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This paper describes the application of space-time ARMA modelling to demand-related data from eight hotels from a single hotel chain in a large US city. Important spatial characteristics of the space-time process are incorporated into the model using a simple weighting matrix based on driving distances between the hotels. Using a hold-out sample, the forecasting performance of this space-time approach was found to be superior to eight separate univariate ARMA models.  相似文献   
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Natural killer cells and cytotoxic T lymphocytes accomplish the critically important function of killing virus-infected and neoplastic cells. They do this by releasing the pore-forming protein perforin and granzyme proteases from cytoplasmic granules into the cleft formed between the abutting killer and target cell membranes. Perforin, a 67-kilodalton multidomain protein, oligomerizes to form pores that deliver the pro-apoptopic granzymes into the cytosol of the target cell. The importance of perforin is highlighted by the fatal consequences of congenital perforin deficiency, with more than 50 different perforin mutations linked to familial haemophagocytic lymphohistiocytosis (type 2 FHL). Here we elucidate the mechanism of perforin pore formation by determining the X-ray crystal structure of monomeric murine perforin, together with a cryo-electron microscopy reconstruction of the entire perforin pore. Perforin is a thin 'key-shaped' molecule, comprising an amino-terminal membrane attack complex perforin-like (MACPF)/cholesterol dependent cytolysin (CDC) domain followed by an epidermal growth factor (EGF) domain that, together with the extreme carboxy-terminal sequence, forms a central shelf-like structure. A C-terminal C2 domain mediates initial, Ca(2+)-dependent membrane binding. Most unexpectedly, however, electron microscopy reveals that the orientation of the perforin MACPF domain in the pore is inside-out relative to the subunit arrangement in CDCs. These data reveal remarkable flexibility in the mechanism of action of the conserved MACPF/CDC fold and provide new insights into how related immune defence molecules such as complement proteins assemble into pores.  相似文献   
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Milk from domestic cows has been a valuable food source for over 8,000 years, especially in lactose-tolerant human societies that exploit dairy breeds. We studied geographic patterns of variation in genes encoding the six most important milk proteins in 70 native European cattle breeds. We found substantial geographic coincidence between high diversity in cattle milk genes, locations of the European Neolithic cattle farming sites (>5,000 years ago) and present-day lactose tolerance in Europeans. This suggests a gene-culture coevolution between cattle and humans.  相似文献   
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我怀着悲伤的心情,阅读了刊登在《自然》杂志上的关于维克托·维斯科普夫(VictorWeisskopf)去世的讣告(Na-ture417,396;(2002)。十二年以前在波多黎各圣胡安,我在  相似文献   
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Summary Administration of cobra venom factor (CVF) at different time periods over a 24-h-period produced a leukocytic response which varied according to the time of day the factor was given. The resulting leukocytic circadian rhythm was achieved by a marked variation and increase in the neutrophil population.This study was supported by U. S. P. H. S. Grant No. HL 16769 and Grant No. AI 09169.  相似文献   
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