3,063 research outputs found

    A decomposition theorem for compact groups with application to supercompactness

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    We show that every compact connected group is the limit of a continuous inverse sequence, in the category of compact groups, where each successor bonding map is either an epimorphism with finite kernel or the projection from a product by a simple compact Lie group. As an application, we present a proof of an unpublished result of Charles Mills from 1978: every compact group is supercompact.Comment: 12 page

    Transcriptomic analysis of autistic brain reveals convergent molecular pathology.

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    Autism spectrum disorder (ASD) is a common, highly heritable neurodevelopmental condition characterized by marked genetic heterogeneity. Thus, a fundamental question is whether autism represents an aetiologically heterogeneous disorder in which the myriad genetic or environmental risk factors perturb common underlying molecular pathways in the brain. Here, we demonstrate consistent differences in transcriptome organization between autistic and normal brain by gene co-expression network analysis. Remarkably, regional patterns of gene expression that typically distinguish frontal and temporal cortex are significantly attenuated in the ASD brain, suggesting abnormalities in cortical patterning. We further identify discrete modules of co-expressed genes associated with autism: a neuronal module enriched for known autism susceptibility genes, including the neuronal specific splicing factor A2BP1 (also known as FOX1), and a module enriched for immune genes and glial markers. Using high-throughput RNA sequencing we demonstrate dysregulated splicing of A2BP1-dependent alternative exons in the ASD brain. Moreover, using a published autism genome-wide association study (GWAS) data set, we show that the neuronal module is enriched for genetically associated variants, providing independent support for the causal involvement of these genes in autism. In contrast, the immune-glial module showed no enrichment for autism GWAS signals, indicating a non-genetic aetiology for this process. Collectively, our results provide strong evidence for convergent molecular abnormalities in ASD, and implicate transcriptional and splicing dysregulation as underlying mechanisms of neuronal dysfunction in this disorder

    Is treatment-resistant schizophrenia categorically distinct from treatment-responsive schizophrenia? A systematic review

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    Abstract Background Schizophrenia is a highly heterogeneous disorder, and around a third of patients are treatment-resistant. The only evidence-based treatment for these patients is clozapine, an atypical antipsychotic with relatively weak dopamine antagonism. It is plausible that varying degrees of response to antipsychotics reflect categorically distinct illness subtypes, which would have significant implications for research and clinical practice. If these subtypes could be distinguished at illness onset, this could represent a first step towards personalised medicine in psychiatry. This systematic review investigates whether current evidence supports conceptualising treatment-resistant and treatment-responsive schizophrenoa as categorically distinct subtypes. Method A systematic literature search was conducted, using PubMed, EMBASE, PsycInfo, CINAHL and OpenGrey databases, to identify all studies which compared treatment-resistant schizophrenia (defined as either a lack of response to two antipsychotic trials or clozapine prescription) to treatment-responsive schizophrenia (defined as known response to non-clozapine antipsychotics). Results Nineteen studies of moderate quality met inclusion criteria. The most robust findings indicate that treatment-resistant patients show glutamatergic abnormalities, a lack of dopaminergic abnormalities, and significant decreases in grey matter compared to treatment-responsive patients. Treatment-resistant patients were also reported to have higher familial loading; however, no individual gene-association study reported their findings surviving correction for multiple comparisons. Conclusions Tentative evidence supports conceptualising treatment-resistant schizophrenia as a categorically different illness subtype to treatment-responsive schizophrenia. However, research is limited and confirmation will require replication and rigorously controlled studies with large sample sizes and prospective study designs

    Low X-Ray Luminosity Galaxy Clusters: Main goals, sample selection, photometric and spectroscopic observations

