Re-expression of CD14 in response to a combined IL-10/TLR stimulus defines monocyte-derived cells with an immunoregulatory phenotype

Interleukin 10 is a central regulator of the antigen-presenting function of myeloid cells. It exerts immunomodulatory effects in vivo and induces a regulatory phenotype in monocyte-derived cells in vitro. We analyzed phenotype and function of monocytic cells in vitro in relation to the cytokine milieu and the timing of TLR-based activation. In GM-CSF/IL-4 cultured human monocytic cells, we identified two, mutually exclusive cell populations arising from undifferentiated cells: CD83$^+$ fully activated dendritic cells and CD14$^+$ macrophage like cells. Re-expression of CD14 occurs primarily after a sequential trigger with a TLR signal following IL-10 preincubation. This cell population with re-expressed CD14 greatly differs in phenotype and function from the CD83+ cells. Detailed analysis of individual subpopulations reveals that exogenous IL-10 is critical for inducing the shift toward the CD14$^+$ population, but does not affect individual changes in marker expression or cell function in most cases. Thus, plasticity of CD14 expression, defining a subset of immunoregulatory cells, is highly relevant for the composition of cellular products (such as DC vaccines) as it affects the function of the total product

The E6 Oncoprotein from HPV16 Enhances the Canonical Wnt/?-Catenin Pathway in Skin Epidermis In Vivo

The contribution of the Wnt signaling pathway to human papilloma virus (HPV)-induced carcinogenesis is poorly understood. In high-grade dysplastic lesions that are caused by high-risk HPVs (HR-HPV), ?-catenin is often located in the cell nucleus, which suggests that Wnt pathway may be involved in the development of HPV-related carcinomas. Most of the oncogenic potential of HR-HPVs resides on the PDZ-binding domain of E6 protein. We hypothesized that the PDZ-binding domain of the HPV16-E6 oncoprotein induces the nuclear accumulation of ?-catenin due to its capacity to degrade PDZ-containing cellular targets. To test this hypothesis, we evaluated the staining pattern of ?-catenin in the skin epidermis of transgenic mice expressing the full-length E6 oncoprotein (K14E6 mice) and measured LacZ gene expression in K14E6 mice that were crossed with a strain expressing LacZ that was knocked into the Axin2 locus (Axin2+/LacZ mice). Here, we show that the E6 oncoprotein enhances the nuclear accumulation of ?-catenin, the accumulation of cellular ?-catenin–responsive genes, and the expression of LacZ. None of these effects were observed when a truncated E6 oncoprotein that lacks the PDZ-binding domain was expressed alone (K14E6?PDZ mice) or in combination with Axin2+/LacZ. Conversely, cotransfection with either E6 or E6?PDZ similarly enhanced canonical Wnt signaling in short-term in vitro assays that used a luciferase Wnt/?-catenin/TCF-dependent promoter. We propose that the activation of canonical Wnt signaling could be induced by the HPV16-E6 oncoprotein; however, the participation of the E6 PDZ-binding domain seems to be important in in vivo models only. Mol Cancer Res; 10(2); 250–8. ©2011 AACR

The Fading Optical Counterpart of GRB~970228, Six Months and One Year Later

We report on observations of the fading optical counterpart of the gamma-ray burst GRB 970228, made with the Hubble Space Telescope STIS CCD approximately six months after outburst and with the HST/NICMOS and Keck/NIRC approximately one year after outburst. The unresolved counterpart is detected by STIS at V=28.0 +/- 0.25, consistent with a continued power-law decline with exponent -1.14 +/- 0.05. The counterpart is located within, but near the edge of, a faint extended source with diameter ~0."8 and integrated magnitude V=25.8 +/- 0.25. A reanalysis of HST and NTT observations performed shortly after the burst shows no evidence of proper motion of the point source or fading of the extended emission. Only the extended source is visible in the NICMOS images with a magnitude of H=23.3 +/- 0.1. The Keck observations find K = 22.8 +/- 0.3. Several distinct and independent means of deriving the foreground extinction in the direction of GRB 970228 all agree with A_V = 0.75 +/- 0.2. After adjusting for Galactic extinction, we find that the size of the observed extended emission is consistent with that of galaxies of comparable magnitude found in the Hubble Deep Field (HDF) and other deep HST images. Only 2% of the sky is covered by galaxies of similar or greater surface brightness; therefore the extended source is almost certainly the host galaxy. Additionally, we find that the extinction-corrected V - H and V - K colors of the host are as blue as any galaxy of comparable or brighter magnitude in the HDF. Taken in concert with recent observations of GRB 970508, GRB 971214, and GRB 980703 our work suggests that all four GRBs with spectroscopic identification or deep multicolor broad-band imaging of the host lie in rapidly star-forming galaxies.Comment: 24 pages, Latex, 4 PostScript figures, to appear in the May 10 issue of The Astrophysical Journal (Note: displayed abstract is abridged

The Multi-Object, Fiber-Fed Spectrographs for SDSS and the Baryon Oscillation Spectroscopic Survey

