Effects of Ketone Bodies on Brain Metabolism and Function in Neurodegenerative Diseases

Under normal physiological conditions the brain primarily utilizes glucose for ATP generation. However, in situations where glucose is sparse, e.g., during prolonged fasting, ketone bodies become an important energy source for the brain. The brain’s utilization of ketones seems to depend mainly on the concentration in the blood, thus many dietary approaches such as ketogenic diets, ingestion of ketogenic medium-chain fatty acids or exogenous ketones, facilitate significant changes in the brain’s metabolism. Therefore, these approaches may ameliorate the energy crisis in neurodegenerative diseases, which are characterized by a deterioration of the brain’s glucose metabolism, providing a therapeutic advantage in these diseases. Most clinical studies examining the neuroprotective role of ketone bodies have been conducted in patients with Alzheimer’s disease, where brain imaging studies support the notion of enhancing brain energy metabolism with ketones. Likewise, a few studies show modest functional improvements in patients with Parkinson’s disease and cognitive benefits in patients with—or at risk of—Alzheimer’s disease after ketogenic interventions. Here, we summarize current knowledge on how ketogenic interventions support brain metabolism and discuss the therapeutic role of ketones in neurodegenerative disease, emphasizing clinical data.     

快速灵敏的LC-MS/MS法测定人血浆中阿莫西林并应用于两种制剂的一致性评价

目的: 建立快速灵敏的LC-MS/MS法测定人血浆中阿莫西林浓度，并用于两种阿莫西林胶囊的一致性评价。方法: 采用岛津公司LCMS-8060型LC-MS/MS仪，以MRM模式测定阿莫西林（m/z 366.00/114.00）的浓度，d4-阿莫西林作内标（m/z 370.10/114.05），离子源为ESI源。色谱柱选用Waters ACQUITY BEH C18（2.1×50 mm，1.7 μm），梯度洗脱。血浆样本加入内标，经甲醇沉淀蛋白后取上清液进样检测。结果: 所建方法经验证，其线性、准确度、精密度、最低定量限、提取回收率、特异性、基质效应、稳定性等各项指标均符合CFDA的指导原则及最新核查标准要求，并较文献报道中的方法有处理简单、灵敏度高、色谱峰形好的优点。结论: 所建方法快速、灵敏，适用于人血浆中阿莫西林浓度的检测。用于一致性评价的样本实测，两种制剂生物等效。     

Animations showing Lego manipulative tasks: Three potential moderators of effectiveness

Evidence suggests that transient visual information, such as animations, may be more challenging to learn than static visualizations. However, when a procedural-manipulative task is involved, our evolved embodied cognition seems to reverse this transitory challenge. Hence, for object manipulative tasks, instructional animations may be more suitable than statics. We investigated this argument further by comparing animations with statics using a Lego task shown to university students, by examining three potential moderators of effectiveness: (a) the environment of manipulation (virtual or physical), (b) the quality of visual information (focused or unfocused), and (c) the presence of hands (no hands or with hands). In Experiment 1 we found an advantage of animation over statics, and no differences among the environments. In Experiment 2, we again observed an animation advantage, a small advantage of focused static information compared to unfocused static information, and a positive effect of not showing the hands.     

药用辅料对CYP3A活性的影响及其对仿制药质量和疗效一致性评价的指导作用

药物制剂的处方和工艺是保证药物质量和疗效的基础，药用辅料是药物制剂处方的重要组成部分。部分药用辅料可影响CYP3A的活性，继而可能影响其底物在体内的代谢和生物利用度。在中国和美国，相对生物利用度是仿制药研究的关键内容。我国正在推进仿制药质量和疗效一致性评价。因此，了解药用辅料对CYP3A的影响及其对一致性评价的指导作用具有十分重要的现实意义。     

Parallel path consistency

Filtering algorithms are well accepted as a means of speeding up the solution of the consistent labeling problem (CLP). Despite the fact that path consistency does a better job of filtering than arc consistency, AC is still the preferred technique because it has a much lower time complexity. We are implementing parallel path consistency algorithms on multiprocessors and comparing their performance to the best sequential and parallel arc consistency algorithms.^(1,2) (See also work by Kerethoet al. ⁽³⁾ and Kasif⁽⁴⁾) Preliminary work has shown linear performance increases for parallelized path consistency and also shown that in many cases performance is significantly better than the theoretical worst case. These two results lead us to believe that parallel path consistency may be a superior filtering technique. Finally, we have implemented path consistency as an outer product computation and have obtained good results (e.g., linear speedup on a 64K-node Connection Machine 2).     

Comment on Greenwood (2007): Solving the puzzle of structure/function relations in the aging brain?

Neuroimaging experiments have shown that prefrontal regions of the brain, which have the most age-related volume loss, are also the regions most likely to be more active in older adults than in younger adults. In an attempt to solve this puzzle, P. M. Greenwood (see record 2007-15625-001) has proposed a cascade that flows from age-related atrophy in the brain to changed processing strategies that result in plastic changes in regions adjacent and contralateral to the atrophic areas, culminating in greater functional activity. This hypothesis should stimulate research into these mechanisms and hopefully will ultimately inform researchers' ability to rehabilitate cognitive disorders in the elderly. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

调整水量法(代用法)测定水泥标准稠度用水量方法的改进

结合兰州市的水泥标准稠度用水量方法测定 (代用法 )的实例 ,分析代用法测定标准稠度用水量的缺点 ,并对此方法提出了一些改进措施     

Measuring consistency in TTL-based caches

We propose a general modeling framework to evaluate the performance of cache consistency algorithms. In addition to the usual hit rate, we introduce the hit^* rate as a consistency measure, which captures the fraction of non-stale downloads from the cache. We apply these ideas to the analysis of the fixed TTL consistency algorithm in the presence of network delays. The hit and hit^* rates are evaluated when requests and updates are modeled by renewal processes. Classical results on the renewal function lead to various bounds.     

Exceptions that prove the rule--Using a theory of motivated social cognition to account for ideological incongruities and political anomalies: Reply to Greenberg and Jonas (2003).

A meta-analysis by J. T. Jost, J. Glaser, A. W. Kruglanski, and F. J. Sulloway (2003) concluded that political conservatism is partially motivated by the management of uncertainty and threat. In this reply to J. Greenberg and E. Jonas (2003), conceptual issues are clarified, numerous political anomalies are explained, and alleged counterexamples are incorporated with a dynamic model that takes into account differences between "young" and "old" movements. Studies directly pitting the rigidity-of-the-right hypothesis against the ideological extremity hypothesis demonstrate strong support for the former. Medium to large effect sizes describe relations between political conservatism and dogmatism and intolerance of ambiguity; lack of openness to experience; uncertainty avoidance; personal needs for order, structure, and closure; fear of death; and system threat. (PsycINFO Database Record (c) 2010 APA, all rights reserved)