308 research outputs found

    Stochastic population growth in spatially heterogeneous environments

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    Classical ecological theory predicts that environmental stochasticity increases extinction risk by reducing the average per-capita growth rate of populations. To understand the interactive effects of environmental stochasticity, spatial heterogeneity, and dispersal on population growth, we study the following model for population abundances in nn patches: the conditional law of Xt+dtX_{t+dt} given Xt=xX_t=x is such that when dtdt is small the conditional mean of Xt+dtiXtiX_{t+dt}^i-X_t^i is approximately [xiμi+j(xjDjixiDij)]dt[x^i\mu_i+\sum_j(x^j D_{ji}-x^i D_{ij})]dt, where XtiX_t^i and μi\mu_i are the abundance and per capita growth rate in the ii-th patch respectivly, and DijD_{ij} is the dispersal rate from the ii-th to the jj-th patch, and the conditional covariance of Xt+dtiXtiX_{t+dt}^i-X_t^i and Xt+dtjXtjX_{t+dt}^j-X_t^j is approximately xixjσijdtx^i x^j \sigma_{ij}dt. We show for such a spatially extended population that if St=(Xt1+...+Xtn)S_t=(X_t^1+...+X_t^n) is the total population abundance, then Yt=Xt/StY_t=X_t/S_t, the vector of patch proportions, converges in law to a random vector YY_\infty as tt\to\infty, and the stochastic growth rate limtt1logSt\lim_{t\to\infty}t^{-1}\log S_t equals the space-time average per-capita growth rate \sum_i\mu_i\E[Y_\infty^i] experienced by the population minus half of the space-time average temporal variation \E[\sum_{i,j}\sigma_{ij}Y_\infty^i Y_\infty^j] experienced by the population. We derive analytic results for the law of YY_\infty, find which choice of the dispersal mechanism DD produces an optimal stochastic growth rate for a freely dispersing population, and investigate the effect on the stochastic growth rate of constraints on dispersal rates. Our results provide fundamental insights into "ideal free" movement in the face of uncertainty, the persistence of coupled sink populations, the evolution of dispersal rates, and the single large or several small (SLOSS) debate in conservation biology.Comment: 47 pages, 4 figure

    Identifying subtypes of patients with neovascular age-related macular degeneration by genotypic and cardiovascular risk characteristics

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    <p>Abstract</p> <p>Background</p> <p>One of the challenges in the interpretation of studies showing associations between environmental and genotypic data with disease outcomes such as neovascular age-related macular degeneration (AMD) is understanding the phenotypic heterogeneity within a patient population with regard to any risk factor associated with the condition. This is critical when considering the potential therapeutic response of patients to any drug developed to treat the condition. In the present study, we identify patient subtypes or clusters which could represent several different targets for treatment development, based on genetic pathways in AMD and cardiovascular pathology.</p> <p>Methods</p> <p>We identified a sample of patients with neovascular AMD, that in previous studies had been shown to be at elevated risk for the disease through environmental factors such as cigarette smoking and genetic variants including the complement factor H gene (<it>CFH</it>) on chromosome 1q25 and variants in the <it>ARMS2</it>/HtrA serine peptidase 1 (<it>HTRA1</it>) gene(s) on chromosome 10q26. We conducted a multivariate segmentation analysis of 253 of these patients utilizing available epidemiologic and genetic data.</p> <p>Results</p> <p>In a multivariate model, cigarette smoking failed to differentiate subtypes of patients. However, four meaningfully distinct clusters of patients were identified that were most strongly differentiated by their cardiovascular health status (histories of hypercholesterolemia and hypertension), and the alleles of <it>ARMS2</it>/<it>HTRA1 </it>rs1049331.</p> <p>Conclusions</p> <p>These results have significant personalized medicine implications for drug developers attempting to determine the effective size of the treatable neovascular AMD population. Patient subtypes or clusters may represent different targets for therapeutic development based on genetic pathways in AMD and cardiovascular pathology, and treatments developed that may elevate CV risk, may be ill advised for certain of the clusters identified.</p

