mutation did not differ significantly between the mismatch repair protein intact or mismatch repair protein loss groups, suggesting that PTEN loss is independent of mismatch protein repair status in this group. However, in non-endometrioid carcinomas, both intact positive PTEN immunohistochemical expression and PTEN wild type were highly associated with retained positive expression of mismatch repair proteins in the tumor. Relevant to screening endometrial cancers for Lynch Syndrome, an initial PTEN immunohistochemistry determination may be able to replace the use of four mismatch repair immunohistochemical markers in 63% of patients with non-endometrioid endometrial carcinoma. Therefore, PTEN immunohistochemistry, in combination with tumor histotype, is a useful adjunct in the clinical evaluation of endometrial carcinomas for Lynch Syndrome.

Spatial Mismatch: A Third Generation Survey.

ERIC Educational Resources Information Center

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…

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

PubMed Central

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

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

PubMed

Hodel, Karl P; de Borja, Richard; Henninger, Erin E; Campbell, Brittany B; Ungerleider, Nathan; Light, Nicholas; Wu, Tong; LeCompte, Kimberly G; Goksenin, A Yasemin; Bunnell, Bruce A; Tabori, Uri; Shlien, Adam; Pursell, Zachary F

2018-02-28

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. © 2018, Hodel et al.

Coordination success and interpersonal perceptions: matching versus mismatching.

PubMed

Abele, Susanne; Stasser, Garold

2008-09-01

Coordination is an essential part of social functioning. The authors distinguish 2 types of coordination: matching and mismatching. In matching, coordination is successful if parties choose the same action. In mismatching, coordination is successful if people choose different actions. In 3 studies, the authors investigated the downstream social consequences of tacit coordination for interpersonal perceptions. In all studies, participants repeatedly choose between 2 bets with equivalent expected values, and payoffs increased either when they choose the same bet or when they choose different bets. In the 1st 2 studies, coordination success increased the perceptions of interpersonal similarity and liking when matching was required but not when mismatching was required. The authors' interpretation is that matching responses and coordination success had countervailing effects in the mismatching task. Also, percentage of matched responses did not affect perceptions when coordination was not required (Experiment 2). In 4 person teams, a frequently matching partner was viewed more favorably (smarter, more similar to self, and more liked) than were other teammates, even when mismatching increased payoffs (Experiment 3).

ABO incompatibility in mismatched unrelated donor allogeneic hematopoietic cell transplantation for acute myeloid leukemia: A report from the acute leukemia working party of the EBMT.

PubMed

Canaani, Jonathan; Savani, Bipin N; Labopin, Myriam; Michallet, Mauricette; Craddock, Charles; Socié, Gerard; Volin, Lisa; Maertens, Johan A; Crawley, Charles; Blaise, Didier; Ljungman, Per T; Cornelissen, Jan; Russell, Nigel; Baron, Frédéric; Gorin, Norbert; Esteve, Jordi; Ciceri, Fabio; Schmid, Christoph; Giebel, Sebastian; Mohty, Mohamad; Nagler, Arnon

2017-08-01

ABO incompatibility is commonly observed in stem cell transplantation and its impact in this setting has been extensively investigated. HLA-mismatched unrelated donors (MMURD) are often used as an alternative stem cell source but are associated with increased transplant related complications. Whether ABO incompatibility affects outcome in MMURD transplantation for acute myeloid leukemia (AML) patients is unknown. We evaluated 1,013 AML patients who underwent MMURD transplantation between 2005 and 2014. Engraftment rates were comparable between ABO matched and mismatched patients, as were relapse incidence [34%; 95% confidence interval (CI), 28-39; for ABO matched vs. 36%; 95% CI, 32-40; for ABO mismatched; P = .32], and nonrelapse mortality (28%; 95% CI, 23-33; for ABO matched vs. 25%; 95% CI, 21-29; for ABO mismatched; P = .2). Three year survival was 40% for ABO matched and 43% for ABO mismatched patients (P = .35), Leukemia free survival rates were also comparable between groups (37%; 95% CI, 32-43; for ABO matched vs. 38%; 95% CI, 33-42; for ABO mismatched; P = .87). Incidence of grade II-IV acute graft versus host disease was marginally lower in patients with major ABO mismatching (Hazard ratio of 0.7, 95% CI, 0.5-1; P = .049]. ABO incompatibility probably has no significant clinical implications in MMURD transplantation. © 2017 Wiley Periodicals, Inc.

Future HLA matching strategies in clinical transplantation.

PubMed

Claas, Frans H J; Roelen, Dave L; Oudshoorn, Machteld; Doxiadis, Ilias I N

2003-01-01

HLA matching has shown to be beneficial in clinical transplantation. Due to the enormous polymorphism of the HLA system, however, it is not feasible to select a completely HLA-matched donor for every potential recipient. Only for patients with frequently occurring HLA phenotypes is it realistic to expect a well-matched donor within a reasonable waiting time. The majority of patients will be transplanted with a partially mismatched donor. In order to select the optimal donor for this category of patients, it is important to take advantage of the differential immunogenicity and thus differential importance of mismatched HLA antigens. Based on retrospective analyses of graft survival data and in vitro tests measuring T-cell alloreactivity, the relative importance of different mismatches was evaluated. It has been possible to define acceptable or permissible mismatches with a low immunogenicity, which are associated with a good graft survival, versus taboo mismatches with a high immunogenicity and a poor graft survival. Further developing this new line of permissible versus taboo mismatches, a new strategy will emerge for future HLA matching, which will not only suit a rare number of patients with frequent haplotypes but a great percentage of all patients. This principle of different immunogenicity of different mismatches can not only be applied to T-cell alloreactivity as shown here, but also to B-cell alloreactivity, where a recently developed computer algorithm (HLA matchmaker) can be instrumental in selecting donors with HLA mismatches, which do not lead to alloantibody formation.

An Evaluation of the Elbit Canary and DynaSense PocketNIRS In-Flight Physiological Monitoring Systems

DTIC Science & Technology

2017-01-04

you have normal pulmonary function? YES NO 6. Have you ever been diagnosed with heart /circulatory disease ? YES NO 7. Do you...total dropout, the Canary system occasionally exhibited long stretches of data with sporadic heart rate signal dropout accompanied by high variance...values as low as 86%. This occurs over a timespan with sporadic heart rate signal dropout and greater mismatch between Canary and Ohmeda HR

[Inhibition and resource capacity during normal aging: a confrontation of the dorsal-ventral and frontal models in a modified version of negative priming].

PubMed

Martin, S; Brouillet, D; Guerdoux, E; Tarrago, R

2006-01-01

Over the past decades, cognitive psychology contribution to our understanding of aging relies on two major perspectives, focusing on the selective impact of age on either cognitive multiple-systems or global factors of cognition: slowing, working memory and inhibition. In the latter, reduction in inhibitory control during aging (in its access, deletion or restraint functions) is associated with poorer performance on a variety of tasks referring to memory, comprehension or language [Hasher, Zacks and May (16)]. The attractiveness of inhibition as an explanatory factor results in part in the absence of negative priming during aging. Negative priming refers to the slow down of latencies when individuals have to respond to recently ignored informations, compared to unrelated informations. The dissociation, between a preserved location negative priming and an absence of identity negative priming during aging, supports the dorsal-ventral model of inhibition which suggests that spatial and identity inhibition are supported by different and independent visual pathways. An alternative model, directly at odds, is that inhibitory mechanisms are supported by the frontal lobe. In this perspective, inhibition is not a central process responsible for the control of working memory contents, but an automatic and local mechanism whose triggering depends on controlled attention. Therefore, working memory drives efficient inhibition by sustaining task instructions and appropriate responses throughout task execution. This hypothesis is consistent with Houghton and Tipper's (17) architecture of selective attention. According to the authors, the presence or absence of automatic inhibition is very closely linked to a Match/Mismatch field whose function is to compare the present stimulus to an internal self-generated internal template. When an information fails to match the subject's current goals, the match/mismatch field causes an automatic inhibitory imbalance which reduces the to-be-ignored properties' responsiveness. In contrast, information matching subjects' goal is enhanced through an automatic excitatory imbalance. The accurate functioning of the Match/Mismatch field requires efficient executive functioning responsible for the uphold of goals and correct responses. In the case of negative priming, manipulating the efficiency of working memory is of interest as it should affect the triggering of slowing, ie, an indirect inhibitory deficit, when the task is resource demanding [Conwayet al. (6)]. Moreover, if inhibition, as reflected by negative priming, is mediated by individual resource capacity, then NP should disappear during aging only when individuals are engaged in a resource-demanding task. To address this issue, we examine whether cognitive control load in a gender decision task contributed to the presence or absence of NP during aging. According to the dorsal-ventral model, task complexity should not have any impact on performance, since gender decision task relies on a conceptual analysis of information. In turn, the frontal model predicts that age differences in performance profile will only differ when individual resource capacity is overloaded. Sixty-four participants (32 young and 32 older adults) performed a gender categorisation task through two experiments. Trials involved two stimuli presented successively at the same location. A word served as a prime and a word as a target. Both prime and target could be male or female. When prime and target matched on gender, we talked about VALID pairs (or compatible). When prime and target mismatched on the manipulated features, we talked about INVALID pairs (or incompatible). Participants' task was to identify the gender of the target. They were explicitly instructed not to respond to primes but to read them silently. Our interest was in response latencies for valid versus invalid pairs. We manipulated task complexity by the absence (experiment 1) or presence (experiment 2) of a distractor during probe trials. For younger adults, primes presented before targets gave rise to behavioural costs when pairs were mapped to the same response compared to pairs that were mapped to opposite ones. This slowing, called Negative Compatibility Effect (NCE), was independent of the presence or absence of a distractor. NCE was reliable for the elderly patients only under condition of no interfering information during the probe trial: pattern of performance of older participants was identical to that of young adults (experiment 1). This effect disappeared as task complexity increased (experiment 2). This result suggests that NCE triggering is dependant on the amount of cognitive control engaged by the task, and therefore that the ability to inhibit irrelevant information is secondary to a general capacity of the working memory. The implications of our data are consistent with the level of processing account, as well as the recent neuroimaging contributions which suggest, for example, the involvement of the dorso-lateral prefrontal cortex (sensitive to aging) when task demands are high, and a ventro-lateral prefrontal implication when demands are low [see Eenshuistra et al. for a review (10)].

Are Educational Mismatches Responsible for the "Inequality Increasing Effect" of Education?

ERIC Educational Resources Information Center

Budria, Santiago

2011-01-01

This paper asks whether educational mismatches can account for the positive association between education and wage inequality found in the data. We use two different data sources, the European Community Household Panel and the Portuguese Labour Force Survey, and consider several types of mismatch, including overqualification, underqualification…

Artificial mismatch hybridization

DOEpatents

Guo, Zhen; Smith, Lloyd M.

1998-01-01

An improved nucleic acid hybridization process is provided which employs a modified oligonucleotide and improves the ability to discriminate a control nucleic acid target from a variant nucleic acid target containing a sequence variation. The modified probe contains at least one artificial mismatch relative to the control nucleic acid target in addition to any mismatch(es) arising from the sequence variation. The invention has direct and advantageous application to numerous existing hybridization methods, including, applications that employ, for example, the Polymerase Chain Reaction, allele-specific nucleic acid sequencing methods, and diagnostic hybridization methods.

Lattice QCD with mismatched fermi surfaces.

PubMed

Yamamoto, Arata

2014-04-25

We study two flavor fermions with mismatched chemical potentials in quenched lattice QCD. We first consider a large isospin chemical potential, where a charged pion is condensed, and then introduce a small mismatch between the chemical potentials of the up quark and the down antiquark. We find that the homogeneous pion condensate is destroyed by the mismatch of the chemical potentials. We also find that the two-point correlation function shows spatial oscillation, which indicates an inhomogeneous ground state, although it is not massless but massive in the present simulation setup.

HLA mismatches and hematopoietic cell transplantation: structural simulations assess the impact of changes in peptide binding specificity on transplant outcome

PubMed Central

Yanover, Chen; Petersdorf, Effie W.; Malkki, Mari; Gooley, Ted; Spellman, Stephen; Velardi, Andrea; Bardy, Peter; Madrigal, Alejandro; Bignon, Jean-Denis; Bradley, Philip

2013-01-01

The success of hematopoietic cell transplantation from an unrelated donor depends in part on the degree of Human Histocompatibility Leukocyte Antigen (HLA) matching between donor and patient. We present a structure-based analysis of HLA mismatching, focusing on individual amino acid mismatches and their effect on peptide binding specificity. Using molecular modeling simulations of HLA-peptide interactions, we find evidence that amino acid mismatches predicted to perturb peptide binding specificity are associated with higher risk of mortality in a large and diverse dataset of patient-donor pairs assembled by the International Histocompatibility Working Group in Hematopoietic Cell Transplantation consortium. This analysis may represent a first step toward sequence-based prediction of relative risk for HLA allele mismatches. PMID:24482668

A teleofunctional account of evolutionary mismatch.

PubMed

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.

The Effect of Basepair Mismatch on DNA Strand Displacement.

PubMed

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.

The spatial mismatch effect is based on global configuration and not on perceptual records within the visual cache.

PubMed

Zimmer, Hubert D; Lehnert, Günther

2006-01-01

If configurations of objects are presented in a S1-S2 matching task for the identity of objects a spatial mismatch effect occurs. Changing the (irrelevant) spatial layout lengthens response times. We investigated what causes this effect. We observed a reliable mismatch effect that was not influenced by a secondary task during maintenance. Neither articulatory suppression (Experiment 1), nor unattended (Experiments 2 and 6) or attended visual material (Experiment 3) reduced the effect, and this was independent of the length of the retention interval (Experiment 6). The effect was also rather independent of the visual appearance of the local elements. It was of similar size with color patches (Experiment 4) and with completely different surface information when testing was cross modal (Experiment 5), and the name-ability of the global configuration was not relevant (Experiments 6 and 7). In contrast, the figurative similarity of the configurations of S1 and S2 systematically influenced the size of the spatial mismatch effect (Experiment 7). We conclude that the spatial mismatch effect is caused by a mismatch of the global shape of the configuration stored together with the objects of S1 and not by a mismatch of templates of perceptual records maintained in a visual cache.

How Psychological Stress Affects Emotional Prosody.

PubMed

Paulmann, Silke; Furnes, Desire; Bøkenes, Anne Ming; Cozzolino, Philip J

2016-01-01

We explored how experimentally induced psychological stress affects the production and recognition of vocal emotions. In Study 1a, we demonstrate that sentences spoken by stressed speakers are judged by naïve listeners as sounding more stressed than sentences uttered by non-stressed speakers. In Study 1b, negative emotions produced by stressed speakers are generally less well recognized than the same emotions produced by non-stressed speakers. Multiple mediation analyses suggest this poorer recognition of negative stimuli was due to a mismatch between the variation of volume voiced by speakers and the range of volume expected by listeners. Together, this suggests that the stress level of the speaker affects judgments made by the receiver. In Study 2, we demonstrate that participants who were induced with a feeling of stress before carrying out an emotional prosody recognition task performed worse than non-stressed participants. Overall, findings suggest detrimental effects of induced stress on interpersonal sensitivity.

How Psychological Stress Affects Emotional Prosody

PubMed Central

Paulmann, Silke; Furnes, Desire; Bøkenes, Anne Ming; Cozzolino, Philip J.

2016-01-01

We explored how experimentally induced psychological stress affects the production and recognition of vocal emotions. In Study 1a, we demonstrate that sentences spoken by stressed speakers are judged by naïve listeners as sounding more stressed than sentences uttered by non-stressed speakers. In Study 1b, negative emotions produced by stressed speakers are generally less well recognized than the same emotions produced by non-stressed speakers. Multiple mediation analyses suggest this poorer recognition of negative stimuli was due to a mismatch between the variation of volume voiced by speakers and the range of volume expected by listeners. Together, this suggests that the stress level of the speaker affects judgments made by the receiver. In Study 2, we demonstrate that participants who were induced with a feeling of stress before carrying out an emotional prosody recognition task performed worse than non-stressed participants. Overall, findings suggest detrimental effects of induced stress on interpersonal sensitivity. PMID:27802287

Impaired prefrontal synaptic gain in people with psychosis and their relatives during the mismatch negativity

PubMed Central

Adams, Rick A.; Díez, Álvaro; Constante, Miguel; Dutt, Anirban; Hall, Mei‐Hua; Maestro Carbayo, Amparo; McDonald, Colm; Petrella, Sabrina; Schulze, Katja; Shaikh, Madiha; Walshe, Muriel; Friston, Karl; Pinotsis, Dimitris; Bramon, Elvira

2015-01-01

Abstract The mismatch negativity (MMN) evoked potential, a preattentive brain response to a discriminable change in auditory stimulation, is significantly reduced in psychosis. Glutamatergic theories of psychosis propose that hypofunction of NMDA receptors (on pyramidal cells and inhibitory interneurons) causes a loss of synaptic gain control. We measured changes in neuronal effective connectivity underlying the MMN using dynamic causal modeling (DCM), where the gain (excitability) of superficial pyramidal cells is explicitly parameterised. EEG data were obtained during a MMN task—for 24 patients with psychosis, 25 of their first‐degree unaffected relatives, and 35 controls—and DCM was used to estimate the excitability (modeled as self‐inhibition) of (source‐specific) superficial pyramidal populations. The MMN sources, based on previous research, included primary and secondary auditory cortices, and the right inferior frontal gyrus. Both patients with psychosis and unaffected relatives (to a lesser degree) showed increased excitability in right inferior frontal gyrus across task conditions, compared to controls. Furthermore, in the same region, both patients and their relatives showed a reversal of the normal response to deviant stimuli; that is, a decrease in excitability in comparison to standard conditions. Our results suggest that psychosis and genetic risk for the illness are associated with both context‐dependent (condition‐specific) and context‐independent abnormalities of the excitability of superficial pyramidal cell populations in the MMN paradigm. These abnormalities could relate to NMDA receptor hypofunction on both pyramidal cells and inhibitory interneurons, and appear to be linked to the genetic aetiology of the illness, thereby constituting potential endophenotypes for psychosis. Hum Brain Mapp 37:351–365, 2016. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:26503033

Validation of Mismatch Negativity and P3a for Use in Multi-Site Studies of Schizophrenia: Characterization of Demographic, Clinical, Cognitive, and Functional Correlates in COGS-2

PubMed Central

Light, Gregory A.; Swerdlow, Neal R.; Thomas, Michael L.; Calkins, Monica E.; Green, Michael F.; Greenwood, Tiffany A.; Gur, Raquel E.; Gur, Ruben C.; Lazzeroni, Laura C.; Nuechterlein, Keith H.; Pela, Marlena; Radant, Allen D.; Seidman, Larry J.; Sharp, Richard F.; Siever, Larry J.; Silverman, Jeremy M.; Sprock, Joyce; Stone, William S.; Sugar, Catherine A.; Tsuang, Debby W.; Tsuang, Ming T.; Braff, David L.; Turetsky, Bruce I.

