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11.
ME Williamson WG Lewis PJ Finan AS Miller PJ Holdsworth D Johnston 《Canadian Metallurgical Quarterly》1995,38(4):411-418
Recently, site-directed mutagenesis has been applied to protein-derived metal ligands in a way that permits the replacement in trans of protein ligands. The chemical diversity of ligands available using this method far exceeds that attainable using standard mutagenesis. Non-conservative ligand replacement can yield novel metalloproteins with altered ligand-binding, enzymatic activities, and spectroscopic properties. Conservative ligand substitution, or 'ligand detachment', allows the structural and functional effects of the covalent linkage between the ligand and the protein to be evaluated; this linkage is often proposed to play a critical role in modulating the structure and reactivity of the metal center. Furthermore, this method can be exploited to study the details of molecular recognition at the structural, thermodynamic, and dynamic levels. 相似文献
12.
A growing body of recent work documents the potential benefits of sub-band processing over wideband processing in automatic speech recognition and, less usually, speaker recognition. It is often found that the sub-band approach delivers performance improvements (especially in the presence of noise), but not always so. This raises the question of precisely when and how sub-band processing might be advantageous, which is difficult to answer because there is as yet only a rudimentary theoretical framework guiding this work. We describe a simple sub-band speaker recognition system designed to facilitate experimentation aimed at increasing understanding of the approach. This splits the time-domain speech signal into 16 sub-bands using a bank of second-order filters spaced on the psychophysical mel scale. Each sub-band has its own separate cepstral-based recognition system, the outputs of which are combined using the sum rule to produce a final decision. We find that sub-band processing leads to worthwhile reductions in both the verification and identification error rates relative to the wideband system, decreasing the identification error rate from 3.33% to 0.56% and equal error rate for verification by approximately 50% for clean speech. The hypothesis is advanced that, unlike the wideband system, sub-band processing effectively constrains the free parameters of the speaker models to be more uniformly deployed across frequency: as such, it offers a practical solution to the bias/variance dilemma of data modeling. Much remains to be done to explore fully the new paradigm of sub-band processing. Accordingly, several avenues for future work are identified. In particular, we aim to explore the hypothesis of a practical solution to the bias/variance dilemma in more depth. 相似文献
13.
Zautra Alex J.; Davis Mary C.; Reich John W.; Nicassario Perry; Tennen Howard; Finan Patrick; Kratz Anna; Parrish Brendt; Irwin Michael R. 《Canadian Metallurgical Quarterly》2008,76(3):408
This research examined whether cognitive behavioral therapy and mindfulness interventions that target responses to chronic stress, pain, and depression reduce pain and improve the quality of everyday life for adults with rheumatoid arthritis (RA). The 144 RA participants were clustered into groups of 6-10 participants and randomly assigned to 1 of 3 treatments: cognitive behavioral therapy for pain (P); mindfulness meditation and emotion regulation therapy (M); or education-only group (E), which served as an attention placebo control. The authors took a multimethod approach, employing daily diaries and laboratory assessment of pain and mitogen-stimulated levels of interleukin-6 (IL-6), a proinflammatory cytokine. Participants receiving P showed the greatest Pre to Post improvement in self-reported pain control and reductions in the IL-6; both P and M groups showed more improvement in coping efficacy than did the E group. The relative value of the treatments varied as a function of depression history. RA patients with recurrent depression benefited most from M across several measures, including negative and positive affect and physicians' ratings of joint tenderness, indicating that the emotion regulation aspects of that treatment were most beneficial to those with chronic depressive features. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
14.
The rate constants of acetylcholine receptor channels (AChR) desensitization and recovery were estimated from the durations and frequencies of clusters of single-channel currents. Diliganded-open AChR desensitize much faster than either unliganded- or diliganded-closed AChR, which indicates that the desensitization rate constant depends on the status of the activation gate rather than the occupancy of the transmitter binding sites. The desensitization rate constant does not change with the nature of the agonist, the membrane potential, the species of permeant cation, channel block by ACh, the subunit composition (epsilon or gamma), or several mutations that are near the transmitter binding sites. The results are discussed in terms of cyclic models of AChR activation, desensitization, and recovery. In particular, a mechanism by which activation and desensitization are mediated by two distinct, but interrelated, gates in the ion permeation pathway is proposed. 相似文献
15.