    Efficient Sparse Coding in Early Sensory Processing: Lessons from Signal Recovery

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    Sensory representations are not only sparse, but often overcomplete: coding units significantly outnumber the input units. For models of neural coding this overcompleteness poses a computational challenge for shaping the signal processing channels as well as for using the large and sparse representations in an efficient way. We argue that higher level overcompleteness becomes computationally tractable by imposing sparsity on synaptic activity and we also show that such structural sparsity can be facilitated by statistics based decomposition of the stimuli into typical and atypical parts prior to sparse coding. Typical parts represent large-scale correlations, thus they can be significantly compressed. Atypical parts, on the other hand, represent local features and are the subjects of actual sparse coding. When applied on natural images, our decomposition based sparse coding model can efficiently form overcomplete codes and both center-surround and oriented filters are obtained similar to those observed in the retina and the primary visual cortex, respectively. Therefore we hypothesize that the proposed computational architecture can be seen as a coherent functional model of the first stages of sensory coding in early vision

    Epigenetics and the power of art

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    This review presents an epigenetic view on complex factors leading to development and perception of “genius.” There is increasing evidence which indicates that artistic creativity is influenced by epigenetic processes that act both as targets and mediators of neurotransmitters as well as steroid hormones. Thus, perception and production of art appear to be closely associated with epigenetic contributions to physical and mental health

    A Structured Model of Video Reproduces Primary Visual Cortical Organisation

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    The visual system must learn to infer the presence of objects and features in the world from the images it encounters, and as such it must, either implicitly or explicitly, model the way these elements interact to create the image. Do the response properties of cells in the mammalian visual system reflect this constraint? To address this question, we constructed a probabilistic model in which the identity and attributes of simple visual elements were represented explicitly and learnt the parameters of this model from unparsed, natural video sequences. After learning, the behaviour and grouping of variables in the probabilistic model corresponded closely to functional and anatomical properties of simple and complex cells in the primary visual cortex (V1). In particular, feature identity variables were activated in a way that resembled the activity of complex cells, while feature attribute variables responded much like simple cells. Furthermore, the grouping of the attributes within the model closely parallelled the reported anatomical grouping of simple cells in cat V1. Thus, this generative model makes explicit an interpretation of complex and simple cells as elements in the segmentation of a visual scene into basic independent features, along with a parametrisation of their moment-by-moment appearances. We speculate that such a segmentation may form the initial stage of a hierarchical system that progressively separates the identity and appearance of more articulated visual elements, culminating in view-invariant object recognition

    Emergence of Visual Saliency from Natural Scenes via Context-Mediated Probability Distributions Coding

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    Visual saliency is the perceptual quality that makes some items in visual scenes stand out from their immediate contexts. Visual saliency plays important roles in natural vision in that saliency can direct eye movements, deploy attention, and facilitate tasks like object detection and scene understanding. A central unsolved issue is: What features should be encoded in the early visual cortex for detecting salient features in natural scenes? To explore this important issue, we propose a hypothesis that visual saliency is based on efficient encoding of the probability distributions (PDs) of visual variables in specific contexts in natural scenes, referred to as context-mediated PDs in natural scenes. In this concept, computational units in the model of the early visual system do not act as feature detectors but rather as estimators of the context-mediated PDs of a full range of visual variables in natural scenes, which directly give rise to a measure of visual saliency of any input stimulus. To test this hypothesis, we developed a model of the context-mediated PDs in natural scenes using a modified algorithm for independent component analysis (ICA) and derived a measure of visual saliency based on these PDs estimated from a set of natural scenes. We demonstrated that visual saliency based on the context-mediated PDs in natural scenes effectively predicts human gaze in free-viewing of both static and dynamic natural scenes. This study suggests that the computation based on the context-mediated PDs of visual variables in natural scenes may underlie the neural mechanism in the early visual cortex for detecting salient features in natural scenes

