丹麦哥本哈根贝拉天空酒店

作爲斯堪的納維亞半島最大的酒店,Balla Sky的開幕不僅成爲哥本哈根現代化的restad地區的象徵,更彰顯了該市在國際會議組織方面日益重要的地位。在哥本哈根任何角落都可領略到的雕塑般的造型,使它成爲該地區的地標,吸引了衆多游客前往restad地區。Bella Sky酒店擁有814間客房和30間會議室,爲哥本哈根Bella會展中心提供了大量新的住宿空間和資源,將使哥本哈根有能力承辦更大規模的國     

联合国城

正协调如一在联合国哥本哈根地区总部的诸多机构和功能,均整合进了这座联合国新城,它就坐落在哥本哈根市中心以北的Marmormolen(大理石墩)。3XN的方案,回应了联合国对建筑图腾的诉求,表达出这一组织的价值观和权威性。更值得一提的是,每个团队独立、高效而专业的品质清晰呈现的同时,它们所植根而共荣的价值观也呼之欲出——协调如一。建筑选址在人工岛上,自然同周边环境     

Toward a cDNA map of the human genome

Advances in the Human Genome Project are shaping the strategies for identifying the 50,000-100,000 human genes. High-resolution genetic maps of the human genome combined with sequencing herald an era of rapid regional definition of disease genes. However, only once their chromosome band location is known will the systematic partial sequencing of thousands of random cDNA clones provide the reagents for teh rapid assessment of the genes responsible for the inherited disorders. We now present an approach to the rapid determination of map position and therefore to the creation of a transcribed map of the human genome. Sensitive fluorescence in situ hybridization has been combined with high-resolution chromosome banding and random cDNA sequencing to map 41 cDNAs with an average insert size of <2 kb to single human chromosome bands. The result provide 15 new genes, with database and functional information, as candidates for human disease. These include the large extracellular signal-related kinase (HUMERK), the ERK activator kinase (PRKMK1), a new member of the RAS oncogene family, protein phosphatase 2 regulatory subunit B alpha isoform (PPP2R2A), and a novel human gene with very high homology to a plant membrane transport family. Further, an analysis of expressed genes associated with pseudogenes showed that by using these techniques, it is possible to detect accurately the transcribed locus within a multigene or processed pseudogene family in most cases. These findings suggest that direct cDNA mapping using fluorescence in situ hybridization provides an accurate and rapid approach to the definition of a transcribed map of the human genome. This low-cost, high-resolution (2-5 Mb) mapping greatly enhances the speed with which these genes can be subsequently assigned to contigs. This assignment provides a necessary first step in understanding the relationship of the genes to both acquired and inherited human diseases.     

Genotype-specific transcriptional regulation of PAI-1 gene by insulin, hypertriglyceridemic VLDL, and Lp(a) in transfected, cultured human endothelial cells

Plasminogen activator inhibitor-1 (PAI-1) has been shown to be an independent risk factor for coronary artery disease. Variations in plasma PAI-1 levels have been attributed to variations in the PAI-1 gene, and associations between PAI-1 levels and PAI-1 genotypes suggest that PAI-1 expression may be regulated in a genotype-specific manner by insulin, hypertriglyceridemic (HTG) very low density lipoprotein (VLDL), or lipoprotein(a) [Lp(a)]. Polymerase chain reaction-amplified 1106-bp fragments of the promoter of the 1/1 and 2/2 PAI-1 genotypes were sequenced and showed 5 regions of small nucleotide differences in the 1/1 versus 2/2 PAI-1 promoters that consistently occurred with high frequency. These fragments were ligated into the luciferase reporter gene, and 1/1 and 2/2 PAI-1 genotype human umbilical vein endothelial cell (HUVEC) cultures were transiently transfected with their respective p1PAI110/luc and p2PAI110/luc constructs and vice versa. Insulin induced an approximately 12- to 16-fold increase in luciferase activity in both the 1/1 and 2/2 PAI-1 genotype HUVEC cultures transfected with the p1PAI110/luc construct. HTG-VLDL and Lp(a) induced luciferase activity by approximately 14- to 16- and approximately 8- to 11-fold, respectively, in both the 1/1 and 2/2 PAI-1 genotype HUVEC cultures transfected with the p2PAI110/luc construct. The positive control interleukin-1 showed an approximately 7- to 12-fold response in the 1/1 and 2/2 PAI-1 genotype HUVEC cultures transfected with either of the constructs. These cross-over results demonstrate that regulation of either the 1/1 or 2/2 PAI-1 genotype by its respective inducer is due to the promoter itself and not to some factor(s) expressed differently in the 1/1 or 2/2 PAI-1 genotype HUVEC cultures.     

