The Distribution of Stellar Orbits in the Giant Elliptical Galaxy NGC 2320

We present direct observational constraints on the orbital distribution of the stars in the giant elliptical NGC 2320. Long-slit spectra along multiple position angles are used to derive the stellar line-of-sight velocity distribution within one effective radius. In addition, the rotation curve and dispersion profile of an ionized gas disk are measured from the [OIII] emission lines. After correcting for the asymmetric drift, we derive the circular velocity of the gas, which provides an independent constraint on the gravitational potential. To interpret the stellar motions, we build axisymmetric three-integral dynamical models based on an extension of the Schwarzschild orbit- superposition technique. We consider two families of gravitational potential, one in which the mass follows the light (i.e. no dark matter) and one with a logarithmic gravitational potential. Using chi^2-statistics, we compare our models to both the stellar and gas data to constrain the value of the V-band mass-to-light ratio Upsilon-V. We find Upsilon-V = 15.0 \pm 0.6 h75 for the mass-follows-light models and Upsilon-V = 17.0 \pm 0.7 h75 for the logarithmic models. For the latter, Upsilon-V is defined within a sphere of 15'' radius. Models with radially constant Upsilon-V and logarithmic models with dark matter provide comparably good fits to the data and possess similar dynamical structure. Across the full range of Upsilon-V permitted by the observational constraints, the models are radially anisotropic in the equatorial plane over the radial range of our kinematical data (1'' < r < 40''). Along the true minor axis, they are more nearly isotropic. (abridged)Comment: 26 pages, 13 figures, accepted for publication in the Astrophysical Journa

Muir-Torre syndrome - Treatment with isotretinoin and interferon alpha-2a can prevent tumour development

Muir-Torre syndrome is a genodermatosis in which multiple internal malignancies are associated with cutaneous sebaceous tumours and kerato-acanthomas. A 57-year-old man presented with multiple sebaceous tumours, kerato-acanthomas, verrucous carcinoma of the nose, renal cell and transitional cell carcinomas of the left kidney, adenoma of the colon and a positive family history of colon carcinoma. He was treated with interferon (IFN-alpha Pa) s.c. 3 x 10(6) U three times a week along with 50 mg isotretinoin daily as well as topical isotretinoin gel. During a follow-up of 29 months, only 1 sebaceous skin tumour developed and was removed, whereas more than 30 such skin tumours had been surgically removed during the last 3 years. No evidence of internal tumour development or recurrence was found. The combination of IFN with retinoids seems to be of promise to prevent tumour development in Muir-Torre syndrome. Copyright (C) 2000 S. Karger AG, Basel

Collisional stripping of planetary crusts

Geochemical studies of planetary accretion and evolution have invoked various degrees of collisional erosion to explain differences in bulk composition between planets and chondrites. Here we undertake a full, dynamical evaluation of 'crustal stripping' during accretion and its key geochemical consequences. We present smoothed particle hydrodynamics simulations of collisions between differentiated rocky planetesimals and planetary embryos. We find that the crust is preferentially lost relative to the mantle during impacts, and we have developed a scaling law that approximates the mass of crust that remains in the largest remnant. Using this scaling law and a recent set of N-body simulations, we have estimated the maximum effect of crustal stripping on incompatible element abundances during the accretion of planetary embryos. We find that on average one third of the initial crust is stripped from embryos as they accrete, which leads to a reduction of ~20% in the budgets of the heat producing elements if the stripped crust does not reaccrete. Erosion of crusts can lead to non-chondritic ratios of incompatible elements, but the magnitude of this effect depends sensitively on the details of the crust-forming melting process. The Lu/Hf system is fractionated for a wide range of crustal formation scenarios. Using eucrites (the products of planetesimal silicate melting, thought to represent the crust of Vesta) as a guide to the Lu/Hf of planetesimal crust partially lost during accretion, we predict the Earth could evolve to a superchondritic 176-Hf/177-Hf (3-5 parts per ten thousand) at present day. Such values are in keeping with compositional estimates of the bulk Earth. Stripping of planetary crusts during accretion can lead to detectable changes in bulk composition of lithophile elements, but the fractionation is relatively subtle, and sensitive to the efficiency of reaccretion.Comment: 15 pages, 9 figures. Accepted for publication in EPSL. Abstract shortened. Accompanying animations can be found at http://www.star.bris.ac.uk/pcarter/crust_strip

