9,137 research outputs found

    Modelling the functional genomics of Parkinson’s disease in Caenorhabditis elegans: LRRK2 and beyond

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    For decades, Parkinson’s disease (PD) cases have been genetically categorised into familial, when caused by mutations in single genes with a clear inheritance pattern in affected families, or idiopathic, in the absence of an evident monogenic determinant. Recently, genome-wide association studies (GWAS) have revealed how common genetic variability can explain up to 36% of PD heritability and that PD manifestation is often determined by multiple variants at different genetic loci. Thus, one of the current challenges in PD research stands in modelling the complex genetic architecture of this condition and translating this into functional studies. Caenorhabditis elegans provide a profound advantage as a reductionist, economical model for PD research, with a short lifecycle, straightforward genome engineering and high conservation of PD relevant neural, cellular and molecular pathways. Functional models of PD genes utilising C. elegans show many phenotypes recapitulating pathologies observed in PD. When contrasted with mammalian in vivo and in vitro models, these are frequently validated, suggesting relevance of C. elegans in the development of novel PD functional models. This review will discuss how the nematode C. elegans PD models have contributed to the uncovering of molecular and cellular mechanisms of disease, with a focus on the genes most commonly found as causative in familial PD and risk factors in idiopathic PD. Specifically, we will examine the current knowledge on a central player in both familial and idiopathic PD, Leucine-rich repeat kinase 2 (LRRK2) and how it connects to multiple PD associated GWAS candidates and Mendelian disease-causing genes

    Out-Of-Focus Holography at the Green Bank Telescope

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    We describe phase-retrieval holography measurements of the 100-m diameter Green Bank Telescope using astronomical sources and an astronomical receiver operating at a wavelength of 7 mm. We use the technique with parameterization of the aperture in terms of Zernike polynomials and employing a large defocus, as described by Nikolic, Hills & Richer (2006). Individual measurements take around 25 minutes and from the resulting beam maps (which have peak signal to noise ratios of 200:1) we show that it is possible to produce low-resolution maps of the wavefront errors with accuracy around a hundredth of a wavelength. Using such measurements over a wide range of elevations, we have calculated a model for the wavefront-errors due to the uncompensated gravitational deformation of the telescope. This model produces a significant improvement at low elevations, where these errors are expected to be the largest; after applying the model, the aperture efficiency is largely independent of elevation. We have also demonstrated that the technique can be used to measure and largely correct for thermal deformations of the antenna, which often exceed the uncompensated gravitational deformations during daytime observing. We conclude that the aberrations induced by gravity and thermal effects are large-scale and the technique used here is particularly suitable for measuring such deformations in large millimetre wave radio telescopes.Comment: 10 pages, 7 figures (accepted by Astronomy & Astrophysics

    Length scale dependence of dynamical heterogeneity in a colloidal fractal gel

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    We use time-resolved dynamic light scattering to investigate the slow dynamics of a colloidal gel. The final decay of the average intensity autocorrelation function is well described by g_2(q,τ)1exp[(τ/τ_f)p]g\_2(q,\tau)-1 \sim \exp[-(\tau/\tau\_\mathrm{f})^p], with τ_fq1\tau\_\mathrm{f} \sim q^{-1} and pp decreasing from 1.5 to 1 with increasing qq. We show that the dynamics is not due to a continuous ballistic process, as proposed in previous works, but rather to rare, intermittent rearrangements. We quantify the dynamical fluctuations resulting from intermittency by means of the variance χ(τ,q)\chi(\tau,q) of the instantaneous autocorrelation function, the analogous of the dynamical susceptibility χ_4\chi\_4 studied in glass formers. The amplitude of χ\chi is found to grow linearly with qq. We propose a simple --yet general-- model of intermittent dynamics that accounts for the qq dependence of both the average correlation functions and χ\chi.Comment: Revised and improved, to appear in Europhys. Let

    Completion of a SCUBA survey of Lynds dark clouds and implications for low-mass star formation

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    We have carried out a survey of optically-selected dark clouds using the bolometer array SCUBA on the James Clerk Maxwell Telescope, at 850 microns wavelength. The survey covers a total of 0.5 square degrees and is unbiased with reference to cloud size, star formation activity, or the presence of infrared emission. Several new protostars and starless cores have been discovered; the protostars are confirmed through the detection of their accompanying outflows in CO(2-1) emission. The survey is believed to be complete for Class 0 and Class I protostars, and yields two important results regarding the lifetimes of these phases. First, the ratio of Class 0 to Class protostars in the sample is roughly unity, very different from the 1:10 ratio that has previously been observed for the rho Ophiuchi star-forming region. Assuming star formation to be a homogeneous process in the dark clouds, this implies that the Class 0 lifetime is similar to the Class I phase, which from infrared surveys has been established to be approximately 200,000 yr. It also suggests there is no rapid initial accretion phase in Class 0 objects. A burst of triggered star formation some 100,000 yr ago can explain the earlier results for rho Ophiuchus. Second, the number of starless cores is approximately twice that of the total number of protostars, indicating a starless core lifetime of approximately 800,000 yr. These starless cores are therefore very short-lived, surviving only two or three free-fall times. This result suggests that, on size scales of 10,000 AU at least, the dynamical evolution of starless cores is probably not controlled by magnetic processes.Comment: 67 pages including 32 figures (highly compressed). Accepted for publication in the Astronomical Journal. Available with full resolution (legible) figures at http://www.mrao.cam.ac.uk/%7ejsr/papers/lynds2.ps.g

    Anthropocene, Capitalocene and Liberal Cosmopolitan IR: A Response to Burke et al.’s Planet Politics

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    This article is a collective response to Anthony Burke et al’s ‘Planet Politics’, published in this journal in 2016, and billed as a ‘Manifesto from the end of IR’. We dispute this claim on the basis that rather than breaking from the discipline, the Manifesto provides a problematic global governance agenda which is dangerously authoritarian and deeply depoliticising. We substantiate this analysis in the claim that Burke et al reproduce an already failed and discredited liberal cosmopolitan framework through the advocacy of managerialism rather than transformation; the top-down coercive approach of international law; and use of abstract modernist political categories. In the closing sections of the article, we discuss the possibility of different approaches, which, taking the Anthropocene as both an epistemological and ontological break with modernist assumptions, could take us beyond IR’s disciplinary confines
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