Exogenous schwann cells migrate, remyelinate and promote clinical recovery in experimental auto-immune encephalomyelitis

Schwann cell (SC) transplantation is currently being discussed as a strategy that may promote functional recovery in patients with multiple sclerosis (MS) and other inflammatory demyelinating diseases of the central nervous system (CNS). However this assumes they will not only survive but also remyelinate demyelinated axons in the chronically inflamed CNS. To address this question we investigated the fate of transplanted SCs in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) in the Dark Agouti rat; an animal model that reproduces the complex inflammatory demyelinating immunopathology of MS. We now report that SCs expressing green fluorescent protein (GFP-SCs) allografted after disease onset not only survive but also migrate to remyelinate lesions in the inflamed CNS. GFP-SCs were detected more frequently in the parenchyma after direct injection into the spinal cord, than via intra-thecal delivery into the cerebrospinal fluid. In both cases the transplanted cells intermingled with astrocytes in demyelinated lesions, aligned with axons and by twenty one days post transplantation had formed Pzero protein immunoreactive internodes. Strikingly, GFP-SCs transplantation was associated with marked decrease in clinical disease severity in terms of mortality; all GFP-SCs transplanted animals survived whilst 80% of controls died within 40 days of disease

The Discovery of the Most Metal-Rich White Dwarf: Composition of a Tidally Disrupted Extrasolar Dwarf Planet

Cool white dwarf stars are usually found to have an outer atmosphere that is practically pure in hydrogen or helium. However, a small fraction have traces of heavy elements that must originate from the accretion of extrinsic material, most probably circumstellar matter. Upon examining thousands of Sloan Digital Sky Survey spectra, we discovered that the helium-atmosphere white dwarf SDSS J073842.56+183509.6 shows the most severe metal pollution ever seen in the outermost layers of such stars. We present here a quantitative analysis of this exciting star by combining high S/N follow-up spectroscopic and photometric observations with model atmospheres and evolutionary models. We determine the global structural properties of our target star, as well as the abundances of the most significant pollutants in its atmosphere, i.e., H, O, Na, Mg, Si, Ca, and Fe. The relative abundances of these elements imply that the source of the accreted material has a composition similar to that of Bulk Earth. We also report the signature of a circumstellar disk revealed through a large infrared excess in JHK photometry. Combined with our inferred estimate of the mass of the accreted material, this strongly suggests that we are witnessing the remains of a tidally disrupted extrasolar body that was as large as Ceres.Comment: 7 pages in emulateapj, 5 figures, accepted for publication in Ap

A simple mean field model for social interactions: dynamics, fluctuations, criticality

We study the dynamics of a spin-flip model with a mean field interaction. The system is non reversible, spacially inhomogeneous, and it is designed to model social interactions. We obtain the limiting behavior of the empirical averages in the limit of infinitely many interacting individuals, and show that phase transition occurs. Then, after having obtained the dynamics of normal fluctuations around this limit, we analize long time fluctuations for critical values of the parameters. We show that random inhomogeneities produce critical fluctuations at a shorter time scale compared to the homogeneous system.Comment: 37 pages, 2 figure

Turnover, account value and diversification of real traders: evidence of collective portfolio optimizing behavior

Despite the availability of very detailed data on financial market, agent-based modeling is hindered by the lack of information about real trader behavior. This makes it impossible to validate agent-based models, which are thus reverse-engineering attempts. This work is a contribution to the building of a set of stylized facts about the traders themselves. Using the client database of Swissquote Bank SA, the largest on-line Swiss broker, we find empirical relationships between turnover, account values and the number of assets in which a trader is invested. A theory based on simple mean-variance portfolio optimization that crucially includes variable transaction costs is able to reproduce faithfully the observed behaviors. We finally argue that our results bring into light the collective ability of a population to construct a mean-variance portfolio that takes into account the structure of transaction costsComment: 26 pages, 9 figures, Fig. 8 fixe

A Semi-Lagrangian scheme for a modified version of the Hughes model for pedestrian flow

In this paper we present a Semi-Lagrangian scheme for a regularized version of the Hughes model for pedestrian flow. Hughes originally proposed a coupled nonlinear PDE system describing the evolution of a large pedestrian group trying to exit a domain as fast as possible. The original model corresponds to a system of a conservation law for the pedestrian density and an Eikonal equation to determine the weighted distance to the exit. We consider this model in presence of small diffusion and discuss the numerical analysis of the proposed Semi-Lagrangian scheme. Furthermore we illustrate the effect of small diffusion on the exit time with various numerical experiments

Integrated Polygenic Tool Substantially Enhances Coronary Artery Disease Prediction