HtrI is a dimer whose interface is sensitive to receptor photoactivation and His-166 replacements in sensory rhodopsin I

Single cysteine substitutions were introduced into three positions of otherwise cysteineless HtrI, a phototaxis transducer found in Halobacterium salinarum that transmits signals from the photoreceptor sensory rhodopsin I (SRI) to a cytoplasmic pathway controlling the cell's motility. Oxidative cross-linking of the monocysteine HtrI mutants in membrane suspensions resulted in dimer forms evident in SDS-polyacrylamide gels. The rate of cross-linking of I64C on the cytoplasmic side of HtrI was accelerated by SRI binding in the dark and further increased by SRI photoactivation. Several residue replacements of His-166 in SRI accelerated the cross-linking rate of I64C in the dark and His-166 mutants that exhibit "inverted signaling" (mediating repellent instead of the normally attractant response to orange light) inverted the light effect on the cross-linking rate of I64C. Secondary structure prediction of HtrI indicates a coiled coil structure in the cytoplasmic region following TM2, a dimerization domain found in a diverse group of proteins. We conclude that 1) HtrI exists as a dimer both in the absence of SRI and in the SRI-HtrI complex, 2) binding of SRI in the dark increases reactivity of the two cysteines at position 64 in the dimer by increasing their proximity or mobility, 3) light activation of wild-type SRI further increases their reactivity, 4) His-166 replacements in the SRI receptor have conformational effects on the structure of HtrI at position 64, and 5) inverted signaling by His-166 mutants likely results from an inverted conformational change at this region induced by SRI photoactivation.     

The specificity of interaction of archaeal transducers with their cognate sensory rhodopsins is determined by their transmembrane helices

Chimeras of the Halobacterium salinarum transducers HtrI and HtrII were constructed to study the structural determinants for their specific interaction with the phototaxis receptors sensory rhodopsins I and II (SRI and SRII), respectively. Interaction of receptors and transducers was assessed by two criteria: phototaxis responses by the cells and transducer-modulation of receptor photochemical reaction kinetics in membranes. Coexpression of HtrI with SRII or HtrII with SRI did not result in interaction by either criterion. Each receptor was coexpressed with chimeric transducers in which various domains of the two transducers were interchanged. The results show that the presence of the two transmembrane helices of HtrI in a chimera is necessary and sufficient for functional transducer complexation with SRI, i.e., for wild-type SRI photoreactions and attractant and 2-photon repellent phototaxis responses. Additionally, a previously demonstrated chaperone-like facilitation of SRI folding or stability by HtrI was shown to depend only on the two transmembrane helices of HtrI in chimeric transducers. Similarly, the two transmembrane helices of HtrII specify interaction with the repellent receptor SRII according to motility analysis and laser-flash spectroscopy. The results support a model in which the membrane domains of the receptor/transducer complexes, consisting of the seven helices of the receptor interacting with the four-helix bundle of the transducer dimer, produce SRI- and SRII-specific signals to the flagellar motor by means of interchangeable cytoplasmic domains.     

优雅与欢乐的融合——挪威曼达尔镇文化中心(拱门)

历史悠久的白色木屋,令人陶醉的狭长街道,河水流经城中,水岸、森林环绕—这就是曼达尔(Mandal),一座汇集挪威南部田园风光精华的小镇。我们也力求在曼达尔镇新的文化中心的设计中,表现出对这一环境的高度敏感。这座被称为拱门(TheAtch)的文化中心造型酷似一块绿色地毯,使拔地而起的建筑融入周边环境景观。大厅使用玻璃立面,朝向河岸开放,也得以拥有充足日照。建筑无论在色彩、尺度还是比例上,都根据沿河岸极富特色的如画般的挪威木屋进行了调整。与自然和水的亲密接触通过将建筑与周围景观相结合,文化中心为原本无人问津的城市工业区平添了吸引力。绿色、精     

Follicle-stimulating hormone, human chorionic gonadotropin, and prolactin receptors in hamster corpora lutea or dispersed luteal cells during pregnancy

In vitro progesterone (P4) production by hamster luteal cells is stimulated throughout pregnancy by FSH and LH. Prolactin (PRL) by itself, however, increases P4 synthesis only on Day 12; on Day 4, FSH+LH+PRL induces optimal P4 secretion [Biol Reprod 1994; 51:43-49]. In light of these findings, in this study we investigated FSH, hCG, and PRL receptors in hamster CL or dispersed luteal cells on Days 4, 8, and 12 of pregnancy. Scatchard analysis of hamster CL on Days 4 and 8 showed considerably more unoccupied hCG receptors than FSH receptors: on Day 4, there was 9.5 fmol/mg protein for FSH binding sites vs. 1741 fmol/mg protein for hCG binding. Moreover, the binding affinity of hCG was greater than for FSH: the Day 4 Kd was 0.136 nM for hCG vs. 0.308 for FSH. Similar differences were observed on Day 8. Dispersed luteal cells (large+small cells) were incubated for 24 h with or without 10 ng of ovine FSH, LH, and PRL or human recombinant FSH (r-hFSH), alone or in different combinations. The cells were then washed and incubated for 4 h with iodinated hCG, FSH, or PRL with or without 100-fold excess of unlabeled hormones. The number of binding sites per 200,000 luteal cells did not change appreciably for FSH and hCG on Days 4 and 12 of pregnancy, whereas PRL binding sites significantly increased on Day 12.(ABSTRACT TRUNCATED AT 250 WORDS)