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Structural design of a practical spherical suspendome with the diameter of 122m was carried out in China Construction (Shenzhen) Design International (CCDI) in 2006. The suspendome structure is a new type of large-span spatial str...
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Structural design of a practical spherical suspendome with the diameter of 122m was carried out in China Construction (Shenzhen) Design International (CCDI) in 2006. The suspendome structure is a new type of large-span spatial structure which is widely used in the sports buildings. Several suspendome structures have been constructed as the structural roof in the sports arena in China in recent years. As is known to all, prestresses in the cable-strut system are crucial to the tensegric system, and the determination of prestress level and distribution is somewhat complicated. However, no provisions has been provided by current Chinese design codes of practice for the suspendome structure. This paper gives out the detailed prestress design procedure for the practical sports arena which is to be built in Jinan City, China. General purpose finite element package ANSYS is utilized for the analyses. The self-internal-force mode and the prestress level ratio among three ring cables are investigated to determine the prestress in the cable. Linear static analyses are then carried out to validate the prestress efficiency. It has been shown that prestress defined by this way has much influence on the deformation and the internal force of the upper reticulated shell structure. The linear elastic buckling and the geometrically nonlinear stability analysis are also presented. The snap-through phenomenon of the structure is investigated to determine the critical load carrying capacity of stability. The infulence of live load distribution patterns and imperfections on suspendome is addressed in details. The results from the studies can not only be refered for direct design use, and also for the design of similar hybrid structures.
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Software refactoring is an effective method for improvement of software quality while software external behavior remains unchanged. To facilitate software refactoring, a number of tools have been proposed for code smell detection ...
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Software refactoring is an effective method for improvement of software quality while software external behavior remains unchanged. To facilitate software refactoring, a number of tools have been proposed for code smell detection and/or for automatic or semi-automatic refactoring. However, these tools are passive and human driven, thus making software refactoring dependent on developers' spontaneity. As a result, software engineers with little experience in software refactoring might miss a number of potential refactorings or may conduct refactorings later than expected. Few refactorings might result in poor software quality, and delayed refactorings may incur higher refactoring cost. To this end, we propose a monitor-based instant refactoring framework to drive inexperienced software engineers to conduct more refactorings promptly. Changes in the source code are instantly analyzed by a monitor running in the background. If these changes have the potential to introduce code smells, i.e., signs of potential problems in the code that might require refactorings, the monitor invokes corresponding smell detection tools and warns developers to resolve detected smells promptly. Feedback from developers, i.e., whether detected smells have been acknowledged and resolved, is consequently used to optimize smell detection algorithms. The proposed framework has been implemented, evaluated, and compared with the traditional human-driven refactoring tools. Evaluation results suggest that the proposed framework could drive inexperienced engineers to resolve more code smells (by an increase of 140 percent) promptly. The average lifespan of resolved smells was reduced by 92 percent. Results also suggest that the proposed framework could help developers to avoid similar code smells through timely warnings at the early stages of software development, thus reducing the total number of code smells by 51 percent.
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Homocysteine is increased during pathological conditions, endangering vascular and cognitive functions, and elevated homocysteine during pregnancy may be correlated with an increased incidence of schizophrenia in the offspring. Th...
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Homocysteine is increased during pathological conditions, endangering vascular and cognitive functions, and elevated homocysteine during pregnancy may be correlated with an increased incidence of schizophrenia in the offspring. This study showed that millimolar homocysteine concentrations in saline medium cause phosphorylation of extracellular-signal regulated kinases 1 and 2 (ERK(1/2)) in cerebellar granule neurons, inhibitable by metabotropic but not ionotropic glutamate receptor antagonists. These findings are analogous to observations by Zieminska et al. (2003), that similar concentrations cause neuronal death. However, these concentrations are much higher than those occurring clinically during hyperhomocysteinemia. It is therefore important that a approximately 10-fold increase in potency occurred in the presence of the glutamate precursor glutamine, when ERK(1/2) phosphorylation became inhibitable by NMDA or non-NMDA antagonists and dependent upon epidermal growth factor (EGF) receptor transactivation. However, glutamate release to the medium was reduced, suggesting that reversal of the cystine/glutamate antiporter, system X(c)(-) could be involved in potentiation of the response by causing a localized release of initially accumulated homocysteine. In agreement with this hypothesis further enhancement of ERK(1/2) phosphorylation occurred in the additional presence of cystine. Pharmacological inhibition of system X(c)(-) prevented the effect of micromolar homocysteine concentrations, and U0126-mediated inhibition of ERK(1/2) phosphorylation enhanced homocysteine-induced death. In conclusion, homocysteine interacts with system X(c)(-) like quisqualate (Venkatraman et al. 1994), by self-sensitization with cystine and/or glutamate, establishing high local homocysteine concentrations, which activate adjacent ionotropic glutamate receptors and cause neurotoxicity.
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Currently, the concept of greening the Internet is emerging with the increasingly acute energy crisis. Reducing the power consumption in IP over wavelength-division multiplexing (WDM) optical networks is of great significance. Fro...
