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51.
Studies were conducted to assess the utility of free solution capillary electrophoresis (CE) for monitoring the effects of selected excipients on the thermal denaturation of a model protein (Ribonuclease A, RNase A) at low pH. Thermal denaturation/unfolding experiments were conducted via temperature-controlled CE using a run buffer of 20 mM citric acid in the pH range of 2.3-3.1, with a marker peptide incorporated to correct for temperature-induced changes in endoosmotic flow. The effects of selected excipients on the thermal unfolding of RNase A were then evaluated by adding either sorbitol, sucrose, polyethylene glycol 400 (PEG 400) or 2-methyl-2,4-pentanediol (MPD) to the electrophoretic run buffer (pH 2.3). Confirmatory denaturation experiments were conducted under the same solution conditions using circular dichroism (CD) spectropolarimetry. Using temperature-controlled CE, an increase in solution pH from 2.3 to 2.7 and 3.1 resulted in an increase in transition temperatures of RNase A by approximately 8 and 13 degrees C, respectively. Similar shifts in transition temperatures were observed when thermal denaturation transitions were monitored by far-UV CD. Sorbitol (0.55-1.1 M) and sucrose (0.55 M) each shifted the denaturation transition temperatures of RNase A to higher values, whereas PEG 400 and MPD had minimal effect on the unfolding transition midpoint at the concentrations evaluated (0.55 M for each). The observed changes in the transition temperatures for RNase A as a function of pH and selected excipients were similar when measured by either CE or far-UV CD. These results support the utility of CE for monitoring the effects of neutral excipients on the thermal denaturation of a model protein under selected conditions. The widespread utility of the technique may be limited by the narrow temperature range of most commercial CE instruments and the need to use extreme pH conditions to monitor the complete denaturation transition.  相似文献   
52.
OBJECTIVE: To examine the relative contribution of psychologic factors and physical symptoms to the variance in fatigue in older women with heart failure. METHODS: Eighty women who had been hospitalized in the previous 12 months for heart failure were interviewed. Fifty-seven women completed second interviews 18 months after the first interview. RESULTS: Fatigue was the most frequently occurring physical symptom at both measurement times, and it significantly increased with time. Other physical symptoms contributed uniquely to the variance in fatigue at both measurement times, but psychologic factors did not. At time 1, sleep difficulties, chest pain, and weakness each explained unique variance in fatigue. At time 2, dyspnea was the only variable that explained unique variance in fatigue (9%). Dyspnea also explained a significant portion of the variance (7%) in time 2 fatigue, when time 1 fatigue was controlled. CONCLUSIONS: Fatigue in older women with heart failure is related more to other physical symptoms than psychologic factors.  相似文献   
53.
BACKGROUND: Hepatocellular carcinoma (HCC) over 10 cm in diameter at the time of diagnosis continues to account for a number of patients undergoing hepatic resection. This study evaluated the clinicopathological features and outcome following surgery for large HCC. METHODS: Forty patients with a large HCC (greater than 10 cm) (group 1) resected between 1991 and 1996 were studied retrospectively. They were compared with 245 patients who had smaller HCCs (10 cm or less) (group 2). RESULTS: No patient in group 1 had hepatitis C infection compared with 22.9 per cent in group 2 (P=0.001). Patients in group 1 were significantly younger, had higher alpha-fetoprotein levels (16750 versus 1864 ng/ml; P < 0.001), better liver function, a higher incidence of multiple tumours (27 of 40 versus 42.0 per cent; P=0.003) and venous invasion (35 of 40 versus 52.2 per cent; P < 0.001), and underwent more major resections (37 of 40 versus 26.5 per cent; P < 0.001) than those in group 2. Morbidity and mortality rates and hospital stay were comparable in the two groups. For group 1, the 1-, 3- and 5-year disease-free survival rates were 42, 30 and 28 per cent respectively. Multiple tumours, venous invasion and impaired liver function were factors associated with recurrence. CONCLUSION: Large HCC had specific clinicopathological features. In selected patients, resection is safe and offers the chance of long-term disease-free survival.  相似文献   
54.
