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Alport syndrome (AS) is a hereditary renal disorder with no etiological therapy. In the preclinical Col4a3-/- model of AS, disease progression and severity vary depending on mouse strain. The sodium-glucose cotransporter 2 (SGLT2) is emerging as an attractive therapeutic target in cardiac/renal pathologies, but its application to AS remains untested. This study investigates cardiorespiratory function and SGLT2 renal expression in Col4a3-/- mice from three different genetic backgrounds, 129x1/SvJ, C57Bl/6 and Balb/C. male Col4a3-/- 129x1/SvJ mice displayed alterations consistent with heart failure with preserved ejection fraction (HFpEF). Female, but not male, C57Bl/6 and Balb/C Col4a3-/- mice exhibited mild changes in systolic and diastolic function of the heart by echocardiography. Male C57Bl/6 Col4a3-/- mice presented systolic dysfunction by invasive hemodynamic analysis. All strains except Balb/C males demonstrated alterations in respiratory function. SGLT2 expression was significantly increased in AS compared to WT mice from all strains. However, cardiorespiratory abnormalities and SGLT2 over-expression were significantly less in AS Balb/C mice compared to the other two strains. Systolic blood pressure was significantly elevated only in mutant 129x1/SvJ mice. The results provide further evidence for strain-dependent cardiorespiratory and hypertensive phenotype variations in mouse AS models, corroborated by renal SGLT2 expression, and support ongoing initiatives to develop SGLT2 inhibitors for the treatment of AS.  相似文献   
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American culture is filled with cultural products. Yet few studies have investigated how changes in cultural products correspond to changes in psychological traits and emotions. The current research fills this gap by testing the hypothesis that one cultural product—word use in popular song lyrics—changes over time in harmony with cultural changes in individualistic traits. Linguistic analyses of the most popular songs from 1980–2007 demonstrated changes in word use that mirror psychological change. Over time, use of words related to self-focus and antisocial behavior increased, whereas words related to other-focus, social interactions, and positive emotion decreased. These findings offer novel evidence regarding the need to investigate how changes in the tangible artifacts of the sociocultural environment can provide a window into understanding cultural changes in psychological processes. (PsycINFO Database Record (c) 2011 APA, all rights reserved)  相似文献   
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1. Introduction The requirement of minimal bottom coverageand thick sidewall coverage for PVD-based films forlow via resistance and improved stress migration isnot easy to achieve with traditional depositionmethods. Modern I-PVD techniques give high bot-tom coverage, due to the ionized component of thedeposition flux. Sidewall coverage tends to be low,which is mainly due to off-normal deposition fluxand a less than unity sticking coefficient.  相似文献   
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低纹波电压正至负压dc/dc转换器如今广泛应用于高频和对噪声敏感的磁盘驱动器、电池供电设备、便携式电脑及汽车电子。类似于正电压降压转换器,如果在V_IN与V_OUT之间接大容量电容器,而不是在输入V_IN与地之间,一个正至负转换器可以获得低的输出纹波电压。人们通常误认为第一种接法的正至负转换器有很大的噪声,  相似文献   
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Automatic quantification of changes in bone in serial MR images of joints   总被引:1,自引:0,他引:1  
Recent innovations in drug therapies have made it highly desirable to obtain sensitive biomarkers of disease progression that can be used to quantify the performance of candidate disease modifying drugs. In order to measure potential image-based biomarkers of disease progression in an experimental model of rheumatoid arthritis (RA), we present two different methods to automatically quantify changes in a bone in in-vivo serial magnetic resonance (MR) images from the model. Both methods are based on rigid and nonrigid image registration to perform the analysis. The first method uses segmentation propagation to delineate a bone from the serial MR images giving a global measure of temporal changes in bone volume. The second method uses rigid body registration to determine intensity change within a bone, and then maps these into a reference coordinate system using nonrigid registration. This gives a local measure of temporal changes in bone lesion volume. We detected significant temporal changes in local bone lesion volume in five out of eight identified candidate bone lesion regions, and significant difference in local bone lesion volume between male and female subjects in three out of eight candidate bone lesion regions. But the global bone volume was found to be fluctuating over time. Finally, we compare our findings with histology of the subjects and the manual segmentation of bone lesions.  相似文献   
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(上接2007年第6期91页) 1.6 快速简便的内部测试有助于有源器件的选择 尽管供应商提供了电子器件的EMC性能参数,但在实际工作环境中的EMC性能通常是无法预知的。在设计部门内部可以采取一些简便快捷的EMC测试方法对功能性电路进行测试,但电路中至少要具有时钟、完整的信号或数据输入/输出功能。有些供应商还可提供用于此类测试的评估板。  相似文献   
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