Preferences for cancer investigation:a vignette-based study of primary-care attendees

SummaryBackgroundThe UK lags behind many European countries in terms of cancer survival. Initiatives to address this disparity have focused on barriers to presentation, symptom recognition, and referral for specialist investigation. Selection of patients for further investigation has come under particular scrutiny, although preferences for referral thresholds in the UK population have not been studied. We investigated preferences for diagnostic testing for colorectal, lung, and pancreatic cancers in primary-care attendees.MethodsIn a vignette-based study, researchers recruited individuals aged at least 40 years attending 26 general practices in three areas of England between Dec 6, 2011, and Aug 1, 2012. Participants completed up to three of 12 vignettes (four for each of lung, pancreatic, and colorectal cancers), which were randomly assigned. The vignettes outlined a set of symptoms, the risk that these symptoms might indicate cancer (1%, 2%, 5%, or 10%), the relevant testing process, probable treatment, possible alternative diagnoses, and prognosis if cancer were identified. Participants were asked whether they would opt for diagnostic testing on the basis of the information in the vignette.Findings3469 participants completed 6930 vignettes. 3052 individuals (88%) opted for investigation in their first vignette. We recorded no strong evidence that participants were more likely to opt for investigation with a 1% increase in risk of cancer (odds ratio [OR] 1·02, 95% CI 0·99–1·06; p=0·189), although the association between risk and opting for investigation was strong when colorectal cancer was analysed alone (1·08, 1·03–1·13; p=0·0001). In multivariable analysis, age had an effect in all three cancer models: participants aged 60–69 years were significantly more likely to opt for investigation than were those aged 40–59 years, and those aged 70 years or older were less likely. Other variables associated with increased likelihood of opting for investigation were shorter travel times to testing centre (colorectal and lung cancers), a family history of cancer (colorectal and lung cancers), and higher household income (colorectal and pancreatic cancers).InterpretationParticipants in our sample expressed a clear preference for diagnostic testing at all risk levels, and individuals want to be tested at risk levels well below those stipulated by UK guidelines. This willingness should be considered during design of cancer pathways, particularly in primary care. The public engagement with our study should encourage general practitioners to involve patients in referral decision making.FundingThe National Institute for Health Research Programme Grants for Applied Research programme

Measuring cosmological weak lensing using the Advanced Camera for Surveys on board the Hubble Space Telescope