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    We present the study of nineteen low X-ray luminosity galaxy clusters (LX∌_X \sim 0.5--45 ×\times 104310^{43} erg s−1^{-1}), selected from the ROSAT Position Sensitive Proportional Counters (PSPC) Pointed Observations (Vikhlinin et al. 1998) and the revised version of Mullis et al. (2003) in the redshift range of 0.16 to 0.7. This is the introductory paper of a series presenting the sample selection, photometric and spectroscopic observations and data reduction. Photometric data in different passbands were taken for eight galaxy clusters at Las Campanas Observatory; three clusters at Cerro Tololo Interamerican Observatory; and eight clusters at the Gemini Observatory. Spectroscopic data were collected for only four galaxy clusters using Gemini telescopes. With the photometry, the galaxies were defined based on the star-galaxy separation taking into account photometric parameters. For each galaxy cluster, the catalogues contain the PSF and aperture magnitudes of galaxies within the 90\% completeness limit. They are used together with structural parameters to study the galaxy morphology and to estimate photometric redshifts. With the spectroscopy, the derived galaxy velocity dispersion of our clusters ranged from 507 km~s−1^{-1} for [VMF98]022 to 775 km~s−1^{-1} for [VMF98]097 with signs of substructure. Cluster membership has been extensively discussed taking into account spectroscopic and photometric redshift estimates. In this sense, members are the galaxies within a projected radius of 0.75 Mpc from the X-ray mission peak and with cluster centric velocities smaller than the cluster velocity dispersion or 6000 km~s−1^{-1}, respectively. These results will be used in forthcoming papers to study, among the main topics, the red cluster sequence, blue cloud and green populations; the galaxy luminosity function and cluster dynamics.Comment: 13 pages, 6 tables, 9 figures. Uses emulateapj. Accepted for publication in The Astronomical Journal. Some formatting errors fixe

    A citizen science based survey method for estimating the density of urban carnivores

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    Globally there are many examples of synanthropic carnivores exploiting growth in urbanisation. As carnivores can come into conflict with humans and are potential vectors of zoonotic disease, assessing densities in suburban areas and identifying factors that influence them are necessary to aid management and mitigation. However, fragmented, privately owned land restricts the use of conventional carnivore surveying techniques in these areas, requiring development of novel methods. We present a method that combines questionnaire distribution to residents with field surveys and GIS, to determine relative density of two urban carnivores in England, Great Britain. We determined the density of: red fox (Vulpes vulpes) social groups in 14, approximately 1km2 suburban areas in 8 different towns and cities; and Eurasian badger (Meles meles) social groups in three suburban areas of one city. Average relative fox group density (FGD) was 3.72 km-2, which was double the estimates for cities with resident foxes in the 1980’s. Density was comparable to an alternative estimate derived from trapping and GPS-tracking, indicating the validity of the method. However, FGD did not correlate with a national dataset based on fox sightings, indicating unreliability of the national data to determine actual densities or to extrapolate a national population estimate. Using species-specific clustering units that reflect social organisation, the method was additionally applied to suburban badgers to derive relative badger group density (BGD) for one city (Brighton, 2.41 km-2). We demonstrate that citizen science approaches can effectively obtain data to assess suburban carnivore density, however publicly derived national data sets need to be locally validated before extrapolations can be undertaken. The method we present for assessing densities of foxes and badgers in British towns and cities is also adaptable to other urban carnivores elsewhere. However this transferability is contingent on species traits meeting particular criteria, and on resident responsiveness

    A machine learning case–control classifier for schizophrenia based on DNA methylation in blood

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    Epigenetic dysregulation is thought to contribute to the etiology of schizophrenia (SZ), but the cell type-specificity of DNA methylation makes population-based epigenetic studies of SZ challenging. To train an SZ case–control classifier based on DNA methylation in blood, therefore, we focused on human genomic regions of systemic interindividual epigenetic variation (CoRSIVs), a subset of which are represented on the Illumina Human Methylation 450K (HM450) array. HM450 DNA methylation data on whole blood of 414 SZ cases and 433 non-psychiatric controls were used as training data for a classification algorithm with built-in feature selection, sparse partial least squares discriminate analysis (SPLS-DA); application of SPLS-DA to HM450 data has not been previously reported. Using the first two SPLS-DA dimensions we calculated a “risk distance” to identify individuals with the highest probability of SZ. The model was then evaluated on an independent HM450 data set on 353 SZ cases and 322 non-psychiatric controls. Our CoRSIV-based model classified 303 individuals as cases with a positive predictive value (PPV) of 80%, far surpassing the performance of a model based on polygenic risk score (PRS). Importantly, risk distance (based on CoRSIV methylation) was not associated with medication use, arguing against reverse causality. Risk distance and PRS were positively correlated (Pearson r = 0.28, P = 1.28 × 10−12), and mediational analysis suggested that genetic effects on SZ are partially mediated by altered methylation at CoRSIVs. Our results indicate two innate dimensions of SZ risk: one based on genetic, and the other on systemic epigenetic variants

