1,623 research outputs found

    Simon Terrill: Crowd Theory 2004-18, Perspectives, Notes and Comments

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    A catalogue publication for a major survey of the monumental Crowd Theory photographs by Melbourne-born, London-based artist Simon Terrill. The publication coincides with an exhibition bringing together all ten Crowd Theory images for the first time, at the Centre for Contemporary Photography, Melbourne. Inside are a range of responses and documents, including images and texts from the time of each event, as well as three newly commissioned essays reflecting on the project

    Quantitative Proteomics Reveals a "Poised Quiescence" Cellular State after Triggering the DNA Replication Origin Activation Checkpoint

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    An origin activation checkpoint has recently been discovered in the G1 phase of the mitotic cell cycle, which can be triggered by loss of DNA replication initiation factors such as the Cdc7 kinase. Insufficient levels of Cdc7 activate cell cycle arrest in normal cells, whereas cancer cells appear to lack this checkpoint response, do not arrest, and proceed with an abortive S phase, leading to cell death. The differential response between normal and tumor cells at this checkpoint has led to widespread interest in the development of pharmacological Cdc7 inhibitors as novel anticancer agents. We have used RNAi against Cdc7 in combination with SILAC-based high resolution MS proteomics to investigate the cellular mechanisms underlying the maintenance of the origin activation checkpoint in normal human diploid fibroblasts. Bioinformatics analysis identified clear changes in wide-ranging biological processes including altered cellular energetic flux, moderate stress response, reduced proliferative capacity, and a spatially distributed response across the mitochondria, lysosomes, and the cell surface. These results provide a quantitative overview of the processes involved in maintenance of the arrested state, show that this phenotype involves active rather than passive cellular adaptation, and highlight a diverse set of proteins responsible for cell cycle arrest and ultimately for promotion of cellular survival. We propose that the Cdc7-depleted proteome maintains cellular arrest by initiating a dynamic quiescence-like response and that the complexities of this phenotype will have important implications for the continued development of promising Cdc7-targeted cancer therapies

    Dietary restriction in ILSXISS mice is associated with widespread changes in splicing regulatory factor expression levels.

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    This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record Dietary restriction (DR) represents one of the most reproducible interventions to extend lifespan and improve health outcomes in a wide range of species, but substantial variability in DR response has been observed, both between and within species. The mechanisms underlying this variation in effect are still not well characterised. Splicing regulatory factors have been implicated in the pathways linked with DR-induced longevity in C. elegans and are associated with lifespan itself in mice and humans. We used qRT-PCR to measure the expression levels of a panel of 20 age- and lifespan-associated splicing regulatory factors in brain, heart and kidney derived from three recombinant inbred strains of mice with variable lifespan responses to short-term (2 months) or long-term (10 months) 40% DR to determine their relationship to DR-induced longevity. We identified 3 patterns of association; i) splicing factors associated with DR alone, ii) splicing factors associated with strain alone or iii) splicing factors associated with both DR and strain. Tissue specific variation was noted in response to short term or long-term DR, with the majority of effects noted in brain following long term DR in the positive responder strain TejJ89. Association in heart and kidney were less evident, and occurred following short term DR. Splicing factors associated with both DR and strain may be mechanistically involved in strain-specific differences in response to DR. We provide here evidence concordant with a role for some splicing factors in the lifespan modulatory effects of DR across different mouse strains and in different tissues

    Algebraic description of spacetime foam

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    A mathematical formalism for treating spacetime topology as a quantum observable is provided. We describe spacetime foam entirely in algebraic terms. To implement the correspondence principle we express the classical spacetime manifold of general relativity and the commutative coordinates of its events by means of appropriate limit constructions.Comment: 34 pages, LaTeX2e, the section concerning classical spacetimes in the limit essentially correcte

    Integrable Generalisations of the 2-dimensional Born Infeld Equation

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    The Born-Infeld equation in two dimensions is generalised to higher dimensions whilst retaining Lorentz Invariance and complete integrability. This generalisation retains homogeneity in second derivatives of the field.Comment: 11 pages, Latex, DTP/93/3

    Cnih3 deletion dysregulates dorsal hippocampal transcription across the estrous cycle

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    In females, the hippocampus, a critical brain region for coordination of learning, memory, and behavior, displays altered physiology and behavioral output across the estrous or menstrual cycle. However, the molecular effectors and cell types underlying these observed cyclic changes have only been partially characterized to date. Recently, profiling of mice null for the AMPA receptor trafficking gen

    HMM based scenario generation for an investment optimisation problem

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    This is the post-print version of the article. The official published version can be accessed from the link below - Copyright @ 2012 Springer-Verlag.The Geometric Brownian motion (GBM) is a standard method for modelling financial time series. An important criticism of this method is that the parameters of the GBM are assumed to be constants; due to this fact, important features of the time series, like extreme behaviour or volatility clustering cannot be captured. We propose an approach by which the parameters of the GBM are able to switch between regimes, more precisely they are governed by a hidden Markov chain. Thus, we model the financial time series via a hidden Markov model (HMM) with a GBM in each state. Using this approach, we generate scenarios for a financial portfolio optimisation problem in which the portfolio CVaR is minimised. Numerical results are presented.This study was funded by NET ACE at OptiRisk Systems
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