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41.
Objective: Peptide YY3–36 [PYY(3–36)] has shown efficacy in appetite suppression when dosed by injection modalities (intraperitoneal (IP)/subcutaneous). Transitioning to needle-free delivery, towards inhalation, often utilizes systemic pharmacokinetics as a key endpoint to compare different delivery methods and doses. Systemic pharmacokinetics were evaluated for PYY3–36 when delivered by IP, subcutaneous, and inhalation, the systemic pharmacokinetics were then used to select doses in an appetite suppression pharmacodynamic study.

Methods: Dry-powder formulations were manufactured by spray drying and delivered to mice via nose only inhalation. The systemic plasma, lung tissue, and bronchoalveolar lavage fluid pharmacokinetics of different inhalation doses of PYY(3–36) were compared to IP and subcutaneous efficacious doses. Based on these pharmacokinetic data, inhalation doses of 70:30 PYY(3–36):Dextran T10 were evaluated in a mouse model of appetite suppression and compared to IP and subcutaneous data.

Results: Inhalation pharmacokinetic studies showed that plasma exposure was similar for a 2?×?higher inhalation dose when compared to subcutaneous and IP delivery. Inhalation doses of 0.22 and 0.65?mg/kg were for efficacy studies. The results showed a dose-dependent (not dose proportional) decrease in food consumption over 4?h, which is similar to IP and subcutaneous delivery routes.