Following from the theory of General Relativity, light-bundles are deflected and differentially distorted while passing through the gravitational potential of matter inhomogeneities. The gravitational lensing effect caused by the large-scale matter distribution in the Universe is termed cosmological weak lensing, and provides a powerful probe of cosmology. By studying the distortions which are imprinted onto the observed shapes of distant galaxies, the statistical properties of the foreground density field can be constrained free of assumptions on the relation between luminous and dark matter. Due to the weakness of the effect, it is challenging to measure and can only be detected statistically from large ensembles of coherently lensed galaxies. In addition, careful correction for systematic effects is required, first of all for the image point-spread-function (PSF). In this PhD thesis we present a detailed cosmological weak lensing analysis using deep high-resolution images from the Advanced Camera for Surveys (ACS) on board the Hubble Space Telescope (HST). Including data from the ACS Parallel Cosmic Shear Survey, the HST/GEMS Survey, and the HST/COSMOS Survey, this data set constitutes the largest survey used to measure cosmological weak lensing from space today. In order to achieve the high accuracy required for weak lensing studies, we developed several upgrades for the data reduction pipeline including careful image registration, improved bad pixel masks, and an optimised weighting scheme. We also perform a thorough investigation of the ACS PSF and develop a new correction scheme for its spatial and temporal variations, which are caused by thermal breathing of the telescope. We present numerous tests of our shear measurement pipeline using simulated images from the STEP Programme, and demonstrate that it achieves a relative shear-measurement accuracy better than 2% for ACS-like images. We perform the analysis of the ACS data in two steps, starting with a pilot study, in which we test the capabilities of ACS for cosmological weak lensing measurements with early parallel observations and the combined GEMS and GOODS ACS mosaic of the Chandra Deep Field South (CDFS, 0.22 deg2). We perform a number of diagnostic tests indicating that the remaining level of systematics is consistent with zero for the GEMS and GOODS data confirming the success of our PSF correction scheme. For the parallel data we detect a low level of remaining systematics which we interpret to be caused by a lack of sufficient dithering of the data. Combining our shear estimate of the GEMS and GOODS observations using 96 galaxies arcmin-2 with the photometric redshift catalogue of the GOODS-MUSIC sample, we determine a local single field estimate for the mass power spectrum normalisation σ8=0.59+0.13-0.17(stat)±0.07(sys) (68% confidence assuming Gaussian sampling variance) at a fixed matter density Ωm=0.24 for a ΛCDM cosmology, where we marginalise over the uncertainty of the Hubble constant and the redshift distribution. This estimate agrees only marginally with the WMAP-3 result of σ8=0.761+0.049-0.048 (Spergel et al. 2007) and is significantly below values found by recent ground-based surveys. From this discrepancy we conclude that the CDFS is subject to strong sampling variance with a significant under-density of compact foreground structures. This is consistent with a recent study by Phleps et al. (2007), who find a strong deficiency of red galaxies in this field. In a second step we perform a preliminary cosmological weak lensing analysis of the HST/COSMOS Survey (1.64 deg2). The significantly increased statistical accuracy reveals previously undetectable residual systematic errors indicated by a significant B-mode signal. So far we have not been able to unambiguously identify their origin, but note that similar indications for remaining systematics have been found in an independent analysis of the same data by Massey et al. (2007). Using only B-mode-free scales (>1' in the shear two-point correlation function), we find σ8 = 0.71±0.09 (68% confidence) from COSMOS for a flat ΛCDM cosmology and fixed Ωm=0.24, where the error includes the uncertainties in the redshift distribution, the Hubble constant, and the shear calibration, as well as a Gaussian estimate for sampling variance. This result is in excellent agreement with the WMAP-3 constraints, but is significantly below the estimates found by Massey et al. (2007). In addition to the cosmological weak lensing analysis we present a reconstruction of the projected mass in the COSMOS field, as well as first results from a weak lensing analysis of the HST/STAGES Survey targeting the galaxy super-cluster Abell 901/902. Furthermore, we briefly summarise ACS studies of galaxy clusters, which make use of the developed data reduction and weak lensing pipeline

SCUBA - A submillimetre camera operating on the James Clerk Maxwell Telescope

The Submillimetre Common-User Bolometer Array (SCUBA) is one of a new generation of cameras designed to operate in the submillimetre waveband. The instrument has a wide wavelength range covering all the atmospheric transmission windows between 300 and 2000 microns. In the heart of the instrument are two arrays of bolometers optimised for the short (350/450 microns) and long (750/850 microns) wavelength ends of the submillimetre spectrum. The two arrays can be used simultaneously, giving a unique dual-wavelength capability, and have a 2.3 arc-minute field of view on the sky. Background-limited performance is achieved by cooling the arrays to below 100 mK. SCUBA has now been in active service for over a year, and has already made substantial breakthroughs in many areas of astronomy. In this paper we present an overview of the performance of SCUBA during the commissioning phase on the James Clerk Maxwell Telescope (JCMT).Comment: 14 pages, 13 figures (1 JPEG), Proc SPIE vol 335

