V1647 Orionis: Reinvigorated Accretion and the Re-Appearance of McNeil's Nebula

In late 2003, the young eruptive variable star V1647 Orionis optically brightened by over 5 magnitudes, stayed bright for around 26 months, and then decline to its pre-outburst level. In August 2008 the star was reported to have unexpectedly brightened yet again and we herein present the first detailed observations of this new outburst. Photometrically, the star is now as bright as it ever was following the 2003 eruption. Spectroscopically, a pronounced P Cygni profile is again seen in Halpha with an absorption trough extending to -700 km/s. In the near-infrared, the spectrum now possesses very weak CO overtone bandhead absorption in contrast to the strong bandhead emission seen soon after the 2003 event. Water vapor absorption is also much stronger than previously seen. We discuss the current outburst below and relate it to the earlier event.Comment: 6 pages, 3 figure

Synthesising, using, and correcting for telluric features in high-resolution astronomical spectra

We present a technique to synthesise telluric absorption and emission features both for in-situ wavelength calibration and for their removal from astronomical spectra. While the presented technique is applicable for a wide variety of optical and infrared spectra, we concentrate in this paper on selected high-resolution near-infrared spectra obtained with the CRIRES spectrograph to demonstrate its performance and limitation. We find that synthetic spectra reproduce telluric absorption features to about 2%, even close to saturated line cores. Thus, synthetic telluric spectra could be used to replace the observation of telluric standard stars, saving valuable observing time. This technique also provides a precise in-situ wavelength calibration, especially useful for high-resolution near-infrared spectra in the absence of other calibration sources.Comment: 11 pages, 11 figures, accepted for publication in A&A (updated version

Targeting angiogenesis in multiple myeloma by the VEGF and HGF blocking DARPin® protein MP0250: a preclinical study

The investigational drug MP0250 is a multi-specific DARPin® molecule that simultaneously binds and neutralizes VEGF and HGF with high specificity and affinity. Here we studied the antiangiogenic effects of the MP0250 in multiple myeloma (MM). In endothelial cells (EC) isolated from bone marrow (BM) of MM patients (MMEC) MP0250 reduces VEGFR2 and cMet phosphorylation and affects their downstream signaling cascades. MP0250 influences the secretory profile of MMEC and inhibits their in vitro angiogenic activities (spontaneous and chemotactic migration, adhesion, spreading and capillarogenesis). Compared to anti-VEGF or anti-HGF neutralizing mAbs, MP0250 strongly reduces capillary network formation and vessel-sprouting in a Matrigel angiogenesis assay. MP0250 potentiates the effect of bortezomib in the same in vitro setting. It significantly reduces the number of newly formed vessels in the choriollantoic membrane assay (CAM) and the Matrigel plug assay. In the syngeneic 5T33MM tumor model, MP0250 decreases the microvessel density (MVD) and the combination MP0250/bortezomib lowers the percentage of idiotype positive cells and the serum levels of M-protein. Overall results define MP0250 as a strong antiangiogenic agent with potential as a novel combination drug for treatment of MM patients

Novel mutations in the WFS1 gene are associated with Wolfram syndrome and systemic inflammation

Mutations in the WFS1 gene, encoding wolframin (WFS1), cause endoplasmic reticulum (ER) stress and are associated with a rare autosomal-recessive disorder known as Wolfram syndrome (WS). WS is clinically characterized by childhood-onset diabetes mellitus, optic atrophy, deafness, diabetes insipidus and neurological signs. We identified two novel WFS1 mutations in a patient with WS, namely, c.316-1G > A (in intron 3) and c.757A > T (in exon 7). Both mutations, located in the N-terminal region of the protein, were predicted to generate a truncated and inactive form of WFS1. We found that although the WFS1 protein was not expressed in peripheral blood mononuclear cells (PBMCs) of the proband, no constitutive ER stress activation could be detected in those cells. In contrast, WS proband's PBMCs produced very high levels of proinflammatory cytokines (i.e. TNF-α, IL-1β, and IL-6) in the absence of any stimulus. WFS1 silencing in PBMCs from control subjects by means of small RNA interference also induced a pronounced proinflammatory cytokine profile. The same cytokines were also significantly higher in sera from the WS patient as compared to matched healthy controls. Moreover, the chronic inflammatory state was associated with a dominance of proinflammatory T helper 17 (Th17)-type cells over regulatory T (Treg) lymphocytes in the WS PBMCs. The identification of a state of systemic chronic inflammation associated with WFS1 deficiency may pave the way to innovative and personalized therapeutic interventions in WS

Gravitational Collapse of a Radiating Shell

We study the collapse of a self-gravitating and radiating shell. Matter constituting the shell is quantized and the construction is viewed as a semiclassical model of possible black hole formation. It is shown that the shell internal degrees of freedom are excited by the quantum non-adiabaticity of the collapse and, consequently, on coupling them to a massless scalar field, the collapsing matter emits a burst of coherent (thermal) radiation.Comment: LaTeX, 34 pages, 21 EPS figures include