2014-01-01

Mismatch negativity (MMN) and P3a are auditory event-related potential (ERP) components that show robust deficits in schizophrenia (SZ) patients and exhibit qualities of endophenotypes, including substantial heritability, test-retest reliability, and trait-like stability. These measures also fulfill criteria for use as cognition and function-linked biomarkers in outcome studies, but have not yet been validated for use in large-scale multi-site clinical studies. This study tested the feasibility of adding MMN and P3a to the ongoing Consortium on the Genetics of Schizophrenia (COGS) study. The extent to which demographic, clinical, cognitive, and functional characteristics contribute to variability in MMN and P3a amplitudes was also examined. Participants (HCS n=824, SZ n=966) underwent testing at 5 geographically distributed COGS laboratories. Valid ERP data was obtained from 91% of HCS and 91% of SZ patients. Highly significant MMN (d=0.96) and P3a (d=0.93) amplitude reductions were observed in SZ patients, comparable in magnitude to those observed in single-lab studies with no appreciable differences across laboratories. Demographic characteristics accounted for 26% and 18% of the variance in MMN and P3a amplitudes, respectively. Significant relationships were observed among demographically-adjusted MMN and P3a measures and medication status as well as several clinical, cognitive, and functional characteristics of the SZ patients. This study demonstrates that MMN and P3a ERP biomarkers can be feasibly used in multi-site clinical studies. As with many clinical tests of brain function, demographic factors contribute to MMN and P3a amplitudes and should be carefully considered in future biomarker-informed clinical studies. PMID:25449710

Validation of mismatch negativity and P3a for use in multi-site studies of schizophrenia: characterization of demographic, clinical, cognitive, and functional correlates in COGS-2.

PubMed

Light, Gregory A; Swerdlow, Neal R; Thomas, Michael L; Calkins, Monica E; Green, Michael F; Greenwood, Tiffany A; Gur, Raquel E; Gur, Ruben C; Lazzeroni, Laura C; Nuechterlein, Keith H; Pela, Marlena; Radant, Allen D; Seidman, Larry J; Sharp, Richard F; Siever, Larry J; Silverman, Jeremy M; Sprock, Joyce; Stone, William S; Sugar, Catherine A; Tsuang, Debby W; Tsuang, Ming T; Braff, David L; Turetsky, Bruce I

2015-04-01

Mismatch negativity (MMN) and P3a are auditory event-related potential (ERP) components that show robust deficits in schizophrenia (SZ) patients and exhibit qualities of endophenotypes, including substantial heritability, test-retest reliability, and trait-like stability. These measures also fulfill criteria for use as cognition and function-linked biomarkers in outcome studies, but have not yet been validated for use in large-scale multi-site clinical studies. This study tested the feasibility of adding MMN and P3a to the ongoing Consortium on the Genetics of Schizophrenia (COGS) study. The extent to which demographic, clinical, cognitive, and functional characteristics contribute to variability in MMN and P3a amplitudes was also examined. Participants (HCS n=824, SZ n=966) underwent testing at 5 geographically distributed COGS laboratories. Valid ERP recordings were obtained from 91% of HCS and 91% of SZ patients. Highly significant MMN (d=0.96) and P3a (d=0.93) amplitude reductions were observed in SZ patients, comparable in magnitude to those observed in single-lab studies with no appreciable differences across laboratories. Demographic characteristics accounted for 26% and 18% of the variance in MMN and P3a amplitudes, respectively. Significant relationships were observed among demographically-adjusted MMN and P3a measures and medication status as well as several clinical, cognitive, and functional characteristics of the SZ patients. This study demonstrates that MMN and P3a ERP biomarkers can be feasibly used in multi-site clinical studies. As with many clinical tests of brain function, demographic factors contribute to MMN and P3a amplitudes and should be carefully considered in future biomarker-informed clinical studies. Published by Elsevier B.V.

The Neural Basis of Taste-visual Modal Conflict Control in Appetitive and Aversive Gustatory Context.

PubMed

Xiao, Xiao; Dupuis-Roy, Nicolas; Jiang, Jun; Du, Xue; Zhang, Mingmin; Zhang, Qinglin

2018-02-21

The functional magnetic resonance imaging (fMRI) technique was used to investigate brain activations related to conflict control in a taste-visual cross-modal pairing task. On each trial, participants had to decide whether the taste of a gustatory stimulus matched or did not match the expected taste of the food item depicted in an image. There were four conditions: Negative match (NM; sour gustatory stimulus and image of sour food), negative mismatch (NMM; sour gustatory stimulus and image of sweet food), positive match (PM; sweet gustatory stimulus and image of sweet food), positive mismatch (PMM; sweet gustatory stimulus and image of sour food). Blood oxygenation level-dependent (BOLD) contrasts between the NMM and the NM conditions revealed an increased activity in the middle frontal gyrus (MFG) (BA 6), the lingual gyrus (LG) (BA 18), and the postcentral gyrus. Furthermore, the NMM minus NM BOLD differences observed in the MFG were correlated with the NMM minus NM differences in response time. These activations were specifically associated with conflict control during the aversive gustatory stimulation. BOLD contrasts between the PMM and the PM condition revealed no significant positive activation, which supported the hypothesis that the human brain is especially sensitive to aversive stimuli. Altogether, these results suggest that the MFG is associated with the taste-visual cross-modal conflict control. A possible role of the LG as an information conflict detector at an early perceptual stage is further discussed, along with a possible involvement of the postcentral gyrus in the processing of the taste-visual cross-modal sensory contrast. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Validation of predictive models for germline mutations in DNA mismatch repair genes in colorectal cancer.

PubMed

Monzon, Jose G; Cremin, Carol; Armstrong, Linlea; Nuk, Jennifer; Young, Sean; Horsman, Doug E; Garbutt, Kristy; Bajdik, Chris D; Gill, Sharlene

2010-02-15

Lynch syndrome is defined by the presence of germline mutations in mismatch repair (MMR) genes. Several models have been recently devised that predict mutation carrier status (Myriad Genetics, Wijnen, Barnetson, PREMM and MMRpro models). Families at moderate-high risk for harboring a Lynch-associated mutation, referred to the BC Cancer Agency (BCCA) Hereditary Cancer Program (HCP), underwent mutation analysis, immunohistochemistry and/or microsatellite testing. Seventy-two tested cases were included. Twenty-five patients were mutation positive (34.7%) and 47 were mutation negative (65.3%). Nineteen of 43 patients who were both microsatellite stable and normal on immunohistochemistry for MLH1 and MSH2 were also genotyped for mutations in these genes; all 19 were negative for MMR gene mutations. Model-derived probabilities of harboring a MMR gene mutation in the proband were calculated and compared to observed results. The area under the ROC curves were 0.75 (95%CI; 0.63-0.87), 0.86 (0.7-0.96), 0.89 (0.82-0.97), 0.89 (0.81-0.98) and 0.93 (0.86-0.99) for the Myriad, Barnetson, Wijnen, MMRpro and PREMM models, respectively. The Amsterdam II criteria had a sensitivity and specificity of 0.76 and 0.74, respectively, in this cohort. The PREMM model demonstrated the best performance for predicting carrier status based on the positive likelihood ratios at the >10%, >20% and >30% probability thresholds. In this referred cohort, the PREMM model had the most favorable concordance index and predictive performance for carrier status based on the positive LR. These prediction models (PREMM, MMRPro and Wijnen) may soon replace the Amsterdam II and revised Bethesda criteria as a prescreening tool for Lynch mutations.

Left hemisphere lateralization for lexical and acoustic pitch processing in Cantonese speakers as revealed by mismatch negativity.

PubMed

Gu, Feng; Zhang, Caicai; Hu, Axu; Zhao, Guoping

2013-12-01

For nontonal language speakers, speech processing is lateralized to the left hemisphere and musical processing is lateralized to the right hemisphere (i.e., function-dependent brain asymmetry). On the other hand, acoustic temporal processing is lateralized to the left hemisphere and spectral/pitch processing is lateralized to the right hemisphere (i.e., acoustic-dependent brain asymmetry). In this study, we examine whether the hemispheric lateralization of lexical pitch and acoustic pitch processing in tonal language speakers is consistent with the patterns of function- and acoustic-dependent brain asymmetry in nontonal language speakers. Pitch contrast in both speech stimuli (syllable /ji/ in Experiment 1) and nonspeech stimuli (harmonic tone in Experiment 1; pure tone in Experiment 2) was presented to native Cantonese speakers in passive oddball paradigms. We found that the mismatch negativity (MMN) elicited by lexical pitch contrast was lateralized to the left hemisphere, which is consistent with the pattern of function-dependent brain asymmetry (i.e., left hemisphere lateralization for speech processing) in nontonal language speakers. However, the MMN elicited by acoustic pitch contrast was also left hemisphere lateralized (harmonic tone in Experiment 1) or showed a tendency for left hemisphere lateralization (pure tone in Experiment 2), which is inconsistent with the pattern of acoustic-dependent brain asymmetry (i.e., right hemisphere lateralization for acoustic pitch processing) in nontonal language speakers. The consistent pattern of function-dependent brain asymmetry and the inconsistent pattern of acoustic-dependent brain asymmetry between tonal and nontonal language speakers can be explained by the hypothesis that the acoustic-dependent brain asymmetry is the consequence of a carryover effect from function-dependent brain asymmetry. Potential evolutionary implication of this hypothesis is discussed. © 2013.

Mismatch negativity to acoustical illusion of beat: how and where the change detection takes place?

PubMed

Chakalov, Ivan; Paraskevopoulos, Evangelos; Wollbrink, Andreas; Pantev, Christo

2014-10-15

In case of binaural presentation of two tones with slightly different frequencies the structures of brainstem can no longer follow the interaural time differences (ITD) resulting in an illusionary perception of beat corresponding to frequency difference between the two prime tones. Hence, the beat-frequency does not exist in the prime tones presented to either ear. This study used binaural beats to explore the nature of acoustic deviance detection in humans by means of magnetoencephalography (MEG). Recent research suggests that the auditory change detection is a multistage process. To test this, we employed 26 Hz-binaural beats in a classical oddball paradigm. However, the prime tones (250 Hz and 276 Hz) were switched between the ears in the case of the deviant-beat. Consequently, when the deviant is presented, the cochleae and auditory nerves receive a "new afferent", although the standards and the deviants are heard identical (26 Hz-beats). This allowed us to explore the contribution of auditory periphery to change detection process, and furthermore, to evaluate its influence on beats-related auditory steady-state responses (ASSRs). LORETA-source current density estimates of the evoked fields in a typical mismatch negativity time-window (MMN) and the subsequent difference-ASSRs were determined and compared. The results revealed an MMN generated by a complex neural network including the right parietal lobe and the left middle frontal gyrus. Furthermore, difference-ASSR was generated in the paracentral gyrus. Additionally, psychophysical measures showed no perceptual difference between the standard- and deviant-beats when isolated by noise. These results suggest that the auditory periphery has an important contribution to novelty detection already at sub-cortical level. Overall, the present findings support the notion of hierarchically organized acoustic novelty detection system. Copyright © 2014 Elsevier Inc. All rights reserved.

Gender differences in lateralization of mismatch negativity in dichotic listening tasks.

PubMed

Ikezawa, Satoru; Nakagome, Kazuyuki; Mimura, Masaru; Shinoda, Junko; Itoh, Kenji; Homma, Ikuo; Kamijima, Kunitoshi

2008-04-01

With the aim of investigating gender differences in the functional lateralization subserving preattentive processing of language stimuli, we compared auditory mismatch negativities (MMNs) using dichotic listening tasks. Forty-four healthy volunteers, including 23 males and 21 females, participated in the study. MMNs generated by pure-tone and phonetic stimuli were compared, to check for the existence of language-specific gender differences in lateralization. Both EEG amplitude and scalp current density (SCD) data were analyzed. With phonetic MMNs, EEG findings revealed significantly larger amplitude in females than males, especially in the right hemisphere, while SCD findings revealed left hemisphere dominance and contralateral dominance in males alone. With pure-tone MMNs, no significant gender differences in hemispheric lateralization appeared in either EEG or SCD findings. While males exhibited left-lateralized activation with phonetic MMNs, females exhibited more bilateral activity. Further, the contralateral dominance of the SCD distribution associated with the ear receiving deviant stimuli in males indicated that ipsilateral input as well as interhemispheric transfer across the corpus callosum to the ipsilateral side was more suppressed in males than in females. The findings of the present study suggest that functional lateralization subserving preattentive detection of phonetic change differs between the genders. These results underscore the significance of considering the gender differences in the study of MMN, especially when phonetic stimulus is adopted. Moreover, they support the view of Voyer and Flight [Voyer, D., Flight, J., 2001. Gender differences in laterality on a dichotic task: the influence of report strategies. Cortex 37, 345-362.] in that the gender difference in hemispheric lateralization of language function is observed in a well-managed-attention condition, which fits the condition adopted in the MMN measurement; subjects are required to focus attention to a distraction task and thereby ignore the phonetic stimuli that elicit MMN.

Neurophysiological mechanisms of cortical plasticity impairments in schizophrenia and modulation by the NMDA receptor agonist D-serine

PubMed Central

Kantrowitz, Joshua T.; Epstein, Michael L.; Beggel, Odeta; Rohrig, Stephanie; Lehrfeld, Jonathan M.; Revheim, Nadine; Lehrfeld, Nayla P.; Reep, Jacob; Parker, Emily; Silipo, Gail; Ahissar, Merav; Javitt, Daniel C.

2016-01-01

Schizophrenia is associated with deficits in cortical plasticity that affect sensory brain regions and lead to impaired cognitive performance. Here we examined underlying neural mechanisms of auditory plasticity deficits using combined behavioural and neurophysiological assessment, along with neuropharmacological manipulation targeted at the N-methyl-D-aspartate type glutamate receptor (NMDAR). Cortical plasticity was assessed in a cohort of 40 schizophrenia/schizoaffective patients relative to 42 healthy control subjects using a fixed reference tone auditory plasticity task. In a second cohort (n = 21 schizophrenia/schizoaffective patients, n = 13 healthy controls), event-related potential and event-related time–frequency measures of auditory dysfunction were assessed during administration of the NMDAR agonist d-serine. Mismatch negativity was used as a functional read-out of auditory-level function. Clinical trials registration numbers were NCT01474395/NCT02156908. Schizophrenia/schizoaffective patients showed significantly reduced auditory plasticity versus healthy controls (P = 0.001) that correlated with measures of cognitive, occupational and social dysfunction. In event-related potential/time-frequency analyses, patients showed highly significant reductions in sensory N1 that reflected underlying impairments in θ responses (P < 0.001), along with reduced θ and β-power modulation during retention and motor-preparation intervals. Repeated administration of d-serine led to intercorrelated improvements in (i) auditory plasticity (P < 0.001); (ii) θ-frequency response (P < 0.05); and (iii) mismatch negativity generation to trained versus untrained tones (P = 0.02). Schizophrenia/schizoaffective patients show highly significant deficits in auditory plasticity that contribute to cognitive, occupational and social dysfunction. d-serine studies suggest first that NMDAR dysfunction may contribute to underlying cortical plasticity deficits and, second, that repeated NMDAR agonist administration may enhance cortical plasticity in schizophrenia. PMID:27913408

Seeing voices: High-density electrical mapping and source-analysis of the multisensory mismatch negativity evoked during the McGurk illusion.

PubMed

Saint-Amour, Dave; De Sanctis, Pierfilippo; Molholm, Sophie; Ritter, Walter; Foxe, John J

2007-02-01

Seeing a speaker's facial articulatory gestures powerfully affects speech perception, helping us overcome noisy acoustical environments. One particularly dramatic illustration of visual influences on speech perception is the "McGurk illusion", where dubbing an auditory phoneme onto video of an incongruent articulatory movement can often lead to illusory auditory percepts. This illusion is so strong that even in the absence of any real change in auditory stimulation, it activates the automatic auditory change-detection system, as indexed by the mismatch negativity (MMN) component of the auditory event-related potential (ERP). We investigated the putative left hemispheric dominance of McGurk-MMN using high-density ERPs in an oddball paradigm. Topographic mapping of the initial McGurk-MMN response showed a highly lateralized left hemisphere distribution, beginning at 175 ms. Subsequently, scalp activity was also observed over bilateral fronto-central scalp with a maximal amplitude at approximately 290 ms, suggesting later recruitment of right temporal cortices. Strong left hemisphere dominance was again observed during the last phase of the McGurk-MMN waveform (350-400 ms). Source analysis indicated bilateral sources in the temporal lobe just posterior to primary auditory cortex. While a single source in the right superior temporal gyrus (STG) accounted for the right hemisphere activity, two separate sources were required, one in the left transverse gyrus and the other in STG, to account for left hemisphere activity. These findings support the notion that visually driven multisensory illusory phonetic percepts produce an auditory-MMN cortical response and that left hemisphere temporal cortex plays a crucial role in this process.

Seeing voices: High-density electrical mapping and source-analysis of the multisensory mismatch negativity evoked during the McGurk illusion

PubMed Central

Saint-Amour, Dave; De Sanctis, Pierfilippo; Molholm, Sophie; Ritter, Walter; Foxe, John J.