We present the design and performance of the multi-object fiber spectrographs for the Sloan Digital Sky Survey (SDSS) and their upgrade for the Baryon Oscillation Spectroscopic Survey (BOSS). Originally commissioned in Fall 1999 on the 2.5-m aperture Sloan Telescope at Apache Point Observatory, the spectrographs produced more than 1.5 million spectra for the SDSS and SDSS-II surveys, enabling a wide variety of Galactic and extra-galactic science including the first observation of baryon acoustic oscillations in 2005. The spectrographs were upgraded in 2009 and are currently in use for BOSS, the flagship survey of the third-generation SDSS-III project. BOSS will measure redshifts of 1.35 million massive galaxies to redshift 0.7 and Lyman-alpha absorption of 160,000 high redshift quasars over 10,000 square degrees of sky, making percent level measurements of the absolute cosmic distance scale of the Universe and placing tight constraints on the equation of state of dark energy. The twin multi-object fiber spectrographs utilize a simple optical layout with reflective collimators, gratings, all-refractive cameras, and state-of-the-art CCD detectors to produce hundreds of spectra simultaneously in two channels over a bandpass covering the near ultraviolet to the near infrared, with a resolving power R = \lambda/FWHM ~ 2000. Building on proven heritage, the spectrographs were upgraded for BOSS with volume-phase holographic gratings and modern CCD detectors, improving the peak throughput by nearly a factor of two, extending the bandpass to cover 360 < \lambda < 1000 nm, and increasing the number of fibers from 640 to 1000 per exposure. In this paper we describe the original SDSS spectrograph design and the upgrades implemented for BOSS, and document the predicted and measured performances.Comment: 43 pages, 42 figures, revised according to referee report and accepted by AJ. Provides background for the instrument responsible for SDSS and BOSS spectra. 4th in a series of survey technical papers released in Summer 2012, including arXiv:1207.7137 (DR9), arXiv:1207.7326 (Spectral Classification), and arXiv:1208.0022 (BOSS Overview

Baryon Acoustic Oscillations in the Ly{\alpha} forest of BOSS DR11 quasars

We report a detection of the baryon acoustic oscillation (BAO) feature in the flux-correlation function of the Ly{\alpha} forest of high-redshift quasars with a statistical significance of five standard deviations. The study uses 137,562 quasars in the redshift range $2.1\le z \le 3.5$ from the Data Release 11 (DR11) of the Baryon Oscillation Spectroscopic Survey (BOSS) of SDSS-III. This sample contains three times the number of quasars used in previous studies. The measured position of the BAO peak determines the angular distance, $D_A(z=2.34)$ and expansion rate, $H(z=2.34)$, both on a scale set by the sound horizon at the drag epoch, $r_d$. We find $D_A/r_d=11.28\pm0.65(1\sigma)^{+2.8}_{-1.2}(2\sigma)$ and $D_H/r_d=9.18\pm0.28(1\sigma)\pm0.6(2\sigma)$ where $D_H=c/H$. The optimal combination, $\sim D_H^{0.7}D_A^{0.3}/r_d$ is determined with a precision of $\sim2\%$. For the value $r_d=147.4~{\rm Mpc}$, consistent with the CMB power spectrum measured by Planck, we find $D_A(z=2.34)=1662\pm96(1\sigma)~{\rm Mpc}$ and $H(z=2.34)=222\pm7(1\sigma)~{\rm km\,s^{-1}Mpc^{-1}}$. Tests with mock catalogs and variations of our analysis procedure have revealed no systematic uncertainties comparable to our statistical errors. Our results agree with the previously reported BAO measurement at the same redshift using the quasar-Ly{\alpha} forest cross-correlation. The auto-correlation and cross-correlation approaches are complementary because of the quite different impact of redshift-space distortion on the two measurements. The combined constraints from the two correlation functions imply values of $D_A/r_d$ and $D_H/r_d$ that are, respectively, 7% low and 7% high compared to the predictions of a flat $\Lambda$CDM cosmological model with the best-fit Planck parameters. With our estimated statistical errors, the significance of this discrepancy is $\approx 2.5\sigma$.Comment: Accepted for publication in A&A. 17 pages, 18 figure

SDSS-III Baryon Oscillation Spectroscopic Survey data release 12 : galaxy target selection and large-scale structure catalogues

The Baryon Oscillation Spectroscopic Survey (BOSS), part of the Sloan Digital Sky Survey (SDSS) III project, has provided the largest survey of galaxy redshifts available to date, in terms of both the number of galaxy redshifts measured by a single survey, and the effective cosmological volume covered. Key to analysing the clustering of these data to provide cosmological measurements is understanding the detailed properties of this sample. Potential issues include variations in the target catalogue caused by changes either in the targeting algorithm or properties of the data used, the pattern of spectroscopic observations, the spatial distribution of targets for which redshifts were not obtained, and variations in the target sky density due to observational systematics. We document here the target selection algorithms used to create the galaxy samples that comprise BOSS. We also present the algorithms used to create large-scale structure catalogues for the final Data Release (DR12) samples and the associated random catalogues that quantify the survey mask. The algorithms are an evolution of those used by the BOSS team to construct catalogues from earlier data, and have been designed to accurately quantify the galaxy sample. The code used, designated mksample, is released with this paper.Publisher PDFPeer reviewe