Mtiraoui N Zammiti W Ghazouani L Braham NJ Saidi S Finan RR Almawi WY Mahjoub T 《Reproduction (Cambridge, England)》2006,131(2):395-401
Because they have been described as strong risk factors for idiopathic recurrent pregnancy losses (RPLs), we assessed the association between the methylenetetrahydrofolate reductase (MTHFR) single-nucleotide polymorphisms (SNPs) C677T and A1298C and hyperhomocysteinemia in Tunisian women with idiopathic RPL. Study subjects comprised 200 patients with more than three consecutive RPLs, and 200 age-matched parous control women. C677T and A1298C SNPs were analyzed by PCR-RFLP analysis, and fasting serum homocysteine was measured with ELISA. The frequency of MTHFR 677T/T (30.0 vs 7.0%) and 1298C/C (13.5 vs 4.0%) genotypes was significantly higher in patients. While it was similar among patients and controls (P = 0.095), higher homocysteine was seen with the T/T (but not 1298A/C and 1298C/C) genotype among patients and controls compared with non-T/T carriers (P < 0.05), and in patients vs controls. Higher prevalence of MTHFR 677T/T was seen in late (P < 0.05) and early-late (P < 0.001) RPL, while higher prevalence of 1298C/C genotype was seen only in early-late RPL (P < 0.001), and the prevalence of double heterozygotes was statistically not significant between patients and controls (P = 0.10; odds ratio = 2.73). Logistic regression analysis showed that, after adjusting for all variables, homozygosity for MTHFR C677T was associated with late (P < 0.001), and combined early-late (P < 0.001), while homozygosity for A1298C was associated only with combined early-late (P = 0.026), as was secondary-level education, which was associated with early (P = 0.005), late (P = 0.026) and combined early-late (P = 0.004) abortions. Homozygosity for MTHFR C677T (late and early-late) and A1298C (early-late) are risk factor for RPLs, irrespectively of total homocysteine levels. 相似文献
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17.
Resistive magnetohydrodynamics (MHD) is described by a set of eight coupled, nonlinear, three-dimensional, time-dependent, partial differential equations. A computer code, IMP (Implicit MHD Program), has been developed to solve these equations numerically by the method of finite differences on an Eulerian mesh. In this model, the equations are expressed in orthogonal curvilinear coordinates, making the code applicable to a variety of coordinate systems. The Douglas-Gunn algorithm for Alternating-Direction Implicit (ADI) temporal advancement is used to avoid the limitations in timestep size imposed by explicit methods. The equations are solved simultaneously to avoid synchronization errors. While the continuity and magnetic field equations are expressed as conservation laws, the momentum and energy equations are nonconservative. This is to: (1) provide enhanced numerical stability by eliminating errors introduced by the nonvanishing of τ · B on the finite difference mesh; and, (2) allow the simulation of low β plasmas. The resulting finite difference equations are a coupled system of nonlinear algebraic equations which are solved by the Newton-Raphson iteration technique. We apply our model to a number of problems of importance in magnetic fusion research. Ideal and resistive internal kink instabilities are simulated in a Cartesian geometry. Growth rates and nonlinear saturation amplitudes are found to be in agreement with previous analytic and numerical predictions. We also simulate these instabilities in a torus, which demonstrates the versatility of the orthogonal curvilinear coordinate representation. 相似文献
18.
