935 resultados para investigation of head-first binding of substrate with the phe557 mutant soybean lipoxygenase-1
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At head of title: 82d Cong. 1st sess. Senate. Report no. 1037
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By Dewey Anderson, executive secretary.
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Purpose : The purpose of this article is to critically review the literature to examine factors that are most consistently related to employment outcome following traumatic brain injury (TBI), with a particular focus on metacognitive skills. It also aims to develop a conceptual model of factors related to employment outcome. Method : The first stage of the review considered 85 studies published between 1980 and December 2003 which investigated factors associated with employment outcome following TBI. English-language studies were identified through searches of Medline and PsycINFO, as well as manual searches of journals and reference lists. The studies were evaluated and rated by two independent raters (Kappa = 0.835) according to the quality of their methodology based upon nine criteria. Fifty studies met the criteria for inclusion in the second stage of the review, which examined the relationship between a broad range of variables and employment outcome. Results : The factors most consistently associated with employment outcome included pre-injury occupational status, functional status at discharge, global cognitive functioning, perceptual ability, executive functioning, involvement in vocational rehabilitation services and emotional status. Conclusions : A conceptual model is presented which emphasises the importance of metacognitive, emotional and social environment factors for improving employment outcome.
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The present study investigated neuropsychological and psychological factors associated with successful treatment outcome following a group intervention for individuals with acquired brain injury (ABI). Participants were classified into two groups (Clinically Improved and Not Improved) based upon the findings of a previous study (Ownsworth, McFarland, & Young, 2000a). A discriminant analysis was used to predict group membership on three outcome measures (Awareness and Strategy Behaviour indices of the Self-Regulation Skills Interview and the Psychosocial Dimension of the Sickness Impact Profile) between pre-assessment and post-assessment, and between pre-assessment and 6 months follow-up. Neuropsychological factors involved measures of executive functioning and psychological factors were assessed using measures of personality-related denial and coping-related denial. Overall, the results indicated that individuals with impaired executive functioning were most likely to be classified as Clinically Improved on measures of awareness, strategy behaviour and psychosocial functioning. Individuals who deny or minimise their ABI symptoms were less likely to improve their psychosocial functioning following the group intervention. Future research needs to evaluate interventions for enhancing self-regulation skills and improving psychosocial functioning for individuals who employ denial as a main strategy for coping following ABI.
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A number of investigators have studied the application of oscillatory energy to a metal undergoing plastic deformation. Their results have shown that oscillatory stresses reduce both the stress required to initiate plastic deformation and the friction forces between the tool and workpiece. The first two sections in this thesis discuss historically and technically the devolopment of the use of oscillatory energy techniques to aid metal forming with particular reference to wire drawing. The remainder of the thesis discusses the research undertaken to study the effect of applying longitudinal oscillations to wire drawing. Oscillations were supplied from an electric hydraulic vibrator at frequencies in the range 25 to 500 c/s., and drawing tests were performed at drawing speeds up to 50 ft/m. on a 2000 lbf. bull-block. Equipment was designed to measure the drawing force, drawing torque, amplitude of die and drum oscillation and drawing speed. Reasons are given for selecting mild steel, pure and hard aluminium, stainless steel and hard copper as the materials to be drawn, and the experimental procedure and calibration of measuring equipment arc described. Results show that when oscillatory stresses are applied at frequencies within the range investigated : (a) There is no reduction in the maximum drawing load. (b) Using sodium stearate lubricant there is a negligible reduction in the coefficient of friction between the die and wire. (c) Pure aluminium does not absorb sufficient oscillatory energy to ease the movement of dislocations. (d) Hard aluminium is not softened by oscillatory energy accelerating the diffusion process. (e) Hard copper is not cyclically softened. A vibration analysis of the bull-block and wire showed that oscillatory drawiing in this frequency range, is a mechanical process of straining; and unstraining the drawn wire, and is dependent upon the stiffness of the material being drawn and the drawing machine. Directions which further work should take are suggested.
