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161.
162.
H R Wilson 《Nature》1974,251(5477):735-736
163.
This paper explores the relationship between the Australian real estate and equity market between 1980 and 1999. The results from this study show three specific outcomes that extend the current literature on real estate finance. First, it is shown that structural shifts in stock and property markets can lead to the emergence of an unstable linear relationship between these markets. That is, full‐sample results support bi‐directional Granger causality between equity and real estate returns, whereas when sub‐samples are chosen that account for structural shifts the results generally show that changes within stock market prices influence real estate market returns, but not vice versa. Second, the results also indicate that non‐linear causality tests show a strong unidirectional relationship running from the stock market to the real estate market. Finally, from this empirical evidence a trading strategy is developed which offers superior performance when compared to adopting a passive strategy for investing in Australian securitized property. These results appear to have important implications for managing property assets in the funds management industry and also for the pricing efficiency within the Australian property market. Copyright © 2002 John Wiley & Sons, Ltd. 相似文献
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165.
Although oxidative damage has long been associated with ageing and neurological disease, mechanistic connections of oxidation to these phenotypes have remained elusive. Here we show that the age-dependent somatic mutation associated with Huntington's disease occurs in the process of removing oxidized base lesions, and is remarkably dependent on a single base excision repair enzyme, 7,8-dihydro-8-oxoguanine-DNA glycosylase (OGG1). Both in vivo and in vitro results support a 'toxic oxidation' model in which OGG1 initiates an escalating oxidation-excision cycle that leads to progressive age-dependent expansion. Age-dependent CAG expansion provides a direct molecular link between oxidative damage and toxicity in post-mitotic neurons through a DNA damage response, and error-prone repair of single-strand breaks. 相似文献
166.
Stamen specification and anther development in rice 总被引:5,自引:0,他引:5
Male reproductive development is a complex biological process which includes the formation of the stamen with differentiated anther tissues, in which microspores/pollens are generated, then anther dehiscence and subsequently pollination. Stamen specification and anther development involve a number of extraordinary events such as meristem transition, cell division and differentiation, cell to cell communication, etc., which need the cooperative interaction of sporophytic and gametophytic genes. The advent of various tools for rice functional gene identification, such as complete genome sequence, genome-wide microarrays, collections of mutants, has greatly facilitated our understanding of mechanisms of rice stamen specification and anther development. Male sterile lines are critical for hybrid rice breeding, therefore understanding these processes will not only contribute greatly to the basic knowledge of crop developmental biology, but also to the development of new varieties for hybrid rice breeding in the future. 相似文献
167.
P Wei WW Wong JS Park EE Corcoran SG Peisajovich JJ Onuffer A Weiss WA Lim 《Nature》2012,488(7411):384-388
Bacterial pathogens have evolved specific effector proteins that, by interfacing with host kinase signalling pathways, provide a mechanism to evade immune responses during infection. Although these effectors contribute to pathogen virulence, we realized that they might also serve as valuable synthetic biology reagents for engineering cellular behaviour. Here we exploit two effector proteins, the Shigella flexneri OspF protein and Yersinia pestis YopH protein, to rewire kinase-mediated responses systematically both in yeast and mammalian immune cells. Bacterial effector proteins can be directed to inhibit specific mitogen-activated protein kinase pathways selectively in yeast by artificially targeting them to pathway-specific complexes. Moreover, we show that unique properties of the effectors generate new pathway behaviours: OspF, which irreversibly inactivates mitogen-activated protein kinases, was used to construct a synthetic feedback circuit that shows novel frequency-dependent input filtering. Finally, we show that effectors can be used in T cells, either as feedback modulators to tune the T-cell response amplitude precisely, or as an inducible pause switch that can temporarily disable T-cell activation. These studies demonstrate how pathogens could provide a rich toolkit of parts to engineer cells for therapeutic or biotechnological applications. 相似文献
168.
