489 research outputs found

    The Casimir Energy in a Separable Potential

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    The Casimir energy is the first-order-in-\hbar correction to the energy of a time-independent field configuration in a quantum field theory. We study the Casimir energy in a toy model, where the classical field is replaced by a separable potential. In this model the exact answer is trivial to compute, making it a good place to examine subtleties of the problem. We construct two traditional representations of the Casimir energy, one from the Greens function, the other from the phase shifts, and apply them to this case. We show that the two representations are correct and equivalent in this model. We study the convergence of the Born approximation to the Casimir energy and relate our findings to computational issues that arise in more realistic models.Comment: 16 pages, 4 EPS figures, REVTeX using BoxedEPS macros; email to [email protected]

    Genesis of ancestral haplotypes: RNA modifications and reverse transcription–mediated polymorphisms

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    Understanding the genesis of the block haplotype structure of the genome is a major challenge. With the completion of the sequencing of the Human Genome and the initiation of the HapMap project the concept that the chromosomes of the mammalian genome are a mosaic, or patchwork, of conserved extended block haplotype sequences is now accepted by the mainstream genomics research community. Ancestral Haplotypes (AHs) can be viewed as a recombined string of smaller Polymorphic Frozen Blocks (PFBs). How have such variant extended DNA sequence tracts emerged in evolution? Here the relevant literature on the problem is reviewed from various fields of molecular and cell biology particularly molecular immunology and comparative and functional genomics. Based on our synthesis we then advance a testable molecular and cellular model. A critical part of the analysis concerns the origin of the strand biased mutation signatures in the transcribed regions of the human and higher primate genome, A-to-G versus T-to-C (ratio ~1.5 fold) and C-to-T versus G-to-A (≥1.5 fold). A comparison and evaluation of the current state of the fields of immunoglobulin Somatic Hypermutation (SHM) and Transcription-Coupled DNA Repair focused on how mutations in newly synthesized RNA might be copied back to DNA thus accounting for some of the genome-wide strand biases (e.g., the A-to-G vs T-to-C component of the strand biased spectrum). We hypothesize that the genesis of PFBs and extended AHs occurs during mutagenic episodes in evolution (e.g., retroviral infections) and that many of the critical DNA sequence diversifying events occur first at the RNA level, e.g., recombination between RNA strings resulting in tandem and dispersed RNA duplications (retroduplications), RNA mutations via adenosine-to-inosine pre-mRNA editing events as well as error prone RNA synthesis. These are then copied back into DNA by a cellular reverse transcription process (also likely to be error-prone) that we have called "reverse transcription-mediated long DNA conversion." Finally we suggest that all these activities and others can be envisaged as being brought physically under the umbrella of special sites in the nucleus involved in transcription known as "transcription factories."

    The London Basin superficial and bedrock LithoFrame 50 Model

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    This report describes the methodology and datasets used in the construction of the 1:50 000 resolution superficial and bedrock geological model of the London Basin. The London Basin study area was divided into twelve 20 x 20 km tiles, with construction of the first tiles beginning in 2006 and completion of the combined model in 2014. This time period coincided with the ongoing development of GSI3D software which was used to construct much of the model. The GSI3D software was used to calculate a rockhead (base Quaternary and Anthropocene) surface that was then used as a capping surface for the modelling of the bedrock geology in the GOCAD® software. The model complements the corresponding DiGMapGB-50 tiles of the area and consists of about 80 modelled geological units, comprising mass movement (landslip), artificial, superficial, and bedrock. This report supersedes an earlier report detailing the construction of the superficial part of this model (Burke et al. 2013). A glossary of technical terms used is included at the end of this report