BACKGROUND: There is considerable interest in whether genetic data can be used to improve standard cardiovascular disease risk calculators, as the latter are routinely used in clinical practice to manage preventative treatment. METHODS: Using the UK Biobank resource, we developed our own polygenic risk score for coronary artery disease (CAD). We used an additional 60 000 UK Biobank individuals to develop an integrated risk tool (IRT) that combined our polygenic risk score with established risk tools (either the American Heart Association/American College of Cardiology pooled cohort equations [PCE] or UK QRISK3), and we tested our IRT in an additional, independent set of 186 451 UK Biobank individuals. RESULTS: The novel CAD polygenic risk score shows superior predictive power for CAD events, compared with other published polygenic risk scores, and is largely uncorrelated with PCE and QRISK3. When combined with PCE into an IRT, it has superior predictive accuracy. Overall, 10.4% of incident CAD cases were misclassified as low risk by PCE and correctly classified as high risk by the IRT, compared with 4.4% misclassified by the IRT and correctly classified by PCE. The overall net reclassification improvement for the IRT was 5.9% (95% CI, 4.7–7.0). When individuals were stratified into age-by-sex subgroups, the improvement was larger for all subgroups (range, 8.3%–15.4%), with the best performance in 40- to 54-year-old men (15.4% [95% CI, 11.6–19.3]). Comparable results were found using a different risk tool (QRISK3) and also a broader definition of cardiovascular disease. Use of the IRT is estimated to avoid up to 12 000 deaths in the United States over a 5-year period. CONCLUSIONS: An IRT that includes polygenic risk outperforms current risk stratification tools and offers greater opportunity for early interventions. Given the plummeting costs of genetic tests, future iterations of CAD risk tools would be enhanced with the addition of a person’s polygenic risk

SDSS DR7 white dwarf catalog

We present a new catalog of spectroscopically confirmed white dwarf stars from the Sloan Digital Sky Survey (SDSS) Data Release 7 spectroscopic catalog. We find 20,407 white dwarf spectra, representing 19,712 stars, and provide atmospheric model fits to 14,120 DA and 1011 DB white dwarf spectra from 12,843 and 923 stars, respectively. These numbers represent more than a factor of two increase in the total number of white dwarf stars from the previous SDSS white dwarf catalogs based on DR4 data. Our distribution of subtypes varies from previous catalogs due to our more conservative, manual classifications of each star in our catalog, supplementing our automatic fits. In particular, we find a large number of magnetic white dwarf stars whose small Zeeman splittings mimic increased Stark broadening that would otherwise result in an overestimated log g if fit as a non-magnetic white dwarf. We calculate mean DA and DB masses for our clean, non-magnetic sample and find the DB mean mass is statistically larger than that for the DAs.Facultad de Ciencias Astronómicas y Geofísica

Dpp Signaling Activity Requires Pentagone to Scale with Tissue Size in the Growing Drosophila Wing Imaginal Disc

The activity of the Dpp morphogen adapts to tissue size in the growing Drosophila wing imaginal disc, and Pentagone, an important secreted feedback regulator of the Dpp pathway, is required for this adaptation

Analysis of scalar perturbations in cosmological models with a non-local scalar field

We develop the cosmological perturbations formalism in models with a single non-local scalar field originating from the string field theory description of the rolling tachyon dynamics. We construct the equation for the energy density perturbations of the non-local scalar field in the presence of the arbitrary potential and formulate the local system of equations for perturbations in the linearized model when both simple and double roots of the characteristic equation are present. We carry out the general analysis related to the curvature and entropy perturbations and consider the most specific example of perturbations when important quantities in the model become complex.Comment: LaTeX, 25 pages, 1 figure, v2: Subsection 3.2 and Section 5 added, references added, accepted for publication in Class. Quant. Grav. arXiv admin note: text overlap with arXiv:0903.517

Patients' experiences of living with and receiving treatment for fibromyalgia syndrome: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Fibromyalgia syndrome (FMS) presents a challenge for patients and health care staff across many medical specialities. The aetiology is multi-dimensional, involving somatic, psychological and social factors. Patients' views were obtained to understand their experience of living with this long-term condition, using qualitative interviews.</p> <p>Methods</p> <p>12 patients were recruited and stratified by age, gender and ethnicity from one rheumatology outpatient clinic, and a departmental held database of patients diagnosed with FMS.</p> <p>Results</p> <p>Patients' accounts of their experience of FMS resonated well with two central concepts: social identity and illness intrusiveness. These suggested three themes for the analytical framework: life before and after diagnosis (e.g. lack of information about FMS, invisibility of FMS); change in health identity (e.g. mental distress, impact on social life) and perceived quality of care (e.g. lack of contact with nurses, attitudes of specialists). The information provided from one male participant did not differ from the female patients, but black and ethnic community patients expressed a degree of suspicion towards the medication prescribed, and the attitudes displayed by some doctors, a finding that has not been previously reported amongst this patient group. Patients expected more consultation time and effective treatment than they received. Subjective experiences and objective physical and emotional changes were non-overlapping. Patients' accounts revealed that their physical, mental and social health was compromised, at times overwhelming and affected their identity.</p> <p>Conclusion</p> <p>FMS is a condition that intrudes upon many aspects of patients' lives and is little understood. At the same time, it is a syndrome that evokes uneasiness in health care staff (as current diagnostic criteria are not well supported by objective markers of physiological or biochemical nature, and indeed because of doubt about the existence of the condition) and places great demands on resources in clinical practice. Greater attention needs to be paid to the links between the explanatory models of patients and staff, and most important, to the interrelationship between the complex physical, psychological and social needs of patients with FMS. Taking a less medical but more holistic approach when drawing up new diagnostic criteria for FMS might match better individuals' somatic and psycho-social symptom profile and may result in more effective treatment.</p