Conclusions: The pharmacokinetic and pharmacodynamics results substantiate the ability of pharmacokinetic data to inform pharmacodynamics dose selection for inhalation delivery of the peptide PYY(3–36). Additionally, engineered PYY(3–36):Dextran T10 particles delivered to the respiratory tract show promise as a non-invasive therapeutic for appetite suppression.  相似文献   
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Two experiments are reported that use patients with visual extinction to examine how visual attention is influenced by action information in images. In Experiment 1 patients saw images of objects that were either correctly or incorrectly colocated for action, with the objects held by hands that were congruent or incongruent with those used premorbidly by the patients. The images were also shown from a 1st- and 3rd-person perspective. There was an overall reduction in extinction for objects colocated for action. In addition, there was an extra benefit when the objects were held in hands congruent with those used by the patients and when the objects were seen from a 1st-person perspective. This last result fits with an effect of motor simulation, over and above a purely visual effect based on positioning objects correctly for action. Experiment 2 showed that effects of hand congruence could emerge with images depicted from a 3rd-person perspective when patients saw themselves holding the objects. The data indicate 2 effects of action information on extinction: (a) an effect of colocating objects for action, which does not depend on a self-reference frame (a visual effect), and (b) an effect sensitive to object–hand congruence, which does depend on a self-reference frame (a motor-based effect). The self-reference frame is induced when stimuli are viewed from a 1st-person perspective and when an image of the self is seen from a 3rd-person perspective. Both visual and motor-based effects of action information facilitate the spread of attention across objects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
44.
通过对一组运行了4年的不锈钢过热器管样内表面机加工区和非机加工区氧化皮的结构和形貌特征进行对比分析,探讨内表面冷作硬化处理对于超超临界机组锅炉用不锈钢管蒸汽氧化性能的影响.结果表明,内表面冷作硬化处理对于改善细晶TP347H FG和Super304奥氏体不锈钢在相对较低温度蒸汽中的抗氧化性能非常有效,但在600℃左右高温蒸汽中Super304管样内表面冷作硬化效应消失,除冷作硬化试样氧化皮的总体厚度略薄外,氧化皮的结构形貌特征与未冷作硬化处理的管样没有多大区别.另外,含Cr量大于22%的SAVE25具有非常优秀的抗蒸汽氧化性能,其机加工区域和未机加工区域的蒸汽氧化行为没有任何区别.  相似文献   
45.
Using Gray and McNaughton's (2000) revised reinforcement sensitivity theory (r-RST), we examined the influence of personality on processing of words presented in gain-framed and loss-framed anti-speeding messages and how the processing biases associated with personality influenced message acceptance. The r-RST predicts that the nervous system regulates personality and that behaviour is dependent upon the activation of the behavioural activation system (BAS), activated by reward cues and the fight-flight-freeze system (FFFS), activated by punishment cues. According to r-RST, individuals differ in the sensitivities of their BAS and FFFS (i.e., weak to strong), which in turn leads to stable patterns of behaviour in the presence of rewards and punishments, respectively. It was hypothesised that individual differences in personality (i.e., strength of the BAS and the FFFS) would influence the degree of both message processing (as measured by reaction time to previously viewed message words) and message acceptance (measured three ways by perceived message effectiveness, behavioural intentions, and attitudes). Specifically, it was anticipated that, individuals with a stronger BAS would process the words presented in the gain-frame messages faster than those with a weaker BAS and individuals with a stronger FFFS would process the words presented in the loss-frame messages faster than those with a weaker FFFS. Further, it was expected that greater processing (faster reaction times) would be associated with greater acceptance for that message. Driver licence holding students (N = 108) were recruited to view one of four anti-speeding messages (i.e., social gain-frame, social loss-frame, physical gain-frame, and physical loss-frame). A computerised lexical decision task assessed participants’ subsequent reaction times to message words, as an indicator of the extent of processing of the previously viewed message. Self-report measures assessed personality and the three message acceptance measures. As predicted, the degree of initial processing of the content of the social gain-framed message mediated the relationship between the reward sensitive trait and message effectiveness. Initial processing of the physical loss-framed message partially mediated the relationship between the punishment sensitive trait and both message effectiveness and behavioural intention ratings. These results show that reward sensitivity and punishment sensitivity traits influence cognitive processing of gain-framed and loss-framed message content, respectively, and subsequently, message effectiveness and behavioural intention ratings. Specifically, a range of road safety messages (i.e., gain-frame and loss-frame messages) could be designed which align with the processing biases associated with personality and which would target those individuals who are sensitive to rewards and those who are sensitive to punishments.  相似文献   
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Based on their predominance in Gari fermentations, as well as suitable technological properties, Lactobacillus plantarum, Lactobacillus fermentum, Weissella paramesenteroides and Leuconostoc mesenteroides strains were investigated for their suitability for development as starter strains for this African traditional fermented cassava product. The strains were grown in optimized growth media in 2 L fermenters, harvested and freeze dried, and then tested in lab-scale cassava mash fermentation trials for their ability to ferment the cassava. The strains performed well and rapidly increased the titratable acidity from 1.1 to 1.3% at 24 h to 1.3–1.6% at 48 h. The benefit of including starter cultures was that it lowered the pH of the product much faster and to lower levels than in the uninoculated control fermentation. The results furthermore indicated that especially the L. plantarum-group strains could be produced as starter strains at low cost. Overall, the results of this study showed that starter strains could be easily and economically produced, and thus represent a feasible possibility for further development for application in the field.  相似文献   
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Starvation of polymer electrolyte fuel cells (PEFC) takes place, especially during transients, if reactants are consumed in the fuel cell faster than they can be supplied. It is one of the main causes of aging and degeneration of fuel cells.  相似文献   
50.
The reconfiguration of the home-work boundary that at-home telework entails has significant implications for gender issues and the use of ubiquitous information and communications technologies (ICTs). By presenting a Marx-inspired dialectical analysis of the family and home as both ‘haven and hell’, we develop a critique of proposed advantages for women home workers. Not only do we question the ability of ICTs to deliver the promises made on their behalf – we show how this socio-technical innovation may in fact contribute to compounding the double-burden of work associated with gender roles within the home. Contemporary critical understanding of the e-society should incorporate the influence of at-home teleworking because of its implications for the use of ubiquitous ICTs in the home environment, the shaping of work relations and its impact on gender issues. This increasing use of ICTs outside of the workplace is matched by the growing consensus within the European Union on the desirability of flexible working coupled with family friendly policies. This paper explores some of the rhetoric and research surrounding the proposed benefits of at home ‘telework’ and the likely cost–benefits, from an employee's perspective, in terms of increased freedom, reduced burden and ‘flexibility’.  相似文献   
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