2006-01-01

Seeing a speaker’s facial articulatory gestures powerfully affects speech perception, helping us overcome noisy acoustical environments. One particularly dramatic illustration of visual influences on speech perception is the “McGurk illusion”, where dubbing an auditory phoneme onto video of an incongruent articulatory movement can often lead to illusory auditory percepts. This illusion is so strong that even in the absence of any real change in auditory stimulation, it activates the automatic auditory change-detection system, as indexed by the mismatch negativity (MMN) component of the auditory event-related potential (ERP). We investigated the putative left hemispheric dominance of McGurk-MMN using high-density ERPs in an oddball paradigm. Topographic mapping of the initial McGurk-MMN response showed a highly lateralized left hemisphere distribution, beginning at 175 ms. Subsequently, scalp activity was also observed over bilateral fronto-central scalp with a maximal amplitude at ~290 ms, suggesting later recruitment of right temporal cortices. Strong left hemisphere dominance was again observed during the last phase of the McGurk-MMN waveform (350–400 ms). Source analysis indicated bilateral sources in the temporal lobe just posterior to primary auditory cortex. While a single source in the right superior temporal gyrus (STG) accounted for the right hemisphere activity, two separate sources were required, one in the left transverse gyrus and the other in STG, to account for left hemisphere activity. These findings support the notion that visually driven multisensory illusory phonetic percepts produce an auditory-MMN cortical response and that left hemisphere temporal cortex plays a crucial role in this process. PMID:16757004

Visual Task Demands and the Auditory Mismatch Negativity: An Empirical Study and a Meta-Analysis

PubMed Central

Wiens, Stefan; Szychowska, Malina; Nilsson, Mats E.

2016-01-01

Because the auditory system is particularly useful in monitoring the environment, previous research has examined whether task-irrelevant, auditory distracters are processed even if subjects focus their attention on visual stimuli. This research suggests that attentionally demanding visual tasks decrease the auditory mismatch negativity (MMN) to simultaneously presented auditory distractors. Because a recent behavioral study found that high visual perceptual load decreased detection sensitivity of simultaneous tones, we used a similar task (n = 28) to determine if high visual perceptual load would reduce the auditory MMN. Results suggested that perceptual load did not decrease the MMN. At face value, these nonsignificant findings may suggest that effects of perceptual load on the MMN are smaller than those of other demanding visual tasks. If so, effect sizes should differ systematically between the present and previous studies. We conducted a selective meta-analysis of published studies in which the MMN was derived from the EEG, the visual task demands were continuous and varied between high and low within the same task, and the task-irrelevant tones were presented in a typical oddball paradigm simultaneously with the visual stimuli. Because the meta-analysis suggested that the present (null) findings did not differ systematically from previous findings, the available evidence was combined. Results of this meta-analysis confirmed that demanding visual tasks reduce the MMN to auditory distracters. However, because the meta-analysis was based on small studies and because of the risk for publication biases, future studies should be preregistered with large samples (n > 150) to provide confirmatory evidence for the results of the present meta-analysis. These future studies should also use control conditions that reduce confounding effects of neural adaptation, and use load manipulations that are defined independently from their effects on the MMN. PMID:26741815

Reduced temporal mismatch negativity in late-life depression: an event-related potential index of cognitive deficit and functional disability?

PubMed

Naismith, Sharon L; Mowszowski, Loren; Ward, Philip B; Diamond, Keri; Paradise, Matthew; Kaur, Manreena; Lewis, Simon J G; Hickie, Ian B; Hermens, Daniel F

2012-04-01

Depression in older people has been consistently linked with a variety of neurobiological brain changes. One measure of preattentive auditory processing, the mismatch negativity (MMN), has not been previously examined in late-life depression. This study examined MMN elicited by duration deviant stimuli in older people with lifetime depression, and explored its relationship with neuropsychological functioning and disability. Twenty-two older health-seeking patients (mean age=65.2 years) with lifetime major depressive disorder and twelve age and sex-matched control participants (mean age=64.6 years) completed detailed clinical and neuropsychological assessments and the WHO-DAS as a measure of disability. MMN amplitudes were elicited using a two-tone passive auditory oddball paradigm and measured at frontal (Fz), central (Cz) and temporal (left and right mastoid: M1 and M2, respectively) sites. Patients with depression demonstrated reduced mean MMN amplitude at temporal (M1, t=3.1, p<0.01; M2, t=3.8, p<0.01), but not fronto-central sites. Reduced temporal MMN amplitudes did not relate to depressive symptom severity, but were associated with reduced semantic fluency and greater self-rated functional disability. The contribution of depressive symptom 'state' and medications on MMN need to be considered. Reduced mean amplitudes of mastoid MMN in older patients with lifetime depression may reflect underlying brain changes. This preattentive marker relates to neuropsychological probes of frontotemporal circuits, and importantly, is associated with disability. Longitudinal analysis of MMN in this group will determine its predictive utility as a biomarker for ongoing cognitive decline and illness chronicity. Copyright © 2012 Elsevier B.V. All rights reserved.

Effects of transcranial direct current stimulation on the auditory mismatch negativity response and working memory performance in schizophrenia: a pilot study.

PubMed

Impey, Danielle; Baddeley, Ashley; Nelson, Renee; Labelle, Alain; Knott, Verner

2017-11-01

Cognitive impairment has been proposed to be the core feature of schizophrenia (Sz). Transcranial direct current stimulation (tDCS) is a non-invasive form of brain stimulation which can improve cognitive function in healthy participants and in psychiatric patients with cognitive deficits. tDCS has been shown to improve cognition and hallucination symptoms in Sz, a disorder also associated with marked sensory processing deficits. Recent findings in healthy controls demonstrate that anodal tDCS increases auditory deviance detection, as measured by the brain-based event-related potential, mismatch negativity (MMN), which is a putative biomarker of Sz that has been proposed as a target for treatment of Sz cognition. This pilot study conducted a randomized, double-blind assessment of the effects of pre- and post-tDCS on MMN-indexed auditory discrimination in 12 Sz patients, moderated by auditory hallucination (AH) presence, as well as working memory performance. Assessments were conducted in three sessions involving temporal and frontal lobe anodal stimulation (to transiently excite local brain activity), and one control session involving 'sham' stimulation (meaning with the device turned off, i.e., no stimulation). Results demonstrated a trend for pitch MMN amplitude to increase with anodal temporal tDCS, which was significant in a subgroup of Sz individuals with AHs. Anodal frontal tDCS significantly increased WM performance on the 2-back task, which was found to positively correlate with MMN-tDCS effects. The findings contribute to our understanding of tDCS effects for sensory processing deficits and working memory performance in Sz and may have implications for psychiatric disorders with sensory deficits.

Language and music: differential hemispheric dominance in detecting unexpected errors in the lyrics and melody of memorized songs.

PubMed

Yasui, Takuya; Kaga, Kimitaka; Sakai, Kuniyoshi L

2009-02-01

Using magnetoencephalography (MEG), we report here the hemispheric dominance of the auditory cortex that is selectively modulated by unexpected errors in the lyrics and melody of songs (lyrics and melody deviants), thereby elucidating under which conditions the lateralization of auditory processing changes. In experiment 1 using familiar songs, we found that the dipole strength of responses to the lyrics deviants was left-dominant at 140 ms (M140), whereas that of responses to the melody deviants was right-dominant at 130 ms (M130). In experiment 2 using familiar songs with a constant syllable or pitch, the dipole strength of frequency mismatch negativity elicited by oddballs was left-dominant. There were significant main effects of experiment (1 and 2) for the peak latencies and for the coordinates of the dipoles, indicating that the M140 and M130 were not the frequency mismatch negativity. In experiment 3 using newly memorized songs, the right-dominant M130 was observed only when the presented note was unexpected one, independent of perceiving unnatural pitch transitions (i.e., perceptual saliency) and of selective attention to the melody of songs. The consistent right-dominance of the M130 between experiments 1 and 3 suggests that the M130 in experiment 1 is due to unexpected notes deviating from well-memorized songs. On the other hand, the left-dominant M140 was elicited by lyrics deviants, suggesting the influence of top-down linguistic information and the memory of the familiar songs. We thus conclude that the left- lateralized M140 and right-lateralized M130 reflect the expectation based on top-down information of language and music, respectively.

Direct Fluorescence Detection of Allele-Specific PCR Products Using Novel Energy-Transfer Labeled Primers.

PubMed

Winn-Deen

1998-12-01

Background: Currently analysis of point mutations can be done by allele-specific polymerase chain reaction (PCR) followed by gel analysis or by gene-specific PCR followed by hybridization with an allele-specific probe. Both of these mutation detection methods require post-PCR laboratory time and run the risk of contaminating subsequent experiments with the PCR product liberated during the detection step. The author has combined the PCR amplification and detection steps into a single procedure suitable for closed-tube analysis. Methods and Results: Allele-specific PCR primers were designed as Sunrise energy-transfer primers and contained a 3' terminal mismatch to distinguish between normal and mutant DNA. Cloned normal (W64) and mutant (R64) templates of the beta3-adrenergic receptor gene were tested to verify amplification specificity and yield. A no-target negative control was also run with each reaction. After PCR, each reaction was tested for fluorescence yield by measuring fluorescence on a spectrofluorimeter or fluorescent microtitreplate reader. The cloned controls and 24 patient samples were tested for the W64R mutation by two methods. The direct fluorescence results with the Sunrise allele-specific PCR method gave comparable genotypes to those obtained with the PCR/ restriction digest/gel electrophoresis control method. No PCR artifacts were observed in the negative controls or in the PCR reactions run with the mismatched target. Conclusions: The results of this pilot study indicate good PCR product and fluorescence yield from allele-specific energy-transfer labeled primers, and the capability of distinguishing between normal and mutant alleles based on fluorescence alone, without the need for restriction digestion, gel electrophoresis, or hybridization with an allele-specific probe.

Chronic effects of cannabis use on the auditory mismatch negativity.

PubMed

Greenwood, Lisa-Marie; Broyd, Samantha J; Croft, Rodney; Todd, Juanita; Michie, Patricia T; Johnstone, Stuart; Murray, Robin; Solowij, Nadia

2014-03-15

Cannabis use is associated with the development of psychotic symptoms and increased risk for schizophrenia. The mismatch negativity (MMN) is a brain event-related potential marker of change detection thought to index glutamatergic N-methyl-D-aspartate receptor-mediated neurotransmission, which is known to be deficient in schizophrenia. This study examined auditory MMN in otherwise healthy chronic cannabis users compared with nonuser control subjects. Forty-two chronic cannabis users and 44 nonuser healthy control subjects completed a multi-feature MMN paradigm, which included duration, frequency, and intensity deviants (deviants 6%; standards 82%). The MMN was compared between users and control subjects as well as between long- and short-term users and age- and gender-matched control subjects. Associations between MMN, cannabis use measures, and symptoms were examined. The MMN amplitude was significantly reduced to frequency but not duration or intensity deviants in overall cannabis users relative to control subjects. Frequency MMN was similarly attenuated in short- and long-term users relative to control subjects. Long-term users also exhibited reduced duration MMN relative to control subjects and short-term users and this was correlated with increased duration of exposure to cannabis and increased psychotic-like experiences during intoxication. In short-term users, a younger age of onset of regular cannabis use and greater frequency of use were associated with greater psychotic-like experiences and symptomatic distress. These results suggest impaired sensory memory that might reflect N-methyl-D-aspartate receptor dysfunction in chronic cannabis users. The pattern of MMN alterations in cannabis users differed from that typically observed in patients with schizophrenia, indicating overlapping but distinct underlying pathology. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Acute effects of Delta9-tetrahydrocannabinol and standardized cannabis extract on the auditory evoked mismatch negativity.

PubMed

Juckel, Georg; Roser, Patrik; Nadulski, Thomas; Stadelmann, Andreas M; Gallinat, Jürgen

2007-12-01

Reduced amplitudes of auditory evoked mismatch negativity (MMN) have often been found in schizophrenic patients, indicating deficient auditory information processing and working memory. Cannabis-induced psychotic states may resemble schizophrenia. Currently, there are discussions focusing on the close relationship between cannabis, the endocannabinoid and dopaminergic system, and the onset of schizophrenic psychosis. This study investigated the effects of cannabis on MMN amplitude in 22 healthy volunteers (age 28+/-6 years, 11 male) by comparing Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and standardized cannabis extract containing Delta(9)-THC and cannabidiol (CBD) in a prospective, double-blind, placebo-controlled cross-over design. The MMNs resulting from 1000 auditory stimuli were recorded by 32 channel EEG. The standard stimuli were 1000 Hz, 80 dB SPL, and 100 ms duration. The deviant stimuli differed in frequency (1500 Hz). Significantly greater MMN amplitude values at central electrodes were found under cannabis extract, but not under Delta(9)-THC. There were no significant differences between MMN amplitudes at frontal electrodes. MMN amplitudes at central electrodes were significantly correlated with 11-OH-THC concentration, the most important psychoactive metabolite of Delta(9)-THC. Since the main difference between Delta(9)-THC and standardized cannabis extract is CBD, which seems to have neuroprotective and anti-psychotic properties, it can be speculated whether the greater MMN amplitude that may imply higher cortical activation and cognitive performance is related to the positive effects of CBD. This effect may be relevant for auditory cortex activity in particular because only MMN amplitudes at the central, but not at the frontal electrodes were enhanced under cannabis.

The effects of exercise during pregnancy on the newborn’s brain: study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background It is generally accepted that an active lifestyle is beneficial for cognition in children, adults and the elderly. Recently, studies using the rat animal model found that the pups of mothers who exercised during pregnancy had increased hippocampal neurogenesis and better memory and learning abilities. The aim of this report is to present the experimental protocol of a study that is designed to verify if an active lifestyle during pregnancy in humans has an impact on the newborn's brain. Methods 60 pregnant women will be included in a randomized controlled study. The experimental group will be asked to exercise a minimum of 20 minutes three times per week, at a minimal intensity of 55% of their maximal aerobic capacity. The control group will not be exercising. The effect of exercise during pregnancy on the newborn's brain will be investigated 8 to 12 days postpartum by means of the mismatch negativity, a neurophysiological brain potential that is associated to auditory sensory memory. We hypothesize that children born to mothers who exercised during their pregnancy will present shorter latencies and larger mismatch negativity amplitudes, indicating more efficient auditory memory processes. Discussion As of September 2011, 17 women have joined the study. Preliminary results show that the experimental group are active 3.1 ± 0.9 days per week while the control group only exercise 0.8 ± 0.6 days per week. The results of this study will present insight on fetal neuroplasticity and will be a valuable tool for health professionals who wish to encourage pregnant women to exercise. Trial registration ClinicalTrials.gov registration: NTC01220778 PMID:22643160

Auditory Evoked Potential Mismatch Negativity in Normal-Hearing Adults

PubMed Central

Schwade, Laura Flach; Didoné, Dayane Domeneghini; Sleifer, Pricila

2017-01-01

Introduction  Mismatch Negativity (MMN) corresponds to a response of the central auditory nervous system. Objective  The objective of this study is to analyze MMN latencies and amplitudes in normal-hearing adults and compare the results between ears, gender and hand dominance. Methods  This is a cross-sectional study. Forty subjects participated, 20 women and 20 men, aged 18 to 29 years and having normal auditory thresholds. A frequency of 1000Hz (standard stimuli) and 2000Hz (deviant stimuli) was used to evoked the MMN. Results  Mean latencies in the right ear were 169.4ms and 175.3ms in the left ear, with mean amplitudes of 4.6µV in the right ear and 4.2µV in the left ear. There was no statistically significant difference between ears. The comparison of latencies between genders showed a statistically significant difference for the right ear, being higher in the men than in women. There was no significant statistical difference between ears for both right-handed and left-handed group. However, the results indicated that the latency of the right ear was significantly higher for the left handers than the right handers. We also found a significant result for the latency of the left ear, which was higher for the right handers. Conclusion  It was possible to obtain references of values for the MMN. There are no differences in the MMN latencies and amplitudes between the ears. Regarding gender, the male group presented higher latencies in relation to the female group in the right ear. Some results indicate that there is a significant statistical difference of the MMN between right- and left-handed individuals. PMID:28680490

Neurophysiological evidence for whole form retrieval of complex derived words: a mismatch negativity study

PubMed Central

Hanna, Jeff; Pulvermüller, Friedemann

2014-01-01

Complex words can be seen as combinations of elementary units, decomposable into stems and affixes according to morphological rules. Alternatively, complex forms may be stored as single lexical entries and accessed as whole forms. This study uses an event-related potential brain response capable of indexing both whole-form retrieval and combinatorial processing, the Mismatch Negativity (MMN), to investigate early brain activity elicited by morphologically complex derived words in German. We presented complex words consisting of stems “sicher” (secure), or “sauber” (clean) combined with abstract nominalizing derivational affixes -heit or -keit, to form either congruent derived words: “Sicherheit” (security) and “Sauberkeit” (cleanliness), or incongruent derived pseudowords: *“Sicherkeit”, and *“Sauberheit”. Using this orthogonal design, it was possible to record brain responses for -heit and -keit in both congruent and incongruent contexts, therefore balancing acoustic variance. Previous research has shown that incongruent combinations of symbols elicit a stronger MMN than congruent combinations, but that single words or constructions stored as whole forms elicit a stronger MMN than pseudowords or non-existent constructions. We found that congruent derived words elicited a stronger MMN than incongruent derived words, beginning about 150 ms after perception of the critical morpheme. This pattern of results is consistent with whole-form storage of morphologically complex derived words as lexical units, or mini-constructions. Using distributed source localization methods, the MMN enhancement for well-formed derivationally complex words appeared to be most prominent in the left inferior anterior-temporal, bilateral superior parietal and bilateral post-central, supra-marginal areas. In addition, neurophysiological results reflected the frequency of derived forms, thus providing further converging evidence for whole form storage and against a combinatorial mechanism. PMID:25414658

Neurophysiological evidence for whole form retrieval of complex derived words: a mismatch negativity study.

