The effect of sequential administration of octreotide alone and octreotide/growth hormone simultaneously on buserelin stimulated ovarian steroid secretion in women with polycystic ovary syndrome

The site of S1-S2 root activation following percutaneous high-voltage electrical (ES) and magnetic stimulation were located by analyzing the variations of the time interval from M to H soleus responses elicited by moving the stimulus point from lumbar to low thoracic levels. ES was effective in activating S1-S2 roots at their origin. However supramaximal motor root stimulation required a dorsoventral montage, the anode being a large, circular surface electrode placed ventrally, midline between the apex of the xiphoid process and the umbilicus. Responses to magnetic stimuli always resulted from the activation of a fraction of the fiber pool, sometimes limited to the low-thresholds afferent component, near its exit from the intervertebral foramina, or even more distally. Normal values for conduction velocity in motor and 1a afferent fibers in the proximal nerve tract are provided.     

One world, one hope: the cost of providing antiretroviral therapy to all nations

OBJECTIVE: To estimate the potential direct cost of making triple combination antiretroviral therapy widely available to HIV-positive adults and children living in countries throughout the world. METHODS: For each country, antiretroviral costs were obtained by multiplying the annual cost of triple antiretroviral therapy by the estimated number of HIV-positive persons accessing therapy. Per capita antiretroviral costs were computed by dividing the antiretroviral costs by the country's total population. The potential economic burden was calculated by dividing per capita antiretroviral costs by the gross national product (GNP) per capita. All values are expressed in 1997 US dollars. RESULTS: The potential cost of making triple combination antiretroviral therapy available to HIV-positive individuals throughout the world was estimated to be over US$ 65.8 billion. By far the greatest financial burden was on sub-Saharan Africa. The highest per capita drug cost in this region would be incurred in the subregions of Southern Africa (US$ 149) followed by East Africa (US$ 116), Middle Africa (US$ 44), and West Africa (US$ 42). In the Americas, subregional data indicated the highest per capita drug cost would be in the Latin Caribbean (US$ 22), followed by the Caribbean (US$ 17), Andean Area (US$ 7), the Southern Cone (US$ 6), North America (US$ 6), and Central American Isthmus (US$ 5). In Asia and Europe the percentage of the GNP necessary to finance drug therapy was less than 1% in most countries examined. CONCLUSION: Our results demonstrate that the cost of making combination antiretroviral therapy available worldwide would be exceedingly high, especially in countries with limited financial resources.     

云环境下基于本体的用户行为分析引擎研究

针对当前大型互联网站提升用户体验的需求,本研究创造性地提出基于本体的用户行为分析引擎的思想,它通过上下文感知技术,实时获取用户访问页面时的上下文信息(以下也称为动态行为),基于本体对用户行为建模,建立基于规则的上下文推理算法,对监测到的动态用户行为进行实时推理,及时反馈结果信息给用户。实验表明:本研究理论上独辟蹊径,设计实现上结合了云存储技术,能够一定程度改善用户体验效果。     

Deposition of Dry Powder Generated by Solovent in Sophia Anatomical Infant Nose-Throat (SAINT) Model

Purpose: To quantify deposition of ^99mtechnetium-labeled powder in the Sophia Anatomical Infant Nose-Throat (SAINT) model of a 9-month old. Methods: Powder was generated by the Solovent (BD Technologies), an active dry powder inhaler with spacer, during 30 seconds of tidal volume (TV) breathing. Activity that passed through the model was captured on a filter and represented powder that was available for deposition in the lungs. Deposition in the nasal cavity, on the filter, and in the spacer was expressed as a percentage of the injected dose into the spacer. Results: Mean (± SD) injected dose averaged 89.5 ± 0.09%, 90.3 ± 0.11%, and 91.3 ± 0.05% at 50, 100, and 200 mL TV, respectively. Mean nasal deposition increased significantly from 50 mL to 100 mL and 200 mL TV with 0.60 ± 0.002%, 1.72 ± 0.007%, and 6.75 ± 07.21%, respectively (all p ≤ 0.05). Similarly, mean filter deposition increased significantly from 50 mL to 100 mL to 200 mL with 0.28 ± 0.00%, 1.14 ± 0.00%, and 3.87 ± 0.01%, respectively (all p < 0.05). Mean retention in the spacer was similar at 50 mL (93.38 ± 0.02%) and at 100 mL TV (89.97 ± 0.04%), but decreased significantly to 71.47 ± 0.05% at 200 mL TV (all p < 0.05). Conclusions: These data suggest for the first time the feasibility of delivering a dry powder formulation to infants and toddlers by actively introducing the powder into a spacer. Lung deposition and nasal deposition, as a percent of injected dose, were dependent on tidal volume with deposition increasing with increasing TV. Nevertheless, deposition, as a percent of injected dose, was low in both regions. This was likely due to significant retention in the spacer at all 3 tidal volumes.

