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101.
    
The cardiovascular disease of atherosclerosis is characterised by aged vascular smooth muscle cells and compromised cell survival. Analysis of human and murine plaques highlights markers of DNA damage such as p53, Ataxia telangiectasia mutated (ATM), and defects in mitochondrial oxidative metabolism as significant observations. The antiageing protein Klotho could prolong VSMC survival in the atherosclerotic plaque and delay the consequences of plaque rupture by improving VSMC phenotype to delay heart attacks and stroke. Comparing wild-type VSMCs from an ApoE model of atherosclerosis with a flox’d Pink1 knockout of inducible mitochondrial dysfunction we show WT Pink1 is essential for normal cell viability, while Klotho mediates energetic switching which may preserve cell survival. Methods: Wild-type ApoE VSMCs were screened to identify potential drug candidates that could improve longevity without inducing cytotoxicity. The central regulator of cell metabolism AMP Kinase was used as a readout of energy homeostasis. Functional energetic switching between oxidative and glycolytic metabolism was assessed using XF24 technology. Live cell imaging was then used as a functional readout for the WT drug response, compared with Pink1 (phosphatase-and-tensin-homolog (PTEN)-induced kinase-1) knockout cells. Results: Candidate drugs were assessed to induce pACC, pAMPK, and pLKB1 before selecting Klotho for its improved ability to perform energetic switching. Klotho mediated an inverse dose-dependent effect and was able to switch between oxidative and glycolytic metabolism. Klotho mediated improved glycolytic energetics in wild-type cells which were not present in Pink1 knockout cells that model mitochondrial dysfunction. Klotho improved WT cell survival and migration, increasing proliferation and decreasing necrosis independent of effects on apoptosis. Conclusions: Klotho plays an important role in VSMC energetics which requires Pink1 to mediate energetic switching between oxidative and glycolytic metabolism. Klotho improved VSMC phenotype and, if targeted to the plaque early in the disease, could be a useful strategy to delay the effects of plaque ageing and improve VSMC survival.  相似文献   
102.
Lead replacement heat stabilizers have made considerable inroads in areas where water resistance is not significant, primarily in wire jackets and insulations not for wet locations. In areas where short-term moisture resistance is required, such as with flexible cord insulation and electrical tapes, nonlead products are either in use or under development. In those areas where long-term water resistance is needed, as with geomembranes and many wire insulations, despite much experimentation, commercial products are not in use as yet in the United States. The factors involved are discussed.  相似文献   
103.
Density functional theory, informed by experimental studies, is used to investigate the interplay of surface morphology, the adsorption site of reactants, the nature of the interaction between adsorbates and the surface, the potential energy landscape for adsorbates on the surface, adsorbate coverage, temperature, and the dynamic evolution of these factors during adsorption and reaction. We summarize our current understanding of Au atom release on the (111) surface and the corresponding effects on adsorption and reactivity. Gold was selected for these investigations because of the recent intense interest in the activity of gold nanoparticles for several important catalytic reactions. Fundamental experimental studies on Au single-crystal surfaces have established that atomic O is extremely active for oxidation of CO and olefins, that the local bonding of O is an important factor in determining the reactivity and selectivity for oxidation, and that Au atom release is induced by electronegative adsorbates, such as O, Cl, and S. These experimental results guided our theoretical studies. Density functional theory is an extremely useful tool since it evaluates the energetics associated with the incorporation of gold into the adsorbate layer, while providing fundamental physical insight into the underlying cause of gold incorporation. We use our results from static DFT calculations along with ab initio molecular dynamics simulations to understand the effect of surface morphology on the activity of gold for CO oxidation. Our investigation of Au atom release and incorporation induced by electronegative atoms clearly illustrates the importance of using experiments in combination with theory to establish the importance of and the underlying reasons for metal atom release and the affect on bonding and reactivity.  相似文献   
104.
A novel and highly accurate electronic technique for phase locking arrays of optical fiber amplifiers is demonstrated. This is the only electronic phase locking technique that does not require a reference beam. The measured phase error for this system is lambda /20. A model for calculating the signal-shot noise-limited phase errors and the phase-modulation-induced phase errors is developed. For the first time, nine fiber amplifiers are coherently combined. The total power in the phase locked array is 100 W.  相似文献   
105.
A planar waveguide laser operating in a negative branch unstable resonator is Q-switched by an acoustooptic modulator in a new configuration, providing effective, high-speed switching. The laser using a 200-mum Nd:YAG core, face pumped by 10 laser diode bars, has produced 100-W output in a good beam quality at 100-kHz pulse rate, and 4.5 mJ at lower frequency with 15-ns pulse duration.  相似文献   
106.