PubMed

Hanna, Jeff; Pulvermüller, Friedemann

2014-01-01

Complex words can be seen as combinations of elementary units, decomposable into stems and affixes according to morphological rules. Alternatively, complex forms may be stored as single lexical entries and accessed as whole forms. This study uses an event-related potential brain response capable of indexing both whole-form retrieval and combinatorial processing, the Mismatch Negativity (MMN), to investigate early brain activity elicited by morphologically complex derived words in German. We presented complex words consisting of stems "sicher" (secure), or "sauber" (clean) combined with abstract nominalizing derivational affixes -heit or -keit, to form either congruent derived words: "Sicherheit" (security) and "Sauberkeit" (cleanliness), or incongruent derived pseudowords: *"Sicherkeit", and *"Sauberheit". Using this orthogonal design, it was possible to record brain responses for -heit and -keit in both congruent and incongruent contexts, therefore balancing acoustic variance. Previous research has shown that incongruent combinations of symbols elicit a stronger MMN than congruent combinations, but that single words or constructions stored as whole forms elicit a stronger MMN than pseudowords or non-existent constructions. We found that congruent derived words elicited a stronger MMN than incongruent derived words, beginning about 150 ms after perception of the critical morpheme. This pattern of results is consistent with whole-form storage of morphologically complex derived words as lexical units, or mini-constructions. Using distributed source localization methods, the MMN enhancement for well-formed derivationally complex words appeared to be most prominent in the left inferior anterior-temporal, bilateral superior parietal and bilateral post-central, supra-marginal areas. In addition, neurophysiological results reflected the frequency of derived forms, thus providing further converging evidence for whole form storage and against a combinatorial mechanism.

Mismatch Negativity Encoding of Prediction Errors Predicts S-ketamine-Induced Cognitive Impairments

PubMed Central

Schmidt, André; Bachmann, Rosilla; Kometer, Michael; Csomor, Philipp A; Stephan, Klaas E; Seifritz, Erich; Vollenweider, Franz X

2012-01-01

Psychotomimetics like the N-methyl--aspartate receptor (NMDAR) antagonist ketamine and the 5-hydroxytryptamine2A receptor (5-HT2AR) agonist psilocybin induce psychotic symptoms in healthy volunteers that resemble those of schizophrenia. Recent theories of psychosis posit that aberrant encoding of prediction errors (PE) may underlie the expression of psychotic symptoms. This study used a roving mismatch negativity (MMN) paradigm to investigate whether the encoding of PE is affected by pharmacological manipulation of NMDAR or 5-HT2AR, and whether the encoding of PE under placebo can be used to predict drug-induced symptoms. Using a double-blind within-subject placebo-controlled design, S-ketamine and psilocybin, respectively, were administrated to two groups of healthy subjects. Psychological alterations were assessed using a revised version of the Altered States of Consciousness (ASC-R) questionnaire. As an index of PE, we computed changes in MMN amplitudes as a function of the number of preceding standards (MMN memory trace effect) during a roving paradigm. S-ketamine, but not psilocybin, disrupted PE processing as expressed by a frontally disrupted MMN memory trace effect. Although both drugs produced positive-like symptoms, the extent of PE processing under placebo only correlated significantly with the severity of cognitive impairments induced by S-ketamine. Our results suggest that the NMDAR, but not the 5-HT2AR system, is implicated in PE processing during the MMN paradigm, and that aberrant PE signaling may contribute to the formation of cognitive impairments. The assessment of the MMN memory trace in schizophrenia may allow detecting early phases of the illness and might also serve to assess the efficacy of novel pharmacological treatments, in particular of cognitive impairments. PMID:22030715

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

PubMed

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

2017-01-01

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

Performance of the SNPforID 52 SNP-plex assay in paternity testing.

PubMed

Børsting, Claus; Sanchez, Juan J; Hansen, Hanna E; Hansen, Anders J; Bruun, Hanne Q; Morling, Niels

2008-09-01

The performance of a multiplex assay with 52 autosomal single nucleotide polymorphisms (SNPs) developed for human identification was tested on 124 mother-child-father trios. The typical paternity indices (PIs) were 10(5)-10(6) for the trios and 10(3)-10(4) for the child-father duos. Using the SNP profiles from the randomly selected trios and 700 previously typed individuals, a total of 83,096 comparisons between mother, child and an unrelated man were performed. On average, 9-10 mismatches per comparison were detected. Four mismatches were genetic inconsistencies and 5-6 mismatches were opposite homozygosities. In only two of the 83,096 comparisons did an unrelated man match perfectly to a mother-child duo, and in both cases the PI of the true father was much higher than the PI of the unrelated man. The trios were also typed for 15 short tandem repeats (STRs) and seven variable number of tandem repeats (VNTRs). The typical PIs based on 15 STRs or seven VNTRs were 5-50 times higher than the typical PIs based on 52 SNPs. Six mutations in tandem repeats were detected among the randomly selected trios. In contrast, there was not found any mutations in the SNP loci. The results showed that the 52 SNP-plex assay is a very useful alternative to currently used methods in relationship testing. The usefulness of SNP markers with low mutation rates in paternity and immigration casework is discussed.

Interfacial relaxation analysis of InGaAs/GaAsP strain-compensated multiple quantum wells and its optical property

NASA Astrophysics Data System (ADS)

Dong, Hailiang; Sun, Jing; Ma, Shufang; Liang, Jian; Jia, Zhigang; Liu, Xuguang; Xu, Bingshe

2018-02-01

InGaAs/GaAsP strain-compensated multiple quantum wells were prepared by metal organic chemical vapor deposition on GaAs (100) substrates with misorientation of 15° toward [111]. In order to obtain better strain-compensated abrupt heterojunction interfaces, the compressive strain and relaxation of different quantum well and the total accumulated strain were investigated by adjusting In composition and the thickness of InxGa1-xAs well and GaAs1-yPy barrier keep constant. High resolution X-ray diffraction results indicate the crystal and interfacial structures of In0.18Ga0.82As (7 nm)/GaAs1-yPy with the least relaxation and total strain mismatch are better than others. From in-situ surface reflectivity curves, we observed the slope of reflectivity curve of multiple quantum wells increases with increasing lattice relaxation. Atomic force microscopic results show surface morphologies of three samples are Volmer-Weber mode. Indium segregation at heterointerface between well and barrier were investigated by secondary ion mass spectrometry which indicate indium diffusion width increase with the increasing total strain mismatch. Finally, a shoulder peak was observed from Gaussian fitting of photoluminescence, stemming from the lattice relaxation. These results demonstrate that the relaxation process is introduced and indium segregation length widens as the relaxation increases. The experimental results will be favorable for optimizing the epitaxial growth of InGaAs/GaAsP strain-compensated quantum wells in order to obtain high quality smooth heterointerface.

[Expression of DNA mismatch repair protein in endometrial carcinomas and its correlation with clinicopathologic features].

PubMed

Bi, R; Tu, X Y; Xiao, Y X; Shan, B E; Wang, H Y; Cai, X; Zhou, X Y; Yang, W T

2016-05-08

To study the expression of mismatch repair protein in a series of endometrial carcinomas and its correlation with clinicopathologic features. The clinical data of 150 consecutive cases of endometrial carcinoma were collected during the period from December, 2014 to August, 2015 in Fudan University Cancer Center. Morphologic features including tumor infiltrating lymphocytes (TIL), peritumoral lymphocytes and tumor heterogeneity were reviewed. Immunohistochemistry for expression of mismatch repair proteins was performed. The correlation with clinicopathologic features was analyzed. Loss of mismatch repair protein expression was observed in 43 cases (28.7%), including loss of MLH1/PMS2 in 27 cases (18%), loss of MSH2/MSH6 in 7 cases (4.7%), loss of MSH6 in 6 cases (4%) and loss of PMS2 in 3 cases (2%). There were 23.3% and 27.1% of mismatch repair protein-deficient endometrial carcinomas in women under and above 50 years of age, respectively, which was not statistically significant. Amongst the 12 cases with family history of tumors, 4 of the 6 mismatch repair protein-deficient cases were under 50 years of age, which was higher than that in the 6 cases with mismatch repair protein expression (P=0.014). The mismatch repair protein-deficient group showed significantly more prominent TIL and peritumoral lymphocytes than protein-expression group (P=0.033 and <0.001). Moreover, there were also significant differences in depth of myometrial invasion and occurrence of synchronous malignancy (2 cases of ovarian clear cell carcinoma and 1 case of colonic carcinoma) between the two groups (P=0.039 and 0.022). However, there were no significant differences in lymph node metastasis, tumor heterogeneity, lower uterine segment involvement and tumor stage between the two groups. Prominent TIL and peritumoral lymphocytes characteristically occur in mismatch repair protein-deficient endometrial carcinomas. Patient age does not significantly correlate with the loss of mismatch repair protein expression, but individuals under 50 years of age are more likely to have no expression if there is family history of tumors.

Recipient/donor HLA and CMV matching in recipients of T-cell-depleted unrelated donor haematopoietic cell transplants.

PubMed

Shaw, B E; Mayor, N P; Szydlo, R M; Bultitude, W P; Anthias, C; Kirkland, K; Perry, J; Clark, A; Mackinnon, S; Marks, D I; Pagliuca, A; Potter, M N; Russell, N H; Thomson, K; Madrigal, J A; Marsh, S G E

2017-05-01

Improving haematopoietic cell transplantation outcomes by selection of an HLA-matched unrelated donor is best practice; however, donor selection by secondary characteristics is controversial. We studied 1271 recipients with haematological malignancies who underwent T-cell-depleted allografts and had complete data on HLA-matching status for six loci (HLA-A, -B, -C, -DRB1, -DQB1, -DPB1) and clinical outcome data. Five-year overall survival was 40.6%. HLA mismatching (at HLA-A, -B, -C, -DRB1, -DQB1) relative risk (RR) 1.22, 95% confidence interval (CI) 1.2-1.5, P=0.033 for 1 mismatch and RR 1.46, 95% CI 1.1-1.9, P=0.009 for >1 mismatch) and CMV mismatching (RR 1.37, 95% CI 1.2-1.6, P<0.001) were significantly associated with inferior survival. Donors aged <30 years showed a trend towards better survival. The multivariate model for mortality, combining CMV and HLA-match status, found an RR of 1.36 (95% CI 1.1-1.7, P=0.003) for HLA matched/CMV mismatched, an RR of 1.22 (95% CI 0.99-1.5, P=0.062) for HLA mismatched/CMV matched and an RR of 1.81 (95% CI 1.4-2.3, P=<0.001) for HLA/ CMV mismatched, compared with the HLA/CMV-matched recipients. These data suggest that HLA and CMV matching status should be considered when selecting unrelated donors and that CMV matching may abrogate the effect of an HLA mismatch.

Utilizing Molecular Dynamics ' Multipotent Methodologies to Measure Microscopic Motions of DNA Molecules: A Magniloquent Manuscript On DNA's Means and Mannerisms

NASA Astrophysics Data System (ADS)

Kingsland, Addie

DNA is an amazing molecule which is the basic template for all genetics. It is the primary molecule for storing biological information, and has many applications in nanotechnology. Double-stranded DNA may contain mismatched base pairs beyond the Watson-Crick pairs guanine-cytosine and adenine-thymine. To date, no one has found a physical property of base pair mismatches which describes the behavior of naturally occurring mismatch repair enzymes. Many materials properties of DNA are also unknown, for instance, when pulling DNA in different configurations, different energy differences are observed with no obvious reason why. DNA mismatches also affect their local environment, for instance changing the quantum yield of nearby azobenzene moieties. We utilize molecular dynamics computer simulations to study the structure and dynamics for both matched and mismatched base pairs, within both biological and materials contexts, and in both equilibrium and biased dynamics. We show that mismatched pairs shift further in the plane normal to the DNA strand and are more likely to exhibit non-canonical structures, including the e-motif. Base pair mismatches alter their local environment, affecting the trans- to cis- photoisomerization quantum yield of azobenzene, as well as increasing the likelihood of observing the e-motif. We also show that by using simulated data, we can give new insights on theoretical models to calculate the energetics of pulling DNA strands apart. These results, all relatively inexpensive on modern computer hardware, can help guide the design of DNA-based nanotechnologies, as well as give new insights into the functioning of mismatch repair systems in cancer prevention.

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

PubMed Central

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

Educational Mismatch of Graduates: A Multidimensional and Fuzzy Indicator

ERIC Educational Resources Information Center

Betti, Gianni; D'Agostino, Antonella; Neri, Laura

2011-01-01

In this paper we attempt to measure the educational mismatch, seen as a problem of overeducation, using a multidimensional and fuzzy methodology. Educational mismatch can be difficult to measure because many factors can converge to its definition and the traditional unidimensional indicators presented in literature can offer a restricted view of…

Effects of Mismatched Pictures on Retention of Illustrated Prose.

ERIC Educational Resources Information Center

Peeck, Joan

A study was conducted to test the findings of two earlier studies (Peeck l974 and Pressley l983) on the effects of occasional mismatches between verbal and pictorial content in children's retention of illustrated prose. While the Peeck study indicated a considerable impact of mismatched pictures, the Pressley study indicated that with some…

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

ERIC Educational Resources Information Center

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…

Educational Mismatch and Retirement

ERIC Educational Resources Information Center

Bender, Keith A.; Heywood, John S.

2017-01-01

Using a panel data set of scientists in the US, we examine the hypothesis that workers in jobs poorly matched to their education are more likely to retire. In pooled estimates, we confirm that the mismatched are more likely to retire and that among retirees, the mismatched retire at younger ages. Hazard function estimates also support the…

University Graduates' Skills Mismatches in Central Asia: Employers' Perspectives from Post-Soviet Tajikistan

ERIC Educational Resources Information Center

Jonbekova, Dilrabo

2015-01-01

This paper examines employers' perspectives about university graduates' skills and preparation for employment in post-Soviet Tajikistan. It explores the mismatch between the skills university graduates acquire and the skills required in the job market, and addresses some of the underlying reasons for the perceived skills mismatch. Thematic…

Educational Mismatch between Graduates' Possessed Skills and Market Demands in Pakistan

ERIC Educational Resources Information Center

Uzair-ul-Hassan, Muhammad; Noreen, Zahida

2013-01-01

Educational mismatch in skills that graduates possess and market requires creates barriers for organizations as well as for job seekers. The study was conducted to find out the educational mismatch between graduates possessed skills and market demands. Convenient sampling was carried out and data were collected from 200 graduates of economics…

Mismatch Repair Balances Leading and Lagging Strand DNA Replication Fidelity

DTIC Science & Technology

2012-10-11

mismatched base stacks with a conserved phenylalanine in Msh6, and/or (iii) DNA flexibility, since MutSa-bound mismatched DNA is kinked, and a...AB, Watt DL , Watts BE, et al. (2010) Genome instability due to ribonucleotide incorporation into DNA. Nat Chem Biol 6: 774–781. 24. Poloumienko A

Selective nanoscale growth of lattice mismatched materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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.

On the Mismatch between Multicultural Education and Its Subjects in the Field

ERIC Educational Resources Information Center

Mizrachi, Nissim

2012-01-01

This article draws attention to the growing evidence of a mismatch between sociological categorization and actors' worlds of meaning as expressed in the classroom. The mismatch is especially blatant in cases where students from disadvantaged groups are introduced to what educators and theorists presume to be the liberating discourse of…

Complete wavelength mismatching effect in a Doppler broadened Y-type six-level EIT atomic medium

NASA Astrophysics Data System (ADS)

Bharti, Vineet; Wasan, Ajay

We present a theoretical study of the Doppler broadened Y-type six-level atomic system, using a density matrix approach, to investigate the effect of varying control field wavelengths and closely spaced hyperfine levels in the 5P state of 87Rb. The closely spaced hyperfine levels in our six-level system affect the optical properties of Y-type system and cause asymmetry in absorption profiles. Depending upon the choices of π-probe, σ+-control and σ--control fields transitions, we consider three regimes: (i) perfect wavelength matching regime (λp=λ=λ), (ii) partial wavelength mismatching regime (λp≠λ=λ), and (iii) complete wavelength mismatching regime (λp≠λ≠λ). The complete wavelength mismatching regime is further distinguished into two situations, i.e., λ<λ and λ>λ. We have shown that in the room temperature atomic vapor, the asymmetric transparency window gets broadened in the partial wavelength mismatching regime as compared to the perfect wavelength matching regime. This broad transparency window also splits at the line center in the complete wavelength mismatching regime.

Enhanced entrainability of genetic oscillators by period mismatch

PubMed Central

Hasegawa, Yoshihiko; Arita, Masanori

2013-01-01

Biological oscillators coordinate individual cellular components so that they function coherently and collectively. They are typically composed of multiple feedback loops, and period mismatch is unavoidable in biological implementations. We investigated the advantageous effect of this period mismatch in terms of a synchronization response to external stimuli. Specifically, we considered two fundamental models of genetic circuits: smooth and relaxation oscillators. Using phase reduction and Floquet multipliers, we numerically analysed their entrainability under different coupling strengths and period ratios. We found that a period mismatch induces better entrainment in both types of oscillator; the enhancement occurs in the vicinity of the bifurcation on their limit cycles. In the smooth oscillator, the optimal period ratio for the enhancement coincides with the experimentally observed ratio, which suggests biological exploitation of the period mismatch. Although the origin of multiple feedback loops is often explained as a passive mechanism to ensure robustness against perturbation, we study the active benefits of the period mismatch, which include increasing the efficiency of the genetic oscillators. Our findings show a qualitatively different perspective for both the inherent advantages of multiple loops and their essentiality. PMID:23389900

Requirement of the yeast MSH3 and MSH6 genes for MSH2-dependent genomic stability.

PubMed

Johnson, R E; Kovvali, G K; Prakash, L; Prakash, S

1996-03-29

Defects in DNA mismatch repair result in instability of simple repetitive DNA sequences and elevated levels of spontaneous mutability. The human G/T mismatch binding protein, GTBP/p160, has been suggested to have a role in the repair of base-base and single nucleotide insertion-deletion mismatches. Here we examine the role of the yeast GTBP homolog, MSH6, in mismatch repair. We show that both MSH6 and MSH3 genes are essential for normal genomic stability. Interestingly, although mutations in either MSH3 or MSH6 do not cause the extreme microsatellite instability and spontaneous mutability observed in the msh2 mutant, yeast cells harboring null mutations in both the MSH3 and MSH6 genes exhibit microsatellite instability and mutability similar to that in the msh2 mutant. Results from epistasis analyses indicate that MSH2 functions in mismatch repair in conjunction with MSH3 or MSH6 and that MSH3 and MSH6 constitute alternate pathways of MSH2-dependent mismatch repair.

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

NASA Astrophysics Data System (ADS)

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.

A Direct Adaptive Control Approach in the Presence of Model Mismatch

NASA Technical Reports Server (NTRS)

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.

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

PubMed

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.

