T-cell modulation for the treatment of chronic plaque psoriasis with efalizumab (Raptiva (TM)): Mechanisms of action

Psoriasis is a chronic, incurable, auto-immune disorder with cutaneous manifestations. New evidence on the central role of the immune system in the pathogenesis of psoriasis increasingly provides insight into pathogenic steps that can be modulated to provide disease control. Numerous biological therapies are in various stages of clinical development, with expectation of providing enhanced safety and efficacy over currently available psoriasis therapies. Efalizumab, a recombinant humanized monoclonal IgG1 antibody, is a novel targeted T-cell modulator that inhibits multiple steps in the immune cascade that result in the production and maintenance of psoriatic plaques, including initial T-cell activation and T-cell trafficking into sites of inflammation, including psoriatic skin, with subsequent reactivation in these sites. This article reviews the pharmacodynamic, pharmacokinetic and clinical effects observed during phase I, II and III efalizumab trials in patients with moderate to severe chronic plaque psoriasis. Copyright (C) 2004 S. Karger AG, Basel

The Onset of Planet Formation in Brown Dwarf Disks

The onset of planet formation in protoplanetary disks is marked by the growth and crystallization of sub-micron-sized dust grains accompanied by dust settling toward the disk mid-plane. Here we present infrared spectra of disks around brown dwarfs and brown dwarf candidates. We show that all three processes occur in such cool disks in a way similar or identical to that in disks around low- and intermediate-mass stars. These results indicate that the onset of planet formation extends to disks around brown dwarfs, suggesting that planet formation is a robust process occurring in most young circumstellar disks.Comment: Published in Science 2005, vol 310, 834; 3 pages in final format, 4 figures + 8 pages Supporting Online Material. For final typeset, see http://www.sciencemag.org/cgi/content/abstract/310/5749/834?eto

The effect of local optically thick regions in the long-wave emission of young circumstellar disks

Multi-wavelength observations of protoplanetary disks in the sub-millimeter continuum have measured spectral indices values which are significantly lower than what is found in the diffuse interstellar medium. Under the assumption that mm-wave emission of disks is mostly optically thin, these data have been generally interpreted as evidence for the presence of mm/cm-sized pebbles in the disk outer regions. In this work we investigate the effect of possible local optically thick regions on the mm-wave emission of protoplanetary disks without mm/cm-sized grains. A significant local increase of the optical depth in the disk can be caused by the concentration of solid particles, as predicted to result from a variety of proposed physical mechanisms. We calculate the filling factors and implied overdensities these optically thick regions would need to significantly affect the millimeter fluxes of disks, and we discuss their plausibility. We find that optically thick regions characterized by relatively small filling factors can reproduce the mm-data of young disks without requesting emission from mm/cm-sized pebbles. However, these optically thick regions require dust overdensities much larger than what predicted by any of the physical processes proposed in the literature to drive the concentration of solids. We find that only for the most massive disks it is possible and plausible to imagine that the presence of optically thick regions in the disk is responsible for the low measured values of the mm spectral index. For the majority of the disk population, optically thin emission from a population of large mm-sized grains remains the most plausible explanation. The results of this analysis further strengthen the scenario for which the measured low spectral indices of protoplanetary disks at mm wavelengths are due to the presence of large mm/cm-sized pebbles in the disk outer regions.Comment: 13 pages, 2 figures, A&A in pres

Connection between jets, winds and accretion in T Tauri stars: the X-shooter view

We have analysed the [OI]6300 A line in a sample of 131 young stars with discs in the Lupus, Chamaeleon and signa Orionis star forming regions, observed with the X-shooter spectrograph at VLT. The stars have mass accretion rates spanning from 10^{-12} to 10^{-7} Mo/yr. The line profile was deconvolved into a low velocity component (LVC, 40 km/s ), originating from slow winds and high velocity jets, respectively. The LVC is by far the most frequent component, with a detection rate of 77%, while only 30% of sources have a HVC. The [OI]6300 luminosity of both the LVC and HVC, when detected, correlates with stellar and accretion parameters of the central sources (i.e. Lstar , Mstar , Lacc , Macc), with similar slopes for the two components. The line luminosity correlates better with the accretion luminosity than with the stellar luminosity or stellar mass. We suggest that accretion is the main drivers for the line excitation and that MHD disc-winds are at the origin of both components. In the sub-sample of Lupus sources observed with ALMA a relationship is found between the HVC peak velocity and the outer disc inclination angle, as expected if the HVC traces jets ejected perpendicularly to the disc plane. Mass loss rates measured from the HVC span from ~ 10^{-13} to ~10^{-7} Mo/yr. The corresponding Mloss/Macc ratio ranges from ~0.01 to ~0.5, with an average value of 0.07. However, considering the upper limits on the HVC, we infer a ratio < 0.03 in more than 40% of sources. We argue that most of these sources might lack the physical conditions needed for an efficient magneto-centrifugal acceleration in the star-disc interaction region. Systematic observations of populations of younger stars, that is, class 0/I, are needed to explore how the frequency and role of jets evolve during the pre-main sequence phase.Comment: 15 pages, 14 figures, Accepted for publication in A&