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Currently, the concept of greening the Internet is emerging with the increasingly acute energy crisis. Reducing the power consumption in IP over wavelength-division multiplexing (WDM) optical networks is of great significance. From the perspective of traffic engineering, green grooming has performed well in terms of power savings. However, in a more realistic network, some traffic characteristics are not taken into account. Moreover, most methods of green grooming are applied to a single network. As the network scale continuously becomes larger, the backbone presents a multidomain structure. Considering the peak traffic distribution in the multidomain network, i.e., that the peak traffic tends to scatter over boundary nodes, we propose a novel hose-model separation to emulate the limited traffic information in a more realistic optical network. To maximize the power efficiency, we determine the inverse power-efficiency ratio by theoretical analysis. We then utilize a heuristic, referred to as minimizing the total inverse power-efficiency ratio (MTPR), to establish lightpaths. The simulation results have demonstrated the effectiveness of MTPR under different topologies and various traffic patterns.
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AIMS: Cardiac glycosides induce cardiomyocyte hypertrophy via yet to be defined mechanisms. These hypertrophic effects are likely related to changes in intracellular signalling secondary to Na(+)-K(+) ATPase (NKA) inhibition which...
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AIMS: Cardiac glycosides induce cardiomyocyte hypertrophy via yet to be defined mechanisms. These hypertrophic effects are likely related to changes in intracellular signalling secondary to Na(+)-K(+) ATPase (NKA) inhibition which would produce elevations in intracellular sodium concentrations. Sodium-hydrogen exchanger isoform 1 (NHE-1) also contributes to intracellular sodium regulation. Accordingly, we determined the contribution of NHE-1 to cardiac glycoside-induced hypertrophy. METHODS AND RESULTS: The majority of the experiments were performed on cultured neonatal rat ventricular myocytes exposed to either ouabain (100 microM) or digoxin (40 microM) for 24 h, although additional experiments were also done using adult left ventricular myocytes with 30 microM of either glycoside. Both glycosides increased cell surface area by 30% and atrial natriuretic peptide gene expression by two- to three-fold (P < 0.05 for both). These effects were associated with a significant reduction in the expression of two NKA isoforms, alpha(2) and alpha(3), whereas the alpha(1) isoform was unaffected. Conversely, both glycosides increased NHE-1 expression in cardiomyocytes by approximately two-fold and significantly increased intracellular sodium concentrations by more than 60% (P < 0.05). Both ouabain and digoxin were also found to significantly increase phosphorylation of mitogen-activated protein kinases. All these effect were prevented when identical experiments were carried out in the presence of the NHE-1 inhibitors EMD 87580 or AVE 4890. Identical results were obtained using adult myocytes, although this was associated with downregulation of all three NKA isoforms. Glycoside-induced increase in cell shortening or intracellular Ca(2+) transients was not significantly affected by NHE-1 inhibition. CONCLUSION: When taken together, these studies show that NHE-1 inhibition attenuates the hypertrophic effect of cardiac glycosides without affecting inotropic parameters and suggest a possible approach to limiting glycoside-induced hypertrophic responses while preserving therapeutic, i.e. inotropic, actions.
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The asymmetric traveling salesman problem (ATSP) appears in various applications. Although there are several heuristic approaches to its solution, the problem is still a difficult combinatorial optimization problem. This work prop...
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The asymmetric traveling salesman problem (ATSP) appears in various applications. Although there are several heuristic approaches to its solution, the problem is still a difficult combinatorial optimization problem. This work proposes a novel hybrid approach specialized for the ATSP. The proposed method incorporates an improved genetic algorithm (IGA) and some optimization strategies that contribute to its effectiveness. In the IGA, both the crossover operation and the mutation operation are improved by selecting the optimum from a set of solutions. Three strategies: immigration, local optimization and global optimization are established based on several empirical optimization strategies to improve the evolution of the IGA. Computational experiments are conducted on 16 ATSP instances available in the TSPLIB (traveling salesman problem library). The comparative study shows that our proposed approach outperforms several other published algorithms.
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For more than a decade, turbo spin echo (TSE) pulse sequences have been suggested as an alternative to echo planar imaging (EPI) sequences for fMRI studies. Recent development in parallel imaging has renewed the interest in develo...
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For more than a decade, turbo spin echo (TSE) pulse sequences have been suggested as an alternative to echo planar imaging (EPI) sequences for fMRI studies. Recent development in parallel imaging has renewed the interest in developing more robust TSE sequences for fMRI. In this study, a modified half Fourier acquisition single-shot TSE (mHASTE) sequence has been developed with a three-fold GRAPPA to improve temporal resolution as well as a preparation time to enhance BOLD sensitivity. Using a classical flashing checkerboard block design, the BOLD signal characteristics of this novel method have been systematically analyzed as a function of several sequence parameters and compared to those of gradient-echo and spin-echo EPI sequences. Experimental studies on visual cortex of five volunteers have provided evidence suggesting that mHASTE can be more sensitive to extra-vascular BOLD effects around microvascular networks, which leads to more accurate function localization. The studies also show that the activation cluster size in mHASTE increases with the refocusing RF flip angle and TE while decreasing with the echo number (n(center)) used to sample the k-space center. Compared to spin-echo EPI, mHASTE incurs an approximately 50% reduction in activation cluster size and an approximately 20% decrease in BOLD contrast. However a higher signal-to-noise ratio and a spatially more uniform temporal stability have been observed in mHASTE as compared to the EPI sequences when the scan times are held constant. With further refinement and optimization, mHASTE can become a viable alternative for fMRI in situations where the conventional EPI sequences are limited or prohibitive.
