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1.
Potential mGAT4 inhibitors derived from the lead substance (S)-SNAP-5114 have been synthesized and characterized for their inhibitory potency. Variations from the parent compound included the substitution of one of its aromatic 4-methoxy and 4-methoxyphenyl groups, respectively, with a more polar moiety, including a carboxylic acid, alcohol, nitrile, carboxamide, sulfonamide, aldehyde or ketone function, or amino acid partial structures. Furthermore, it was investigated how the substitution of more than one of the aromatic 4-methoxy groups affects the potency and selectivity of the resulting compounds. Among the synthesized test substances (S)-1-{2-[(4-formylphenyl)bis(4-methoxyphenyl)-methoxy]ethyl}piperidine-3-carboxylic acid, that features a carbaldehyde function in place of one of the aromatic 4-methoxy moieties of (S)-SNAP-5114, was found to have a pIC50 value of 5.89±0.07, hence constituting a slightly more potent mGAT4 inhibitor than the parent substance while showing comparable subtype selectivity.  相似文献   
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过去因为机箱通常自带电源。所以我们很少主动去挑选,以为整合的东西很好,至少省事。但后来电脑硬件百花齐放般地发展,使得大家开始注意它。而且随着电脑进入64位跗代,单独选购一款大功率电源也非常有必要,但自选也带来不少问题,面对众多品牌我们该如何下手,更有奸商提供的产品比整合的电源还便宜,伴随着种种疑问,希望笔者提供的分析能帮大家早日找到自己的“心中所属”。[编者按]  相似文献   
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The immunopathology of AD is still unclear, but evidence for an immune response polarized towards Th2 activity has been provided. The CD30 molecule belongs to the tumour necrosis factor (TNF) receptor family and is expressed on activated T cells with a sustained expression in Th2 cells. This molecule also exists in a soluble form (sCD30). Elevated serum levels of sCD30 have been found in patients with Hodgkin's disease, chronic hepatitis B infection and HIV infection. Studies were undertaken to compare the serum levels of sCD30 in patients with AD (n=49) and healthy non-atopic controls (n=94). The presence of sCD30 was analysed with ELISA. A significantly higher concentration of sCD30 was noted in AD patients, median sCD30 level 29 U/ml (range 1-708 U/ml), compared with healthy non-atopic controls (P<0.001), where the median level was 11 U/ml with a range of 1-1042 U/ml. No correlation was found between sCD30 levels and total serum IgE, or between the AD patients' SCORAD values and concentration of sCD30. sCD30 levels were also analysed in 20 AD patients, which during ketoconazole treatment had improved their clinical scores and reduced their serum IgE and eosinophil cationic protein levels. However, no significant decrease in sCD30 levels was noted after treatment. The results show that patients with AD have elevated levels of sCD30, but without correlation to total serum IgE or disease activity.  相似文献   
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The morphology and electronic transport of ultrathin Au films with thicknesses d = 1 ? 5 monolayers (ML) deposited on Si(111)7 × 7 surfaces is investigated by in situ scanning tunneling microscopy and electrical resistance measurements for temperatures T = 2 ? 300 K. With decreasing film thickness, i.e. decreasing sheet conductance Gs, a transition from a weakly conducting regime described by a logarithmic temperature dependence to an insulating regime occurs. In the insulating regime, the temperature dependence is described by Gsexp[?(T 0 /T) n] with an exponent n which gradually changes from 0.69 to 1 with decreasing film thickness. In contrast, for the Si(111)6 × 6-Au reconstruction obtained after annealing, an exponent n = 1/2 is found suggesting the formation of a soft Coulomb gap due to electron-electron interaction. PACS numbers: 68.37.-d, 68.55.-a, 73.50.-h, 73.25.+i, 81.15.-z  相似文献   
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The objective of this study is to describe usual medical management and costs associated with recurrent respiratory infections in subjects with chronic obstructive bronchitis in France. A prospective survey was performed in Autumn 1994 on a national sample of private practice pulmonologists (N = 71). Two hundred forty-four patients, presenting at least one infection of the lower respiratory tract, were included. Bronchitis was the most frequent acute exacerbation observed (94%). Pneumonia concerned 9% of the patients. Biological tests, X-rays and pulmonary function tests were prescribed for, respectively, 59, 65 and 45% of the patients. Following the visit, 15 patients were hospitalized (6%). The direct medical cost per acute exacerbation was estimated 3,289 francs (1994 value) of which 60% were hospital-related. An average 10.4 day sick-leave was prescribed to 21% of patients in employment. For those patients, this sick-leave was associated to an extra-cost of 1,264-1,876 francs for Social Security and of 0-2,553 francs out of pocket per episode varying according to their Benefit Regimen.  相似文献   
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The fracture assessment of structures subjected to secondary loading systems was studied by FEM-analysis of a few illustrative two-dimensional examples. The first example is an edge-cracked plate with a thermal gradient. The FEM-calculations revealed that a purely elastic analysis yielded J-values that are in most cases considerably more conservative than the ones calculated from an elastic-plastic analysis. The results were further compared with different engineering type non-linear estimates. As a second example a crack emanating from a semi-circular notch in a rectangular plate was chosen. The plate was subjected to uniaxial tension along its boundaries. It turned out that for the cases considered the J-values were fairly close to those elastically predicted.  相似文献   
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如果购买了不合格的CPU就会给电脑装上一颗脆弱的“芯”,后果很可能烧坏其他配件,给我们带来麻烦。认清假冒伪劣产品的真实面目。法和如何辨别做一翻介绍,让大家认清假冒伪劣产品的真实面目。[编者按]  相似文献   
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