Sample records for conventional mismatch controls

  1. The mismatch between conventional house price modeling and regulated markets: insights from The Netherlands.

    PubMed

    Tu, Qi; de Haan, Jan; Boelhouwer, Peter

    2017-01-01

    House price modeling has been frequently used to investigate the dynamics of housing markets, especially competitive markets; yet less attention has been given to markets that have experienced considerable interventions. The aim of this study is to demonstrate a mismatch between conventional house price models and the case of the Netherlands and to provide reasons of such mismatch. We first describe and classify the conventional house price models into asset-pricing house price model, stock-flow model, multi-period utility model, and repayment model. These models are subsequently applied to the Netherlands, where considerable government interventions took place. As expected, the empirical results are unsatisfactory to explain the Dutch house price development. The degree of mismatch of the repayment model and the multi-period utility model, however, seems to be fairly limited.

  2. Neighboring extremal optimal control design including model mismatch errors

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

    Kim, T.J.; Hull, D.G.

    1994-11-01

    The mismatch control technique that is used to simplify model equations of motion in order to determine analytic optimal control laws is extended using neighboring extremal theory. The first variation optimal control equations are linearized about the extremal path to account for perturbations in the initial state and the final constraint manifold. A numerical example demonstrates that the tuning procedure inherent in the mismatch control method increases the performance of the controls to the level of a numerically-determined piecewise-linear controller.

  3. 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.

  4. Novel disturbance-observer-based control for systems with high-order mismatched disturbances

    NASA Astrophysics Data System (ADS)

    Fang, Xing; Liu, Fei; Wang, Zhiguo; Dong, Na

    2018-01-01

    A novel disturbance-observer-based control method is investigated to attenuate the high-order mismatched disturbances. First, a finite-time disturbance observer (FTDO) is proposed to estimate the disturbances as well as the derivatives. By incorporating the outputs of FTDO, the original system is then reconstructed, where the mismatched disturbances are transformed to the matched ones that are compensated by feed-forward algorithm. Moreover, a feedback control law is developed to achieve the stability and tracking performance requirements for the systems. Finally, the proposed composite control method is applied to an unmanned helicopter system. The simulation results demonstrate that the proposed control method exhibits excellent control performance in the presence of high-order matched and mismatched disturbances.

  5. 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.

  6. 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.

  7. 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.…

  8. Mismatches in genetic markers in a large family study.

    PubMed Central

    Ashton, G C

    1980-01-01

    The Hawaii Family Study of Cognition provided an opportunity to investigate the frequency and implications of non-agreement, or mismatches, between observed and expected genetic marker phenotypes of husbands, wives, and children. Mismatch data from 68 families in which one or both spouses were known not to be a biological parent were used to determine the rate of undeclared nonparentage in 1,748 families in which conventional relationships were claimed. Two independent approaches gave consistent estimates, suggesting that approximately 2.3% of the 2,839 tested children from these families were probably the result of infidelity, concealed adoption, or another event. About two-thirds of the mismatches detected were probably due to properties of the techniques employed. PMID:6930820

  9. Visual-perceptual mismatch in robotic surgery.

    PubMed

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

    2017-08-01

    The principal objective of the experiment was to analyze the effects of the clutch operation of robotic surgical systems on the performance of the operator. The relative coordinate system introduced by the clutch operation can introduce a visual-perceptual mismatch which can potentially have negative impact on a surgeon's performance. We also assess the impact of the introduction of additional tactile sensory information on reducing the impact of visual-perceptual mismatch on the performance of the operator. We asked 45 novice subjects to complete peg transfers using the da Vinci IS 1200 system with grasper-mounted, normal force sensors. The task involves picking up a peg with one of the robotic arms, passing it to the other arm, and then placing it on the opposite side of the view. Subjects were divided into three groups: aligned group (no mismatch), the misaligned group (10 cm z axis mismatch), and the haptics-misaligned group (haptic feedback and z axis mismatch). Each subject performed the task five times, during which the grip force, time of completion, and number of faults were recorded. Compared to the subjects that performed the tasks using a properly aligned controller/arm configuration, subjects with a single-axis misalignment showed significantly more peg drops (p = 0.011) and longer time to completion (p < 0.001). Additionally, it was observed that addition of tactile feedback helps reduce the negative effects of visual-perceptual mismatch in some cases. Grip force data recorded from grasper-mounted sensors showed no difference between the different groups. The visual-perceptual mismatch created by the misalignment of the robotic controls relative to the robotic arms has a negative impact on the operator of a robotic surgical system. Introduction of other sensory information and haptic feedback systems can help in potentially reducing this effect.

  10. 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

  11. Continuous uniformly finite time exact disturbance observer based control for fixed-time stabilization of nonlinear systems with mismatched disturbances

    PubMed Central

    Liu, Chongxin; Liu, Hang

    2017-01-01

    This paper presents a continuous composite control scheme to achieve fixed-time stabilization for nonlinear systems with mismatched disturbances. The composite controller is constructed in two steps: First, uniformly finite time exact disturbance observers are proposed to estimate and compensate the disturbances. Then, based on adding a power integrator technique and fixed-time stability theory, continuous fixed-time stable state feedback controller and Lyapunov functions are constructed to achieve global fixed-time system stabilization. The proposed control method extends the existing fixed-time stable control results to high order nonlinear systems with mismatched disturbances and achieves global fixed-time system stabilization. Besides, the proposed control scheme improves the disturbance rejection performance and achieves performance recovery of nominal system. Simulation results are provided to show the effectiveness, the superiority and the applicability of the proposed control scheme. PMID:28406966

  12. Receiver IQ mismatch estimation in PDM CO-OFDM system using training symbol

    NASA Astrophysics Data System (ADS)

    Peng, Dandan; Ma, Xiurong; Yao, Xin; Zhang, Haoyuan

    2017-07-01

    Receiver in-phase/quadrature (IQ) mismatch is hard to mitigate at the receiver via using conventional method in polarization division multiplexed (PDM) coherent optical orthogonal frequency division multiplexing (CO-OFDM) system. In this paper, a novel training symbol structure is proposed to estimate IQ mismatch and channel distortion. Combined this structure with Gram Schmidt orthogonalization procedure (GSOP) algorithm, we can get lower bit error rate (BER). Meanwhile, based on this structure one estimation method is deduced in frequency domain which can achieve the estimation of IQ mismatch and channel distortion independently and improve the system performance obviously. Numerical simulation shows that the proposed two methods have better performance than compared method at 100 Gb/s after 480 km fiber transmission. Besides, the calculation complexity is also analyzed.

  13. 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.

  14. Robust MOE Detector for DS-CDMA Systems with Signature Waveform Mismatch

    NASA Astrophysics Data System (ADS)

    Lin, Tsui-Tsai

    In this letter, a decision-directed MOE detector with excellent robustness against signature waveform mismatch is proposed for DS-CDMA systems. Both the theoretic analysis and computer simulation results demonstrate that the proposed detector can provide better SINR performance than that of conventional detectors.

  15. Temperature-dependent spectral mismatch corrections

    DOE PAGES

    Osterwald, Carl R.; Campanelli, Mark; Moriarty, Tom; ...

    2015-11-01

    This study develops the mathematical foundation for a translation of solar cell short-circuit current from one thermal and spectral irradiance operating condition to another without the use of ill-defined and error-prone temperature coefficients typically employed in solar cell metrology. Using the partial derivative of quantum efficiency with respect to temperature, the conventional isothermal expression for spectral mismatch corrections is modified to account for changes of current due to temperature; this modification completely eliminates the need for short-circuit-current temperature coefficients. An example calculation is provided to demonstrate use of the new translation.

  16. Dimensionality Controlled Octahedral Symmetry-Mismatch and Functionalities in Epitaxial LaCoO₃/SrTiO₃ Heterostructures.

    PubMed

    Qiao, Liang; Jang, Jae Hyuck; Singh, David J; Gai, Zheng; Xiao, Haiyan; Mehta, Apurva; Vasudevan, Rama K; Tselev, Alexander; Feng, Zhenxing; Zhou, Hua; Li, Sean; Prellier, Wilfrid; Zu, Xiaotao; Liu, Zijiang; Borisevich, Albina; Baddorf, Arthur P; Biegalski, Michael D

    2015-07-08

    Epitaxial strain provides a powerful approach to manipulate physical properties of materials through rigid compression or extension of their chemical bonds via lattice-mismatch. Although symmetry-mismatch can lead to new physics by stabilizing novel interfacial structures, challenges in obtaining atomic-level structural information as well as lack of a suitable approach to separate it from the parasitical lattice-mismatch have limited the development of this field. Here, we present unambiguous experimental evidence that the symmetry-mismatch can be strongly controlled by dimensionality and significantly impact the collective electronic and magnetic functionalities in ultrathin perovskite LaCoO3/SrTiO3 heterojunctions. State-of-art diffraction and microscopy reveal that symmetry breaking dramatically modifies the interfacial structure of CoO6 octahedral building-blocks, resulting in expanded octahedron volume, reduced covalent screening, and stronger electron correlations. Such phenomena fundamentally alter the electronic and magnetic behaviors of LaCoO3 thin-films. We conclude that for epitaxial systems, correlation strength can be tuned by changing orbital hybridization, thus affecting the Coulomb repulsion, U, instead of by changing the band structure as the common paradigm in bulks. These results clarify the origin of magnetic ordering for epitaxial LaCoO3 and provide a route to manipulate electron correlation and magnetic functionality by orbital engineering at oxide heterojunctions.

  17. 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.

  18. A Modular Multilevel Converter with Power Mismatch Control for Grid-Connected Photovoltaic Systems

    DOE PAGES

    Duman, Turgay; Marti, Shilpa; Moonem, M. A.; ...

    2017-05-17

    A modular multilevel power converter configuration for grid connected photovoltaic (PV) systems is proposed. The converter configuration replaces the conventional bulky line frequency transformer with several high frequency transformers, potentially reducing the balance of systems cost of PV systems. The front-end converter for each port is a neutral-point diode clamped (NPC) multi-level dc-dc dual-active bridge (ML-DAB) which allows maximum power point tracking (MPPT). The integrated high frequency transformer provides the galvanic isolation between the PV and grid side and also steps up the low dc voltage from PV source. Following the ML-DAB stage, in each port, is a NPC inverter.more » N number of NPC inverters’ outputs are cascaded to attain the per-phase line-to-neutral voltage to connect directly to the distribution grid (i.e., 13.8 kV). The cascaded NPC (CNPC) inverters have the inherent advantage of using lower rated devices, smaller filters and low total harmonic distortion required for PV grid interconnection. The proposed converter system is modular, scalable, and serviceable with zero downtime with lower foot print and lower overall cost. A novel voltage balance control at each module based on power mismatch among N-ports, have been presented and verified in simulation. Analysis and simulation results are presented for the N-port converter. The converter performance has also been verified on a hardware prototype.« less

  19. A Modular Multilevel Converter with Power Mismatch Control for Grid-Connected Photovoltaic Systems

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

    Duman, Turgay; Marti, Shilpa; Moonem, M. A.

    A modular multilevel power converter configuration for grid connected photovoltaic (PV) systems is proposed. The converter configuration replaces the conventional bulky line frequency transformer with several high frequency transformers, potentially reducing the balance of systems cost of PV systems. The front-end converter for each port is a neutral-point diode clamped (NPC) multi-level dc-dc dual-active bridge (ML-DAB) which allows maximum power point tracking (MPPT). The integrated high frequency transformer provides the galvanic isolation between the PV and grid side and also steps up the low dc voltage from PV source. Following the ML-DAB stage, in each port, is a NPC inverter.more » N number of NPC inverters’ outputs are cascaded to attain the per-phase line-to-neutral voltage to connect directly to the distribution grid (i.e., 13.8 kV). The cascaded NPC (CNPC) inverters have the inherent advantage of using lower rated devices, smaller filters and low total harmonic distortion required for PV grid interconnection. The proposed converter system is modular, scalable, and serviceable with zero downtime with lower foot print and lower overall cost. A novel voltage balance control at each module based on power mismatch among N-ports, have been presented and verified in simulation. Analysis and simulation results are presented for the N-port converter. The converter performance has also been verified on a hardware prototype.« less

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

    PubMed

    Cai, Shuiming; Hao, Junjun; Liu, Zengrong

    2011-06-01

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

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

    PubMed

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

    2011-07-01

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

  2. 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…

  3. 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.

  4. 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.

  5. 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

  6. Synchronization error estimation and controller design for delayed Lur'e systems with parameter mismatches.

    PubMed

    He, Wangli; Qian, Feng; Han, Qing-Long; Cao, Jinde

    2012-10-01

    This paper investigates the problem of master-slave synchronization of two delayed Lur'e systems in the presence of parameter mismatches. First, by analyzing the corresponding synchronization error system, synchronization with an error level, which is referred to as quasi-synchronization, is established. Some delay-dependent quasi-synchronization criteria are derived. An estimation of the synchronization error bound is given, and an explicit expression of error levels is obtained. Second, sufficient conditions on the existence of feedback controllers under a predetermined error level are provided. The controller gains are obtained by solving a set of linear matrix inequalities. Finally, a delayed Chua's circuit is chosen to illustrate the effectiveness of the derived results.

  7. 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.

  8. 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

  9. 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.

  10. Infrequent identity mismatches are frequently undetected

    PubMed Central

    Goldinger, Stephen D.

    2014-01-01

    The ability to quickly and accurately match faces to photographs bears critically on many domains, from controlling purchase of age-restricted goods to law enforcement and airport security. Despite its pervasiveness and importance, research has shown that face matching is surprisingly error prone. The majority of face-matching research is conducted under idealized conditions (e.g., using photographs of individuals taken on the same day) and with equal proportions of match and mismatch trials, a rate that is likely not observed in everyday face matching. In four experiments, we presented observers with photographs of faces taken an average of 1.5 years apart and tested whether face-matching performance is affected by the prevalence of identity mismatches, comparing conditions of low (10 %) and high (50 %) mismatch prevalence. Like the low-prevalence effect in visual search, we observed inflated miss rates under low-prevalence conditions. This effect persisted when participants were allowed to correct their initial responses (Experiment 2), when they had to verify every decision with a certainty judgment (Experiment 3) and when they were permitted “second looks” at face pairs (Experiment 4). These results suggest that, under realistic viewing conditions, the low-prevalence effect in face matching is a large, persistent source of errors. PMID:24500751

  11. 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…

  12. Ice Nucleation Efficiency of Hydroxylated Organic Surfaces Is Controlled by Their Structural Fluctuations and Mismatch to Ice.

    PubMed

    Qiu, Yuqing; Odendahl, Nathan; Hudait, Arpa; Mason, Ryan; Bertram, Allan K; Paesani, Francesco; DeMott, Paul J; Molinero, Valeria

    2017-03-01

    Heterogeneous nucleation of ice induced by organic materials is of fundamental importance for climate, biology, and industry. Among organic ice-nucleating surfaces, monolayers of long chain alcohols are particularly effective, while monolayers of fatty acids are significantly less so. As these monolayers expose to water hydroxyl groups with an order that resembles the one in the basal plane of ice, it was proposed that lattice matching between ice and the surface controls their ice-nucleating efficiency. Organic monolayers are soft materials and display significant fluctuations. It has been conjectured that these fluctuations assist in the nucleation of ice. Here we use molecular dynamic simulations and laboratory experiments to investigate the relationship between the structure and fluctuations of hydroxylated organic surfaces and the temperature at which they nucleate ice. We find that these surfaces order interfacial water to form domains with ice-like order that are the birthplace of ice. Both mismatch and fluctuations decrease the size of the preordered domains and monotonously decrease the ice freezing temperature. The simulations indicate that fluctuations depress the freezing efficiency of monolayers of alcohols or acids to half the value predicted from lattice mismatch alone. The model captures the experimental trend in freezing efficiencies as a function of chain length and predicts that alcohols have higher freezing efficiency than acids of the same chain length. These trends are mostly controlled by the modulation of the structural mismatch to ice. We use classical nucleation theory to show that the freezing efficiencies of the monolayers are directly related to their free energy of binding to ice. This study provides a general framework to relate the equilibrium thermodynamics of ice binding to a surface and the nonequilibrium ice freezing temperature and suggests that these could be predicted from the structure of interfacial water.

  13. [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.

  14. High-performance, lattice-mismatched InGaAs/InP monolithic interconnected modules (MIMs)

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

    Fatemi, Navid S.; Wilt, David M.; Hoffman, Richard W., Jr.

    1998-10-01

    High performance, lattice-mismatched p/n InGaAs/lnP monolithic interconnected module (MIM) structures were developed for thermophotovoltaic (TPV) applications. A MIM device consists of several individual InGaAs photovoltaic (PV) cells series-connected on a single semi-insulating (S.I.) InP substrate. Both interdigitated and conventional (i.e., non-interdigitated) MIMs were fabricated. The energy bandgap (Eg) for these devices was 0.60 eV. A compositionally step-graded InPAs buffer was used to accommodate a lattice mismatch of 1.1% between the active InGaAs cell structure and the InP substrate. 1x1-cm, 15-cell, 0.60-eV MIMs demonstrated an open-circuit voltage (Voc) of 5.2 V (347 mV per cell) and a fill factor of 68.6%more » at a short-circuit current density (Jsc) of 2.0 A/cm{sup 2}, under flashlamp testing. The reverse saturation current density (Jo) was 1.6x10{sup {minus}6} A/cm{sup 2}. Jo values as low as 4.1x10{sup {minus}7} A/cm{sup 2} were also observed with a conventional planar cell geometry.« less

  15. 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.

  16. 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.

  17. Influence of sequence mismatches on the specificity of recombinase polymerase amplification technology.

    PubMed

    Daher, Rana K; Stewart, Gale; Boissinot, Maurice; Boudreau, Dominique K; Bergeron, Michel G

    2015-04-01

    Recombinase polymerase amplification (RPA) technology relies on three major proteins, recombinase proteins, single-strand binding proteins, and polymerases, to specifically amplify nucleic acid sequences in an isothermal format. The performance of RPA with respect to sequence mismatches of closely-related non-target molecules is not well documented and the influence of the number and distribution of mismatches in DNA sequences on RPA amplification reaction is not well understood. We investigated the specificity of RPA by testing closely-related species bearing naturally occurring mismatches for the tuf gene sequence of Pseudomonas aeruginosa and/or Mycobacterium tuberculosis and for the cfb gene sequence of Streptococcus agalactiae. In addition, the impact of the number and distribution of mismatches on RPA efficiency was assessed by synthetically generating 14 types of mismatched forward primers for detecting five bacterial species of high diagnostic relevance such as Clostridium difficile, Staphylococcus aureus, S. agalactiae, P. aeruginosa, and M. tuberculosis as well as Bacillus atropheus subsp. globigii for which we use the spores as internal control in diagnostic assays. A total of 87 mismatched primers were tested in this study. We observed that target specific RPA primers with mismatches (n > 1) at their 3'extrimity hampered RPA reaction. In addition, 3 mismatches covering both extremities and the center of the primer sequence negatively affected RPA yield. We demonstrated that the specificity of RPA was multifactorial. Therefore its application in clinical settings must be selected and validated a priori. We recommend that the selection of a target gene must consider the presence of closely-related non-target genes. It is advisable to choose target regions with a high number of mismatches (≥36%, relative to the size of amplicon) with respect to closely-related species and the best case scenario would be by choosing a unique target gene. Copyright © 2014

  18. 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.

  19. 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.

  20. Educational Mismatches and Labor Market Outcomes: Evidence from Both Vertical and Horizontal Mismatches in Thailand

    ERIC Educational Resources Information Center

    Pholphirul, Piriya

    2017-01-01

    Purpose: Educational mismatches constitute negative impacts on labor markets in most countries, Thailand is no exception. The purpose of this paper is to quantify the degree of educational mismatch in Thailand and its impacts on labor market outcomes. Design/methodology/approach: This study analyzes data obtained from Thailand's Labor Force Survey…

  1. Repair of naturally occurring mismatches can induce mutations in flanking DNA

    PubMed Central

    Chen, Jia; Miller, Brendan F; Furano, Anthony V

    2014-01-01

    ‘Normal’ genomic DNA contains hundreds of mismatches that are generated daily by the spontaneous deamination of C (U/G) and methyl-C (T/G). Thus, a mutagenic effect of their repair could constitute a serious genetic burden. We show here that while mismatches introduced into human cells on an SV40-based episome were invariably repaired, this process induced mutations in flanking DNA at a significantly higher rate than no mismatch controls. Most mutations involved the C of TpC, the substrate of some single strand-specific APOBEC cytidine deaminases, similar to the mutations that can typify the ‘mutator phenotype’ of numerous tumors. siRNA knockdowns and chromatin immunoprecipitation showed that TpC preferring APOBECs mediate the mutagenesis, and siRNA knockdowns showed that both the base excision and mismatch repair pathways are involved. That naturally occurring mispairs can be converted to mutators, represents an heretofore unsuspected source of genetic changes that could underlie disease, aging, and evolutionary change. DOI: http://dx.doi.org/10.7554/eLife.02001.001 PMID:24843013

  2. High-performance, lattice-mismatched InGaAs/InP monolithic interconnected modules (MIMs)

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

    Fatemi, Navid S.; Wilt, David M.; Hoffman, Richard W.

    1999-03-01

    High performance, lattice-mismatched p/n InGaAs/InP monolithic interconnected module (MIM) structures were developed for thermophotovoltaic (TPV) applications. A MIM device consists of several individual InGaAs photovoltaic (PV) cells series-connected on a single semi-insulating (S.I.) InP substrate. Both interdigitated and conventional (i.e., non-interdigitated) MIMs were fabricated. The energy bandgap (Eg) for these devices was 0.60 eV. A compositionally step-graded InPAs buffer was used to accommodate a lattice mismatch of 1.1{percent} between the active InGaAs cell structure and the InP substrate. 1{times}1-cm, 15-cell, 0.60-eV MIMs demonstrated an open-circuit voltage (Voc) of 5.2 V (347 mV per cell) and a fill factor of 68.6{percent}more » at a short-circuit current density (Jsc) of 2.0 A/cm{sup 2}, under flashlamp testing. The reverse saturation current density (Jo) was 1.6{times}10{sup {minus}6}&hthinsp;A/cm{sup 2}. Jo values as low as 4.1{times}10{sup {minus}7}&hthinsp;A/cm{sup 2} were also observed with a conventional planar cell geometry. {copyright} {ital 1999 American Institute of Physics.}« less

  3. 1.3 micrometers Wavelength Vertical Cavity Surface Emitting Laser Fabricated by Orientation-Mismatched Wafer Bonding: A Prospect for Polarization Control

    DTIC Science & Technology

    2005-06-01

    mismatched wafer bonding: A prospect for polarization control Yae L. Okuno,a) Jon Geske , Kian-Giap Gan, Yi-Jen Chiu, Steven P. DenBaars, and John E. Bowers...Uomi, M. Aoki, and T. Tsuchiya, IEEE J. Quantum Electron. 33, 959 ~1997!. 20 Y. L. Okuno, J. Geske , Y.-J. Chiu, S. P. DenBaars, and J. E. Bowers, Proc

  4. Origins of the WHO Framework Convention on Tobacco Control

    PubMed Central

    Roemer, Ruth; Taylor, Allyn; Lariviere, Jean

    2005-01-01

    The World Health Organization (WHO) Framework Convention on Tobacco Control originated in 1993 with a decision by Ruth Roemer and Allyn Taylor to apply to tobacco control Taylor’s idea that the WHO should utilize its constitutional authority to develop international conventions to advance global health. In 1995, Taylor and Ruth Roemer proposed various options to WHO, recommending the framework convention-protocol approach conceptualized by Taylor. Despite initial resistance by some WHO officials, this approach gained wide acceptance. In 1996, the World Health Assembly voted to proceed with its development. Negotiations by WHO member states led the World Health Assembly in May 2003 to adopt by consensus the WHO Framework Convention on Tobacco Control—the first international treaty adopted under WHO auspices. The treaty formally entered into force for state parties on February 27, 2005. PMID:15914812

  5. 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.

  6. 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

  7. 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.

  8. HMI conventions for process control graphics.

    PubMed

    Pikaar, Ruud N

    2012-01-01

    Process operators supervise and control complex processes. To enable the operator to do an adequate job, instrumentation and process control engineers need to address several related topics, such as console design, information design, navigation, and alarm management. In process control upgrade projects, usually a 1:1 conversion of existing graphics is proposed. This paper suggests another approach, efficiently leading to a reduced number of new powerful process graphics, supported by a permanent process overview displays. In addition a road map for structuring content (process information) and conventions for the presentation of objects, symbols, and so on, has been developed. The impact of the human factors engineering approach on process control upgrade projects is illustrated by several cases.

  9. 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…

  10. 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.

  11. 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

  12. 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

  13. Conformational arm-wrestling: battles for stereochemical control in benzamides bearing matched and mismatched chiral 2- and 6-substituents.

    PubMed

    Clayden, Jonathan; Foricher, Yann J Y; Helliwell, Madeleine; Johnson, Paul; Mitjans, David; Vinader, Victoria

    2006-02-07

    The orientation of a tertiary amide group adjacent to an aromatic ring may be governed by the stereochemistry of an adjacent chiral substituent. With a chiral substituent in both ortho positions, matched/mismatched pairs of isomers result. Evidence for matched stereochemistry is provided by the clean NMR spectra of single conformers, while mismatching gives poor or unexpected selectivities in the formation of chiral substituents, or mixtures of amide conformers. Attempts to use the match-mismatch effect to select for racemic pairs of enantiomeric substituents, and hence develop a "racemate-sequestering" reagent, are described, along with the use of "matching" to scavenge a single enantiomer of a diamine from material of incomplete enantiomeric purity.

  14. Quasi-finite-time control for high-order nonlinear systems with mismatched disturbances via mapping filtered forwarding technique

    NASA Astrophysics Data System (ADS)

    Zhang, X.; Huang, X. L.; Lu, H. Q.

    2017-02-01

    In this study, a quasi-finite-time control method for designing stabilising control laws is developed for high-order strict-feedback nonlinear systems with mismatched disturbances. By using mapping filtered forwarding technique, a virtual control is designed to force the off-the-manifold coordinate to converge to zero in quasi-finite time at each step of the design; at the same time, the manifold is rendered insensitive to time-varying, bounded and unknown disturbances. In terms of standard forwarding methodology, the algorithm proposed here not only does not require the Lyapunov function for controller design, but also avoids to calculate the derivative of sign function. As far as the dynamic performance of closed-loop systems is concerned, we essentially obtain the finite-time performances, which is typically reflected in the following aspects: fast and accurate responses, high tracking precision, and robust disturbance rejection. Spring, mass, and damper system and flexible joints robot are tested to demonstrate the proposed controller performance.

  15. 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

  16. Intensive versus conventional glucose control in critically ill patients.

    PubMed

    Finfer, Simon; Chittock, Dean R; Su, Steve Yu-Shuo; Blair, Deborah; Foster, Denise; Dhingra, Vinay; Bellomo, Rinaldo; Cook, Deborah; Dodek, Peter; Henderson, William R; Hébert, Paul C; Heritier, Stephane; Heyland, Daren K; McArthur, Colin; McDonald, Ellen; Mitchell, Imogen; Myburgh, John A; Norton, Robyn; Potter, Julie; Robinson, Bruce G; Ronco, Juan J

    2009-03-26

    The optimal target range for blood glucose in critically ill patients remains unclear. Within 24 hours after admission to an intensive care unit (ICU), adults who were expected to require treatment in the ICU on 3 or more consecutive days were randomly assigned to undergo either intensive glucose control, with a target blood glucose range of 81 to 108 mg per deciliter (4.5 to 6.0 mmol per liter), or conventional glucose control, with a target of 180 mg or less per deciliter (10.0 mmol or less per liter). We defined the primary end point as death from any cause within 90 days after randomization. Of the 6104 patients who underwent randomization, 3054 were assigned to undergo intensive control and 3050 to undergo conventional control; data with regard to the primary outcome at day 90 were available for 3010 and 3012 patients, respectively. The two groups had similar characteristics at baseline. A total of 829 patients (27.5%) in the intensive-control group and 751 (24.9%) in the conventional-control group died (odds ratio for intensive control, 1.14; 95% confidence interval, 1.02 to 1.28; P=0.02). The treatment effect did not differ significantly between operative (surgical) patients and nonoperative (medical) patients (odds ratio for death in the intensive-control group, 1.31 and 1.07, respectively; P=0.10). Severe hypoglycemia (blood glucose level, < or = 40 mg per deciliter [2.2 mmol per liter]) was reported in 206 of 3016 patients (6.8%) in the intensive-control group and 15 of 3014 (0.5%) in the conventional-control group (P<0.001). There was no significant difference between the two treatment groups in the median number of days in the ICU (P=0.84) or hospital (P=0.86) or the median number of days of mechanical ventilation (P=0.56) or renal-replacement therapy (P=0.39). In this large, international, randomized trial, we found that intensive glucose control increased mortality among adults in the ICU: a blood glucose target of 180 mg or less per deciliter

  17. 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)).

  18. Investigating the (Mis)Match between Natural Pest Control Knowledge and the Intensity of Pesticide Use.

    PubMed

    Mall, David; Larsen, Ashley E; Martin, Emily A

    2018-01-05

    Transforming modern agriculture towards both higher yields and greater sustainability is critical for preserving biodiversity in an increasingly populous and variable world. However, the intensity of agricultural practices varies strongly between crop systems. Given limited research capacity, it is crucial to focus efforts to increase sustainability in the crop systems that need it most. In this study, we investigate the match (or mismatch) between the intensity of pesticide use and the availability of knowledge on the ecosystem service of natural pest control across various crop systems. Using a systematic literature search on pest control and publicly available pesticide data, we find that pest control literature is not more abundant in crops where insecticide input per hectare is highest. Instead, pest control literature is most abundant, with the highest number of studies published, in crops with comparatively low insecticide input per hectare but with high world harvested area. These results suggest that a major increase of interest in agroecological research towards crops with high insecticide input, particularly cotton and horticultural crops such as citrus and high value-added vegetables, would help meet knowledge needs for a timely ecointensification of agriculture.

  19. Investigating the (Mis)Match between Natural Pest Control Knowledge and the Intensity of Pesticide Use

    PubMed Central

    Larsen, Ashley E.

    2018-01-01

    Transforming modern agriculture towards both higher yields and greater sustainability is critical for preserving biodiversity in an increasingly populous and variable world. However, the intensity of agricultural practices varies strongly between crop systems. Given limited research capacity, it is crucial to focus efforts to increase sustainability in the crop systems that need it most. In this study, we investigate the match (or mismatch) between the intensity of pesticide use and the availability of knowledge on the ecosystem service of natural pest control across various crop systems. Using a systematic literature search on pest control and publicly available pesticide data, we find that pest control literature is not more abundant in crops where insecticide input per hectare is highest. Instead, pest control literature is most abundant, with the highest number of studies published, in crops with comparatively low insecticide input per hectare but with high world harvested area. These results suggest that a major increase of interest in agroecological research towards crops with high insecticide input, particularly cotton and horticultural crops such as citrus and high value-added vegetables, would help meet knowledge needs for a timely ecointensification of agriculture. PMID:29304005

  20. 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

  1. 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

  2. Oxygen Diode Formed in Nickelate Heterostructures by Chemical Potential Mismatch

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

    Guo, Erjia; Liu, Yaohua; Sohn, Changhee

    Deliberate control of oxygen vacancy formation and migration in perovskite oxide thin films is important for developing novel electronic and iontronic devices. Here in this paper, it is found that the concentration of oxygen vacancies (V O) formed in LaNiO 3 (LNO) during pulsed laser deposition is strongly affected by the chemical potential mismatch between the LNO film and its proximal layers. Increasing the V O concentration in LNO significantly modifies the degree of orbital polarization and drives the metal–insulator transition. Changes in the nickel oxidization state and carrier concentration in the films are confirmed by soft X-ray absorption spectroscopymore » and optical spectroscopy. The ability to unidirectional-control the oxygen flow across the heterointerface, e.g., a so-called “oxygen diode”, by exploiting chemical potential mismatch at interfaces provides a new avenue to tune the physical and electrochemical properties of complex oxides.« less

  3. Oxygen Diode Formed in Nickelate Heterostructures by Chemical Potential Mismatch

    DOE PAGES

    Guo, Erjia; Liu, Yaohua; Sohn, Changhee; ...

    2018-03-07

    Deliberate control of oxygen vacancy formation and migration in perovskite oxide thin films is important for developing novel electronic and iontronic devices. Here in this paper, it is found that the concentration of oxygen vacancies (V O) formed in LaNiO 3 (LNO) during pulsed laser deposition is strongly affected by the chemical potential mismatch between the LNO film and its proximal layers. Increasing the V O concentration in LNO significantly modifies the degree of orbital polarization and drives the metal–insulator transition. Changes in the nickel oxidization state and carrier concentration in the films are confirmed by soft X-ray absorption spectroscopymore » and optical spectroscopy. The ability to unidirectional-control the oxygen flow across the heterointerface, e.g., a so-called “oxygen diode”, by exploiting chemical potential mismatch at interfaces provides a new avenue to tune the physical and electrochemical properties of complex oxides.« less

  4. 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

  5. Repeated human leukocyte antigen mismatches in lung re-transplantation.

    PubMed

    Sommer, Wiebke; Hallensleben, Michael; Ius, Fabio; Kühn, Christian; Tudorache, Igor; Avsar, Murat; Salman, Jawad; Siemeni, Thierry; Greer, Mark; Gottlieb, Jens; Boethig, Dietmar; Blasczyk, Rainer; Haverich, Axel; Warnecke, Gregor

    2017-02-01

    The role of HLA-sensitization in the absence of detectable DSA in lung re-transplantation is unclear. Antigens of the second donor matching the HLA typing of the first donor are considered 'unacceptable', by some tissue typing laboratories, especially in kidney re-transplantation. Thus, we performed a retrospective analysis of all lung re-transplantations focussing on the impact of HLA-homologies between the first and the second donor ('unacceptable' antigens; repeated HLA mismatch) on patient and graft survival. A total of 132 lung re-transplantations were performed at our centre between 1985 and 2014, of which 120 with complete HLA data were analysed. 55.8% of the recipients received re-transplants with repeated HLA mismatched antigens whereas 43.2% of the re-transplants were transplanted without repeated HLA mismatched antigens. Postoperative survival showed no difference between re-transplant procedures with or without repeated HLA mismatches (p=0.99). While neither homologies on the HLA-A, -B, -C, or -DR locus, nor the addition of several locus homologies (p=0.72) had an impact on survival, unexpectedly, repeated HLA mismatching on the HLA-DQ locus was correlated with better survival. Re-transplantations with repeated HLA mismatches did not result in more development of CLAD as compared to recipients without repeated HLA mismatches (p=0.99). Neither the number of repeated HLA mismatched antigens (p=0.52) nor the HLA locus (HLA-A(p=0.34), HLA-B(p=0.97), HLA-C (p=0.80), HLA-DR(p=0.49) and HLA-DQ(p=0.07)) had an impact on the development of CLAD after re-transplantation. Transplantation with repeated HLA mismatches due to sensitization by a previous transplantation in the absence of detectable HLA-antibodies does not have a negative impact on patient or graft survival. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. 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).

  7. 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…

  8. 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

  9. 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.

  10. 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.

  11. 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

  12. Women's Contraceptive Preference-Use Mismatch

    PubMed Central

    He, Katherine; Dalton, Vanessa K.; Zochowski, Melissa K.

    2017-01-01

    Abstract Background: Family planning research has not adequately addressed women's preferences for different contraceptive methods and whether women's contraceptive experiences match their preferences. Methods: Data were drawn from the Women's Healthcare Experiences and Preferences Study, an Internet survey of 1,078 women aged 18–55 randomly sampled from a national probability panel. Survey items assessed women's preferences for contraceptive methods, match between methods preferred and used, and perceived reasons for mismatch. We estimated predictors of contraceptive preference with multinomial logistic regression models. Results: Among women at risk for pregnancy who responded with their preferred method (n = 363), hormonal methods (non-LARC [long-acting reversible contraception]) were the most preferred method (34%), followed by no method (23%) and LARC (18%). Sociodemographic differences in contraception method preferences were noted (p-values <0.05), generally with minority, married, and older women having higher rates of preferring less effective methods, compared to their counterparts. Thirty-six percent of women reported preference-use mismatch, with the majority preferring more effective methods than those they were using. Rates of match between preferred and usual methods were highest for LARC (76%), hormonal (non-LARC) (65%), and no method (65%). The most common reasons for mismatch were cost/insurance (41%), lack of perceived/actual need (34%), and method-specific preference concerns (19%). Conclusion: While preference for effective contraception was common among this sample of women, we found substantial mismatch between preferred and usual methods, notably among women of lower socioeconomic status and women using less effective methods. Findings may have implications for patient-centered contraceptive interventions. PMID:27710196

  13. 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/

  14. 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

  15. Foot-to-shoe mismatch and rates of referral in Special Olympics athletes.

    PubMed

    Jenkins, David W; Cooper, Kimbal; O'Connor, Rachel; Watanabe, Liane

    2012-01-01

    Improperly fitted shoes are frequently seen in athletes participating in Special Olympics competitions. This foot-to-shoe mismatch may result in deformities as well as discomfort and reduced performance or injuries in competitions. A primary purpose for providing medical screenings is to identify conditions unknown and to promptly refer to an appropriate provider for evaluation and care. This study attempts to determine the prevalence of improperly fitted shoes and the rate of referral for Special Olympics athletes screened at Fit Feet venues. To evaluate the foot-to-shoe mismatch and rate of referral, 4,094 Fit Feet screenings of Special Olympics athletes participating in US competitions in 2005 to 2009 were analyzed. The participants were 58.5% male and 41.5% female, with a median age of 25.6 years. A power analysis and the χ(2) test were used. The athletes voluntarily underwent a foot screening that followed the standardized Special Olympics Fit Feet protocol. The Brannock Device for measuring feet was used to assess proper fit. A proper fit was found in 58.56% of the athletes, with 28.60% wearing shoes too big and 12.84% wearing shoes too small. Unrelated to shoe fit, 20% of the athletes required referrals for professional follow-up based on abnormal clinical findings. There is a significant (41.44%) mismatch of foot to shoe in Special Olympics athletes. The most common mismatch is a shoe too big, with a much smaller number of athletes having shoes too small. Awareness of this foot-to-shoe incompatibility may be useful for the development of shoes better designed for athletes with a foot structure not consistent with conventional shoes. Because 20% of the athletes required a referral for professional follow-up, Fit Feet examinations are important for identifying athletes with conditions that can be more readily evaluated and treated, thus improving the athletes' comfort and performance. Beyond knowing the rate of referral, future studies can determine the

  16. 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.

  17. Extracting and compensating dispersion mismatch in ultrahigh-resolution Fourier domain OCT imaging of the retina

    PubMed Central

    Choi, WooJhon; Baumann, Bernhard; Swanson, Eric A.; Fujimoto, James G.

    2012-01-01

    We present a numerical approach to extract the dispersion mismatch in ultrahigh-resolution Fourier domain optical coherence tomography (OCT) imaging of the retina. The method draws upon an analogy with a Shack-Hartmann wavefront sensor. By exploiting mathematical similarities between the expressions for aberration in optical imaging and dispersion mismatch in spectral / Fourier domain OCT, Shack-Hartmann principles can be extended from the two-dimensional paraxial wavevector space (or the x-y plane in the spatial domain) to the one-dimensional wavenumber space (or the z-axis in the spatial domain). For OCT imaging of the retina, different retinal layers, such as the retinal nerve fiber layer (RNFL), the photoreceptor inner and outer segment junction (IS/OS), or all the retinal layers near the retinal pigment epithelium (RPE) can be used as point source beacons in the axial direction, analogous to point source beacons used in conventional two-dimensional Shack-Hartman wavefront sensors for aberration characterization. Subtleties regarding speckle phenomena in optical imaging, which affect the Shack-Hartmann wavefront sensor used in adaptive optics, also occur analogously in this application. Using this approach and carefully suppressing speckle, the dispersion mismatch in spectral / Fourier domain OCT retinal imaging can be successfully extracted numerically and used for numerical dispersion compensation to generate sharper, ultrahigh-resolution OCT images. PMID:23187353

  18. Test report for twinax cable (Rockwell type MB0150-051). [effects of mismatched termination

    NASA Technical Reports Server (NTRS)

    Doland, G. D.

    1978-01-01

    A controlled impedance twisted pair shielded cable was tested to determine the frequency response and effects of mismatched termination. It was found that a long length of this cable, about 100 feet, exhibited a frequency sensitive attenuation roll-off greater than 1.5 db down at 5 MHz. It was also determined that improper termination resulted in losses of 1/2 to 1 db within the frequency range of 200 KHz to greater than 1-1/2 MHz. The test results indicate a possible problem where mismatched connectors are used in video signal cables.

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

    PubMed

    Joseph, Thomas T; Osman, Roman

    2012-01-01

    In RNA interference, a guide strand derived from a short dsRNA such as a microRNA (miRNA) is loaded into Argonaute, the central protein in the RNA Induced Silencing Complex (RISC) that silences messenger RNAs on a sequence-specific basis. The positions of any mismatched base pairs in an miRNA determine which Argonaute subtype is used. Subsequently, the Argonaute-guide complex binds and silences complementary target mRNAs; certain Argonautes cleave the target. Mismatches between guide strand and the target mRNA decrease cleavage efficiency. Thus, loading and silencing both require that signals about the presence of a mismatched base pair are communicated from the mismatch site to effector sites. These effector sites include the active site, to prevent target cleavage; the binding groove, to modify nucleic acid binding affinity; and surface allosteric sites, to control recruitment of additional proteins to form the RISC. To examine how such signals may be propagated, we analyzed the network of internal allosteric pathways in Argonaute exhibited through correlations of residue-residue interactions. The emerging network can be described as a set of pathways emanating from the core of the protein near the active site, distributed into the bulk of the protein, and converging upon a distributed cluster of surface residues. Nucleotides in the guide strand "seed region" have a stronger relationship with the protein than other nucleotides, concordant with their importance in sequence selectivity. Finally, any of several seed region guide-target mismatches cause certain Argonaute residues to have modified correlations with the rest of the protein. This arises from the aggregation of relatively small interaction correlation changes distributed across a large subset of residues. These residues are in effector sites: the active site, binding groove, and surface, implying that direct functional consequences of guide-target mismatches are mediated through the cumulative effects of

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

    PubMed Central

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

    2018-01-01

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

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. Lattice mismatch modeling of aluminum alloys

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

    Shin, Dongwon; Roy, Shibayan; Watkins, Thomas R.