Exploring Modality Switching Effects in Negated Sentences: Further Evidence for Grounded Representations

PubMed Central

Hald, Lea A.; Hocking, Ian; Vernon, David; Marshall, Julie-Ann; Garnham, Alan

2013-01-01

Theories of embodied cognition (e.g., Perceptual Symbol Systems Theory; Barsalou, 1999, 2009) suggest that modality specific simulations underlie the representation of concepts. Supporting evidence comes from modality switch costs: participants are slower to verify a property in one modality (e.g., auditory, BLENDER-loud) after verifying a property in a different modality (e.g., gustatory, CRANBERRIES-tart) compared to the same modality (e.g., LEAVES-rustling, Pecher et al., 2003). Similarly, modality switching costs lead to a modulation of the N400 effect in event-related potentials (ERPs; Collins et al., 2011; Hald et al., 2011). This effect of modality switching has also been shown to interact with the veracity of the sentence (Hald et al., 2011). The current ERP study further explores the role of modality match/mismatch on the processing of veracity as well as negation (sentences containing “not”). Our results indicate a modulation in the ERP based on modality and veracity, plus an interaction. The evidence supports the idea that modality specific simulations occur during language processing, and furthermore suggest that these simulations alter the processing of negation. PMID:23450002

Blockade of LAG3 enhances responses of tumor-infiltrating T cells in mismatch repair-proficient liver metastases of colorectal cancer

PubMed Central

Noordam, Lisanne; Sprengers, Dave; Boor, Patrick P. C.; Mancham, Shanta; Menon, Anand G.; Lange, Johan F.; Burger, Pim J. W. A.; Brandt, Alexandra; Galjart, Boris; Kwekkeboom, Jaap; Bruno, Marco J.

2018-01-01

ABSTRACT Purpose: Liver metastasis develops in >50% of patients with colorectal cancer (CRC), and is a leading cause of CRC-related mortality. We aimed to identify which inhibitory immune checkpoint pathways can be targeted to enhance functionality of intra-tumoral T-cells in mismatch repair-proficient liver metastases of colorectal cancer (LM-CRC). Methodology: Intra-tumoral expression of multiple inhibitory molecules was compared among mismatch repair-proficient LM-CRC, peritoneal metastases of colorectal cancer (PM-CRC) and primary CRC. Expression of inhibitory molecules was also analyzed on leukocytes isolated from paired resected metastatic liver tumors, tumor-free liver tissues, and blood of patients with mismatch repair-proficient LM-CRC. The effects of blocking inhibitory pathways on tumor-infiltrating T-cell responses were studied in ex vivo functional assays. Results: Mismatch repair-proficient LM-CRC showed higher expression of inhibitory receptors on intra-tumoral T-cells and contained higher proportions of CD8+ T-cells, dendritic cells and monocytes than mismatch repair-proficient primary CRC and/or PM-CRC. Inhibitory receptors LAG3, PD-1, TIM3 and CTLA4 were higher expressed on CD8+ T-cells, CD4+ T-helper and/or regulatory T-cells in LM-CRC tumors compared with tumor-free liver and blood. Antibody blockade of LAG3 or PD-L1 increased proliferation and effector cytokine production of intra-tumoral T-cells isolated from LM-CRC in response to both polyclonal and autologous tumor-specific stimulations. Higher LAG3 expression on intra-tumoral CD8+ T-cells associated with longer progression-free survival of LM-CRC patients. Conclusion: Mismatch repair-proficient LM-CRC may be more sensitive to immune checkpoint inhibitors than mismatch repair-proficient primary CRC. Blocking LAG3 enhances tumor-infiltrating T-cell responses of mismatch repair-proficient LM-CRC, and therefore may be a new promising immunotherapeutic target for LM-CRC.

Relationship between PTEN, DNA Mismatch Repair, and Tumor Histotype in Endometrial Carcinoma: Retained Positive Expression of PTEN Preferentially Identifies Sporadic Non-Endometrioid Carcinomas

PubMed Central

Djordjevic, Bojana; Barkoh, Bedia A.; Luthra, Rajyalakshmi; Broaddus, Russell R.

2013-01-01

Loss of PTEN (phosphatase and tensin homolog) expression and microsatellite instability are two of the more common molecular alterations in endometrial carcinoma. From the published literature, it is controversial as to whether there is a relationship between these different molecular mechanisms. Therefore, a cohort of 187 pure endometrioid and non-endometrioid endometrial carcinomas, carefully characterized as to clinical and pathological features, was examined for PTEN sequence abnormalities and the immunohistochemical expression of PTEN and the DNA mismatch repair proteins MLH1, MSH2, MSH6 and PMS2. MLH1 methylation analysis was performed when tumors had loss of MLH1 protein. Mismatch repair protein loss was more frequent in endometrioid carcinomas compared to non-endometrioid carcinomas, a difference primarily attributable to the presence of MLH1 methylation in a greater proportion of endometrioid tumors. Among the non-endometrioid group, mixed endometrioid/non-endometrioid carcinomas were the histotype that most commonly had loss of a mismatch repair protein. In endometrioid tumors, the frequency of PTEN loss measured by immunohistochemistry and mutation did not differ significantly between the mismatch repair protein intact or mismatch repair protein loss groups, suggesting that PTEN loss is independent of mismatch protein repair status in this group. However, in non-endometrioid carcinomas, both intact positive PTEN immunohistochemical expression and PTEN wild type were highly associated with retained positive expression of mismatch repair proteins in the tumor. Relevant to screening endometrial cancers for Lynch Syndrome, an initial PTEN immunohistochemistry determination may be able to replace the use of four mismatch repair immunohistochemical markers in 63% of patients with non-endometrioid endometrial carcinoma. Therefore, PTEN immunohistochemistry, in combination with tumor histotype, is a useful adjunct in the clinical evaluation of endometrial carcinomas for Lynch Syndrome. PMID:23599155

Robust image matching via ORB feature and VFC for mismatch removal

NASA Astrophysics Data System (ADS)

Ma, Tao; Fu, Wenxing; Fang, Bin; Hu, Fangyu; Quan, Siwen; Ma, Jie

2018-03-01

Image matching is at the base of many image processing and computer vision problems, such as object recognition or structure from motion. Current methods rely on good feature descriptors and mismatch removal strategies for detection and matching. In this paper, we proposed a robust image match approach based on ORB feature and VFC for mismatch removal. ORB (Oriented FAST and Rotated BRIEF) is an outstanding feature, it has the same performance as SIFT with lower cost. VFC (Vector Field Consensus) is a state-of-the-art mismatch removing method. The experiment results demonstrate that our method is efficient and robust.

An Approach to the Quantitative Study of Sea Floor Topography.

DTIC Science & Technology

1980-01-01

Basement in the Pacific Ocean MAGNETIC TOTAL RMS ANOMALY SPREADING RELIEF MEAN RMS RIDGE WINDOW RATE (cm/yr) (meters) RELIEF (meters) Nazca-Cocos 0-2’ 6 104...investigation. V. CONCLUSIONS The sea floor and the lithologic boundaries below it can generally be thought of as interfaces of acoustic impedance mismatch... Magnetic Anomalies , and Plate Tectonic History of the Mouth of the Gulf of California. Geol. Soc. Am. Bull., v. 83, p. 3345-3360. Luyendyk, B. P

pH imaging reveals worsened tissue acidification in diffusion kurtosis lesion than the kurtosis/diffusion lesion mismatch in an animal model of acute stroke.

PubMed

Wang, Enfeng; Wu, Yin; Cheung, Jerry S; Zhou, Iris Yuwen; Igarashi, Takahiro; Zhang, XiaoAn; Sun, Phillip Zhe

2017-10-01

Diffusion weighted imaging (DWI) has been commonly used in acute stroke examination, yet a portion of DWI lesion may be salvageable. Recently, it has been shown that diffusion kurtosis imaging (DKI) defines the most severely damaged DWI lesion that does not renormalize following early reperfusion. We postulated that the diffusion and kurtosis lesion mismatch experience heterogeneous hemodynamic and/or metabolic injury. We investigated tissue perfusion, pH, diffusion, kurtosis and relaxation from regions of the contralateral normal area, diffusion lesion, kurtosis lesion and their mismatch in an animal model of acute stroke. Our study revealed significant kurtosis and diffusion lesion volume mismatch (19.7 ± 10.7%, P < 0.01). Although there was no significant difference in perfusion and diffusion between the kurtosis lesion and kurtosis/diffusion lesion mismatch, we showed lower pH in the kurtosis lesion (pH = 6.64 ± 0.12) from that of the kurtosis/diffusion lesion mismatch (6.84 ± 0.11, P < 0.05). Moreover, pH in the kurtosis lesion and kurtosis/diffusion mismatch agreed well with literature values for regions of ischemic core and penumbra, respectively. Our work documented initial evidence that DKI may reveal the heterogeneous metabolic derangement within the commonly used DWI lesion.

Automatic change detection: does the auditory system use representations of individual stimulus features or gestalts?

PubMed

Deacon, D; Nousak, J M; Pilotti, M; Ritter, W; Yang, C M

1998-07-01

The effects of global and feature-specific probabilities of auditory stimuli were manipulated to determine their effects on the mismatch negativity (MMN) of the human event-related potential. The question of interest was whether the automatic comparison of stimuli indexed by the MMN was performed on representations of individual stimulus features or on gestalt representations of their combined attributes. The design of the study was such that both feature and gestalt representations could have been available to the comparator mechanism generating the MMN. The data were consistent with the interpretation that the MMN was generated following an analysis of stimulus features.

Is there pre-attentive memory-based comparison of pitch?

PubMed

Jacobsen, T; Schröger, E

2001-07-01

The brain's responsiveness to changes in sound frequency has been demonstrated by an overwhelming number of studies. Change detection occurs unintentionally and automatically. It is generally assumed that this brain response, the so-called mismatch negativity (MMN) of the event-related brain potential or evoked magnetic field, is based on the outcome of a memory-comparison mechanism rather than being due to a differential state of refractoriness of tonotopically organized cortical neurons. To the authors' knowledge, however, there is no entirely compelling evidence for this belief. An experimental protocol controlling for refractoriness effects was developed and a true memory-comparison-based brain response to pitch change was demonstrated.

Related transplantation with HLA-1 Ag mismatch in the GVH direction and HLA-8/8 allele-matched unrelated transplantation: a nationwide retrospective study.

PubMed

Kanda, Junya; Saji, Hiroh; Fukuda, Takahiro; Kobayashi, Takeshi; Miyamura, Koichi; Eto, Tetsuya; Kurokawa, Mineo; Kanamori, Heiwa; Mori, Takehiko; Hidaka, Michihiro; Iwato, Koji; Yoshida, Takashi; Sakamaki, Hisashi; Tanaka, Junji; Kawa, Keisei; Morishima, Yasuo; Suzuki, Ritsuro; Atsuta, Yoshiko; Kanda, Yoshinobu

2012-03-08

To clarify which is preferable, a related donor with an HLA-1 Ag mismatch at the HLA-A, HLA-B, or HLA-DR loci in the graft-versus-host (GVH) direction (RD/1AG-MM-GVH) or an HLA 8/8-allele (HLA-A, HLA-B, HLA-C, and HLA-DRB1)-matched unrelated donor (8/8-MUD), we evaluated 779 patients with acute leukemia, chronic myelogenous leukemia, or myelodysplastic syndrome who received a T cell-replete graft from an RD/1AG-MM-GVH or 8/8-MUD. The use of an RD/1AG-MM-GVH donor was significantly associated with a higher overall mortality rate than the use of an 8/8-MUD in a multivariate analysis (hazard ratio, 1.49; P < .001), and this impact was statistically significant only in patients with standard-risk diseases (P = .001). Among patients with standard-risk diseases who received transplantation from an RD/1AG-MM-GVH donor, the presence of an HLA-B Ag mismatch was significantly associated with a lower overall survival rate than an HLA-DR Ag mismatch because of an increased risk of treatment-related mortality. The HLA-C Ag mismatch or multiple allelic mismatches were frequently observed in the HLA-B Ag-mismatched group, and were possibly associated with the poor outcome. In conclusion, an 8/8-MUD should be prioritized over an RD/1AG-MM-GVH donor during donor selection. In particular, an HLA-B Ag mismatch in the GVH direction has an adverse effect on overall survival and treatment-related mortality in patients with standard-risk diseases.

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

PubMed

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.

Genome-wide minor histocompatibility matching as related to the risk of graft-versus-host disease.

PubMed

Martin, Paul J; Levine, David M; Storer, Barry E; Warren, Edus H; Zheng, Xiuwen; Nelson, Sarah C; Smith, Anajane G; Mortensen, Bo K; Hansen, John A

2017-02-09

The risk of acute graft-versus-host disease (GVHD) is higher after allogeneic hematopoietic cell transplantation (HCT) from unrelated donors as compared with related donors. This difference has been explained by increased recipient mismatching for major histocompatibility antigens or minor histocompatibility antigens. In the current study, we used genome-wide arrays to enumerate single nucleotide polymorphisms (SNPs) that produce graft-versus-host (GVH) amino acid coding differences between recipients and donors. We then tested the hypothesis that higher degrees of genome-wide recipient GVH mismatching correlate with higher risks of GVHD after allogeneic HCT. In HLA-genotypically matched sibling recipients, the average recipient mismatching of coding SNPs was 9.35%. Each 1% increase in genome-wide recipient mismatching was associated with an estimated 20% increase in the hazard of grades III-IV GVHD (hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.05-1.37; P = .007) and an estimated 22% increase in the hazard of stage 2-4 acute gut GVHD (HR, 1.22; 95% CI, 1.02-1.45; P = .03). In HLA-A, B, C, DRB1, DQA1, DQB1, DPA1, DPB1-phenotypically matched unrelated recipients, the average recipient mismatching of coding SNPs was 17.3%. The estimated risks of GVHD-related outcomes in HLA-phenotypically matched unrelated recipients were low, relative to the large difference in genome-wide mismatching between the 2 groups. In contrast, the risks of GVHD-related outcomes were higher in HLA-DP GVH-mismatched unrelated recipients than in HLA-matched sibling recipients. Taken together, these results suggest that the increased GVHD risk after unrelated HCT is predominantly an effect of HLA-mismatching. © 2017 by The American Society of Hematology.

Seventeen-millimeter St. Jude Medical Regent valve in patients with small aortic annulus: dose moderate prosthesis-patient mismatch matter?

PubMed

Hu, Jia; Qian, Hong; Li, Ya-jiao; Gu, Jun; Zhao, Jing Janice; Zhang, Er-yong

2014-01-17

The study was designed to evaluate the effects of moderate prosthesis-patient mismatch (defined as 0.65 cm(2)/m(2) 

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

PubMed

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 < 0.01), and male donors were younger than female donors (33.4 ± 12.7 vs. 38.2 ± 12.3; P < 0.01). No further relevant differences related to donor sex were detected. In the univariate analysis, mismatch was associated with mortality in men (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.06-1.32; P = 0.003) but not in women (HR, 0.91; 95% CI 0.74-1.12; P = 0.4). A significant interaction was detected between sex mismatch and recipient 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.

Indirectly Recognized HLA-C Mismatches and Their Potential Role in Transplant Outcome

PubMed Central

Thus, Kirsten A.; Te Boome, Liane; Kuball, Jürgen; Spierings, Eric

2014-01-01

HLA-C mismatches are clearly associated to alloreactivity after hematopoietic stem-cell transplantation; in a number of large cohorts, HLA-C mismatches are correlated to an increased risk of acute graft-versus-host disease (GVHD) or even impaired survival. While for HLA-A and -B, both antigenic as well as allelic mismatches are associated with an increased risk of acute GVHD, such an increased risk is only observed for antigenic HLA-C mismatches and not for allelic mismatches. These observations raise the question what sets HLA-C apart from HLA-A and -B. The difference may well be related to the reduced levels of cell-surface expression of HLA-C as compared to HLA-A and -B, possibly due to, among other factors, a limited peptide-binding capacity. This limited peptide-binding capacity may retain HLA-C in the ER and enhance degradation of the HLA-C protein. Once degraded, HLA-C-derived peptides can be presented to the immune system via other HLA alleles and are thus available for indirect recognition. Indeed, such HLA-C-derived peptides have previously been eluted from other HLA alleles. We have recently developed an approach to predict indirect recognition of HLA molecules, by establishing the numbers of predicted indirectly recognizable HLA epitopes (PIRCHES). The number of PIRCHES presented on HLA class I and II (PIRCHE-I and -II, respectively), are highly correlated to clinical measures of alloreactivity, such as acute GVHD. In the present “Hypothesis & Theory,” we reviewed the current knowledge on HLA-C mismatches and alloreactivity. Moreover, we speculate about the role of direct and indirect recognition of HLA-C and the consequences for donor selection in HLA-C mismatched stem-cell transplantation. PMID:24860572

HLA AND CROSS·REACTIVE ANTIGEN GROUP MATCHING FOR CADAVER KIDNEY ALLOCATION1

PubMed Central

Starzl, Thomas E.; Eliasziw, Michael; Gjertson, David; Terasaki, Paul I.; Fung, John J.; Trucco, Massimo; Martell, Joan; McMichael, John; Scantlebury, Velma; Shapiro, Ron; Donner, Allan

2010-01-01

Background Allocation of cadaver kidneys by graded human leukocyte antigen (HLA) compatibility scoring arguably has had little effect on overall survival while prejudicing the transplant candidacy of African-American and other hard to match populations. Consequently, matching has been proposed of deduced amino acid residues of the individual HLA molecules shared by cross-reactive antigen groups (CREGs). We have examined the circumstances under which compatibility with either method impacted graft survival. Methods Using Cox proportional hazards regression modeling, we studied the relationship between levels of conventional HLA mismatch and other donor and recipient factors on primary cadaver kidney survival between 1981 and 1995 at the University of Pittsburgh (n=1,780) and in the United Network for Organ Sharing (UNOS) Scientific Registry during 1991–1995 (n=31,291). The results were compared with those obtained by the matching of amino acid residues that identified CREG-compatible cases with as many as four (but not five and six) HLA mismatches. Results With more than one HLA mismatch (>85% of patients in both series), most of the survival advantage of a zero mismatch was lost. None of the HLA loci were “weak.” In the UNOS (but not Pittsburgh) category of one-HLA mismatch (n=1334), a subgroup of CREG-matched recipients (35.3%) had better graft survival than the remaining 64.7%, who were CREG-mismatched. There was no advantage of a CREG match in the two- to four-HLA incompatibility tiers. Better graft survival with tacrolimus was observed in both the Pittsburgh and UNOS series. Conclusions Obligatory national sharing of cadaver kidneys is justifiable only for zero-HLA-mismatched kidneys. The potential value of CREG matching observed in the one-HLA-mismatched recipients of the UNOS (but not the Pittsburgh) experience deserves further study. PMID:9381546

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Weina; Hellinga, Homme W.; Beese, Lorena S.