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Athletic training is an allied health profession recognized by the American Medical Association requiring certification by examination. There are two routes towards certification as an athletic trainer: attending a university with an accredited athletic training program or with an internship program By 2004, the only route towards certification will be by attending a Commission on Accreditation of Allied Health Education Programs (CAAHEP) or National Athletic Trainers' Association (NATA) accredited athletic training program. CAAHEP looks at passing rates on the NATA Board of Certification (NATABOC) examination when granting accreditation. This study examined characteristics of programs associated with first time passing rates. ^ Directors from 39 CAAHEP or NATA accredited athletic training programs completed a descriptive 17-question survey regarding academic characteristics, faculty characteristics, and program characteristics. Analysis used Spearman's rho correlation coefficient, with significance of p = <.05. Four program directors were interviewed to gather additional insight. ^ There were three program characteristics that showed a significant positive association with first attempt passing rates: the number of full-time and part-time approved clinical instructors (ACIs), and the number of students in the program. Further investigation found a statistically significant association between a low ratio of ACIs to athletic training students and first time passing rates. ACIs are certified athletic trainers (ATCs) who have received special training in order to supervise athletic training students. CAAHEP mandates a 1:8 ratio of ATCs to athletic training student. This study showed that a smaller ratio of ATC to student in combination with ACI training was significantly associated with higher first time passing rates. The number of courses above the required 13 delineated by the Education Council showed a significant negative association with first attempt passing rates. ^ Universities seeking or maintaining accreditation should incorporate characteristics associated with a higher passing rate on the NATABOC examination. Characteristics include utilizing a large number of full-time and part-time ACIs, admitting a large number of students into the program while maintaining a low ACI to athletic training student ratio, and offering curricula that focuses on the 13 courses that have been deemed relevant to the athletic training curriculum by the Education Council. ^
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Hydrogeologic variables controlling groundwater exchange with inflow and flow-through lakes were simulated using a three-dimensional numerical model (MODFLOW) to investigate and quantify spatial patterns of lake bed seepage and hydraulic head distributions in the porous medium surrounding the lakes. Also, the total annual inflow and outflow were calculated as a percentage of lake volume for flow-through lake simulations. The general exponential decline of seepage rates with distance offshore was best demonstrated at lower anisotropy ratio (i.e., Kh/Kv = 1, 10), with increasing deviation from the exponential pattern as anisotropy was increased to 100 and 1000. 2-D vertical section models constructed for comparison with 3-D models showed that groundwater heads and seepages were higher in 3-D simulations. Addition of low conductivity lake sediments decreased seepage rates nearshore and increased seepage rates offshore in inflow lakes, and increased the area of groundwater inseepage on the beds of flow-through lakes. Introduction of heterogeneity into the medium decreased the water table and seepage ratesnearshore, and increased seepage rates offshore in inflow lakes. A laterally restricted aquifer located at the downgradient side of the flow-through lake increased the area of outseepage. Recharge rate, lake depth and lake bed slope had relatively little effect on the spatial patterns of seepage rates and groundwater exchange with lakes.
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A first-principles method is applied to find the intra and intervalley n-type carrier scattering rates for substitutional carbon in silicon. The method builds on a previously developed first-principles approach with the introduction of an interpolation technique to determine the intravalley scattering rates. Intravalley scattering is found to be the dominant alloy scattering process in Si1-xCx, followed by g-type intervalley scattering. Mobility calculations show that alloy scattering due to substitutional C alone cannot account for the experimentally observed degradation of the mobility. We show that the incorporation of additional charged impurity scattering due to electrically active interstitial C complexes models this residual resistivity well.
