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11.
Xiangdong Su Dr. Fabienne Pradaux‐Caggiano Dr. Mark P. Thomas Dr. Michelle W. Y. Szeto Dr. Heather A. Halem Dr. Michael D. Culler Dr. Nigel Vicker Dr. Barry V. L. Potter Prof. 《ChemMedChem》2010,5(7):1026-1044
11β‐Hydroxysteroid dehydrogenases (11β‐HSDs) are key enzymes regulating the pre‐receptor metabolism of glucocorticoid hormones. The modulation of 11β‐HSD type 1 activity with selective inhibitors has beneficial effects on various conditions including insulin resistance, dyslipidemia and obesity. Inhibition of tissue‐specific glucocorticoid action by regulating 11β‐HSD1 constitutes a promising treatment for metabolic and cardiovascular diseases. A series of novel adamantyl ethanone compounds was identified as potent inhibitors of human 11β‐HSD1. The most active compounds identified ( 52 , 62 , 72 , 92 , 103 and 104 ) display potent inhibition of 11β‐HSD1 with IC50 values in the 50–70 nM range. Compound 72 also proved to be metabolically stable when incubated with human liver microsomes. Furthermore, compound 72 showed very weak inhibitory activity for human cytochrome P450 enzymes and is therefore a candidate for in vivo studies. Comparison of the publicly available X‐ray crystal structures of human 11β‐HSD1 led to docking studies of the potent compounds, revealing how these molecules may interact with the enzyme and cofactor. 相似文献
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CC Szeto CC Chow GT Ko KY Li VT Yeung CS Cockram 《Canadian Metallurgical Quarterly》1997,73(855):39-40
A 22-year-old Chinese man, a HBsAg carrier, presented with relapse of thyrotoxic Graves' disease complicated by thrombocytopenia and hepatitis. Platelet count and liver enzymes gradually improved following successful treatment of the thyrotoxicosis with radioactive iodine. Possible pathogenetic links and therapeutic implications are discussed. 相似文献
14.
Joseph Ignatius Teye Buertey Augustine Kaku Miezah Theophilus Adjei Kumi 《土木工程与建筑:英文版》2014,(3):367-377
Delay to large scale projects, which is as a result of actions or inactions of some project stakeholders, is becoming a global phenomena and Ghana is no exception. The objective of the research is to identify, rate and rank the most significant risk factors that causes delay on projects and examine the social impact of these delays to recommend modalities to help mitigate these risk factors. The study adopted quantitative methods with the distribution of 144 questionnaires to built environment professionals receiving a response rate of 75.7%. The instrument listed 58 common factors under eight categories that contribute to the causes of delay for respondents to rate. Analysis of data non-parametric test revealed that client, contractor, material and finance category factors significantly resulted in the schedule delay of large infrastructural projects. The survey analysis revealed that micro-factors that result in delays to large construction projects are time constraint, cost overrun, payment problems, dispute and litigation. The research recommended the following modalities to minimize such delays: availability of resources, improved communication and coordination, proper scope definition and feasibilities, utilization of modern technology, appropriate application of technologically based systems and competent project management's structures. 相似文献
15.