Grain growth and dust settling in a brown dwarf disk: Gemini/T-ReCS observations of CFHT-BD-Tau 4

We present accurate mid-infrared observations of the disk around the young, bona-fide brown dwarf CFHT-BD-Tau 4. We report GEMINI/T-ReCS measurements in the 7.9, 10.4 and 12.3 micron filters, from which we infer the presence of a prominent, broad silicate emission feature. The shape of the silicate feature is dominated by emission from 2 micron amorphous olivine grains. Such grains, being an order of magnitude larger than those in the interstellar medium, are a first proof of dust processing and grain growth in disks around brown dwarfs. The object's spectral energy distribution is below the prediction of the classical flared disk model but higher than that of the two-layer flat disk. A good match can be achieved by using an intermediate disk model with strongly reduced but non-zero flaring. Grain growth and dust settling processes provide a natural explanation for this disk geometry and we argue that such intermediate flaring might explain the observations of several other brown dwarf disks as well.Comment: Accepted for publication in Astronomy & Astrophysics Letters, 4.5 pages with 1 figur

Exploring the dimming event of RW Aur A through multi-epoch VLT/X-Shooter spectroscopy

RW Aur A is a CTTS that has suddenly undergone three major dimming events since 2010. We aim to understand the dimming properties, examine accretion variability, and derive the physical properties of the inner disc traced by the CO ro-vibrational emission at NIR wavelengths (2.3 mic). We compared two epochs of X-Shooter observations, during and after the dimming. We modelled the rarely detected CO bandhead emission in both epochs to examine whether the inner disc properties had changed. The SED was used to derive the extinction properties of the dimmed spectrum and compare the infrared excess between the two epochs. Lines tracing accretion were used to derive the mass accretion rate in both states. The CO originates from a region with physical properties of T=3000 K, N$_{CO}$=1x10$^{21}$ cm$^{-2}$ and vsini=113 km/s. The extinction properties of the dimming layer were derived with the effective optical depth ranging from teff 2.5-1.5 from the UV to the NIR. The inferred mass accretion rate Macc is $1.5x 10^{-8}$ Msun/yr and $\sim 2x 10^{-8}$ Msun/yr after and during the dimming respectively. By fitting the SED, additional emission is observed in the IR during the dimming event from dust grains with temperatures of 500-700K. The physical conditions traced by the CO are similar for both epochs, indicating that the inner gaseous disc properties do not change during the dimming events. The extinction curve is flatter than that of the ISM, and large grains of a few hundred microns are thus required. When we correct for the observed extinction, Macc is constant in the two epochs, suggesting that the accretion is stable and therefore does not cause the dimming. The additional hot emission in the NIR is located at about 0.5 au from the star. The dimming events could be due to a dust-laden wind, a severe puffing-up of the inner rim, or a perturbation caused by the recent star-disc encounter.Comment: Accepted by Astronomy & Astrophysic

X-Shooter study of accretion in Chamaeleon I: II. A steeper increase of accretion with stellar mass for very low mass stars?