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Multidrug resistance arising from the activity of integral membrane transporter proteins presents a global public health threat. In bacteria such as Escherichia coli, transporter proteins belonging to the major facilitator superfamily make a considerable contribution to multidrug resistance by catalysing efflux of myriad structurally and chemically different antimicrobial compounds. Despite their clinical relevance, questions pertaining to mechanistic details of how these promiscuous proteins function remain outstanding, and the role(s) played by individual amino acid residues in recognition, binding and subsequent transport of different antimicrobial substrates by multidrug efflux members of the major facilitator superfamily requires illumination. Using in silico homology modelling, molecular docking and mutagenesis studies in combination with substrate binding and transport assays, we identified several amino acid residues that play important roles in antimicrobial substrate recognition, binding and transport by Escherichia coli MdtM, a representative multidrug efflux protein of the major facilitator superfamily. Furthermore, our studies suggested that 'aromatic clamps' formed by tyrosine and phenylalanine residues located within the substrate binding pocket of MdtM may be important for antimicrobial substrate recognition and transport by the protein. Such 'clamps' may be a structurally and functionally important feature of all major facilitator multidrug efflux proteins.
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G protein-coupled receptors (GPCRs) are seven-pass integral membrane proteins that act as transducers of extracellular signals across the lipid bilayer. Their location and involvement in basic and pathological physiological processes has secured their role as key targets for pharmaceutical intervention. GPCRs are targeted by many of the best-selling drugs on the market and there are a substantial number of GPCRs that are yet to be characterised; these could offer interest for therapeutic targeting. GPR35 is one such receptor that, as a result of gene knockout and genome wide association studies, has attracted interest through its association with cardiovascular and gastrointestinal disease. Elucidation of the basic physiological function of GPR35 has, however, been difficult due a paucity of potent and selective ligands in addition to a lack of consensus on the endogenous ligand. Herein, a focussed drug discovery effort was carried out to identify agonists of GPR35. Various in vitro cellular assays were employed in conjunction with N- or C-terminally manipulated forms of the receptor to investigate GPR35’s signalling profile and to provide an assay format suitable for the characterisation of newly identified ligands. Although GPR35 associates with both Gαi/o and Gα13 families of small heterotrimeric G proteins, the G protein-independent β-arrestin-2 recruitment format was found to be the most suited to drug screening efforts. Small molecule compound screening, carried out in conjunction with the Medical Research Council Technology, identified compound 1 as the most potent ligand of human GPR35 reported at that time. However, the lower efficacy and potency of compound 1 at the rodent species orthologues of GPR35 prevented its use in in vivo studies. A subsequent effort, carried out with Novartis, focused on mast cell stabilisers as putative agonists of GPR35, revealed lodoxamide and bufrolin as highly potent agonists that activated human and rat GPR35 with equal potency. This finding offered–for the first time–the opportunity to employ the same GPR35 ligand between species at a similar concentration, an important factor to consider when translating rodent in vivo functional studies to those in man. Additionally, using molecular modelling and site directed mutagenesis studies, these newly identified compounds were used to aid characterisation of the ligand binding pockets of human and rat GPR35 to reveal the molecular basis of species selectivity at this receptor. In summary, this research effort presents GPR35 tool compounds that can now be used to dissect the basic biology of GPR35 and investigate its contribution to disease.
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In this work, we investigate the influence of some growth parameters such as high microwave power ranging from 3.0 to 4.0 kW and N2 additive on the incorporation of bonded hydrogen defects in nanocrystalline diamond (NCD) films grown through a small amount of pure N2 addition into conventional 4% CH4/H2 plasma using a 5 kW microwave plasma CVD system. Incorporation form and content of hydrogen point defects in the NCD films produced with pure N2 addition was analyzed by employing Fourier-transform infrared (FTIR) spectroscopy for the first time. A large amount of hydrogen related defects was detected in all the produced NCD films with N2 additive ranging from 29 to 87 µm thick with grain size from 47 nm to 31 nm. Furthermore, a specific new H related sharp absorption peak appears in all the NCD films grown with pure N2/CH4/H2 plasma at high powers and becomes stronger at powers higher than 3.0 kW and is even stronger than the 2920 cm−1 peak, which is commonly found in CVD diamond films. Based on these experimental findings, the role of high power and pure nitrogen addition on the growth of NCD films including hydrogen defect formation is analyzed and discussed.