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We had prepared earlier a prokaryotic-expressed tumor necrosis factor-alpha (TNF-[alpha]) mutant that exhibited a higher antitumor activity and a lower systemic toxicity compared with that of wild-type TNF-[alpha] in both syngenei...
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We had prepared earlier a prokaryotic-expressed tumor necrosis factor-alpha (TNF-[alpha]) mutant that exhibited a higher antitumor activity and a lower systemic toxicity compared with that of wild-type TNF-[alpha] in both syngeneic murine tumor models and human tumor xenografts models. For its clinical use as an antitumor agent, we evaluated repeated-dose toxicity, anaphylaxis, genetic toxicity, pharmacokinetic, and metabolism in different animals according to the criteria of the biological investigational new drug application. It was found to be safe at a dose of 4x10(6) IU/kg/day for 60 days after administration in rhesus monkeys, but the TNF-[alpha] antibody level and liver toxicity needed to be monitored. No systemic anaphylaxis or genetic toxicity was found and the pharmacokinetic characteristics of the recombinant mutated human TNF-[alpha] (rmhTNF-[alpha]) were suited for clinical use. More than 96.3% of rmhTNF-[alpha] could be reclaimed from the urine and feces in 24 h after administration, which indicated the main excretion route. The results proved that the characteristics of this rmhTNF-[alpha] satisfied clinical trial requirements. The related positive clinical trial results will be reported in future. This study of novel rmhTNF-[alpha] is of considerable importance, not only given the proven usefulness of TNF-[alpha] local application therapies under isolated limp perfusion and isolated hepatic perfusion conditions for selected indications, but also implicated for systemic application of TNF-[alpha].
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Walking speed is associated with attention and executive control processes subserved by the prefrontal cortex. Because polymorphisms in catechol-O-methyltransferase (COMT) influence these cognitive processes we hypothesized that t...
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Walking speed is associated with attention and executive control processes subserved by the prefrontal cortex. Because polymorphisms in catechol-O-methyltransferase (COMT) influence these cognitive processes we hypothesized that the same polymorphisms may influence gait velocity. We examined the associations between the Val(158)Met polymorphism in COMT and gait velocity as well as attention and executive function. Participants were 278 non-demented older adults. The results revealed that methionine (Met)/valine (Val) was associated with faster gait velocity. This association can be explained by the putative role of the Val allele in regulating tonic dopamine release in the striatum. In contrast, Met/Met was associated with better attention and executive function. Stratification by gender revealed that the association between COMT genotype and gait was significant only in men. Conversely, the association between COMT genotype and attention and executive function was significant only in women. These findings suggest a differential effect in relating the Val(158)Met polymorphism to gait and to cognitive function while supporting the previously described sexual dimorphism in the phenotypic expressions of COMT.
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Our previous work demonstrated that berberine (BBR) increases insulin receptor (InsR) expression and improves glucose utility both in vitro and in animal models. Here, we study the InsR-up-regulating and glucose-lowering activitie...
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Our previous work demonstrated that berberine (BBR) increases insulin receptor (InsR) expression and improves glucose utility both in vitro and in animal models. Here, we study the InsR-up-regulating and glucose-lowering activities of BBR in humans. Our results showed that BBR increased InsR messenger RNA and protein expression in a variety of human cell lines, including CEM, HCT-116, SW1990, HT1080, 293T, and hepatitis B virus-transfected human liver cells. Accordingly, insulin-stimulated phosphorylations of InsR beta-subunit and Akt were increased after BBR treatment in cultured cells. In the clinical study, BBR significantly lowered fasting blood glucose (FBG), hemoglobin A(1c), triglyceride, and insulin levels in patients with type 2 diabetes mellitus (T2DM). The FBG- and hemoglobin A(1c)-lowering efficacies of BBR were similar to those of metformin and rosiglitazone. In the BBR-treated patients, the percentages of peripheral blood lymphocytes that express InsR were significantly elevated after therapy. Berberine also lowered FBG effectively in chronic hepatitis B and hepatitis C patients with T2DM or impaired fasting glucose. Liver function was improved greatly in these patients by showing reduction of liver enzymes. Our results confirmed the activity of BBR on InsR in humans and its relationship with the glucose-lowering effect. Together with our previous report, we strongly suggest BBR as an ideal medicine for T2DM with a mechanism different from metformin and rosiglitazone.
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