Zhang J Benavente CA McEvoy J Flores-Otero J Ding L Chen X Ulyanov A Wu G Wilson M Wang J Brennan R Rusch M Manning AL Ma J Easton J Shurtleff S Mullighan C Pounds S Mukatira S Gupta P Neale G Zhao D Lu C Fulton RS Fulton LL Hong X Dooling DJ Ochoa K Naeve C Dyson NJ Mardis ER Bahrami A Ellison D Wilson RK Downing JR Dyer MA 《Nature》2012,481(7381):329-334
Retinoblastoma is an aggressive childhood cancer of the developing retina that is initiated by the biallelic loss of RB1. Tumours progress very quickly following RB1 inactivation but the underlying mechanism is not known. Here we show that the retinoblastoma genome is stable, but that multiple cancer pathways can be epigenetically deregulated. To identify the mutations that cooperate with RB1 loss, we performed whole-genome sequencing of retinoblastomas. The overall mutational rate was very low; RB1 was the only known cancer gene mutated. We then evaluated the role of RB1 in genome stability and considered non-genetic mechanisms of cancer pathway deregulation. For example, the proto-oncogene SYK is upregulated in retinoblastoma and is required for tumour cell survival. Targeting SYK with a small-molecule inhibitor induced retinoblastoma tumour cell death in vitro and in vivo. Thus, retinoblastomas may develop quickly as a result of the epigenetic deregulation of key cancer pathways as a direct or indirect result of RB1 loss. 相似文献
169.
Barretina J Caponigro G Stransky N Venkatesan K Margolin AA Kim S Wilson CJ Lehár J Kryukov GV Sonkin D Reddy A Liu M Murray L Berger MF Monahan JE Morais P Meltzer J Korejwa A Jané-Valbuena J Mapa FA Thibault J Bric-Furlong E Raman P Shipway A Engels IH Cheng J Yu GK Yu J Aspesi P de Silva M Jagtap K Jones MD Wang L Hatton C Palescandolo E Gupta S Mahan S Sougnez C Onofrio RC Liefeld T MacConaill L Winckler W Reich M Li N Mesirov JP Gabriel SB Getz G Ardlie K Chan V Myer VE Weber BL Porter J 《Nature》2012,483(7391):603-607
The systematic translation of cancer genomic data into knowledge of tumour biology and therapeutic possibilities remains challenging. Such efforts should be greatly aided by robust preclinical model systems that reflect the genomic diversity of human cancers and for which detailed genetic and pharmacological annotation is available. Here we describe the Cancer Cell Line Encyclopedia (CCLE): a compilation of gene expression, chromosomal copy number and massively parallel sequencing data from 947 human cancer cell lines. When coupled with pharmacological profiles for 24 anticancer drugs across 479 of the cell lines, this collection allowed identification of genetic, lineage, and gene-expression-based predictors of drug sensitivity. In addition to known predictors, we found that plasma cell lineage correlated with sensitivity to IGF1 receptor inhibitors; AHR expression was associated with MEK inhibitor efficacy in NRAS-mutant lines; and SLFN11 expression predicted sensitivity to topoisomerase inhibitors. Together, our results indicate that large, annotated cell-line collections may help to enable preclinical stratification schemata for anticancer agents. The generation of genetic predictions of drug response in the preclinical setting and their incorporation into cancer clinical trial design could speed the emergence of 'personalized' therapeutic regimens. 相似文献
170.
This article uses a recently proposed measure, the overall replacement ratio or ORR, to assess the extent to which migration alters intergenerational replacement within the United Kingdom. The UK as a whole can be seen to experience 'replacement migration' as immigration compensates for fertility below the replacement level. However, the article shows that the impact of migration differs radically in the different regions of the country. South East England experiences very substantial immigration from both the rest of the UK and overseas, far more than is needed for intergenerational replacement, whereas most of the rest of the UK sees little or no net immigration and the ORR remains below the replacement level. 相似文献