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261.
This paper examines the predictive relationship of consumption‐related and news‐related Google Trends data to changes in private consumption in the USA. The results suggest that (1) Google Trends‐augmented models provide additional information about consumption over and above survey‐based consumer sentiment indicators, (2) consumption‐related Google Trends data provide information about pre‐consumption research trends, (3) news‐related Google Trends data provide information about changes in durable goods consumption, and (4) the combination of news and consumption‐related data significantly improves forecasting models. We demonstrate that applying these insights improves forecasts of private consumption growth over forecasts that do not utilize Google Trends data and over forecasts that use Google Trends data, but do not take into account the specific ways in which it informs forecasts.  相似文献   
262.
The anonymous set of astronomical tables preserved in Paris, Bibliothèque nationale de France, MS lat. 10262, is the first set of displaced tables to be found in a medieval Latin text. These tables are a reworking of the standard Alfonsine tables and yield the same results. However, the mean motions are defined differently, the presentation of the tables is unprecedented, and some new functions are introduced for computing true planetary longitudes. The absence of any instructions as well as unusual technical terms in the headings make it difficult to appreciate the cleverness that went into the construction of these tables that are extant in a unique copy. In this article we provide a detailed analysis of these tables and their underlying parameters. The displaced tables are typical of a pervasive tendency in Islamic science to provide extensive and elegant numerical tables for the convenience of practitioners. The underlying astronomical theory is neither questioned nor affected. Edward S. Kennedy   相似文献   
263.
264.
Cytosine methylation is a repressive, epigenetically propagated DNA modification. Although patterns of DNA methylation seem tightly regulated in mammals, it is unclear how these are specified and to what extent this process entails genetic or epigenetic regulation. To dissect the role of the underlying DNA sequence, we sequentially inserted over 50 different DNA elements into the same genomic locus in mouse stem cells. Promoter sequences of approximately 1,000 bp autonomously recapitulated correct DNA methylation in pluripotent cells. Moreover, they supported proper de novo methylation during differentiation. Truncation analysis revealed that this regulatory potential is contained within small methylation-determining regions (MDRs). MDRs can mediate both hypomethylation and de novo methylation in cis, and their activity depends on developmental state, motifs for DNA-binding factors and a critical CpG density. These results demonstrate that proximal sequence elements are both necessary and sufficient for regulating DNA methylation and reveal basic constraints of this regulation.  相似文献   
265.
Endometriosis is a common gynecological disease associated with pelvic pain and subfertility. We conducted a genome-wide association study (GWAS) in 3,194 individuals with surgically confirmed endometriosis (cases) and 7,060 controls from Australia and the UK. Polygenic predictive modeling showed significantly increased genetic loading among 1,364 cases with moderate to severe endometriosis. The strongest association signal was on 7p15.2 (rs12700667) for 'all' endometriosis (P = 2.6 × 10??, odds ratio (OR) = 1.22, 95% CI 1.13-1.32) and for moderate to severe disease (P = 1.5 × 10??, OR = 1.38, 95% CI 1.24-1.53). We replicated rs12700667 in an independent cohort from the United States of 2,392 self-reported, surgically confirmed endometriosis cases and 2,271 controls (P = 1.2 × 10?3, OR = 1.17, 95% CI 1.06-1.28), resulting in a genome-wide significant P value of 1.4 × 10?? (OR = 1.20, 95% CI 1.13-1.27) for 'all' endometriosis in our combined datasets of 5,586 cases and 9,331 controls. rs12700667 is located in an intergenic region upstream of the plausible candidate genes NFE2L3 and HOXA10.  相似文献   
266.
The WTCCC study identified 49 SNPs putatively associated with rheumatoid arthritis at P = 1 x 10(-4) - 1 x 10(-5) (tier 3). Here we show that three of these SNPs, mapping to chromosome 10p15 (rs4750316), 12q13 (rs1678542) and 22q13 (rs3218253), are also associated (trend P = 4 x 10(-5), P = 4 x 10(-4) and P = 4 x 10(-4), respectively) in a validation study of 4,106 individuals with rheumatoid arthritis and an expanded reference group of 11,238 subjects, confirming them as true susceptibility loci in individuals of European ancestry.  相似文献   
267.
Fair color increases risk of cutaneous melanoma (CM) and basal cell carcinoma (BCC). Recent genome-wide association studies have identified variants affecting hair, eye and skin pigmentation in Europeans. Here, we assess the effect of these variants on risk of CM and BCC in European populations comprising 2,121 individuals with CM, 2,163 individuals with BCC and over 40,000 controls. A haplotype near ASIP, known to affect a similar spectrum of pigmentation traits as MC1R variants, conferred significant risk of CM (odds ratio (OR) = 1.45, P = 1.2 x 10(-9)) and BCC (OR = 1.33, P = 1.2 x 10(-6)). The variant in TYR encoding the R402Q amino acid substitution, previously shown to affect eye color and tanning response, conferred risk of CM (OR = 1.21, P = 2.8 x 10(-7)) and BCC (OR = 1.14, P = 6.1 x 10(-4)). An eye color variant in TYRP1 was associated with risk of CM (OR = 1.15, P = 4.6 x 10(-4)). The association of all three variants is robust with respect to adjustment for the effect of pigmentation.  相似文献   
268.
Summary Data on haemoglobin do not support suggestions that the aoudadAmmotragus lervia is close to a hypothetical ancestor to the genusOvis in general or to the domesticated sheepOvis aries in particular.Ammotragus haemoglobin is more like that from the domestic goatCapra hircus than that from the domestic sheepOvis aries, but also shows some unique characteristics, perhaps more specialized than primitive.  相似文献   
269.
S Goldstein  D P Singal 《Nature》1974,251(5477):719-721
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270.
Regulation of the mevalonate pathway   总被引:193,自引:0,他引:193  
J L Goldstein  M S Brown 《Nature》1990,343(6257):425-430
The mevalonate pathway produces isoprenoids that are vital for diverse cellular functions, ranging from cholesterol synthesis to growth control. Several mechanisms for feedback regulation of low-density-lipoprotein receptors and of two enzymes involved in mevalonate biosynthesis ensure the production of sufficient mevalonate for several end-products. Manipulation of this regulatory system could be useful in treating certain forms of cancer as well as heart disease.  相似文献   
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