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In this paper, we present an explanatory objection to Norton's material theory of induction, as applied to predictive inferences. According to the objection we present, there is an explanatory disconnect between our beliefs about the future and the relevant future facts. We argue that if we recognize such a disconnect, we are no longer rationally entitled to our future beliefs.  相似文献   
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We consider the problem of online prediction when it is uncertain what the best prediction model to use is. We develop a method called dynamic latent class model averaging, which combines a state‐space model for the parameters of each of the candidate models of the system with a Markov chain model for the best model. We propose a polychotomous regression model for the transition weights to assume that the probability of a change in time depends on the past through the values of the most recent time periods and spatial correlation among the regions. The evolution of the parameters in each submodel is defined by exponential forgetting. This structure allows the ‘correct’ model to vary over both time and regions. In contrast to existing methods, the proposed model naturally incorporates clustering and prediction analysis in a single unified framework. We develop an efficient Gibbs algorithm for computation, and we demonstrate the value of our framework on simulated experiments and on a real‐world problem: forecasting IBM's corporate revenue. Copyright © 2014 John Wiley & Sons, Ltd.  相似文献   
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We describe activity patterns, relative abundances and pollen transport by insect floral visitors in the Skukuza Ranger District, Kruger National Park, Republic of South Africa, based on field surveys conducted during the early rainy seasons of years 2006 to 2012 (inclusive). Diagnostic notes, illustrations and natural history observations are provided for species in the families Buprestidae, Cerambycidae, Cleridae, Lycidae and Scarabaeidae (Coleoptera), Muscidae, Platystomatidae and Tabanidae (Diptera), Apidae, Halictidae, Megachilidae, Sphecidae and Vespidae (Hymenoptera), and Pieridae and Thyrididae (Lepidoptera) that transported pollen of tree or shrub species. Observations on floral phenology and pollination syndrome are presented for 27 flowering tree or shrub species. To provide a foundation for studies of the effects of drought and climate change on pollination services in the Kruger National Park, we applied methods of food web analysis to characterise this plant-pollinator assemblage. The food web analysis shows moderate levels of redundancy in plant-pollinator interactions (with connectance values averaging 0.19 for plant species and 0.20 for pollinator species), suggesting that pollination services in this system may exhibit some resilience to environmental perturbations. Possible conservation strategies for maintaining pollination services in this ecological system are discussed, including habitat management to conserve larval or nesting areas for social and solitary bees and scarab beetles, as well as further inventories and long-term monitoring of pollinator species.  相似文献   
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Attention deficit hyperactivity disorder (ADHD) is a common, heritable neuropsychiatric disorder of unknown etiology. We performed a whole-genome copy number variation (CNV) study on 1,013 cases with ADHD and 4,105 healthy children of European ancestry using 550,000 SNPs. We evaluated statistically significant findings in multiple independent cohorts, with a total of 2,493 cases with ADHD and 9,222 controls of European ancestry, using matched platforms. CNVs affecting metabotropic glutamate receptor genes were enriched across all cohorts (P = 2.1 × 10(-9)). We saw GRM5 (encoding glutamate receptor, metabotropic 5) deletions in ten cases and one control (P = 1.36 × 10(-6)). We saw GRM7 deletions in six cases, and we saw GRM8 deletions in eight cases and no controls. GRM1 was duplicated in eight cases. We experimentally validated the observed variants using quantitative RT-PCR. A gene network analysis showed that genes interacting with the genes in the GRM family are enriched for CNVs in ~10% of the cases (P = 4.38 × 10(-10)) after correction for occurrence in the controls. We identified rare recurrent CNVs affecting glutamatergic neurotransmission genes that were overrepresented in multiple ADHD cohorts.  相似文献   
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Neutrophils are being increasingly recognized as an important element in tumor progression. They have been shown to exert important effects at nearly every stage of tumor progression with a number of studies demonstrating that their presence is critical to tumor development. Novel aspects of neutrophil biology have recently been elucidated and its contribution to tumorigenesis is only beginning to be appreciated. Neutrophil extracellular traps (NETs) are neutrophil-derived structures composed of DNA decorated with antimicrobial peptides. They have been shown to trap and kill microorganisms, playing a critical role in host defense. However, their contribution to tumor development and metastasis has recently been demonstrated in a number of studies highlighting NETs as a potentially important therapeutic target. Here, studies implicating NETs as facilitators of tumor progression and metastasis are reviewed. In addition, potential mechanisms by which NETs may exert these effects are explored. Finally, the ability to target NETs therapeutically in human neoplastic disease is highlighted.  相似文献   
8.
