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Position 18 in a parathyroid hormone (PTH) antagonist, [Nle8,18,Tyr34]bPTH(7-34)NH2 (ii), was shown to tolerate substitutions by a range of amino acids with retention of inhibitory activity. The effects of hydrophobic substitutions at this position as a means of enhancing binding interactions with the receptor were evaluated. Substitution of Nle at position 18 with either D-Ala, D-Trp, or L-Trp in analog ii or with Trp (D or L) in the recently reported, highly potent antagonist, [Nle8,18,D-Trp12,Tyr34]bPTH(7-34)NH2 (in vitro activities; Kb = 15 nM and Ki = 125 nM), was performed. In terms of activity on renal receptors, one antagonist, [Nle8,D-Trp12,18,Tyr34]bPTH(7-34)NH2, is the most active in vitro PTH antagonist yet reported (Kb = 4 nM; Ki = 30 nM). The rationale for design of this antagonist and the conclusions regarding PTH-receptor interactions are discussed.  相似文献   
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This article interprets the meanings and motivations of refusal to pay water bills within a context of fragmented sovereignty. Residents of a village in the occupied Palestinian West Bank call for solutions to water shortages and failed infrastructure, but do so amidst capricious power, where would-be sovereigns evade accountability. Lacking avenues for direct engagement with authorities, residents speak in generalized ethical terms of their legitimate water claims, and they resort to bill refusal. Setting villagers’ bill refusals within the broader set of interactions between would-be sovereigns and subjects, this article contributes to anthropological scholarship on refusal by demonstrating how it can be a way of not only dismantling state power, but also summoning a responsible sovereign. Furthermore, it highlights how common dilemmas faced by refusers – dismissal and co-optation – can be exacerbated by the same evasive accountability against which they protest.  相似文献   
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Adapted tango dancing improves mobility and balance in older adults and additional populations with balance impairments. It is composed of very simple step elements. Adapted tango involves movement initiation and cessation, multi-directional perturbations, varied speeds and rhythms. Focus on foot placement, whole body coordination, and attention to partner, path of movement, and aesthetics likely underlie adapted tango’s demonstrated efficacy for improving mobility and balance. In this paper, we describe the methodology to disseminate the adapted tango teaching methods to dance instructor trainees and to implement the adapted tango by the trainees in the community for older adults and individuals with Parkinson’s Disease (PD). Efficacy in improving mobility (measured with the Timed Up and Go, Tandem stance, Berg Balance Scale, Gait Speed and 30 sec chair stand), safety and fidelity of the program is maximized through targeted instructor and volunteer training and a structured detailed syllabus outlining class practices and progression.  相似文献   
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