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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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A Bengtsson L Holm O B?ck J Fransson A Scheynius 《Canadian Metallurgical Quarterly》1997,109(3):533-537
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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S. Klages M. Schöck C. Sürgers H. v. Löhneysen 《Journal of Low Temperature Physics》2004,137(3-4):509-522
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 Gs ∝ exp[?(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
6.
B Brismar JE Akerlund S Sj?stedt C Johansson A T?rnqvist B B?ckstrand H B?ng L And?ker PO Gustafsson N Darle M Anger?s A Falk G Tunevall B Kasholm-Tengve T Skau PO Nystr?m T Gasslander A Hagelb?ck B Olsson-Liljequist AE Eklund CE Nord 《Canadian Metallurgical Quarterly》1996,28(5):507-512
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
7.
K Ungersb?ck D Tenckhoff A Heimann W Wagner OS Kempski 《Canadian Metallurgical Quarterly》1995,36(1):147-56; discussion 156-7
The effect of increased intracranial pressure on the flow velocity of the basilar artery was measured with transcranial ultrasonic Doppler in New Zealand White rabbits under alpha-chloralose anesthesia and artificial respiration. Laser Doppler flowmetry served to study changes of the cortical microcirculation. The results confirm a high inverse correlation of the diastolic flow velocity, the pulsatility index, and the resistance index with the cerebral perfusion pressure (CPP). During acute intracranial hypertension, however, these parameters do not show a good correlation with the local cortical blood flow. The absence of a correlation was evident over a wide CPP range down to values of 35 mm Hg. Only at CPP values below this critical threshold is the microcirculation impaired. The threshold is reached at pulsatility index values of more than 2.0 and at resistance index values of more than 0.8. Therefore, transcranial Doppler indices permit the detection of critical reductions of microcirculatory blood flow. The Cushing reaction occurred with a constant time lag of 5.5 +/- 0.7 seconds after the loss of CPP. The Cushing reaction did not establish systolic blood flow, which remained below the functional threshold, as concluded from the temporary loss of somatosensory evoked potentials. 相似文献
8.
Nils Hallbäck Fred Nilsson 《Fatigue & Fracture of Engineering Materials & Structures》1992,15(2):173-185
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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10.
The binding of 125I-labelled tissue plasminogen activator (tPA), the tPA A- or B-chain to endothelial cells (EC) were studied in suspensions of cultured human umbilical vein EC (HUVEC) or immortalized microvascular EC (HMEC). By determinations of the concentration-dependent binding it was shown that both the A-chain and the B-chain, which were isolated after partial reduction of two-chain tPA, contain ligands for binding to EC. The affinity for the B-chain was much higher than for the A-chain according to Scatchard analysis (Kd 24 and 515 nM, respectively), whereas the number of binding sites was higher for the A-chain than for the B-chain (Bmax 8 x 10(5) and 1.2 x 10(5), respectively). There were no cross interactions between the A- and B-chains and their binding sites. The binding of tPA to EC induced an almost 100-fold increase of the activation rate when compared to the same amount of enzyme in free solution, which in contrast to the fibrin-induced stimulation was not inhibited by antibodies against fibrin. The enzymatic activity of the B-chain was much less affected by the association to the cells. Both tPA and the tPA B-chain were largely protected against inhibition by an excess plasminogen activator type-1 (PAI-1) when bound to EC, whereas the same amount of free tPA was totally inactivated. The competition studies strongly indicated that an N-terminal segment in the B-chain, AKHRRSPGER, may be the ligand part of the B-chain. It is interesting to note that this polypeptide segment also participates in a binding site for PAI-1, necessary for effective inhibition. This implies a possible competition between PAI-1 and a tPA-receptor for binding of tPA. High molecular weight urokinase had no quenching effect on the binding of the B-chain to EC. 相似文献