    We present a theoretical framework to accurately predict the lattice mismatch between the fcc matrix and precipitates in the multi-component aluminum alloys as a function of temperature and composition. We use a computational thermodynamic approach to model the lattice parameters of the multi-component fcc solid solution and θ'-Al2Cu precipitate phase. Better agreement between the predicted lattice parameters of fcc aluminum in five commercial alloys (206, 319, 356, A356, and A356 + 0.5Cu) and experimental data from the synchrotron X-ray diffraction (SXD) has been obtained when simulating supersaturated rather than equilibrium solid solutions. We use the thermal expansion coefficient of thermodynamicallymore » stable θ-Al2Cu to describe temperature-dependent lattice parameters of meta-stable θ' and to show good agreement with the SXD data. Both coherent and semi-coherent interface mismatches between the fcc aluminum matrix and θ' in Al-Cu alloys are presented as a function of temperature. Our calculation results show that the concentration of solute atoms, particularly Cu, in the matrix greatly affects the lattice mismatch« less

  8. 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

  9. 15 CFR 742.18 - Chemical Weapons Convention (CWC or Convention).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 2 2011-01-01 2011-01-01 false Chemical Weapons Convention (CWC or... REGULATIONS CONTROL POLICY-CCL BASED CONTROLS § 742.18 Chemical Weapons Convention (CWC or Convention). States... Use of Chemical Weapons and on Their Destruction, also known as the Chemical Weapons Convention (CWC...

  10. 15 CFR 742.18 - Chemical Weapons Convention (CWC or Convention).

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 15 Commerce and Foreign Trade 2 2013-01-01 2013-01-01 false Chemical Weapons Convention (CWC or... REGULATIONS CONTROL POLICY-CCL BASED CONTROLS § 742.18 Chemical Weapons Convention (CWC or Convention). States... Use of Chemical Weapons and on Their Destruction, also known as the Chemical Weapons Convention (CWC...

  11. A comparison of the real-time controllability of pattern recognition to conventional myoelectric control for discrete and simultaneous movements

    PubMed Central

    2014-01-01

    Myoelectric control has been used for decades to control powered upper limb prostheses. Conventional, amplitude-based control has been employed to control a single prosthesis degree of freedom (DOF) such as closing and opening of the hand. Within the last decade, new and advanced arm and hand prostheses have been constructed that are capable of actuating numerous DOFs. Pattern recognition control has been proposed to control a greater number of DOFs than conventional control, but has traditionally been limited to sequentially controlling DOFs one at a time. However, able-bodied individuals use multiple DOFs simultaneously, and it may be beneficial to provide amputees the ability to perform simultaneous movements. In this study, four amputees who had undergone targeted motor reinnervation (TMR) surgery with previous training using myoelectric prostheses were configured to use three control strategies: 1) conventional amplitude-based myoelectric control, 2) sequential (one-DOF) pattern recognition control, 3) simultaneous pattern recognition control. Simultaneous pattern recognition was enabled by having amputees train each simultaneous movement as a separate motion class. For tasks that required control over just one DOF, sequential pattern recognition based control performed the best with the lowest average completion times, completion rates and length error. For tasks that required control over 2 DOFs, the simultaneous pattern recognition controller performed the best with the lowest average completion times, completion rates and length error compared to the other control strategies. In the two strategies in which users could employ simultaneous movements (conventional and simultaneous pattern recognition), amputees chose to use simultaneous movements 78% of the time with simultaneous pattern recognition and 64% of the time with conventional control for tasks that required two DOF motions to reach the target. These results suggest that when amputees are given the

  12. Civil society and the negotiation of the Framework Convention on Tobacco Control

    PubMed Central

    MAMUDU, H. M.

    2008-01-01

    Tobacco control civil society organisations mobilised to influence countries during the negotiation of the World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC) between 1999 and 2003. Tobacco control civil society organisations and coalitions around the world embraced the idea of an international tobacco control treaty and came together as the Framework Convention Alliance (FCA), becoming an important non-state actor within the international system of tobacco control. Archival documents and interviews demonstrate that the FCA successfully used strategies including publication of a newsletter, shaming, symbolism and media advocacy to influence policy positions of countries during the FCTC negotiation. The FCA became influential in the negotiation process by mobilising tobacco control civil society organisations and resources with the help of the Internet and framing the tobacco control discussion around global public health. PMID:19333806

  13. A new fractional-order sliding mode controller via a nonlinear disturbance observer for a class of dynamical systems with mismatched disturbances.

    PubMed

    Pashaei, Shabnam; Badamchizadeh, Mohammadali

    2016-07-01

    This paper investigates the stabilization and disturbance rejection for a class of fractional-order nonlinear dynamical systems with mismatched disturbances. To fulfill this purpose a new fractional-order sliding mode control (FOSMC) based on a nonlinear disturbance observer is proposed. In order to design the suitable fractional-order sliding mode controller, a proper switching surface is introduced. Afterward, by using the sliding mode theory and Lyapunov stability theory, a robust fractional-order control law via a nonlinear disturbance observer is proposed to assure the existence of the sliding motion in finite time. The proposed fractional-order sliding mode controller exposes better control performance, ensures fast and robust stability of the closed-loop system, eliminates the disturbances and diminishes the chattering problem. Finally, the effectiveness of the proposed fractional-order controller is depicted via numerical simulation results of practical example and is compared with some other controllers. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

  14. Maladaptation and phenotypic mismatch in hatchery-reared Atlantic salmon Salmo salar released in the wild.

    PubMed

    Stringwell, R; Lock, A; Stutchbury, C J; Baggett, E; Taylor, J; Gough, P J; Garcia de Leaniz, C

    2014-12-01

    Changes in body shape, fluctuating asymmetry (FA) and crypsis were compared among Atlantic salmon Salmo salar fry kept as controls in captivity and those released and subsequently recaptured in the wild according to a before-after-control-impact (BACI) design. Hatchery fish that survived in the wild became more cryptic and displayed a much lower incidence of fin erosion and of asymmetric individuals than control fish kept in captivity. Significant differences in body shape were also apparent, and survivors had longer heads, thicker caudal peduncles and a more streamlined body shape than hatchery controls as early as 20 days following stocking, most likely as a result of phenotypic plasticity and non-random, selective mortality of maladapted phenotypes. Hatchery-reared fish typically perform poorly in the wild and the results of this study indicate that this may be due to phenotypic mismatch, i.e. because hatcheries generate fish that are phenotypically mismatched to the natural environment. © 2014 The Fisheries Society of the British Isles.

  15. Convergent Transmission of RNAi Guide-Target Mismatch Information across Argonaute Internal Allosteric Network

    PubMed Central

    Joseph, Thomas T.; Osman, Roman

    2012-01-01

    In RNA interference, a guide strand derived from a short dsRNA such as a microRNA (miRNA) is loaded into Argonaute, the central protein in the RNA Induced Silencing Complex (RISC) that silences messenger RNAs on a sequence-specific basis. The positions of any mismatched base pairs in an miRNA determine which Argonaute subtype is used. Subsequently, the Argonaute-guide complex binds and silences complementary target mRNAs; certain Argonautes cleave the target. Mismatches between guide strand and the target mRNA decrease cleavage efficiency. Thus, loading and silencing both require that signals about the presence of a mismatched base pair are communicated from the mismatch site to effector sites. These effector sites include the active site, to prevent target cleavage; the binding groove, to modify nucleic acid binding affinity; and surface allosteric sites, to control recruitment of additional proteins to form the RISC. To examine how such signals may be propagated, we analyzed the network of internal allosteric pathways in Argonaute exhibited through correlations of residue-residue interactions. The emerging network can be described as a set of pathways emanating from the core of the protein near the active site, distributed into the bulk of the protein, and converging upon a distributed cluster of surface residues. Nucleotides in the guide strand “seed region” have a stronger relationship with the protein than other nucleotides, concordant with their importance in sequence selectivity. Finally, any of several seed region guide-target mismatches cause certain Argonaute residues to have modified correlations with the rest of the protein. This arises from the aggregation of relatively small interaction correlation changes distributed across a large subset of residues. These residues are in effector sites: the active site, binding groove, and surface, implying that direct functional consequences of guide-target mismatches are mediated through the cumulative

  16. Decreased functional diversity and biological pest control in conventional compared to organic crop fields.

    PubMed

    Krauss, Jochen; Gallenberger, Iris; Steffan-Dewenter, Ingolf

    2011-01-01

    Organic farming is one of the most successful agri-environmental schemes, as humans benefit from high quality food, farmers from higher prices for their products and it often successfully protects biodiversity. However there is little knowledge if organic farming also increases ecosystem services like pest control. We assessed 30 triticale fields (15 organic vs. 15 conventional) and recorded vascular plants, pollinators, aphids and their predators. Further, five conventional fields which were treated with insecticides were compared with 10 non-treated conventional fields. Organic fields had five times higher plant species richness and about twenty times higher pollinator species richness compared to conventional fields. Abundance of pollinators was even more than one-hundred times higher on organic fields. In contrast, the abundance of cereal aphids was five times lower in organic fields, while predator abundances were three times higher and predator-prey ratios twenty times higher in organic fields, indicating a significantly higher potential for biological pest control in organic fields. Insecticide treatment in conventional fields had only a short-term effect on aphid densities while later in the season aphid abundances were even higher and predator abundances lower in treated compared to untreated conventional fields. Our data indicate that insecticide treatment kept aphid predators at low abundances throughout the season, thereby significantly reducing top-down control of aphid populations. Plant and pollinator species richness as well as predator abundances and predator-prey ratios were higher at field edges compared to field centres, highlighting the importance of field edges for ecosystem services. In conclusion organic farming increases biodiversity, including important functional groups like plants, pollinators and predators which enhance natural pest control. Preventative insecticide application in conventional fields has only short-term effects on aphid

  17. CONTROL OF CRYPTOSPORIDIUM OOCYSTS BY STEADY-STATE CONVENTIONAL TREATMENT

    EPA Science Inventory

    Pilot-scale experiments have been performed to assess the ability of conventional treatment to control Cryptosporidium oocysts under steady-state conditions. The work was performed with a pilot plant that was designed to minimize flow rates and, as a result, the number of oocyst...

  18. Improved design of constrained model predictive tracking control for batch processes against unknown uncertainties.

    PubMed

    Wu, Sheng; Jin, Qibing; Zhang, Ridong; Zhang, Junfeng; Gao, Furong

    2017-07-01

    In this paper, an improved constrained tracking control design is proposed for batch processes under uncertainties. A new process model that facilitates process state and tracking error augmentation with further additional tuning is first proposed. Then a subsequent controller design is formulated using robust stable constrained MPC optimization. Unlike conventional robust model predictive control (MPC), the proposed method enables the controller design to bear more degrees of tuning so that improved tracking control can be acquired, which is very important since uncertainties exist inevitably in practice and cause model/plant mismatches. An injection molding process is introduced to illustrate the effectiveness of the proposed MPC approach in comparison with conventional robust MPC. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

  19. [Constitutional mismatch repair deficiency syndrome].

    PubMed

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

    2015-01-01

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

  20. Sliding mode control for generalized robust synchronization of mismatched fractional order dynamical systems and its application to secure transmission of voice messages.

    PubMed

    Muthukumar, P; Balasubramaniam, P; Ratnavelu, K

    2017-07-26

    This paper proposes a generalized robust synchronization method for different dimensional fractional order dynamical systems with mismatched fractional derivatives in the presence of function uncertainty and external disturbance by a designing sliding mode controller. Based on the proposed theory of generalized robust synchronization criterion, a novel audio cryptosystem is proposed for sending or sharing voice messages secretly via insecure channel. Numerical examples are given to verify the potency of the proposed theories. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

  1. 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

  2. Comparison of conventional rule based flow control with control processes based on fuzzy logic in a combined sewer system.

    PubMed

    Klepiszewski, K; Schmitt, T G

    2002-01-01

    While conventional rule based, real time flow control of sewer systems is in common use, control systems based on fuzzy logic have been used only rarely, but successfully. The intention of this study is to compare a conventional rule based control of a combined sewer system with a fuzzy logic control by using hydrodynamic simulation. The objective of both control strategies is to reduce the combined sewer overflow volume by an optimization of the utilized storage capacities of four combined sewer overflow tanks. The control systems affect the outflow of four combined sewer overflow tanks depending on the water levels inside the structures. Both systems use an identical rule base. The developed control systems are tested and optimized for a single storm event which affects heterogeneously hydraulic load conditions and local discharge. Finally the efficiencies of the two different control systems are compared for two more storm events. The results indicate that the conventional rule based control and the fuzzy control similarly reach the objective of the control strategy. In spite of the higher expense to design the fuzzy control system its use provides no advantages in this case.

  3. 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…

  4. 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…

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

    PubMed

    Fraundorf, Scott H; Benjamin, Aaron S

    2016-09-01

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

  6. 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

  7. 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

  8. 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

  9. A Jobs Mismatch. Commentary

    ERIC Educational Resources Information Center

    Marina, Brenda L. H.

    2011-01-01

    In the article "A Jobs Mismatch", Jaschik has compiled the findings of a new report that was released by the Georgetown University Center on Education and the Workforce. The Georgetown University report claims that there is a severe shortage of college graduates in America, and that this shortage has the United States on a…

  10. 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

  11. Method for reducing or eliminating interface defects in mismatched semiconductor epilayers

    DOEpatents

    Fitzgerald, Jr., Eugene A.; Ast, Dieter G.

    1992-01-01

    The present invention and process relates to crystal lattice mismatched semiconductor composite having a first semiconductor layer and a second semiconductor growth layer deposited thereon to form an interface wherein the growth layer can be deposited at thicknesses in excess of the critical thickness, even up to about 10.times. critical thickness. Such composite has an interface which is substantially free of interface defects. For example, the size of the growth areas in a mismatched In.sub.0.05 Ga.sub.0.95 As/(001)GaAs interface was controlled by fabricating 2-.mu.m high pillars of various lateral geometries and lateral dimensions before the epitaxial deposition of 3500.ANG. of In.sub.0.05 Ga.sub.0.95 As. The linear dislocation density at the interface was reduced from >5000 dislocations/cm to about zero for 25-.mu.m lateral dimensions and to less than 800 dislocations/cm for lateral dimensions as large as 100 .mu.m. The fabricated pillars control the lateral dimensions of the growth layer and block the glide of misfit dislocations with the resultant decrease in dislocation density.

  12. Method for reducing or eliminating interface defects in mismatched semiconductor eiplayers

    DOEpatents

    Fitzgerald, Jr., Eugene A.; Ast, Dieter G.

    1991-01-01

    The present invention and process relates to crystal lattice mismatched semiconductor composite having a first semiconductor layer and a second semiconductor growth layer deposited thereon to form an interface wherein the growth layer can be deposited at thicknesses in excess of the critical thickness, even up to about 10x critical thickness. Such composite has an interface which is substantially free of interface defects. For example, the size of the growth areas in a mismatched In.sub.0.05 Ga.sub.0.95 As/(001)GaAs interface was controlled by fabricating 2-.mu.m high pillars of various lateral geometries and lateral dimensions before the epitaxial deposition of 3500.ANG. of In.sub.0.05 Ga.sub.0.95 As. The linear dislocation density at the interface was reduced from >5000 dislocations/cm to about zero for 25-.mu.m lateral dimensions and to less than 800 dislocations/cm for lateral dimensions as large as 100 .mu.m. The fabricated pillars control the lateral dimensions of the growth layer and block the glide of misfit dislocations with the resultant decrease in dislocation density.

  13. Method for reducing or eliminating interface defects in mismatched semiconductor epilayers

    DOEpatents

    Fitzgerald, E.A. Jr.; Ast, D.G.

    1992-10-20

    The present invention and process relates to crystal lattice mismatched semiconductor composite having a first semiconductor layer and a second semiconductor growth layer deposited thereon to form an interface wherein the growth layer can be deposited at thicknesses in excess of the critical thickness, even up to about 10[times] critical thickness. Such composite has an interface which is substantially free of interface defects. For example, the size of the growth areas in a mismatched In[sub 0.05]Ga[sub 0.95]As/(001)GaAs interface was controlled by fabricating 2-[mu]m high pillars of various lateral geometries and lateral dimensions before the epitaxial deposition of 3500 [angstrom] of In[sub 0.05]Ga[sub 0.95]As. The linear dislocation density at the interface was reduced from >5000 dislocations/cm to about zero for 25-[mu]m lateral dimensions and to less than 800 dislocations/cm for lateral dimensions as large as 100 [mu]m. The fabricated pillars control the lateral dimensions of the growth layer and block the glide of misfit dislocations with the resultant decrease in dislocation density. 7 figs.

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

    ERIC Educational Resources Information Center

    Kampelmann, Stephan; Rycx, Francois

    2012-01-01

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

  15. Decreased Functional Diversity and Biological Pest Control in Conventional Compared to Organic Crop Fields

    PubMed Central

    Krauss, Jochen; Gallenberger, Iris; Steffan-Dewenter, Ingolf

    2011-01-01

    Organic farming is one of the most successful agri-environmental schemes, as humans benefit from high quality food, farmers from higher prices for their products and it often successfully protects biodiversity. However there is little knowledge if organic farming also increases ecosystem services like pest control. We assessed 30 triticale fields (15 organic vs. 15 conventional) and recorded vascular plants, pollinators, aphids and their predators. Further, five conventional fields which were treated with insecticides were compared with 10 non-treated conventional fields. Organic fields had five times higher plant species richness and about twenty times higher pollinator species richness compared to conventional fields. Abundance of pollinators was even more than one-hundred times higher on organic fields. In contrast, the abundance of cereal aphids was five times lower in organic fields, while predator abundances were three times higher and predator-prey ratios twenty times higher in organic fields, indicating a significantly higher potential for biological pest control in organic fields. Insecticide treatment in conventional fields had only a short-term effect on aphid densities while later in the season aphid abundances were even higher and predator abundances lower in treated compared to untreated conventional fields. Our data indicate that insecticide treatment kept aphid predators at low abundances throughout the season, thereby significantly reducing top-down control of aphid populations. Plant and pollinator species richness as well as predator abundances and predator-prey ratios were higher at field edges compared to field centres, highlighting the importance of field edges for ecosystem services. In conclusion organic farming increases biodiversity, including important functional groups like plants, pollinators and predators which enhance natural pest control. Preventative insecticide application in conventional fields has only short-term effects on aphid

  16. Phase mismatched optical parametric generation in semiconductor magnetoplasma

    NASA Astrophysics Data System (ADS)

    Dubey, Swati; Ghosh, S.; Jain, Kamal

    2017-05-01

    Optical parametric generation involves the interaction of pump, signal, and idler waves satisfying law of conservation of energy. Phase mismatch parameter plays important role for the spatial distribution of the field along the medium. In this paper instead of exactly matching wave vector, a small mismatch is admitted with a degree of phase velocity mismatch between these waves. Hence the medium must possess certain finite coherence length. This wave mixing process is well explained by coupled mode theory and one dimensional hydrodynamic model. Based on this scheme, expressions for threshold pump field and transmitted intensity have been derived. It is observed that the threshold pump intensity and transmitted intensity can be manipulated by varying doping concentration and magnetic field under phase mismatched condition. A compound semiconductor crystal of n-InSb is assumed to be shined at 77 K by a 10.6μm CO2 laser with photon energy well below band gap energy of the crystal, so that only free charge carrier influence the optical properties of the medium for the I.R. parametric generation in a semiconductor plasma medium. Favorable parameters were explored to incite the said process keeping in mind the cost effectiveness and conversion efficiency of the process.

  17. Discriminating DNA mismatches by electrochemical and gravimetric techniques.

    PubMed

    Mazouz, Zouhour; Fourati, Najla; Zerrouki, Chouki; Ommezine, Asma; Rebhi, Lamia; Yaakoubi, Nourdin; Kalfat, Rafik; Othmane, Ali

    2013-10-15

    A silicon nitride functionalized electrode and a 104 MHz lithium tantalate (LiTaO₃) surface acoustic wave (SAW) sensor have been used to investigate target-probe recognition processes. Electrochemical and gravimetric measurements have been considered to monitor hybridization of single base mismatch (SBM) in synthetic oligonucleotides and single-nucleotide polymorphisms ApoE in real clinical genotypes. Obvious discrimination of SBM in nucleotides has been shown by both gravimetric and electrochemical techniques, without labeling nor amplification. Investigations on mismatches nature and position have also been considered. For guanine-adenine (GA), guanine-thymine (GT) and guanine-guanine (GG) mismatches, the sensors responses present a dependence upon positions. Considering the capacitance variations and hybridization rates, results showed that gravimetric transduction is more sensitive than electrochemical one. Moreover, the highest value of GT hybridization rate (in the middle position) was found in accordance with the nearest-neighbor model, where the considered configuration appears as the most thermodynamically stable. For the real samples, where the electrochemical transduction, by combining capacitance and flat-band potential measurements, were found more sensitive, the results show that the realized sensor permits an unambiguous discrimination of recognition between fully complementary, non-complementary and single base mismatched targets, and even between the combination of differently matched strands. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. 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…

  19. Implications of segment mismatch for influenza A virus evolution

    PubMed Central

    White, Maria C.; Lowen, Anice C.

    2018-01-01

    Influenza A virus (IAV) is an RNA virus with a segmented genome. These viral properties allow for the rapid evolution of IAV under selective pressure, due to mutation occurring from error-prone replication and the exchange of gene segments within a co-infected cell, termed reassortment. Both mutation and reassortment give rise to genetic diversity, but constraints shape their impact on viral evolution: just as most mutations are deleterious, most reassortment events result in genetic incompatibilities. The phenomenon of segment mismatch encompasses both RNA- and protein-based incompatibilities between co-infecting viruses and results in the production of progeny viruses with fitness defects. Segment mismatch is an important determining factor of the outcomes of mixed IAV infections and has been addressed in multiple risk assessment studies undertaken to date. However, due to the complexity of genetic interactions among the eight viral gene segments, our understanding of segment mismatch and its underlying mechanisms remain incomplete. Here, we summarize current knowledge regarding segment mismatch and discuss the implications of this phenomenon for IAV reassortment and diversity. PMID:29244017

  20. Magnetic resonance diffusion-perfusion mismatch in acute ischemic stroke: An update

    PubMed Central

    Chen, Feng; Ni, Yi-Cheng

    2012-01-01

    The concept of magnetic resonance perfusion-diffusion mismatch (PDM) provides a practical and approximate measure of the tissue at risk and has been increasingly applied for the evaluation of hyperacute and acute stroke in animals and patients. Recent studies demonstrated that PDM does not optimally define the ischemic penumbra; because early abnormality on diffusion-weighted imaging overestimates the infarct core by including part of the penumbra, and the abnormality on perfusion weighted imaging overestimates the penumbra by including regions of benign oligemia. To overcome these limitations, many efforts have been made to optimize conventional PDM. Various alternatives beyond the PDM concept are under investigation in order to better define the penumbra. The PDM theory has been applied in ischemic stroke for at least three purposes: to be used as a practical selection tool for stroke treatment; to test the hypothesis that patients with PDM pattern will benefit from treatment, while those without mismatch pattern will not; to be a surrogate measure for stroke outcome. The main patterns of PDM and its relation with clinical outcomes were also briefly reviewed. The conclusion was that patients with PDM documented more reperfusion, reduced infarct growth and better clinical outcomes compared to patients without PDM, but it was not yet clear that thrombolytic therapy is beneficial when patients were selected on PDM. Studies based on a larger cohort are currently under investigation to further validate the PDM hypothesis. PMID:22468186

  1. 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…

  2. 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.

  3. 40 CFR 434.74 - Effluent limitations attainable by application of the best conventional pollutant control...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... application of the best conventional pollutant control technology (BCT). 434.74 Section 434.74 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS COAL MINING POINT... Effluent limitations attainable by application of the best conventional pollutant control technology (BCT...

  4. 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

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

    PubMed

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

    2017-07-01

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

  6. 1.3 μm wavelength vertical cavity surface emitting laser fabricated by orientation-mismatched wafer bonding: A prospect for polarization control

    NASA Astrophysics Data System (ADS)

    Okuno, Yae L.; Geske, Jon; Gan, Kian-Giap; Chiu, Yi-Jen; DenBaars, Steven P.; Bowers, John E.

    2003-04-01

    We propose and demonstrate a long-wavelength vertical cavity surface emitting laser (VCSEL) which consists of a (311)B InP-based active region and (100) GaAs-based distributed Bragg reflectors (DBRs), with an aim to control the in-plane polarization of output power. Crystal growth on (311)B InP substrates was performed under low-migration conditions to achieve good crystalline quality. The VCSEL was fabricated by wafer bonding, which enables us to combine different materials regardless of their lattice and orientation mismatch without degrading their quality. The VCSEL was polarized with a power extinction ratio of 31 dB.

  7. Cooperative Mmonitoring Center Occasional Paper/5: Propspects of Conventional Arms Control in South Asia

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

    Gupta, Amit; Kamal, Nazir

    1998-11-01

    The intensely adversarial relationship between India and Pakistan is marked by military rivalry, mutual distrust, and suspicion. The most dividing disagreement has been over the Kashmir region. An inability to discuss the Kashmir issue has prevented discussion on other important issues. Since there is little prospect of detente, at least in the near-term, the question is whether this rivalry can be contained by other means, such as arms control approaches. Conventional arms control has been applied flexibly and successfully in some regions to reduce threat-perceptions and achieve reassuring military stability. Some lessons from other international models might be applied tomore » the India/Pakistan context. This paper discusses the status of conventional arms control in South Asia, the dominant Indian and Pakistani perceptions about arms control, the benefits that could be derived from arms control, as well as the problems and prospects of arms control. It also discusses existing conventional arms control agreements at the regional and global levels as well as the potential role of cooperative monitoring technology.« less

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

    PubMed Central

    Fraundorf, Scott H.; Benjamin, Aaron S.

    2015-01-01

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

  9. Frequency-response mismatch effects in Johnson noise thermometry

    NASA Astrophysics Data System (ADS)

    White, D. R.; Qu, J.-F.

    2018-02-01

    Johnson noise thermometry is of considerable interest at present due to the planned redefinition of the kelvin in 2019, and several determinations of the Boltzmann constant have recently been published in support of the redefinition. To determine the Boltzmann constant by noise thermometry, the thermal noise from a sensing resistor at the triple point of water is compared to a pseudo-random noise with a calculable power spectral density traceable to quantum electrical standards. In all the measurements to date, the two dominant sources of measurement uncertainty are strongly influenced by a single factor: the frequency-response mismatch between the sets of leads connecting the thermometer to the two noise sources. In the most recent determination at the National Institute of Metrology, China, substantial changes were made to the connecting leads to reduce the mismatch effects. The aims of this paper are, firstly, to describe and explain the rationale for the changes, and secondly, to better understand the effects of the least-squares fits and the bias-variance compromise in the analysis of measurements affected by the mismatch effects. While significant improvements can be made to the connecting leads to lessen the effects of the frequency-response mismatch, the efforts are unlikely to be rewarded by a significant increase in bandwidth or a significant reduction in uncertainty.

  10. 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.

  11. 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.

  12. 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

  13. Mismatch Responses to Lexical Tone, Initial Consonant, and Vowel in Mandarin-Speaking Preschoolers

    ERIC Educational Resources Information Center

    Lee, Chia-Ying; Yen, Huei-ling; Yeh, Pei-wen; Lin, Wan-Hsuan; Cheng, Ying-Ying; Tzeng, Yu-Lin; Wu, Hsin-Chi

    2012-01-01

    The present study investigates how age, phonological saliency, and deviance size affect the presence of mismatch negativity (MMN) and positive mismatch response (P-MMR). This work measured the auditory mismatch responses to Mandarin lexical tones, initial consonants, and vowels in 4- to 6-year-old preschoolers using the multiple-deviant oddball…

  14. Allogeneic major histocompatibility complex-mismatched equine bone marrow-derived mesenchymal stem cells are targeted for death by cytotoxic anti-major histocompatibility complex antibodies.

    PubMed

    Berglund, A K; Schnabel, L V

    2017-07-01

    Allogeneic mesenchymal stem cells (MSCs) are a promising cell source for treating musculoskeletal injuries in horses. Controversy exists, however, over whether major histocompatibility complex (MHC)-mismatched MSCs are recognised by the recipient immune system and targeted for death by a cytotoxic antibody response. To determine if cytotoxic anti-MHC antibodies generated in vivo following MHC-mismatched MSC injections are capable of initiating complement-dependent cytotoxicity of MSCs. Experimental controlled study. Antisera previously collected at Days 0, 7, 14 and 21 post-injection from 4 horses injected with donor MHC-mismatched equine leucocyte antigen (ELA)-A2 haplotype MSCs and one control horse injected with donor MHC-matched ELA-A2 MSCs were utilised in this study. Antisera were incubated with ELA-A2 MSCs before adding complement in microcytotoxicity assays and cell death was analysed via eosin dye exclusion. ELA-A2 peripheral blood leucocytes (PBLs) were used in the assays as a positive control. Antisera from all 4 horses injected with MHC-mismatched MSCs contained antibodies that caused the death of ELA-A2 haplotype MSCs in the microcytotoxicity assays. In 2 of the 4 horses, antibodies were present as early as Day 7 post-injection. MSC death was consistently equivalent to that of ELA-A2 haplotype PBL death at all time points and antisera dilutions. Antisera from the control horse that was injected with MHC-matched MSCs did not contain cytotoxic ELA-A2 antibodies at any of the time points examined. This study examined MSC death in vitro only and utilized antisera from a small number of horses. The cytotoxic antibody response induced in recipient horses following injection with donor MHC-mismatched MSCs is capable of killing donor MSCs in vitro. These results suggest that the use of allogeneic MHC-mismatched MSCs must be cautioned against, not only for potential adverse events, but also for reduced therapeutic efficacy due to targeted MSC death. © 2016 The

  15. 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.

  16. 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

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

    NASA Astrophysics Data System (ADS)

    Wu, Bin

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

  18. An Integrated Ransac and Graph Based Mismatch Elimination Approach for Wide-Baseline Image Matching

    NASA Astrophysics Data System (ADS)

    Hasheminasab, M.; Ebadi, H.; Sedaghat, A.

    2015-12-01

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

  19. Analysis of mismatch and shading effects in a photovoltaic array using different technologies

    NASA Astrophysics Data System (ADS)

    Guerrero, J.; Muñoz, Y.; Ibáñez, F.; Ospino, A.

    2014-06-01

    In this paper, we analyze the performance of a photovoltaic array implemented in the Universidad Politécnica de Valencia which consists of modules of different technologies and power, connected in series, in order to quantify the energy losses due to mismatch and the effect of the shadows. To do this, the performance of the modules was measured in operation under ambient conditions with field measurement equipment (AMPROBE Solar Analyzer, Solar - 4000), which allows the extrapolation of measures to standard conditions STC. For the data validation, measures under controlled conditions were taken to some modules in the flash test laboratory of the Institute of Energy Technology ITE of Valencia in Spain. Subsequently the array curves measured were validated with a photovoltaic array model developed in MATLAB-Simulink for the same conditions and technologies. The results of this particular array are lost up to 20% of the energy supplied due to the modules mismatch. The study shows the curves and the energy loss due to shadows modules. This result opens scenarios for conceivable modifications to the PV field configurations today, chosen during the design stage and unchangeable during the operating stage; and gives greater importance to the energy loss by mismatch in the PV array.

  20. 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.

  1. Hydrophobic mismatch sorts SNARE proteins into distinct membrane domains

    PubMed Central

    Milovanovic, Dragomir; Honigmann, Alf; Koike, Seiichi; Göttfert, Fabian; Pähler, Gesa; Junius, Meike; Müllar, Stefan; Diederichsen, Ulf; Janshoff, Andreas; Grubmüller, Helmut; Risselada, Herre J.; Eggeling, Christian; Hell, Stefan W.; van den Bogaart, Geert; Jahn, Reinhard

    2015-01-01

    The clustering of proteins and lipids in distinct microdomains is emerging as an important principle for the spatial patterning of biological membranes. Such domain formation can be the result of hydrophobic and ionic interactions with membrane lipids as well as of specific protein–protein interactions. Here using plasma membrane-resident SNARE proteins as model, we show that hydrophobic mismatch between the length of transmembrane domains (TMDs) and the thickness of the lipid membrane suffices to induce clustering of proteins. Even when the TMDs differ in length by only a single residue, hydrophobic mismatch can segregate structurally closely homologous membrane proteins in distinct membrane domains. Domain formation is further fine-tuned by interactions with polyanionic phosphoinositides and homo and heterotypic protein interactions. Our findings demonstrate that hydrophobic mismatch contributes to the structural organization of membranes. PMID:25635869

  2. Interfacial Octahedral Rotation Mismatch Control of the Symmetry and Properties of SrRuO 3

    DOE PAGES

    Gao, Ran; Dong, Yongqi; Xu, Han; ...

    2016-05-24

    We can use epitaxial strain to tune the properties of complex oxides with perovskite structure. Beyond just lattice mismatch, the use of octahedral rotation mismatch at heterointerfaces could also provide a route to manipulate material properties. We examine the evolution of the lattice (i.e., parameters, symmetry, and octahedral rotations) of SrRuO 3 films grown on substrates engineered to have the same lattice parameters, but 2 different octahedral rotations. SrRuO 3 films grown on SrTiO 3 (001) (no octahedral rotations) and GdScO 3-buffered SrTiO 3 (001) (with octahedral rotations) substrates are found to exhibit monoclinic and tetragonal symmetry, respectively. Electrical transportmore » and magnetic measurements reveal that the tetragonal films exhibit higher resistivity, lower magnetic Curie temperatures, and more isotropic magnetism as compared to those with monoclinic structure. Synchrotron-based half-order Bragg peak analysis reveals that the octahedral rotation pattern in both film variants is the same (albeit with slightly different magnitudes of in-plane rotation angles). Furthermore, the abnormal rotation pattern observed in tetragonal SrRuO 3 indicates a possible decoupling between the internal octahedral rotation and lattice symmetry, which could provide new opportunities to engineer thin-film structure and properties.« less

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

    NASA Astrophysics Data System (ADS)

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

    2018-04-01

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

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

    USGS Publications Warehouse

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

    2018-01-01

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

  5. 40 CFR 439.13 - Effluent limitations attainable by the application of the best conventional pollutant control...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... application of the best conventional pollutant control technology (BCT). 439.13 Section 439.13 Protection of...) PHARMACEUTICAL MANUFACTURING POINT SOURCE CATEGORY Fermentation Products § 439.13 Effluent limitations attainable by the application of the best conventional pollutant control technology (BCT). Except as provided in...

  6. 40 CFR 439.13 - Effluent limitations attainable by the application of the best conventional pollutant control...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... application of the best conventional pollutant control technology (BCT). 439.13 Section 439.13 Protection of...) PHARMACEUTICAL MANUFACTURING POINT SOURCE CATEGORY Fermentation Products § 439.13 Effluent limitations attainable by the application of the best conventional pollutant control technology (BCT). Except as provided in...

  7. 40 CFR 439.13 - Effluent limitations attainable by the application of the best conventional pollutant control...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... application of the best conventional pollutant control technology (BCT). 439.13 Section 439.13 Protection of...) PHARMACEUTICAL MANUFACTURING POINT SOURCE CATEGORY Fermentation Products § 439.13 Effluent limitations attainable by the application of the best conventional pollutant control technology (BCT). Except as provided in...

  8. 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.

  9. Epitaxial Growth of Lattice-Mismatched Core-Shell TiO2 @MoS2 for Enhanced Lithium-Ion Storage.

    PubMed

    Dai, Rui; Zhang, Anqi; Pan, Zhichang; Al-Enizi, Abdullah M; Elzatahry, Ahmed A; Hu, Linfeng; Zheng, Gengfeng

    2016-05-01

    Core-shell structured nanohybrids are currently of significant interest due to their synergetic properties and enhanced performances. However, the restriction of lattice mismatch remains a severe obstacle for heterogrowth of various core-shells with two distinct crystal structures. Herein, a controlled synthesis of lattice-mismatched core-shell TiO2 @MoS2 nano-onion heterostructures is successfully developed, using unilamellar Ti0.87 O2 nanosheets as the starting material and the subsequent epitaxial growth of MoS2 on TiO2 . The formation of these core-shell nano-onions is attributed to an amorphous layer-induced heterogrowth mechanism. The number of MoS2 layers can be well tuned from few to over ten layers, enabling layer-dependent synergistic effects. The core-shell TiO2 @MoS2 nano-onion heterostructures exhibit significantly enhanced energy storage performance as lithium-ion battery anodes. The approach has also been extended to other lattice-mismatched systems such as TiO2 @MoSe2 , thus suggesting a new strategy for the growth of well-designed lattice-mismatched core-shell structures. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Mismatch repair gene MSH3 polymorphism is associated with the risk of sporadic prostate cancer.

    PubMed

    Hirata, Hiroshi; Hinoda, Yuji; Kawamoto, Ken; Kikuno, Nobuyuki; Suehiro, Yutaka; Okayama, Naoko; Tanaka, Yuichiro; Dahiya, Rajvir

    2008-05-01

    The mismatch repair system is a DNA repair mechanism that corrects mispaired bases during DNA replication errors. Cancer cells deficient in MMR proteins have a 10(2) to 10(3)-fold increase in the mutation rate. Single nucleotide polymorphisms of mismatch repair genes have been shown to cause a decrease in DNA repair activity. We hypothesized that mismatch repair gene polymorphism could be a risk factor for prostate cancer and p53 Pro/Pro genotype carriers could influence MSH3 and MSH6 polymorphisms. DNA samples from 110 patients with prostate cancer and 110 healthy controls were analyzed by single strand conformational polymorphism and polymerase chain reaction-restriction fragment length polymorphism to determine the genotypic frequency of 5 polymorphic loci on 2 MMR genes (MSH3 and MSH6) and p53 codon72. The chi-square test was applied to compare genotype frequency between patients and controls. A significant increase in the G/A+A/A genotype of MSH3 Pro222Pro was observed in patients compared to controls (OR 1.87, 95% CI 1.0-3.5). The frequency of A/G + G/G genotypes of MSH3 exon23 Thr1036Ala also tended to increase in patients (OR 1.57, 95% CI 0.92-2.72). In p53 codon72 Arg/Pro + Pro/Pro carriers the frequency of the AG + GG genotype of MSH3 exon23 was significantly increased in patients compared to controls (OR 2.1, 95% CI 1.05-4.34). To our knowledge this is the first report of the association of MSH3 gene polymorphisms in prostate cancer. These results suggest that the MSH3 polymorphism may be a risk factor for prostate cancer.

  11. 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.

  12. 40 CFR 439.13 - Effluent limitations attainable by the application of the best conventional pollutant control...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... application of the best conventional pollutant control technology (BCT). 439.13 Section 439.13 Protection of... MANUFACTURING POINT SOURCE CATEGORY Fermentation Products § 439.13 Effluent limitations attainable by the application of the best conventional pollutant control technology (BCT). Except as provided in 40 CFR 125.30...

  13. 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…

  14. 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.

  15. Phenotypic Mismatches Reveal Escape from Arms-Race Coevolution

    PubMed Central

    Hanifin, Charles T; Brodie, Edmund D; Brodie, Edmund D

    2008-01-01

    Because coevolution takes place across a broad scale of time and space, it is virtually impossible to understand its dynamics and trajectories by studying a single pair of interacting populations at one time. Comparing populations across a range of an interaction, especially for long-lived species, can provide insight into these features of coevolution by sampling across a diverse set of conditions and histories. We used measures of prey traits (tetrodotoxin toxicity in newts) and predator traits (tetrodotoxin resistance of snakes) to assess the degree of phenotypic mismatch across the range of their coevolutionary interaction. Geographic patterns of phenotypic exaggeration were similar in prey and predators, with most phenotypically elevated localities occurring along the central Oregon coast and central California. Contrary to expectations, however, these areas of elevated traits did not coincide with the most intense coevolutionary selection. Measures of functional trait mismatch revealed that over one-third of sampled localities were so mismatched that reciprocal selection could not occur given current trait distributions. Estimates of current locality-specific interaction selection gradients confirmed this interpretation. In every case of mismatch, predators were “ahead” of prey in the arms race; the converse escape of prey was never observed. The emergent pattern suggests a dynamic in which interacting species experience reciprocal selection that drives arms-race escalation of both prey and predator phenotypes at a subset of localities across the interaction. This coadaptation proceeds until the evolution of extreme phenotypes by predators, through genes of large effect, allows snakes to, at least temporarily, escape the arms race. PMID:18336073

  16. 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.

  17. Achieving the Framework Convention on Tobacco Control's potential by investing in national capacity.

    PubMed

    Wipfli, H; Stillman, F; Tamplin, S; da Costa e Silva, V Luiza; Yach, D; Samet, J

    2004-12-01

    May 2003 marked a critical achievement in efforts to stem the global tobacco epidemic, as the member states of the World Health Organization unanimously endorsed the Framework Convention on Tobacco Control (FCTC). However, the adoption of the FCTC signifies only the end of the beginning of effective global action to control tobacco. Over the next several years the utility of the FCTC process and the treaty itself will be tested as individual countries seek to ratify and implement the treaty's obligations. Significant barriers to the treaty's long term success exist in many countries. It is crucial that the international tobacco control community now refocuses its efforts on national capacity building and ensures that individual countries have the knowledge, tools, data, people, and organisations needed to implement the convention and develop sustained tobacco control programmes. This paper provides a model of national tobacco control capacity and offers a prioritised agenda for action.

