We investigated the effects of angiotensin II (Ang II) type 1 receptor blockade with losartan on the renin-angiotensin-aldosterone system in hypertensive patients (supine diastolic blood pressure, 95 to 110 mm Hg). Qualifying patients (n = 51) were allocated to placebo, 25 or 100 mg losartan, or 20 mg enalapril. Blood pressure, plasma drug concentrations, and renin-angiotensin-aldosterone system mediators were measured on 4 inpatient days: end of placebo run-in, after first dose, and 2 and 6 weeks of treatment. Plasma drug concentrations were similar after the first and last doses of losartan. At 6 weeks, 100 mg losartan and 20 mg enalapril showed comparable antihypertensive activity. Four hours after dosing, compared with the run-in day, 100 mg losartan increased plasma renin activity 1.7-fold and Ang II 2.5-fold, whereas enalapril increased plasma renin activity 2.8-fold and decreased Ang II 77%. Both drugs decreased plasma aldosterone concentration. For losartan, plasma renin activity and Ang II increases were greater at 2 than at 6 weeks. Effects of losartan were dose related. After the last dose of losartan, plasma renin activity and Ang II changes were similar to placebo changes by 36 hours. These results indicate that long-term blockade of the feedback Ang II receptor in hypertensive patients produces modest increases of plasma renin activity and Ang II that do not appear to affect the antihypertensive response to the antagonist.

Lithium-ion batteries are used in a wide variety of consumer devices and are the dominant form of mobile energy storage. But the production of Li-ion batteries negatively impacts the environment and imposes a substantial cost on the consumer. Extending the lifetime of Li-ion batteries can reduce both the environmental and monetary cost of battery production. This thesis explores the factors that limit battery lifetime, and provides guidance for extending lifetime. It also evaluates how companies, whose devices contain Li-ion batteries, explain these factors to users. This work has been published under the same title in the Journal of Energy Storage with the following citation:

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This paper highlights results from a collaborative life-cycle design project between the University of Michigan, the US Environment Protection Agency and United Solar Systems Corporation. Energy analysis is a critical planning and design tool for photovoltaic (PV) modules. A set of model equations for evaluating the life-cycle energy performance of PV systems and other electricity-generating systems are presented. The total PV life-cycle, encompassing material production, manufacturing and assembly, use and end-of-life management, was investigated. Three metrics Ð energy payback time, electricity production eciency and lifecycle conversion eciency Ð were de®ned for PV modules with and without balanceof-system (BOS) components. These metrics were evaluated for a United Solar UPM-880 amorphous silicon PV module based on average insolation in Detroit, Boulder and Phoenix. Based on these metrics, a minimum condition for assessing the sustainability of electricity-generating systems was proposed and discussed. The life-cycle energy analysis indicated that the aluminum frame is responsible for a signi®cant fraction of the energy invested in the UPM-880 module.

The design of a novel selective estrogen receptor modulator (SERM) for the potential treatment of uterine leiomyoma is described. 16 (LY2066948-HCl) binds with high affinity to estrogen receptors alpha and beta (ERalpha and ERbeta, respectively) and is a potent uterine antagonist with minimal effects on the ovaries as determined by serum biomarkers and histologic evaluation.

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