The adsorption and the redox processes of two first-generation salicylaldiamine dendritic ligands and their copper, cobalt and nickel metallo-functionalized complexes have been studied at two types of carbon electrode surface. Glassy carbon (GC) was used in an electrochemistry study and highly oriented pyrolitic graphite (HOPG) in ex situ atomic force microscopy (AFM) imaging. All salicylaldimine ligands and their metallo-functionalized complexes adsorb on the surface of the HOPG electrode, resulting in the formation of nanoclusters and films, which vary between 0.9 and 6 nm in size, depending on the metallo-functionalized salicylaldimine dendrimer chemical composition and solution concentration. Differential pulse voltammetry of the surface-confined films has shown that the anodic reactions observed correspond to the oxidation of the hydroxyl groups present in the ligand structure of all compounds. However, by following the changes in peak currents, potentials and width at half height it has been shown that destabilization of the ligand internal structure occurred in the metallo-functionalized complexes depending on the metal involved. The electrochemical behaviour of the surface-confined films observed in buffer solution was related to the morphology, obtained by AFM, of the immobilised first-generation salicylaldiamine dendritic ligands and corresponding salicylaldimine metallo-functionalized complexes.  相似文献   
107.
This dialogue concerns the nature of ethical responsibility in contemporary art practice, and its relation to questions of creativity; the role of writing in shaping the perception of transgenic art and related practices; and the problems that may be associated with trusting artists to act with integrity in the unchartered waters of their enthusiastic engagement with genetic technologies.  相似文献   
108.
The residence times of the components of two- and three-component mixtures of fine (195 µm), coarse (1315 µm) and very coarse (5040 µm) sands were measured in a pilot-scale cascading rotary dryer. The effects of mixture composition and air velocity (0-5.4 m s-1) were determined. With no air flowing through the drum, the residence times of the individual components were almost the same as that of the overall mixture. Increasing the gas velocity caused a large decrease in residence time. In contrast, particle size had very little effect. The spread of residence times increased with air velocity, peaking between 2 and 4 m s-1; composition had very little effect on the spread. The residence time of the overall mixture could be calculated using the particle transport model of Matchett and Baker if both the modified drag coefficient Φd and the particle Reynolds number Rep were based on the superficial air velocity and the mass-average particle diameter.  相似文献   
109.
BACKGROUND: The need for cardiopulmonary bypass in the treatment of penetrating heart injuries is debated. OBJECTIVES: To review our experience with penetrating heart injuries and determine the indications and outcome for cardiopulmonary bypass. DESIGN: Retrospective review. SETTING: A university-based, level I trauma center. PATIENTS: All victims of penetrating heart injury presenting between July 1, 1989, and December 31, 1995. METHODS: Medical records were reviewed for demographic and physiological data, operative findings, and outcome. RESULTS: Overall survival for 106 patients with penetrating heart injury was 55%. In an effort to resuscitate the heart, 4 patients with unresponsive cardiogenic shock were placed on cardiopulmonary bypass; none survived. Of 30 patients with multiple-chamber injuries, 11 presented with signs of life and 7 survived. Cardiopulmonary bypass was essential to repair complex injuries in 2 of the 7 survivors. CONCLUSION: Cardiopulmonary bypass was ineffective in salvaging patients with cardiogenic shock but was essential in some patients with complex multiple-chamber cardiac injuries that could not be exposed and repaired by other means.  相似文献   
110.
We re-evaluated three schemes of liver organization: the classic lobule, the portal lobule, and Rappaport's liver acinus. The lobular angioarchitecture of normal rat liver and the three-dimensional structure of pseudolubules found in rat livers with fibrosis induced by swine serum were compared with the classic lobule of the pig. Normal and fibrotic rat livers and pig livers were perfused, injected with either India ink or 0.75% OsO4 through the portal and/or hepatic vein, and immersionfixed. Whole lobes and hand-cut thick sections were made transparent with a solution of benzyl benzoate and methyl salicylate. The angioarchitecture of normal rat liver differs from pig liver. In the former, terminal portal branches and central veins interdigitate, and in the latter, numerous terminal portal branches that arise from interlobular portal veins establish a vascular basket surrounding one central vein and forming classic lobule. The structure of liver acinus is never found in the pig liver. The terminal portal branch, together with the terminal hepatic artery and bile duct, are present inside each pseudolobule of fibrotic rat livers. Blood from the terminal portal branch flows through inlet venules into radiating sinusoids, and, at the periphery converges into newly formed septal and angular outlet venules; these venules terminate in fibrotic central veins located at each corner. Pseudolobules are not rugby ball-like as Rappaport's liver acini are but are polyhedron in shape. The rat pseudolobules are comparable with the portal lobule; its structure and microcirculation are the reverse of the pig classic lobule. Rat pseudolobules are different from liver acini, as shown by the following: 1) their three-dimensional shape is different; and 2) they have a reverse relationship to classic lobules while acini are defined to subdivide classic lobules. In normal and fibrotic rat livers, the liver unit is the portal lobule with a terminal portal branch as the axial branch and central veins at the periphery. The co-existence of liver acini and classic lobules is doubtful.  相似文献   
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