Even though high-fidelity polymerases copy DNA with remarkable accuracy, some base-pair mismatches are incorporated at low frequency, leading to spontaneous mutagenesis. Using high-resolution X-ray crystallographic analysis of a DNA polymerase that catalyzes replication in crystals, we observe that a C {center_dot} A mismatch can mimic the shape of cognate base pairs at the site of incorporation. This shape mimicry enables the mismatch to evade the error detection mechanisms of the polymerase, which would normally either prevent mismatch incorporation or promote its nucleolytic excision. Movement of a single proton on one of the mismatched bases alters the hydrogen-bonding pattern such thatmore » a base pair forms with an overall shape that is virtually indistinguishable from a canonical, Watson-Crick base pair in double-stranded DNA. These observations provide structural evidence for the rare tautomer hypothesis of spontaneous mutagenesis, a long-standing concept that has been difficult to demonstrate directly.« less

Minimizing the effect of process mismatch in a neuromorphic system using spike-timing-dependent adaptation.

PubMed

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.

Perceived match or mismatch on the Gottman conflict styles: associations with relationship outcome variables.

PubMed

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.

Effect of deep cryogenic temperature on silicon-on-insulator CMOS mismatch: A circuit designer’s perspective

NASA Astrophysics Data System (ADS)

Das, Kushal; Lehmann, Torsten

2014-07-01

The effect of ultra low operating temperature on mismatch among identically designed Silicon-on-Sapphire CMOS devices is investigated in detail from a circuit design view point. The evolution of transistor matching properties for different operating conditions at both room and 4.2 K temperature are presented. The statistical analysis reveals that mismatch at low temperature is effectively unrelated to that at room temperature, which disagrees with previously published literature. The measurement data was used to extract key transistor parameters and the consequence of temperature lowering on their respective variance is estimated. We find that standard deviation of the threshold-voltage mismatch deteriorates by a factor ∼2 at 4.2 K temperature. Similar to room temperature operation, mismatch at 4.2 K is bias point dependent and the degradation of matching at very low temperature depends to some extent on how the bias point shifts upon cooling.

HLA amino acid residue matching in 2575 kidney transplants.

PubMed

Tan, J; Qiu, J; Tang, X

2007-06-01

Donor-recipient HLA matching was retrospectively evaluated in 2575 renal transplants by comparing amino acid residue matches (Res M) with conventional six-antigen matches (Ag M). Only 6% of donor-recipient combinations had 0 to 1 mismatches using Ag M, whereas 42.8% of the recipients had no mismatch by Res M. Compared with the first year results of residue mismatched recipients, the 1102 patients with 0 residue mismatching displayed a low incidence of rejection (12.07% vs 5.37%) and less anti-HLA antibody production (class I 13.76 vs 38.12%; class II 7.66% vs 31.11%). The 1-to 10-year graft survival of the residue-matched group was similar to that of the Ag-matched group, and significantly better than the residue-mismatched recipients. In summary, Res M could be a good matching system for renal transplantation in the Han population.

Influence of donor–recipient gender mismatch on graft function and survival following lung transplantation†

PubMed Central

Alvarez, Antonio; Moreno, Paula; Illana, Jennifer; Espinosa, Dionisio; Baamonde, Carlos; Arango, Elisabet; Algar, Francisco Javier; Salvatierra, Angel

2013-01-01

OBJECTIVES In current practice, donors and recipients are not matched for gender in lung transplantation. However, some data have suggested a possible effect of gender combinations on lung transplant outcomes. We examined whether donor–recipient (D/R) gender mismatch is related to adverse outcomes after lung transplantation in terms of early and long-term graft function and survival. METHODS We reviewed 256 donors and lung transplant recipients over a 14-year period. Patients were distributed into four groups: Group A (D/R: female/female), Group B (D/R: male/male), Group C (D/R: female/male), Group D (D/R: male/female). Donor and recipient variables were compared among groups, including early graft function, 30-day mortality, freedom from bronchiolitis obliterans syndrome (BOS), and long-term survival. RESULTS Group A: 57 (22%), Group B: 99 (39%), Group C: 62 (24%), Group D: 38 (15%) transplants (P = 0.001). Donor age was 29 ± 14, 27 ± 12, 33 ± 13 and 23 ± 12 years for Groups A, B, C and D, respectively (P = 0.004). Recipient age was 31 ± 15, 44 ± 17, 42 ± 16 and 30 ± 16 years for Groups A, B, C and D, respectively (P = 0.000). PaO2/FiO2 (mmHg) 24 h post-transplant was: Group A: 276 ± 144, Group B: 297 ± 131, Group C: 344 ± 133 and Group D: 238 ± 138 (P = 0.015). Primary graft dysfunction developed in 23, 14, 17 and 21% of recipients from Groups A, B, C and D, respectively (P = 0.45). Operative mortality was 4.4, 6.5, 5.2 and 2%, for recipients from Groups A, B, C and D, respectively (P = 0.66). Freedom from BOS was 73, 59 and 36% for gender-matched transplants vs 76, 67 and 40% for gender-mismatched transplants at 3, 5 and 10 years, respectively (P = 0.618), without differences among groups. A non-significant survival benefit was observed for female recipients, irrespective of the donor gender. CONCLUSIONS Donor–recipient gender mismatch does not have a negative impact on early graft function and mortality following lung transplantation. There is a trend towards a survival benefit for female recipients, irrespective of the donor gender. PMID:23322094

A prediction of templates in the auditory cortex system

NASA Astrophysics Data System (ADS)

Ghanbeigi, Kimia

In this study variation of human auditory evoked mismatch field amplitudes in response to complex tones as a function of the removal in single partials in the onset period was investigated. It was determined: 1-A single frequency elimination in a sound stimulus plays a significant role in human brain sound recognition. 2-By comparing the mismatches of the brain response due to a single frequency elimination in the "Starting Transient" and "Sustain Part" of the sound stimulus, it is found that the brain is more sensitive to frequency elimination in the Starting Transient. This study involves 4 healthy subjects with normal hearing. Neural activity was recorded with stimulus whole-head MEG. Verification of spatial location in the auditory cortex was determined by comparing with MRI images. In the first set of stimuli, repetitive ('standard') tones with five selected onset frequencies were randomly embedded in the string of rare ('deviant') tones with randomly varying inter stimulus intervals. In the deviant tones one of the frequency components was omitted relative to the deviant tones during the onset period. The frequency of the test partial of the complex tone was intentionally selected to preclude its reinsertion by generation of harmonics or combination tones due to either the nonlinearity of the ear, the electronic equipment or the brain processing. In the second set of stimuli, time structured as above, repetitive ('standard') tones with five selected sustained frequency components were embedded in the string of rare '(deviant') tones for which one of these selected frequencies was omitted in the sustained tone. In both measurements, the carefully frequency selection precluded their reinsertion by generation of harmonics or combination tones due to the nonlinearity of the ear, the electronic equipment and brain processing. The same considerations for selecting the test frequency partial were applied. Results. By comparing MMN of the two data sets, the relative contribution to sound recognition of the omitted partial frequency components in the onset and sustained regions has been determined. Conclusion. The presence of significant mismatch negativity, due to neural activity of auditory cortex, emphasizes that the brain recognizes the elimination of a single frequency of carefully chosen anharmonic frequencies. It was shown this mismatch is more significant if the single frequency elimination occurs in the onset period.

Using medication list--problem list mismatches as markers of potential error.

PubMed Central

Carpenter, James D.; Gorman, Paul N.

2002-01-01

The goal of this project was to specify and develop an algorithm that will check for drug and problem list mismatches in an electronic medical record (EMR). The algorithm is based on the premise that a patient's problem list and medication list should agree, and a mismatch may indicate medication error. Successful development of this algorithm could mean detection of some errors, such as medication orders entered into a wrong patient record, or drug therapy omissions, that are not otherwise detected via automated means. Additionally, mismatches may identify opportunities to improve problem list integrity. To assess the concept's feasibility, this study compared medications listed in a pharmacy information system with findings in an online nursing adult admission assessment, serving as a proxy for the problem list. Where drug and problem list mismatches were discovered, examination of the patient record confirmed the mismatch, and identified any potential causes. Evaluation of the algorithm in diabetes treatment indicates that it successfully detects both potential medication error and opportunities to improve problem list completeness. This algorithm, once fully developed and deployed, could prove a valuable way to improve the patient problem list, and could decrease the risk of medication error. PMID:12463796

Mismatch cleavage by single-strand specific nucleases

PubMed Central

Till, Bradley J.; Burtner, Chris; Comai, Luca; Henikoff, Steven

2004-01-01

We have investigated the ability of single-strand specific (sss) nucleases from different sources to cleave single base pair mismatches in heteroduplex DNA templates used for mutation and single-nucleotide polymorphism analysis. The TILLING (Targeting Induced Local Lesions IN Genomes) mismatch cleavage protocol was used with the LI-COR gel detection system to assay cleavage of amplified heteroduplexes derived from a variety of induced mutations and naturally occurring polymorphisms. We found that purified nucleases derived from celery (CEL I), mung bean sprouts and Aspergillus (S1) were able to specifically cleave nearly all single base pair mismatches tested. Optimal nicking of heteroduplexes for mismatch detection was achieved using higher pH, temperature and divalent cation conditions than are routinely used for digestion of single-stranded DNA. Surprisingly, crude plant extracts performed as well as the highly purified preparations for this application. These observations suggest that diverse members of the S1 family of sss nucleases act similarly in cleaving non-specifically at bulges in heteroduplexes, and single-base mismatches are the least accessible because they present the smallest single-stranded region for enzyme binding. We conclude that a variety of sss nucleases and extracts can be effectively used for high-throughput mutation and polymorphism discovery. PMID:15141034

Requirement for Msh6, but not for Swi4 (Msh3), in Msh2-dependent repair of base-base mismatches and mononucleotide loops in Schizosaccharomyces pombe.

PubMed

Tornier, C; Bessone, S; Varlet, I; Rudolph, C; Darmon, M; Fleck, O

2001-05-01

The msh6 mismatch repair gene of Schizosaccharomyces pombe was cloned, sequenced, and inactivated. Strains bearing all combinations of inactivated msh6, msh2, and swi4 (the S. pombe MSH3 ortholog) alleles were tested for their defects in mitotic and meiotic mismatch repair. Mitotic mutation rates were similarly increased in msh6 and msh2 mutants, both for reversion of a base-base substitution as well as of an insertion of one nucleotide in a mononucleotide run. Tetrad analysis and intragenic two-factor crosses revealed that meiotic mismatch repair was affected in msh6 to the same extent as in msh2 background. In contrast, loss of Swi4 likely did not cause a defect in mismatch repair, but rather resulted in reduced recombination frequency. Consistently, a mutated swi4 caused a two- to threefold reduction of recombinants in intergenic crosses, while msh2 and msh6 mutants were not significantly different from wild type. In summary, our study showed that Msh6 plays the same important role as Msh2 in the major mismatch repair pathway of S. pombe, while Swi4 rather functions in recombination.

Computer simulation studies of the growth of strained layers by molecular-beam epitaxy

NASA Astrophysics Data System (ADS)

Faux, D. A.; Gaynor, G.; Carson, C. L.; Hall, C. K.; Bernholc, J.

1990-08-01

Two new types of discrete-space Monte Carlo computer simulation are presented for the modeling of the early stages of strained-layer growth by molecular-beam epitaxy. The simulations are more economical on computer resources than continuous-space Monte Carlo or molecular dynamics. Each model is applied to the study of growth onto a substrate in two dimensions with use of Lennard-Jones interatomic potentials. Up to seven layers are deposited for a variety of lattice mismatches, temperatures, and growth rates. Both simulations give similar results. At small lattice mismatches (<~4%) the growth is in registry with the substrate, while at high mismatches (>~6%) the growth is incommensurate with the substrate. At intermediate mismatches, a transition from registered to incommensurate growth is observed which commences at the top of the crystal and propagates down to the first layer. Faster growth rates are seen to inhibit this transition. The growth mode is van der Merwe (layer-by-layer) at 2% lattice mismatch, but at larger mismatches Volmer-Weber (island) growth is preferred. The Monte Carlo simulations are assessed in the light of these results and the ease at which they can be extended to three dimensions and to more sophisticated potentials is discussed.

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

PubMed Central

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

2017-01-01

Eukaryotic MutLα (mammalian MLH1–PMS2 heterodimer; MLH1–PMS1 in yeast) functions in early steps of mismatch repair as a latent endonuclease that requires a mismatch, MutSα/β, and DNA-loaded proliferating cell nuclear antigen (PCNA) for activation. We show here that human PCNA and MutLα interact specifically but weakly in solution to form a complex of approximately 1:1 stoichiometry that depends on PCNA interaction with the C-terminal endonuclease domain of the MutLα PMS2 subunit. Amino acid substitution mutations within a PMS2 C-terminal 721QRLIAP motif attenuate or abolish human MutLα interaction with PCNA, as well as PCNA-dependent activation of MutLα endonuclease, PCNA- and DNA-dependent activation of MutLα ATPase, and MutLα function in in vitro mismatch repair. Amino acid substitution mutations within the corresponding yeast PMS1 motif (723QKLIIP) reduce or abolish mismatch repair in vivo. Coupling of a weak allele within this motif (723AKLIIP) with an exo1Δ null mutation, which individually confer only weak mutator phenotypes, inactivates mismatch repair in the yeast cell. PMID:28439008

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

PubMed

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

2017-05-09

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

Should pediatric patients wait for HLA-DR-matched renal transplants?

PubMed

Gritsch, H A; Veale, J L; Leichtman, A B; Guidinger, M K; Magee, J C; McDonald, R A; Harmon, W E; Delmonico, F L; Ettenger, R B; Cecka, J M

2008-10-01

Graft survival rates from deceased donors aged 35 years or less among all primary pediatric kidney transplant recipients in the United States between 1996 and 2004 were retrospectively examined to determine the effect of HLA-DR mismatches on graft survival. Zero HLA-DR-mismatched kidneys had statistically comparable 5-year graft survival (71%), to 1-DR-mismatched kidneys (69%) and 2-DR-mismatched kidneys (71%). When compared to donors less than 35 years of age, the relative rate of allograft failure was 1.32 (p = 0.0326) for donor age greater than or equal to age 35. There was no statistical increase in the odds of developing a panel-reactive antibody (PRA) greater than 30% at the time of second waitlisting, based upon the degree of HLA-A, -B or -DR mismatch of the first transplant, nor was there a 'dose effect' when more HLA antigens were mismatched between the donor and recipient. Therefore, pediatric transplant programs should utilize the recently implemented Organ Procurement and Transplantation Network's (OPTN)allocation policy, which prioritizes pediatric recipients to receive kidneys from deceased donors less than 35 years of age, and should not turn down such kidney offers to wait for a better HLA-DR-matched kidney.

Learning partnership--the experience of peer tutoring among nursing students: a qualitative study.

PubMed

Loke, Alice J T Yuen; Chow, Filomena L W

2007-02-01

Peer tutoring involves students helping each other to learn. It places teaching and learning commitments and responsibilities on students. Considerable evidence supports the positive effects of peer tutoring, including cognitive gains, improved communication, self-confidence, and social support among students. Peer tutors are also said to better understand the learning problems of fellow peer learners than teachers do. This study intended to facilitate the development of 'cooperative learning' among nursing students through a peer-tutoring scheme. Undergraduate nursing students were invited to join a peer-tutoring scheme. Fourteen students studying year 3 were recruited to serve as peer tutors and 16 students from year 2 of the same program participated as tutees. Peer tutors attended a training workshop and received a guideline for peer-tutoring activities. They were to provide a total of '10 weekly tutoring sessions throughout the semester on a one-to-one basis for their tutees. Focus groups and individual interviews were conducted in the middle and at the end of the semester to evaluate the students' experiences in the tutoring process. Content analysis of the interview scripts identified that students had both positive and negative experiences from the peer tutoring, but that positive experiences predominated. Positive aspects included enhancement of learning skills/intellectual gains and personal growth. Negative experiences stemmed mainly from frustrations in dealing with mismatched learning styles between tutors and tutees, and the required time commitment. Both tutors and tutees benefited to some extent from this peer-tutoring process. Further studies in an education program for students in all years should be implemented to examine peer-tutoring effects. Implementation of peer tutoring should address the frustrations and difficulties encountered by the students to facilitate better outcomes.

Critique of early models of the demographic impact of HIV/AIDS in sub-Saharan Africa based on contemporary empirical data from Zimbabwe

PubMed Central

Gregson, Simon; Nyamukapa, Constance; Lopman, Ben; Mushati, Phyllis; Garnett, Geoffrey P.; Chandiwana, Stephen K.; Anderson, Roy M.

2007-01-01

Early mathematical models varied in their predictions of the impact of HIV/AIDS on population growth from minimal impact to reductions in growth, in pessimistic scenarios, from positive to negative values over a period of 25 years. Models predicting negative rates of natural increase forecast little effect on the dependency ratio. Twenty years later, HIV prevalence in small towns, estates, and rural villages in eastern Zimbabwe, has peaked within the intermediate range predicted by the early models, but the demographic impact has been more acute than was predicted. Despite concurrent declines in fertility, fueled in part by HIV infections (total fertility is now 8% lower than expected without an epidemic), and a doubling of the crude death rate because of HIV/AIDS, the rate of natural population increase between 1998 and 2005 remained positive in each socioeconomic stratum. In the worst-affected areas (towns with HIV prevalence of 33%), HIV/AIDS reduced growth by two-thirds from 2.9% to 1.0%. The dependency ratio fell from 1.21 at the onset of the HIV epidemic to 0.78, the impact of HIV-associated adult mortality being outweighed by fertility decline. With the benefit of hindsight, the more pessimistic early models overestimated the demographic impact of HIV epidemics by overextrapolating initial HIV growth rates or not allowing for heterogeneity in key parameters such as transmissibility and sexual risk behavior. Data collected since the late 1980s show that there was a mismatch between the observed growth in the HIV epidemic and assumptions made about viral transmission. PMID:17761795

Successful ABO-Incompatible Renal Transplantation:  Blood Group A1B Donor Into A2B Recipient With Anti-A1 Isoagglutinins.