Gene flow links the genetic and demographic structures of species. Despite the fact that similar genetic and demographic patterns shape both local population structure and regional phylogeography, the 2 levels of population connectivity are rarely studied simultaneously. Here, we studied gene flow in the California vole ( Microtus californicus ), a small-bodied rodent with limited vagility but high local abundance. Within a 4.86-km 2 preserve in central California, genetic diversity in 6 microsatellites was high, and Bayesian methods indicated a single genetic cluster. However, individual-based genetic analysis detected a clear signal for isolation-by-distance (IBD) and fine-scale population structure. Mitochondrial cytochrome b sequencing revealed 11 unique haplotypes from the one local area where we sequenced 62 individuals. Phylogeographic analysis of these individuals combined with those sampled from the northern geographic range of the species (the range of the species spans western North America from southern Oregon to northern Mexico and is centered geographically within the state of California) again indicated a lack of structure but a signal for IBD. Patterns of gene flow thus are consistent across spatial scales: while dispersal of the California vole is limited across geographic distance, there is nonetheless considerable movement across the landscape. We conclude that in this species, high local population abundances overcome the potential genetic and demographic effects of limited dispersal.  相似文献   
9.
Expression of the glycosylphosphatidylinositol-anchored membrane protein CD24 correlates with a poor prognosis for many human cancers, and in experimental tumors can promote metastasis. However, the mechanism by which CD24 contributes to tumor progression remains unclear. Here we report that in MTLy breast cancer cells CD24 interacts with and augments the kinase activity of c-src, a protein strongly implicated in promoting invasion and metastasis. This occurs within and is dependent upon intact lipid rafts. CD24-augmented c-src kinase activity increased formation of focal adhesion complexes, accelerated phosphorylation of FAK and paxillin and consequently enhanced integrin-mediated adhesion. Loss and gain of function approaches showed that c-src activity is necessary and sufficient to mediate the effects of CD24 on integrin-dependent adhesion and cell spreading, as well as on invasion. Together these results indicate that c-src is a CD24-activated mediator that promotes integrin-mediated adhesion and invasion, and suggest a mechanism by which CD24 might contribute to tumor progression through stimulating the activity of c-src or another member of the Src family.  相似文献   
10.
All cancers carry somatic mutations in their genomes. A subset, known as driver mutations, confer clonal selective advantage on cancer cells and are causally implicated in oncogenesis, and the remainder are passenger mutations. The driver mutations and mutational processes operative in breast cancer have not yet been comprehensively explored. Here we examine the genomes of 100 tumours for somatic copy number changes and mutations in the coding exons of protein-coding genes. The number of somatic mutations varied markedly between individual tumours. We found strong correlations between mutation number, age at which cancer was diagnosed and cancer histological grade, and observed multiple mutational signatures, including one present in about ten per cent of tumours characterized by numerous mutations of cytosine at TpC dinucleotides. Driver mutations were identified in several new cancer genes including AKT2, ARID1B, CASP8, CDKN1B, MAP3K1, MAP3K13, NCOR1, SMARCD1 and TBX3. Among the 100 tumours, we found driver mutations in at least 40 cancer genes and 73 different combinations of mutated cancer genes. The results highlight the substantial genetic diversity underlying this common disease.  相似文献   
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