ATPase Inhibitory Factor-1 Disrupts Mitochondrial Ca2+ Handling and Promotes Pathological Cardiac Hypertrophy through CaMKIIδ

ATPase inhibitory factor-1 (IF1) preserves cellular ATP under conditions of respiratory collapse, yet the function of IF1 under normal respiring conditions is unresolved. We tested the hypothesis that IF1 promotes mitochondrial dysfunction and pathological cardiomyocyte hypertrophy in the context of heart failure (HF). Methods and results: Cardiac expression of IF1 was increased in mice and in humans with HF, downstream of neurohumoral signaling pathways and in patterns that resembled the fetal-like gene program. Adenoviral expression of wild-type IF1 in primary cardiomyocytes resulted in pathological hypertrophy and metabolic remodeling as evidenced by enhanced mitochondrial oxidative stress, reduced mitochondrial respiratory capacity, and the augmentation of extramitochondrial glycolysis. Similar perturbations were observed with an IF1 mutant incapable of binding to ATP synthase (E55A mutation), an indication that these effects occurred independent of binding to ATP synthase. Instead, IF1 promoted mitochondrial fragmentation and compromised mitochondrial Ca²⁺ handling, which resulted in sarcoplasmic reticulum Ca²⁺ overloading. The effects of IF1 on Ca²⁺ handling were associated with the cytosolic activation of calcium–calmodulin kinase II (CaMKII) and inhibition of CaMKII or co-expression of catalytically dead CaMKIIδC was sufficient to prevent IF1 induced pathological hypertrophy. Conclusions: IF1 represents a novel member of the fetal-like gene program that contributes to mitochondrial dysfunction and pathological cardiac remodeling in HF. Furthermore, we present evidence for a novel, ATP-synthase-independent, role for IF1 in mitochondrial Ca²⁺ handling and mitochondrial-to-nuclear crosstalk involving CaMKII.     

Models for Wireless Data Communications in Indoor Train Environment

The provisioning of wireless data services in the railway environment will become increasingly important for train operators and train constructors in the upcoming years. In this paper, we present models to predict train-to-wayside wireless data communications characteristics in terms of throughput, jitter, and packet loss predictions for 2G/3G networks. To this end, an extensive measurement campaign is carried out along a Belgian Intercity railway track. Based on these measurements, we apply a multiple regression, window mean, and autoregressive model. We find that the window mean model is recommended for the prediction of throughput and jitter, while the multiple regression model is more favorable for the prediction of packet loss. The implementation of these predictions in train-to-wayside communication systems can enhance the provisioning of seamless network connection necessary for a wide variety of data services.     

One thousand-hour long term characteristics of a propane-fueled solid oxide fuel cell hot zone

One thousand-hour continuous test of a propane-fueled portable solid oxide fuel cell (SOFC) based hot zone has been successfully performed in order to assess the degradation characteristics of its performance. Comparing the different operating modes, the degradation rate based on constant current mode was three times lower than that based on constant voltage mode. The stack power output initially increased 3.7% during the first 34 h probably due to electrode activation processes improving cell performance under polarization during the early stage of operation, and then gradually decreased. It has been clearly illustrated that operating condition of constant current is more beneficial to the long term performance test. Further, based on thermodynamics analysis, the electromotive force of nickel oxidation is 13.2 V for the stack voltage at the stack temperature of 740 °C. From the initial current-power curve data, it can be derived that if the hot zone durability test was performed at constant current of 9 A from the beginning, the stack degradation rate would be 15% per 1000 h. The 1000-h durability test and analysis can better understand how to run longer term stability on the hot zone and guide the optimization of hot zone operating conditions.     

The preparation of tissue-type Plasminogen Activator (t-PA) containing liposomes: entrapment efficiency and ultracentrifugation damage

In this study, a method was developed for the efficient entrapment of active tissue-type Plasminogen Activator (t-PA) into liposomes. Experimental conditions were varied to optimize t-PA entrapment: different buffer solutions were used (pH 4 and 7.5), the effect of the incubation concentrations of phospholipid (PL) and t-PA was monitored and the influence of liposome-size was examined. Furthermore, the effect of ultracentrifugation on t-PA containing liposomes was determined in the presence and absence of Tween 80. t-PA entrapment strongly depended on experimental conditions and ranged from 30 up to 90%. Almost quantitative+ (90%) entrapment (entrapment percentage defined as absolute entrapment (IU t-PA/mumol PL) divided by total incubation ratio (IU t-PA/mumol PL), times 100%) was obtained in Hepes buffer pH 7.5, devoid of arginine, with low ionic strength. Ultracentrifugation, used for removal of non-entrapped t-PA, was shown to have a damaging effect on the liposomes (especially in the presence of 0.05% Tween 80), leading to t-PA loss. However, because acceptable alternatives were not available, ultracentrifugation was used during this study. Therefore, the encapsulation-percentage values shown in this study are in fact underestimates for the true entrapment of t-PA. In conclusion: almost quantitative t-PA entrapment in liposomes can be achieved by selecting the proper milieu and inducing a strong interaction between t-PA and bilayer.     

