Recent Decisions

Comments on recent decisions by J. Patrick O\u27Malley, Peter H. Lousberg, David J. Eardley, James M. Corcoran, Jr., Joseph B. Joyce, James E. Murray, Edmund L. White, Berry L. Reece, Jr., A. J. Deutsch, and George N. Tompkins, Jr

Oct2 enhances antibody-secreting cell differentiation through regulation of IL-5 receptor α chain expression on activated B cells

Mice lacking a functional gene for the Oct2 transcriptional activator display several developmental and functional deficiencies in the B lymphocyte lineage. These include defective B cell receptor (BCR) and Toll-like receptor 4 signaling, an absence of B-1 and marginal zone populations, and globally reduced levels of serum immunoglobulin (Ig) in naive and immunized animals. Oct2 was originally identified through its ability to bind to regulatory regions in the Ig loci, but genetic evidence has not supported an essential role for Oct2 in the expression of Ig genes. We describe a new Oct2-mediated role in B cells. Oct2 augments the ability of activated B cells to differentiate to antibody-secreting plasma cells (ASCs) under T cell–dependent conditions through direct regulation of the gene encoding the α chain of the interleukin (IL) 5 receptor. Ectopic expression of IL-5Rα in oct2-deficient B cells largely restores their ability to differentiate to functional ASCs in vitro but does not correct other phenotypic defects in the mutants, such as the maturation and specialization of peripheral B cells, which must therefore rely on distinct Oct2 target genes. IL-5 augments ASC differentiation in vitro, and we show that IL-5 directly activates the plasma cell differentiation program by enhancing blimp1 expression

First trimester serum biomarkers to predict gestational diabetes in a high-risk cohort: Striving for clinically useful thresholds

Objectives: Screening and diagnosis of gestational diabetes (GDM) has been a source of controversy. The prevalence has increased in line with an obesity epidemic and a trend towards delayed child-bearing. Treatment of even modest glycaemic impairment in pregnancy has been shown to be beneficial in preventing its clinical sequalae. However the cumbersome nature and timing of the oral glucose tolerance test coupled with debate around universal versus risk factor based screening have been problematic. This group aimed to investigate a panel of biomarkers which have shown promise in the literature to predict GDM from the first trimester in a group of high risk women. Methods: Serum samples were drawn on 248 women deemed at risk of GDM before 15 weeks\u27 gestation to measure C-reactive protein, sex hormone binding globulin, adiponectin and 1,5 anhydroglucitol. Patients underwent an oral glucose tolerance test as per IADPSG criteria at 28 weeks\u27 gestation. Multiple logistic regression was used to examine the link between incidence of GDM and early pregnancy serum biomarkers. Results: Adiponectin levels in the first trimester are independently linked to the risk of GDM. Serum adiponectin \u3c8.9 μg/ml gives an odds ratio of 3.3 for GDM.Mean 1,5 AG levels are significantly lower in those that go on to develop GDM. SHBG levels measured in the first trimester were linked to the risk of GDM. However, this was no longer statistically significant once BMI, ethnicity and family history were taken into consideration. First trimester measurement of CRP is not a useful indicator of GDM risk. Conclusions: First trimester measurement of Adiponectin and 1,5 Anhydroglucitol are potential early biomarkers for the later onset of GDM. Risk stratification using these biomarkers may facilitate early diagnosis and management of GDM to mitigate against its complications

Dislocation Emission around Nanoindentations on a (001) fcc Metal Surface Studied by STM and Atomistic Simulations

We present a combined study by Scanning Tunneling Microscopy and atomistic simulations of the emission of dissociated dislocation loops by nanoindentation on a (001) fcc surface. The latter consist of two stacking-fault ribbons bounded by Shockley partials and a stair-rod dislocation. These dissociated loops, which intersect the surface, are shown to originate from loops of interstitial character emitted along the directions and are usually located at hundreds of angstroms away from the indentation point. Simulations reproduce the nucleation and glide of these dislocation loops.Comment: 10 pages, 4 figure