  18. Mismatch in microbial food webs: predators but not prey perform better in their local biotic and abiotic conditions.

    PubMed

    Parain, Elodie C; Gravel, Dominique; Rohr, Rudolf P; Bersier, Louis-Félix; Gray, Sarah M

    2016-07-01

    Understanding how trophic levels respond to changes in abiotic and biotic conditions is key for predicting how food webs will react to environmental perturbations. Different trophic levels may respond disproportionately to change, with lower levels more likely to react faster, as they typically consist of smaller-bodied species with higher reproductive rates. This response could cause a mismatch between trophic levels, in which predators and prey will respond differently to changing abiotic or biotic conditions. This mismatch between trophic levels could result in altered top-down and bottom-up control and changes in interaction strength. To determine the possibility of a mismatch, we conducted a reciprocal-transplant experiment involving Sarracenia purpurea food webs consisting of bacterial communities as prey and a subset of six morphologically similar protozoans as predators. We used a factorial design with four temperatures, four bacteria and protozoan biogeographic origins, replicated four times. This design allowed us to determine how predator and prey dynamics were altered by abiotic (temperature) conditions and biotic (predators paired with prey from either their local or non-local biogeographic origin) conditions. We found that prey reached higher densities in warmer temperature regardless of their temperature of origin. Conversely, predators achieved higher densities in the temperature condition and with the prey from their origin. These results confirm that predators perform better in abiotic and biotic conditions of their origin while their prey do not. This mismatch between trophic levels may be especially significant under climate change, potentially disrupting ecosystem functioning by disproportionately affecting top-down and bottom-up control.

  19. 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…

  20. 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

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

    PubMed

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

    2016-03-01

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

  2. 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.

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

    PubMed Central

    Barboza, Perry; Adams, Layne; Griffith, Brad; Whitten, Kenneth

    2017-01-01

    Climate-induced shifts in plant phenology may adversely affect animals that cannot or do not shift the timing of their reproductive cycle. The realized effect of potential trophic “mismatches” between a consumer and its food varies with the degree to which species rely on dietary income and stored capital. Large Arctic herbivores rely heavily on maternal capital to reproduce and give birth near the onset of the growing season but are they vulnerable to trophic mismatch? We evaluated the long-term changes in the temperatures and characteristics of the growing seasons (1970–2013), and compared growing conditions and dynamics of forage quality for caribou at peak parturition, peak lactation, and peak forage biomass, and plant senescence between two distinct time periods over 36 years (1977 and 2011–13). Despite advanced thaw dates (7−12 days earlier), increased growing season lengths (15−21 days longer), and consistent parturition dates, we found no decline in forage quality and therefore no evidence within this dataset for a trophic mismatch at peak parturition or peak lactation from 1977 to 2011–13. In Arctic ungulates that use stored capital for reproduction, reproductive demands are largely met by body stores deposited in the previous summer and autumn, which reduces potential adverse effects of any mismatch between food availability and timing of parturition. Climate-induced effects on forages growing in the summer and autumn ranges, however, do correspond with the demands of female caribou and their offspring to gain mass for the next reproductive cycle and winter. Therefore, we suggest the window of time to examine the match-mismatch framework in Arctic ungulates is not at parturition but in late summer-autumn, where the multiplier effects of small changes in forage quality are amplified by forage abundance, peak forage intake, and resultant mass gains in mother-offspring pairs. PMID:28231256

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

    USGS Publications Warehouse

    Gustine, David D.; Barboza, Perry; Adams, Layne G.; Griffith, Brad; Cameron, Raymond D.; Whitten, Kenneth R.

    2017-01-01

    Climate-induced shifts in plant phenology may adversely affect animals that cannot or do not shift the timing of their reproductive cycle. The realized effect of potential trophic “mismatches” between a consumer and its food varies with the degree to which species rely on dietary income and stored capital. Large Arctic herbivores rely heavily on maternal capital to reproduce and give birth near the onset of the growing season but are they vulnerable to trophic mismatch? We evaluated the long-term changes in the temperatures and characteristics of the growing seasons (1970–2013), and compared growing conditions and dynamics of forage quality for caribou at peak parturition, peak lactation, and peak forage biomass, and plant senescence between two distinct time periods over 36 years (1977 and 2011–13). Despite advanced thaw dates (7−12 days earlier), increased growing season lengths (15−21 days longer), and consistent parturition dates, we found no decline in forage quality and therefore no evidence within this dataset for a trophic mismatch at peak parturition or peak lactation from 1977 to 2011–13. In Arctic ungulates that use stored capital for reproduction, reproductive demands are largely met by body stores deposited in the previous summer and autumn, which reduces potential adverse effects of any mismatch between food availability and timing of parturition. Climate-induced effects on forages growing in the summer and autumn ranges, however, do correspond with the demands of female caribou and their offspring to gain mass for the next reproductive cycle and winter. Therefore, we suggest the window of time to examine the match-mismatch framework in Arctic ungulates is not at parturition but in late summer-autumn, where the multiplier effects of small changes in forage quality are amplified by forage abundance, peak forage intake, and resultant mass gains in mother-offspring pairs.

  5. Improvement of helicopter attitude stability by active control of the conventional swash plate

    NASA Technical Reports Server (NTRS)

    Ham, Norman D.

    1993-01-01

    The Final Report on improvement of helicopter attitude stability by active control of the conventional swash plate covering the period from Nov. 1986 to Dec. 1993 is presented. A paper on the history, principles, and applications of helicopter individual-blade-control is included.

  6. Quantitative analysis and predictive engineering of self-rolling of nanomembranes under anisotropic mismatch strain

    NASA Astrophysics Data System (ADS)

    Chen, Cheng; Song, Pengfei; Meng, Fanchao; Li, Xiao; Liu, Xinyu; Song, Jun

    2017-12-01

    The present work presents a quantitative modeling framework for investigating the self-rolling of nanomembranes under different lattice mismatch strain anisotropy. The effect of transverse mismatch strain on the roll-up direction and curvature has been systematically studied employing both analytical modeling and numerical simulations. The bidirectional nature of the self-rolling of nanomembranes and the critical role of transverse strain in affecting the rolling behaviors have been demonstrated. Two fabrication strategies, i.e., third-layer deposition and corner geometry engineering, have been proposed to predictively manipulate the bidirectional rolling competition of strained nanomembranes, so as to achieve controlled, unidirectional roll-up. In particular for the strategy of corner engineering, microfabrication experiments have been performed to showcase its practical application and effectiveness. Our study offers new mechanistic knowledge towards understanding and predictive engineering of self-rolling of nanomembranes with improved roll-up yield.

  7. 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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2014-04-01

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

  10. An Experimental Database for Conventional and Alternate Control Concepts on the HSR 1.675% Reference H Model

    NASA Technical Reports Server (NTRS)

    McMillin, Naomi; Allen, Jerry; Erickson, Gary; Campbell, Jim; Mann, Mike; Kubiatko, Paul; Yingling, David; Mason, Charlie

    1999-01-01

    The objective was to experimentally evaluate the longitudinal and lateral-directional stability and control characteristics of the Reference H configuration at supersonic and transonic speeds. A series of conventional and alternate control devices were also evaluated at supersonic and transonic speeds. A database on the conventional and alternate control devices was to be created for use in the HSR program.

  11. Low loss fusion splicing polarization-maintaining photonic crystal fiber and conventional polarization-maintaining fiber

    NASA Astrophysics Data System (ADS)

    Zuoming, Sun; Ningfang, Song; Jing, Jin; Jingming, Song; Pan, Ma

    2012-12-01

    An efficient and simple method of fusion splicing of a Polarization-Maintaining Photonic Crystal Fiber (PM-PCF) and a conventional Polarization-Maintaining Fiber (PMF) with a low loss of 0.65 dB in experiment is reported. The minimum bending diameter of the joint can reach 2 cm. Theoretical calculation of the splicing loss based on mode field diameters (MFDs) mismatch of the two kinds of fibers is given. All parameters affected the splicing loss were studied.

  12. Prevalence, Treatment, and Control Rates of Conventional and Ambulatory Hypertension Across 10 Populations in 3 Continents.

    PubMed

    Melgarejo, Jesus D; Maestre, Gladys E; Thijs, Lutgarde; Asayama, Kei; Boggia, José; Casiglia, Edoardo; Hansen, Tine W; Imai, Yutaka; Jacobs, Lotte; Jeppesen, Jørgen; Kawecka-Jaszcz, Kalina; Kuznetsova, Tatiana; Li, Yan; Malyutina, Sofia; Nikitin, Yuri; Ohkubo, Takayoshi; Stolarz-Skrzypek, Katarzyna; Wang, Ji-Guang; Staessen, Jan A

    2017-07-01

    Hypertension is a major global health problem, but prevalence rates vary widely among regions. To determine prevalence, treatment, and control rates of hypertension, we measured conventional blood pressure (BP) and 24-hour ambulatory BP in 6546 subjects, aged 40 to 79 years, recruited from 10 community-dwelling cohorts on 3 continents. We determined how between-cohort differences in risk factors and socioeconomic factors influence hypertension rates. The overall prevalence was 49.3% (range between cohorts, 40.0%-86.8%) for conventional hypertension (conventional BP ≥140/90 mm Hg) and 48.7% (35.2%-66.5%) for ambulatory hypertension (ambulatory BP ≥130/80 mm Hg). Treatment and control rates for conventional hypertension were 48.0% (33.5%-74.1%) and 38.6% (10.1%-55.3%) respectively. The corresponding rates for ambulatory hypertension were 48.6% (30.5%-71.9%) and 45.6% (18.6%-64.2%). Among 1677 untreated subjects with conventional hypertension, 35.7% had white coat hypertension (23.5%-56.2%). Masked hypertension (conventional BP <140/90 mm Hg and ambulatory BP ≥130/80 mm Hg) occurred in 16.9% (8.8%-30.5%) of 3320 untreated subjects who were normotensive on conventional measurement. Exclusion of participants with diabetes mellitus, obesity, hypercholesterolemia, or history of cardiovascular complications resulted in a <9% reduction in the conventional and 24-hour ambulatory hypertension rates. Higher social and economic development, measured by the Human Development Index, was associated with lower rates of conventional and ambulatory hypertension. In conclusion, high rates of hypertension in all cohorts examined demonstrate the need for improvements in prevention, treatment, and control. Strategies for the management of hypertension should continue to not only focus on preventable and modifiable risk factors but also consider societal issues. © 2017 American Heart Association, Inc.

  13. 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.

  14. ELECTRICAL AND ELECTRONIC INDUSTRIAL CONTROL. A-C CONVENTIONAL MAGNETIC MOTOR CONTROL, PART I, UNIT 5, ASSIGNMENTS.

    ERIC Educational Resources Information Center

    SUTTON, MACK C.

    THIS GUIDE IS FOR INDIVIDUAL STUDENT USE IN STUDYING ALTERNATING CURRENT CONVENTIONAL MAGNETIC MOTOR CONTROL IN ELECTRICAL-ELECTRONIC PROGRAMS. IT WAS DEVELOPED BY AN INSTRUCTIONAL MATERIALS SPECIALIST AND ADVISERS. EACH OF THE 10 ASSIGNMENT SHEETS PROVIDES THE LESSON SUBJECT, PURPOSE, INTRODUCTORY INFORMATION, STUDY REFERENCES, SUPPLEMENTARY…

  15. Bandpass mismatch error for satellite CMB experiments I: estimating the spurious signal

    NASA Astrophysics Data System (ADS)

    Thuong Hoang, Duc; Patanchon, Guillaume; Bucher, Martin; Matsumura, Tomotake; Banerji, Ranajoy; Ishino, Hirokazu; Hazumi, Masashi; Delabrouille, Jacques

    2017-12-01

    Future Cosmic Microwave Background (CMB) satellite missions aim to use the B mode polarization to measure the tensor-to-scalar ratio r with a sensitivity σr lesssim 10-3. Achieving this goal will not only require sufficient detector array sensitivity but also unprecedented control of all systematic errors inherent in CMB polarization measurements. Since polarization measurements derive from differences between observations at different times and from different sensors, detector response mismatches introduce leakages from intensity to polarization and thus lead to a spurious B mode signal. Because the expected primordial B mode polarization signal is dwarfed by the known unpolarized intensity signal, such leakages could contribute substantially to the final error budget for measuring r. Using simulations we estimate the magnitude and angular spectrum of the spurious B mode signal resulting from bandpass mismatch between different detectors. It is assumed here that the detectors are calibrated, for example using the CMB dipole, so that their sensitivity to the primordial CMB signal has been perfectly matched. Consequently the mismatch in the frequency bandpass shape between detectors introduces differences in the relative calibration of galactic emission components. We simulate this effect using a range of scanning patterns being considered for future satellite missions. We find that the spurious contribution to r from the reionization bump on large angular scales (l < 10) is ≈ 10-3 assuming large detector arrays and 20 percent of the sky masked. We show how the amplitude of the leakage depends on the nonuniformity of the angular coverage in each pixel that results from the scan pattern.

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

    PubMed

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

    2017-10-25

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

  17. 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.

  18. Mismatch and G-Stack Modulated Probe Signals on SNP Microarrays

    PubMed Central

    Binder, Hans; Fasold, Mario; Glomb, Torsten

    2009-01-01

    Background Single nucleotide polymorphism (SNP) arrays are important tools widely used for genotyping and copy number estimation. This technology utilizes the specific affinity of fragmented DNA for binding to surface-attached oligonucleotide DNA probes. We analyze the variability of the probe signals of Affymetrix GeneChip SNP arrays as a function of the probe sequence to identify relevant sequence motifs which potentially cause systematic biases of genotyping and copy number estimates. Methodology/Principal Findings The probe design of GeneChip SNP arrays enables us to disentangle different sources of intensity modulations such as the number of mismatches per duplex, matched and mismatched base pairings including nearest and next-nearest neighbors and their position along the probe sequence. The effect of probe sequence was estimated in terms of triple-motifs with central matches and mismatches which include all 256 combinations of possible base pairings. The probe/target interactions on the chip can be decomposed into nearest neighbor contributions which correlate well with free energy terms of DNA/DNA-interactions in solution. The effect of mismatches is about twice as large as that of canonical pairings. Runs of guanines (G) and the particular type of mismatched pairings formed in cross-allelic probe/target duplexes constitute sources of systematic biases of the probe signals with consequences for genotyping and copy number estimates. The poly-G effect seems to be related to the crowded arrangement of probes which facilitates complex formation of neighboring probes with at minimum three adjacent G's in their sequence. Conclusions The applied method of “triple-averaging” represents a model-free approach to estimate the mean intensity contributions of different sequence motifs which can be applied in calibration algorithms to correct signal values for sequence effects. Rules for appropriate sequence corrections are suggested. PMID:19924253

  19. Spatial mismatch between sea lamprey behaviour and trap location explains low success at trapping for control

    USGS Publications Warehouse

    Rous, Andrew M.; McLean, Adrienne R.; Barber, Jessica; Bravener, Gale; Castro-Santos, Theodore; Holbrook, Christopher M.; Imre, Istvan; Pratt, Thomas C.; McLaughlin, Robert L.

    2017-01-01

    Crucial to the management of invasive species is understanding space use and the environmental features affecting space use. Improved understanding of space use by invasive sea lamprey (Petromyzon marinus) could help researchers discern why trap success in large rivers is lower than needed for effective control. We tested whether manipulating discharge nightly could increase trap success at a hydroelectric generating station on the St. Marys River. We quantified numbers of acoustically tagged sea lampreys migrating up to, and their space use at, the hydroelectric generating station. In 2011 and 2012, 78% and 68%, respectively, of tagged sea lampreys reached the generating station. Sea lampreys were active along the face, but more likely to occur at the bottom and away from the traps near the surface, especially when discharge was high. Our findings suggest that a low probability of encountering traps was due to spatial (vertical) mismatch between space use by sea lamprey and trap locations and that increasing discharge did not alter space use in ways that increased trap encounter. Understanding space use by invasive species can help managers assess the efficacy of trapping and ways of improving trapping success.

  20. Ground Truthing the 'Conventional Wisdom' of Lead Corrosion Control Using Mineralogical Analysis

    EPA Science Inventory

    For drinking water distribution systems (DWDS) with lead-bearing plumbing materials some form of corrosion control is typically necessary, with the goal of mitigating lead release by forming adherent, stable corrosion scales composed of low-solubility mineral phases. Conventional...

  1. 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…

  2. HLA Mismatching Strategies for Solid Organ Transplantation – A Balancing Act

    PubMed Central

    Zachary, Andrea A.; Leffell, Mary S.

    2016-01-01

    HLA matching provides numerous benefits in organ transplantation including better graft function, fewer rejection episodes, longer graft survival, and the possibility of reduced immunosuppression. Mismatches are attended by more frequent rejection episodes that require increased immunosuppression that, in turn, can increase the risk of infection and malignancy. HLA mismatches also incur the risk of sensitization, which can reduce the opportunity and increase waiting time for a subsequent transplant. However, other factors such as donor age, donor type, and immunosuppression protocol, can affect the benefit derived from matching. Furthermore, finding a well-matched donor may not be possible for all patients and usually prolongs waiting time. Strategies to optimize transplantation for patients without a well-matched donor should take into account the immunologic barrier represented by different mismatches: what are the least immunogenic mismatches considering the patient’s HLA phenotype; should repeated mismatches be avoided; is the patient sensitized to HLA and, if so, what are the strengths of the patient’s antibodies? This information can then be used to define the HLA type of an immunologically optimal donor and the probability of such a donor occurring. A probability that is considered to be too low may require expanding the donor population through paired donation or modifying what is acceptable, which may require employing treatment to overcome immunologic barriers such as increased immunosuppression or desensitization. Thus, transplantation must strike a balance between the risk associated with waiting for the optimal donor and the risk associated with a less than optimal donor. PMID:28003816

  3. Robust integral variable structure controller and pulse-width pulse-frequency modulated input shaper design for flexible spacecraft with mismatched uncertainty/disturbance.

    PubMed

    Hu, Qinglei

    2007-10-01

    This paper presents a dual-stage control system design method for the flexible spacecraft attitude maneuvering control by use of on-off thrusters and active vibration control by input shaper. In this design approach, attitude control system and vibration suppression were designed separately using lower order model. As a stepping stone, an integral variable structure controller with the assumption of knowing the upper bounds of the mismatched lumped perturbation has been designed which ensures exponential convergence of attitude angle and angular velocity in the presence of bounded uncertainty/disturbances. To reconstruct estimates of the system states for use in a full information variable structure control law, an asymptotic variable structure observer is also employed. In addition, the thruster output is modulated in pulse-width pulse-frequency so that the output profile is similar to the continuous control histories. For actively suppressing the induced vibration, the input shaping technique is used to modify the existing command so that less vibration will be caused by the command itself, which only requires information about the vibration frequency and damping of the closed-loop system. The rationale behind this hybrid control scheme is that the integral variable structure controller can achieve good precision pointing, even in the presence of uncertainties/disturbances, whereas the shaped input attenuator is applied to actively suppress the undesirable vibrations excited by the rapid maneuvers. Simulation results for the spacecraft model show precise attitude control and vibration suppression.

  4. 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.

  5. Optimization of single-base-pair mismatch discrimination in oligonucleotide microarrays

    NASA Technical Reports Server (NTRS)

    Urakawa, Hidetoshi; El Fantroussi, Said; Smidt, Hauke; Smoot, James C.; Tribou, Erik H.; Kelly, John J.; Noble, Peter A.; Stahl, David A.

    2003-01-01

    The discrimination between perfect-match and single-base-pair-mismatched nucleic acid duplexes was investigated by using oligonucleotide DNA microarrays and nonequilibrium dissociation rates (melting profiles). DNA and RNA versions of two synthetic targets corresponding to the 16S rRNA sequences of Staphylococcus epidermidis (38 nucleotides) and Nitrosomonas eutropha (39 nucleotides) were hybridized to perfect-match probes (18-mer and 19-mer) and to a set of probes having all possible single-base-pair mismatches. The melting profiles of all probe-target duplexes were determined in parallel by using an imposed temperature step gradient. We derived an optimum wash temperature for each probe and target by using a simple formula to calculate a discrimination index for each temperature of the step gradient. This optimum corresponded to the output of an independent analysis using a customized neural network program. These results together provide an experimental and analytical framework for optimizing mismatch discrimination among all probes on a DNA microarray.

  6. Experimental investigation of piston heat transfer under conventional diesel and reactivity-controlled compression ignition combustion regimes

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

    Splitter, Derek A; Hendricks, Terry Lee; Ghandhi, Jaal B

    2014-01-01

    The piston of a heavy-duty single-cylinder research engine was instrumented with 11 fast-response surface thermocouples, and a commercial wireless telemetry system was used to transmit the signals from the moving piston. The raw thermocouple data were processed using an inverse heat conduction method that included Tikhonov regularization to recover transient heat flux. By applying symmetry, the data were compiled to provide time-resolved spatial maps of the piston heat flux and surface temperature. A detailed comparison was made between conventional diesel combustion and reactivity-controlled compression ignition combustion operations at matched conditions of load, speed, boost pressure, and combustion phasing. The integratedmore » piston heat transfer was found to be 24% lower, and the mean surface temperature was 25 C lower for reactivity-controlled compression ignition operation as compared to conventional diesel combustion, in spite of the higher peak heat release rate. Lower integrated piston heat transfer for reactivity-controlled compression ignition was found over all the operating conditions tested. The results showed that increasing speed decreased the integrated heat transfer for conventional diesel combustion and reactivity-controlled compression ignition. The effect of the start of injection timing was found to strongly influence conventional diesel combustion heat flux, but had a negligible effect on reactivity-controlled compression ignition heat flux, even in the limit of near top dead center high-reactivity fuel injection timings. These results suggest that the role of the high-reactivity fuel injection does not significantly affect the thermal environment even though it is important for controlling the ignition timing and heat release rate shape. The integrated heat transfer and the dynamic surface heat flux were found to be insensitive to changes in boost pressure for both conventional diesel combustion and reactivity-controlled compression

  7. 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.

  8. Analysis and compensation of reference frequency mismatch in multiple-frequency feedforward active noise and vibration control system

    NASA Astrophysics Data System (ADS)

    Liu, Jinxin; Chen, Xuefeng; Yang, Liangdong; Gao, Jiawei; Zhang, Xingwu

    2017-11-01

    In the field of active noise and vibration control (ANVC), a considerable part of unwelcome noise and vibration is resulted from rotational machines, making the spectrum of response signal multiple-frequency. Narrowband filtered-x least mean square (NFXLMS) is a very popular algorithm to suppress such noise and vibration. It has good performance since a priori-knowledge of fundamental frequency of the noise source (called reference frequency) is adopted. However, if the priori-knowledge is inaccurate, the control performance will be dramatically degraded. This phenomenon is called reference frequency mismatch (RFM). In this paper, a novel narrowband ANVC algorithm with orthogonal pair-wise reference frequency regulator is proposed to compensate for the RFM problem. Firstly, the RFM phenomenon in traditional NFXLMS is closely investigated both analytically and numerically. The results show that RFM changes the parameter estimation problem of the adaptive controller into a parameter tracking problem. Then, adaptive sinusoidal oscillators with output rectification are introduced as the reference frequency regulator to compensate for the RFM problem. The simulation results show that the proposed algorithm can dramatically suppress the multiple-frequency noise and vibration with an improved convergence rate whether or not there is RFM. Finally, case studies using experimental data are conducted under the conditions of none, small and large RFM. The shaft radial run-out signal of a rotor test-platform is applied to simulate the primary noise, and an IIR model identified from a real steel structure is applied to simulate the secondary path. The results further verify the robustness and effectiveness of the proposed algorithm.

  9. 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…

  10. Behavioral and physiological responses to prey match-mismatch in larval herring

    NASA Astrophysics Data System (ADS)

    Illing, Björn; Moyano, Marta; Berg, Julia; Hufnagl, Marc; Peck, Myron A.

    2018-02-01

    The year-class success of Atlantic herring (Clupea harengus) spawning in the autumn/winter in the North Sea (NSAS stock) and in the spring in the western Baltic Sea (WBSS) appears driven by prey match-mismatch dynamics affecting the survival of larvae during the first weeks of life. To better understand and model the consequences of prey match-mismatch from an individual-based perspective, we measured aspects of the physiology and behavior of NSAS and WBSS herring larvae foraging in markedly different prey concentrations. When matched with prey (ad libitum concentrations of the copepod Acartia tonsa) larval growth, swimming activity, nutritional condition and metabolic rates were relatively high. When prey was absent (mismatch), swimming and feeding behavior rapidly declined within 2 and 4 days, for WBSS and NSAS larvae, respectively, concomitant with reductions in nutritional (RNA-DNA ratio) and somatic (weight-at-length) condition. After several days without prey, respiration measurements made on WBSS larvae suggested metabolic down-regulation (8-34%). An individual-based model depicting the time course of these Behavioral and physiological responses suggested that 25-mm larvae experiencing a mismatch would survive 25-33% (10, 7 °C) longer than 12-mm larvae. Warmer temperatures exacerbate starvation-induced decrements in performance. Without Behavioral and metabolic adjustments, survival of 25-mm larvae would be reduced from 8 to 6 days at 7 °C. Our findings highlight how adaptive Behavioral and physiological responses are tightly linked to prey match-mismatch dynamics in larval herring and how these responses can be included in models to better explore how bottom-up processes regulate larval fish growth and survival.

  11. Phonological mismatch makes aided speech recognition in noise cognitively taxing.

    PubMed

    Rudner, Mary; Foo, Catharina; Rönnberg, Jerker; Lunner, Thomas

    2007-12-01

    The working memory framework for Ease of Language Understanding predicts that speech processing becomes more effortful, thus requiring more explicit cognitive resources, when there is mismatch between speech input and phonological representations in long-term memory. To test this prediction, we changed the compression release settings in the hearing instruments of experienced users and allowed them to train for 9 weeks with the new settings. After training, aided speech recognition in noise was tested with both the trained settings and orthogonal settings. We postulated that training would lead to acclimatization to the trained setting, which in turn would involve establishment of new phonological representations in long-term memory. Further, we postulated that after training, testing with orthogonal settings would give rise to phonological mismatch, associated with more explicit cognitive processing. Thirty-two participants (mean=70.3 years, SD=7.7) with bilateral sensorineural hearing loss (pure-tone average=46.0 dB HL, SD=6.5), bilaterally fitted for more than 1 year with digital, two-channel, nonlinear signal processing hearing instruments and chosen from the patient population at the Linköping University Hospital were randomly assigned to 9 weeks training with new, fast (40 ms) or slow (640 ms), compression release settings in both channels. Aided speech recognition in noise performance was tested according to a design with three within-group factors: test occasion (T1, T2), test setting (fast, slow), and type of noise (unmodulated, modulated) and one between-group factor: experience setting (fast, slow) for two types of speech materials-the highly constrained Hagerman sentences and the less-predictable Hearing in Noise Test (HINT). Complex cognitive capacity was measured using the reading span and letter monitoring tests. PREDICTION: We predicted that speech recognition in noise at T2 with mismatched experience and test settings would be associated with more

  12. Mismatch or cumulative stress: toward an integrated hypothesis of programming effects.

    PubMed

    Nederhof, Esther; Schmidt, Mathias V

    2012-07-16

    This paper integrates the cumulative stress hypothesis with the mismatch hypothesis, taking into account individual differences in sensitivity to programming. According to the cumulative stress hypothesis, individuals are more likely to suffer from disease as adversity accumulates. According to the mismatch hypothesis, individuals are more likely to suffer from disease if a mismatch occurs between the early programming environment and the later adult environment. These seemingly contradicting hypotheses are integrated into a new model proposing that the cumulative stress hypothesis applies to individuals who were not or only to a small extent programmed by their early environment, while the mismatch hypothesis applies to individuals who experienced strong programming effects. Evidence for the main effects of adversity as well as evidence for the interaction between adversity in early and later life is presented from human observational studies and animal models. Next, convincing evidence for individual differences in sensitivity to programming is presented. We extensively discuss how our integrated model can be tested empirically in animal models and human studies, inviting researchers to test this model. Furthermore, this integrated model should tempt clinicians and other intervenors to interpret symptoms as possible adaptations from an evolutionary biology perspective. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. 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

  14. [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

  15. 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.

  16. Reduction of conductance mismatch in Fe/Al2O3/MoS2 system by tunneling-barrier thickness control

    NASA Astrophysics Data System (ADS)

    Hayakawa, Naoki; Muneta, Iriya; Ohashi, Takumi; Matsuura, Kentaro; Shimizu, Jun’ichi; Kakushima, Kuniyuki; Tsutsui, Kazuo; Wakabayashi, Hitoshi

    2018-04-01

    Molybdenum disulfide (MoS2) among two-dimensional semiconductor films is promising for spintronic devices because it has a longer spin-relaxation time with contrasting spin splitting than silicon. However, it is difficult to fabricate integrated circuits by the widely used exfoliation method. Here, we investigate the contact characteristics in the Fe/Al2O3/sputtered-MoS2 system with various thicknesses of the Al2O3 film. Current density increases with increasing thickness up to 2.5 nm because of both thermally-assisted and direct tunneling currents. On the other hand, it decreases with increasing thickness over 2.5 nm limited by direct tunneling currents. These results suggest that the Schottky barrier width can be controlled by changing thicknesses of the Al2O3 film, as supported by calculations. The reduction of conductance mismatch with this technique can lead to highly efficient spin injection from iron into the MoS2 film.

  17. On compensation of mismatched recording conditions in the Bayesian approach for forensic automatic speaker recognition.

    PubMed

    Botti, F; Alexander, A; Drygajlo, A

    2004-12-02

    This paper deals with a procedure to compensate for mismatched recording conditions in forensic speaker recognition, using a statistical score normalization. Bayesian interpretation of the evidence in forensic automatic speaker recognition depends on three sets of recordings in order to perform forensic casework: reference (R) and control (C) recordings of the suspect, and a potential population database (P), as well as a questioned recording (QR) . The requirement of similar recording conditions between suspect control database (C) and the questioned recording (QR) is often not satisfied in real forensic cases. The aim of this paper is to investigate a procedure of normalization of scores, which is based on an adaptation of the Test-normalization (T-norm) [2] technique used in the speaker verification domain, to compensate for the mismatch. Polyphone IPSC-02 database and ASPIC (an automatic speaker recognition system developed by EPFL and IPS-UNIL in Lausanne, Switzerland) were used in order to test the normalization procedure. Experimental results for three different recording condition scenarios are presented using Tippett plots and the effect of the compensation on the evaluation of the strength of the evidence is discussed.

  18. Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct.

    PubMed

    Nogueira, Raul G; Jadhav, Ashutosh P; Haussen, Diogo C; Bonafe, Alain; Budzik, Ronald F; Bhuva, Parita; Yavagal, Dileep R; Ribo, Marc; Cognard, Christophe; Hanel, Ricardo A; Sila, Cathy A; Hassan, Ameer E; Millan, Monica; Levy, Elad I; Mitchell, Peter; Chen, Michael; English, Joey D; Shah, Qaisar A; Silver, Frank L; Pereira, Vitor M; Mehta, Brijesh P; Baxter, Blaise W; Abraham, Michael G; Cardona, Pedro; Veznedaroglu, Erol; Hellinger, Frank R; Feng, Lei; Kirmani, Jawad F; Lopes, Demetrius K; Jankowitz, Brian T; Frankel, Michael R; Costalat, Vincent; Vora, Nirav A; Yoo, Albert J; Malik, Amer M; Furlan, Anthony J; Rubiera, Marta; Aghaebrahim, Amin; Olivot, Jean-Marc; Tekle, Wondwossen G; Shields, Ryan; Graves, Todd; Lewis, Roger J; Smith, Wade S; Liebeskind, David S; Saver, Jeffrey L; Jovin, Tudor G

    2018-01-04

    The effect of endovascular thrombectomy that is performed more than 6 hours after the onset of ischemic stroke is uncertain. Patients with a clinical deficit that is disproportionately severe relative to the infarct volume may benefit from late thrombectomy. We enrolled patients with occlusion of the intracranial internal carotid artery or proximal middle cerebral artery who had last been known to be well 6 to 24 hours earlier and who had a mismatch between the severity of the clinical deficit and the infarct volume, with mismatch criteria defined according to age (<80 years or ≥80 years). Patients were randomly assigned to thrombectomy plus standard care (the thrombectomy group) or to standard care alone (the control group). The coprimary end points were the mean score for disability on the utility-weighted modified Rankin scale (which ranges from 0 [death] to 10 [no symptoms or disability]) and the rate of functional independence (a score of 0, 1, or 2 on the modified Rankin scale, which ranges from 0 to 6, with higher scores indicating more severe disability) at 90 days. A total of 206 patients were enrolled; 107 were assigned to the thrombectomy group and 99 to the control group. At 31 months, enrollment in the trial was stopped because of the results of a prespecified interim analysis. The mean score on the utility-weighted modified Rankin scale at 90 days was 5.5 in the thrombectomy group as compared with 3.4 in the control group (adjusted difference [Bayesian analysis], 2.0 points; 95% credible interval, 1.1 to 3.0; posterior probability of superiority, >0.999), and the rate of functional independence at 90 days was 49% in the thrombectomy group as compared with 13% in the control group (adjusted difference, 33 percentage points; 95% credible interval, 24 to 44; posterior probability of superiority, >0.999). The rate of symptomatic intracranial hemorrhage did not differ significantly between the two groups (6% in the thrombectomy group and 3% in the

  19. Acoustic evidence for phonologically mismatched speech errors.

    PubMed

    Gormley, Andrea

    2015-04-01

    Speech errors are generally said to accommodate to their new phonological context. This accommodation has been validated by several transcription studies. The transcription methodology is not the best choice for detecting errors at this level, however, as this type of error can be difficult to perceive. This paper presents an acoustic analysis of speech errors that uncovers non-accommodated or mismatch errors. A mismatch error is a sub-phonemic error that results in an incorrect surface phonology. This type of error could arise during the processing of phonological rules or they could be made at the motor level of implementation. The results of this work have important implications for both experimental and theoretical research. For experimentalists, it validates the tools used for error induction and the acoustic determination of errors free of the perceptual bias. For theorists, this methodology can be used to test the nature of the processes proposed in language production.

  20. 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…

  1. Mismatch repair polymorphisms and the risk of colorectal cancer.

    PubMed

    Berndt, Sonja I; Platz, Elizabeth A; Fallin, M Daniele; Thuita, Lucy W; Hoffman, Sandra C; Helzlsouer, Kathy J

    2007-04-01

    Rare germline variants in mismatch repair genes have been linked to hereditary nonpolyposis colorectal cancer; however, it is unknown whether common polymorphisms in these genes alter the risk of colorectal cancer. To examine the association between common variants in mismatch repair genes and colorectal cancer, we conducted a case-cohort study within the CLUE II cohort. Four single nucleotide polymorphisms in 3 mismatch repair genes (MSH3 R940Q, MSH3 T1036A, MSH6 G39E and MLH1 I219V) were genotyped in 237 colorectal cancer cases and a subcohort of 2,189 participants. Incidence rate ratios (RRs) and 95% confidence intervals (95% CIs) for each polymorphism were estimated. The MSH3 1036A variant was found to be associated with an increased risk of colorectal cancer (RR=1.28, 95% CI: 0.94-1.74 and RR=1.65, 95% CI: 1.01-2.70 for the AT and TT genotypes, respectively, with p(trend)=0.02), particularly proximal colon cancer. Although the MSH3 940Q variant was only weakly associated with colorectal cancer overall (p(trend)=0.07), it was associated with a significant increased risk of proximal colon cancer (RR=1.69, 95% CI: 1.10-2.61 and RR=2.68, 95% CI: 0.96-7.47 for the RQ and QQ genotypes, respectively with p(trend)=0.005). Processed meat intake appeared to modify the association between the MSH3 polymorphisms and colorectal cancer (p(interaction) < 0.10 for both). No association was observed with the MSH6 and MLH1 polymorphisms overall. This study suggests that common polymorphisms in the mismatch repair gene, MSH3, may increase the risk of colorectal cancer, especially proximal colon cancer. (c) 2006 Wiley-Liss, Inc.

  2. Mismatch removal via coherent spatial relations

    NASA Astrophysics Data System (ADS)

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

    2014-07-01

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

  3. Localization by interaural time difference (ITD): Effects of interaural frequency mismatch

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

    Bonham, B.H.; Lewis, E.R.

    1999-07-01

    A commonly accepted physiological model for lateralization of low-frequency sounds by interaural time delay (ITD) stipulates that binaural comparison neurons receive input from frequency-matched channels from each ear. Here, the effects of hypothetical interaural frequency mismatches on this model are reported. For this study, the cat{close_quote}s auditory system peripheral to the binaural comparison neurons was represented by a neurophysiologically derived model, and binaural comparison neurons were represented by cross-correlators. The results of the study indicate that, for binaural comparison neurons receiving input from one cochlear channel from each ear, interaural CF mismatches may serve to either augment or diminish themore » effective difference in ipsilateral and contralateral axonal time delays from the periphery to the binaural comparison neuron. The magnitude of this increase or decrease in the effective time delay difference can be up to 400 {mu}s for CF mismatches of 0.2 octaves or less for binaural neurons with CFs between 250 Hz and 2.5 kHz. For binaural comparison neurons with nominal CFs near 500 Hz, the 25-{mu}s effective time delay difference caused by a 0.012-octave CF mismatch is equal to the ITD previously shown to be behaviorally sufficient for the cat to lateralize a low-frequency sound source. {copyright} {ital 1999 Acoustical Society of America.}« less

  4. 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.

  5. Robust control for uncertain structures

    NASA Technical Reports Server (NTRS)

    Douglas, Joel; Athans, Michael

    1991-01-01

    Viewgraphs on robust control for uncertain structures are presented. Topics covered include: robust linear quadratic regulator (RLQR) formulas; mismatched LQR design; RLQR design; interpretations of RLQR design; disturbance rejection; and performance comparisons: RLQR vs. mismatched LQR.

  6. Ground Truthing the ‘Conventional Wisdom’ of Lead Corrosion Control Using Mineralogical Analysis

    EPA Science Inventory

    For drinking water distribution systems (DWDS) with lead-bearing plumbing materials some form of corrosion control is typically necessary, with the goal of mitigating lead release by forming adherent, stable corrosion scales composed of low-solubility mineral phases. Conventional...

  7. 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.

  8. Structure of the EndoMS-DNA Complex as Mismatch Restriction Endonuclease.

    PubMed

    Nakae, Setsu; Hijikata, Atsushi; Tsuji, Toshiyuki; Yonezawa, Kouki; Kouyama, Ken-Ichi; Mayanagi, Kouta; Ishino, Sonoko; Ishino, Yoshizumi; Shirai, Tsuyoshi

    2016-11-01

    Archaeal NucS nuclease was thought to degrade the single-stranded region of branched DNA, which contains flapped and splayed DNA. However, recent findings indicated that EndoMS, the orthologous enzyme of NucS, specifically cleaves double-stranded DNA (dsDNA) containing mismatched bases. In this study, we determined the structure of the EndoMS-DNA complex. The complex structure of the EndoMS dimer with dsDNA unexpectedly revealed that the mismatched bases were flipped out into binding sites, and the overall architecture most resembled that of restriction enzymes. The structure of the apo form was similar to the reported structure of Pyrococcus abyssi NucS, indicating that movement of the C-terminal domain from the resting state was required for activity. In addition, a model of the EndoMS-PCNA-DNA complex was preliminarily verified with electron microscopy. The structures strongly support the idea that EndoMS acts in a mismatch repair pathway. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2017-10-01

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

  10. 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.

  11. 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

  12. 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.

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

    NASA Astrophysics Data System (ADS)

    Pompea, S. M.

    2001-05-01

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

  14. Label-free optical detection of single-base mismatches by the combination of nuclease and gold nanoparticles.

    PubMed

    Liu, Meiying; Yuan, Min; Lou, Xinhui; Mao, Hongju; Zheng, Dongmei; Zou, Ruxing; Zou, Nengli; Tang, Xiangrong; Zhao, Jianlong

    2011-07-15

    We report here an optical approach that enables highly selective and colorimetric single-base mismatch detection without the need of target modification, precise temperature control or stringent washes. The method is based on the finding that nucleoside monophosphates (dNMPs), which are digested elements of DNA, can better stabilize unmodified gold nanoparticles (AuNPs) than single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) with the same base-composition and concentration. The method combines the exceptional mismatch discrimination capability of the structure-selective nucleases with the attractive optical property of AuNPs. Taking S1 nuclease as one example, the perfectly matched 16-base synthetic DNA target was distinctively differentiated from those with single-base mutation located at any position of the 16-base synthetic target. Single-base mutations present in targets with varied length up to 80-base, located either in the middle or near to the end of the targets, were all effectively detected. In order to prove that the method can be potentially used for real clinic samples, the single-base mismatch detections with two HBV genomic DNA samples were conducted. To further prove the generality of this method and potentially overcome the limitation on the detectable lengths of the targets of the S1 nuclease-based method, we also demonstrated the use of a duplex-specific nuclease (DSN) for color reversed single-base mismatch detection. The main limitation of the demonstrated methods is that it is limited to detect mutations in purified ssDNA targets. However, the method coupled with various convenient ssDNA generation and purification techniques, has the potential to be used for the future development of detector-free testing kits in single nucleotide polymorphism screenings for disease diagnostics and treatments. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. 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

  16. Randomized controlled pilot study to compare Homeopathy and Conventional therapy in Acute Otitis Media.

    PubMed

    Sinha, M N; Siddiqui, V A; Nayak, C; Singh, Vikram; Dixit, Rupali; Dewan, Deepti; Mishra, Alok

    2012-01-01

    To compare the effectiveness of Homeopathy and Conventional therapy in Acute Otitis Media (AOM). A randomized placebo-controlled parallel group pilot study of homeopathic vs conventional treatment for AOM was conducted in Jaipur, India. Patients were randomized by a computer generated random number list to receive either individualized homeopathic medicines in fifty millesimal (LM) potencies, or conventional treatment including analgesics, antipyretics and anti-inflammatory drugs. Patients who did not improve were prescribed antibiotics at the 3rd day. Outcomes were assessed by the Acute Otitis Media-Severity of Symptoms (AOM-SOS) Scale and Tympanic Membrane Examination over 21 days. 81 patients were included, 80 completed follow-up: 41 for conventional and 40 for homeopathic treatment. In the Conventional group, all 40 (100%) patients were cured, in the Homeopathy group, 38 (95%) patients were cured while 02 (5%) patients were lost to the last two follow-up. By the 3rd day of treatment, 4 patients were cured in Homeopathy group but in Conventional group only one patient was cured. In the Conventional group antibiotics were prescribed in 39 (97.5%), no antibiotics were required in the Homeopathy group. 85% of patients were prescribed six homeopathic medicines. Individualized homeopathy is an effective conventional treatment in AOM, there were no significant differences between groups in the main outcome. Symptomatic improvement was quicker in the Homeopathy group, and there was a large difference in antibiotic requirements, favouring homeopathy. Further work on a larger scale should be conducted. Copyright © 2011 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

  17. 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.