Aggressive and sexual social stimuli do not phase shift the circadian temperature rhythm in rats

Photosensitizers used normally in treating cancers have considerable potential for treatment of other diseases. One such photosensitizer is the endogenously synthesized photosensitizer protoporphyrin IX (PpIX). To better understand how protoporphyrin might be used in transplantation or in treating autoimmune diseases, information must be obtained on how the photosensitizer affects all immune cells. We used a combination of flow cytometry and in vitro activation assays (recall assays and mixed-lymphocyte reactions) to examine the effects of PpIX on the antigen specific component, lymphocytes and the non-antigen specific component, the macrophages/monocytes and dendritic cells of the immune system. Whereas, lymphocytes accumulate PpIX only when activated, both macrophages and dendritic cells accumulated PpIX immediately, without in vitro activation, as measured by flow cytometry. ALA-PDT (aminolevulenic acid-photodynamic therapy) treated adherent cells in the recall assay had a decreased capability to activate lymphocytes. By increasing the light dose in the recall assay, antigen primed lymphocytes were selectively eliminated from a population of cells. Stimulator cells in an MLR had a decreased stimulatory capacity following ALA-PDT treatment. Functional alterations are seen in both the antigen specific     

向家坝水电站VII坝址三维地质建模研究

以向家坝水电站VII坝址为例,讨论了三维地质建模的几个关键问题及其处理方法:①多源数据的整合方法;②采用Laplace插值点和原始数据点共同构造地质曲面的方法;③基于裁剪的近层状地质体的构造方法。展示了向家坝VII坝址三维地质模型在显示、自动成图、虚拟现实漫游和三维数值计算等方面的应用效果。     

Estimation of Peak Flow Rates for Small Drainage Areas

Runoff plots are important for soil loss measurements, and increasing numbers of plots use automatic equipment. To choose equipment with appropriate capacities, the peak flow rate must be known. The peak flow rate is also an important parameter in the modified universal soil loss equation (MUSLE) which calculate the soil loss from upland slope. The available peak flow rate equations are primarily for the watershed scale, not for small drainage areas like runoff plot. This study’s purpose was to derive an equation suitable for the small drainage areas. A total of 149 runoff events on 5 runoff plots were used to develop a peak flow rate equation for the hillslope scale. All plots are located in the Tuanshangou catchment, Zizhou county, Shaanxi province, China. Dimensionless analyses were used to determine the equation form of linear regression analyses. The results revealed that the peak flow rate was significantly correlated with plot area, slope steepness, runoff depth, rainfall depth and the maximum 30-min rainfall intensity. Two equations were developed to estimate peak flow. The model efficiencies of both equations exceeded 0.9. The equations developed in this study represent an important complement to existing peak flow rate equations. These new equations will facilitate the design of soil conservation practices and/or the selection of flow-observation equipment for small drainage areas.     

Oxygen uptake methods as a tool to determine the mechanism of action of hindered amine light stabilizers1

The UV-degradation of an unstabilized and two HALS stabilized polyethylene (PE) films is described. The degradations are characterized by measuring the oxygen uptake, the formation of CO and CO₂, the FT-IR spectra, the mechanical properties, the stabilizer concentration and the oxygen content of the film. The oxygen uptake of the unstabilized PE film led to the expected changes in the IR spectra and embrittlement of the film, while the oxygen uptake by the HALS stabilized films caused only minor changes. The differences between the results for the unstabilized and the HALS stabilized polymers are explained assuming that the initiation of the photodegradation of PE is due to charge transfer complexes.     

Response of spontaneously hypertensive rats to inhalation of fine and ultrafine particles from traffic: experimental controlled study

Background  

Many epidemiological studies have shown that mass concentrations of ambient particulate matter (PM) are associated with adverse health effects in the human population. Since PM is still a very crude measure, this experimental study has explored the role of two distinct size fractions: ultrafine (<0.15 μm) and fine (0.15- 2.5 μm) PM. In a series of 2-day inhalation studies, spontaneously hypersensitive (SH) rats were exposed to fine, concentrated, ambient PM (fCAP) at a city background location or a combination of ultrafine and fine (u+fCAP) PM at a location dominated by traffic. We examined the effect on inflammation and both pathological and haematological indicators as markers of pulmonary and cardiovascular injury. Exposure concentrations ranged from 399 μg/m³ to 3613 μg/m³ for fCAP and from 269μg/m³ to 556 μg/m³ for u+fCAP.