The dependence of the mass accretion rate on the stellar properties is a key constraint for star formation and disk evolution studies. Here we present a study of a sample of stars in the Chamaeleon I star forming region carried out using the VLT/X-Shooter spectrograph. The sample is nearly complete down to M~0.1Msun for the young stars still harboring a disk in this region. We derive the stellar and accretion parameters using a self-consistent method to fit the broad-band flux-calibrated medium resolution spectrum. The correlation between the accretion luminosity to the stellar luminosity, and of the mass accretion rate to the stellar mass in the logarithmic plane yields slopes of 1.9 and 2.3, respectively. These slopes and the accretion rates are consistent with previous results in various star forming regions and with different theoretical frameworks. However, we find that a broken power-law fit, with a steeper slope for stellar luminosity smaller than ~0.45 Lsun and for stellar masses smaller than ~ 0.3 Msun, is slightly preferred according to different statistical tests, but the single power-law model is not excluded. The steeper relation for lower mass stars can be interpreted as a faster evolution in the past for accretion in disks around these objects, or as different accretion regimes in different stellar mass ranges. Finally, we find two regions on the mass accretion versus stellar mass plane empty of objects. One at high mass accretion rates and low stellar masses, which is related to the steeper dependence of the two parameters we derived. The second one is just above the observational limits imposed by chromospheric emission. This empty region is located at M~0.3-0.4Msun, typical masses where photoevaporation is known to be effective, and at mass accretion rates ~10^-10 Msun/yr, a value compatible with the one expected for photoevaporation to rapidly dissipate the inner disk.Comment: Accepted for publication on Astronomy & Astrophysics. Abstract shortened for arxiv constraints. Revised version after language editin

A reconsideration of disk properties in Herbig Ae stars

This paper presents state-of-the-art spectral energy distributions (SEDs) of four Herbig Ae stars, based in part on new data in the mid and far-infrared and at millimeter wavelengths. The SEDs are discussed in the context of circumstellar disk models. We show that models of irradiated disks provide a good fit to the observations over the whole range of wavelengths. We offer a possible solution to the long-standing puzzle caused by the excess emission of Herbig Ae stars, where a large fraction of the stellar luminosity is re-radiated between ~1.25 and 7 μm, with a peak at about 3 μm. We suggest that this general behaviour can be caused by dust evaporation in disks where the gas component is optically thin to the stellar radiation, as expected if the accretion rate is very low. The creation of a puffed-up inner wall of optically thick dust at the dust sublimation radius can account for the near-infrared characteristics of the SEDs. It can also naturally explain the H and K band interferometric observations of AB Aur (Millan-Gabet et al. [CITE]), which reveal a ring of emission of radius ~0.3 AU. Finally, irradiated disk models can easily explain the observed intensity of the 10 μm silicate features and their variation from star to star

A mid-infrared study of very low mass stars and brown dwarfs in Upper Scorpius

We report the results of mid-IR observations with VISIR at the VLT of 10 ultracool dwarfs members of the nearby Upper Scorpius OB association in four filters ranging between 8.59 (PAH1) to 12.8 $\mu$m (Ne II), and one brown dwarf with Spitzer between 3.6 and 24 $\mu$m. Seven of our targets are detected in at least one of the bands, and we derive upper limits on the fluxes of the remaining 4. These results combined with previous studies from the literature lead to an improved disk frequency of 50$\pm$12%. This frequency is significantly higher than that of accretors (16.3%$\pm$6.2%). Only one object showing mid-IR excess also has H$\alpha$ emission at a level indicating that it must be accreting. Four of the detected targets are multiple system candidates. The observed disk frequency for sub-stellar objects in the Upper Scorpius association is similar to that of stars, consistent with a common formation scenario. It is also similar to the disk fractions observed in younger clusters, suggesting that the disk lifetimes might be longer for ultracool dwarfs than for higher-mass stars.Comment: 10 pages, 4 figures, accepted for A&

Millimeter imaging of HD 163296: probing the disk structure and kinematics

We present new multi-wavelength millimeter interferometric observations of the Herbig Ae star HD 163296 obtained with the IRAM/PBI, SMA and VLA arrays both in continuum and in the 12CO, 13CO and C18O emission lines. Gas and dust properties have been obtained comparing the observations with self-consistent disk models for the dust and CO emission. The circumstellar disk is resolved both in the continuum and in CO. We find strong evidence that the circumstellar material is in Keplerian rotation around a central star of 2.6 Msun. The disk inclination with respect to the line of sight is 46+-4 deg with a position angle of 128+-4 deg. The slope of the dust opacity measured between 0.87 and 7 mm (beta=1) confirms the presence of mm/cm-size grains in the disk midplane. The dust continuum emission is asymmetric and confined inside a radius of 200 AU while the CO emission extends up to 540 AU. The comparison between dust and CO temperature indicates that CO is present only in the disk interior. Finally, we obtain an increasing depletion of CO isotopomers from 12CO to 13CO and C18O. We argue that these results support the idea that the disk of HD 163296 is strongly evolved. In particular, we suggest that there is a strong depletion of dust relative to gas outside 200 AU; this may be due to the inward migration of large bodies that form in the outer disk or to clearing of a large gap in the dust distribution by a low mass companion.Comment: Accepted for publication on A&A, 16 page