No abstract

A static model is used to investigate how the exchange rate movement affect the distribution of productivity within an industry. Quantile regression is then used to empirically test the effects of RMB exchange rate appreciation on the distribution of labor productivity within industries. Based on China’s manufacturing micro-enterprise survey data from 1998 to 2007, we characterize how exchange rate changes affect the distribution of productivity through three mechanisms. We find that the exchange rate appreciation increases the dispersion of the productivity distribution and decrease the efficiency of resource allocation and aggregate productivity. The distribution of the import intensity may be the main cause for the increase in the productivity dispersion and the deterioration of the industrial resource allocation efficiency, which implies that foreign inputs improve the mean productivity of firms but decrease the resource allocation efficiency. China should tradeoff the gain in productivity and loss in allocation efficiency when it aims to implement a more elastic RMB exchange rate regime.

No abstract

Flow separation and different kinds of stall flows occur under low load conditions for steam turbine last stage blades. In order to delay the flow separation and increase turbine power production, we applied suction side tubercles on steam turbine low-pressure last stage blades in the present study. The amplitude, wavelength, position, and thickness were considered as our design variables. We used the orthogonal test method (OTM) to generate modified blades with different tubercle variables that were then numerically simulated by a three-dimensional computational fluid dynamics (CFD) analysis. The blade axial torque of the nine modified tests was compared with the original blade. The results showed that the application of bionic tubercles on the suction side of the steam turbine blade is a promising solution to improve the blade axial torque for all modified tests with a maximum increase of 33.32% due to the turbulent vortices generated by bionic tubercles.

Background Since many peptide and proteins are susceptible to oligomerization analogous to Aβ and tau, there is evolutionary pressure to inhibit deleterious protein misfolding; likewise, the immunoinflammatory cascade triggered by such misfolding is also subject to homeostatic regulation. Accordingly, it is reasonable to postulate the existence of endogenous molecules within the human brain that could modulate or even interrupt the neurotoxic cascade of AD by blocking both the proteopathy and immunopathy of Alzheimer's disease (AD). Such compounds would constitute platforms for future drug development. Method We sought to identify a single anti‐proteopathic and anti‐immunopathic agent endogenous to the human central nervous system; to find this compound, we created a comprehensive library of 1,376 molecules (molecular weight < 600 Da) naturally occurring within the human brain and employed an in silico screening assay. Using computer‐aided screening with a molecular mechanics force field, we docked these endogenous molecules against computer models of in Aβ(HHQK16LVFF), tau(KKAK144), IL‐1R1(HKEK80), IL‐1β(KLRK76), C1qA(KKGH225), IFN‐gamma(KKKR112) and RANTES(RKNR70). Additional molecular dynamics simulations were done to refine the docking. Finally, multiple in vitro assays were done, verifying that the in silico hits had correctly predicted the ability to block oligomerization and to bind to multiple immunopeptides. Result Several zwitterionic and aromatic‐anionic compounds capable of binding to these multiple amyloid, tau and immunoprotein targets were identified. Strong in silico hits included 2‐aminoethanesulfonic acid, L‐phosphoserine, 5‐hydroxytryptamine and 3‐hydroxyanthranilic acid. These predictions were verified using in vitro assays, including the kinetic Thioflavin T [ThT] aggregation assay. Conclusion Searching for an “endogenous anti‐AD compound” represents an unexplored concept. Our in silico and in vitro studies suggest that compounds endogenous to the human brain can inhibit pathological both the proteopathic and immunopathic pathogeneses of AD. The value of a novel in silico screening assay to identify such endogenous agent capable of "one‐drug‐multiple‐targets" has also been demonstrated.

No abstract

To determine the mechanisms by which nucleotide concentrations change in the heart during ischemia and reperfusion, data from Kroll et al. [Am. J. Physiol. 272:H2567‐2576, 1997] were analyzed using a computational model of cardiac energy metabolism and metabolite transport. In the experiments of Kroll et al., rabbit hearts were subjected to 10 minutes of perfusion at basal conditions; then 45 minutes of ischemia with 95% flow reduction; and then reperfusion. Phosphate metabolite concentrations were measured by 31P‐Magnetic Resonance Spectroscopy (31P‐MRS) and oxygen flux by arterial‐venous differences in oxygen tension during the ischemia reperfusion protocol. Data were analyzed by integrating open adenosine kinetics into a previously developed computational model [Wu et al., J. Physiol. 586:4193‐4208, 2008]. Our analyses find that during ischemia/anoxia the heart actively down‐regulates ATP hydrolysis rate in the cytoplasm, while inhibiting mitochondrial ATP consumption. Down‐regulation of mitochondria ATP consumption during anoxia may be associated with inhibition of F1Fo‐ATPase reversal or reduction of mitochondrial proton leak. During the reperfusion period, the mitochondrial ATP synthesis capacity is largely restored, while mitochondrial proton leak is significantly magnified resulting in a slightly impaired efficiency of mitochondrial oxidative phosphorylation. The loss of adenosine nucleotides during ischemia does not limit the mitochondrial oxidative capacity during reperfusion.

The ability of mitochondria to oxidatively synthesize ATP from ADP and inorganic phosphate is compromised in the failing heart. Specifically, the magnitude of the free energy at which ATP is synthesized in heart failure is diminished compared to control. However the causal mechanisms involved are not clearly understood. Here we used computer simulation to analyze the impact of reduction in three cytoplasmic metabolic pools that is observed with hypertrophic remodeling and heart failure. Our simulations, which are validated based on in vivo data on phosphate metabolites in both the healthy and diseased heart, predict that, given a prescribed reduction in the total adenine nucleotide pool, the pools of total creatine and total exchangeable phosphate are maintained at levels that maintain the ATP hydrolysis potential of the heart at near the normal physiological value.