On Ptolemaic metric simplicial complexes

We show that under certain mild conditions, a metric simplicial complex which satisfies the Ptolemy inequality is a CAT(0) space. Ptolemy's inequality is closely related to inversions of metric spaces. For a large class of metric simplicial complexes, we characterize those which are isometric to Euclidean space in terms of metric inversions.Comment: 13 page

Computational methods for Bayesian model choice

In this note, we shortly survey some recent approaches on the approximation of the Bayes factor used in Bayesian hypothesis testing and in Bayesian model choice. In particular, we reassess importance sampling, harmonic mean sampling, and nested sampling from a unified perspective.Comment: 12 pages, 4 figures, submitted to the proceedings of MaxEnt 2009, July 05-10, 2009, to be published by the American Institute of Physic

Dark energy constraints and correlations with systematics from CFHTLS weak lensing, SNLS supernovae Ia and WMAP5

We combine measurements of weak gravitational lensing from the CFHTLS-Wide survey, supernovae Ia from CFHT SNLS and CMB anisotropies from WMAP5 to obtain joint constraints on cosmological parameters, in particular, the dark energy equation of state parameter w. We assess the influence of systematics in the data on the results and look for possible correlations with cosmological parameters. We implement an MCMC algorithm to sample the parameter space of a flat CDM model with a dark-energy component of constant w. Systematics in the data are parametrised and included in the analysis. We determine the influence of photometric calibration of SNIa data on cosmological results by calculating the response of the distance modulus to photometric zero-point variations. The weak lensing data set is tested for anomalous field-to-field variations and a systematic shape measurement bias for high-z galaxies. Ignoring photometric uncertainties for SNLS biases cosmological parameters by at most 20% of the statistical errors, using supernovae only; the parameter uncertainties are underestimated by 10%. The weak lensing field-to-field variance pointings is 5%-15% higher than that predicted from N-body simulations. We find no bias of the lensing signal at high redshift, within the framework of a simple model. Assuming a systematic underestimation of the lensing signal at high redshift, the normalisation sigma_8 increases by up to 8%. Combining all three probes we obtain -0.10<1+w<0.06 at 68% confidence (-0.18<1+w<0.12 at 95%), including systematic errors. Systematics in the data increase the error bars by up to 35%; the best-fit values change by less than 0.15sigma. [Abridged]Comment: 14 pages, 10 figures. Revised version, matches the one to be published in A&A. Modifications have been made corresponding to the referee's suggestions, including reordering of some section

Isomer shift and magnetic moment of the long-lived 1/2+^{+} isomer in 3079^{79}_{30}Zn49_{49}: signature of shape coexistence near 78^{78}Ni

Collinear laser spectroscopy has been performed on the $^{79}_{30}$Zn$_{49}$ isotope at ISOLDE-CERN. The existence of a long-lived isomer with a few hundred milliseconds half-life was confirmed, and the nuclear spins and moments of the ground and isomeric states in $^{79}$Zn as well as the isomer shift were measured. From the observed hyperfine structures, spins $I = 9/2$ and $I = 1/2$ are firmly assigned to the ground and isomeric states. The magnetic moment $\mu$ ($^{79}$Zn) = $-$1.1866(10) $\mu_{\rm{N}}$, confirms the spin-parity $9/2^{+}$ with a $\nu g_{9/2}^{-1}$ shell-model configuration, in excellent agreement with the prediction from large scale shell-model theories. The magnetic moment $\mu$ ($^{79m}$Zn) = $-$1.0180(12) $\mu_{\rm{N}}$ supports a positive parity for the isomer, with a wave function dominated by a 2h-1p neutron excitation across the $N = 50$ shell gap. The large isomer shift reveals an increase of the intruder isomer mean square charge radius with respect to that of the ground state: $\delta \langle r^{2}_{c}\rangle^{79,79m}$ = +0.204(6) fm$^{2}$, providing first evidence of shape coexistence.Comment: 5 pages, 4 figures, 1 table, Accepeted by Phys. Rev. Lett. (2016

Effects of ATX-MS-1467 immunotherapy over 16 weeks in relapsing multiple sclerosis

Objective: To assess safety, tolerability and efficacy of the antigen-specific immunotherapy ATX-MS-1467 in participants with relapsing multiple sclerosis (RMS) using different treatment protocols to induce tolerance. Methods: Two open-label trials in adult participants with RMS. Study 1 was a multicentre Phase 1b safety evaluation comparing intradermal (i.d., Cohort 1) with subcutaneous (Cohort 2) administration in 43 participants. Both cohorts received ATX-MS-1467 dosed at 25, 50, 100, 400, and 800 μg at 14-day intervals over 8 weeks, followed by 8 weeks with 4 additional 800 μg doses at 14-day intervals and 32 weeks off study medication. Study 2 was a Phase 2a, multicentre, single-arm, trial enrolling 37 participants. ATX-MS-1467 was titrated from 50 µg i.d. on Day 1 to 200 µg on Day 15 and 800 µg on Day 29 followed by biweekly administration of 800 μg for 16 weeks and 16 weeks off study medication. Efficacy was evaluated on MRI parameters and clinical variables. Safety end points included treatment-emergent adverse events and injection-site reactions. Results: In Study 1 there was a significant decrease in new/persisting T1 GdE lesions in Cohort 1 from baseline to Week 16, returning to baseline values at week 48. In Study 2, the number of T1 GdE lesions were significantly reduced on treatment and remained reduced at study completion. Safety results were unremarkable in both studies. Conclusion: Relatively slow ATX-MS-1467 titration and a longer full-dose i.d. treatment period is associated with reduction in GdE lesions and a sustained effect post-treatment. Further trials of ATX-MS-1467 are warranted. Classification of Evidence: This work provides Class IV evidence that for patients with relapsing multiple sclerosis, slow ATX-MS-1467 titration and a longer full-dose i.d. treatment period is associated with reduction in GdE lesions