  18. Evidence supporting the match/mismatch hypothesis of psychiatric disorders.

    PubMed

    Santarelli, Sara; Lesuis, Sylvie L; Wang, Xiao-Dong; Wagner, Klaus V; Hartmann, Jakob; Labermaier, Christiana; Scharf, Sebastian H; Müller, Marianne B; Holsboer, Florian; Schmidt, Mathias V

    2014-06-01

    Chronic stress is one of the predominant environmental risk factors for a number of psychiatric disorders, particularly for major depression. Different hypotheses have been formulated to address the interaction between early and adult chronic stress in psychiatric disease vulnerability. The match/mismatch hypothesis of psychiatric disease states that the early life environment shapes coping strategies in a manner that enables individuals to optimally face similar environments later in life. We tested this hypothesis in female Balb/c mice that underwent either stress or enrichment early in life and were in adulthood further subdivided in single or group housed, in order to provide aversive or positive adult environments, respectively. We studied the effects of the environmental manipulation on anxiety-like, depressive-like and sociability behaviors and gene expression profiles. We show that continuous exposure to adverse environments (matched condition) is not necessarily resulting in an opposite phenotype compared to a continuous supportive environment (matched condition). Rather, animals with mismatched environmental conditions behaved differently from animals with matched environments on anxious, social and depressive like phenotypes. These results further support the match/mismatch hypothesis and illustrate how mild or moderate aversive conditions during development can shape an individual to be optimally adapted to similar conditions later in life. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  19. Educational Mismatch and the Careers of Scientists

    ERIC Educational Resources Information Center

    Bender, Keith A.; Heywood, John S.

    2011-01-01

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

  20. Minor access control of Hong Kong under the Framework Convention on Tobacco Control.

    PubMed

    Kan, Ming-yue; Lau, Maggie

    2010-05-01

    Asia's tobacco control movement was strengthened owing to the need to fulfill the Framework Convention on Tobacco Control (FCTC). The present study aims to assess the compliance rates of tobacco retailers to the law forbidding the sales of tobacco to minors in Hong Kong before and after the growth of the tobacco control movement brought by the enactment of the newly amended tobacco control law with effect from 2007. The legislation was enacted to fulfill the FCTC. Two waves of territory-wide compliance checks conducted in 2006 and 2008 were compared. The compliance check was conducted using Standard Protocol. The overall compliance rate was still low though it increased from 18.9% in 2006 to 27.0% in 2008. The compliance rate of convenience stores and newspaper stands improved whereas the rate for restaurants, grocery stores and petrol stations worsened. Less tobacco retailing outlets displayed a specified warning sign required in 2008 (33.7%) comparing to 2006 (41.4%). The indoor smoking ban of the FCTC unintentionally changed the cigarette retailing landscape and finally improved the compliance rate. The case study also demonstrated that the Asia region still has much room for improvement in fulfilling the FCTC in term of effective implementation and enforcement. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

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

    PubMed

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

    2017-11-01

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

  2. Mismatch of desired versus perceived social support and associated levels of anxiety and depression in newly diagnosed cancer patients.

    PubMed

    Linden, Wolfgang; Vodermaier, Andrea

    2012-07-01

    Perceived social support serves as a buffer against stress in cancer patients as well as in the healthy. However, not all individuals low in support necessarily want more support. We, therefore, tested a match-mismatch model (low versus high perceived support relative to low versus high desired support) with regard to its association with emotional distress. Participants included two large samples of n = 576 consecutively recruited, newly diagnosed cancer patients and n = 383 healthy controls. The hypothesized interaction effects of perceived and desired support and its impact on anxiety and depressive symptoms were tested via hierarchical linear regression. Perceived social support and desire for support were orthogonal in cancer patients (r = -0.03, p = 0.56). In accordance with the match-mismatch model, only those cancer patients with a high desire for support but who perceived low support exceeded cut-offs suggestive of anxiety and/or depressive disorder, whereas the other patient groups did not show clinical symptoms. Results for healthy controls were weaker. The findings support the hypothesized match-mismatch model suggesting that lack of social support is only associated with emotional distress when patients desire more support than they actually perceive as having. Perceived as well as desired social support are, therefore, relevant and non-overlapping constructs to be included in screening tools for emotional distress in order to heighten the utility of screening as a decision aid to guide psycho-oncological follow-up.

  3. Clinical Management and Tumor Surveillance Recommendations of Inherited Mismatch Repair Deficiency in Childhood.

    PubMed

    Tabori, Uri; Hansford, Jordan R; Achatz, Maria Isabel; Kratz, Christian P; Plon, Sharon E; Frebourg, Thierry; Brugières, Laurence

    2017-06-01

    Replication proofreading is crucial to avoid mutation accumulation in dividing cells. In humans, proofreading and replication repair is maintained by the exonuclease domains of DNA polymerases and the mismatch repair system. Individuals harboring germline mutations in genes involved in this process are at increased risk of early cancers from multiple organs. Biallelic mutations in any of the four mismatch repair genes MSH2, MSH6, MLH1 , and PMS2 result in one of the most aggressive childhood cancer predisposition syndromes, termed constitutional mismatch repair deficiency or constitutional mismatch repair deficiency syndrome (CMMRD). Data gathered in the last decade allow us to better define the clinical manifestations, tumor spectrum, and diagnostic algorithms for CMMRD. In this article, we summarize this information and present a comprehensive consensus surveillance protocol for these individuals. Ongoing research will allow for further definition of replication repair-deficient cancer syndromes, assessing the cost-effectiveness of such surveillance protocols and potential therapeutic interventions for these children and families. Clin Cancer Res; 23(11); e32-e37. ©2017 AACR See all articles in the online-only CCR Pediatric Oncology Series. ©2017 American Association for Cancer Research.

  4. Understanding the conventional arms trade

    NASA Astrophysics Data System (ADS)

    Stohl, Rachel

    2017-11-01

    The global conventional arms trade is worth tens of billions of dollars every year and is engaged in by every country in the world. Yet, it is often difficult to control the legal trade in conventional arms and there is a thriving illicit market, willing to arm unscrupulous regimes and nefarious non-state actors. This chapter examines the international conventional arms trade, the range of tools that have been used to control it, and challenges to these international regimes.

  5. Dominant phonon polarization conversion across dimensionally mismatched interfaces: Carbon-nanotube-graphene junction

    NASA Astrophysics Data System (ADS)

    Shi, Jingjing; Lee, Jonghoon; Dong, Yalin; Roy, Ajit; Fisher, Timothy S.; Ruan, Xiulin

    2018-04-01

    Dimensionally mismatched interfaces are emerging for thermal management applications, but thermal transport physics remains poorly understood. Here we consider the carbon-nanotube-graphene junction, which is a dimensionally mismatched interface between one- and two-dimensional materials and is the building block for carbon-nanotube (CNT)-graphene three-dimensional networks. We predict the transmission function of individual phonon modes using the wave packet method; surprisingly, most incident phonon modes show predominantly polarization conversion behavior. For instance, longitudinal acoustic (LA) polarizations incident from CNTs transmit mainly into flexural transverse (ZA) polarizations in graphene. The frequency stays the same as the incident mode, indicating elastic transmission. Polarization conversion is more significant as the phonon wavelength increases. We attribute such unique phonon polarization conversion behavior to the dimensional mismatch across the interface, and it opens significantly new phonon transport channels as compared to existing theories where polarization conversion is neglected.

  6. 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.

  7. A smart rotary technique versus conventional pulpectomy for primary teeth: A randomized controlled clinical study.

    PubMed

    Mokhtari, Negar; Shirazi, Alireza-Sarraf; Ebrahimi, Masoumeh

    2017-11-01

    Techniques with adequate accuracy of working length determination along with shorter duration of treatment in pulpectomy procedure seems to be essential in pediatric dentistry. The aim of the present study was to evaluate the accuracy of root canal length measurement with Root ZX II apex locator and rotary system in pulpectomy of primary teeth. In this randomized control clinical trial complete pulpectomy was performed on 80 mandibular primary molars in 80, 4-6-year-old children. The study population was randomly divided into case and control groups. In control group conventional pulpectomy was performed and in the case group working length was determined by electronic apex locator Root ZXII and instrumented with Mtwo rotary files. Statistical evaluation was performed using Mann-Whitney and Chi-Square tests ( P <0.05). There were no significant differences between electronic apex locator Root ZXII and conventional method in accuracy of root canal length determination. However significantly less time was needed for instrumenting with rotary files ( P =0.000). Considering the comparable results in accuracy of root canal length determination and the considerably shorter instrumentation time in Root ZXII apex locator and rotary system, it may be suggested for pulpectomy in primary molar teeth. Key words: Rotary technique, conventional technique, pulpectomy, primary teeth.

  8. 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

  9. 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

  10. 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.

  11. Processing Control Information in a Nominal Control Construction: An Eye-Tracking Study.

    PubMed

    Kwon, Nayoung; Sturt, Patrick

    2016-08-01

    In an eye-tracking experiment, we examined the processing of the nominal control construction. Participants' eye-movements were monitored while they read sentences that included either giver control nominals (e.g. promise in Luke's promise to Sophia to photograph himself) or recipient control nominals (e.g. plea in Luke's plea to Sophia to photograph herself). In order to examine both the initial access of control information, and its later use in on-line processing, we combined a manipulation of nominal control with a gender match/mismatch paradigm. Results showed that there was evidence of processing difficulty for giver control sentences (relative to recipient control sentences) at the point where the control dependency was initially created, suggesting that control information was accessed during the early parsing stages. This effect is attributed to a recency preference in the formation of control dependencies; the parser prefers to assign a recent antecedent to PRO. In addition, readers slowed down after reading a reflexive pronoun that mismatched with the gender of the antecedent indicated by the control nominal (e.g. Luke's promise to Sophia to photograph herself). The mismatch cost suggests that control information of the nominal control construction was used to constrain dependency formation involving a controller, PRO and a reflexive, confirming the use of control information in on-line interpretation.

  12. A microfluidic-based lid device for conventional cell culture dishes to automatically control oxygen level.

    PubMed

    Lee, Seung Yeob; Yang, Sung

    2018-04-25

    Most conventional hypoxic cell culture systems undergo reoxygenation during experimental manipulations, resulting in undesirable effects including the reduction of cell viability. A lid device was developed herein for conventional cell culture dishes to resolve this limitation. The integration of multilayered microfluidic channels inside a thin membrane was designed to prevent the reoxygenation caused by reagent infusion and automatically control the oxygen level. The experimental data clearly show the reducibility of the dissolved oxygen in the infusing reagent and the controllability of the oxygen level inside the dish. The feasibility of the device for hypoxia studies was confirmed by HIF-1α experiments. Therefore, the device could be used as a compact and convenient hypoxic cell culture system to prevent reoxygenation-related issues.

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

    PubMed

    Ma, Xingyi; Sim, Sang Jun

    2013-03-21

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

  14. Penalized or Protected? Gender and the Consequences of Nonstandard and Mismatched Employment Histories

    PubMed Central

    Pedulla, David S.

    2016-01-01

    Millions of workers are employed in positions that deviate from the full-time, standard employment relationship or work in jobs that are mismatched with their skills, education, or experience. Yet, little is known about how employers evaluate workers who have experienced these employment arrangements, limiting our knowledge about how part-time work, temporary agency employment, and skills underutilization affect workers’ labor market opportunities. Drawing on original field and survey experiment data, I examine three questions: (1) What are the consequences of having a nonstandard or mismatched employment history for workers’ labor market opportunities? (2) Are the effects of nonstandard or mismatched employment histories different for men and women? and (3) What are the mechanisms linking nonstandard or mismatched employment histories to labor market outcomes? The field experiment shows that skills underutilization is as scarring for workers as a year of unemployment, but that there are limited penalties for workers with histories of temporary agency employment. Additionally, although men are penalized for part-time employment histories, women face no penalty for part-time work. The survey experiment reveals that employers’ perceptions of workers’ competence and commitment mediate these effects. These findings shed light on the consequences of changing employment relations for the distribution of labor market opportunities in the “new economy.” PMID:27182069

  15. Motif mismatches in microsatellites: insights from genome-wide investigation among 20 insect species.

    PubMed

    Behura, Susanta K; Severson, David W

    2015-02-01

    We present a detailed genome-wide comparative study of motif mismatches of microsatellites among 20 insect species representing five taxonomic orders. The results show that varying proportions (∼15-46%) of microsatellites identified in these species are imperfect in motif structure, and that they also vary in chromosomal distribution within genomes. It was observed that the genomic abundance of imperfect repeats is significantly associated with the length and number of motif mismatches of microsatellites. Furthermore, microsatellites with a higher number of mismatches tend to have lower abundance in the genome, suggesting that sequence heterogeneity of repeat motifs is a key determinant of genomic abundance of microsatellites. This relationship seems to be a general feature of microsatellites even in unrelated species such as yeast, roundworm, mouse and human. We provide a mechanistic explanation of the evolutionary link between motif heterogeneity and genomic abundance of microsatellites by examining the patterns of motif mismatches and allele sequences of single-nucleotide polymorphisms identified within microsatellite loci. Using Drosophila Reference Genetic Panel data, we further show that pattern of allelic variation modulates motif heterogeneity of microsatellites, and provide estimates of allele age of specific imperfect microsatellites found within protein-coding genes. © The Author 2014. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

  16. Investigating a memory-based account of negative priming: support for selection-feature mismatch.

    PubMed

    MacDonald, P A; Joordens, S

    2000-08-01

    Using typical and modified negative priming tasks, the selection-feature mismatch account of negative priming was tested. In the modified task, participants performed selections on the basis of a semantic feature (e.g., referent size). This procedure has been shown to enhance negative priming (P. A. MacDonald, S. Joordens, & K. N. Seergobin, 1999). Across 3 experiments, negative priming occurred only when the repeated item mismatched in terms of the feature used as the basis for selections. When the repeated item was congruent on the selection feature across the prime and probe displays, positive priming arose. This pattern of results appeared in both the ignored- and the attended-repetition conditions. Negative priming does not result from previously ignoring an item. These findings strongly support the selection-feature mismatch account of negative priming and refute both the distractor inhibition and the episodic-retrieval explanations.

  17. 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.

  18. Randomized controlled within-subject evaluation of digital and conventional workflows for the fabrication of lithium disilicate single crowns. Part I: digital versus conventional unilateral impressions.

    PubMed

    Benic, Goran I; Mühlemann, Sven; Fehmer, Vincent; Hämmerle, Christoph H F; Sailer, Irena

    2016-11-01

    Trials comparing the overall performance of fully digital and conventional workflows in reconstructive dentistry are needed. The purpose of the first part of this randomized controlled clinical trial was to determine whether optical impressions produce different results from conventional impressions with respect to time efficiency and patient and operator perceptions of the clinical workflow. Three digital impressions and 1 conventional impression were made in each of 10 participants according to a randomly generated sequence. The digital systems were Lava COS, iTero, and Cerec Bluecam. The conventional impression was made with the closed-mouth technique and polyvinyl siloxane material. The time needed for powdering, impressions, and interocclusal record was recorded. Patient and clinician perceptions of the procedures were rated by means of visual analog scales. The paired t test with Bonferroni correction was applied to detect differences (α=.05/6=.0083). The mean total working time ±standard deviation amounted to 260 ±66 seconds for the conventional impression, 493 ±193 seconds for Lava, 372 ±126 seconds for iTero, and 357 ±55 seconds for Cerec. The total working time for the conventional impression was significantly lower than that for Lava and Cerec. With regard to the working time without powdering, the differences between the methods were not statistically significant. The patient rating (very uncomfortable=0; comfortable=100) measured 61 ±34 for conventional impression, 71 ±18 for Lava, 66 ±20 for iTero, and 48 ±18 for Cerec. The differences were not statistically significant. The clinician rating (simple=0; very difficult=100) was 13 ±13 for the conventional impression, 54 ±27 for Lava, 22 ±11 for iTero, and 36 ±23 for Cerec. The differences between the conventional impression and Lava and between iTero and Lava were statistically significant. The conventional impression was more time-effective than the digital impressions. In terms of

  19. A smart rotary technique versus conventional pulpectomy for primary teeth: A randomized controlled clinical study

    PubMed Central

    Mokhtari, Negar; Shirazi, Alireza-Sarraf

    2017-01-01

    Background Techniques with adequate accuracy of working length determination along with shorter duration of treatment in pulpectomy procedure seems to be essential in pediatric dentistry. The aim of the present study was to evaluate the accuracy of root canal length measurement with Root ZX II apex locator and rotary system in pulpectomy of primary teeth. Material and Methods In this randomized control clinical trial complete pulpectomy was performed on 80 mandibular primary molars in 80, 4-6-year-old children. The study population was randomly divided into case and control groups. In control group conventional pulpectomy was performed and in the case group working length was determined by electronic apex locator Root ZXII and instrumented with Mtwo rotary files. Statistical evaluation was performed using Mann-Whitney and Chi-Square tests (P<0.05). Results There were no significant differences between electronic apex locator Root ZXII and conventional method in accuracy of root canal length determination. However significantly less time was needed for instrumenting with rotary files (P=0.000). Conclusions Considering the comparable results in accuracy of root canal length determination and the considerably shorter instrumentation time in Root ZXII apex locator and rotary system, it may be suggested for pulpectomy in primary molar teeth. Key words:Rotary technique, conventional technique, pulpectomy, primary teeth. PMID:29302280

  20. 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.

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

    PubMed Central

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

    2017-01-01

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

  2. Tuning thermal mismatch between turbine rotor parts with a thermal medium

    DOEpatents

    Schmidt, Mark Christopher

    2001-01-01

    In a turbine rotor, an aft shaft wheel and the final-stage wheel of the rotor are coupled together, including by a rabbeted joint. During shutdown and startup of the turbine, a thermal mismatch between the aft shaft wheel and final-stage wheel is avoided by respectively heating and cooling the aft shaft wheel to maintain the thermal mismatch within acceptable limits, thereby avoiding opening of the rabbeted joint and the potential for unbalancing the rotor and rotor vibration. The thermal medium may be supplied by piping in the aft bearing cavity into the cavity between the forward closure plate and the aft shaft wheel.

  3. 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.

  4. 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

  5. Hippocampal Mismatch Signals Are Modulated by the Strength of Neural Predictions and Their Similarity to Outcomes.

    PubMed

    Long, Nicole M; Lee, Hongmi; Kuhl, Brice A

    2016-12-14

    The hippocampus is thought to compare predicted events with current perceptual input, generating a mismatch signal when predictions are violated. However, most prior studies have only inferred when predictions occur without measuring them directly. Moreover, an important but unresolved question is whether hippocampal mismatch signals are modulated by the degree to which predictions differ from outcomes. Here, we conducted a human fMRI study in which subjects repeatedly studied various word-picture pairs, learning to predict particular pictures (outcomes) from the words (cues). After initial learning, a subset of cues was paired with a novel, unexpected outcome, whereas other cues continued to predict the same outcome. Critically, when outcomes changed, the new outcome was either "near" to the predicted outcome (same visual category as the predicted picture) or "far" from the predicted outcome (different visual category). Using multivoxel pattern analysis, we indexed cue-evoked reactivation (prediction) within neocortical areas and related these trial-by-trial measures of prediction strength to univariate hippocampal responses to the outcomes. We found that prediction strength positively modulated hippocampal responses to unexpected outcomes, particularly when unexpected outcomes were close, but not identical, to the prediction. Hippocampal responses to unexpected outcomes were also associated with a tradeoff in performance during a subsequent memory test: relatively faster retrieval of new (updated) associations, but relatively slower retrieval of the original (older) associations. Together, these results indicate that hippocampal mismatch signals reflect a comparison between active predictions and current outcomes and that these signals are most robust when predictions are similar, but not identical, to outcomes. Although the hippocampus is widely thought to signal "mismatches" between memory-based predictions and outcomes, previous research has not linked

  6. 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

  7. Wii-based interactive video games as a supplement to conventional therapy for rehabilitation of children with cerebral palsy: A pilot, randomized controlled trial.

    PubMed

    Sajan, Jane Elizabeth; John, Judy Ann; Grace, Pearlin; Sabu, Sneha Sara; Tharion, George

    2017-08-01

    To assess the effect of interactive video gaming (IVG) with Nintendo Wii (Wii) supplemented to conventional therapy in rehabilitation of children with cerebral palsy (CP). Randomized, controlled, assessor-blinded study. Children with CP; 10 children each in the control and intervention groups. IVG using Wii, given as a supplement to conventional therapy, for 45 min per day, 6 days a week for 3 weeks. The children in the control group received conventional therapy alone. Posture control and balance, upper limb function, visual-perceptual skills, and functional mobility. Significant improvement in upper limb functions was seen in the intervention group but not in the control group. Improvements in balance, visual perception, and functional mobility were not significantly different between control and intervention groups. Wii-based IVG may be offered as an effective supplement to conventional therapy in the rehabilitation of children with CP.

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. An Efficient Modulation Strategy for Cascaded Photovoltaic Systems Suffering From Module Mismatch

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

    Wang, Cheng; Zhang, Kai; Xiong, Jian

    Modular multilevel cascaded converter (MMCC) is a promising technique for medium/high-voltage high-power photovoltaic systems due to its modularity, scalability, and capability of distributed maximum power point tracking (MPPT) etc. However, distributed MPPT under module-mismatch might polarize the distribution of ac output voltages as well as the dc-link voltages among the modules, distort grid currents, and even cause system instability. For the better acceptance in practical applications, such issues need to be well addressed. Based on mismatch degree that is defined to consider both active power distribution and maximum modulation index, this paper presents an efficient modulation strategy for a cascaded-H-bridge-basedmore » MMCC under module mismatch. It can operate in loss-reducing mode or range-extending mode. By properly switching between the two modes, performance indices such as system efficiency, grid current quality, and balance of dc voltages, can be well coordinated. In this way, the MMCC system can maintain high-performance over a wide range of operating conditions. As a result, effectiveness of the proposed modulation strategy is proved with experiments.« less

  14. An Efficient Modulation Strategy for Cascaded Photovoltaic Systems Suffering From Module Mismatch

    DOE PAGES

    Wang, Cheng; Zhang, Kai; Xiong, Jian; ...

    2017-09-26

    Modular multilevel cascaded converter (MMCC) is a promising technique for medium/high-voltage high-power photovoltaic systems due to its modularity, scalability, and capability of distributed maximum power point tracking (MPPT) etc. However, distributed MPPT under module-mismatch might polarize the distribution of ac output voltages as well as the dc-link voltages among the modules, distort grid currents, and even cause system instability. For the better acceptance in practical applications, such issues need to be well addressed. Based on mismatch degree that is defined to consider both active power distribution and maximum modulation index, this paper presents an efficient modulation strategy for a cascaded-H-bridge-basedmore » MMCC under module mismatch. It can operate in loss-reducing mode or range-extending mode. By properly switching between the two modes, performance indices such as system efficiency, grid current quality, and balance of dc voltages, can be well coordinated. In this way, the MMCC system can maintain high-performance over a wide range of operating conditions. As a result, effectiveness of the proposed modulation strategy is proved with experiments.« less

  15. Randomized Controlled Double-blind Trial Comparing Haloperidol Combined With Conventional Therapy to Conventional Therapy Alone in Patients With Symptomatic Gastroparesis.

    PubMed

    Roldan, Carlos J; Chambers, Kimberly A; Paniagua, Linda; Patel, Sonali; Cardenas-Turanzas, Marylou; Chathampally, Yashwant

    2017-11-01

    Gastroparesis is a debilitating condition that causes nausea, vomiting, and abdominal pain. Management includes analgesics and antiemetics, but symptoms are often refractory. Haloperidol has been utilized in the palliative care setting for similar symptoms. The study objective was to determine whether haloperidol as an adjunct to conventional therapy would improve symptoms in gastroparesis patients presenting to the emergency department (ED). This was a randomized, double-blind, placebo-controlled trial of adult ED patients with acute exacerbation of previously diagnosed gastroparesis. The treatment group received 5 mg of haloperidol plus conventional therapy (determined by the treating physician). The control group received a placebo plus conventional therapy. The severity of each subject's abdominal pain and nausea were assessed before intervention and every 15 minutes thereafter for 1 hour using a 10-point scale for pain and a 5-point scale for nausea. Primary outcomes were decreased pain and nausea 1 hour after treatment. Of the 33 study patients, 15 were randomized to receive haloperidol. Before treatment, the mean intensity of pain was 8.5 in the haloperidol group and 8.28 in the placebo group; mean pretreatment nausea scores were 4.53 and 4.11, respectively. One hour after therapy, the mean pain and nausea scores in the haloperidol group were 3.13 and 1.83 compared to 7.17 and 3.39 in the placebo group. The reduction in mean pain intensity therapy was 5.37 in the haloperidol group (p ≤ 0.001) compared to 1.11 in the placebo group (p = 0.11). The reduction in mean nausea score was 2.70 in the haloperidol group (p ≤ 0.001) and 0.72 in the placebo group (p = 0.05). Therefore, the reductions in symptom scores were statistically significant in the haloperidol group but not in the placebo group. No adverse events were reported. Haloperidol as an adjunctive therapy is superior to placebo for acute gastroparesis symptoms. © 2017 by the Society for Academic

  16. 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.

  17. Access and benefit sharing (ABS) under the convention on biological diversity (CBD): implications for microbial biological control

    USDA-ARS?s Scientific Manuscript database

    Researchers and implementers of biological control are confronted with a variety of scientific, regulatory and administrative challenges to their biological control programs. One developing challenge will arise from the implementation of provisions of the Convention on Biological Diversity (CBD) co...

  18. 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

  19. 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…

  20. Genomic amplification of the human DHFR/MSH3 locus remodels mismatch recognition and repair activities.

    PubMed

    Drummond, J T

    1999-01-01

    Mismatch recognition in human cells is mediated by two heterodimers, MutS alpha and MutS beta. MutS alpha appears to shoulder primary responsibility for mismatch correction during replication, based on its relative abundance and ability to recognize a broad spectrum of base-base and base-insertion mismatches. Because MutS alpha and MutS beta share a common component, MSH2, conditions that influence the expression or degradation of MSH3 or MSH6 can redistribute the profile of mismatch recognition and repair. MSH3 is linked by a shared promoter with DHFR, connecting two pathways with key roles in DNA metabolism. In a classic example of gene amplification, the DHFR (and MSH3) locus can become amplified to several hundred copies in the presence of methotrexate. Under these conditions, MutS beta forms at the expense of MutS alpha, and the mutation rate in these tumor cells rises more than 100-fold. The implications for cancer chemotherapy include a potential increase in mutability when tumors are treated with methotrexate, which could increase the frequency of subsequent mutations that influence the tumor's drug sensitivity or aggressiveness. Because processing certain types of DNA damage by the mismatch repair pathway has also been implicated in tumor sensitivity to agents such as cisplatin, changes in expression at the DHFR/MSH3 locus may have further relevance to the outcome of multi-drug treatment regimens.

  1. Idiopathic pulmonary fibrosis. A rare cause of scintigraphic ventilation-perfusion mismatch

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

    Pochis, W.T.; Krasnow, A.Z.; Collier, B.D.

    1990-05-01

    A case of idiopathic pulmonary fibrosis with multiple areas of mismatch on ventilation-perfusion lung imaging in the absence of pulmonary embolism is presented. Idiopathic pulmonary fibrosis is one of the few nonembolic diseases producing a pulmonary ventilation-perfusion mismatch. In this condition, chest radiographs may not detect the full extent of disease, and xenon-133 ventilation imaging may be relatively insensitive to morbid changes in small airways. Thus, when examining patients with idiopathic pulmonary fibrosis, one should be aware that abnormal perfusion imaging patterns without matching ventilation abnormalities are not always due to embolism. In this setting, contrast pulmonary angiography is oftenmore » needed for accurate differential diagnosis.« less

  2. Effects of impedance mismatch and coaxial cable length on absolute gravimeters

    NASA Astrophysics Data System (ADS)

    Křen, Petr; Pálinkáš, Vojtech; Mašika, Pavel; Vaľko, Miloš

    2017-04-01

    The systematic effects of absolute gravimeters have to be investigated to fully utilize their capabilities in metrology and geosciences. In Křen et al (2016 Metrologia 53 27-40) we found that for an FG5 gravimeter, even a few meter long coaxial cable used for transmission of fringe signal causes systematic features in residuals and errors at the level of 1-2 µGal. In this paper, we present experimental results and appropriate models to explain the effects that were found to be caused by impedance mismatches of electronic components and dispersion effects in coaxial cables of gravimeters. The experimental results have been obtained for analogue and transistor-transistor logic (TTL) compatible signals in the FG5-215 gravimeter and for a TTL signal in the FG5X-251 gravimeter. We found that dispersion and impedance mismatch effects are similar for both gravimeters. Furthermore, we describe a model of the dispersion that allows an evaluation of the effect/correction for a given range of the free-fall and thus it is also applicable to other gravimeters. The effect of impedance mismatch for the analogue fringe signal is modelled as an effect of the reflected electronic signal on the evaluation of zero-crossings. The applicability of this model for TTL signal is also discussed.

  3. Experimental comparison of conventional and nonlinear model-based control of a mixing tank

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

    Haeggblom, K.E.

    1993-11-01

    In this case study concerning control of a laboratory-scale mixing tank, conventional multiloop single-input single-output (SISO) control is compared with model-based'' control where the nonlinearity and multivariable characteristics of the process are explicitly taken into account. It is shown, especially if the operating range of the process is large, that the two outputs (level and temperature) cannot be adequately controlled by multiloop SISO control even if gain scheduling is used. By nonlinear multiple-input multiple-output (MIMO) control, on the other hand, very good control performance is obtained. The basic approach to nonlinear control used in this study is first to transformmore » the process into a globally linear and decoupled system, and then to design controllers for this system. Because of the properties of the resulting MIMO system, the controller design is very easy. Two nonlinear control system designs based on a steady-state and a dynamic model, respectively, are considered. In the dynamic case, both setpoint tracking and disturbance rejection can be addressed separately.« less

  4. Mismatch repair gene MSH3 polymorphism is associated with the risk of sporadic prostate cancer

    PubMed Central

    Hirata, Hiroshi; Hinoda, Yuji; Kawamoto, Ken; Kikuno, Nobuyuki; Suehiro, Yutaka; Okayama, Naoko; Tanaka, Yuichiro; Dahiya, Rajvir

    2014-01-01

    Purpose The mismatch repair (MMR) system is a DNA repair mechanism that corrects mispaired bases during DNA replication errors. Cancer cells deficient in the MMR proteins have a 102 –103-fold increase in the mutation rate. Single nucleotide polymorphisms (SNPs) of MMR genes have been shown to cause a reduction in DNA repair activity. We hypothesized that mismatch repair gene polymorphism could be a risk factor for prostate cancer (PC) and that p53 Pro/Pro genotype carriers could influence MSH3 and MSH6 polymorphisms. Material and Methods DNA samples from 110 cases of prostate cancer and healthy controls (n=110) were analyzed by SSCP and PCR-RFLP to determine the genotypic frequency of five different polymorphic loci on two MMR genes (MSH3 and MSH6) and p53 codon72. The chi-square test was applied to compare the genotype frequency between patients and controls. Results A significant increase in the G/A+A/A genotype of MSH3 Pro222Pro was observed in patients compared to controls (OR, 1.87; 95% CI, 1.0–3.5). The frequency of A/G + G/G genotypes of MSH3 exon23 Thr1036Ala also tended to increase in patients (OR, 1.57; 95% CI, 0.92–2.72). Among p53 codon72 Arg/Pro + Pro/Pro carriers, the frequency of the AG + GG genotype of MSH3 exon23 was significantly increased in patients compared to controls (OR = 2.1, 95% CI; 1.05–4.34). Conclusion This is the first report on the association of MSH3 gene polymorphisms in prostate cancer. These results suggest that the MSH3 polymorphism may be a risk factor for prostate cancer. PMID:18355840

  5. 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…

  6. 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

  7. Mismatch Negativity in Children with Autism and Typical Development

    ERIC Educational Resources Information Center

    Dunn, Michelle A.; Gomes, Hilary; Gravel, Judith

    2008-01-01

    Children with autism are often characterized as having abnormalities in auditory processing. This study examined automatic and active processing of simple auditory stimuli in children using a component of event related potentials, the mismatch negativity (MMN). Amplitude of MMN in children with autism was significantly smaller than in children…

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

    PubMed

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

    2009-06-01

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

  9. 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.

  10. Dental Students' Perceptions of Digital and Conventional Impression Techniques: A Randomized Controlled Trial.

    PubMed

    Zitzmann, Nicola U; Kovaltschuk, Irina; Lenherr, Patrik; Dedem, Philipp; Joda, Tim

    2017-10-01

    The aim of this randomized controlled trial was to analyze inexperienced dental students' perceptions of the difficulty and applicability of digital and conventional implant impressions and their preferences including performance. Fifty undergraduate dental students at a dental school in Switzerland were randomly divided into two groups (2×25). Group A first took digital impressions in a standardized phantom model and then conventional impressions, while the procedures were reversed for Group B. Participants were asked to complete a VAS questionnaire (0-100) on the level of difficulty and applicability (user/patient-friendliness) of both techniques. They were asked which technique they preferred and perceived to be more efficient. A quotient of "effective scan time per software-recorded time" (TRIOS) was calculated as an objective quality indicator for intraoral optical scanning (IOS). The majority of students perceived IOS as easier than the conventional technique. Most (72%) preferred the digital approach using IOS to take the implant impression to the conventional method (12%) or had no preference (12%). Although total work was similar for males and females, the TRIOS quotient indicated that male students tended to use their time more efficiently. In this study, dental students with no clinical experience were very capable of acquiring digital tools, indicating that digital impression techniques can be included early in the dental curriculum to help them catch up with ongoing development in computer-assisted technologies used in oral rehabilitation.

  11. Novel HPLC Analysis of Hydrocortisone in Conventional and Controlled-Release Pharmaceutical Preparations.

    PubMed

    Adi-Dako, Ofosua; Oppong Bekoe, Samuel; Ofori-Kwakye, Kwabena; Appiah, Enoch; Peprah, Paul

    2017-01-01

    An isocratic sensitive and precise reverse phase high-performance liquid chromatography (RP-HPLC) method was developed and validated for the determination and quantification of hydrocortisone in controlled-release and conventional (tablets and injections) pharmaceutical preparations. Chromatographic separation was achieved on an ODS (C18), 5  μ m, 4.6 × 150 mm, with an isocratic elution using a freshly prepared mobile phase of composition methanol : water : acetic acid (60 : 30 : 10, v/v/v) at a flow rate of 1.0 ml/min. The detection of the drug was successfully achieved at a wavelength of 254 nm. The retention time obtained for the drug was 2.26 min. The proposed method produced linear detectable responses in the concentration range of 0.02 to 0.4 mg/ml of hydrocortisone. High recoveries of 98-101% were attained at concentration levels of 80%, 100%, and 120%. The intraday and interday precision (RSD) were 0.19-0.55% and 0.33-0.71%, respectively. A comparison of hydrocortisone analyses data from the developed method and the official USP method showed no significant difference ( p > 0.05) at a 95% confidence interval. The method was successfully applied to the determination and quantification of hydrocortisone in six controlled-release and fifteen conventional release pharmaceutical preparations.

  12. Novel HPLC Analysis of Hydrocortisone in Conventional and Controlled-Release Pharmaceutical Preparations

    PubMed Central

    Oppong Bekoe, Samuel; Appiah, Enoch; Peprah, Paul

    2017-01-01

    An isocratic sensitive and precise reverse phase high-performance liquid chromatography (RP-HPLC) method was developed and validated for the determination and quantification of hydrocortisone in controlled-release and conventional (tablets and injections) pharmaceutical preparations. Chromatographic separation was achieved on an ODS (C18), 5 μm, 4.6 × 150 mm, with an isocratic elution using a freshly prepared mobile phase of composition methanol : water : acetic acid (60 : 30 : 10, v/v/v) at a flow rate of 1.0 ml/min. The detection of the drug was successfully achieved at a wavelength of 254 nm. The retention time obtained for the drug was 2.26 min. The proposed method produced linear detectable responses in the concentration range of 0.02 to 0.4 mg/ml of hydrocortisone. High recoveries of 98–101% were attained at concentration levels of 80%, 100%, and 120%. The intraday and interday precision (RSD) were 0.19–0.55% and 0.33–0.71%, respectively. A comparison of hydrocortisone analyses data from the developed method and the official USP method showed no significant difference (p > 0.05) at a 95% confidence interval. The method was successfully applied to the determination and quantification of hydrocortisone in six controlled-release and fifteen conventional release pharmaceutical preparations. PMID:28660092

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. 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

  18. Evaluation of Mismatch Losses due to Shunts in industrial Silicon Photovoltaic Modules

    NASA Astrophysics Data System (ADS)

    Somasundaran, P.; Shilpi, M.; Gupta, R.

    2017-05-01

    In order to achieve higher efficiencies in photovoltaic module technology, it is important to characterize the shunts and other defects which degrade the performance of cells and modules as well as decrease their efficiency. These shunts also affect the reliability of cells and modules. It is important to understand how much fill factor and power loss is caused by the presence of shunts in the module. Shunts not only reduce the module power output, but also affect the I-V characteristics of the cell and hence the characteristics of the shunted cells are different from those of the shunt-free cells connected in the module leading to the mismatch effect. This is an interesting effect which has been systematically investigated in the present work. Moreover, the flow of increased shunt current will give rise to increased temperature in the region of shunt, which will affect the cell and hence module performance. In the present study, the distributed diode model has been extended to the module level and applied to evaluate the electrical mismatch losses and thermal mismatch losses due to shunts in industrial Silicon PV modules.

  19. Fabrication and characterization of multiband solar cells based on highly mismatched alloys

    NASA Astrophysics Data System (ADS)

    López, N.; Braña, A. F.; García Núñez, C.; Hernández, M. J.; Cervera, M.; Martínez, M.; Yu, K. M.; Walukiewicz, W.; García, B. J.

    2015-10-01

    Multiband solar cells are one type of third generation photovoltaic devices in which an increase of the power conversion efficiency is achieved through the absorption of low energy photons while preserving a large band gap that determines the open circuit voltage. The ability to absorb photons from different parts of the solar spectrum originates from the presence of an intermediate energy band located within the band gap of the material. This intermediate band, acting as a stepping stone allows the absorption of low energy photons to transfer electrons from the valence band to the conduction band by a sequential two photons absorption process. It has been demonstrated that highly mismatched alloys offer a potential to be used as a model material system for practical realization of multiband solar cells. Dilute nitride GaAs1-xNx highly mismatched alloy with low mole fraction of N is a prototypical multiband semiconductor with a well-defined intermediate band. Currently, we are using chemical beam epitaxy to synthesize dilute nitride highly mismatched alloys. The materials are characterized by a variety of structural and optical methods to optimize their properties for multiband photovoltaic devices.

  20. Manufacturer-provided effective orifice area index charts and the prevention of prosthesis-patient mismatch.

    PubMed

    House, Chad M; Nelson, William B; Kroshus, Timothy J; Dahiya, Ranjan; Pibarot, Philippe

    2012-01-01

    Prosthesis-patient mismatch (PPM) occurs when an implanted prosthesis is too small relative to the patient's body surface area (BSA). However, mismatch can often be prevented by indexing the expected effective orifice area (EOA) of a prosthesis to the patient's BSA and then selecting the largest implantable prosthesis to avoid mismatch. Previously, prosthesis manufacturers have attempted to simplify this process by providing charts that include the expected EOA for their prosthesis, already indexed into an array of BSA values. One caveat with these charts is that the expected EOA data must truly be reliable, or the charts will misguide the implanting surgeon. Manufacturer-provided charts could be improved by standardizing the EOA data, with one potential source being the hemodynamic data submitted to the United States Food and Drug Administration. This review discusses PPM, manufacturer-provided EOA charts, and the regulation of EOA data.