PubMed

Fadeyi, Emmanuel A; Stratta, Robert J; Farney, Alan C; Pomper, Gregory J

2016-08-01

Transplantation of the blood group A2B in a recipient was successfully performed in the setting of receiving a deceased donor kidney from an "incompatible" A1B donor. The donor and recipient were both typed for ABO blood group, including ABO genotyping. The donor and recipient were tested for ABO, non-ABO, and human leukocyte antigen (HLA) antibodies. The donor and recipient were typed for HLA antigens, including T- and B-flow cytometry crossmatch tests. The recipient's RBCs were negative with A1 lectin, and immunoglobulin G anti-A1 was demonstrated in the recipient's plasma. The donor-recipient pair was a four-antigen HLA mismatch, but final T- and B-flow cytometry crossmatch tests were compatible. The transplant procedure was uneventful; the patient experienced immediate graft function with no episodes of rejection or readmissions more than 2 years later. It may be safe to transplant across the A1/A2 blood group AB mismatch barrier in the setting of low titer anti-A1 isoagglutinins without the need for pretransplant desensitization even if the antibody produced reacts with anti-human globulin. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A novel technology for the detection, enrichment, and separation of trace amounts of target DNA based on amino-modified fluorescent magnetic composite nanoparticles.

PubMed

Wang, Guannan; Su, Xingguang

2010-06-01

A novel, highly sensitive technology for the detection, enrichment, and separation of trace amounts of target DNA was developed on the basis of amino-modified fluorescent magnetic composite nanoparticles (AFMN). In this study, the positively charged amino-modified composite nanoparticles conjugate with the negatively charged capture DNA through electrostatic binding. The optimal combination of AFMN and capture DNA was measured by dynamic light scattering (DLS) and UV-vis absorption spectroscopy. The highly sensitive detection of trace amounts of target DNA was achieved through enrichment by means of AFMN. The detection limit for target DNA is 0.4 pM, which could be further improved by using a more powerful magnet. Because of their different melting temperatures, single-base mismatched target DNA could be separated from perfectly complementary target DNA. In addition, the photoluminescence (PL) signals of perfectly complementary target DNA and single-base mismatched DNA as well as the hybridization kinetics of different concentrations of target DNA at different reaction times have also been studied. Most importantly, the detection, enrichment, and separation ability of AFMN was further verified with milk. Simple and satisfactory results were obtained, which show the great potential in the fields of mutation identification and clinical diagnosis.

Conducting electrospun fibres with polyanionic grafts as highly selective, label-free, electrochemical biosensor with a low detection limit for non-Hodgkin lymphoma gene.

PubMed

Kerr-Phillips, Thomas E; Aydemir, Nihan; Chan, Eddie Wai Chi; Barker, David; Malmström, Jenny; Plesse, Cedric; Travas-Sejdic, Jadranka

2018-02-15

A highly selective, label-free sensor for the non-Hodgkin lymphoma gene, with an aM detection limit, utilizing electrochemical impedance spectroscopy (EIS) is presented. The sensor consists of a conducting electrospun fibre mat, surface-grafted with poly(acrylic acid) (PAA) brushes and a conducting polymer sensing element with covalently attached oligonucleotide probes. The sensor was fabricated from electrospun NBR rubber, embedded with poly(3,4-ethylenedioxythiophene) (PEDOT), followed by grafting poly(acrylic acid) brushes and then electrochemically polymerizing a conducting polymer monomer with ssDNA probe sequence pre-attached. The resulting non-Hodgkin lymphoma gene sensor showed a detection limit of 1aM (1 × 10 -18 mol/L), more than 400 folds lower compared to a thin-film analogue. The sensor presented extraordinary selectivity, with only 1%, 2.7% and 4.6% of the signal recorded for the fully non-complimentary, T-A and G-C base mismatch oligonucleotide sequences, respectively. We suggest that such greatly enhanced selectivity is due to the presence of negatively charged carboxylic acid moieties from PAA grafts that electrostatically repel the non-complementary and mismatch DNA sequences, overcoming the non-specific binding. Copyright © 2017 Elsevier B.V. All rights reserved.

Mismatch between herbivore behavior and demographics contributes to scale-dependence of host susceptibility in two pine species

USGS Publications Warehouse

Ylioja, T.; Slone, D.H.; Ayres, M.P.

2005-01-01

The impacts on forests of tree-killing bark beetles can depend on the species composition of potential host trees. Host susceptibility might be an intrinsic property of tree species, or it might depend on spatial patterning of alternative host species. We compared the susceptibility of loblolly pine (Pinus taeda) and Virginia pine (P. virginiana) to southern pine beetle (Dendroctonus frontalis) at two hierarchical levels of geographic scale: within beetle infestations in heterospecific stands (extent ranging from 0.28 to 0.65 ha), and across a forest landscape (extent 72,500 ha) that was dominated by monospecific stands. In the former, beetles preferentially attacked Virginia pine (tree mortality = 65-100% in Virginia pine versus 0-66% in loblolly pine), but in the latter, loblolly stands were more susceptible than Virginia stands. This hierarchical transition in host susceptibility was predicted from knowledge of (1) a behavioral preference of beetles for attacking loblolly versus Virginia pine, (2) a negative correlation between preference and performance, and (3) a mismatch in the domain of scale between demographics and host selection by individuals. There is value for forest management in understanding the processes that can produce hierarchical transitions in ecological patterns. Copyright ?? 2005 by the Society of American Foresters.

Spatial and identity negative priming in audition: evidence of feature binding in auditory spatial memory.

PubMed

Mayr, Susanne; Buchner, Axel; Möller, Malte; Hauke, Robert

2011-08-01

Two experiments are reported with identical auditory stimulation in three-dimensional space but with different instructions. Participants localized a cued sound (Experiment 1) or identified a sound at a cued location (Experiment 2). A distractor sound at another location had to be ignored. The prime distractor and the probe target sound were manipulated with respect to sound identity (repeated vs. changed) and location (repeated vs. changed). The localization task revealed a symmetric pattern of partial repetition costs: Participants were impaired on trials with identity-location mismatches between the prime distractor and probe target-that is, when either the sound was repeated but not the location or vice versa. The identification task revealed an asymmetric pattern of partial repetition costs: Responding was slowed down when the prime distractor sound was repeated as the probe target, but at another location; identity changes at the same location were not impaired. Additionally, there was evidence of retrieval of incompatible prime responses in the identification task. It is concluded that feature binding of auditory prime distractor information takes place regardless of whether the task is to identify or locate a sound. Instructions determine the kind of identity-location mismatch that is detected. Identity information predominates over location information in auditory memory.

Electromagnetic correlates of musical expertise in processing of tone patterns.

PubMed

Kuchenbuch, Anja; Paraskevopoulos, Evangelos; Herholz, Sibylle C; Pantev, Christo

2012-01-01

Using magnetoencephalography (MEG), we investigated the influence of long term musical training on the processing of partly imagined tone patterns (imagery condition) compared to the same perceived patterns (perceptual condition). The magnetic counterpart of the mismatch negativity (MMNm) was recorded and compared between musicians and non-musicians in order to assess the effect of musical training on the detection of deviants to tone patterns. The results indicated a clear MMNm in the perceptual condition as well as in a simple pitch oddball (control) condition in both groups. However, there was no significant mismatch response in either group in the imagery condition despite above chance behavioral performance in the task of detecting deviant tones. The latency and the laterality of the MMNm in the perceptual condition differed significantly between groups, with an earlier MMNm in musicians, especially in the left hemisphere. In contrast the MMNm amplitudes did not differ significantly between groups. The behavioral results revealed a clear effect of long-term musical training in both experimental conditions. The obtained results represent new evidence that the processing of tone patterns is faster and more strongly lateralized in musically trained subjects, which is consistent with other findings in different paradigms of enhanced auditory neural system functioning due to long-term musical training.

Modeling the response of a monopulse radar to impulsive jamming signals using the Block Oriented System Simulator (BOSS)

NASA Astrophysics Data System (ADS)

Long, Jeffrey K.

1989-09-01

This theses developed computer models of two types of amplitude comparison monopulse processors using the Block Oriented System Simulation (BOSS) software package and to determine the response to these models to impulsive input signals. This study was an effort to determine the susceptibility of monopulse tracking radars to impulsing jamming signals. Two types of amplitude comparison monopulse receivers were modeled, one using logarithmic amplifiers and the other using automatic gain control for signal normalization. Simulations of both types of systems were run under various conditions of gain or frequency imbalance between the two receiver channels. The resulting errors from the imbalanced simulations were compared to the outputs of similar, baseline simulations which had no electrical imbalances. The accuracy of both types of processors was directly affected by gain or frequency imbalances in their receiver channels. In most cases, it was possible to generate both positive and negative angular errors, dependent upon the type and degree of mismatch between the channels. The system most susceptible to induced errors was a frequency imbalanced processor which used AGC circuitry. Any errors introduced will be a function of the degree of mismatch between the channels and therefore would be difficult to exploit reliably.

Early sensory encoding of affective prosody: neuromagnetic tomography of emotional category changes.

PubMed

Thönnessen, Heike; Boers, Frank; Dammers, Jürgen; Chen, Yu-Han; Norra, Christine; Mathiak, Klaus

2010-03-01

In verbal communication, prosodic codes may be phylogenetically older than lexical ones. Little is known, however, about early, automatic encoding of emotional prosody. This study investigated the neuromagnetic analogue of mismatch negativity (MMN) as an index of early stimulus processing of emotional prosody using whole-head magnetoencephalography (MEG). We applied two different paradigms to study MMN; in addition to the traditional oddball paradigm, the so-called optimum design was adapted to emotion detection. In a sequence of randomly changing disyllabic pseudo-words produced by one male speaker in neutral intonation, a traditional oddball design with emotional deviants (10% happy and angry each) and an optimum design with emotional (17% happy and sad each) and nonemotional gender deviants (17% female) elicited the mismatch responses. The emotional category changes demonstrated early responses (<200 ms) at both auditory cortices with larger amplitudes at the right hemisphere. Responses to the nonemotional change from male to female voices emerged later ( approximately 300 ms). Source analysis pointed at bilateral auditory cortex sources without robust contribution from other such as frontal sources. Conceivably, both auditory cortices encode categorical representations of emotional prosodic. Processing of cognitive feature extraction and automatic emotion appraisal may overlap at this level enabling rapid attentional shifts to important social cues. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Cancer screening behaviors and risk perceptions among family members of colorectal cancer patients with unexplained mismatch repair deficiency.

PubMed

Katz, Lior H; Advani, Shailesh; Burton-Chase, Allison M; Fellman, Bryan; Polivka, Katrina M; Yuan, Ying; Lynch, Patrick M; Peterson, Susan K

2017-04-01

Communication gaps in families with unexplained mismatch repair (MMR) deficiency (UMMRD) could negatively impact the screening behaviors of relatives of individual with UMMRD. We evaluated cancer risk perception, screening behaviors, and family communication among relatives of colorectal cancer (CRC) patients with UMMRD. Fifty-one family members of 17 probands with UMMRD completed a questionnaire about cancer risk perception, adherence to Lynch syndrome (LS) screening recommendations, and communication with relatives. Clinical data about the probands were obtained from medical records. Thirty-eight participants (78%) were worried from having cancer and twenty-one participants (42%) had undergone colonoscopy in the past 2 years, as recommended for LS families. In terms of screening for extracolonic cancers, only two eligible participants (3.9%) were screened for gastric, endometrial (10.0%), and ovarian (9.5%) cancers. Additionally, 5 participants (10%) underwent genetic counseling. Most participants were not told by anyone to be screened for extracolonic cancers (84, 85, and 95% for gastric, ovarian, and endometrial cancers, respectively). A minority of family members of CRC patients with UMMRD follow cancer screening as recommended for LS families. Health care providers should encourage patients with UMMRD to share information on LS-related cancers screening, especially extracolonic cancers, with their relatives.

Investigating the effects of musical training on functional brain development with a novel Melodic MMN paradigm.

PubMed

Putkinen, Vesa; Tervaniemi, Mari; Saarikivi, Katri; de Vent, Nathalie; Huotilainen, Minna

2014-04-01

Sensitivity to changes in various musical features was investigated by recording the mismatch negativity (MMN) auditory event-related potential (ERP) in musically trained and nontrained children semi-longitudinally at the ages of 9, 11, and 13 years. The responses were recorded using a novel Melodic multi-feature paradigm which allows fast (<15 min) recording of an MMN profile for changes in melody, rhythm, musical key, timbre, tuning and timing. When compared to the nontrained children, the musically trained children displayed enlarged MMNs for the melody modulations by the age 13 and for the rhythm modulations, timbre deviants and slightly mistuned tones already at the age of 11. Also, a positive mismatch response elicited by delayed tones was larger in amplitude in the musically trained than in the nontrained children at age 13. No group differences were found at the age 9 suggesting that the later enhancement of the MMN in the musically trained children resulted from training and not pre-existing difference between the groups. The current study demonstrates the applicability of the Melodic multi-feature paradigm in school-aged children and indicates that musical training enhances auditory discrimination for musically central sound dimensions in pre-adolescence. Copyright © 2014 Elsevier Inc. All rights reserved.

Twelve months of active musical training in 8- to 10-year-old children enhances the preattentive processing of syllabic duration and voice onset time.

PubMed

Chobert, Julie; François, Clément; Velay, Jean-Luc; Besson, Mireille

2014-04-01

Musical training has been shown to positively influence linguistic abilities. To follow the developmental dynamics of this transfer effect at the preattentive level, we conducted a longitudinal study over 2 school years with nonmusician children randomly assigned to music or to painting training. We recorded the mismatch negativity (MMN), a cortical correlate of preattentive mismatch detection, to syllables that differed in vowel frequency, vowel duration, and voice onset time (VOT), using a test-training-retest procedure and 3 times of testing: before training, after 6 months and after 12 months of training. While no between-group differences were found before training, enhanced preattentive processing of syllabic duration and VOT, as reflected by greater MMN amplitude, but not of frequency, was found after 12 months of training in the music group only. These results demonstrate neuroplasticity in the child brain and suggest that active musical training rather than innate predispositions for music yielded the improvements in musically trained children. These results also highlight the influence of musical training for duration perception in speech and for the development of phonological representations in normally developing children. They support the importance of music-based training programs for children's education and open new remediation strategies for children with language-based learning impairments.

Cancer screening behaviors and risk perceptions among family members of colorectal cancer patients with unexplained mismatch repair deficiency

PubMed Central

Advani, Shailesh; Burton-Chase, Allison M.; Fellman, Bryan; Polivka, Katrina M.; Yuan, Ying; Lynch, Patrick M.; Peterson, Susan K.

2018-01-01

Communication gaps in families with unexplained mismatch repair (MMR) deficiency (UMMRD) could negatively impact the screening behaviors of relatives of individual with UMMRD. We evaluated cancer risk perception, screening behaviors, and family communication among relatives of colorectal cancer (CRC) patients with UMMRD. Fifty-one family members of 17 probands with UMMRD completed a questionnaire about cancer risk perception, adherence to Lynch syndrome (LS) screening recommendations, and communication with relatives. Clinical data about the probands were obtained from medical records. Thirty-eight participants (78%) were worried from having cancer and twenty-one participants (42%) had undergone colonoscopy in the past 2 years, as recommended for LS families. In terms of screening for extracolonic cancers, only two eligible participants (3.9%) were screened for gastric, endometrial (10.0%), and ovarian (9.5%) cancers. Additionally, 5 participants (10%) underwent genetic counseling. Most participants were not told by anyone to be screened for extracolonic cancers (84, 85, and 95% for gastric, ovarian, and endometrial cancers, respectively). A minority of family members of CRC patients with UMMRD follow cancer screening as recommended for LS families. Health care providers should encourage patients with UMMRD to share information on LS-related cancers screening, especially extracolonic cancers, with their relatives. PMID:27832499

Educational mismatch and health status among foreign-born workers in Sweden.

PubMed

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.

Replication infidelity via a mismatch with Watson–Crick geometry

PubMed Central

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

Replication infidelity via a mismatch with Watson-Crick geometry.

PubMed

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.

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

NASA Astrophysics Data System (ADS)

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.

Structure and Dynamics of DNA and RNA Double Helices Obtained from the CCG and GGC Trinucleotide Repeats.

PubMed

Pan, Feng; Man, Viet Hoang; Roland, Christopher; Sagui, Celeste

2018-04-26

Expansions of both GGC and CCG sequences lead to a number of expandable, trinucleotide repeat (TR) neurodegenerative diseases. Understanding of these diseases involves, among other things, the structural characterization of the atypical DNA and RNA secondary structures. We have performed molecular dynamics simulations of (GCC) n and (GGC) n homoduplexes in order to characterize their conformations, stability, and dynamics. Each TR has two reading frames, which results in eight nonequivalent RNA/DNA homoduplexes, characterized by CpG or GpC steps between the Watson-Crick base pairs. Free energy maps for the eight homoduplexes indicate that the C-mismatches prefer anti-anti conformations, while G-mismatches prefer anti-syn conformations. Comparison between three modifications of the DNA AMBER force field shows good agreement for the mismatch free energy maps. The mismatches in DNA-GCC (but not CCG) are extrahelical, forming an extended e-motif. The mismatched duplexes exhibit characteristic sequence-dependent step twist, with strong variations in the G-rich sequences and the e-motif. The distribution of Na + is highly localized around the mismatches, especially G-mismatches. In the e-motif, there is strong Na + binding by two G(N7) atoms belonging to the pseudo GpC step created when cytosines are extruded and by extrahelical cytosines. Finally, we used a novel technique based on fast melting by means of an infrared laser pulse to classify the relative stability of the different DNA-CCG and -GGC homoduplexes.