Results from a Monte Carlo investigation of the dual photopeak window (DPW) scatter correction method are presented for point and extended sources of Tc-99m in both homogeneous and nonhomogeneous attenuating media. The DPW method uses the ratio of counts in two nonoverlapping energy windows within the photopeak region as input to a regression relation. A pixel-by-pixel estimate of the scatter in the summed windows is obtained and subtracted to yield an estimate of the primary. An approximate tenfold decrease in the scatter fraction and an excellent agreement with the shape of the true scatter distribution were observed  相似文献   
55.
The Toyota Production System (TPS) can result in huge benefits for companies and has been widely implemented around the world. Nevertheless, most adopters emphasize only the technical practices of the TPS, but neglect the critical role of human factors in the implementation of the TPS. Therefore, this study aims at developing an integrated TPS model that fully integrates the technical elements and human elements of the TPS with Total Quality Management (TQM) practices. An empirical study was conducted to confirm the causal relationships among these constructs. In the empirical study, questionnaires were mailed and e‐mailed to 620 companies that had implemented the TPS, and 151 of the completed questionnaires were valid. These 151 respondents were divided into eight categories. The results revealed that the implementation level of each construct was significantly different in each industry. The automobile and motorcycle industries have put a great deal of effort into the application of Humanity, Human Resource Management (HRM), and TQM practices and obtained good results. Other industries, however, ignored the implementation of HRM practices. The results also revealed that the early adopters enjoyed significant benefits from the implementation of the TPS, which led high‐tech companies to start adopting TPS practices and become lean enterprises. © 2011 Wiley Periodicals, Inc.  相似文献   
56.
The Na/K-ATPase is the specific receptor for cardiotonic steroids (CTS) such as ouabain and digoxin. At pharmacological concentrations used in the treatment of cardiac conditions, CTS inhibit the ion-pumping function of Na/K-ATPase. At much lower concentrations, in the range of those reported for endogenous CTS in the blood, they stimulate hypertrophic growth of cultured cardiac myocytes through initiation of a Na/K-ATPase-mediated and reactive oxygen species (ROS)-dependent signaling. To examine a possible effect of endogenous concentrations of CTS on cardiac structure and function in vivo, we compared mice expressing the naturally resistant Na/K-ATPase α1 and age-matched mice genetically engineered to express a mutated Na/K-ATPase α1 with high affinity for CTS. In this model, total cardiac Na/K-ATPase activity, α1, α2, and β1 protein content remained unchanged, and the cardiac Na/K-ATPase dose–response curve to ouabain shifted to the left as expected. In males aged 3–6 months, increased α1 sensitivity to CTS resulted in a significant increase in cardiac carbonylated protein content, suggesting that ROS production was elevated. A moderate but significant increase of about 15% of the heart-weight-to-tibia-length ratio accompanied by an increase in the myocyte cross-sectional area was detected. Echocardiographic analyses did not reveal any change in cardiac function, and there was no fibrosis or re-expression of the fetal gene program. RNA sequencing analysis indicated that pathways related to energy metabolism were upregulated, while those related to extracellular matrix organization were downregulated. Consistent with a functional role of the latter, an angiotensin-II challenge that triggered fibrosis in the α1r/rα2s/s mouse failed to do so in the α1s/sα2s/s. Taken together, these results are indicative of a link between circulating CTS, Na/K-ATPase α1, ROS, and physiological cardiac hypertrophy in mice under baseline laboratory conditions.  相似文献   
57.