Copyright 2012 American Association for Aerosol Research     

Applying dry powder coatings to pharmaceutical powders using a comil for improving powder flow and bulk density

A method for applying nano-sized silicon dioxide guest particles onto host pharmaceutical particles (a.k.a. “dry-coating” or “nanocoating”) has been developed using conventional pharmaceutical processing equipment. It has been demonstrated that under selected conditions, a comil can be used to induce sufficient shear to disperse silicon dioxide particles onto the surfaces of host particles such as active pharmaceutical ingredients (API) without significant host particle attrition. In accordance with previous studies on dry coating, the dispersed silicon dioxide adheres to the host particle surface through van der Waals attractions, and reduces bulk powder cohesion. In this work, laboratory and pilot scale comils were used to dry coat pharmaceutical API and excipient powders with 1% w/w silicon dioxide by passing them through the mill with an appropriate combination of screen and impeller. In general, the uncoated powders exhibited poor flow and/or low bulk density. After dry coating with a comil, the powders exhibited a considerable and in some cases outstanding improvement in flow performance and bulk density. This coating process was successful at both the laboratory and pilot scale with similar improvements in flow. The superior performance of the coated powders translated to subsequent formulated blends, demonstrating the benefit of using nanocoated powders over uncoated powders. This particle engineering work describes the first successful demonstration of using a traditional pharmaceutical unit operation that can be run continuously to produce uniform nanocoating and highlights the substantial improvements to powder flow properties when this approach is used.     

Ubiquitin C-Terminal Hydrolase L1: Biochemical and Cellular Characterization of a Covalent Cyanopyrrolidine-Based Inhibitor

The deubiquitinase (DUB) ubiquitin C-terminal hydrolase L1 (UCHL1) is expressed primarily in the central nervous system under normal physiological conditions. However, UCHL1 is overexpressed in various aggressive forms of cancer with strong evidence supporting UCHL1 as an oncogene in lung, glioma, and blood cancers. In particular, the level of UCHL1 expression in these cancers correlates with increased invasiveness and metastatic behavior, as well as poor patient prognosis. Although UCHL1 is considered an oncogene with potential as a therapeutic target, there remains a significant lack of useful small-molecule probes to pharmacologically validate in vivo targeting of the enzyme. Herein, we describe the characterization of a new covalent cyanopyrrolidine-based UCHL1 inhibitory scaffold in biochemical and cellular studies to better understand the utility of this inhibitor in elucidating the role of UCHL1 in cancer biology.     

A highly regioselective synthesis of δ-lactones from meadowfoam fatty acids

Meadowfoam fatty acids, when treated with mineral acid catalysts in the presence of polar nonparticipating solvents, undergo a facile ring closure to form δ-lactones. Perchloric and sulfuric acids catalyze the cyclization at concentrations of 0.6–13 mole equivalents, both neat and in the presence of solvent. Under constant acid concentrations, methylene chloride was found to increase the rate of reaction, the regioselectivity for the formation of δ-lactone, and the overall yield. In the absence of solvent, increased acid concentration improved the yield of lactone but reduced regioselectivity for the δ-isomer. Solvent polarity plays a significant role in the regioselectivity of the cyclization for δ-lactone, with solvents of higher dielectric strength providing larger δ/γ ratios (38:1) and higher yields up to 92%.     

Similarity and assumed similarity in personality reports of well-acquainted persons.

The authors obtained self- and observer reports of personality from pairs of well-acquainted college students. Consistent with previous findings, results of Study 1 showed strong cross-source agreement for all 6 HEXACO personality factors (rs ≈ .55). In addition, the authors found modest levels of similarity (r ≈ .25) between dyad members' self-reports on each of 2 dimensions, Honesty-Humility and Openness to Experience. For these same 2 factors, dyad members' self-reports were correlated with their observer reports of the other dyad member (r ≈ .40), thus indicating moderately high assumed similarity. In Study 2, Honesty-Humility and Openness to Experience were the 2 personality factors most strongly associated with the 2 major dimensions of personal values, which also showed substantial assumed similarity. In Study 3, assumed similarity was considerably stronger for close friends than for nonfriend acquaintances. Results suggest that assumed similarity for Honesty-Humility and Openness to Experience reflects a tendency to overestimate one's similarity to persons with whom one has a close relationship, but only on those personality characteristics whose relevance to values gives them central importance to one's identity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)