  1. MHC-mismatched mixed chimerism restores peripheral tolerance of noncross-reactive autoreactive T cells in NOD mice

    PubMed Central

    Zhang, Mingfeng; Racine, Jeremy J.; Lin, Qing; Liu, Yuqing; Tang, Shanshan; Qin, Qi; Qi, Tong; Riggs, Arthur D.; Zeng, Defu

    2018-01-01

    Autoimmune type 1 diabetes (T1D) and other autoimmune diseases are associated with particular MHC haplotypes and expansion of autoreactive T cells. Induction of MHC-mismatched but not -matched mixed chimerism by hematopoietic cell transplantation effectively reverses autoimmunity in diabetic nonobese diabetic (NOD) mice, even those with established diabetes. As expected, MHC-mismatched mixed chimerism mediates deletion in the thymus of host-type autoreactive T cells that have T-cell receptor (TCR) recognizing (cross-reacting with) donor-type antigen presenting cells (APCs), which have come to reside in the thymus. However, how MHC-mismatched mixed chimerism tolerizes host autoreactive T cells that recognize only self-MHC–peptide complexes remains unknown. Here, using NOD.Rag1−/−.BDC2.5 or NOD.Rag1−/−.BDC12-4.1 mice that have only noncross-reactive transgenic autoreactive T cells, we show that induction of MHC-mismatched but not -matched mixed chimerism restores immune tolerance of peripheral noncross-reactive autoreactive T cells. MHC-mismatched mixed chimerism results in increased percentages of both donor- and host-type Foxp3+ Treg cells and up-regulated expression of programmed death-ligand 1 (PD-L1) by host-type plasmacytoid dendritic cells (pDCs). Furthermore, adoptive transfer experiments showed that engraftment of donor-type dendritic cells (DCs) and expansion of donor-type Treg cells are required for tolerizing the noncross-reactive autoreactive T cells in the periphery, which are in association with up-regulation of host-type DC expression of PD-L1 and increased percentage of host-type Treg cells. Thus, induction of MHC-mismatched mixed chimerism may establish a peripheral tolerogenic DC and Treg network that actively tolerizes autoreactive T cells, even those with no TCR recognition of the donor APCs. PMID:29463744

  2. 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.

  3. Effects of refractive index mismatch in optical CT imaging of polymer gel dosimeters.

    PubMed

    Manjappa, Rakesh; Makki S, Sharath; Kumar, Rajesh; Kanhirodan, Rajan

    2015-02-01

    Proposing an image reconstruction technique, algebraic reconstruction technique-refraction correction (ART-rc). The proposed method takes care of refractive index mismatches present in gel dosimeter scanner at the boundary, and also corrects for the interior ray refraction. Polymer gel dosimeters with high dose regions have higher refractive index and optical density compared to the background medium, these changes in refractive index at high dose results in interior ray bending. The inclusion of the effects of refraction is an important step in reconstruction of optical density in gel dosimeters. The proposed ray tracing algorithm models the interior multiple refraction at the inhomogeneities. Jacob's ray tracing algorithm has been modified to calculate the pathlengths of the ray that traverses through the higher dose regions. The algorithm computes the length of the ray in each pixel along its path and is used as the weight matrix. Algebraic reconstruction technique and pixel based reconstruction algorithms are used for solving the reconstruction problem. The proposed method is tested with numerical phantoms for various noise levels. The experimental dosimetric results are also presented. The results show that the proposed scheme ART-rc is able to reconstruct optical density inside the dosimeter better than the results obtained using filtered backprojection and conventional algebraic reconstruction approaches. The quantitative improvement using ART-rc is evaluated using gamma-index. The refraction errors due to regions of different refractive indices are discussed. The effects of modeling of interior refraction in the dose region are presented. The errors propagated due to multiple refraction effects have been modeled and the improvements in reconstruction using proposed model is presented. The refractive index of the dosimeter has a mismatch with the surrounding medium (for dry air or water scanning). The algorithm reconstructs the dose profiles by estimating

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Mismatch in Law School. NBER Working Paper No. 14275

    ERIC Educational Resources Information Center

    Rothstein, Jesse; Yoon, Albert

    2008-01-01

    An important criticism of race-based higher education admission preferences is that they may hurt minority students who attend more selective schools than they would in the absence of such preferences. We categorize the non-experimental research designs available for the study of so-called "mismatch" effects and evaluate the likely biases in each.…

  13. 1 μm-thickness ultra-flexible and high electrode-density surface electromyogram measurement sheet with 2 V organic transistors for prosthetic hand control.

    PubMed

    Fuketa, Hiroshi; Yoshioka, Kazuaki; Shinozuka, Yasuhiro; Ishida, Koichi; Yokota, Tomoyuki; Matsuhisa, Naoji; Inoue, Yusuke; Sekino, Masaki; Sekitani, Tsuyoshi; Takamiya, Makoto; Someya, Takao; Sakurai, Takayasu

    2014-12-01

    A 64-channel surface electromyogram (EMG) measurement sheet (SEMS) with 2 V organic transistors on a 1 μm-thick ultra-flexible polyethylene naphthalate (PEN) film is developed for prosthetic hand control. The surface EMG electrodes must satisfy the following three requirements; high mechanical flexibility, high electrode density and high signal integrity. To achieve high electrode density and high signal integrity, a distributed and shared amplifier (DSA) architecture is proposed, which enables an in-situ amplification of the myoelectric signal with a fourfold increase in EMG electrode density. In addition, a post-fabrication select-and-connect (SAC) method is proposed to cope with the large mismatch of organic transistors. The proposed SAC method reduces the area and the power overhead by 96% and 98.2%, respectively, compared with the use of conventional parallel transistors to reduce the transistor mismatch by a factor of 10.

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

    ERIC Educational Resources Information Center

    Castro, Claudio de Moura; de Andrade, Antonio Cabral

    1990-01-01

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

  15. Care in a birth room versus a conventional setting: a controlled trial.

    PubMed Central

    Klein, M; Papageorgiou, A; Westreich, R; Spector-Dunsky, L; Elkins, V; Kramer, M S; Gelfand, M M

    1984-01-01

    A controlled clinical trial was carried out to assess whether a birth room setting would influence the care of mothers and newborns. Of the 163 low-risk women enrolled, 49 (30%) manifested some prenatal risk and were excluded. The remaining 114 were allocated by strict alternation to a birth room or a conventional setting. Of the 56 women allocated to the birth room, 63% of the primiparas and 19% of the multiparas were later transferred. The numbers in the two settings who had oxytocin stimulation, epidural anesthesia, forceps delivery or cesarean section did not show statistically significant differences. The episiotomy rates were slightly lower in the birth room than in the conventional setting, and the rates of an intact perineum were higher in the birth room. Neither the Apgar scores nor the morbidity rates of the infants showed statistically significant differences related to the setting to which the mother had been allocated, although more infants from the conventional setting were admitted to a special care unit. Both "experimental" groups of women less often received routine perineal shaving, enemas or intravenous infusions than did an obstetrically similar nonexperimental comparison group. Despite the apparent inability in this setting for the birth room to influence the rate of major obstetric procedures (except for episiotomy) and outcomes, the authors believe that a birth room is desirable in tertiary care centres as well as in community hospitals. PMID:6388776

  16. Numerical study of supersonic combustors by multi-block grids with mismatched interfaces

    NASA Technical Reports Server (NTRS)

    Moon, Young J.

    1990-01-01

    A three dimensional, finite rate chemistry, Navier-Stokes code was extended to a multi-block code with mismatched interface for practical calculations of supersonic combustors. To ensure global conservation, a conservative algorithm was used for the treatment of mismatched interfaces. The extended code was checked against one test case, i.e., a generic supersonic combustor with transverse fuel injection, examining solution accuracy, convergence, and local mass flux error. After testing, the code was used to simulate the chemically reacting flow fields in a scramjet combustor with parallel fuel injectors (unswept and swept ramps). Computational results were compared with experimental shadowgraph and pressure measurements. Fuel-air mixing characteristics of the unswept and swept ramps were compared and investigated.

  17. The conceptual mismatch: transportation stressors and experiences for low-income adults.

    DOT National Transportation Integrated Search

    2015-10-01

    Physical access to jobs has long been identified as a barrier to employment and earnings, with prior : research identifying the spatial mismatch between suburban entry-level jobs and low-income workers. : However, existing transportation resear...

  18. 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.

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

    USGS Publications Warehouse

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

    2017-01-01

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

  20. Drastic stability change of X-X mismatch in d(CXG) trinucleotide repeat disorders under molecular crowding condition.

    PubMed

    Teng, Ye; Pramanik, Smritimoy; Tateishi-Karimata, Hisae; Ohyama, Tatsuya; Sugimoto, Naoki

    2018-02-05

    The trinucleotide repeat d(CXG) (X = A, C, G or T) is the most common sequence causing repeat expansion disorders. The formation of non-canonical structures, such as hairpin structures with X-X mismatches, has been proposed to affect gene expression and regulation, which are important in pathological studies of these devastating neurological diseases. However, little information is available regarding the thermodynamics of the repeat sequence under crowded cellular conditions where many non-canonical structures such as G-quadruplexes are highly stabilized, while duplexes are destabilised. In this study, we investigated the different stabilities of X-X mismatches in the context of internal d(CXG) self-complementary sequences in an environment with a high concentration of cosolutes to mimic the crowding conditions in cells. The stabilities of full-matched duplexes and duplexes with A-A, G-G, and T-T mismatched base pairs under molecular crowding conditions were notably decreased compared to under dilute conditions. However, the stability of the DNA duplex with a C-C mismatch base pair was only slightly destabilised. Investigating different stabilities of X-X mismatches in d(CXG) sequences is important for improving our understanding of the formation and transition of multiple non-canonical structures in trinucleotide repeat diseases, and may provide insights for pathological studies and drug development. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. 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

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

    PubMed Central

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

    2017-01-01

    Background Allografts from living donors survive longer than those from deceased donors but the role of HLA mismatching in living kidney donation is still in question. We examined the effect of HLA compatibility on kidney allograft survival from living donors by studying all first adult kidney transplants performed in the United States over 25 years. Methods Using the United Network for Organ Sharing data, we identified first kidney transplants between October 1, 1987, and December 31, 2013. Recipients were classified by their number of HLA mismatches and stratified by donor origin. Cox multivariate regression analyses adjusting for recipient and donor transplant characteristics were performed to determine impact of HLA compatibility on kidney allograft survival for all living donors and for living related and living unrelated subsets. Results There were 66 596 first adult transplants from living donors with 348 960 years of follow-up. We found a linear relationship between HLA mismatch and allograft survival. In adjusted analyses, among all living donors, 1 mismatch conferred a 44% higher risk, whereas 6 mismatches conferred a twofold higher risk of allograft failure. When using 0-mismatched full siblings as a reference, living-donor kidneys reduce the hazard of failure by approximately 34% when compared with deceased donors. Twenty-five years of transplant experience, stratified by donor source, was summarized and presented as a guide for allocation. Conclusions These data reinforce the importance of optimizing HLA matching to further improve survival in first adult kidney allografts in the future, especially in living unrelated donations, when possible. PMID:28573187

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

    PubMed

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

    2017-05-01

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

  4. Involvement of Mismatch Repair in the Reciprocal Control of Motility and Adherence of Uropathogenic Escherichia coli

    PubMed Central

    Cooper, Lauren A.; Simmons, Lyle A.

    2012-01-01

    Type 1 fimbriae and flagella, two surface organelles critical for colonization of the urinary tract by uropathogenic Escherichia coli (UPEC), mediate opposing virulence objectives. Type 1 fimbriae facilitate adhesion to mucosal cells and promote bacterial persistence in the urinary tract, while flagella propel bacteria through urine and along mucous layers during ascension to the upper urinary tract. Using a transposon screen of the E. coli CFT073 fim locked-ON (L-ON) mutant, a construct that constitutively expresses type 1 fimbriae and represses motility, we identified six mutants that exhibited a partial restoration of motility. Among these six mutated genes was mutS, which encodes a component of the methyl-directed mismatch repair (MMR) system. When complemented with mutS in trans, motility was again repressed. To determine whether the MMR system, in general, is involved in this reciprocal control, we characterized the effects of gene deletions of other MMR components on UPEC motility. Isogenic deletions of mutS, mutH, and mutL were constructed in both wild-type CFT073 and fim L-ON backgrounds. All MMR mutants showed an increase in motility in the wild-type background, and ΔmutH and ΔmutS mutations increased motility in the fim L-ON background. Cochallenge of the wild-type strain with an MMR-defective strain showed a subtle but significant competitive advantage in the bladder and spleen for the MMR mutant using the murine model of ascending urinary tract infection after 48 h. Our findings demonstrate that the MMR system generally affects the reciprocal regulation of motility and adherence and thus could contribute to UPEC pathogenesis during urinary tract infections. PMID:22473602

  5. A review of climate-driven mismatches between interdependent phenophases in terrestrial and aquatic ecosystems.

    PubMed

    Donnelly, Alison; Caffarra, Amelia; O'Neill, Bridget F

    2011-11-01

    Mismatches in phenology between mutually dependent species, resulting from climate change, can have far-reaching consequences throughout an ecosystem at both higher and lower trophic levels. Rising temperatures, due to climate warming, have resulted in advances in development and changes in behaviour of many organisms around the world. However, not all species or phenophases are responding to this increase in temperature at the same rate, thus creating a disruption to previously synchronised interdependent key life-cycle stages. Mismatches have been reported between plants and pollinators, predators and prey, and pests and hosts. Here, we review mismatches between interdependent phenophases at different trophic levels resulting from climate change. We categorized the studies into (1) terrestrial (natural and agricultural) ecosystems, and (2) aquatic (freshwater and marine) ecosystems. As expected, we found reports of 'winners' and 'losers' in each system, such as earlier emergence of prey enabling partial avoidance of predators, potential reductions in crop yield if herbivore pests emerge before their predators and possible declines in marine biodiversity due to disruption in plankton-fish phenologies. Furthermore, in the marine environment rising temperatures have resulted in synchrony in a previously mismatched prey and predator system, resulting in an abrupt population decline in the prey species. The examples reviewed suggest that more research into the complex interactions between species in terrestrial and aquatic ecosystems is necessary to make conclusive predictions of how climate warming may impact the fragile balances within ecosystems in future.

  6. 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

  7. Cross-scale feedbacks and scale mismatches as influences on cultural services and the resilience of protected areas.

    PubMed

    Maciejewski, Kristine; De Vos, Alta; Cumming, Graeme S; Moore, Christine; Biggs, Duan

    2015-01-01

    Protected areas are a central strategy for achieving global conservation goals, but their continued existence depends heavily on maintaining sufficient social and political support to outweigh economic interests or other motives for land conversion. Thus, the resilience of protected areas can be considered a function of their perceived benefits to society. Nature-based tourism (NBT), a cultural ecosystem service, provides a key source of income to protected areas, facilitating a sustainable solution to conservation. The ability of tourism to generate income depends, however, on both the scales at which this cultural service is provided and the scales at which tourists respond to services on offer. This observation raises a set of location-, context-, and scale-related questions that need to be confronted before we can understand and value cultural service provision appropriately. We combine elements of resilience analysis with a systems ecology framework and apply this to NBT in protected areas to investigate cross-scale interactions and scale mismatches. We postulate that cross-scale effects can either have a positive effect on protected area resilience or lead to scale mismatches, depending on their interactions with cross-scale feedbacks. To demonstrate this, we compare spatial scales and nested levels of institutions to develop a typology of scale mismatches for common scenarios in NBT. In our new typology, the severity of a scale mismatch is expressed as the ratio of spatial scale to institutional level, producing 25 possible outcomes with differing consequences for system resilience. We predict that greater differences between interacting scales and levels, and greater magnitudes of cross-scale interactions, will lead to greater magnitudes of scale mismatch. Achieving a better understanding of feedbacks and mismatches, and finding ways of aligning spatial and institutional scales, will be critical for strengthening the resilience of protected areas that

  8. Deconstructing the Polymerase Chain Reaction: Understanding and Correcting Bias Associated with Primer Degeneracies and Primer-Template Mismatches

    PubMed Central

    Green, Stefan J.; Venkatramanan, Raghavee; Naqib, Ankur

    2015-01-01

    The polymerase chain reaction (PCR) is sensitive to mismatches between primer and template, and mismatches can lead to inefficient amplification of targeted regions of DNA template. In PCRs in which a degenerate primer pool is employed, each primer can behave differently. Therefore, inefficiencies due to different primer melting temperatures within a degenerate primer pool, in addition to mismatches between primer binding sites and primers, can lead to a distortion of the true relative abundance of targets in the original DNA pool. A theoretical analysis indicated that a combination of primer-template and primer-amplicon interactions during PCR cycles 3–12 is potentially responsible for this distortion. To test this hypothesis, we developed a novel amplification strategy, entitled “Polymerase-exonuclease (PEX) PCR”, in which primer-template interactions and primer-amplicon interactions are separated. The PEX PCR method substantially and significantly improved the evenness of recovery of sequences from a mock community of known composition, and allowed for amplification of templates with introduced mismatches near the 3’ end of the primer annealing sites. When the PEX PCR method was applied to genomic DNA extracted from complex environmental samples, a significant shift in the observed microbial community was detected. Furthermore, the PEX PCR method provides a mechanism to identify which primers in a primer pool are annealing to target gDNA. Primer utilization patterns revealed that at high annealing temperatures in the PEX PCR method, perfect match annealing predominates, while at lower annealing temperatures, primers with up to four mismatches with templates can contribute substantially to amplification. The PEX PCR method is simple to perform, is limited to PCR mixes and a single exonuclease step which can be performed without reaction cleanup, and is recommended for reactions in which degenerate primer pools are used or when mismatches between primers

  9. 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

  10. 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.

  11. 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.

  12. The Framework Convention on Tobacco Control (FCTC) and the adoption of domestic tobacco control policies: the Ecuadorian experience.

    PubMed

    Albuja, S; Daynard, R A

    2009-02-01

    The present work concerns the adoption of domestic tobacco control legislation in Ecuador after ratification of the World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC). Analysis of legislation, and data collection via interviews with key actors involved in the adoption and implementation of domestic legislation passed purportedly to implement the FCTC and research of the Ecuadorian Congressional Archives. While the FCTC helped raise awareness about tobacco's imminent and future threats to public health, paradoxically, it had the effect of further entrenching tobacco-friendly norms. Philip Morris, with 87% dominance over the Ecuadorian tobacco market, subtly harnessed the FCTC to protect its interests. This outcome was also influenced by poor governmental readiness and intervention, lack of legislative technical capabilities and weak civil society involvement. The Ecuadorian experience suggests that more support should be provided to health ministries, legislatures and local tobacco control organisations to offset the power of the tobacco industry as developing nations get ready to adopt domestic tobacco control legislation.

  13. The DNA mismatch repair genes Msh3 and Msh6 cooperate in intestinal tumor suppression.

    PubMed

    Edelmann, W; Umar, A; Yang, K; Heyer, J; Kucherlapati, M; Lia, M; Kneitz, B; Avdievich, E; Fan, K; Wong, E; Crouse, G; Kunkel, T; Lipkin, M; Kolodner, R D; Kucherlapati, R

    2000-02-15

    Repair of mismatches in DNA in mammalian cells is mediated by a complex of proteins that are members of two highly conserved families of genes referred to as MutS and MutL homologues. Germline mutations in several members of these families, MSH2, MSH6, MLH1, and PMS2, but not MSH3, are responsible for hereditary non-polyposis colorectal cancer. To examine the role of MSH3, we generated a mouse with a null mutation in this gene. Cells from Msh3-/- mice are defective in repair of insertion/ deletion mismatches but can repair base-base mismatches. Msh3-/- mice develop tumors at a late age. When the Msh3-/- and Msh6-/- mutations are combined, the tumor predisposition phenotype is indistinguishable from Msh2-/- or Mlh1-/- mice. These results suggest that MSH3 cooperates with MSH6 in tumor suppression.

  14. High performance, high bandgap, lattice-mismatched, GaInP solar cells

    DOEpatents

    Wanlass, Mark W; Carapella, Jeffrey J; Steiner, Myles A

    2016-11-01

    High performance, high bandgap, lattice-mismatched, photovoltaic cells (10), both transparent and non-transparent to sub-bandgap light, are provided as devices for use alone or in combination with other cells in split spectrum apparatus or other applications.

  15. High performance, high bandgap, lattice-mismatched, GaInP solar cells

    DOEpatents

    Wanlass, Mark W.; Carapella, Jeffrey J.; Steiner, Myles A.

    2014-07-08

    High performance, high bandgap, lattice-mismatched, photovoltaic cells (10), both transparent and non-transparent to sub-bandgap light, are provided as devices for use alone or in combination with other cells in split spectrum apparatus or other applications.

  16. Match and mismatch between opening area and resistance in mild and moderate rheumatic mitral stenosis.

    PubMed

    El-Dosouky, Ibtesam Ibrahim

    2016-12-01

    Mitral valve resistance (MVR) is a hemodynamic consequence of mitral stenosis (MS), but it has no clear threshold with a shortage of data to be reliable. We aimed to investigate match and mismatch between opening area and resistance especially in patients with moderate and mild MS. This study comprised 88 patients with moderate and mild rheumatic MS. Transthoracic echocardiographic study estimated the following: mitral valve area (MVA) by both planimetry (2D) and pressure half-time (PHT), mitral valve score (MVS), mean transmitral pressure gradient (MPG), diastolic filling time (DFT), left ventricular out flow tract diameter (LVOTd) and velocity-time integral (LVOTvti), and MVR = MPG/aortic flow ratio [(LVOTd) (LVOTvti)/DFT] in dynes·s/cm 5 . Patients were classified into two groups: group 1 (51 patients) with matched MVR and group 2 (37 patients) with mismatched higher MVR. In the matched group, moderate MS showed MVR <105 dynes·s/cm 5 and <76dynes·s/cm 5 with mild MS. Group 2 compared to group 1 had higher NYHA class (1.4±0.6 vs 1.2±0.4, P<.05) and higher MVS (8.1±1.8 vs 7±0.9, P<.05). MVR showed positive correlation with MVS (r=.5, P<.05), and logistic regression analysis showed that MVS is the only independent predictor of the MVR severity in the mismatched group (i.e., with higher MVR compared to the ROC analysis results) (B±SE=6.997±2.826, t=2.476, 95% CI 1.241±12.752 with an odds ratio=0.412, P<.05). On investigating match and mismatch between opening area and resistance, the only independent predictor of mismatch is the mitral valve score. © 2016, Wiley Periodicals, Inc.

  17. 40 CFR 439.33 - Effluent limitations attainable by the application of the best conventional pollutant control...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Effluent limitations attainable by the application of the best conventional pollutant control technology (BCT). 439.33 Section 439.33 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS PHARMACEUTICAL...

  18. 40 CFR 439.23 - Effluent limitations attainable by the application of the best conventional pollutant control...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Effluent limitations attainable by the application of the best conventional pollutant control technology (BCT). 439.23 Section 439.23 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS PHARMACEUTICAL...

  19. 40 CFR 439.13 - Effluent limitations attainable by the application of the best conventional pollutant control...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Effluent limitations attainable by the application of the best conventional pollutant control technology (BCT). 439.13 Section 439.13 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS PHARMACEUTICAL...

  20. 40 CFR 439.43 - Effluent limitations attainable by the application of the best conventional pollutant control...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Effluent limitations attainable by the application of the best conventional pollutant control technology (BCT). 439.43 Section 439.43 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS PHARMACEUTICAL...

  1. Modified bases enable high-efficiency oligonucleotide-mediated allelic replacement via mismatch repair evasion

    PubMed Central

    Wang, Harris H.; Xu, George; Vonner, Ashley J.; Church, George

    2011-01-01

    Genome engineering using single-stranded oligonucleotides is an efficient method for generating small chromosomal and episomal modifications in a variety of host organisms. The efficiency of this allelic replacement strategy is highly dependent on avoidance of the endogenous mismatch repair (MMR) machinery. However, global MMR inactivation generally results in significant accumulation of undesired background mutations. Here, we present a novel strategy using oligos containing chemically modified bases (2′-Fluoro-Uridine, 5-Methyl-deoxyCytidine, 2,6-Diaminopurine or Iso-deoxyGuanosine) in place of the standard T, C, A or G to avoid mismatch detection and repair, which we tested in Escherichia coli. This strategy increases transient allelic-replacement efficiencies by up to 20-fold, while maintaining a 100-fold lower background mutation level. We further show that the mismatched bases between the full length oligo and the chromosome are often not incorporated at the target site, probably due to nuclease activity at the 5′ and 3′ termini of the oligo. These results further elucidate the mechanism of oligo-mediated allelic replacement (OMAR) and enable improved methodologies for efficient, large-scale engineering of genomes. PMID:21609953

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

    PubMed

    Thomas, Kevin J A

    2015-03-01

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

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

    PubMed

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

    2017-04-17

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

  4. 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) mismatch early after implantation of a 17-mm Regent valve at aortic position were included. Both clinical and echocardiographic assessments were performed preoperatively, at discharge and during follow-up period (mean follow-up time 52.6 ± 11.9 months). The prevalence of moderate prosthesis-patient mismatch was documented in 46 patients (43.4%) at discharge. During the follow-up period, no difference in the regression of left ventricular mass, decrease of transvalvular pressure gradients, mortality and prosthesis-related complications was observed between patients with and without moderate prosthesis-patient mismatch. After adjustment for several risk factors, moderate prosthesis-patient mismatch was associated with increased midterm mortality in patients with baseline left ventricular ejection fraction<50% (HR: 1.80, p=0.02), but with normal prognosis in those with preserved LV function. Younger age (cut off value=65 years) was not an independent predictor of increased midterm mortality and valve-related complications in patients with moderate prosthesis-patient mismatch. Moderate prosthesis-patient mismatch after aortic valve replacement with a small mechanical prosthesis is associated with increased mortality and adverse events in patients with pre-existing left ventricular dysfunction. Selected patients with small aortic annulus can experience satisfactory clinical improvements and midterm survival after aortic valve replacement with a 17-mm Regent valve.

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

    PubMed

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

    2014-03-01

    Constitutional mismatch repair deficiency (CMMRD) is a devastating cancer predisposition syndrome for which data regarding clinical manifestations, molecular screening tools and management are limited. We established an international CMMRD consortium and collected comprehensive clinical and genetic data. Molecular diagnosis of tumour and germline biospecimens was performed. A surveillance protocol was developed and implemented. Overall, 22/23 (96%) of children with CMMRD developed 40 different tumours. While childhood CMMRD related tumours were observed in all families, Lynch related tumours in adults were observed in only 2/14 families (p=0.0007). All children with CMMRD had café-au-lait spots and 11/14 came from consanguineous families. Brain tumours were the most common cancers reported (48%) followed by gastrointestinal (32%) and haematological malignancies (15%). Importantly, 12 (30%) of these were low grade and resectable cancers. Tumour immunohistochemistry was 100% sensitive and specific in diagnosing mismatch repair (MMR) deficiency of the corresponding gene while microsatellite instability was neither sensitive nor specific as a diagnostic tool (p<0.0001). Furthermore, screening of normal tissue by immunohistochemistry correlated with genetic confirmation of CMMRD. The surveillance protocol detected 39 lesions which included asymptomatic malignant gliomas and gastrointestinal carcinomas. All tumours were amenable to complete resection and all patients undergoing surveillance are alive. CMMRD is a highly penetrant syndrome where family history of cancer may not be contributory. Screening tumours and normal tissues using immunohistochemistry for abnormal expression of MMR gene products may help in diagnosis and early implementation of surveillance for these children. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. 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

  7. 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

  8. From public health to international law: possible protocols for inclusion in the Framework Convention on Tobacco Control.

    PubMed Central

    Joossens, L.

    2000-01-01

    Faced with a difficult business environment in the United States and the falling demand for cigarettes in industrialized countries, multinational tobacco companies have been competing fiercely to expand their sales in developing countries. Because of the worldwide threat posed by smoking to health and the emphasis being placed by international tobacco companies on marketing in developing countries, an international regulatory strategy, such as the WHO proposed Framework Convention on Tobacco Control, is needed. This review describes from a public health perspective the possible scope and key considerations of protocols that should be included in the convention. The key international areas that should be considered in tobacco control are: prices, smuggling; tax-free tobacco products; advertising and sponsorship; the Internet; testing methods; package design and labelling; agriculture; and information sharing. PMID:10994267

  9. Experimental Investigation of Piston Heat Transfer in a Light Duty Engine Under Conventional Diesel, Homogeneous Charge Compression Ignition, and Reactivity Controlled Compression Ignition Combustion Regimes

    DTIC Science & Technology

    2014-01-15

    in a Light Duty Engine Under Conventional Diesel, Homogeneous Charge Compression Ignition , and Reactivity Controlled Compression Ignition ...Conventional Diesel (CDC), Homogeneous Charge Compression Ignition (HCCI), and Reactivity Controlled Compression Ignition (RCCI) combustion...LTC) regimes, including reactivity controlled compression ignition (RCCI), partially premixed combustion (PPC), and homogenous charge compression

  10. Mechanism of mismatch recognition revealed by human MutSβ bound to unpaired DNA loops

    PubMed Central

    Gupta, Shikha; Gellert, Martin; Yang, Wei

    2011-01-01

    DNA mismatch repair corrects replication errors, thus reducing mutation rates and microsatellite instability. Genetic defects in this pathway cause Lynch Syndrome and various cancers in humans. Binding of a mispaired or unpaired base by bacterial MutS and eukaryotic MutSα is well characterized. We report here crystal structures of human MutSβ complexed with DNA containing insertion-deletion loops (IDL) of 2, 3, 4, or 6 unpaired nucleotides. In contrast to eukaryotic MutSα and bacterial MutS, which bind the base of a mismatched nucleotide, MutSβ binds three phosphates in an IDL. DNA is severely bent at the IDL; unpaired bases are flipped out into the major groove and partially exposed to solvent. A normal downstream basepair can become unpaired; thereby a single unpaired base can be converted to an IDL of 2 nucleotides and recognized by MutSβ. The C-terminal dimerization domains form an integral part of the MutS structure and coordinate asymmetrical ATP hydrolysis by Msh2 and Msh3 with mismatch binding to signal for repair. PMID:22179786

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

    PubMed

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

    2017-07-03

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

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

    PubMed

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

    2012-06-01

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

  13. Effective oligonucleotide-mediated gene disruption in ES cells lacking the mismatch repair protein MSH3.

    PubMed

    Dekker, M; Brouwers, C; Aarts, M; van der Torre, J; de Vries, S; van de Vrugt, H; te Riele, H

    2006-04-01

    We have previously demonstrated that site-specific insertion, deletion or substitution of one or two nucleotides in mouse embryonic stem cells (ES cells) by single-stranded deoxyribo-oligonucleotides is several hundred-fold suppressed by DNA mismatch repair (MMR) activity. Here, we have investigated whether compound mismatches and larger insertions escape detection by the MMR machinery and can be effectively introduced in MMR-proficient cells. We identified several compound mismatches that escaped detection by the MMR machinery to some extent, but could not define general rules predicting the efficacy of complex base-pair substitutions. In contrast, we found that four-nucleotide insertions were largely subject to suppression by the MSH2/MSH3 branch of MMR and could be effectively introduced in Msh3-deficient cells. As these cells have no overt mutator phenotype and Msh3-deficient mice do not develop cancer, Msh3-deficient ES cells can be used for oligonucleotide-mediated gene disruption. As an example, we present disruption of the Fanconi anemia gene Fancf.

  14. Mechanical Strength of the Side-to-Side Tendon Attachment for Mismatched Tendon Sizes and Shapes

    PubMed Central

    Fridén, Jan; Tirrell, Timothy F.; Bhola, Siddharth; Lieber, Richard L.

    2015-01-01

    Summary Certain combinations are advised against in tendon transfers due to size or shape mismatches between donor and recipient tendons. In this study, ultimate load, stiffness and Young’s modulus were measured in two tendon-to-tendon attachments with intentionally mismatched donor and recipient tendons - pronator teres (PT)-to-extensor carpi radialis brevis (ECRB) and flexor carpi ulnaris (FCU)-to-extensor digitorum communis (EDC). FCU-EDC attachments failed at higher loads than PT-to-ECRB attachments but they had similar modulus and stiffness values. Ultimate tensile strength of the tendon attachments exceeded the maximum predicted contraction force of any of the affected muscles, with safety factors of 4x and 2x for the FCU-to-EDC and PT-to-ECRB constructs, respectively. This implies that size and shape mismatch should not be a contraindication to tendon attachment in transfers. Further, these safety factors strongly suggest that no postoperative immobilization of these attachments is necessary. PMID:24413573

  15. Warthin tumors do not have microsatellite instability and express normal DNA mismatch repair proteins.

    PubMed

    Hunt, Jennifer L

    2006-01-01

    Warthin tumors are controversial entities with a poorly understood etiology. Although some investigators have suggested a neoplastic origin, others have supported a developmental anomaly. A recent study described the absence of staining for hMLH1 and hMSH2 proteins in the epithelial component of Warthin tumors, suggesting that they arise secondary to defects in the DNA mismatch repair system. To determine if Warthin tumors exhibit evidence of DNA mismatch repair defects. Immunostains for hMLH1 and hMSH2 were performed using a standard approach. Microdissection of the epithelial component was followed by DNA extraction from the tissue fragments. Polymerase chain reaction and capillary electrophoresis analyses were performed for the following 5 National Cancer Institute-recommended microsatellites: D2s123, D5s346, D17s250, BAT25, and BAT26. Twelve patients with Warthin tumors were included. The immunostains for hMLH1 and hMSH2 showed preserved expression in the nuclei of the epithelial component of all Warthin tumors. No microsatellite instability was detected, and no loss of heterozygosity was seen. These results are not concordant with previously reported results showing loss of expression of the hMLH1 and hMSH2 DNA mismatch repair enzymes in the epithelial component of Warthin tumors. Furthermore, no microsatellite instability was detected in the 5 loci tested for each tumor in this series. These data demonstrate that Warthin tumors do not have evidence of DNA mismatch repair defects at the genomic or protein expression level.

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

    PubMed Central

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

    2014-01-01

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

  17. Skills Mismatch among University Graduates in the Nigeria Labor Market

    ERIC Educational Resources Information Center

    Pitan, Oluyomi S.; Adedeji, S. O.

    2012-01-01

    University graduates in Nigeria have been reported to be poorly prepared for work in recent years. This has implications on the relevance of university education, the employability and productivity of university graduates. One of the reasons suggested for this condition by previous studies was skill mismatch--a situation where there is a disparity…

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

    ERIC Educational Resources Information Center

    Beduwe, Catherine; Giret, Jean-Francois

    2011-01-01

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

  19. Elastic mismatch induced reduction of the thermal conductivity of silicon with aluminum nano-inclusions

    NASA Astrophysics Data System (ADS)

    Donovan, Brian F.; Jensen, Wade A.; Chen, Long; Giri, Ashutosh; Poon, S. Joseph; Floro, Jerrold A.; Hopkins, Patrick E.

    2018-05-01

    We use aluminum nano-inclusions in silicon to demonstrate the dominance of elastic modulus mismatch induced scattering in phonon transport. We use time domain thermoreflectance to measure the thermal conductivity of thin films of silicon co-deposited with aluminum via molecular beam epitaxy resulting in a Si film with 10% clustered Al inclusions with nanoscale dimensions and a reduction in thermal conductivity of over an order of magnitude. We compare these results with well-known models in order to demonstrate that the reduction in the thermal transport is driven by elastic mismatch effects induced by aluminum in the system.

  20. 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.

  1. 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.

  2. 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.

  3. Effects of recombinant human activated protein C on the fibrinolytic system of patients undergoing conventional or tight glycemic control.

    PubMed

    Polli, F; Savioli, M; Cugno, M; Taccone, P; Bellani, G; Spanu, P; Pesenti, A; Iapichino, G; Gattinoni, L

    2009-01-01

    Recombinant human activated protein C (rh-APC) and tight glycemic control (TGC) have been shown to reduce mortality in septic patients. Both interventions can reduce the plasma concentration and/or activity of the most powerful suppressor of fibrinolysis, plasminogen activator inhibitor-1 (PAI-1). Our aim was to evaluate the effects on the fibrinolytic system after the administration of rh-APC in septic patients undergoing conventional or TGC. Posthoc analysis of data was collected from 90 patients with severe sepsis/septic shock, randomized to either conventional or TGC groups. Independent of these treatments, patients with at least two organ dysfunctions simultaneously received rh-APC. Plasma levels of multiple biochemical markers for fibrinolysis, coagulation, and inflammation were determined every day for the 1st week and then on study days 9, 11, 13, 18, 23, and 28. Clinical data and sepsis-related organ failure assessment (SOFA) scores were also recorded. Patients who had received rh-APC exhibited significantly more impairments in fibrinolysis at baseline (PAI-1 activity 49.76 [24.61-71.82] vs 21.92 [6.47-55-83] IU/mL, P=0.03). The reductions in plasma PAI-1 activity over time associated with rh-APC treatment were different according to whether the treatment was administered to patients undergoing conventional or TGC (P=0.01). However, the most prominent reductions were in patients undergoing conventional glycemic control. Significant interactions between the two study interventions were also found for PAI-1 concentration (P<0.001), C-reactive protein (P=0.02), and interleukin-6 levels (P<0.001). Both rh-APC and TGC appear to improve fibrinolysis in septic patients. The reduction in the impairment of fibrinolysis associated with rh-APC treatment seems greater in patients undergoing conventional glycemic control than in those undergoing TGC.

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

    PubMed Central

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

    2018-01-01

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

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

    USGS Publications Warehouse

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

    2018-01-01

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

  6. Recruitment Variability in North Atlantic Cod and Match-Mismatch Dynamics

    PubMed Central

    Kristiansen, Trond; Drinkwater, Kenneth F.; Lough, R. Gregory; Sundby, Svein

    2011-01-01

    Background Fisheries exploitation, habitat destruction, and climate are important drivers of variability in recruitment success. Understanding variability in recruitment can reveal mechanisms behind widespread decline in the abundance of key species in marine and terrestrial ecosystems. For fish populations, the match-mismatch theory hypothesizes that successful recruitment is a function of the timing and duration of larval fish abundance and prey availability. However, the underlying mechanisms of match-mismatch dynamics and the factors driving spatial differences between high and low recruitment remain poorly understood. Methodology/Principal Findings We used empirical observations of larval fish abundance, a mechanistic individual-based model, and a reanalysis of ocean temperature data from 1960 to 2002 to estimate the survival of larval cod (Gadus morhua). From the model, we quantified how survival rates changed during the warmest and coldest years at four important cod spawning sites in the North Atlantic. The modeled difference in survival probability was not large for any given month between cold or warm years. However, the cumulative effect of higher growth rates and survival through the entire spawning season in warm years was substantial with 308%, 385%, 154%, and 175% increases in survival for Georges Bank, Iceland, North Sea, and Lofoten cod stocks, respectively. We also found that the importance of match-mismatch dynamics generally increased with latitude. Conclusions/Significance Our analyses indicate that a key factor for enhancing survival is the duration of the overlap between larval and prey abundance and not the actual timing of the peak abundance. During warm years, the duration of the overlap between larval fish and their prey is prolonged due to an early onset of the spring bloom. This prolonged season enhances cumulative growth and survival, leading to a greater number of large individuals with enhanced potential for survival to recruitment

  7. Minority Students and Research Universities: How to Overcome the "Mismatch"

    ERIC Educational Resources Information Center

    Tapia, Richard A.

    2009-01-01

    A controversial theory much in the news lately claims that affirmative action is often unfair to the very students it is intended to help. Called the "mismatch" theory, it suggests that underrepresented minority students are more likely to leave science, math, and engineering when, because of affirmative action, they attend colleges for which they…

  8. Graft and patient outcomes of zero-human leucocyte-antigen-mismatched deceased and live donor kidney transplant recipients.

    PubMed

    Lim, Wai H; Gray, Nicholas A; Chadban, Steven J; Pilmore, Helen; Wong, Germaine

    2015-05-01

    Greater compatibility of human leucocyte antigen (HLA) alleles between kidney donors and recipients may lead to improved graft outcomes. This study aimed to compare the incidence of acute rejection and graft failure in zero-HLA-mismatched recipients of living-related (LD) and deceased donor (DD) kidney transplants. Using data from the Australia and New Zealand Dialysis and Transplant Registry, we compared the risk of any acute rejection and biopsy-proven acute rejection (BPAR) and graft failure in recipients of zero-HLA-mismatched kidneys between LD and DD using logistic and Cox regression models. Of the 931 zero-HLA-mismatched recipients transplanted between 1990 and 2012, 19 (2.0%) received kidneys from monozygotic/dizygotic twins (twin), 500 (53.7%) from nontwin LD and 412 (44.3%) from DD. Twin kidney transplant recipients did not experience rejection. Compared to DD transplant recipients, the risk of any acute rejection (adjusted odds ratio 0.52, 95%CI 0.34-0.79, P = 0.002) and overall graft failure (adjusted hazard ratio 0.55, 95%CI 0.41-0.73, P < 0.001) was significantly lower in LD recipients independent of initial immunosuppression, but not for BPAR (adjusted odds ratio 0.52, 95%CI 0.16-1.64, P = 0.263). Zero-HLA-mismatched DD kidney transplant recipients have a significantly higher risk of any acute rejection episodes and graft loss compared to zero-HLA-mismatched LD kidney transplant recipients. A cautious and careful approach in reducing immunosuppression appears to be warranted in this group of transplant recipients. © 2015 Steunstichting ESOT.

  9. Characterization of Arabidopsis thaliana mismatch specific endonucleases: application to mutation discovery by TILLING in pea.

    PubMed

    Triques, Karine; Sturbois, Bénédicte; Gallais, Stéphane; Dalmais, Marion; Chauvin, Stéphanie; Clepet, Christian; Aubourg, Sébastien; Rameau, Catherine; Caboche, Michel; Bendahmane, Abdelhafid

    2007-09-01

    Scanning DNA sequences for mutations and polymorphisms has become one of the most challenging, often expensive and time-consuming obstacles in many molecular genetic applications, including reverse genetic and clinical diagnostic applications. Enzymatic mutation detection methods are based on the cleavage of heteroduplex DNA at the mismatch sites. These methods are often limited by the availability of a mismatch-specific endonuclease, their sensitivity in detecting one allele in a pool of DNA and their costs. Here, we present detailed biochemical analysis of five Arabidopsis putative mismatch-specific endonucleases. One of them, ENDO1, is presented as the first endonuclease that recognizes and cleaves all types of mismatches with high efficiency. We report on a very simple protocol for the expression and purification of ENDO1. The ENDO1 system could be exploited in a wide range of mutation diagnostic tools. In particular, we report the use of ENDO1 for discovery of point mutations in the gibberellin 3beta-hydrolase gene of Pisum sativum. Twenty-one independent mutants were isolated, five of these were characterized and two new mutations affecting internodes length were identified. To further evaluate the quality of the mutant population we screened for mutations in four other genes and identified 5-21 new alleles per target. Based on the frequency of the obtained alleles we concluded that the pea population described here would be suitable for use in a large reverse-genetics project.