Clusters of galaxies : observational properties of the diffuse radio emission

Clusters of galaxies, as the largest virialized systems in the Universe, are ideal laboratories to study the formation and evolution of cosmic structures...(abridged)... Most of the detailed knowledge of galaxy clusters has been obtained in recent years from the study of ICM through X-ray Astronomy. At the same time, radio observations have proved that the ICM is mixed with non-thermal components, i.e. highly relativistic particles and large-scale magnetic fields, detected through their synchrotron emission. The knowledge of the properties of these non-thermal ICM components has increased significantly, owing to sensitive radio images and to the development of theoretical models. Diffuse synchrotron radio emission in the central and peripheral cluster regions has been found in many clusters. Moreover large-scale magnetic fields appear to be present in all galaxy clusters, as derived from Rotation Measure (RM) studies. Non-thermal components are linked to the cluster X-ray properties, and to the cluster evolutionary stage, and are crucial for a comprehensive physical description of the intracluster medium. They play an important role in the cluster formation and evolution. We review here the observational properties of diffuse non-thermal sources detected in galaxy clusters: halos, relics and mini-halos. We discuss their classification and properties. We report published results up to date and obtain and discuss statistical properties. We present the properties of large-scale magnetic fields in clusters and in even larger structures: filaments connecting galaxy clusters. We summarize the current models of the origin of these cluster components, and outline the improvements that are expected in this area from future developments thanks to the new generation of radio telescopes.Comment: Accepted for the publication in The Astronomy and Astrophysics Review. 58 pages, 26 figure

One-loop f(R) gravity in de Sitter universe

Motivated by the dark energy issue, the one-loop quantization approach for a family of relativistic cosmological theories is discussed in some detail. Specifically, general $f(R)$ gravity at the one-loop level in a de Sitter universe is investigated, extending a similar program developed for the case of pure Einstein gravity. Using generalized zeta regularization, the one-loop effective action is explicitly obtained off-shell, what allows to study in detail the possibility of (de)stabilization of the de Sitter background by quantum effects. The one-loop effective action maybe useful also for the study of constant curvature black hole nucleation rate and it provides the plausible way of resolving the cosmological constant problem.Comment: 25 pages, Latex file. Discussion enlarged, new references added. Version accepted in JCA

Renormalization Group Flow in Scalar-Tensor Theories. II

We study the UV behaviour of actions including integer powers of scalar curvature and even powers of scalar fields with Functional Renormalization Group techniques. We find UV fixed points where the gravitational couplings have non-trivial values while the matter ones are Gaussian. We prove several properties of the linearized flow at such a fixed point in arbitrary dimensions in the one-loop approximation and find recursive relations among the critical exponents. We illustrate these results in explicit calculations in $d=4$ for actions including up to four powers of scalar curvature and two powers of the scalar field. In this setting we notice that the same recursive properties among the critical exponents, which were proven at one-loop order, still hold, in such a way that the UV critical surface is found to be five dimensional. We then search for the same type of fixed point in a scalar theory with minimal coupling to gravity in $d=4$ including up to eight powers of scalar curvature. Assuming that the recursive properties of the critical exponents still hold, one would conclude that the UV critical surface of these theories is five dimensional.Comment: 14 pages. v.2: Minor changes, some references adde

CLOUDS search for variability in brown dwarf atmospheres

Context: L-type ultra-cool dwarfs and brown dwarfs have cloudy atmospheres that could host weather-like phenomena. The detection of photometric or spectral variability would provide insight into unresolved atmospheric heterogeneities, such as holes in a global cloud deck. Aims: It has been proposed that growth of heterogeneities in the global cloud deck may account for the L- to T-type transition as brown dwarf photospheres evolve from cloudy to clear conditions. Such a mechanism is compatible with variability. We searched for variability in the spectra of five L6 to T6 brown dwarfs in order to test this hypothesis. Methods: We obtained spectroscopic time series using VLT/ISAAC, over 0.99-1.13um, and IRTF/SpeX for two of our targets, in J, H and K bands. We search for statistically variable lines and correlation between those. Results: High spectral-frequency variations are seen in some objects, but these detections are marginal and need to be confirmed. We find no evidence for large amplitude variations in spectral morphology and we place firm upper limits of 2 to 3% on broad-band variability, on the time scale of a few hours. The T2 transition brown dwarf SDSS J1254-0122 shows numerous variable features, but a secure variability diagnosis would require further observations. Conclusions: Assuming that any variability arises from the rotation of patterns of large-scale clear and cloudy regions across the surface, we find that the typical physical scale of cloud cover disruption should be smaller than 5-8% of the disk area for four of our targets. The possible variations seen in SDSS J1254-0122 are not strong enough to allow us to confirm the cloud breaking hypothesis.Comment: 17 pages, 14 figures, accepted by A&

Engagement of nuclear coactivator 7 by 3-hydroxyanthranilic acid enhances activation of aryl hydrocarbon receptor in immunoregulatory dendritic cells

Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the first step in the kynurenine pathway of tryptophan (Trp) degradation that produces several biologically active Trp metabolites. L-kynurenine (Kyn), the first byproduct by IDO1, promotes immunoregulatory effects via activation of the Aryl hydrocarbon Receptor (AhR) in dendritic cells (DCs) and T lymphocytes. We here identified the nuclear coactivator 7 (NCOA7) as a molecular target of 3-hydroxyanthranilic acid (3-HAA), a Trp metabolite produced downstream of Kyn along the kynurenine pathway. In cells overexpressing NCOA7 and AhR, the presence of 3-HAA increased the association of the two molecules and enhanced Kyn-driven, AhR-dependent gene transcription. Physiologically, conventional (cDCs) but not plasmacytoid DCs or other immune cells expressed high levels of NCOA7. In cocultures of CD4+ T cells with cDCs, the co-addition of Kyn and 3-HAA significantly increased the induction of Foxp3+ regulatory T cells and the production of immunosuppressive transforming growth factor β in an NCOA7-dependent fashion. Thus, the co-presence of NCOA7 and the Trp metabolite 3-HAA can selectively enhance the activation of ubiquitary AhR in cDCs and consequent immunoregulatory effects. Because NCOA7 is often overexpressed and/or mutated in tumor microenvironments, our current data may provide evidence for a new immune check-point mechanism based on Trp metabolism and AhR