Sarka Jelinkova Yvonne Sleiman Petr Fojtík Franck Aimond Amanda Finan Gerald Hugon Valerie Scheuermann Deborah Beckerov Olivier Cazorla Marie Vincenti Pascal Amedro Sylvain Richard Josef Jaros Petr Dvorak Alain Lacampagne Gilles Carnac Vladimir Rotrekl Albano C. Meli 《International journal of molecular sciences》2021,22(9)
Duchenne muscular dystrophy (DMD) is a devastating condition shortening the lifespan of young men. DMD patients suffer from age-related dilated cardiomyopathy (DCM) that leads to heart failure. Several molecular mechanisms leading to cardiomyocyte death in DMD have been described. However, the pathological progression of DMD-associated DCM remains unclear. In skeletal muscle, a dramatic decrease in stem cells, so-called satellite cells, has been shown in DMD patients. Whether similar dysfunction occurs with cardiac muscle cardiovascular progenitor cells (CVPCs) in DMD remains to be explored. We hypothesized that the number of CVPCs decreases in the dystrophin-deficient heart with age and disease state, contributing to DCM progression. We used the dystrophin-deficient mouse model (mdx) to investigate age-dependent CVPC properties. Using quantitative PCR, flow cytometry, speckle tracking echocardiography, and immunofluorescence, we revealed that young mdx mice exhibit elevated CVPCs. We observed a rapid age-related CVPC depletion, coinciding with the progressive onset of cardiac dysfunction. Moreover, mdx CVPCs displayed increased DNA damage, suggesting impaired cardiac muscle homeostasis. Overall, our results identify the early recruitment of CVPCs in dystrophic hearts and their fast depletion with ageing. This latter depletion may participate in the fibrosis development and the acceleration onset of the cardiomyopathy. 相似文献
19.
Finan P. H.; Okun M. A.; Kruszewski D.; Davis M. C.; Zautra A. J.; Tennen H. 《Canadian Metallurgical Quarterly》2010,29(4):429
Objective: The purpose of this study was to examine the interaction of daily concurrent positive interpersonal events (PIE) and negative interpersonal events (NIE) on the daily experience of negative affect and fatigue in a sample of men and women with rheumatoid arthritis. Two hypotheses were made. The blunting hypothesis predicted that NIE would nullify the beneficial influence of PIE on outcome measures, and the buffering hypothesis predicted that PIE would offset the adverse influence of NIE. Design: Participants completed up to 30 consecutive daily diaries. Multilevel modeling was used to examine the day-to-day dependencies among study variables. Main Outcome Measures: The primary outcomes were daily negative affect and fatigue. Results: In support of the blunting hypothesis, on days when NIE were diminished, PIE were associated with a greater reduction in fatigue. In contrast, consistent with the buffering hypothesis, on days when PIE were elevated, NIE were associated with a lesser increase in negative affect. Conclusion: The examination of concurrent PIE and NIE provides a unique perspective on the role of interpersonal events in affective and physiological outcomes, beyond that which can be gained from the examination of either type of event in isolation. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
20.
Finan Patrick H.; Zautra Alex J.; Davis Mary C.; Lemery-Chalfant Kathryn; Covault Jonathan; Tennen Howard 《Canadian Metallurgical Quarterly》2010,29(3):245
Reports an error in Genetic influences on the dynamics of pain and affect in fibromyalgia by Patrick H. Finan, Alex J. Zautra, Mary C. Davis, Kathryn Lemery–Chalfant, Jonathan Covault and Howard Tennen (Health Psychology, 2010[Mar], Vol 29[2], 134-142). In the article, grant information was omitted from the author note. The authors wish to acknowledge grant support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01 AR046034: Alex J. Zautra, PI). (The following abstract of the original article appeared in record 2010-04888-006.) Objective: The purpose of the present investigation was to determine if variation in the catechol- O-methyltransferase (COMT) and mu-opioid receptor (OPRM1) genes is associated with pain-related positive affective regulation in fibromyalgia (FM). Design: Forty-six female patients with FM completed an electronic diary that included daily assessments of positive affect and pain. Between- and within-person analyses were conducted with multilevel modeling. Main Outcome Measure: Daily positive affect was the primary outcome measure. Results: Analyses revealed a significant gene × experience interaction for COMT, such that individuals with met/met genotype experienced a greater decline in positive affect on days when pain was elevated than did either val/met or val/val individuals. This finding supports a role for catecholamines in positive affective reactivity to FM pain. A gene × experience interaction for OPRM1 also emerged, indicating that individuals with at least one asp?? allele maintained greater positive affect despite elevations in daily pain than those homozygous for the asn?? allele. This finding may be explained by the asp?? allele’s role in reward processing. Conclusions: Together, the findings offer researchers ample reason to further investigate the contribution of the catecholamine and opioid systems, and their associated genomic variants, to the still poorly understood experience of FM. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献