  10. 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

  11. 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.

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

    PubMed

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

    2015-06-01

    Several risk factors and causes of adjacent segment disease have been debated; however, no quantitative relationship to spino-pelvic parameters has been established so far. A retrospective case-control study was carried out to investigate spino-pelvic alignment in patients with adjacent segment disease compared to a control group. 45 patients (ASDis) were identified that underwent revision surgery for adjacent segment disease after on average 49 months (7-125), 39 patients were selected as control group (CTRL) similar in the distribution of the matching variables, such as age, gender, preoperative degenerative changes, and numbers of segments fused with a mean follow-up of 84 months (61-142) (total n = 84). Several radiographic parameters were measured on pre- and postoperative radiographs, including lumbar lordosis measured (LL), sacral slope, pelvic incidence (PI), and tilt. Significant differences between ASDis and CTRL groups on preoperative radiographs were seen for PI (60.9 ± 10.0° vs. 51.7 ± 10.4°, p = 0.001) and LL (48.1 ± 12.5° vs. 53.8 ± 10.8°, p = 0.012). Pelvic incidence was put into relation to lumbar lordosis by calculating the difference between pelvic incidence and lumbar lordosis (∆PILL = PI-LL, ASDis 12.5 ± 16.7° vs. CTRL 3.4 ± 12.1°, p = 0.001). A cutoff value of 9.8° was determined by logistic regression and ROC analysis and patients classified into a type A (∆PILL <10°) and a type B (∆PILL ≥10°) alignment according to pelvic incidence-lumbar lordosis mismatch. In type A spino-pelvic alignment, 25.5 % of patients underwent revision surgery for adjacent segment disease, whereas 78.3 % of patients classified as type B alignment had revision surgery. Classification of patients into type A and B alignments yields a sensitivity for predicting adjacent segment disease of 71 %, a specificity of 81 % and an odds ratio of 10.6. In degenerative disease of the lumbar spine a high pelvic incidence with diminished lumbar lordosis seems

  13. 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.

  14. Coalescence induced dislocation reduction in selectively grown lattice-mismatched heteroepitaxy: Theoretical prediction and experimental verification

    NASA Astrophysics Data System (ADS)

    Yako, Motoki; Ishikawa, Yasuhiko; Wada, Kazumi

    2018-05-01

    A method for reduction of threading dislocation density (TDD) in lattice-mismatched heteroepitaxy is proposed, and the reduction is experimentally verified for Ge on Si. Flat-top epitaxial layers are formed through coalescences of non-planar selectively grown epitaxial layers, and enable the TDD reduction in terms of image force. Numerical calculations and experiments for Ge on Si verify the TDD reduction by this method. The method should be applicable to not only Ge on Si but also other lattice-mismatched heteroepitaxy such as III-V on Si.

  15. Effects of refractive index mismatch in optical CT imaging of polymer gel dosimeters

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

    Manjappa, Rakesh; Makki S, Sharath; Kanhirodan, Rajan, E-mail: rajan@physics.iisc.ernet.in

    2015-02-15

    Purpose: Proposing an image reconstruction technique, algebraic reconstruction technique-refraction correction (ART-rc). The proposed method takes care of refractive index mismatches present in gel dosimeter scanner at the boundary, and also corrects for the interior ray refraction. Polymer gel dosimeters with high dose regions have higher refractive index and optical density compared to the background medium, these changes in refractive index at high dose results in interior ray bending. Methods: The inclusion of the effects of refraction is an important step in reconstruction of optical density in gel dosimeters. The proposed ray tracing algorithm models the interior multiple refraction at themore » inhomogeneities. Jacob’s ray tracing algorithm has been modified to calculate the pathlengths of the ray that traverses through the higher dose regions. The algorithm computes the length of the ray in each pixel along its path and is used as the weight matrix. Algebraic reconstruction technique and pixel based reconstruction algorithms are used for solving the reconstruction problem. The proposed method is tested with numerical phantoms for various noise levels. The experimental dosimetric results are also presented. Results: The results show that the proposed scheme ART-rc is able to reconstruct optical density inside the dosimeter better than the results obtained using filtered backprojection and conventional algebraic reconstruction approaches. The quantitative improvement using ART-rc is evaluated using gamma-index. The refraction errors due to regions of different refractive indices are discussed. The effects of modeling of interior refraction in the dose region are presented. Conclusions: The errors propagated due to multiple refraction effects have been modeled and the improvements in reconstruction using proposed model is presented. The refractive index of the dosimeter has a mismatch with the surrounding medium (for dry air or water scanning). The

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

    ERIC Educational Resources Information Center

    Croce, Giuseppe; Ghignoni, Emanuela

    2015-01-01

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

  17. 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.

  18. The Association of Intergenerational Mismatch With Adiposity and Blood Pressure in Childhood and Adolescence.

    PubMed

    Hui, L L; Nelson, E Anthony S; Wong, M Y; Chung, Thomas W H; Lee, Karen K Y; Leung, Gabriel M; Schooling, C Mary

    2018-01-01

    An intergenerational "mismatch," a transition from limited to plentiful living conditions over generations, may increase cardiovascular disease risks. In a migrant population within a homogenous culture, we tested the hypothesis that an intergenerational mismatch in childhood living condition is associated with higher body mass index (BMI) and blood pressure in childhood and adolescence. We used data from 6,965 native born Chinese in Hong Kong (participated in "Children of 1997" birth cohort) and migrant Chinese born elsewhere in China in 1997 (N = 9,845). We classified children into those with intergenerational mismatch (child migrants or first-generation migrants) or those without (second+-generation migrants). Generalized estimating equations were used to examine the associations of migration status (child migrants, first-generation migrants or second+-generation migrants) with age- and sex-specific BMI z-score at 8-15 years and age-, sex-, and height-specific blood pressure z-score at 11-13 years, adjusted for sex, month of birth, and age. Compared with second+-generation migrants, first-generation migrants had higher diastolic blood pressure z-score (.04, 95% confidence interval (CI) .02, .06) and BMI z-score (.12, 95% CI .06, .18), whereas child migrants had higher diastolic blood pressure z-score (.03, 95% CI .01, .05) regardless of age at migration and higher BMI z-score if they had migrated in infancy (.17, 95% CI .11, .23). Different relations for blood pressure and BMI suggest that intergenerational mismatch and proximal exposures may have different impacts on adiposity and blood pressure. Copyright © 2017 The Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  19. 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.

  20. Unrelated cord blood transplantation vs. related transplantation with HLA 1-antigen mismatch in the GVH direction.

    PubMed

    Kanda, Junya

    2015-05-01

    The donor selection superiority of HLA 1-antigen mismatched related donor versus unrelated cord blood (UCB) is an important issue for patients without an HLA-matched related or unrelated donor. Using Japanese registry data, we analyzed patients with leukemia and myelodysplastic syndrome who received transplantation using UCB or from a related donor with 1-antigen mismatch in the graft-versus-host (GVH) direction (RD/1AG-MM-GVH). Compared to the UCB group, neutrophil engraftment was significantly faster, and the incidences of acute and chronic GVHD were significantly higher in the RD/1AG-MM-GVH group. As a result, there was no significant difference in overall survival between transplantation using the RD/1AG-MM-GVH and UCB. However, the HLA-B-antigen mismatched group showed significantly inferior overall survival. The RD/1AG-MM-GVH group using anti-thymocyte globulin (ATG) showed neutrophil engraftment comparable to that of the non-ATG group and a GVHD incidence similar to that of the UCB group, which resulted in a better overall survival rate in the ATG than in the UCB group. In particular, the adverse effects of HLA-B mismatch were not observed in the ATG group. RD/1AGMM-GVH transplantation using ATG could potentially improve outcomes, and a prospective study of RD/1AGMM-GVH transplantation using low-dose ATG is currently ongoing.

  1. Analysis of MSH3 in endometrial cancers with defective DNA mismatch repair.

    PubMed

    Swisher, E M; Mutch, D G; Herzog, T J; Rader, J S; Kowalski, L D; Elbendary, A; Goodfellow, P J

    1998-01-01

    To clarify the origin of defective mismatch repair (MMR) in sporadic endometrial cancers with microsatellite instability (MSI), a thorough mutation analysis was performed on the human mismatch repair gene MSH3. Twenty-eight MSI-positive endometrial cancers were investigated for mutations in the human mismatch repair gene MSH3 using single-strand conformation variant (SSCV) analysis of all 24 exons. All variants were sequenced. Loss of heterozygosity was investigated at all MSH3 polymorphisms discovered. A subset of tumors were investigated for methylation of the 5' promoter region of MSH3 using Southern blot hybridization. An identical single-base deletion (delta A) predicted to result in a truncated proteins was discovered in six tumors (21.4%). This deletion occurs in a string of eight consecutive adenosine residues (A8). Because simple repeat sequences are unstable in cells with defective MMR, the observed mutation may be an effect, rather than a cause, of MSI. Evidence of inactivation of the second MSH3 allele in tumors with the delta A mutation would strongly support a causal role for these MSH3 mutations. However, there was no evidence of a second mutation, loss of sequences, or methylation of the promoter region in any of the tumors with the delta A mutation. Although the delta A mutation is a frequent event in sporadic MSI-positive endometrial cancers, it may not be causally associated with defective DNA MMR.

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

    NASA Astrophysics Data System (ADS)

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

    2018-01-01

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

  3. Gastrointestinal toxicity among patients taking selective COX-2 inhibitors or conventional NSAIDs, alone or combined with proton pump inhibitors: a case-control study.

    PubMed

    Bakhriansyah, Mohammad; Souverein, Patrick C; de Boer, Anthonius; Klungel, Olaf H

    2017-10-01

    To assess the risk of gastrointestinal perforation, ulcers, or bleeding (PUB) associated with the use of conventional nonsteroidal anti-inflammatory drugs (NSAIDs) with proton pump inhibitors (PPIs) and selective COX-2 inhibitors, with or without PPIs compared with conventional NSAIDs. A case-control study was performed within conventional NSAIDs and/or selective COX-2 inhibitors users identified from the Dutch PHARMO Record Linkage System in the period 1998-2012. Cases were patients aged ≥18 years with a first hospital admission for PUB. For each case, up to four controls were matched for age and sex at the date a case was hospitalized (index date). Logistic regression analysis was used to calculate odds ratios (ORs). At the index date, 2634 cases and 5074 controls were current users of conventional NSAIDs or selective COX-2 inhibitors. Compared with conventional NSAIDs, selective COX-2 inhibitors with PPIs had the lowest risk of PUB (adjusted OR 0.51, 95% confidence interval [CI]: 0.35-0.73) followed by selective COX-2 inhibitors (adjusted OR 0.66, 95%CI: 0.48-0.89) and conventional NSAIDs with PPIs (adjusted OR 0.79, 95%CI: 0.68-0.92). Compared with conventional NSAIDs, the risk of PUB was lower for those aged ≥75 years taking conventional NSAIDs with PPIs compared with younger patients (adjusted interaction OR 0.79, 95%CI: 0.64-0.99). However, those aged ≥75 years taking selective COX-2 inhibitors, the risk was higher compared with younger patients (adjusted interaction OR 1.22, 95%CI: 1.01-1.47). Selective COX-2 inhibitors with PPIs, selective COX-2 inhibitors, and conventional NSAIDs with PPIs were associated with lower risks of PUB compared with conventional NSAIDs. These effects were modified by age. © 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd. © 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd.

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

    PubMed Central

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

    2013-01-01

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

  5. Gaming and Conventional Exercises for Improvement of Arm Function After Stroke: A Randomized Controlled Pilot Study.

    PubMed

    Kottink, Anke I R; Prange, Gerdienke B; Krabben, Thijs; Rietman, Johan S; Buurke, Jaap H

    2014-06-01

    The use of new technologies in rehabilitation, such as virtual reality and/or computerized gaming exercises, may be useful to enable patients to practice intensively in a motivating way. The objective of the present randomized controlled pilot study was to compare the effect of reach training using a target group specific-designed rehabilitation game to time-matched standardized conventional reach training on arm function after stroke. Twenty chronic stroke patients were randomized to either the rehabilitation game group or the conventional training group. Both groups received three arm training sessions of 30 minutes each week, during a period of 6 weeks. Arm (the upper extremity part of Fugl-Meyer [FM] assessment) and hand (the Action Research Arm [ARA] test) functions were tested 1 week before (T0) and 1 week after (T1) training. A follow-up measurement was performed at 1 month after T1 (T2). ARA and FM scores improved significantly within both groups. Post hoc comparisons revealed significant increases in test scores between T0 and T1 and between T0 and T2 for both ARA and FM, but not for changes from T1 to T2. There were no significant differences between both groups for either clinical test. The present randomized controlled pilot study showed that both arm and hand function improved as much after training with a rehabilitation game as after time-matched conventional training.

  6. Costa Rica’s implementation of the Framework Convention on Tobacco Control: Overcoming decades of industry dominance

    PubMed Central

    Crosbie, Eric; Sosa, Patricia; Glantz, Stanton A

    2016-01-01

    Objective To analyze the passage of Costa Rica’s 2012 tobacco control law. Materials and methods Review of legislation, newspaper articles, and key informant interviews. Results Tobacco control advocates, in close collaboration with international health groups, recruited national, regional and international experts to testify in the Legislative Assembly, implemented grassroots advocacy campaigns, and generated media coverage to enact strong legislation in March 2012 consistent with the World Health Organization Framework Convention on Tobacco Control, despite tobacco industry lobbying efforts that for decades blocked effective tobacco control legislation. Conclusion Costa Rica’s experience illustrates how with resources, good strategic planning, aggressive tactics and perseverance tobacco control advocates can overcome tobacco industry opposition in the Legislative Assembly and Executive Branch. This determined approach has positioned Costa Rica to become a regional leader in tobacco control. PMID:26879509

  7. Diff-seq: A high throughput sequencing-based mismatch detection assay for DNA variant enrichment and discovery

    PubMed Central

    Karas, Vlad O; Sinnott-Armstrong, Nicholas A; Varghese, Vici; Shafer, Robert W; Greenleaf, William J; Sherlock, Gavin

    2018-01-01

    Abstract Much of the within species genetic variation is in the form of single nucleotide polymorphisms (SNPs), typically detected by whole genome sequencing (WGS) or microarray-based technologies. However, WGS produces mostly uninformative reads that perfectly match the reference, while microarrays require genome-specific reagents. We have developed Diff-seq, a sequencing-based mismatch detection assay for SNP discovery without the requirement for specialized nucleic-acid reagents. Diff-seq leverages the Surveyor endonuclease to cleave mismatched DNA molecules that are generated after cross-annealing of a complex pool of DNA fragments. Sequencing libraries enriched for Surveyor-cleaved molecules result in increased coverage at the variant sites. Diff-seq detected all mismatches present in an initial test substrate, with specific enrichment dependent on the identity and context of the variation. Application to viral sequences resulted in increased observation of variant alleles in a biologically relevant context. Diff-Seq has the potential to increase the sensitivity and efficiency of high-throughput sequencing in the detection of variation. PMID:29361139

  8. 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…

  9. 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.

  10. Influence of hydrophobic mismatch on the catalytic activity of Escherichia coli GlpG rhomboid protease

    PubMed Central

    Foo, Alexander C Y; Harvey, Brandon G R; Metz, Jeff J; Goto, Natalie K

    2015-01-01

    Rhomboids comprise a broad family of intramembrane serine proteases that are found in a wide range of organisms and participate in a diverse array of biological processes. High-resolution structures of the catalytic transmembrane domain of the Escherichia coli GlpG rhomboid have provided numerous insights that help explain how hydrolytic cleavage can be achieved below the membrane surface. Key to this are observations that GlpG hydrophobic domain dimensions may not be sufficient to completely span the native lipid bilayer. This formed the basis for a model where hydrophobic mismatch Induces thinning of the local membrane environment to promote access to transmembrane substrates. However, hydrophobic mismatch also has the potential to alter the functional properties of the rhomboid, a possibility we explore in the current work. For this purpose, we purified the catalytic transmembrane domain of GlpG into phosphocholine or maltoside detergent micelles of varying alkyl chain lengths, and assessed proteolytic function with a model water-soluble substrate. Catalytic turnover numbers were found to depend on detergent alkyl chain length, with saturated chains containing 10–12 carbon atoms supporting maximal activity. Similar results were obtained in phospholipid bicelles, with no proteolytic activity being detected in longer-chain lipids. Although differences in thermal stability and GlpG oligomerization could not explain these activity differences, circular dichroism spectra suggest that mismatch gives rise to a small change in structure. Overall, these results demonstrate that hydrophobic mismatch can exert an inhibitory effect on rhomboid activity, with the potential for changes in local membrane environment to regulate activity in vivo. PMID:25307614

  11. Symptom-Hemodynamic Mismatch and Heart Failure Event Risk

    PubMed Central

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

    2014-01-01

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

  12. Control of DNA hybridization by photoswitchable molecular glue.

    PubMed

    Dohno, Chikara; Nakatani, Kazuhiko

    2011-12-01

    Hybridization of DNA is one of the most intriguing events in molecular recognition and is essential for living matter to inherit life beyond generations. In addition to the function of DNA as genetic material, DNA hybridization is a key to control the function of DNA-based materials in nanoscience. Since the hybridization of two single stranded DNAs is a thermodynamically favorable process, dissociation of the once formed DNA duplex is normally unattainable under isothermal conditions. As the progress of DNA-based nanoscience, methodology to control the DNA hybridization process has become increasingly important. Besides many reports using the chemically modified DNA for the regulation of hybridization, we focused our attention on the use of a small ligand as the molecular glue for the DNA. In 2001, we reported the first designed molecule that strongly and specifically bound to the mismatched base pairs in double stranded DNA. Further studies on the mismatch binding molecules provided us a key discovery of a novel mode of the binding of a mismatch binding ligand that induced the base flipping. With these findings we proposed the concept of molecular glue for DNA for the unidirectional control of DNA hybridization and, eventually photoswitchable molecular glue for DNA, which enabled the bidirectional control of hybridization under photoirradiation. In this tutorial review, we describe in detail how we integrated the mismatch binding ligand into photoswitchable molecular glue for DNA, and the application and perspective in DNA-based nanoscience.

  13. 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.

  14. Influence of the Strength Mismatch of a Narrow Gap Welded Joint of SA508 on the Plastic η Factor

    NASA Astrophysics Data System (ADS)

    Koo, J. M.; Huh, Y.; Seok, C. S.

    2012-11-01

    In this article, the influence of the strength mismatch of a narrow gap welded joint of SA508 on the η factor was evaluated. The η factor is the principal parameter that determines the plastic portion of the J-integral. The specimens for tensile and hardness tests were collected from piping with narrow gap welding and the stress-strain curve and hardness were obtained from those. From these results, the Ramberg-Osgood (R-O) constant was obtained. Also, the finite element analysis was performed with variations in the strength mismatch and the weld width. The η factor equation considering the strength mismatch and the weld width of a narrow gap welded joint was suggested.

  15. Spontaneous vaginal delivery in the birth-chair versus in the conventional dorsal position: a matched controlled comparison.

    PubMed

    Scholz, H S; Benedicic, C; Arikan, M G; Haas, J; Petru, E

    2001-09-17

    The aim of the study was to assess the effect of a birth-chair on obstetric outcome. We reviewed the hospital records of 220 consecutive pregnant women who gave birth on a birth-chair at our institution. The control group consisted of 440 pregnant women who preceded and followed the index cases and who had spontaneous vaginal deliveries in the conventional dorsal supine position. The controls were matched for parity and for the attending mid-wife. Patients who delivered in the birth-chair had significantly lower rates of episiotomy and manual separation of the placenta. The umbilical blood cord pH was significantly higher in neonates of the birth-chair group. The duration of labour, rate of perineal and vaginal injury, Apgar scores and rate of admission to a neonatal intermediate care unit were not influenced by the mode of delivery. Our data support previous studies that a birth-chair delivery may be a safe alternative to conventional delivery in the supine position.

  16. 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

  17. 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

  18. 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

  19. 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.

  20. Temperature-induced mismatches between consumption and metabolism reduce consumer fitness.

    PubMed

    Lemoine, Nathan P; Burkepile, Deron E

    2012-11-01

    As physiological processes of ectotherms are coupled to environmental temperature, climate change will likely alter their fundamental biological rates, including metabolism, consumption, growth, and reproduction. Here we combine the metabolic theory of ecology (MTE) with metabolism and consumption measurements of a model organism, the urchin Lytechinus variegatus, to test how climate change will affect consumer fitness. Unexpectedly, we found that metabolism and consumption exhibit different scaling relationships with temperature and are mismatched at high temperatures. This led to a dramatic reduction in ingestion efficiency and potentially in consumer fitness. Using metaanalysis, we showed that such temperature-driven mismatches between consumption and metabolism are common across taxa and frequently lead to reduced consumer fitness. Our empirical and synthetic analyses identify a mechanism by which climate change reduces the fitness of ectotherm consumers that may be applied to a broad array of taxonomic groups. Moreover, we showed that the assumptions of MTE do not hold at temperatures near the upper range of species' thermal tolerances for a wide array of taxa. Models using MTE to predict the effects of climate change on consumer-resource dynamics may therefore be underestimating the consequences of rising temperatures on population and community dynamics.

  1. Phosphorylation-dependent signaling controls degradation of DNA mismatch repair protein PMS2.

    PubMed

    Hinrichsen, Inga; Weßbecher, Isabel M; Huhn, Meik; Passmann, Sandra; Zeuzem, Stefan; Plotz, Guido; Biondi, Ricardo M; Brieger, Angela

    2017-12-01

    MutLα, a heterodimer consisting of MLH1 and PMS2, plays an important role in DNA mismatch repair and has been shown to be additionally involved in several other important cellular mechanisms. Previous work indicated that AKT could modulate PMS2 stability by phosphorylation. Still, the mechanisms of regulation of MutLα remain unclear. The stability of MutLα subunits was investigated by transiently overexpression of wild type and mutant forms of MLH1 and PMS2 using immunoblotting for measuring the protein levels after treatment. We found that treatment with the cell-permeable serine/threonine phosphatase inhibitor, Calyculin, leads to degradation of PMS2 when MLH1 or its C-terminal domain is missing or if amino acids of MLH1 essential for PMS2 interaction are mutated. In addition, we discovered that the C-terminal tail of PMS2 is relevant for this Calyculin-dependent degradation. A direct involvement of AKT, which was previously described to be responsible for PMS2 degradation, could not be detected. The multi-kinase inhibitor Sorafenib, in contrast, was able to avoid the degradation of PMS2 which postulates that cellular phosphorylation is involved in this process. Together, we show that pharmacologically induced phosphorylation by Calyculin can induce the selective proteasome-dependent degradation of PMS2 but not of MLH1 and that the PMS2 degradation could be blocked by Sorafenib treatment. Curiously, the C-terminal Lynch Syndrome-variants MLH1 L749P and MLH1 Y750X make PMS2 prone to Calyculin induced degradation. Therefore, we conclude that the specific degradation of PMS2 may represent a new mechanism to regulate MutLα. © 2017 Wiley Periodicals, Inc.

  2. 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.

  3. Dependence of the cytotoxicity of DNA-damaging agents on the mismatch repair status of human cells.

    PubMed

    Papouli, Efterpi; Cejka, Petr; Jiricny, Josef

    2004-05-15

    Mismatch repair (MMR) deficiency was reported to increase resistance of mammalian cells to killing by several genotoxic substances. However, although MMR-deficient cells are approximately 100-fold more resistant to killing by S(N)1 type methylating agents than MMR-proficient controls, the sensitivity differences reported for the other agents were typically <2-fold. To test whether these differences were linked to factors other than MMR status, we studied the cytotoxicities of mitomycin C, chloroethylcyclohexyl nitrosourea, melphalan, psoralen-UVA, etoposide, camptothecin, ionizing radiation, and cis-dichlorodiaminoplatinum (cisplatin) in a strictly isogenic system. We now report that MMR deficiency reproducibly desensitized cells solely to cisplatin.

  4. 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.

  5. Large lattice mismatch effects on the epitaxial growth and magnetic properties of FePt films

    NASA Astrophysics Data System (ADS)

    Deng, Jinyu; Dong, Kaifeng; Yang, Ping; Peng, Yingguo; Ju, Ganping; Hu, Jiangfeng; Chow, Gan Moog; Chen, Jingsheng

    2018-01-01

    Heteroepitaxial film growth is crucial for magnetic and electronic devices. In this work, we reported the effects of the large lattice mismatch and film thickness on the epitaxial growth and magnetic properties of FePt films on ZrxTi1-xN (0 0 1) intermediate layer. FePt films with different thickness were deposited on ZrTiN intermediate layers with various doping concentration of TiN in ZrN. The increase in doping concentration of TiN caused a decrease in the lattice parameters of ZrTiN intermediate layer. It was found that (0 0 1) epitaxy of FePt 10 nm films was only achieved on ZrTiN intermediate layer when the TiN composition was ≥25 vol%, while (0 0 1) texture of 5 nm films was achieved on ZrTiN intermediate layer with a minimum of 50 vol% TiN composition. The in-plane lattice constants of FePt and Zr0.70Ti0.30N (25 vol% TiN) were 3.870 Å and 4.476 Å, respectively, which resulted in a lattice mismatch as large as 15.7%. These large lattice mismatch heterostructures adopted 7/6 domain matching epitaxy. The magneto-crystalline anisotropy of FePt films was improved with the increase in lattice mismatch. Intrinsic magnetic properties were extrapolated for FePt (30 nm)/Zr0.70Ti0.30N (30 nm)/TaN (30 nm)/MgO, and the Ms(0 K) and K1(0 K) were 1042 emu/cc and 5.10 × 107 erg/cc, respectively, which is comparable to that of bulk L10 FePt.

  6. Dynamics of spontaneous flipping of a mismatched base in DNA duplex.

    PubMed

    Yin, Yandong; Yang, Lijiang; Zheng, Guanqun; Gu, Chan; Yi, Chengqi; He, Chuan; Gao, Yi Qin; Zhao, Xin Sheng

    2014-06-03

    DNA base flipping is a fundamental theme in DNA biophysics. The dynamics for a B-DNA base to spontaneously flip out of the double helix has significant implications in various DNA-protein interactions but are still poorly understood. The spontaneous base-flipping rate obtained previously via the imino proton exchange assay is most likely the rate of base wobbling instead of flipping. Using the diffusion-decelerated fluorescence correlation spectroscopy together with molecular dynamics simulations, we show that a base of a single mismatched base pair (T-G, T-T, or T-C) in a double-stranded DNA can spontaneously flip out of the DNA duplex. The extrahelical lifetimes are on the order of 10 ms, whereas the intrahelical lifetimes range from 0.3 to 20 s depending on the stability of the base pairs. These findings provide detailed understanding on the dynamics of DNA base flipping and lay down foundation to fully understand how exactly the repair proteins search and locate the target mismatched base among a vast excess of matched DNA bases.

  7. Intensive glucose control versus conventional glucose control for type 1 diabetes mellitus.

    PubMed

    Fullerton, Birgit; Jeitler, Klaus; Seitz, Mirjam; Horvath, Karl; Berghold, Andrea; Siebenhofer, Andrea

    2014-02-14

    Clinical guidelines differ regarding their recommended blood glucose targets for patients with type 1 diabetes and recent studies on patients with type 2 diabetes suggest that aiming at very low targets can increase the risk of mortality. To assess the effects of intensive versus conventional glycaemic targets in patients with type 1 diabetes in terms of long-term complications and determine whether very low, near normoglycaemic values are of additional benefit. A systematic literature search was performed in the databases The Cochrane Library, MEDLINE and EMBASE. The date of the last search was December 2012 for all databases. We included all randomised controlled trials (RCTs) that had defined different glycaemic targets in the treatment arms, studied patients with type 1 diabetes, and had a follow-up duration of at least one year. Two review authors independently extracted data, assessed studies for risk of bias, with differences resolved by consensus. Overall study quality was evaluated by the 'Grading of Recommendations Assessment, Development, and Evaluation' (GRADE) system. Random-effects models were used for the main analyses and the results are presented as risk ratios (RR) with 95% confidence intervals (CI) for dichotomous outcomes. We identified 12 trials that fulfilled the inclusion criteria, including a total of 2230 patients. The patient populations varied widely across studies with one study only including children, one study only including patients after a kidney transplant, one study with newly diagnosed adult patients, and several studies where patients had retinopathy or microalbuminuria at baseline. The mean follow-up duration across studies varied between one and 6.5 years. The majority of the studies were carried out in the 1980s and all trials took place in Europe or North America. Due to the nature of the intervention, none of the studies could be carried out in a blinded fashion so that the risk of performance bias, especially for

  8. Mechanism of mismatch recognition revealed by human MutS[beta] bound to unpaired DNA loops

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

    Gupta, Shikha; Gellert, Martin; Yang, Wei

    2012-04-17

    DNA mismatch repair corrects replication errors, thus reducing mutation rates and microsatellite instability. Genetic defects in this pathway cause Lynch syndrome and various cancers in humans. Binding of a mispaired or unpaired base by bacterial MutS and eukaryotic MutS{alpha} is well characterized. We report here crystal structures of human MutS{beta} in complex with DNA containing insertion-deletion loops (IDL) of two, three, four or six unpaired nucleotides. In contrast to eukaryotic MutS{alpha} and bacterial MutS, which bind the base of a mismatched nucleotide, MutS{beta} binds three phosphates in an IDL. DNA is severely bent at the IDL; unpaired bases are flippedmore » out into the major groove and partially exposed to solvent. A normal downstream base pair can become unpaired; a single unpaired base can thereby be converted to an IDL of two nucleotides and recognized by MutS{beta}. The C-terminal dimerization domains form an integral part of the MutS structure and coordinate asymmetrical ATP hydrolysis by Msh2 and Msh3 with mismatch binding to signal for repair.« less

  9. Global health, equity and the WHO Framework Convention on Tobacco Control

    PubMed Central

    Collin, Jeff

    2015-01-01

    The report of the WHO Commission on Social Determinants of Health demonstrates the renewed salience of health inequalities within the international health policy agenda. The tobacco pandemic is characterized by an escalating burden of death and disease that is increasingly being borne by developing countries. Efforts to promote global health equity must therefore prioritize reductions in tobacco consumption. The WHO Framework Convention on Tobacco Control (FCTC) offers a remarkable opportunity to address the health inequalities associated with tobacco use, and represents an important innovation within global governance. But the FCTC’s failure to adequately address the health impacts of trade liberalization highlights the difficulties of ensuring policy coherence across international health, development and economic policies. Recognition of such limitations is important both to inform the further development of the FCTC and to ensure that appropriate lessons are drawn for future initiatives. PMID:20595357

  10. Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial

    PubMed Central

    Nutting, Christopher M; Morden, James P; Harrington, Kevin J; Urbano, Teresa Guerrero; Bhide, Shreerang A; Clark, Catharine; Miles, Elizabeth A; Miah, Aisha B; Newbold, Kate; Tanay, MaryAnne; Adab, Fawzi; Jefferies, Sarah J; Scrase, Christopher; Yap, Beng K; A'Hern, Roger P; Sydenham, Mark A; Emson, Marie; Hall, Emma

    2011-01-01

    Summary Background Xerostomia is the most common late side-effect of radiotherapy to the head and neck. Compared with conventional radiotherapy, intensity-modulated radiotherapy (IMRT) can reduce irradiation of the parotid glands. We assessed the hypothesis that parotid-sparing IMRT reduces the incidence of severe xerostomia. Methods We undertook a randomised controlled trial between Jan 21, 2003, and Dec 7, 2007, that compared conventional radiotherapy (control) with parotid-sparing IMRT. We randomly assigned patients with histologically confirmed pharyngeal squamous-cell carcinoma (T1–4, N0–3, M0) at six UK radiotherapy centres between the two radiotherapy techniques (1:1 ratio). A dose of 60 or 65 Gy was prescribed in 30 daily fractions given Monday to Friday. Treatment was not masked. Randomisation was by computer-generated permuted blocks and was stratified by centre and tumour site. Our primary endpoint was the proportion of patients with grade 2 or worse xerostomia at 12 months, as assessed by the Late Effects of Normal Tissue (LENT SOMA) scale. Analyses were done on an intention-to-treat basis, with all patients who had assessments included. Long-term follow-up of patients is ongoing. This study is registered with the International Standard Randomised Controlled Trial register, number ISRCTN48243537. Findings 47 patients were assigned to each treatment arm. Median follow-up was 44·0 months (IQR 30·0–59·7). Six patients from each group died before 12 months and seven patients from the conventional radiotherapy and two from the IMRT group were not assessed at 12 months. At 12 months xerostomia side-effects were reported in 73 of 82 alive patients; grade 2 or worse xerostomia at 12 months was significantly lower in the IMRT group than in the conventional radiotherapy group (25 [74%; 95% CI 56–87] of 34 patients given conventional radiotherapy vs 15 [38%; 23–55] of 39 given IMRT, p=0·0027). The only recorded acute adverse event of grade 2 or worse

  11. 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.

  12. Labour Market Mismatch among UK Graduates: An Analysis Using REFLEX Data

    ERIC Educational Resources Information Center

    McGuinness, Seamus; Sloane, Peter J.

    2011-01-01

    There is much disagreement in the literature over the extent to which graduates are mismatched in the labour market and the reasons for this. In this paper we utilise the Flexible Professional in the Knowledge Society (REFLEX) data set to cast light on these issues, based on data for UK graduates. We find substantial pay penalties for…

  13. 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.

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

    PubMed

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

    2018-03-02

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

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

    PubMed Central

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

    2018-01-01

    Structural human leukocyte antigen (HLA) matching at the eplet level can be identified by HLAMatchmaker, which requires the entry of four-digit alleles. The aim of this study was to evaluate the agreement between eplet mismatches calculated by serological and two-digit typing methods compared to high-resolution four-digit typing. In a cohort of 264 donor/recipient pairs, the evaluation of measurement error was assessed using intra-class correlation to confirm the absolute agreement between the number of eplet mismatches at class I (HLA-A, -B, C) and II loci (HLA-DQ and -DR) calculated using serological or two-digit molecular typing compared to four-digit molecular typing methods. The proportion of donor/recipient pairs with a difference of >5 eplet mismatches between the HLA typing methods was also determined. Intra-class correlation coefficients between serological and four-digit molecular typing methods were 0.969 (95% confidence intervals [95% CI] 0.960–0.975) and 0.926 (95% CI 0.899–0.944), respectively; and 0.995 (95% CI 0.994–0.996) and 0.993 (95% CI 0.991–0.995), respectively between two-digit and four-digit molecular typing methods. The proportion of donor/recipient pairs with a difference of >5 eplet mismatches at class I and II loci was 4% and 16% for serological versus four-digit molecular typing methods, and 0% and 2% for two-digit versus four-digit molecular typing methods, respectively. In this small predominantly Caucasian population, compared with serology, there is a high level of agreement in the number of eplet mismatches calculated using two-compared to four-digit molecular HLA-typing methods, suggesting that two-digit typing may be sufficient in determining eplet mismatch load in kidney transplantation. PMID:29568344

  16. Control of linear uncertain systems utilizing mismatched state observers

    NASA Technical Reports Server (NTRS)

    Goldstein, B.

    1972-01-01

    The control of linear continuous dynamical systems is investigated as a problem of limited state feedback control. The equations which describe the structure of an observer are developed constrained to time-invarient systems. The optimal control problem is formulated, accounting for the uncertainty in the design parameters. Expressions for bounds on closed loop stability are also developed. The results indicate that very little uncertainty may be tolerated before divergence occurs in the recursive computation algorithms, and the derived stability bound yields extremely conservative estimates of regions of allowable parameter variations.

  17. 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

  18. Use of capecitabine to prevent acute renal allograft rejection in dog erythrocyte antigen-mismatched mongrel dogs.

    PubMed

    Milovancev, Milan; Schmiedt, Chad W; Bentley, Ellison; Schwab, Michelle; Dubielzig, Richard R; Gendron-Fitzpatrick, Annette P; McAnulty, Jonathan F

    2007-01-01

    To assess efficacy and toxicity of a capecitabine (CAP)-based regimen for preventing rejection of renal allografts in dog erythrocyte antigen (DEA)-mismatched mongrel dogs. Prospective, pilot study. Eight healthy, unrelated, DEA mismatched, adult mongrel dogs. All dogs received CAP, starting at 50 mg/m2 PO b.i.d. 4 days preoperatively, increasing to 200 mg/m2 PO b.i.d. by the day of surgery. All dogs received cyclosporine-A (CsA) and prednisolone starting 2 days preoperatively. Standard heterotopic renal transplantation with native nephrectomy was performed. After 90 days, surviving dogs were euthanatized and histopathologic examination was performed. Two of 8 dogs developed acute neurotoxicity leading to death or euthanasia within 5 days of surgery. For the 6 remaining dogs, there were no statistically significant changes in complete blood count or serum biochemical values. No opportunistic infections developed during the study period. Five of 6 dogs had no to minimal evidence of graft rejection. Two of 6 dogs developed superficial and pigmentary keratitis. Significant histopathologic findings in all dogs included mild lymphoplasmacytic gastroenteritis, steroid hepatopathy, and corneal epithelial thinning. One dog had moderate interstitial nephritis and pyelitis. In this experimental model, a CAP-CsA-prednisolone immunosuppressive regimen was effective in preventing rejection of allografts in DEA-mismatched dogs. Severe, unpredictable neurotoxicity and variable ocular toxicity significantly limit clinical applications at this time. A CAP-CsA-prednisolone protocol is an effective, oral immunosuppressive regimen for prevention of allograft rejection in DEA-mismatched mongrel dogs. For clinical application, identification of patients susceptible to toxic side effects would be necessary.

  19. Comparison between microprocessor-controlled ankle/foot and conventional prosthetic feet during stair negotiation in people with unilateral transtibial amputation.

    PubMed

    Agrawal, Vibhor; Gailey, Robert S; Gaunaurd, Ignacio A; O'Toole, Christopher; Finnieston, Adam A

    2013-01-01

    Contrary to stance-phase dorsiflexion of conventional prosthetic feet, the microprocessor-controlled Proprio foot permits swing-phase dorsiflexion on stairs. The purpose of this study was to compare Symmetry in External Work (SEW) between a microprocessor-controlled foot and conventional prosthetic feet in two groups with unilateral transtibial amputation (Medicare Functional Classification Levels K-Level-2 and K-Level-3) during stair ascent and descent. Ten subjects were evaluated while wearing three conventional prosthetic feet- solid ankle cushion heel (SACH), stationary attachment flexible endoskeleton (SAFE), and Talux-and the Proprio foot using a study socket and were given a 10- to 14-day accommodation period with each foot. Ground reaction forces were collected using F-scan sensors during stair ascent and descent. The SEW between the intact and amputated limbs was calculated for each foot. During stair ascent, the Proprio foot resulted in a higher interlimb symmetry than conventional prosthetic feet, with significant differences between the Pro prio and SACH/SAFE feet. The swing-phase dorsiflexion appeared to promote greater interlimb symmetry because it facilitated forward motion of the body, resulting in a heel-to-toe center of pressure trajectory. During stair descent, all feet had low symmetry without significant differences between feet. The movement strategy used when descending stairs, which is to roll over the edge of a step, had a greater influence on symmetry than the dorsiflexion features of prosthetic feet.

  20. 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.

  1. Differential effects of the mismatch repair genes MSH2 and MSH3 on homeologous recombination in Saccharomyces cerevisiae.

    PubMed

    Selva, E M; Maderazo, A B; Lahue, R S

    1997-12-01

    The products of the yeast mismatch repair genes MSH2 and MSH3 participate in the inhibition of genetic recombination between homeologous (divergent) DNA sequences. In strains deficient for these genes, homeologous recombination rates between repeated elements are elevated due to the loss of this inhibition. In this study, the effects of these mutations were further analyzed by quantitation of mitotic homeologous recombinants as crossovers, gene conversions or exceptional events in wild-type, msh2, msh3 and msh2 msh3 mutant strains. When homeologous sequences were present as a direct repeat in one orientation, crossovers and gene conversions were elevated in msh2, msh3 and msh2 msh3 strains. The increases were greater in the msh2 msh3 double mutant than in either single mutant. When the order of the homeologous sequences was reversed, the msh2 mutation again yielded increased rates of crossovers and gene conversions. However, in an msh3 strain, gene conversions occurred at higher levels but interchromosomal crossovers were not increased and intrachromosomal crossovers were reduced relative to wild type. The msh2 msh3 double mutant behaved like the msh2 single mutant in this orientation. Control strains harboring homologous duplications were largely but not entirely unaffected in mutant strains, suggesting specificity for the mismatched intermediates of homeologous recombination. In all strains, very few (< 10%) recombinants could be attributed to exceptional events. These results suggest that MSH2 and MSH3 can function differentially to control homeologous exchanges.

  2. Education-Job Mismatch among Canadian University Graduates: Implications for Employers and Educators.

    ERIC Educational Resources Information Center

    Redpath, Lindsay

    1994-01-01

    A recent study of education-job mismatch among 487 Canadian university graduates are analyzed, and the implications in the debate over shortages of skilled employees are considered. It is suggested that the perceived skills shortage is rather a problem of inadequate skill utilization, implying greater employer responsibility. (MSE)

  3. 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.