Cold Dust in Three Massive Evolved Stars in the LMC

Massive evolved stars can produce large amounts of dust, and far-infrared (IR) data are essential for determining the contribution of cold dust to the total dust mass. Using Herschel, we search for cold dust in three very dusty massive evolved stars in the Large Magellanic Cloud: R71 is a Luminous Blue Variable, HD36402 is a Wolf-Rayet triple system, and IRAS05280-6910 is a red supergiant. We model the spectral energy distributions using radiative transfer codes and find that these three stars have mass-loss rates up to 10^-3 solar masses/year, suggesting that high-mass stars are important contributors to the life-cycle of dust. We found far-IR excesses in two objects, but these excesses appear to be associated with ISM and star-forming regions. Cold dust (T < 100 K) may thus not be an important contributor to the dust masses of evolved stars.Comment: accepted to A&A as part of the Herschel first results special issu

AMI observations of Lynds Dark Nebulae: further evidence for anomalous cm-wave emission

Observations at 14.2 to 17.9 GHz made with the AMI Small Array towards fourteen Lynds Dark Nebulae with a resolution of 2' are reported. These sources are selected from the SCUBA observations of Visser et al. (2001) as small angular diameter clouds well matched to the synthesized beam of the AMI Small Array. Comparison of the AMI observations with radio observations at lower frequencies with matched uv-plane coverage is made, in order to search for any anomalous excess emission which can be attributed to spinning dust. Possible emission from spinning dust is identified as a source within a 2' radius of the Scuba position of the Lynds dark nebula, exhibiting an excess with respect to lower frequency radio emission. We find five sources which show a possible spinning dust component in their spectra. These sources have rising spectral indices in the frequency range 14.2--17.9 GHz. Of these five one has already been reported, L1111, we report one new definite detection, L675, and three new probable detections (L944, L1103 and L1246). The relative certainty of these detections is assessed on the basis of three criteria: the extent of the emission, the coincidence of the emission with the Scuba position and the likelihood of alternative explanations for the excess. Extended microwave emission makes the likelihood of the anomalous emission arising as a consequence of a radio counterpart to a protostar or a proto-planetary disk unlikely. We use a 2' radius in order to be consistent with the IRAS identifications of dark nebulae (Parker 1988), and our third criterion is used in the case of L1103 where a high flux density at 850 microns relative to the FIR data suggests a more complicated emission spectrum.Comment: submitted MNRA

Estimating the bispectrum of the Very Small Array data

We estimate the bispectrum of the Very Small Array data from the compact and extended configuration observations released in December 2002, and compare our results to those obtained from Gaussian simulations. There is a slight excess of large bispectrum values for two individual fields, but this does not appear when the fields are combined. Given our expected level of residual point sources, we do not expect these to be the source of the discrepancy. Using the compact configuration data, we put an upper limit of 5400 on the value of f_NL, the non-linear coupling parameter, at 95 per cent confidence. We test our bispectrum estimator using non-Gaussian simulations with a known bispectrum, and recover the input values.Comment: 17 pages, 16 figures, replaced with version accepted by MNRAS. Primordial bispectrum recalculated and figure 11 change

Varicella-zoster virus infections in immunocompromised patients - a single centre 6-years analysis

Background: Infection with varicella-zoster virus (VZV) contemporaneously with malignant disease or immunosuppression represents a particular challenge and requires individualized decisions and treatment. Although the increasing use of varicella-vaccines in the general population and rapid initiation of VZVimmunoglobulins and acyclovir in case of exposure has been beneficial for some patients, immunocompromised individuals are still at risk for unfavourable courses. Methods: In this single center, 6-year analysis we review incidence, hospitalization and complication rates of VZVinfections in our center and compare them to published data. Furthermore, we report three instructive cases. Results: Hospitalization rate of referred children with VZV-infections was 45%, among these 17% with malignancies and 9% under immunosuppressive therapy. Rate of complications was not elevated in these two high-risk cohorts, but one ALL-patient died due to VZV-related complications. We report one 4-year old boy with initial diagnosis of acute lymphoblastic leukemia who showed a rapidly fatal outcome of his simultaneous varicella-infection, one 1.8-year old boy with an identical situation but a mild course of his disease, and an 8.5-year old boy with a steroiddependent nephrotic syndrome. This boy developed severe hepatic involvement during his varicella-infection but responded to immediate withdrawl of steroids and administration of acyclovir plus single-dose cidofovir after nonresponse to acyclovir after 48 h. Conclusion: Our data show that patients with malignant diseases or immunosuppressive therapy should be hospitalized and treated immediately with antiviral agents. Despite these measures the course of VZV-infections can be highly variable in these patients. We discuss aids to individual decision-making for these difficult situations