An adaptive Metropolis-Hastings scheme: sampling and optimization

We propose an adaptive Metropolis-Hastings algorithm in which sampled data are used to update the proposal distribution. We use the samples found by the algorithm at a particular step to form the information-theoretically optimal mean-field approximation to the target distribution, and update the proposal distribution to be that approximatio. We employ our algorithm to sample the energy distribution for several spin-glasses and we demonstrate the superiority of our algorithm to the conventional MH algorithm in sampling and in annealing optimization.Comment: To appear in Europhysics Letter

A multispectral view of the periodic events in eta Carinae

A full description of the 5.5-yr low excitation events in Eta Carinae is presented. We show that they are not as simple and brief as previously thought, but a combination of two components. The first, the 'slow variation' component, is revealed by slow changes in the ionization level of circumstellar matter across the whole cycle and is caused by gradual changes in the wind-wind collision shock-cone orientation, angular opening and gaseous content. The second, the 'collapse' component, is restricted to around the minimum, and is due to a temporary global collapse of the wind-wind collision shock. High energy photons (E > 16 eV) from the companion star are strongly shielded, leaving the Weigelt objects at low ionization state for >6 months. High energy phenomena are sensitive only to the 'collapse', low energy only to the 'slow variation' and intermediate energies to both components. Simple eclipses and mechanisms effective only near periastron (e.g., shell ejection or accretion onto the secondary star) cannot account for the whole 5.5-yr cycle. We find anti-correlated changes in the intensity and the radial velocity of P Cygni absorption profiles in FeII 6455 and HeI 7065 lines, indicating that the former is associated to the primary and the latter to the secondary star. We present a set of light curves representative of the whole spectrum, useful for monitoring the next event (2009 January 11).Comment: 16 pages, 7 EPS figures, accepted for publication on MNRA

A dozen colliding wind X-ray binaries in the star cluster R136 in the 30Doradus region

We analyzed archival Chandra X-ray observations of the central portion of the 30 Doradus region in the Large Magellanic Cloud. The image contains 20 X-ray point sources with luminosities between $5 \times 10^{32}$ and $2 \times 10^{35}$ erg s$^{-1}$ (0.2 -- 3.5 keV). A dozen sources have bright WN Wolf-Rayet or spectral type O stars as optical counterparts. Nine of these are within $\sim 3.4$pc of R136, the central star cluster of NGC2070. We derive an empirical relation between the X-ray luminosity and the parameters for the stellar wind of the optical counterpart. The relation gives good agreement for known colliding wind binaries in the Milky Way Galaxy and for the identified X-ray sources in NGC2070. We conclude that probably all identified X-ray sources in NGC2070 are colliding wind binaries and that they are not associated with compact objects. This conclusion contradicts Wang (1995) who argued, using ROSAT data, that two earlier discovered X-ray sources are accreting black-hole binaries. Five of the eighteen brightest stars in R136 are not visible in our X-ray observations. These stars are either single, have low mass companions or very wide orbits. The resulting binary fraction among early type stars is then unusually high (at least 70%).Comment: 23 pages, To appear in August in Ap

Gamma-ray follow-up studies on Eta Carinae

Observations of high energy gamma rays recently revealed a persistent source in spatial coincidence with the binary system Eta Carinae. Since modulation of the observed gamma-ray flux on orbital time scales has not been reported so far, an unambiguous identification was hitherto not possible. Particularly the observations made by the Fermi Large Area Telescope (LAT) posed additional questions regarding the actual emission scenario owing to the existence of two energetically distinct components in the gamma-ray spectrum of this source, best described by an exponentially cutoff power-law function (CPL) at energies below 10 GeV and a power-law (PL) component dominant at higher energies. The increased exposure in conjunction with the improved instrumental response functions of the LAT now allow us to perform a more detailed investigation of location, spectral shape, and flux time history of the observed gamma-ray emission. For the first time, we are able to report a weak but regular flux decrease over time. This can be understood and interpreted in a colliding-wind binary scenario for orbital modulation of the gamma-ray emission. We find the spectral shape of the gamma-ray signal in agreement with a single emitting particle population in combination with significant absorption by gamma-gamma pair production. Studying the correlation of the flux decrease with the orbital separation of the binary components allows us to predict the behaviour up to the next periastron passage in 2014.Comment: 11 pages, 9 figure