Laser Cooling With Ultrafast Pulse Trains

DTIC Science & Technology

2005-09-30

MHz] FIG. 5: Transmission spectrum of the FPI for (a) correct FPI length with p = 1, q = 2; ( b ) FPI length mismatched by - 700 ym. The transmission...signal for (a) is a factor of - 50 higher and narrower than for ( b ), and the signal-to-noise ratio is increased by a factor of - 2500. lasers. An...the positions of the laser beams with respect to the ion cloud, ( b ) adjusted the mode-locked beam waist radius to optimize total two-photon transition

Realization and Integration of Large Lattice Mismatched Materials for Device Innovation: A Comprehensive Approach to the Underlying Science and Practical Application

DTIC Science & Technology

2011-07-08

Nastasi. Effects of Hydrogen Implantation Conditions on the Trapping of Hydrogen in InP, Applied Physics Letters ( ) 2006/07/25 10:01:57 1 TOTAL: 6...formation of 20 nm PMMA cylinder in a matrix of polystyrene. This cylinder pattern can be transferred to an underlying dielectric mask and used in...allowing for selective hydrogen implantation . The implanted wafers were bonded to acceptor substrates and transfer was initiated. The surface of the

Composites Strengthening.

DTIC Science & Technology

1987-11-01

transformation strain 1 1 or eigenstrain (22) is given in the fiber domain 12 as 0 aj, where a is the strain due to the mis- match of the thermal ex...3), (5) and (6), we obtain ij= - Vw(e - e ij ) (8) According to Eshelby, eij is related to the total eigenstrain ek as e = S e (9) ij ijkl ki where...strain [I I] or eigenstrain [22] is given in the o fiber domain 0 as ii, where a,* is the strain due to the mismatch of the thermal expansion

The Role of Education Pathways in the Relationship between Job Mismatch, Wages and Job Satisfaction: A Panel Estimation Approach

ERIC Educational Resources Information Center

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…

The Impact of Major-Job Mismatch on College Graduates' Early Career Earnings: Evidence from China

ERIC Educational Resources Information Center

Zhu, Rong

2014-01-01

This paper assesses the impact of the mismatch between a college major and job on college graduates' early career earnings using a sample from China. On average, a major-job mismatched college graduate is found to suffer from an income loss that is much lower than the penalty documented in previous studies. The income losses are also found to be…

Investigating methods for determining mismatch in near side vehicle impacts - biomed 2009.

PubMed

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 occupants. By analyzing the vehicle information and occupant injuries, it was found that the vehicle mismatch problem involves differences in vehicle weights and heights and also results in severe injuries to multiple body regions for the near side occupant involved. There was a low correlation of vehicle height difference to occupant ISS.

Reliable scar scoring system to assess photographs of burn patients.

PubMed

Mecott, Gabriel A; Finnerty, Celeste C; Herndon, David N; Al-Mousawi, Ahmed M; Branski, Ludwik K; Hegde, Sachin; Kraft, Robert; Williams, Felicia N; Maldonado, Susana A; Rivero, Haidy G; Rodriguez-Escobar, Noe; Jeschke, Marc G

2015-12-01

Several scar-scoring scales exist to clinically monitor burn scar development and maturation. Although scoring scars through direct clinical examination is ideal, scars must sometimes be scored from photographs. No scar scale currently exists for the latter purpose. We modified a previously described scar scale (Yeong et al., J Burn Care Rehabil 1997) and tested the reliability of this new scale in assessing burn scars from photographs. The new scale consisted of three parameters as follows: scar height, surface appearance, and color mismatch. Each parameter was assigned a score of 1 (best) to 4 (worst), generating a total score of 3-12. Five physicians with burns training scored 120 representative photographs using the original and modified scales. Reliability was analyzed using coefficient of agreement, Cronbach alpha, intraclass correlation coefficient, variance, and coefficient of variance. Analysis of variance was performed using the Kruskal-Wallis test. Color mismatch and scar height scores were validated by analyzing actual height and color differences. The intraclass correlation coefficient, the coefficient of agreement, and Cronbach alpha were higher for the modified scale than those of the original scale. The original scale produced more variance than that in the modified scale. Subanalysis demonstrated that, for all categories, the modified scale had greater correlation and reliability than the original scale. The correlation between color mismatch scores and actual color differences was 0.84 and between scar height scores and actual height was 0.81. The modified scar scale is a simple, reliable, and useful scale for evaluating photographs of burn patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Association between mismatch repair gene MSH3 codons 1036 and 222 polymorphisms and sporadic prostate cancer in the Iranian population.

PubMed

Jafary, Fariba; Salehi, Mansoor; Sedghi, Maryam; Nouri, Nayereh; Jafary, Farzaneh; Sadeghi, Farzaneh; Motamedi, Shima; Talebi, Maede

2012-01-01

The mismatch repair system (MMR) is a post-replicative DNA repair mechanism whose defects can lead to cancer. The MSH3 protein is an essential component of the system. We postulated that MSH3 gene polymorphisms might therefore be associated with prostate cancer (PC). We studied MSH3 codon 222 and MSH3 codon 1036 polymorphisms in a group of Iranian sporadic PC patients. A total of 60 controls and 18 patients were assessed using the polymerase chain reaction and single strand conformational polymorphism. For comparing the genotype frequencies of patients and controls the chi-square test was applied. The obtained result indicated that there was significantly association between G/A genotype of MSH3 codon 222 and G/G genotype of MSH3 codon 1036 with an increased PC risk (P=0.012 and P=0.02 respectively). Our results demonstrated that MSH3 codon 222 and MSH3 codon 1036 polymorphisms may be risk factors for sporadic prostate cancer in the Iranian population.

Influenza vaccine effectiveness estimates in the Dutch population from 2003 to 2014: The test-negative design case-control study with different control groups.

PubMed

van Doorn, Eva; Darvishian, Maryam; Dijkstra, Frederika; Donker, Gé A; Overduin, Pieter; Meijer, Adam; Hak, Eelko

2017-05-15

Information about influenza vaccine effectiveness (IVE) is important for vaccine strain selection and immunization policy decisions. The test-negative design (TND) case-control study is commonly used to obtain IVE estimates. However, the definition of the control patients may influence IVE estimates. We have conducted a TND study using the Dutch Sentinel Practices of NIVEL Primary Care Database which includes data from patients who consulted the General Practitioner (GP) for an episode of acute influenza-like illness (ILI) or acute respiratory infection (ARI) with known influenza vaccination status. Cases were patients tested positive for influenza virus. Controls were grouped into those who tested (1) negative for influenza virus (all influenza negative), (2) negative for influenza virus, but positive for respiratory syncytial virus, rhinovirus or enterovirus (non-influenza virus positive), and (3) negative for these four viruses (pan-negative). We estimated the IVE over all epidemic seasons from 2003/2004 through 2013/2014, pooled IVE for influenza vaccine partial/full matched and mismatched seasons and the individual seasons using generalized linear mixed-effect and multiple logistic regression models. The overall IVE adjusted for age, GP ILI/ARI diagnosis, chronic disease and respiratory allergy was 35% (95% CI: 15-48), 64% (95% CI: 49-75) and 21% (95% CI: -1 to 39) for all influenza negative, non-influenza virus positive and pan-negative controls, respectively. In both the main and subgroup analyses IVE estimates were the highest using non-influenza virus positive controls, likely due to limiting inclusion of controls without laboratory-confirmation of a virus causing the respiratory disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

West Nile virus (WNV) genome RNAs with up to three adjacent mutations that disrupt long distance 5'-3' cyclization sequence basepairs are viable

DOE Office of Scientific and Technical Information (OSTI.GOV)

Basu, Mausumi; Brinton, Margo A., E-mail: mbrinton@gsu.ed

2011-03-30

Mosquito-borne flavivirus genomes contain conserved 5' and 3' cyclization sequences (CYC) that facilitate long distance RNA-RNA interactions. In previous studies, flavivirus replicon RNA replication was completely inhibited by single or multiple mismatching CYC nt substitutions. In the present study, full-length WNV genomes with one, two or three mismatching CYC substitutions showed reduced replication efficiencies but were viable and generated revertants with increased replication efficiency. Several different three adjacent mismatching CYC substitution mutant RNAs were rescued by a second site mutation that created an additional basepair (nts 147-10913) on the internal genomic side of the 5'-3' CYC. The finding that full-lengthmore » genomes with up to three mismatching CYC mutations are viable and can be rescued by a single nt spontaneous mutation indicates that more than three adjacent CYC basepair substitutions would be required to increase the safety of vaccine genomes by creating mismatches in inter-genomic recombinants.« less

Cytosine-based nucleoside analogs are selectively lethal to DNA mismatch repair-deficient tumour cells by enhancing levels of intracellular oxidative stress

PubMed Central

Hewish, M; Martin, S A; Elliott, R; Cunningham, D; Lord, C J; Ashworth, A

2013-01-01

Background: DNA mismatch repair deficiency is present in a significant proportion of a number of solid tumours and is associated with distinct clinical behaviour. Methods: To identify the therapeutic agents that might show selectivity for mismatch repair-deficient tumour cells, we screened a pair of isogenic MLH1-deficient and MLH1-proficient tumour cell lines with a library of clinically used drugs. To test the generality of hits in the screen, selective agents were retested in cells deficient in the MSH2 mismatch repair gene. Results: We identified cytarabine and other related cytosine-based nucleoside analogues as being selectively toxic to MLH1 and MSH2-deficient tumour cells. The selective cytotoxicity we observed was likely caused by increased levels of cellular oxidative stress, as it could be abrogated by antioxidants. Conclusion: We propose that cytarabine-based chemotherapy regimens may represent a tumour-selective treatment strategy for mismatch repair-deficient cancers. PMID:23361057

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

PubMed

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.

A Monofunctional Platinum Complex Coordinated to a Rhodium Metalloinsertor Selectively Binds Mismatched DNA in the Minor Groove

PubMed Central

Weidmann, Alyson G.; Barton, Jacqueline K.

2015-01-01

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 non-classically 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 triggers cell death via an apoptotic pathway, rather than the necrotic pathway induced by rhodium metalloinsertors. PMID:26397309

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

PubMed

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.

Unnatural substrates reveal the importance of 8-oxoguanine for in vivo mismatch repair by MutY

PubMed Central

Livingston, Alison L.; O’Shea, Valerie L.; Kim, Taewoo; Kool, Eric T.; David, Sheila S.

2009-01-01

Escherchia coli MutY plays an important role in preventing mutations associated with the oxidative lesion 7,8-dihydro-8-oxo-2′-deoxyguanosine (OG) in DNA by excising adenines from OG:A mismatches as the first step of base excision repair. To determine the importance of specific steps in the base pair recognition and base removal process of MutY, we have evaluated the effects of modifications of the OG:A substrate on the kinetics of base removal, mismatch affinity and repair to G:C in an Escherchia coli-based assay. Surprisingly, adenine modification was tolerated in the cellular assay, while modification of OG results in minimal cellular repair. High affinity for the mismatch and efficient base removal require the presence of OG. Taken together, these results suggest that the presence of OG is a critical feature for MutY to locate OG:A mismatches and select the appropriate adenines for excision to initiate repair in vivo prior to replication. PMID:18026095

Effect of T-cell-epitope matching at HLA-DPB1 in recipients of unrelated-donor haemopoietic-cell transplantation: a retrospective study

PubMed Central

Fleischhauer, Katharina; Gooley, Theodore; Malkki, Mari; Bardy, Peter; Bignon, Jean-Denis; Dubois, Valérie; Horowitz, Mary M; Madrigal, J Alejandro; Morishima, Yasuo; Oudshoorn, Machteld; Ringden, Olle; Spellman, Stephen; Velardi, Andrea; Zino, Elisabetta; Petersdorf, Effie W

2013-01-01

Summary Background The risks after unrelated-donor haemopoietic-cell transplantation with matched HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1 alleles between donor and recipient (10/10 matched) can be decreased by selection of unrelated donors who also match for HLA-DPB1; however, such donors are difficult to find. Classification of HLA-DPB1 mismatches based on T-cell-epitope groups could identify mismatches that might be tolerated (permissive) and those that would increase risks (non-permissive) after transplantation. We did a retrospective study to compare outcomes between permissive and non-permissive HLA-DPB1 mismatches in unrelated-donor haemopoietic-cell transplantation. Methods HLA and clinical data for unrelated-donor transplantations submitted to the International Histocompatibility Working Group in haemopoietic-cell transplantation were analysed retrospectively. HLA-DPB1 T-cell-epitope groups were assigned according to a functional algorithm based on alloreactive T-cell crossreactivity patterns. Recipients and unrelated donors matching status were classified as HLA-DPB1 match, non-permissive HLA-DPB1 mismatch (those with mismatched T-cell-epitope groups), or permissive HLA-DPB1 mismatch (those with matched T-cell-epitope groups). The clinical outcomes assessed were overall mortality, non-relapse mortality, relapse, and severe (grade 3–4) acute graft-versus-host disease (aGvHD). Findings Of 8539 transplantations, 5428 (64%) were matched for ten of ten HLA alleles (HLA 10/10 matched) and 3111 (36%) for nine of ten alleles (HLA 9/10 matched). Of the group overall, 1719 (20%) were HLA-DPB1 matches, 2670 (31%) non-permissive HLA-DPB1 mismatches, and 4150 (49%) permissive HLA-DPB1 mismatches. In HLA 10/10-matched transplantations, non-permissive mismatches were associated with a significantly increased risk of overall mortality (hazard ratio [HR] 1·15, 95% CI 1·05–1·25; p=0·002), non-relapse mortality (1·28, 1·14–1·42; p<0·0001), and severe aGvHD (odds ratio [OR] 1·31, 95% CI 1·11–1·54; p=0·001), but not relapse (HR 0·89, 95% CI 0·77–1·02; p=0·10), compared with permissive mismatches. There were significant differences between permissive HLA-DPB1 mismatches and HLA-DPB1 matches in terms of non-relapse mortality (0·86, 0·75–0·98; p=0·03) and relapse (1·34, 1·17–1·54; p<0·0001), but not for overall mortality (0·96, 0·87–1·06; p=0·40) or aGvHD (OR 0·84, 95% CI 0·69–1·03; p=0·09). In the HLA 9/10 matched population, non-permissive HLA-DPB1 mismatches also increased the risk of overall mortality (HR 1·10, 95% CI 1·00–1·22; p=0·06), non-relapse mortality (1·19, 1·05–1·36; p=0·007), and severe aGvHD (OR 1·37, 95% CI 1·13–1·66; p=0·002) compared with permissive mismatches, but the risk of relapse was the same in both groups (HR 0·93, 95% CI 0·78–1·11; p=0·44). Outcomes for HLA 10/10-matched transplantations with non-permissive HLA-DPB1 mismatches did not differ substantially from those for HLA 9/10-matched transplantations with permissive HLA-DPB1 mismatches or HLA-DPB1 matches. Interpretation T-cell-epitope matching defines permissive and non-permissive HLA-DPB1 mismatches. Avoidance of an unrelated donor with a non-permissive T-cell-epitope mismatch at HLA-DPB1 might provide a practical clinical strategy for lowering the risks of mortality after unrelated-donor haemopoietic-cell transplantation. Funding National Institutes of Health; Associazione Italiana per la Ricerca sul Cancro; Telethon Foundation; Italian Ministry of Health; Cariplo Foundation; National Cancer Institute; National Heart, Lung and Blood Institute; National Institute of Allergy and Infectious Diseases; Office of Naval Research; IRGHET Paris; Swedish Cancer Society; Children's Cancer Foundation; Swedish Research Council; Cancer Society in Stockholm; Karolinska Institutet; and Leukemia and Lymphoma Society. PMID:22340965

Proximity to AGCT sequences dictates MMR-independent versus MMR-dependent mechanisms for AID-induced mutation via UNG2

PubMed Central

Thientosapol, Eddy Sanchai; Sharbeen, George; Lau, K.K. Edwin; Bosnjak, Daniel; Durack, Timothy; Stevanovski, Igor; Weninger, Wolfgang

2017-01-01

Abstract AID deaminates C to U in either strand of Ig genes, exclusively producing C:G/G:C to T:A/A:T transition mutations if U is left unrepaired. Error-prone processing by UNG2 or mismatch repair diversifies mutation, predominantly at C:G or A:T base pairs, respectively. Here, we show that transversions at C:G base pairs occur by two distinct processing pathways that are dictated by sequence context. Within and near AGCT mutation hotspots, transversion mutation at C:G was driven by UNG2 without requirement for mismatch repair. Deaminations in AGCT were refractive both to processing by UNG2 and to high-fidelity base excision repair (BER) downstream of UNG2, regardless of mismatch repair activity. We propose that AGCT sequences resist faithful BER because they bind BER-inhibitory protein(s) and/or because hemi-deaminated AGCT motifs innately form a BER-resistant DNA structure. Distal to AGCT sequences, transversions at G were largely co-dependent on UNG2 and mismatch repair. We propose that AGCT-distal transversions are produced when apyrimidinic sites are exposed in mismatch excision patches, because completion of mismatch repair would require bypass of these sites. PMID:28039326

Size mismatch in liver transplantation.

PubMed

Fukazawa, Kyota; Nishida, Seigo

2016-08-01

Size mismatch is an unique and inevitable but critical issue in live donor liver transplantation. Unmatched metabolic demand of recipient as well as physiologic mismatch aggravates the damage to liver graft, inevitably leading to graft failure on recipient. Also, an excessive resection of liver graft for better recipient outcome in live donor liver transplant may jeopardize the healthy donor well-being and even put donor life in danger. There is a fine balance between resected graft volume required to meet the recipient's metabolic demand and residual graft volume required for donor safety. The obvious clinical necessity of finding that balance has prompted a clinical need and promoted the improvement of knowledge and development of management strategies for size-mismatched transplants. The development of the size-matching methodology has significantly improved graft outcome and recipient survival in live donor liver transplants. On the other hand, the effect of size mismatch in cadaveric transplants has never been observed as being so pronounced. The importance of matching of the donor recipient size has been unrecognized in cadaveric liver transplant. In this review, we attempt to summarize the current most updated knowledge on the subject, particularly addressing the definition and complications of size-mismatched cadaveric liver transplant, as well as management strategies. © 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

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

PubMed

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.

Detecting mismatches of bird migration stopover and tree phenology in response to changing climate

USGS Publications Warehouse

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.