  4. Helicopter pilots' views of air traffic controller responsibilities: a mismatch.

    PubMed

    Martin, Daniel; Nixon, Jim

    2018-02-21

    Controllers and pilots must work together to ensure safe and efficient helicopter flight within the London control zone. Subjective ratings of pilot perception of controller responsibility for five key flight tasks were obtained from thirty helicopter pilots. Three types of airspace were investigated. Results indicate that there is variation in pilot understanding of controller responsibility compared to the formal regulations that define controller responsibility. Significant differences in the perception of controller responsibility were found for the task of aircraft separation in class D airspace and along helicopter routes. Analysis of the patterns of response suggests that task type rather than the airspace type may be the key factor. Results are framed using the concept of a shared mental model. This research demonstrates that pilots flying in complex London airspace have an expectation of controller responsibility for certain flight tasks, in certain airspace types that is not supported by aviation regulation. Practitioner Summary: The responsibility for tasks during flight varies according to the flight rules used and airspace type. Helicopter pilots may attribute responsibility to controllers for tasks when controllers have no responsibility as defined by regulation. This variation between pilot perceptions of controller responsibility could affect safety within the London control zone.

  5. Time efficiency, difficulty, and operator's preference comparing digital and conventional implant impressions: a randomized controlled trial.

    PubMed

    Joda, Tim; Lenherr, Patrik; Dedem, Philipp; Kovaltschuk, Irina; Bragger, Urs; Zitzmann, Nicola U

    2017-10-01

    The aim of this randomized controlled trial was to analyze implant impression techniques applying intraoral scanning (IOS) and the conventional method according to time efficiency, difficulty, and operator's preference. One hundred participants (n = 100) with diverse levels of dental experience were included and randomly assigned to Group A performing digital scanning (TRIOS Pod) first or Group B conducting conventional impression (open tray with elastomer) first, while the second method was performed consecutively. A customized maxillary model with a bone-level-type implant in the right canine position (FDI-position 13) was mounted on a phantom training unit realizing a standardized situation for all participants. Outcome parameter was time efficiency, and potential influence of clinical experience, operator's perception of level of difficulty, applicability of each method, and subjective preferences were analyzed with Wilcoxon -Mann-Whitney and Kruskal-Wallis tests. Mean total work time varied between 5.01 ± 1.56 min (students) and 4.53 ± 1.34 min (dentists) for IOS, and between 12.03 ± 2.00 min (students) and 10.09 ± 1.15 min (dentists) for conventional impressions with significant differences between the two methods. Neither assignment to Group A or B, nor gender nor number of impression-taking procedures did influence working time. Difficulty and applicability of IOS was perceived more favorable compared to conventional impressions, and effectiveness of IOS was rated better by the majority of students (88%) and dentists (64%). While 76% of the students preferred IOS, 48% of the dentists were favoring conventional impressions, and 26% each IOS and either technique. For single-implant sites, the quadrant-like intraoral scanning (IOS) was more time efficient than the conventional full-arch impression technique in a phantom head simulating standardized optimal conditions. A high level of acceptance for IOS was observed among students and

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

    PubMed

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

    2017-07-01

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

  7. Epistatic role of base excision repair and mismatch repair pathways in mediating cisplatin cytotoxicity

    PubMed Central

    Kothandapani, Anbarasi; Sawant, Akshada; Dangeti, Venkata Srinivas Mohan Nimai; Sobol, Robert W.; Patrick, Steve M.

    2013-01-01

    Base excision repair (BER) and mismatch repair (MMR) pathways play an important role in modulating cis-Diamminedichloroplatinum (II) (cisplatin) cytotoxicity. In this article, we identified a novel mechanistic role of both BER and MMR pathways in mediating cellular responses to cisplatin treatment. Cells defective in BER or MMR display a cisplatin-resistant phenotype. Targeting both BER and MMR pathways resulted in no additional resistance to cisplatin, suggesting that BER and MMR play epistatic roles in mediating cisplatin cytotoxicity. Using a DNA Polymerase β (Polβ) variant deficient in polymerase activity (D256A), we demonstrate that MMR acts downstream of BER and is dependent on the polymerase activity of Polβ in mediating cisplatin cytotoxicity. MSH2 preferentially binds a cisplatin interstrand cross-link (ICL) DNA substrate containing a mismatch compared with a cisplatin ICL substrate without a mismatch, suggesting a novel mutagenic role of Polβ in activating MMR in response to cisplatin. Collectively, these results provide the first mechanistic model for BER and MMR functioning within the same pathway to mediate cisplatin sensitivity via non-productive ICL processing. In this model, MMR participation in non-productive cisplatin ICL processing is downstream of BER processing and dependent on Polβ misincorporation at cisplatin ICL sites, which results in persistent cisplatin ICLs and sensitivity to cisplatin. PMID:23761438

  8. 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

  9. 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.

  10. Role of the mismatch repair gene, Msh6, in suppressing genome instability and radiation-induced mutations

    PubMed Central

    Barrera-Oro, Julio; Liu, Tzu-Yang; Gorden, Erin; Kucherlapati, Raju; Shao, Changshun; Tischfield, Jay A

    2008-01-01

    Mismatch repair (MMR) is critical for preserving genomic integrity. Failure of this system can accelerate somatic mutation and increase the risk of developing cancer. MSH6, in complex with MSH2, is the MMR protein that mediates DNA repair through the recognition of 1- and 2-bp mismatches. To evaluate the effects of MSH6 deficiency on genomic stability we compared the frequency of in vivo loss of heterozygosity (LOH) between MSH6-proficient and deficient, 129S2 x C57BL/6 F1 hybrid mice that were heterozygous for our reporter gene Aprt. We recovered mutant cells that had functionally lost APRT protein activity and categorized the spectrum of mutations responsible for the LOH events. We also measured the mutant frequency at the X-linked gene, Hprt, as a second reporter for point mutation. In Msh6−/−Aprt+/− mice, mutation frequency at Aprt was elevated in both T cells and fibroblasts by 2.5-fold and 5.7-fold, respectively, over Msh6+/+Aprt+/− littermate controls. While a modest increase in mitotic recombination (MR) was observed in MSH6-deficient fibroblasts compared to wild type controls, point mutation was the predominant mechanism leading to APRT deficiency in both cell types. Base substitution, consisting of multiple types of transitions, accounted for all of the point mutations identified within the Aprt coding region. We also assessed the role of MSH6 in preventing mutations caused by a common environmental mutagen, ionizing radiation (IR). In Msh6−/−Aprt+/− mice, 4 Gy of X-irradiation induced a significant increase in point mutations at both Aprt and Hprt in T cells, but not in fibroblasts. These findings indicate that MutSα reduces spontaneous and IR-induced mutation in a cell-type dependant manner. PMID:18538799

  11. 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 N100

  12. 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.

  13. Affirmative Action in Higher Education in India: Targeting, Catch Up, and Mismatch

    ERIC Educational Resources Information Center

    Frisancho, Veronica; Krishna, Kala

    2016-01-01

    Using detailed data on the 2008 graduating class from an elite engineering institution in India, we evaluate the impact of affirmative action policies in higher education focusing on three issues: targeting, catch up, and mismatch. We find that admission preferences effectively target minority students who are poorer than average displaced…

  14. Geographic Skills Mismatch, Job Search, and Race. Discussion Paper No. 1288-04

    ERIC Educational Resources Information Center

    Stoll, Michael A.

    2004-01-01

    This paper examines whether a geographic skills mismatch exists between the location of less-educated minorities, in particular African Americans, and high-skill job concentrations, and if so, whether it contributes to the relatively poor employment outcomes of this group. It explores these questions by examining data on the recent geographic…

  15. Strategies for the control of Rhipicephalus microplus ticks in a world of conventional acaricide and macrocyclic lactone resistance.

    PubMed

    Rodriguez-Vivas, Roger I; Jonsson, Nicholas N; Bhushan, Chandra

    2018-01-01

    Infestations with the cattle tick, Rhipicephalus microplus, constitute the most important ectoparasite problem for cattle production in tropical and subtropical regions worldwide, resulting in major economic losses. The control of R. microplus is mostly based on the use of conventional acaricides and macrocyclic lactones. However, the intensive use of such compounds has resulted in tick populations that exhibit resistance to all major acaricide chemical classes. Consequently, there is a need for the development of alternative approaches, possibly including the use of animal husbandry practices, synergized pesticides, rotation of acaricides, pesticide mixture formulations, manual removal of ticks, selection for host resistance, nutritional management, release of sterile male hybrids, environmental management, plant species that are unfavourable to ticks, pasture management, plant extracts, essential oils and vaccination. Integrated tick management consists of the systematic combination of at least two control technologies aiming to reduce selection pressure in favour of acaricide-resistant individuals, while maintaining adequate levels of animal production. The purpose of this paper is to present a current review on conventional acaricide and macrocyclic lactone resistance for better understanding and control of resistant ticks with particular emphasis on R. microplus on cattle.

  16. Ferrocene conjugated oligonucleotide for electrochemical detection of DNA base mismatch.

    PubMed

    Hasegawa, Yusuke; Takada, Tadao; Nakamura, Mitsunobu; Yamana, Kazushige

    2017-08-01

    We describe the synthesis, binding, and electrochemical properties of ferrocene-conjugated oligonucleotides (Fc-oligos). The key step for the preparation of Fc-oligos contains the coupling of vinylferrocene to 5-iododeoxyuridine via Heck reaction. The Fc-conjugated deoxyuridine phosphoramidite was used in the Fc-oligonucleotide synthesis. We show that thiol-modified Fc-oligos deposited onto gold electrodes possess potential ability in electrochemical detection of DNA base mismatch. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. IFN-γ Blocks CD4+CD25+ Tregs and Abolishes Immune Privilege of Minor Histocompatibility Mismatched Corneal Allografts

    PubMed Central

    Cunnusamy, Khrishen; Niederkorn, Jerry Y.

    2014-01-01

    Th1 CD4+ cells are believed to be the primary mediators of corneal allograft rejection. However, rejection of fully allogeneic C57BL/6 corneal allografts soared from 50% to 90% in both INF-γ−/− and anti-IFN-γ-treated BALB/c mice. In contrast, similar deficits in IFN-γ in BALB/c hosts enhanced immune privilege of BALB.B (minor histocompatibility antigen-matched, MHC-mismatched) and NZB (major histocompatibility complex-matched, minor histocompatibility antigen-mismatched) corneal allografts – decreasing rejection from 80% to ~20%. This effect of IFN-γ was independent of CD4+ T cell lineage commitment as both anti-IFN-γ-treated acceptor and rejector mice displayed a Th2 cytokine profile. The presence of IFN-γ prevented the generation of alloantigen-specific CD4+CD25+ Tregs in hosts receiving either MHC only mismatched BALB.B or minor only histocompatibility (minor H)-mismatched NZB corneal allografts. Tregs in these hosts, promoted corneal allograft survival by suppressing Th2 effector cells. By contrast, IFN-γ was necessary for the generation of CD4+CD25+ Tregs that prevented rejection of fully allogeneic C57BL/6 corneal allografts in BALB/c hosts. These findings suggest that MHC-matching in combination with blockade of IFN-γ holds promise as a means of enhancing corneal allograft survival. PMID:24119152

  18. P1088Match and mismatch between opening area and resistance in mild and moderate rheumatic mitral stenosis.

    PubMed

    El-Dosouky, I

    2016-12-01

    Mitral valve resistance (MVR) is a hemodynamic consequence of mitral stenosis but it has no clear threshold and it has a shortage of data to be reliable. is to investigate match and mismatch between opening area and resistance especially in patients with moderate and mild mitral stenosis. This cross section case control study comprised 88 patients with moderate and mild rheumatic mitral stenosis. Transthorathic echocardiographic study estimated: mitral valve area (MVA) both by planimerty (2D) and pressure half time (PHT), mitral valve score (MVS), mean transmitral pressure gradient (MPG), diastolic filling time(DFT), left ventricular out flow tract diameter (LVOTd) and velocity time integral (LVOT vti) , the MVR was calculated as: MPG/aortic flow ratio [(LVOTd) (LVOTvti)/ DFT] in dynes.sec.cm5, NYHA function class of all patients was estimated. We classified our patients into 2 groups, group 1 (51 patients) with matched MVR and group 2 (37 patients) with unmatched MVR (unexpected high MVR in relation to valve area). Patients with moderate mitral stenosis have MVR less than 105 dynes.sec/cm5, while patient with mild mitral stenosis have MVR less than 76 dynes.sec/cm5 this is in the matched group, but there are patients with unmatched higher MVR. Group 2 compared to group 1; had higher NYHA function class (1.4±0.6 vs. 1.2±0.4, P < 0.05), MVS (8.1±1.8 vs 7±0.9, P < 0.05), MPG (11,3±3.7 vs.7.8±2.5 mmHg, P < 0.01) and higher MVR (122.37±29.87 vs. 67.18±20.12 dynes.sec/cm5 , P < 0.01), MVR showed positive correlation with MVS (r=0.5, P < 0.05), Step wise logistic regression analysis showed that MVS is the only independent predictor of the MVR severity in the mismatched (unexpected high) group , so the higher the MVS the higher the expected MVR whatever the MVA is ; (B±SE=6.997±2.826, t=2.476, 95% CI 1.241±12.752 with an odds ratio=0.412, P < 0.05). It would make much more sense to investigate match and mismatch between opening area and resistance in rheumatic

  19. Toward a phenological mismatch in estuarine pelagic food web?

    PubMed

    Chevillot, Xavier; Drouineau, Hilaire; Lambert, Patrick; Carassou, Laure; Sautour, Benoit; Lobry, Jérémy

    2017-01-01

    Alterations of species phenology in response to climate change are now unquestionable. Until now, most studies have reported precocious occurrence of life cycle events as a major phenological response. Desynchronizations of biotic interactions, in particular predator-prey relationships, are however assumed to strongly impact ecosystems' functioning, as formalized by the Match-Mismatch Hypothesis (MMH). Temporal synchronicity between juvenile fish and zooplankton in estuaries is therefore of essential interest since estuaries are major nursery grounds for many commercial fish species. The Gironde estuary (SW France) has suffered significant alterations over the last three decades, including two Abrupt Ecosystem Shifts (AES), and three contrasted intershift periods. The main objective of this study was to depict modifications in fish and zooplankton phenology among inter-shift periods and discuss the potential effects of the resulting mismatches at a community scale. A flexible Bayesian method was used to estimate and compare yearly patterns of species abundance in the estuary among the three pre-defined periods. Results highlighted (1) an earlier peak of zooplankton production and entrance of fish species in the estuary and (2) a decrease in residence time of both groups in the estuary. Such species-specific phenological changes led to changes in temporal overlap between juvenile fish and their zooplanktonic prey. This situation questions the efficiency and potentially the viability of nursery function of the Gironde estuary, with potential implications for coastal marine fisheries of the Bay of Biscay.

  20. Toward a phenological mismatch in estuarine pelagic food web?

    PubMed Central

    Chevillot, Xavier; Drouineau, Hilaire; Lambert, Patrick; Carassou, Laure; Sautour, Benoit; Lobry, Jérémy

    2017-01-01

    Alterations of species phenology in response to climate change are now unquestionable. Until now, most studies have reported precocious occurrence of life cycle events as a major phenological response. Desynchronizations of biotic interactions, in particular predator-prey relationships, are however assumed to strongly impact ecosystems’ functioning, as formalized by the Match-Mismatch Hypothesis (MMH). Temporal synchronicity between juvenile fish and zooplankton in estuaries is therefore of essential interest since estuaries are major nursery grounds for many commercial fish species. The Gironde estuary (SW France) has suffered significant alterations over the last three decades, including two Abrupt Ecosystem Shifts (AES), and three contrasted intershift periods. The main objective of this study was to depict modifications in fish and zooplankton phenology among inter-shift periods and discuss the potential effects of the resulting mismatches at a community scale. A flexible Bayesian method was used to estimate and compare yearly patterns of species abundance in the estuary among the three pre-defined periods. Results highlighted (1) an earlier peak of zooplankton production and entrance of fish species in the estuary and (2) a decrease in residence time of both groups in the estuary. Such species-specific phenological changes led to changes in temporal overlap between juvenile fish and their zooplanktonic prey. This situation questions the efficiency and potentially the viability of nursery function of the Gironde estuary, with potential implications for coastal marine fisheries of the Bay of Biscay. PMID:28355281

  1. 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.

  2. Twisting Right to Left: A…A Mismatch in a CAG Trinucleotide Repeat Overexpansion Provokes Left-Handed Z-DNA Conformation

    PubMed Central

    2015-01-01

    Conformational polymorphism of DNA is a major causative factor behind several incurable trinucleotide repeat expansion disorders that arise from overexpansion of trinucleotide repeats located in coding/non-coding regions of specific genes. Hairpin DNA structures that are formed due to overexpansion of CAG repeat lead to Huntington’s disorder and spinocerebellar ataxias. Nonetheless, DNA hairpin stem structure that generally embraces B-form with canonical base pairs is poorly understood in the context of periodic noncanonical A…A mismatch as found in CAG repeat overexpansion. Molecular dynamics simulations on DNA hairpin stems containing A…A mismatches in a CAG repeat overexpansion show that A…A dictates local Z-form irrespective of starting glycosyl conformation, in sharp contrast to canonical DNA duplex. Transition from B-to-Z is due to the mechanistic effect that originates from its pronounced nonisostericity with flanking canonical base pairs facilitated by base extrusion, backbone and/or base flipping. Based on these structural insights we envisage that such an unusual DNA structure of the CAG hairpin stem may have a role in disease pathogenesis. As this is the first study that delineates the influence of a single A…A mismatch in reversing DNA helicity, it would further have an impact on understanding DNA mismatch repair. PMID:25876062

  3. Instrument Display Visual Angles for Conventional Aircraft and the MQ-9 Ground Control Station

    NASA Technical Reports Server (NTRS)

    Bendrick, Gregg A.; Kamine, Tovy Haber

    2008-01-01

    Aircraft instrument panels should be designed such that primary displays are in optimal viewing location to minimize pilot perception and response time. Human Factors engineers define three zones (i.e. "cones") of visual location: 1) "Easy Eye Movement" (foveal vision); 2) "Maximum Eye Movement" (peripheral vision with saccades), and 3) "Head Movement" (head movement required). Instrument display visual angles were measured to determine how well conventional aircraft (T-34, T-38, F- 15B, F-16XL, F/A-18A, U-2D, ER-2, King Air, G-III, B-52H, DC-10, B747-SCA) and the MQ-9 ground control station (GCS) complied with these standards, and how they compared with each other. Methods: Selected instrument parameters included: attitude, pitch, bank, power, airspeed, altitude, vertical speed, heading, turn rate, slip/skid, AOA, flight path, latitude, longitude, course, bearing, range and time. Vertical and horizontal visual angles for each component were measured from the pilot s eye position in each system. Results: The vertical visual angles of displays in conventional aircraft lay within the cone of "Easy Eye Movement" for all but three of the parameters measured, and almost all of the horizontal visual angles fell within this range. All conventional vertical and horizontal visual angles lay within the cone of "Maximum Eye Movement". However, most instrument vertical visual angles of the MQ-9 GCS lay outside the cone of "Easy Eye Movement", though all were within the cone of "Maximum Eye Movement". All the horizontal visual angles for the MQ-9 GCS were within the cone of "Easy Eye Movement". Discussion: Most instrument displays in conventional aircraft lay within the cone of "Easy Eye Movement", though mission-critical instruments sometimes displaced less important instruments outside this area. Many of the MQ-9 GCS systems lay outside this area. Specific training for MQ-9 pilots may be needed to avoid increased response time and potential error during flight.

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

    NASA Astrophysics Data System (ADS)

    Lee, Chang-Chun; Huang, Pei-Chen

    2018-05-01

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

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

    PubMed

    Fiacconi, Chris M; Milliken, Bruce

    2012-08-01

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

  6. The influence of Cu+ binding to hypoxanthine on stabilization of mismatches involving hypoxanthine and DNA bases: A DFT study.

    PubMed

    Masoodi, Hamid Reza; Bagheri, Sotoodeh; Ghaderi, Zahra

    2018-05-14

    In the present work, the influence of Cu + binding to N3- and N7-positions of hypoxanthine on energetic, geometrical and topological properties of hypoxanthine-guanine, hypoxanthine-adenine, hypoxanthine-cytosine, hypoxanthine-thymine and hypoxanthine-hypoxanthine mismatches is theoretically investigated. The calculations, in gas phase, are performed at B3LYP/6-311++G(3df,3pd) level of theory. Unlike the other mispairs, Cu + binding to N3-position of hypoxanthine causes the proton transfer process from enol form of hypoxanthine to imino forms of adenine and cytosine. This process also occurs in all mismatches having enol form of hypoxanthine when Cu + binds to N7-position of hypoxanthine. The mismatches are stabilized by hydrogen bonds. The influence of Cu + on hydrogen bonds is also examined by atoms in molecules (AIM) and natural bond orbital (NBO) analyses.

  7. Analysis of the functional domains of the mismatch repair homologue Msh1p and its role in mitochondrial genome maintenance.

    PubMed

    Mookerjee, Shona A; Lyon, Hiram D; Sia, Elaine A

    2005-02-01

    Mitochondrial DNA (mtDNA) repair occurs in all eukaryotic organisms and is essential for the maintenance of mitochondrial function. Evidence from both humans and yeast suggests that mismatch repair is one of the pathways that functions in overall mtDNA stability. In the mitochondria of the yeast Saccharomyces cerevisiae, the presence of a homologue to the bacterial MutS mismatch repair protein, MSH1, has long been known to be essential for mitochondrial function. The mechanisms for which it is essential are unclear, however. Here, we analyze the effects of two point mutations, msh1-F105A and msh1-G776D, both predicted to be defective in mismatch repair; and we show that they are both able to maintain partial mitochondrial function. Moreover, there are significant differences in the severity of mitochondrial disruption between the two mutants that suggest multiple roles for Msh1p in addition to mismatch repair. Our overall findings suggest that these additional predicted functions of Msh1p, including recombination surveillance and heteroduplex rejection, may be primarily responsible for its essential role in mtDNA stability.

  8. Building capacity for implementation of the framework convention for tobacco control in Vietnam: lessons for developing countries

    PubMed Central

    Stillman, Frances A.; David, Annette M.; Kibria, Naseeb; Phan, Hai Thi

    2014-01-01

    Effective implementation of the WHO international Framework Convention on Tobacco Control (FCTC) is the key to controlling the tobacco epidemic. Within countries, strong national tobacco control capacity is the primary determinant for successful implementation of the FCTC. This case study of tobacco control policy describes the experience of building national tobacco control capacity in Vietnam under the Reduce Smoking in Vietnam Partnership project within a national capacity-building framework. In the Vietnam experience, four components of tobacco control capacity emerged as especially important to achieve ‘quality’ outputs and measurable outcomes at the implementation level: (i) organizational structure/infrastructure; (ii) leadership and expertise; (iii) partnerships and networks and (iv) data and evidence from research. The experience gained in this project helps in adapting our tobacco control capacity-building model, and the lessons that emerged from this country case study can provide guidance to global funders, tobacco control technical assistance providers and nations as governments endeavor to meet their commitment to the FCTC. PMID:23411160

  9. DOMAIN MISMATCH COMPENSATION FOR SPEAKER RECOGNITION USING A LIBRARY OF WHITENERS

    DTIC Science & Technology

    2015-05-29

    DOMAIN MISMATCH COMPENSATION FOR SPEAKER RECOGNITION USING A LIBRARY OF WHITENERS Elliot Singer and Douglas Reynolds Massachusetts Institute of...development data is assumed to be unavailable. The method is based on a generalization of data whitening used in association with i-vector length...normalization and utilizes a library of whitening transforms trained at system development time using strictly out-of-domain data. The approach is

  10. Instrument Display Visual Angles for Conventional Aircraft and the MQ-9 Ground Control Station

    NASA Technical Reports Server (NTRS)

    Kamine, Tovy Haber; Bendrick, Gregg A.

    2008-01-01

    Aircraft instrument panels should be designed such that primary displays are in optimal viewing location to minimize pilot perception and response time. Human Factors engineers define three zones (i.e. cones ) of visual location: 1) "Easy Eye Movement" (foveal vision); 2) "Maximum Eye Movement" (peripheral vision with saccades), and 3) "Head Movement (head movement required). Instrument display visual angles were measured to determine how well conventional aircraft (T-34, T-38, F- 15B, F-16XL, F/A-18A, U-2D, ER-2, King Air, G-III, B-52H, DC-10, B747-SCA) and the MQ-9 ground control station (GCS) complied with these standards, and how they compared with each other. Selected instrument parameters included: attitude, pitch, bank, power, airspeed, altitude, vertical speed, heading, turn rate, slip/skid, AOA, flight path, latitude, longitude, course, bearing, range and time. Vertical and horizontal visual angles for each component were measured from the pilot s eye position in each system. The vertical visual angles of displays in conventional aircraft lay within the cone of "Easy Eye Movement" for all but three of the parameters measured, and almost all of the horizontal visual angles fell within this range. All conventional vertical and horizontal visual angles lay within the cone of Maximum Eye Movement. However, most instrument vertical visual angles of the MQ-9 GCS lay outside the cone of Easy Eye Movement, though all were within the cone of Maximum Eye Movement. All the horizontal visual angles for the MQ-9 GCS were within the cone of "Easy Eye Movement". Most instrument displays in conventional aircraft lay within the cone of Easy Eye Movement, though mission-critical instruments sometimes displaced less important instruments outside this area. Many of the MQ-9 GCS systems lay outside this area. Specific training for MQ-9 pilots may be needed to avoid increased response time and potential error during flight. The learning objectives include: 1) Know three

  11. [Ten years of the WHO Framework Convention on Tobacco Control: progress in the Americas].

    PubMed

    Blanco, Adriana; Sandoval, Rosa Carolina; Martínez-López, Leticia; Caixeta, Roberta de Betânia

    2017-01-01

    The objective of this article is to analyze the progress made in the Americas in the implementation of the World Health Organization Framework Convention on Tobacco Control (FCTC) after its tenth anniversary of entry into force. At the time of the analysis, 30 of the 35 countries of the Americas are Parties to the FCTC. While progress has been made in implementing the measures contained in the FCTC, the level of implementation has not been homogeneous either across mandates or across countries. Forty percent of Parties to the Convention in the Americas are yet to implement any of the measures at their highest level of implementation according to the WHO classification. It is crucial that the countries of the Americas continue to progress towards the full implementation of the FCTC progressively. In these efforts, it is important to take into account that FCTC measures such as those related to smoke-free environments and adoption of effective health warnings are basic public health measures, which are almost entirely within the competence of health authorities and therefore susceptible to be implemented in a prompt fashion in all countries of the region.

  12. Mismatch repair deficiency associated with overexpression of the MSH3 gene.

    PubMed

    Marra, G; Iaccarino, I; Lettieri, T; Roscilli, G; Delmastro, P; Jiricny, J

    1998-07-21

    We tested the ability of recombinant hMutSalpha (hMSH2/hMSH6) and hMutSbeta (hMSH2/hMSH3) heterodimers to complement the mismatch repair defect of HEC59, a human cancer cell line whose extracts lack all three MutS homologues. Although repair of both base/base mispairs and insertion-deletion loops was restored by hMutSalpha, only the latter substrates were addressed in extracts supplemented with hMutSbeta. hMutSalpha was also able to complement a defect in the repair of base/base mispairs in CHO R and HL60R cell extracts. In these cells, methotrexate-induced amplification of the dihydrofolate reductase (DHFR) locus, which also contains the MSH3 gene, led to an overexpression of MSH3 and thus to a dramatic change in the relative levels of MutSalpha and MutSbeta. As a rule, MSH2 is primarily complexed with MSH6. MutSalpha is thus relatively abundant in mammalian cell extracts, whereas MutSbeta levels are generally low. In contrast, in cells that overexpress MSH3, the available MSH2 protein is sequestered predominantly into MutSbeta. This leads to degradation of the partnerless MSH6 and depletion of MutSalpha. CHO R and HL60R cells therefore lack correction of base/base mispairs, whereas loop repair is maintained by MutSbeta. Consequently, frameshift mutations in CHO R are rare, whereas transitions and transversions are acquired at a rate two orders of magnitude above background. Our data thus support and extend the findings of Drummond et al. [Drummond, J. T., Genschel, J., Wolf, E. & Modrich, P. (1997) Proc. Natl. Acad. Sci. USA 94, 10144-10149] and demonstrate that mismatch repair deficiency can arise not only through mutation or transcriptional silencing of a mismatch repair gene, but also as a result of imbalance in the relative amounts of the MSH3 and MSH6 proteins.

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

    PubMed

    Svetlanov, Anton; Cohen, Paula E

    2004-05-15

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

  14. Extended phase matching of second-harmonic generation in periodically poled KTiOPO4 with zero group-velocity mismatch

    NASA Astrophysics Data System (ADS)

    König, Friedrich; Wong, Franco N. C.

    2004-03-01

    Under extended phase-matching conditions, the first frequency derivative of the wave-vector mismatch is zero and the phase-matching bandwidth is greatly increased. We present extensive three-wave mixing measurements of the wave-vector mismatch and obtain improved Sellmeier equations for KTiOPO4. We observed a type-II extended phase-matching bandwidth of 100 nm for second-harmonic generation in periodically poled KTiOPO4, centered at the fundamental wavelength of 1584 nm. Applications in quantum entanglement and frequency metrology are discussed.

  15. Control of damping-off of organic and conventional cucumber with extracts from a plant-associated bacterium rivals a seed treatment pesticide

    USDA-ARS?s Scientific Manuscript database

    Environmentally friendly control measures are needed for soilborne diseases of crops grown in organic and conventional production systems. We tested ethanol extracts from cultures of Serratia marcescens N4-5 and N2-4, Burkholderia cepacia BC-1 and BC-2, and B. ambifaria BC-F for control of damping-o...

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

    PubMed Central

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

    2017-01-01

    Epidemiological data demonstrated that hormone replace treatment has protective effect against colorectal cancer (CRC). Our previous studies showed that this effect may be associated with DNA mismatch repair. This study aims to investigate the mechanism of estrogen induction of MLH1, and whether colorectal tumor proliferation can be inhibited through induction of MLH1 by estrogen signal pathway. Human CRC cell lines were used to examine the regulation of MLH1 expression by over-expression and depletion of estrogen receptor-α (ERα) and estrogen receptor-β (ERβ), under the treatment with 17β-estradiol or β-Estradiol 6-(O-carboxy-methyl)oxime:BSA, followed by a real-time Q-PCR and Western blotting analysis. Luciferase reporter and chromatin immunoprecipitation assays were used to identify the estrogen response elements in the proximal promoter of MLH1 gene. Then, the influence of estrogen-induced MLH1 on CRC tumor growth were determined in vitro and in vivo. We found that mismatch repair ability and microsatellite stability of cells were enhanced by estrogen via induction of MLH1 expression, which was mediated by ERβ, through a transcriptional activation process. Furthermore, we identified that ERβ exerted an inhibitory effect on CRC tumor proliferation in vitro and in vivo, combined with 5-FU, through up-regulation of MLH1 expression. Finally, we concluded that estrogen enhances mismatch repair ability and tumor inhibition effect in vitro and in vivo, via induction of MLH1 expression mediated by ERβ. PMID:28404976

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

    PubMed

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

    2017-06-13

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

  18. Mismatch Negativity Elicited by Tones and Speech Sounds: Changed Topographical Distribution in Aphasia

    ERIC Educational Resources Information Center

    Becker, Frank; Reinvang, Ivar

    2007-01-01

    This study used the event-related brain potential mismatch negativity (MMN) to investigate preconscious discrimination of harmonically rich tones (differing in duration) and consonant-vowel syllables (differing in the initial consonant) in aphasia. Eighteen Norwegian aphasic patients, examined on average 3 months after brain injury, were compared…

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

    PubMed

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

    2016-01-01

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

  20. Daytime Locations in Spatial Mismatch: Job Accessibility and Employment at Reentry From Prison

    PubMed Central

    Lens, Michael C.

    2017-01-01

    Individuals recently released from prison confront many barriers to employment. One potential obstacle is spatial mismatch—the concentration of low-skilled, nonwhite job-seekers within central cities and the prevalence of relevant job opportunities in outlying areas. Prior research has found mixed results about the importance of residential place for reentry outcomes. In this article, we propose that residential location matters for finding work, but this largely static measure does not capture the range of geographic contexts that individuals inhabit throughout the day. We combine novel, real-time GPS information on daytime locations and self-reported employment collected from smartphones with sophisticated measures of job accessibility to test the relative importance of spatial mismatch based on residence and daytime locations. Our findings suggest that the ability of low-skilled, poor, and urban individuals to compensate for their residential deficits by traveling to job-rich areas is an overlooked and salient consideration in spatial mismatch perspectives. PMID:28224468

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

    PubMed

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

    1993-05-01

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

  2. A functional comparison of conventional knee-ankle-foot orthoses and a microprocessor-controlled leg orthosis system based on biomechanical parameters.

    PubMed

    Schmalz, Thomas; Pröbsting, Eva; Auberger, Roland; Siewert, Gordon

    2016-04-01

    The microprocessor-controlled leg orthosis C-Brace enables patients with paretic or paralysed lower limb muscles to use dampened knee flexion under weight-bearing and speed-adapted control of the swing phase. The objective of the present study was to investigate the new technical functions of the C-Brace orthosis, based on biomechanical parameters. The study enrolled six patients. The C-Brace orthosis is compared with conventional leg orthoses (four stance control orthoses, two locked knee-ankle-foot orthoses) using biomechanical parameters of level walking, descending ramps and descending stairs. Ground reaction forces, joint moments and kinematic parameters were measured for level walking as well as ascending and descending ramps and stairs. With the C-Brace, a nearly natural stance phase knee flexion was measured during level walking (mean value 11° ± 5.6°). The maximum swing phase knee flexion angle of the C-Brace approached the normal value of 65° more closely than the stance control orthoses (66° ± 8.5° vs 74° ± 6.4°). No significant differences in the joint moments were found between the C-Brace and stance control orthosis conditions. In contrast to the conventional orthoses, all patients were able to ambulate ramps and stairs using a step-over-step technique with C-Brace (flexion angle 64.6° ± 8.2° and 70.5° ± 12.4°). The results show that the functions of the C-Brace for situation-dependent knee flexion under weight bearing have been used by patients with a high level of confidence. The functional benefits of the C-Brace in comparison with the conventional orthotic mechanisms could be demonstrated most clearly for descending ramps and stairs. The C-Brace orthosis is able to combine improved orthotic function with sustained orthotic safety. © The International Society for Prosthetics and Orthotics 2014.

  3. Design of complex bone internal structure using topology optimization with perimeter control.

    PubMed

    Park, Jaejong; Sutradhar, Alok; Shah, Jami J; Paulino, Glaucio H

    2018-03-01

    Large facial bone loss usually requires patient-specific bone implants to restore the structural integrity and functionality that also affects the appearance of each patient. Titanium alloys (e.g., Ti-6Al-4V) are typically used in the interfacial porous coatings between the implant and the surrounding bone to promote stability. There exists a property mismatch between the two that in general leads to complications such as stress-shielding. This biomechanical discrepancy is a hurdle in the design of bone replacements. To alleviate the mismatch, the internal structure of the bone replacements should match that of the bone. Topology optimization has proven to be a good technique for designing bone replacements. However, the complex internal structure of the bone is difficult to mimic using conventional topology optimization methods without additional restrictions. In this work, the complex bone internal structure is recovered using a perimeter control based topology optimization approach. By restricting the solution space by means of the perimeter, the intricate design complexity of bones can be achieved. Three different bone regions with well-known physiological loadings are selected to illustrate the method. Additionally, we found that the target perimeter value and the pattern of the initial distribution play a vital role in obtaining the natural curvatures in the bone internal structures as well as avoiding excessive island patterns. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Interaural time discrimination of envelopes carried on high-frequency tones as a function of level and interaural carrier mismatch

    PubMed Central

    Blanks, Deidra A.; Buss, Emily; Grose, John H.; Fitzpatrick, Douglas C.; Hall, Joseph W.

    2009-01-01

    Objectives The present study investigated interaural time discrimination for binaurally mismatched carrier frequencies in listeners with normal hearing. One goal of the investigation was to gain insights into binaural hearing in patients with bilateral cochlear implants, where the coding of interaural time differences may be limited by mismatches in the neural populations receiving stimulation on each side. Design Temporal envelopes were manipulated to present low frequency timing cues to high frequency auditory channels. Carrier frequencies near 4 kHz were amplitude modulated at 128 Hz via multiplication with a half-wave rectified sinusoid, and that modulation was either in-phase across ears or delayed to one ear. Detection thresholds for non-zero interaural time differences were measured for a range of stimulus levels and a range of carrier frequency mismatches. Data were also collected under conditions designed to limit cues based on stimulus spectral spread, including masking and truncation of sidebands associated with modulation. Results Listeners with normal hearing can detect interaural time differences in the face of substantial mismatches in carrier frequency across ears. Conclusions The processing of interaural time differences in listeners with normal hearing is likely based on spread of excitation into binaurally matched auditory channels. Sensitivity to interaural time differences in listeners with cochlear implants may depend upon spread of current that results in the stimulation of neural populations that share common tonotopic space bilaterally. PMID:18596646

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

    PubMed

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

    2015-05-01

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

  6. Moon Convention

    NASA Image and Video Library

    2015-03-23

    People with similar jobs or interests hold conventions and meetings, so why shouldn't moons? Pandora, Prometheus, and Pan -- seen here, from right to left -- also appear to be holding some sort of convention in this image. Some moons control the structure of nearby rings via gravitational "tugs." The cumulative effect of the moon's tugs on the ring particles can keep the rings' edges from spreading out as they are naturally inclined to do, much like shepherds control their flock. Pan is a prototypical shepherding moon, shaping and controlling the locations of the inner and outer edges of the Encke gap through a mechanism suggested in 1978 to explain the narrow Uranian rings. However, though Prometheus and Pandora have historically been called "the F ring shepherd moons" due to their close proximity to the ring, it has long been known that the standard shepherding mechanism that works so well for Pan does not apply to these two moons. The mechanism for keeping the F ring narrow, and the roles played -- if at all -- by Prometheus and Pandora in the F ring's configuration are not well understood. This is an ongoing topic for study by Cassini scientists. This view looks toward the sunlit side of the rings from about 29 degrees above the ringplane. The image was taken in visible light with the Cassini spacecraft narrow-angle camera on Jan. 2, 2015. The view was obtained at a distance of approximately 1.6 million miles (2.6 million kilometers) from the rings and at a Sun-ring-spacecraft, or phase, angle of 86 degrees. Image scale is 10 miles (15 kilometers) per pixel. http://photojournal.jpl.nasa.gov/catalog/pia18306

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

    PubMed

    Turner, D P; Connolly, B A

    2000-12-15

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

  8. Tobacco Control and the World Trade Organization: Mapping Member States’ Positions after the Framework Convention on Tobacco Control

    PubMed Central

    Holden, Chris; Callard, Cynthia

    2016-01-01

    Objective To note the frequency of discussions and disputes about tobacco control measures at the World Trade Organization (WTO) before and after the coming into force of the Framework Convention on Tobacco Control (FCTC). To review trends or patterns in the positions taken by members of the WTO with respect to tobacco control measures. To discuss possible explanations for these observed trends/patterns. Methods We gathered data on tobacco related disputes in the WTO since its establishment in 1995 and its forerunner, the General Agreement on Tariffs and Trade (GATT), prior- and post-FCTC. We also looked at debates on tobacco control measures within the WTO more broadly. To this end, we classified and coded the positions of WTO member states during discussions on tobacco control and the FCTC, from 1995 until 2013, within the Technical Barriers to Trade (TBT) Committee and the Trade-Related Aspects of Intellectual Property Rights (TRIPS) Council. Results There is a growing interest within the WTO for tobacco related issues and opposition to tobacco control measures is moving away from high-income countries towards low(er) income countries. Conclusion The growing prominence of tobacco issues in the WTO can be attributed at least in part to the fact that during the last decade tobacco firms have been marginalised from the domestic policy-making process in many countries, which has forced them to look for other ways and forums to influence decision-making. Furthermore, the finding that almost all recent opposition within the WTO to stronger tobacco regulations came from developing countries is consistent with a relative shift of transnational tobacco companies’ lobbying efforts from developed to developing countries. PMID:26585705

  9. 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

  10. Tumor Budding and PDC Grade Are Stage Independent Predictors of Clinical Outcome in Mismatch Repair Deficient Colorectal Cancer.

    PubMed

    Ryan, Éanna; Khaw, Yi Ling; Creavin, Ben; Geraghty, Robert; Ryan, Elizabeth J; Gibbons, David; Hanly, Ann; Martin, Sean T; O'Connell, P Ronan; Winter, Desmond C; Sheahan, Kieran

    2018-01-01

    Mismatch repair deficient (dMMR) colorectal cancer (CRC) despite its association with poor histologic grade often has improved prognosis compared with MMR proficient CRC. Tumor budding and poorly differentiated clusters (PDCs) may predict metastatic potential of colorectal adenocarcinoma (CRC). In addition, their assessment may be more reproducible than the evaluation of other histopathologic parameters. Therefore, we wished to determine their potential as prognostic indicators in a cohort of dMMR CRC patients relative to histologic grade. We investigated the predictive value of conventional WHO grade, budding, PDC grade and other histopathologic parameters on the presence of lymph node metastasis (LNM) and clinical outcome in 238 dMMR CRCs. MMR status was determined by immunohistochemistry for the mismatch repair proteins hMLH1, hMSH2, hMSH6, and hPMS2. Tumor budding and PDCs were highly correlated (r=0.701; P<0.000). Both budding and PDC grade were associated with WHO grade, perineural invasion, lympho-vascular invasion, and extramural vascular invasion, and the presence of LNM in dMMR CRC (P<0.009). Independent predictors of LNM were PDC grade (odds ratio, 4.12; 95% confidence interval [CI], 1.69-10.04; P=0.011) and EMVI (odds ratio, 3.81; 95% CI, 1.56-9.19; P<0.000). Only pTstage (hazard ratio [HR], 4.11; 95% CI, 1.48-11.36; P=0.007) and tumor budding (HR, 2.99; 95% CI, 1.72-5.19; P<0.000) were independently associated with worse disease-free survival (DFS). If tumor budding was excluded from the model, PDC grade became significant for DFS (HR, 2.34; 95% CI, 1.34-4.09; P=0.003). WHO Grade does not independently correlate with clinical outcome in dMMR CRC. PDC grade and extramural vascular invasion are independent predictors of LNM. Tumor budding and pTstage are the best predictors of DFS. If tumor budding cannot be assessed, PDC grade may be used as a prognostic surrogate.