    Sexual selection, automata and ethics in George Eliot's The Mill on the Floss and Olive Schreiner's Undine and From Man to Man

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    This paper brings together two related areas of debate in the latter half of the nineteenth century. The first concerns how the courtship plot of the nineteenth-century novel responded to, and helped to shape, scientific ideas of sexual competition and selection. In The Mill on the Floss (1860), George Eliot strikingly prefigures Darwin's later work on sexual selection, drawing from her own extensive knowledge of the wider debates within which evolutionary theory developed. Maggie Tulliver's characterisation allows Eliot to explore the ethical complexities raised by an increasingly powerful scientific naturalism, where biology is seen to be embedded within morality in newly specific ways. The second strand of the paper examines the extension of scientific method to human mind and motivation which constituted the new psychology. It argues that there are crucial continuities of long-established ethical and religious ideas within this increasingly naturalistic view of human mind and motivation. The contention that such ideas persist and are transformed, rather than simply jettisoned, is illustrated through the example of Thomas Henry Huxley's 1874 essay on automata. Turning finally to focus on Olive Schreiner's Undine (1929) and From Man to Man (1926), the paper explores the importance of these persistent ethical and religious ideas in two novels which remained unpublished during her lifetime. It argues that they produce both difficulty and opportunity for imagining love plots within the context of increasingly assertive biological and naturalistic accounts of human beings

    From Harm to Robustness: A Principled Approach to Vice Regulation

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    John Stuart Mill’s harm principle maintains that adult behavior cannot justifiably be subject to social coercion unless the behavior involves harm or a significant risk of harm to non-consenting others. The absence of harms to others, however, is one of the distinguishing features of many manifestations of “vices” such as the consumption of alcohol, nicotine, recreational drugs, prostitution, pornography, and gambling. It is with respect to vice policy, then, that the harm principle tends to be most constraining, and some current vice controls, such as prohibitions on drug possession and prostitution, violate Mill’s precept. In the vice arena, we seem to be willing to accept social interference with what Mill termed “self-regarding” behavior. But does that willingness then imply that any social intervention into private affairs is justifiable, that the government has just as much right to outlaw Protestantism, or shag carpets, or spicy foods, as it does to outlaw drugs? In this paper I argue that advances in neuroscience and behavioral economics offer strong evidence that vices and other potentially addictive goods or activities frequently involve less-than-rational choices, and hence are exempt from the full force of the harm principle. As an alternative guide to vice policy, and following some guidance from Mill, I propose the “robustness principle”: public policy towards addictive or vicious activities engaged in by adults should be robust with respect to departures from full rationality. That is, policies should work pretty well if everyone is completely rational, and policies should work pretty well even if many people are occasionally (or frequently) irrational in their vice-related choices. The harm and robustness principles cohere in many ways, but the robustness principle offers more scope for policies that try to direct people “for their own good,” without opening the door to tyrannical inroads upon self-regarding behavior

    European “freedoms”: a critical analysis

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    Faced with the present migrant crisis and the dismal record of Europe in protecting vulnerable refugees’ and migrants’ rights, what could be the view of the moral philosopher? The contrast between the principles enshrined in the European Charter of Fundamental Rights and the reality of present policies is shocking, but more scrutiny will show that it is the result of a larger trend towards an understanding of freedom mostly in economic terms, at a time when economists such as Amartya Sen have revised their approach to economic growth and prosperity, noting the central role played by a much richer conception of freedom. The paper will scrutinize these inconsistencies and the conception of the person from which they derive and will provide an alternative and more coherent moral vision that could strengthen the legitimacy of the European Charter, at a time of growing dissatisfaction and so-called democratic deficit. Such a vision could help reconnect the Charter with a conception of the human person as in need not solely of passive legal protection, but also of active promotion of her self-respect and capabilities, and of her aspiration to a valuable life
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