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The aim of this study was to determine the frequency of leukemia in parents of patients with nonsyndromic cleft lip and/or cleft palate (NSCL/P). This case-control study evaluated first-degree family members of 358 patients with NSCL/P and 1,432 subjects without craniofacial alterations or syndromes. Statistical analysis was carried out using Fisher's test. From the 358 subjects with NSCL/P, 3 first-degree parents had history of leukemia, while 2 out of 1,432 subjects from the unaffected group had a family history of leukemia. The frequency of positive family history of leukemia was not significantly increased in first-degree relatives of patients with NSCL/P.
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A new species of the formerly monotypic genus Trichogenes is described from a high-altitude stream of the rio Itapemirim system, an isolated Atlantic drainage in the State of Espírito Santo, southeastern Brazil. Trichogenes claviger, new species, differs from all other trichomycterids by the sexually dimorphic posterior process of the opercle, much elongated in males; the terminal mouth; the deeply bifurcated anterior neural spines and the presence of a large anterodorsal claw-like process on the neural arches of the anterior four free vertebrae. The new species also differs from its only congener, T. longipinnis, by a number of additional traits, including the the lack of branched anal-fin rays in specimens of any size; the broader than long posterior nostril; the deeper head (head depth 72.9-86.6% HL); the presence of a fine dark line along the base of the anal fin; the lack of dark spots on cheeks; the shape of the interopercle; the presence of odontodes on a bony expansion on the posterodorsal margin of the interopercle; the fewer vertebrae (35); the absence of an antorbital; and the fewer pleural ribs (eight). Small juveniles of the new species are also strikingly different from those of all other Trichomycteridae, including T. longipinnis, having a very large lateral eye, an upturned mouth, and compressed head. Trichogenes claviger occurs in shaded sectors of a blackwater sluggish stream with sandy substrate and patchy accumulations of vegetable debris, a habitat markedly different from the rocky torrential environment known for T. longipinnis. A comparison of the internal anatomy of the two species provides the basis for a hypothesis of a monophyletic Trichogenes. Data from the new species further support a sister-group relationship between Trichogeninae and Copionodontinae, as well as the position of that clade as sister group to all remaining Trichomycteridae.
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Transparent conducting oxides (TCO) are widely used in technological applications ranging from photovoltaics to thin-film transparent field-effect transistors. In this work we report a first-principles investigation, based on density-functional theory, of the atomic and electronic properties of Ga(2)O(3)(ZnO)(6) (GZO(6)), which is a promising candidate to be used as host oxide for wide band gap TCO applications. We identify a low-energy configuration for the coherent distribution of the Ga and Zn atoms in the cation positions within the experimentally reported orthorhombic GZO(6) structure. Four Ga atoms are located in four-fold sites, while the remaining 12 Ga atoms in the unit cell form four shared Ga agglomerates (a motif of four atoms). The Zn atoms are distributed in the remaining cation sites with effective coordination numbers from 3.90 to 4.50. Furthermore, we identify the natural formation of twin-boundaries in GZO(6), which can explain the zigzag modulations observed experimentally by high-resolution transmission electron microscopy in GZO(n) (n=9). Due to the intrinsic twin-boundary formation, polarity inversion in the ZnO tetrahedrons is present which is facilitated by the formation of the Ga agglomerates. Our analysis shows that the formation of fourfold Ga sites and Ga agglomerates are stabilized by the electronic octet rule, while the distribution of Ga atoms and the formation of the twin-boundary help alleviate excess strain. Finally we identify that the electronic properties of GZO(6) are essentially determined by the electronic properties of ZnO, i.e., there are slight changes in the band gap and optical absorption properties.