  11. Mismatch or allostatic load? Timing of life adversity differentially shapes gray matter volume and anxious temperament.

    PubMed

    Kuhn, Manuel; Scharfenort, Robert; Schümann, Dirk; Schiele, Miriam A; Münsterkötter, Anna L; Deckert, Jürgen; Domschke, Katharina; Haaker, Jan; Kalisch, Raffael; Pauli, Paul; Reif, Andreas; Romanos, Marcel; Zwanzger, Peter; Lonsdorf, Tina B

    2016-04-01

    Traditionally, adversity was defined as the accumulation of environmental events (allostatic load). Recently however, a mismatch between the early and the later (adult) environment (mismatch) has been hypothesized to be critical for disease development, a hypothesis that has not yet been tested explicitly in humans. We explored the impact of timing of life adversity (childhood and past year) on anxiety and depression levels (N = 833) and brain morphology (N = 129). Both remote (childhood) and proximal (recent) adversities were differentially mirrored in morphometric changes in areas critically involved in emotional processing (i.e. amygdala/hippocampus, dorsal anterior cingulate cortex, respectively). The effect of adversity on affect acted in an additive way with no evidence for interactions (mismatch). Structural equation modeling demonstrated a direct effect of adversity on morphometric estimates and anxiety/depression without evidence of brain morphology functioning as a mediator. Our results highlight that adversity manifests as pronounced changes in brain morphometric and affective temperament even though these seem to represent distinct mechanistic pathways. A major goal of future studies should be to define critical time periods for the impact of adversity and strategies for intervening to prevent or reverse the effects of adverse childhood life experiences. © The Author (2015). Published by Oxford University Press.

  12. Mismatch or allostatic load? Timing of life adversity differentially shapes gray matter volume and anxious temperament

    PubMed Central

    Kuhn, Manuel; Scharfenort, Robert; Schümann, Dirk; Schiele, Miriam A.; Münsterkötter, Anna L.; Deckert, Jürgen; Domschke, Katharina; Haaker, Jan; Kalisch, Raffael; Pauli, Paul; Reif, Andreas; Romanos, Marcel; Zwanzger, Peter

    2016-01-01

    Traditionally, adversity was defined as the accumulation of environmental events (allostatic load). Recently however, a mismatch between the early and the later (adult) environment (mismatch) has been hypothesized to be critical for disease development, a hypothesis that has not yet been tested explicitly in humans. We explored the impact of timing of life adversity (childhood and past year) on anxiety and depression levels (N = 833) and brain morphology (N = 129). Both remote (childhood) and proximal (recent) adversities were differentially mirrored in morphometric changes in areas critically involved in emotional processing (i.e. amygdala/hippocampus, dorsal anterior cingulate cortex, respectively). The effect of adversity on affect acted in an additive way with no evidence for interactions (mismatch). Structural equation modeling demonstrated a direct effect of adversity on morphometric estimates and anxiety/depression without evidence of brain morphology functioning as a mediator. Our results highlight that adversity manifests as pronounced changes in brain morphometric and affective temperament even though these seem to represent distinct mechanistic pathways. A major goal of future studies should be to define critical time periods for the impact of adversity and strategies for intervening to prevent or reverse the effects of adverse childhood life experiences. PMID:26568620

  13. Thermal Protection Supplement for Reducing Interface Thermal Mismatch

    NASA Technical Reports Server (NTRS)

    Stewart, David A. (Inventor); Leiser, Daniel B. (Inventor)

    2017-01-01

    A thermal protection system that reduces a mismatch of thermal expansion coefficients CTE between a first material layer (CTE1) and a second material layer (CTE2) at a first layer-second layer interface. A portion of aluminum borosilicate (abs) or another suitable additive (add), whose CTE value, CTE(add), satisfies (CTE(add)-CTE1)(CTE(add)-CTE2)<0, is distributed with variable additive density,.rho.(z;add), in the first material layer and/or in the second material layer, with.rho.(z;add) near the materials interface being relatively high (alternatively, relatively low) and.rho.(z;add) in a region spaced apart from the interface being relatively low (alternatively, relatively high).

  14. An Index-Mismatch Scattering Approach to Optical Limiting

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

    Exarhos, Gregory J.; Ferris, Kim F.; Windisch, Charles F.

    A densely packed bed of alkaline earth fluoride particles percolated by a fluid medium has been investigated as a potential index-matched optical limiter in the spirit of a Christiansen-Shelyubskii filter. Marked optical limiting was observed through this transparent medium under conditions where the focused second-harmonic output of a Q-swtiched Nd: YAG laser was on the order of about 1 J/cm2. An open-aperture Z-scan technique was used to quantify the limiting behavior. In this case, the mechanism of optical limiting is thought to be a nonlinear shift in the fluid index of refraction, resulting in an index mismatch between the disparatemore » phases at high laser fluence.« less

  15. Digital Versus Conventional Impressions in Fixed Prosthodontics: A Review.

    PubMed

    Ahlholm, Pekka; Sipilä, Kirsi; Vallittu, Pekka; Jakonen, Minna; Kotiranta, Ulla

    2018-01-01

    To conduct a systematic review to evaluate the evidence of possible benefits and accuracy of digital impression techniques vs. conventional impression techniques. Reports of digital impression techniques versus conventional impression techniques were systematically searched for in the following databases: Cochrane Central Register of Controlled Trials, PubMed, and Web of Science. A combination of controlled vocabulary, free-text words, and well-defined inclusion and exclusion criteria guided the search. Digital impression accuracy is at the same level as conventional impression methods in fabrication of crowns and short fixed dental prostheses (FDPs). For fabrication of implant-supported crowns and FDPs, digital impression accuracy is clinically acceptable. In full-arch impressions, conventional impression methods resulted in better accuracy compared to digital impressions. Digital impression techniques are a clinically acceptable alternative to conventional impression methods in fabrication of crowns and short FDPs. For fabrication of implant-supported crowns and FDPs, digital impression systems also result in clinically acceptable fit. Digital impression techniques are faster and can shorten the operation time. Based on this study, the conventional impression technique is still recommended for full-arch impressions. © 2016 by the American College of Prosthodontists.

  16. Evaluation of Isotopic Data Mismatches on DOE-STD-1027 Facility Categorization Inventories for the K-1065 Complex and the Above Grade Storage Facility (AGSF)

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

    McHugh, M.G.; Coleman, G.H.

    2006-07-01

    The contents of a safety basis (SB) are based upon the facility's purpose of operation, radiological inventory, and safety systems in place to mitigate any releases to the employees, general public and environment. Specifically, the radiological inventory is used for facility categorizations (e.g., Category 2, Category 3) and determining the material at risk used in the associated nuclear safety analysis calculations. Radiological inventory discrepancies, referred to as 'mismatches', have the potential to adversely impact the SB. This paper summarizes a process developed to: 1) identify these 'mismatches' based on a facility's radiological inventory, 2) categorize these 'mismatches' according to availablemore » data, and then 3) determine if these 'mismatches' yield either trivial or significant cumulative impacts on credited assumptions associated with a particular facility's SB. The two facilities evaluated for 'mismatches' were the K-1065 Complex and the Above Grade Storage Facility (AGSF). The randomly selected containers from each facility were obtained along with screening the radiological inventories found in the Waste Information Tracking System (WITS) database and the Request for Disposal (RFD) forms. Ideally, the radiological inventory, which is comprised of isotopic data for each container, is maintained in the WITS database. However, the RFD is the official repository record for isotopic data for each container. Historically, neither WITS nor the RFDs were required to contain isotopic data. Based on the WITS and RFD data, the containers were then categorized into five (5) separate conditions: Condition 1) Isotopic data in the RFD matches the isotopic data in WITS; Condition 2) Isotopic data in the RFD does not match the isotopic data in WITS; Condition 3) Isotopic data are in the RFD, but are not in WITS; Condition 4) No isotopic data in the RFD, but isotopic data are found in WITS; Condition 5) No isotopic data found in either the RFD or WITS. The

  17. Complete spatial and temporal locking in phase-mismatched second-harmonic generation.

    PubMed

    Fazio, Eugenio; Pettazzi, Federico; Centini, Marco; Chauvet, Mathieu; Belardini, Alessandro; Alonzo, Massimo; Sibilia, Concita; Bertolotti, Mario; Scalora, Micheal

    2009-03-02

    We experimentally demonstrate simultaneous phase and group velocity locking of fundamental and generated second harmonic pulses in Lithium Niobate, under conditions of material phase mismatch. In phase-mismatched, pulsed second harmonic generation in addition to a reflected signal two forward-propagating pulses are also generated at the interface between a linear and a second order nonlinear material: the first pulse results from the solution of the homogeneous wave equation, and propagates at the group velocity expected from material dispersion; the second pulse is the solution of the inhomogeneous wave equation, is phase-locked and trapped by the pump pulse, and follows the pump trajectory. At normal incidence, the normal and phase locked pulses simply trail each other. At oblique incidence, the consequences can be quite dramatic. The homogeneous pulse refracts as predicted by material dispersion and Snell's law, yielding at least two spatially separate second harmonic spots at the medium's exit. We thus report the first experimental results showing that, at oblique incidence, fundamental and phase-locked second harmonic pulses travel with the same group velocity and follow the same trajectory. This is direct evidence that, at least up to first order, the effective dispersion of the phase-locked pulse is similar to the dispersion of the pump pulse.

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

    PubMed

    Atmeh, Kamal; Andruszkiewicz, Anna; Zub, Karol

    2018-05-24

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

  19. Increase in Speech Recognition due to Linguistic Mismatch Between Target and Masker Speech: Monolingual and Simultaneous Bilingual Performance

    PubMed Central

    Calandruccio, Lauren; Zhou, Haibo

    2014-01-01

    Purpose To examine whether improved speech recognition during linguistically mismatched target–masker experiments is due to linguistic unfamiliarity of the masker speech or linguistic dissimilarity between the target and masker speech. Method Monolingual English speakers (n = 20) and English–Greek simultaneous bilinguals (n = 20) listened to English sentences in the presence of competing English and Greek speech. Data were analyzed using mixed-effects regression models to determine differences in English recogition performance between the 2 groups and 2 masker conditions. Results Results indicated that English sentence recognition for monolinguals and simultaneous English–Greek bilinguals improved when the masker speech changed from competing English to competing Greek speech. Conclusion The improvement in speech recognition that has been observed for linguistically mismatched target–masker experiments cannot be simply explained by the masker language being linguistically unknown or unfamiliar to the listeners. Listeners can improve their speech recognition in linguistically mismatched target–masker experiments even when the listener is able to obtain meaningful linguistic information from the masker speech. PMID:24167230

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

    PubMed

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

    2017-10-01

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

  1. Intensive versus conventional glucose control in critically ill patients with traumatic brain injury: long-term follow-up of a subgroup of patients from the NICE-SUGAR study.

    PubMed

    Finfer, Simon; Chittock, Dean; Li, Yang; Foster, Denise; Dhingra, Vinay; Bellomo, Rinaldo; Cook, Deborah; Dodek, Peter; Hebert, Paul; Henderson, William; Heyland, Daren; Higgins, Alisa; McArthur, Colin; Mitchell, Imogen; Myburgh, John; Robinson, Bruce; Ronco, Juan

    2015-06-01

    To compare the effect of intensive versus conventional blood glucose control in patients with traumatic brain injury. In a large international randomized trial patients were randomly assigned to a target blood glucose (BG) range of either 4.5-6.0 mmol/L (intensive control) or <10 mmol/L (conventional control). Patients with traumatic brain injury (TBI) were identified at randomization and data were collected to examine the extended Glasgow outcome score (includes mortality) at 24 months. Of the 6104 randomized patients, 391 satisfied diagnostic criteria for TBI; 203 (51.9%) were assigned to intensive and 188 (48.1%) to conventional control; the primary outcome was available for 166 (81.8%) and 149 (79.3%) patients, respectively. The two groups had similar baseline characteristics. At 2 years 98 (58.7%) patients in the intensive group and 79 (53.0%) in the conventional group had a favorable neurological outcome (odds ratio [OR] 1.26, 95% CI 0.81-1.97; P = 0.3); 35 patients (20.9%) in the intensive group and 34 (22.8%) in the conventional group had died (OR 0.90, 95% CI 0.53-1.53; P = 0.7); moderate hypoglycemia (BG 2.3-3.9 mmol/L; 41-70 mg/dL) occurred in 160/202 (79.2%) and 17/188 (9.0%), respectively (OR 38.3, 95% CI 21.0-70.1; P < 0.0001); severe hypoglycemia (BG ≤ 2.2 mmol/L; ≤40 mg/dL) in 10 (4.9%) and 0 (0.0%), respectively (OR 20.5 95% CI 1.2-351.6, P = 0.003). Although patients with traumatic brain injury randomly assigned to intensive compared to conventional glucose control experienced moderate and severe hypoglycemia more frequently, we found no significant difference in clinically important outcomes.

  2. Building capacity for implementation of the framework convention for tobacco control in Vietnam: lessons for developing countries.

    PubMed

    Stillman, Frances A; David, Annette M; Kibria, Naseeb; Phan, Hai Thi

    2014-09-01

    Effective implementation of the WHO international Framework Convention on Tobacco Control (FCTC) is the key to controlling the tobacco epidemic. Within countries, strong national tobacco control capacity is the primary determinant for successful implementation of the FCTC. This case study of tobacco control policy describes the experience of building national tobacco control capacity in Vietnam under the Reduce Smoking in Vietnam Partnership project within a national capacity-building framework. In the Vietnam experience, four components of tobacco control capacity emerged as especially important to achieve 'quality' outputs and measurable outcomes at the implementation level: (i) organizational structure/infrastructure; (ii) leadership and expertise; (iii) partnerships and networks and (iv) data and evidence from research. The experience gained in this project helps in adapting our tobacco control capacity-building model, and the lessons that emerged from this country case study can provide guidance to global funders, tobacco control technical assistance providers and nations as governments endeavor to meet their commitment to the FCTC. © The Author (2013). Published by Oxford University Press.

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

    PubMed

    Baharoglu, Zeynep; Mazel, Didier

    2014-01-01

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

  4. A randomized controlled trial of the Arctic Sun Temperature Management System versus conventional methods for preventing hypothermia during off-pump cardiac surgery.

    PubMed

    Grocott, Hilary P; Mathew, Joseph P; Carver, Elizabeth H; Phillips-Bute, Barbara; Landolfo, Kevin P; Newman, Mark F

    2004-02-01

    In this trial we compared the hypothermia avoidance abilities of the Arctic Sun Temperature Management System (a servo-regulated system that circulates temperature-controlled water through unique energy transfer pads adherent to the patient's body) with conventional temperature control methods. Patients undergoing off-pump coronary artery bypass (OPCAB) surgery were randomized to either the Arctic Sun System alone (AS group) or conventional methods (control group; increased room temperature, heated IV fluids, convective forced air warming system) for the prevention of hypothermia (defined by a temperature <36 degrees C). The AS group had nasopharyngeal temperature servo-regulated to a target of 36.8 degrees C. Temperature was recorded throughout the operative period and comparisons were made between groups for both the time and area under the curve (AUC) for a temperature <36 degrees C (AUC<36 degrees C). Twenty-nine patients (AS group = 14, control group = 15) were studied. The AS group had significantly less hypothermia than the control group, both for duration of time <36 degrees C (2.5 [0-22] min, median [interquartile range] AS group versus 118 [49-192] min, control group; P = 0.0008) as well as for AUC<36 degrees C (0.3 [0-2.2] degrees C x min, AS group versus 17.1 [3.6-173.4] degrees C x min, control group; P = 0.002). The Arctic Sun Temperature Management System significantly reduced intraoperative hypothermia during OPCAB surgery. Importantly, this was achieved in the absence of any other temperature modulating techniques, including the use of IV fluid warming or increases in the ambient operating room temperature. The Arctic Sun Temperature Management System was more effective than conventional methods in preventing hypothermia during off-pump coronary artery bypass graft surgery.

  5. Early pest development and loss of biological control are associated with urban warming.

    PubMed

    Meineke, Emily K; Dunn, Robert R; Frank, Steven D

    2014-11-01

    Climate warming is predicted to cause many changes in ectotherm communities, one of which is phenological mismatch, wherein one species' development advances relative to an associated species or community. Phenological mismatches already lead to loss of pollination services, and we predict that they also cause loss of biological control. Here, we provide evidence that a pest develops earlier due to urban warming but that phenology of its parasitoid community does not similarly advance. This mismatch is associated with greater egg production that likely leads to more pests on trees. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

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

    PubMed

    Suerink, M; Potjer, T P; Versluijs, A B; Ten Broeke, S W; Tops, C M; Wimmer, K; Nielsen, M

    2018-01-01

    Constitutional mismatch repair deficiency (CMMRD) is a rare, recessively inherited childhood cancer predisposition syndrome caused by biallelic germline mutations in one of the mismatch repair genes. The CMMRD phenotype overlaps with that of neurofibromatosis type 1 (NF1), since many patients have multiple café-au-lait macules (CALM) and other NF1 signs, but no germline NF1 mutations. We report of a case of a healthy 6-year-old girl who fulfilled the diagnostic criteria of NF1 with >6 CALM and freckling. Since molecular genetic testing was unable to confirm the diagnosis of NF1 or Legius syndrome and the patient was a child of consanguineous parents, we suspected CMMRD and found a homozygous PMS2 mutation that impairs MMR function. Current guidelines advise testing for CMMRD only in cancer patients. However, this case illustrates that including CMMRD in the differential diagnosis in suspected sporadic NF1 without causative NF1 or SPRED1 mutations may facilitate identification of CMMRD prior to cancer development. We discuss the advantages and potential risks of this CMMRD testing scenario. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. The thermal mismatch hypothesis explains host susceptibility to an emerging infectious disease.

    PubMed

    Cohen, Jeremy M; Venesky, Matthew D; Sauer, Erin L; Civitello, David J; McMahon, Taegan A; Roznik, Elizabeth A; Rohr, Jason R

    2017-02-01

    Parasites typically have broader thermal limits than hosts, so large performance gaps between pathogens and their cold- and warm-adapted hosts should occur at relatively warm and cold temperatures, respectively. We tested this thermal mismatch hypothesis by quantifying the temperature-dependent susceptibility of cold- and warm-adapted amphibian species to the fungal pathogen Batrachochytrium dendrobatidis (Bd) using laboratory experiments and field prevalence estimates from 15 410 individuals in 598 populations. In both the laboratory and field, we found that the greatest susceptibility of cold- and warm-adapted hosts occurred at relatively warm and cool temperatures, respectively, providing support for the thermal mismatch hypothesis. Our results suggest that as climate change shifts hosts away from their optimal temperatures, the probability of increased host susceptibility to infectious disease might increase, but the effect will depend on the host species and the direction of the climate shift. Our findings help explain the tremendous variation in species responses to Bd across climates and spatial, temporal and species-level variation in disease outbreaks associated with extreme weather events that are becoming more common with climate change. © 2017 John Wiley & Sons Ltd/CNRS.

  8. The Effects of Composition and gamma'/gamma Lattice Parameter Mismatch on the Critical Resolved Shear Stresses for Octahedral and Cube Slip in NiAlCrX Alloys

    NASA Technical Reports Server (NTRS)

    Miner, R. V.

    1997-01-01

    Prototypical single-crystal NiAlCrX superalloys were studied to examine the effects of the common major alloying elements, Co, Mo, Nb, Ta, Ti, and W, on yielding behavior. The alloys contained about 10 at. pct Cr, 60 vol pct of the gamma' phase, and about 3 at. pct of X in the gamma'. The critical resolved shear stresses (CRSSs) for octahedral and primary cube slip were measured at 760 C, which is about the peak strength temperature. The CRSS(sub oct) and CRSS(sub cube) are discussed in relation to those of Ni, (Al, X) gamma' alloys taken from the literature and the gamma'/gamma lattice mismatch. The CRSS(sub oct) of the gamma + gamma' alloys reflected a similar compositional dependence to that of both the CRSS(sub cube) of the gamma' phase and the gamma'/gamma lattice parameter mismatch. The CRSS(sub cube) of the gamma + gamma' alloys also reflected the compositional dependence of the gamma'/gamma mismatch, but bore no similarity to that of CRSS(sub cube) for gamma' alloys since it is controlled by the gamma matrix. The ratio of CRSS(sub cube)/CRSS(sub oct) was decreased by all alloying elements except Co, which increased the ratio. The decrease in CRSS(sub cube)/CRSS(sub oct) was related to the degree in which elements partition to the gamma' rather than the gamma phase.

  9. DNA Mismatch Repair Status Predicts Need for Future Colorectal Surgery for Metachronous Neoplasms in Young Individuals Undergoing Colorectal Cancer Resection.

    PubMed

    Aronson, Melyssa; Holter, Spring; Semotiuk, Kara; Winter, Laura; Pollett, Aaron; Gallinger, Steven; Cohen, Zane; Gryfe, Robert

    2015-07-01

    The treatment of colorectal cancer in young patients involves both management of the incident cancer and consideration of the possibility of Lynch syndrome and the development of metachronous colorectal cancers. This study aims to assess the prognostic role of DNA mismatch repair deficiency and extended colorectal resection for metachronous colorectal neoplasia risk in young patients with colorectal cancer. This is a retrospective review of 285 patients identified in our GI cancer registry with colorectal cancer diagnosed at 35 years or younger in the absence of polyposis. Using univariate and multivariate analysis, we assessed the prognostic role of mismatch repair deficiency and standard clinicopathologic characteristics, including the extent of resection, on the rate of developing metachronous colorectal neoplasia requiring resection. Mismatch repair deficiency was identified in biospecimens from 44% of patients and was significantly associated with an increased risk for metachronous colorectal neoplasia requiring resection (10-year cumulative risk, 13.5% ± 4.2%) compared with 56% of patients with mismatch repair-intact colorectal cancer (10-year cumulative risk, 5.8% ± 3.3%; p = 0.011). In multivariate analysis, mismatch repair deficiency was associated with a HR of 3.65 (95% CI, 1.44-9.21; p = 0.006) for metachronous colorectal neoplasia, whereas extended resection with ileorectal or ileosigmoid anastomosis significantly decreased the risk of metachronous colorectal neoplasia (HR, 0.21; 95% CI, 0.05-0.90; p = 0.036). This study had a retrospective design, and, therefore, recommendations for colorectal cancer surgery and screening were not fully standardized. Quality of life after colorectal cancer surgery was not assessed. Young patients with colorectal cancer with molecular hallmarks of Lynch syndrome were at significantly higher risk for the development of subsequent colorectal neoplasia. This risk was significantly reduced in those who underwent extended

  10. Comparison of the conformation of an oligonucleotide containing a central G-T base pair with the non-mismatch sequence by proton NMR.

    PubMed Central

    Quignard, E; Fazakerley, G V; van der Marel, G; van Boom, J H; Guschlbauer, W

    1987-01-01

    We have recorded NOESY spectra of two non-selfcomplementary undecanucleotide duplexes. From the observed NOEs we do not detect any significant distortion of the helix when a G-C pair is replaced by a G-T pair and the normal interresidue connectivities can be followed through the mismatch site. We conclude that the 2D spectra of the non-exchangeable protons do not allow differentiation between a wobble or rare tautomer form for the mismatch. NOE measurements in H2O, however, clearly show that the mismatch adopts a wobble structure and give information on the hydration in the minor groove for the G-T base pair which is embedded between two A-T base pairs in the sequence. PMID:3033602

  11. Tobacco control and the World Trade Organization: mapping member states' positions after the framework convention on tobacco control.

    PubMed

    Eckhardt, Jappe; Holden, Chris; Callard, Cynthia D

    2016-11-01

    To note the frequency of discussions and disputes about tobacco control measures at the World Trade Organization (WTO) before and after the coming into force of the Framework Convention on Tobacco Control (FCTC). To review trends or patterns in the positions taken by members of the WTO with respect to tobacco control measures. To discuss possible explanations for these observed trends/patterns. We gathered data on tobacco-related disputes in the WTO since its establishment in 1995 and its forerunner, the General Agreement on Tariffs and Trade (GATT), prior-FCTC and post-FCTC. We also looked at debates on tobacco control measures within the WTO more broadly. To this end, we classified and coded the positions of WTO member states during discussions on tobacco control and the FCTC, from 1995 until 2013, within the Technical Barriers to Trade (TBT) Committee and the Trade-Related Aspects of Intellectual Property Rights (TRIPS) Council. There is a growing interest within the WTO for tobacco-related issues and opposition to tobacco control measures is moving away from high-income countries towards low(er) income countries. The growing prominence of tobacco issues in the WTO can be attributed at least in part to the fact that during the past decade tobacco firms have been marginalised from the domestic policy-making process in many countries, which has forced them to look for other ways and forums to influence decision-making. Furthermore, the finding that almost all recent opposition within the WTO to stronger tobacco regulations came from developing countries is consistent with a relative shift of transnational tobacco companies' lobbying efforts from developed to developing countries. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  12. Neuro-Fuzzy Computational Technique to Control Load Frequency in Hydro-Thermal Interconnected Power System

    NASA Astrophysics Data System (ADS)

    Prakash, S.; Sinha, S. K.

    2015-09-01

    In this research work, two areas hydro-thermal power system connected through tie-lines is considered. The perturbation of frequencies at the areas and resulting tie line power flows arise due to unpredictable load variations that cause mismatch between the generated and demanded powers. Due to rising and falling power demand, the real and reactive power balance is harmed; hence frequency and voltage get deviated from nominal value. This necessitates designing of an accurate and fast controller to maintain the system parameters at nominal value. The main purpose of system generation control is to balance the system generation against the load and losses so that the desired frequency and power interchange between neighboring systems are maintained. The intelligent controllers like fuzzy logic, artificial neural network (ANN) and hybrid fuzzy neural network approaches are used for automatic generation control for the two area interconnected power systems. Area 1 consists of thermal reheat power plant whereas area 2 consists of hydro power plant with electric governor. Performance evaluation is carried out by using intelligent (ANFIS, ANN and fuzzy) control and conventional PI and PID control approaches. To enhance the performance of controller sliding surface i.e. variable structure control is included. The model of interconnected power system has been developed with all five types of said controllers and simulated using MATLAB/SIMULINK package. The performance of the intelligent controllers has been compared with the conventional PI and PID controllers for the interconnected power system. A comparison of ANFIS, ANN, Fuzzy and PI, PID based approaches shows the superiority of proposed ANFIS over ANN, fuzzy and PI, PID. Thus the hybrid fuzzy neural network controller has better dynamic response i.e., quick in operation, reduced error magnitude and minimized frequency transients.

  13. Sector-Based Analysis of the Education-Occupation Mismatch in the Turkish Labor Market

    ERIC Educational Resources Information Center

    Mercan, Murat Anil; Karakas, Mesut; Citci, Sadettin Haluk; Babacan, Mehmet

    2015-01-01

    The aim of this study was to investigate the existence of sectorial undereducation and overeducation problems in the Turkish labor market. In order to cope with this issue, the 2009 Household Labor Force Survey (TurkStat), which covers 145,934 individuals within 27 sectors, was utilized. An objective measure of education-occupation mismatch based…

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

    PubMed

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

    2018-03-25

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

  15. 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

  16. Model mismatch analysis and compensation for modal phase measuring deflectometry

    DOE PAGES

    Huang, Lei; Xue, Junpeng; Gao, Bo; ...

    2017-01-11

    The correspondence residuals due to the discrepancy between the reality and the shape model in use are analyzed for the modal phase measuring deflectometry. Slope residuals are calculated from these discrepancies between the modal estimation and practical acquisition. Since the shape mismatch mainly occurs locally, zonal integration methods which are good at dealing with local variations are used to reconstruct the height residual for compensation. Finally, results of both simulation and experiment indicate the proposed height compensation method is effective, which can be used as a post-complement for the modal phase measuring deflectometry.

  17. Effects of High-Definition and Conventional tDCS on Response Inhibition.

    PubMed

    Hogeveen, J; Grafman, J; Aboseria, M; David, A; Bikson, M; Hauner, K K

    2016-01-01

    Response inhibition is a critical executive function, enabling the adaptive control of behavior in a changing environment. The inferior frontal cortex (IFC) is considered to be critical for response inhibition, leading researchers to develop transcranial direct current stimulation (tDCS) montages attempting to target the IFC and improve inhibitory performance. However, conventional tDCS montages produce diffuse current through the brain, making it difficult to establish causality between stimulation of any one given brain region and resulting behavioral changes. Recently, high-definition tDCS (HD-tDCS) methods have been developed to target brain regions with increased focality relative to conventional tDCS. Remarkably few studies have utilized HD-tDCS to improve cognitive task performance, however, and no study has directly compared the behavioral effects of HD-tDCS to conventional tDCS. In the present study, participants received either HD-tDCS or conventional tDCS to the IFC during performance of a response inhibition task (stop-signal task, SST) or a control task (choice reaction time task, CRT). A third group of participants completed the same behavioral protocols, but received tDCS to a control site (mid-occipital cortex). Post-stimulation improvement in SST performance was analyzed as a function of tDCS group and the task performed during stimulation using both conventional and Bayesian parameter estimation analyses. Bayesian estimation of the effects of HD- and conventional tDCS to IFC relative to control site stimulation demonstrated enhanced response inhibition for both conditions. No improvements were found after control task (CRT) training in any tDCS condition. Results support the use of both HD- and conventional tDCS to the IFC for improving response inhibition, providing empirical evidence that HD-tDCS can be used to facilitate performance on an executive function task. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Tuning quadratic nonlinear photonic crystal fibers for zero group-velocity mismatch.

    PubMed

    Bache, Morten; Nielsen, Hanne; Laegsgaard, Jesper; Bang, Ole

    2006-06-01

    We consider an index-guiding silica photonic crystal fiber with a triangular hole pattern and a periodically poled quadratic nonlinearity. By tuning the pitch and the relative hole size, second-harmonic generation with zero group-velocity mismatch is found for any fundamental wavelength above 780 nm. The nonlinear strength is optimized when the fundamental has maximum confinement in the core. The conversion bandwidth allows for femtosecond-pulse conversion, and 4%-180%W(-1)cm(-2) relative efficiencies were found.

  19. 10 CFR 429.23 - Conventional cooking tops, conventional ovens, microwave ovens.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 3 2013-01-01 2013-01-01 false Conventional cooking tops, conventional ovens, microwave... Conventional cooking tops, conventional ovens, microwave ovens. (a) Sampling plan for selection of units for... and microwave ovens; and (2) For each basic model of conventional cooking tops, conventional ovens and...

  20. 10 CFR 429.23 - Conventional cooking tops, conventional ovens, microwave ovens.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 3 2014-01-01 2014-01-01 false Conventional cooking tops, conventional ovens, microwave... Conventional cooking tops, conventional ovens, microwave ovens. (a) Sampling plan for selection of units for... and microwave ovens; and (2) For each basic model of conventional cooking tops, conventional ovens and...

  1. 10 CFR 429.23 - Conventional cooking tops, conventional ovens, microwave ovens.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 3 2012-01-01 2012-01-01 false Conventional cooking tops, conventional ovens, microwave... Conventional cooking tops, conventional ovens, microwave ovens. (a) Sampling plan for selection of units for... and microwave ovens; and (2) For each basic model of conventional cooking tops, conventional ovens and...

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

    PubMed

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

    2017-06-01

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

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

    PubMed

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

    2018-01-01

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

  4. Job Supply and Demand for University Graduates in Spain: A (Relative) Mismatch Perspective

    ERIC Educational Resources Information Center

    Parellada, Marti; Duch, Nestor; Alvarez, Montserrat

    2009-01-01

    This article provides an analysis of job supply by Spanish firms and the demand for work, and the mismatch that occurs between these two variables. Data are taken for the year 2006, with particular attention to jobs offered by firms that require people with university degrees or other higher education qualifications. Demand and supply are broken…

  5. The Mortality Risk of Conventional Antipsychotics in Elderly Patients: A Systematic Review and Meta-analysis of Randomized Placebo-Controlled Trials.

    PubMed

    Hulshof, Tessa A; Zuidema, Sytse U; Ostelo, Raymond W J G; Luijendijk, Hendrika J

    2015-10-01

    Numerous observational studies have reported an increased risk of mortality for conventional antipsychotics in elderly patients, and for haloperidol in particular. Subsequently, health authorities have warned against use of conventional antipsychotics in dementia. Experimental evidence is lacking. To assess the mortality risk of conventional antipsychotics in elderly patients with a meta-analysis of trials. Original studies were identified in electronic databases, online trial registers, and hand-searched references of published reviews. Two investigators found 28 potentially eligible studies, and they selected 17 randomized placebo-controlled trials in elderly patients with dementia, delirium, or a high risk of delirium. Two investigators independently abstracted trial characteristics and deaths, and 3 investigators assessed the risk of bias. Deaths were pooled with RevMan to obtain risk differences and risk ratios. Data of 17 trials with a total of 2387 participants were available. Thirty-two deaths occurred. The pooled risk difference of 0.1% was not statistically significant (95% confidence interval (CI) -1.0%-1.2%). The risk ratio was 1.07 (95% CI 0.54-2.13). Eleven of 17 trials tested haloperidol (n = 1799). The risk difference was 0.4% (95% CI -0.9%-1.6%), the risk ratio was 1.25 (95% CI 0.59-2.65). This meta-analysis of placebo-controlled randomized trials does not show that conventional antipsychotics in general or haloperidol in particular increase the risk of mortality in elderly patients. It questions the observational findings and the warning based on these findings. Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

  6. Auditory Magnetic Mismatch Field Latency: A Biomarker for Language Impairment in Autism

    PubMed Central

    Roberts, Timothy P.L.; Cannon, Katelyn M.; Tavabi, Kambiz; Blaskey, Lisa; Khan, Sarah Y.; Monroe, Justin F.; Qasmieh, Saba; Levy, Susan E.; Edgar, J. Christopher

    2011-01-01

    Background Auditory processing abnormalities are frequently observed in Autism Spectrum Disorders (ASD), and these abnormalities may have sequelae in terms of clinical language impairment (LI). The present study assessed associations between language impairment and the amplitude and latency of the superior temporal gyrus magnetic mismatch field (MMF) in response to changes in an auditory stream of tones or vowels. Methods 51 children with ASD and 27 neurotypical controls, all aged 6-15 years, underwent neuropsychological evaluation, including tests of language function, as well as magnetoencephalographic (MEG) recording during presentation of tones and vowels. The MMF was identified in the difference waveform obtained from subtraction of responses to standard stimuli from deviant stimuli. Results MMF latency was significantly prolonged (p<0.001) in children with ASD compared to neurotypical controls. Furthermore, this delay was most pronounced (∼50ms) in children with concomitant LI, with significant differences in latency between children with ASD with LI and those without (p<0.01). Receiver operator characteristic analysis indicated a sensitivity of 82.4% and specificity of 71.2% for diagnosing LI based on MMF latency. Conclusion Neural correlates of auditory change detection (the MMF) are significantly delayed in children with ASD, and especially those with concomitant LI suggesting both a neurobiological basis for LI as well as a clinical biomarker for LI in ASD. PMID:21392733

  7. 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

  8. Conventional and nonconventional strategies for controlling bacterial contamination in fuel ethanol fermentations.

    PubMed

    Ceccato-Antonini, Sandra Regina

    2018-05-25

    Ethanol bio-production in Brazil has some unique characteristics that inevitably lead to bacterial contamination, which results in the production of organic acids and biofilms and flocculation that impair the fermentation yield by affecting yeast viability and diverting sugars to metabolites other than ethanol. The ethanol-producing units commonly give an acid treatment to the cells after each fermentative cycle to decrease the bacterial number, which is not always effective. An alternative strategy must be employed to avoid bacterial multiplication but must be compatible with economic, health and environmental aspects. This review analyzes the issue of bacterial contamination in sugarcane-based fuel ethanol fermentation, and the potential strategies that may be utilized to control bacterial growth besides acid treatment and antibiotics. We have emphasized the efficiency and suitability of chemical products other than acids and those derived from natural sources in industrial conditions. In addition, we have also presented bacteriocins, bacteriophages, and beneficial bacteria as non-conventional antimicrobial agents to mitigate bacterial contamination in the bioethanol industry.

  9. Interaural envelope correlation change discrimination in bilateral cochlear implantees: effects of mismatch, centering, and onset of deafness.

    PubMed

    Goupell, Matthew J

    2015-03-01

    Bilateral cochlear implant (CI) listeners can perform binaural tasks, but they are typically worse than normal-hearing (NH) listeners. To understand why this difference occurs and the mechanisms involved in processing dynamic binaural differences, interaural envelope correlation change discrimination sensitivity was measured in real and simulated CI users. In experiment 1, 11 CI (eight late deafened, three early deafened) and eight NH listeners were tested in an envelope correlation change discrimination task. Just noticeable differences (JNDs) were best for a matched place-of-stimulation and increased for an increasing mismatch. In experiment 2, attempts at intracranially centering stimuli did not produce lower JNDs. In experiment 3, the percentage of correct identifications of antiphasic carrier pulse trains modulated by correlated envelopes was measured as a function of mismatch and pulse rate. Sensitivity decreased for increasing mismatch and increasing pulse rate. The experiments led to two conclusions. First, envelope correlation change discrimination necessitates place-of-stimulation matched inputs. However, it is unclear if previous experience with acoustic hearing is necessary for envelope correlation change discrimination. Second, NH listeners presented with CI simulations demonstrated better performance than real CI listeners. If the simulations are realistic representations of electrical stimuli, real CI listeners appear to have difficulty processing interaural information in modulated signals.

  10. 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.

  11. 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

  12. Robotic hysterectomy versus conventional laparoscopic hysterectomy: outcome and cost analyses of a matched case-control study.

    PubMed

    Sarlos, Dimitri; Kots, Lavonne; Stevanovic, Nebojsa; Schaer, Gabriel

    2010-05-01

    Robotic surgery, with its technical advances, promises to open a new window to minimally invasive surgery in gynaecology. Feasibility and safety of this surgical innovation have been demonstrated in several studies, and now a critical analysis of these new developments regarding outcome and costs is in place. So far only a few studies compare robotic with conventional laparoscopic surgery in gynaecology. Our objective was to evaluate our initial experience performing total robot-assisted hysterectomy with the da Vinci surgical system and compare peri-operative outcome and costs with total laparoscopic hysterectomy. For this prospective matched case-control study at our institution, peri-operative data from our first 40 consecutive total robot-assisted hysterectomies for benign indications were recorded and matched 1:1 with total laparoscopic hysterectomies according to age, BMI and uterus weight. Surgical costs were calculated for both procedures. Surgeons' subjective impressions of robotics were evaluated with a self-developed questionnaire. No conversions to laparotomy or severe peri-operative complications occurred. Mean operating time was 109 (113; 50-170) min for the robotic group and 83 (80; 55-165) min for the conventional laparoscopic group. Mean postoperative hospitalisation for robotic surgery was 3.3 (3; 2-6) days versus 3.9 (4; 2-7) days for the conventional laparoscopic group. Average surgical cost of a robot-assisted laparoscopic hysterectomy was 4067 euros compared to 2151 euros for the conventional laparoscopic procedure at our institution. For the robotic group wider range of motion of the instruments and better ergonomics were considered to be an advantage, and lack of direct access to the patient was stated as a disadvantage. Robot-assited hysterectomy is a feasible and interesting new technique with comparable outcome to total laparoscopic hysterectomy. Operating times of total laparoscopic hysterectomy seem to be achieved quickly especially for

  13. 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.

  14. Instantaneous Conventions

    PubMed Central

    Misyak, Jennifer; Noguchi, Takao; Chater, Nick

    2016-01-01

    Humans can communicate even with few existing conventions in common (e.g., when they lack a shared language). We explored what makes this phenomenon possible with a nonlinguistic experimental task requiring participants to coordinate toward a common goal. We observed participants creating new communicative conventions using the most minimal possible signals. These conventions, furthermore, changed on a trial-by-trial basis in response to shared environmental and task constraints. Strikingly, as a result, signals of the same form successfully conveyed contradictory messages from trial to trial. Such behavior is evidence for the involvement of what we term joint inference, in which social interactants spontaneously infer the most sensible communicative convention in light of the common ground between them. Joint inference may help to elucidate how communicative conventions emerge instantaneously and how they are modified and reshaped into the elaborate systems of conventions involved in human communication, including natural languages. PMID:27793986

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  18. Effects of coupler height mismatch on the structural integrity of railroad tank car stub sills.

    DOT National Transportation Integrated Search

    2001-12-01

    This project evaluated the safety implications of coupler height mismatches on the integrity of railroad tank car stub sills, through a series of static and impact tests. The test car was a loaded tank car instrumented with strain gages at critical l...

  19. Can Mismatch Negativity Be Linked to Synaptic Processes? A Glutamatergic Approach to Deviance Detection

    ERIC Educational Resources Information Center

    Strelnikov, Kuzma

    2007-01-01

    This article aims to provide a theoretical framework to elucidate the neurophysiological underpinnings of deviance detection as reflected by mismatch negativity. A six-step model of the information processing necessary for deviance detection is proposed. In this model, predictive coding of learned regularities is realized by means of long-term…

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

    PubMed

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

    2013-11-01

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