    Whole brain radiotherapy with radiosensitizer for brain metastases

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    <p>Abstract</p> <p>Purpose</p> <p>To study the efficacy of whole brain radiotherapy (WBRT) with radiosensitizer in comparison with WBRT alone for patients with brain metastases in terms of overall survival, disease progression, response to treatment and adverse effects of treatment.</p> <p>Methods</p> <p>A meta-analysis of randomized controlled trials (RCT) was performed in order to compare WBRT with radiosensitizer for brain metastases and WBRT alone. The MEDLINE, EMBASE, LILACS, and Cochrane Library databases, in addition to Trial registers, bibliographic databases, and recent issues of relevant journals were researched. Significant reports were reviewed by two reviewers independently.</p> <p>Results</p> <p>A total of 8 RCTs, yielding 2317 patients were analyzed. Pooled results from this 8 RCTs of WBRT with radiosensitizer have not shown a meaningful improvement on overall survival compared to WBRT alone OR = 1.03 (95% CI0.84–1.25, p = 0.77). Also, there was no difference in local brain tumor response OR = 0.8(95% CI 0.5 – 1.03) and brain tumor progression (OR = 1.11, 95% CI 0.9 – 1.3) when the two arms were compared.</p> <p>Conclusion</p> <p>Our data show that WBRT with the following radiosentizers (ionidamine, metronidazole, misonodazole, motexafin gadolinium, BUdr, efaproxiral, thalidomide), have not improved significatively the overall survival, local control and tumor response compared to WBRT alone for brain metastases. However, 2 of them, motexafin- gadolinium and efaproxiral have been shown in recent publications (lung and breast) to have positive action in lung and breast carcinoma brain metastases in association with WBRT.</p

    Bringing the real world into the fMRI scanner: Repetition effects for pictures versus real objects

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    Our understanding of the neural underpinnings of perception is largely built upon studies employing 2-dimensional (2D) planar images. Here we used slow event-related functional imaging in humans to examine whether neural populations show a characteristic repetition-related change in haemodynamic response for real-world 3-dimensional (3D) objects, an effect commonly observed using 2D images. As expected, trials involving 2D pictures of objects produced robust repetition effects within classic object-selective cortical regions along the ventral and dorsal visual processing streams. Surprisingly, however, repetition effects were weak, if not absent on trials involving the 3D objects. These results suggest that the neural mechanisms involved in processing real objects may therefore be distinct from those that arise when we encounter a 2D representation of the same items. These preliminary results suggest the need for further research with ecologically valid stimuli in other imaging designs to broaden our understanding of the neural mechanisms underlying human vision

    Overexpression of HTRA1 Leads to Ultrastructural Changes in the Elastic Layer of Bruch's Membrane via Cleavage of Extracellular Matrix Components

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    Variants in the chromosomal region 10q26 are strongly associated with an increased risk for age-related macular degeneration (AMD). Two potential AMD genes are located in this region: ARMS2 and HTRA1 (high-temperature requirement A1). Previous studies have suggested that polymorphisms in the promotor region of HTRA1 result in overexpression of HTRA1 protein. This study investigated the role of HTRA1 overexpression in the pathogenesis of AMD. Transgenic Htra1 mice overexpressing the murine protein in the retinal pigment epithelium (RPE) layer of the retina were generated and characterized by transmission electron microscopy, immunofluorescence staining and Western Blot analysis. The elastic layer of Bruch's membrane (BM) in the Htra1 transgenic mice was fragmented and less continuous than in wild type (WT) controls. Recombinant HTRA1 lacking the N-terminal domain cleaved various extracellular matrix (ECM) proteins. Subsequent Western Blot analysis revealed an overexpression of fibronectin fragments and a reduction of fibulin 5 and tropoelastin in the RPE/choroid layer in transgenic mice compared to WT. Fibulin 5 is essential for elastogenesis by promoting elastic fiber assembly and maturation. Taken together, our data implicate that HTRA1 overexpression leads to an altered elastogenesis in BM through fibulin 5 cleavage. It highlights the importance of ECM related proteins in the development of AMD and links HTRA1 to other AMD risk genes such as fibulin 5, fibulin 6, ARMS2 and TIMP3
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