Bayesian Fit of Exclusive b→sℓˉℓb \to s \bar\ell\ell Decays: The Standard Model Operator Basis

We perform a model-independent fit of the short-distance couplings $C_{7,9,10}$ within the Standard Model set of $b\to s\gamma$ and $b\to s\bar\ell\ell$ operators. Our analysis of $B \to K^* \gamma$, $B \to K^{(*)} \bar\ell\ell$ and $B_s \to \bar\mu\mu$ decays is the first to harness the full power of the Bayesian approach: all major sources of theory uncertainty explicitly enter as nuisance parameters. Exploiting the latest measurements, the fit reveals a flipped-sign solution in addition to a Standard-Model-like solution for the couplings $C_i$. Each solution contains about half of the posterior probability, and both have nearly equal goodness of fit. The Standard Model prediction is close to the best-fit point. No New Physics contributions are necessary to describe the current data. Benefitting from the improved posterior knowledge of the nuisance parameters, we predict ranges for currently unmeasured, optimized observables in the angular distributions of $B\to K^*(\to K\pi)\,\bar\ell\ell$.Comment: 42 pages, 8 figures; v2: Using new lattice input for f_Bs, considering Bs-mixing effects in BR[B_s->ll]. Main results and conclusion unchanged, matches journal versio

Epigenetic modification of the PD-1 (Pdcd1) promoter in effector CD4(+) T cells tolerized by peptide immunotherapy

Clinically effective antigen-based immunotherapy must silence antigen-experienced effector T cells (Teff) driving ongoing immune pathology. Using CD4+ autoimmune Teff cells, we demonstrate that peptide immunotherapy (PIT) is strictly dependent upon sustained T cell expression of the co-inhibitory molecule PD-1. We found high levels of 5-hydroxymethylcytosine (5hmC) at the PD-1 (Pdcd1) promoter of non-tolerant T cells. 5hmC was lost in response to PIT, with DNA hypomethylation of the promoter. We identified dynamic changes in expression of the genes encoding the Ten-Eleven-Translocation (TET) proteins that are associated with the oxidative conversion 5-methylcytosine and 5hmC, during cytosine demethylation. We describe a model whereby promoter demethylation requires the co-incident expression of permissive histone modifications at the Pdcd1 promoter together with TET availability. This combination was only seen in tolerant Teff cells following PIT, but not in Teff that transiently express PD-1. Epigenetic changes at the Pdcd1 locus therefore determine the tolerizing potential of TCR-ligation. - See more at: http://elifesciences.org/content/3/e03416#sthash.n6isQlkn.dpu

Regulatory T Cell Migration Is Dependent on Glucokinase-Mediated Glycolysis.

Migration of activated regulatory T (Treg) cells to inflamed tissue is crucial for their immune-modulatory function. While metabolic reprogramming during Treg cell differentiation has been extensively studied, the bioenergetics of Treg cell trafficking remains undefined. We have investigated the metabolic demands of migrating Treg cells in vitro and in vivo. We show that glycolysis was instrumental for their migration and was initiated by pro-migratory stimuli via a PI3K-mTORC2-mediated pathway culminating in induction of the enzyme glucokinase (GCK). Subsequently, GCK promoted cytoskeletal rearrangements by associating with actin. Treg cells lacking this pathway were functionally suppressive but failed to migrate to skin allografts and inhibit rejection. Similarly, human carriers of a loss-of-function GCK regulatory protein gene-leading to increased GCK activity-had reduced numbers of circulating Treg cells. These cells displayed enhanced migratory activity but similar suppressive function, while conventional T cells were unaffected. Thus, GCK-dependent glycolysis regulates Treg cell migration

Spinal involvement in mucopolysaccharidosis IVA (Morquio-Brailsford or Morquio A syndrome): presentation, diagnosis and management.

Mucopolysaccharidosis IVA (MPS IVA), also known as Morquio-Brailsford or Morquio A syndrome, is a lysosomal storage disorder caused by a deficiency of the enzyme N-acetyl-galactosamine-6-sulphate sulphatase (GALNS). MPS IVA is multisystemic but manifests primarily as a progressive skeletal dysplasia. Spinal involvement is a major cause of morbidity and mortality in MPS IVA. Early diagnosis and timely treatment of problems involving the spine are critical in preventing or arresting neurological deterioration and loss of function. This review details the spinal manifestations of MPS IVA and describes the tools used to diagnose and monitor spinal involvement. The relative utility of radiography, computed tomography (CT) and magnetic resonance imaging (MRI) for the evaluation of cervical spine instability, stenosis, and cord compression is discussed. Surgical interventions, anaesthetic considerations, and the use of neurophysiological monitoring during procedures performed under general anaesthesia are reviewed. Recommendations for regular radiological imaging and neurologic assessments are presented, and the need for a more standardized approach for evaluating and managing spinal involvement in MPS IVA is addressed