    A geological model of London and the Thames Valley, southeast England

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    Many geological survey organisations have started delivering digital geological models as part of their role. This article describes the British Geological Survey (BGS) model for London and the Thames Valley in southeast England. The model covers 4800 km2 and extends to several hundred metres depth. It includes extensive spreads of Quaternary river terraces and alluvium of the Thames drainage system resting on faulted and folded Palaeogene and Cretaceous bedrock strata. The model extends to the base of the Jurassic sedimentary rocks. The baseline datasets used and the uses and limitations of the model are given. The model has been used to generate grids for the elevation of the base of the Quaternary, the thickness of Quaternary deposits, and enabled a reassessment of the subcrop distribution and faulting of the Palaeogene and Cretaceous bedrock units especially beneath the Quaternary deposits. Digital outputs from the model include representations of geological surfaces, which can be used in GIS, CAD and geological modelling software, and also graphic depictions such as a fence diagram of cross-sections through the model. The model can be viewed as a whole, and be dissected, in the BGS Lithoframe Viewer. Spatial queries of this and other BGS models, at specific points, along defined lines or at a specified depth, can be performed with the new BGS Groundhog application, which delivers template-based reports. The model should be viewed as a first version that should be improved further, and kept up to date, as new data and understanding emerges

    Genomic evolution and polymorphism: Segmental duplications and haplotypes at 108 regions on 21 chromosomes

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    We describe here extensive, previously unknown, genomic polymorphism in 120 regions, covering 19 autosomes and both sex chromosomes. Each contains duplication within multigene clusters. Of these, 108 are extremely polymorphic with multiple haplotypes.We used the genomic matching technique (GMT), previously used to characterise the major histocompatibility complex (MHC) and regulators of complement activation (RCA).This genome-wide extension of this technique enables the examination of many underlying cis, trans and epistatic interactions responsible for phenotypic differences especially in relation to individuality, evolution and disease susceptibility.The extent of the diversity could not have been predicted and suggests a new model of primate evolution based on conservation of polymorphism rather than de novo mutation

    A multistate model of health transitions in older people: a secondary analysis of ASPREE clinical trial data

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    Background: Understanding the nature of transitions from a healthy state to chronic diseases and death is important for planning health-care system requirements and interventions. We aimed to quantify the trajectories of disease and disability in a population of healthy older people. Methods: We conducted a secondary analysis of data from the ASPREE trial, which was done in 50 sites in Australia and the USA and recruited community-dwelling, healthy individuals who were aged 70 years or older (≥65 years for Black and Hispanic people in the USA) between March 10, 2010, and Dec 24, 2014. Participants were followed up with annual face-to-face visits, biennial assessments of cognitive function, and biannual visits for physical function until death or June 12, 2017, whichever occurred first. We used multistate models to examine transitions from a healthy state to first intermediate disease events (ie, cancer events, stroke events, cardiac events, and physical disability or dementia) and, ultimately, to death. We also examined the effects of age and sex on transition rates using Cox proportional hazards regression models. Findings: 19 114 participants with a median age of 74·0 years (IQR 71·6–77·7) were included in our analyses. During a median follow-up of 4·7 years (IQR 3·6–5·7), 1933 (10·1%) of 19 114 participants had an incident cancer event, 487 (2·5%) had an incident cardiac event, 398 (2·1%) had an incident stroke event, 924 (4·8%) developed persistent physical disability or dementia, and 1052 (5·5%) died. 15 398 (80·6%) individuals did not have any of these events during follow-up. The highest proportion of deaths followed incident cancer (501 [47·6%] of 1052) and 129 (12·3%) participants transitioned from disability or dementia to death. Among 12 postulated transitions, transitions from the intermediate states to death had much higher rates than transitions from a healthy state to death. The progression rates to death were 158 events per 1000 person-years (95% CI 144–172) from cancer, 112 events per 1000 person-years (86–145) from stroke, 88 events per 1000 person-years (68–111) from cardiac disease, 69 events per 1000 person-years (58–82) from disability or dementia, and four events per 1000 person-years (4–5) from a healthy state. Age was significantly associated with an accelerated rate for most transitions. Male sex (vs female sex) was significantly associated with an accelerate rate for five of 12 transitions. Interpretation: We describe a multistate model in a healthy older population in whom the most common transition was from a healthy state to cancer. Our findings provide unique insights into the frequency of events, their transition rates, and the impact of age and sex. These results have implications for preventive health interventions and planning for appropriate levels of residential care in healthy ageing populations. Funding: The National Institutes of Health
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