An heuristic filtering tool to identify phenotype-associated genetic variants applied to human intellectual disability and canine coat colors

Background: Identification of one or several disease causing variant(s) from the large collection of variants present in an individual is often achieved by the sequential use of heuristic filters. The recent development of whole exome sequencing enrichment designs for several non-model species created the need for a species-independent, fast and versatile analysis tool, capable of tackling a wide variety of standard and more complex inheritance models. With this aim, we developed "Mendelian", an R-package that can be used for heuristic variant filtering. Results: The R-package Mendelian offers fast and convenient filters to analyze putative variants for both recessive and dominant models of inheritance, with variable degrees of penetrance and detectance. Analysis of trios is supported. Filtering against variant databases and annotation of variants is also included. This package is not species specific and supports parallel computation. We validated this package by reanalyzing data from a whole exome sequencing experiment on intellectual disability in humans. In a second example, we identified the mutations responsible for coat color in the dog. This is the first example of whole exome sequencing without prior mapping in the dog. Conclusion: We developed an R-package that enables the identification of disease-causing variants from the long list of variants called in sequencing experiments. The software and a detailed manual are available at https://github.com/BartBroeckx/Mendelian

IS SKELETAL MUSCLE TITIN AN ACTIVATABLE MOLECULAR SPRING?

INTRODUCTION Titin is a viscoelastic spring protein that provides 95% of the passive force in single myofibrils (1). Recently, we discovered that titin is a virtually elastic spring if unfolding of its immunoglobulin (Ig) domains can be prevented and that this elastic property can be used at variable sarcomere lengths, thus minimizing energy loss in passive muscle function (2). There is evidence that titin changes its mechanical properties when a muscle is activated. Specifically, titin is thought to bind calcium upon muscle activation (3, 4) and attach to actin thereby increasing its spring stiffness and decreasing its spring length, respectively (5). If this is indeed the case, titin’s contribution to force in an active muscle should be much greater than in a passive muscle. However, this has never been tested for dynamic muscle contractions. Therefore, the purpose of this study was to determine titin’s force contribution to active and passive muscles. This aim was achieved by stretching active and passive single myofibrils to lengths beyond actin-myosin filament overlap where titin is known to be the only contributor to force (1, 2). METHODS Rabbit psoas muscles were harvested, the connective tissue chemically digested, and individual myofibrils mechanically separated (2). Myofibrils (n=11) were then mounted on a motorized glass lever that controlled myofibril length and a silicon nitrate lever that measured myofibril force. Myofibrils were set at sarcomere lengths of 3.0µm and were stretched actively and passively to sarcomere lengths of ~4.5-5.0µm. Activated and passive myofibrils were then subjected to ten shortening-stretch cycles of 0.5µm/sarcomere, and then returned to their starting length. All stretches were performed at a speed of 0.1µm/sarcomere/second. RESULTS Actively stretched myofibrils (Figure 1, label A) had much greater force contributions from titin (compare forces at sarcomere lengths greater than 4.0µm) than passively stretched myofibrils (Figure 1, label B). Furthermore, active myofibrils had greater hystereses and greater reductions in peak forces (Figure 1, label 2) during the ten shortening-stretch cycles compared to the passive myofibrils (Figure 1, label 3). The exemplar results shown in figure (1) for single actively and passively stretched myofibrils were the same for all myofibrils tested in this study. DISCUSSION AND CONCLUSIONS The dramatically increased forces in the region beyond actin-myosin filament overlap (sarcomere lengths&gt;4.0µm) in the activated compared to the passive myofibrils is exclusively attributable to titin. This result unequivocally indicates that titin is “activated” in some unknown manner during muscle contraction, thereby vastly increasing its force contribution in active compared to passive muscle. The increased hystereses and peak force reduction during the repeat shortening-stretch cycles suggests that this activation is associated with an engagement of titin’s Ig domains in the active myofibrils. The molecular details of this newly found dynamic “activation” of titin requires further study to uncover the molecular details of titin’s force regulation upon muscle activation