Gas hydrates formed in oil production pipelines are crystalline solids where hydrocarbon gas molecules such as methane, propane, and their mixtures are trapped in a cagelike structure by hydrogen‐bonded water molecules to form undesirable plugs. Methanol and glycol are currently used to prevent these plugs via thermodynamic inhibition. Small amounts of water‐soluble polymers may provide an alternate approach for preventing gas hydrates. In this study, we expand the fundamental understanding of water–polymer systems with differential scanning calorimetry. Nonfreezable bound water was used to quantify polymer–water interactions and relate them to the chemical structure for a series of polymers, including acrylamides, cyclic lactams, and n‐vinyl amides. For good interactions, the water structure needs to be stabilized through hydrophobic interactions. An increased hydrophobicity of the pendant group also appears to favor polymer performance as a gas hydrate inhibitor. Good inhibitors, such as poly(diethyl acrylamide) and poly(N‐vinyl caprolactam), also show higher heat capacities, which indicate higher hydrophobicity, than poor performers such as polyzwitterions, in which hydrophilicity dominated. The phase behavior and thermodynamic properties of dilute polymer solutions were also evaluated through measurements of the heat of demixing and lower critical solution temperature. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 2642–2653, 2007  相似文献   
58.
In this paper we describe an apparatus for reproducibly measuring thermal shock resistance of thick polymer layers bonded to metals. The thermal shock behavior is discussed in terms of epoxy samples bonded to an aluminum substrate. It was found that both high resin toughness and low resin thermal expansion coefficient improved thermal shock resistance of thick coatings, but only a sample containing 60wt. % glass beads did not develop a failure crack. Effects of sample thickness, temperature gradient, and resin composition on thermal shock behavior are discussed.  相似文献   
59.
Numerical methods for elliptic partial differential equations (PDEs) within both continuous and hybridized discontinuous Galerkin (HDG) frameworks share the same general structure: local (elemental) matrix generation followed by a global linear system assembly and solve. The lack of inter-element communication and easily parallelizable nature of the local matrix generation stage coupled with the parallelization techniques developed for the linear system solvers make a numerical scheme for elliptic PDEs a good candidate for implementation on streaming architectures such as modern graphical processing units (GPUs). We propose an algorithmic pipeline for mapping an elliptic finite element method to the GPU and perform a case study for a particular method within the HDG framework. This study provides comparison between CPU and GPU implementations of the method as well as highlights certain performance-crucial implementation details. The choice of the HDG method for the case study was dictated by the computationally-heavy local matrix generation stage as well as the reduced trace-based communication pattern, which together make the method amenable to the fine-grained parallelism of GPUs. We demonstrate that the HDG method is well-suited for GPU implementation, obtaining total speedups on the order of 30–35 times over a serial CPU implementation for moderately sized problems.  相似文献   
60.
Future climate change is expected to have wide ranging impacts on the hydrology of mountain rivers because of changes in the magnitudes and timing of rain and snow, as well as the significant spatial variability of topography and other catchment characteristics. In New Zealand, hydropower generation in mountain basins is the primary source of electricity and renewable energy resource in the country. The goal of this study was to simulate and evaluate the potential effects of climate change on hydropower operations in three mountain headwater lakes (lakes Pukaki, Tekapo, and Ohau) in the Upper Waitaki Basin of the central South Island. The TopNet hydrological model was used to estimate catchment runoff and lake inflows based on the 1990s (baseline), 2040s, and 2090s periods. Average temperature and precipitation results from an ensemble of 12 Global Circulation Models based on the IPCC 4th Assessment Report A1B emissions scenario were used as input to TopNet. Linked hydropower lake water balance models were developed and used to simulate hydropower operations including discharge, hydroelectric power generation, and spill based on TopNet future inflow predictions, projected electricity demand, and lake storage and outflow characteristics. Our results indicate that annual lake inflows increase under future climate scenarios, but that there are seasonal effects with increasing flows in winter and early spring, and summer flows decreasing somewhat as a result of increasing temperatures and greater winter rain with less snow. Although overall hydropower generation can increase with the increasing flows and projected electricity demand, the seasonal changes result in demand being met in winter and spring with potential shortfalls in summer and autumn. Maximum annual generation can be achieved for some generating stations, but generation will decrease at other stations and more spill will likely be required through the 2090s because of the seasonal changes. Therefore flood and drought risk could also increase for downstream areas. Results also indicate that by the 2090s electricity demand could exceed generation capacity for these headwater lakes. Copyright © 2016 John Wiley & Sons, Ltd.  相似文献   
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