P M?kel?-Bengs N J?rvinen K Vuopala A Suomalainen J Ignatius M Sipil? R Herva A Palotie L Peltonen 《Canadian Metallurgical Quarterly》1998,63(2):506-516
Lethal congenital contracture syndrome (LCCS) is an autosomal recessive disease leading to death before the 32d gestational week. It is characterized by the fetal akinesia phenotype, with highly focused degeneration of motoneurons in the spinal cord as the main neuropathological finding. We report here the assignment of the LCCS locus to a defined region of chromosome 9q34, between markers D9S1825 and D9S1830. The initial genome scan was performed with the DNA samples of only five affected individuals from two unrelated LCCS families. The conventional linkage analysis performed with 20 affected individuals and their families was focused on those chromosomal regions in which the affected siblings were identical by descent in the initial scan. One core haplotype of 3 cM was observed in LCCS alleles, supporting the assumption of one major mutation underlying LCCS, and linkage disequilibrium analysis restricted the critical chromosomal region to <100 kb in the vicinity of marker D9S61. Two genes, NGAL (neutrophil gelatinase-associated lipocalin and NOTCH 1, were excluded as causative genes for LCCS 相似文献
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CC Szeto CC Chow KY Li TC Ko VT Yeung CS Cockram 《Canadian Metallurgical Quarterly》1996,35(3):289-291
We report a case of oesophageal disease as the first manifestation in a patient with CREST syndrome. A 46-year-old man with achalasia-like syndrome developed CREST syndrome 4 years later. A pneumatic dilatation of the cardia was performed. After pneumatic dilatation the dysphagia and regurgitation disappeared but the patient developed reflux oesophagitis. Four years after diagnosis of oesophageal disease he presented with a clinical picture of CREST syndrome. An acute ileus and constipation developed later. After receiving medical therapy with omeprazole and cisapride the patient is free of oesophageal symptoms and bowel movements are normal. Oesophageal disease is common in patients with limited and diffuse scleroderma, but to our knowledge achalasia-like syndrome has not been previously described as the first manifestation of the systemic disease. 相似文献
18.
一种基于多Agent协同的准并行遗传算法 总被引:10,自引:1,他引:9
提出了一种基于多Agent协同操作的准并行遗传算法结构.该算法由若干运行简单遗传算法的计算单元组成,每个单元也就是独立的计算Agent.算法依照资源分配向量为各单元分配不同的计算资源,并根据个体迁移矩阵驱动它们进行个体交换.从多Agent系统的观点看,资源的分配体现了算法对各Agent的协调,个体的迁移则体现了Agent之间的协作.该算法很容易在串行计算机上实现,此时各个计算单元具有微观上串行、宏观上并行的准并行关系.对二维准并行算法动态性能的分析表明:由于统筹考虑了各计算单元间的协同关系,算法能够更充分有效地利用有限的计算资源,在解决不同的优化问题时表现出了很高的性能. 相似文献
19.
The effects of midazolam (MID) on the in vitro growth and differentiation of two murine myeloid leukemia WEHI 3B (JCS) and M1 cells were studied. MID inhibits the proliferation of both M1 and JCS cells in a dose-dependent manner. At the concentration of 10 micrograms/ml, MID was found to induce both monocytic and granulocytic differentiation of the JCS but not M1 cells. Induction of morphological differentiation of the JCS cells was also associated with the enhanced expression of the differentiation antigens Mac-1, F4/80, and Gr-1 for the cells. Results from mRNA phenotyping experiments also indicated that the expression of tumor necrosis factor (TNF-alpha) and neutrophil-specific J11d differentiation marker was significantly upregulated in MID-treated JCS cells. In addition, the phagocytic activity of MID-treated JCS cells was increased towards opsonized yeast cells. Results from this investigation suggested that MID may be used as an inducer for further study on the mechanisms of differentiation in these myeloid leukemia cells. 相似文献
20.
Mohamed Lebbai Jang-Kyo Kim W. K. Szeto Matthew M. F. Yuen Pin Tong 《Journal of Electronic Materials》2003,32(6):558-563
Copper-oxide coating applied onto the copper substrate has emerged as an alternative to metallic coatings to improve adhesion
with polymeric adhesives and molding compounds. The interfacial-bond strengths between the black oxide-coated Cu substrate
and epoxy-based, glob-top resin were measured in button-shear tests, and the failure mechanisms were identified from the fracture-surface
examination. The emphasis was to establish the correlation between the coating thickness, the surface roughness, and the interfacial
adhesion with respect to treatment time. It was found that at the initial stage of treatment a thin layer of flat, cuprous
oxide developed, above which fibrillar-cupric oxide was formed with further treatment until saturation with densified fibrils
at about 150 sec. The interfacial-bond strength between the oxide-coated copper substrate and glob-top resin increased gradually
with increasing treatment time, until the bond strength reached a plateau constant after a treatment for about 150 sec. There
was a functional similarity between the oxide thickness, the surface roughness, and the interface-bond strength with respect
to treatment time. A treatment time of 150 sec is considered an optimal condition that can impart the highest interface adhesion. 相似文献