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41.
In each decade, population estimates are rebased using data from the most recent census. However, this would lead to a step change in the population estimates series. To avoid this discontinuity the backseries for 1992 to 2000, was revised to bring it into line with the 2001 Census. This article discusses the methodology used to produce the final revised backseries for 1992 to 2000 published by ONS in October 2004. The final estimates were produced after a long period of research into the best methodology to use. Traditionally, the backseries have been revised using an interim simple period method, followed by a final simple cohort method. The approach taken following the 2001 Census was much more comprehensive. This article outlines this approach, summarises the range of methods available and describes in detail the final method selected.  相似文献   
42.
The aspergilli comprise a diverse group of filamentous fungi spanning over 200 million years of evolution. Here we report the genome sequence of the model organism Aspergillus nidulans, and a comparative study with Aspergillus fumigatus, a serious human pathogen, and Aspergillus oryzae, used in the production of sake, miso and soy sauce. Our analysis of genome structure provided a quantitative evaluation of forces driving long-term eukaryotic genome evolution. It also led to an experimentally validated model of mating-type locus evolution, suggesting the potential for sexual reproduction in A. fumigatus and A. oryzae. Our analysis of sequence conservation revealed over 5,000 non-coding regions actively conserved across all three species. Within these regions, we identified potential functional elements including a previously uncharacterized TPP riboswitch and motifs suggesting regulation in filamentous fungi by Puf family genes. We further obtained comparative and experimental evidence indicating widespread translational regulation by upstream open reading frames. These results enhance our understanding of these widely studied fungi as well as provide new insight into eukaryotic genome evolution and gene regulation.  相似文献   
43.
Strategic policy has to be implemented within complex operating environments where organisations have to perform within an inter-dependent production process in a dynamic mix of competition and cooperation. This suggests that network structures need to be in place that allow for both collaboration and competition whilst mitigating against structural fragmentation. The aim of this research was to further the understanding of control and communication mechanisms and collaboration in policy implementation networks and focus upon problems of structural fragmentation in these complex policy environments. This research used a systems approach to develop a methodological framework based on Beer’s Viable System Model, work by Espejo and Social Network Analysis. The research was set in a tourism ‘cluster’ in an English seaside context, which is that part of the Yorkshire coast covered by the Scarborough Borough Council local authority, where a more culturally focussed tourism product was being introduced.  相似文献   
44.
Marvier M  Grant J  Kareiva P 《Nature》2006,443(7113):749-50; author reply 750
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45.
美国加州理工学院每年春季的“恶作剧日”可能是激发创造性和独立思维的方式之一——最近,我发现科学家们已经背上了难以管理的坏名声。一位从事管理工作的同事告诉我,他们甚至修了一门专门来对付我们的课程。“牧猫”这个说法目前很盛行,说的是管理教授就像是“牧猫”;而一直令管理者们恼怒的是:科学家被分配了一项工作后,第一件事就是问一些令人恼怒的问题,例如“我们为什么做这件  相似文献   
46.
Embryonal tumours of the central nervous system (CNS) represent a heterogeneous group of tumours about which little is known biologically, and whose diagnosis, on the basis of morphologic appearance alone, is controversial. Medulloblastomas, for example, are the most common malignant brain tumour of childhood, but their pathogenesis is unknown, their relationship to other embryonal CNS tumours is debated, and patients' response to therapy is difficult to predict. We approached these problems by developing a classification system based on DNA microarray gene expression data derived from 99 patient samples. Here we demonstrate that medulloblastomas are molecularly distinct from other brain tumours including primitive neuroectodermal tumours (PNETs), atypical teratoid/rhabdoid tumours (AT/RTs) and malignant gliomas. Previously unrecognized evidence supporting the derivation of medulloblastomas from cerebellar granule cells through activation of the Sonic Hedgehog (SHH) pathway was also revealed. We show further that the clinical outcome of children with medulloblastomas is highly predictable on the basis of the gene expression profiles of their tumours at diagnosis.  相似文献   
47.
Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma   总被引:3,自引:0,他引:3  
Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) are the two most common non-Hodgkin lymphomas (NHLs). Here we sequenced tumour and matched normal DNA from 13 DLBCL cases and one FL case to identify genes with mutations in B-cell NHL. We analysed RNA-seq data from these and another 113 NHLs to identify genes with candidate mutations, and then re-sequenced tumour and matched normal DNA from these cases to confirm 109 genes with multiple somatic mutations. Genes with roles in histone modification were frequent targets of somatic mutation. For example, 32% of DLBCL and 89% of FL cases had somatic mutations in MLL2, which encodes a histone methyltransferase, and 11.4% and 13.4% of DLBCL and FL cases, respectively, had mutations in MEF2B, a calcium-regulated gene that cooperates with CREBBP and EP300 in acetylating histones. Our analysis suggests a previously unappreciated disruption of chromatin biology in lymphomagenesis.  相似文献   
48.
Snyder JS  Soumier A  Brewer M  Pickel J  Cameron HA 《Nature》2011,476(7361):458-461
Glucocorticoids are released in response to stressful experiences and serve many beneficial homeostatic functions. However, dysregulation of glucocorticoids is associated with cognitive impairments and depressive illness. In the hippocampus, a brain region densely populated with receptors for stress hormones, stress and glucocorticoids strongly inhibit adult neurogenesis. Decreased neurogenesis has been implicated in the pathogenesis of anxiety and depression, but direct evidence for this role is lacking. Here we show that adult-born hippocampal neurons are required for normal expression of the endocrine and behavioural components of the stress response. Using either transgenic or radiation methods to inhibit adult neurogenesis specifically, we find that glucocorticoid levels are slower to recover after moderate stress and are less suppressed by dexamethasone in neurogenesis-deficient mice than intact mice, consistent with a role for the hippocampus in regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Relative to controls, neurogenesis-deficient mice also showed increased food avoidance in a novel environment after acute stress, increased behavioural despair in the forced swim test, and decreased sucrose preference, a measure of anhedonia. These findings identify a small subset of neurons within the dentate gyrus that are critical for hippocampal negative control of the HPA axis and support a direct role for adult neurogenesis in depressive illness.  相似文献   
49.
This paper presents a framework that addresses a public child welfare agency??s need for a highly trained child welfare workforce with specialized competencies, situating these competencies within the human services educational profession??s accreditation standards, while simultaneously meeting the learning needs of professionals returning to school for additional graduate training. The framework integrates three disparate literatures. The first that frames employees returning to a university setting for additional education and training as a human resources benefit. The second body of literature that addresses the annual review of employee performance via employment assessment systems. And the final body that examines parallel organizational processes related to the development of a product, in our case, a professional with a graduate degree. The framework, developed using a soft system methodology approach, and evaluated by means of an electronic portfolio, integrates these three bodies of literature and allows for the real time curricular and agency assessment of competency achievement. While using a professional graduate training program as an exemplar, implications for broader systemic practice are discussed.  相似文献   
50.
The existence of low-elevation populations of Neotoma cinera in the northern Bonneville Basin shows either that these mammals can survive thousands of years in xeric habitats or that they can move across xeric lowlands far more readily than has been appreciated, or both. Current models of Great Basin small mammal biogeography are far too static to encompass properly the interaction of the wide range of geographical and biological variability that has produced the modern distribution of those mammals that have, for several decades, been treated as ""montane"" within the Great Basin.  相似文献   
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