Complement Activation Determines the Therapeutic Activity of Rituximab In Vivo

Rituximab is an anti-CD20 chimeric mAb effective for the treatment of B-NHL. It can lyse lymphoma cells in vitro through both C- and Ab-dependent cellular cytotoxicity. The mechanism of action of rituximab in vivo is however still unclear. We have set up a new in vivo model in nonimmunodeficient mice by stable transduction of the human CD20 cDNA in the murine lymphoma line EL4. Animals injected i.v. with the EL4-CD20+ lymphoma cells died within 30 days with evident liver, spleen, and bone marrow involvement, confirmed by immunohistochemistry and PCR analysis. A single injection of rituximab or the murine anti-CD20 Ab 1F5, given i.p. 1 day after the tumor, cured 100% of the animals. Indeed, at week 4 after tumor cell inoculation, CD20+ cells were undetectable in all organs analyzed in rituximab-treated animals, as determined by immunohistochemistry and PCR. Rituximab had no direct effect on tumor growth in vitro. Depletion of either NK cells or neutrophils or both in tumor-injected animals did not affect the therapeutic activity of the drug. Similarly, rituximab was able to eradicate tumor cells in athymic nude mice, suggesting that its activity is T cell independent. In contrast, the protective activity of rituximab or the 1F5 Ab was completely abolished in syngeneic knockout animals lacking C1q, the first component of the classical pathway of C (C1qa−/−). These data demonstrate that C activation is fundamental for rituximab therapeutic activity in vivo

Time-domain Study of the Young Massive Cluster Westerlund 2 with the Hubble Space Telescope. I

Time-domain studies of pre-main-sequence (PMS) stars have long been used to investigate star properties during their early evolutionary phases and to trace the evolution of circumstellar environments. Historically these studies have been confined to the nearest, low-density, star-forming regions. We used the Wide Field Camera 3 on board the Hubble Space Telescope to extend, for the first time, the study of PMS variability to one of the few young massive clusters in the Milky Way, Westerlund 2. Our analysis reveals that at least one-third of the intermediate- and low-mass PMS stars in Westerlund 2 are variable. Based on the characteristics of their light curves, we classified ~11% of the variable stars as weak-line T Tauri candidates, ~52% as classical T Tauri candidates, ~5% as dippers, and ~26% as bursters. In addition, we found that 2% of the stars below 6 M ⊙ (~6% of the variables) are eclipsing binaries, with orbital periods shorter than 80 days. The spatial distribution of the different populations of variable PMS stars suggests that stellar feedback and UV radiation from massive stars play an important role in the evolution of circumstellar and planetary disks

Polarimetric Evidence of Non-Spherical Winds

Polarization observations yield otherwise unobtainable information about the geometrical structure of unresolved objects. In this talk we review the evidences for non-spherically symmetric structures around Luminous Hot Stars from polarimetry and what we can learn with this technique. Polarimetry has added a new dimension to the study of the envelopes of Luminous Blue Variables, Wolf-Rayet stars and B[e] stars, all of which are discussed in some detail.Comment: 8 pages, 2 encapsulated Postscript figures, uses lamuphys.sty. Invited review to appear in IAU Coll. 169, Variable and Non-Spherical Stellar Winds in Luminous Hot Stars, eds. B. Wolf, A.Fullerton and O. Stahl (Springer

MN112: a new Galactic candidate Luminous Blue Variable

We report the discovery of a new Galactic candidate Luminous Blue Variable (cLBV) via detection of an infrared circular nebula and follow-up spectroscopy of its central star. The nebula, MN112, is one of many dozens of circular nebulae detected at $24 \mu$m in the {\it Spitzer Space Telescope} archival data, whose morphology is similar to that of nebulae associated with known (c)LBVs and related evolved massive stars. Specifically, the core-halo morphology of MN112 bears a striking resemblance to the circumstellar nebula associated with the Galactic cLBV GAL 079.29+00.46, which suggests that both nebulae might have a similar origin and that the central star of MN112 is a LBV. The spectroscopy of the central star showed that its spectrum is almost identical to that of the bona fide LBV P Cygni, which also supports the LBV classification of the object. To further constrain the nature of MN112, we searched for signatures of possible high-amplitude (\ga 1 mag) photometric variability of the central star using archival and newly obtained photometric data covering a 45 year period. We found that the B magnitude of the star was constant ($\simeq$ 17.1$\pm$0.3 mag) over this period, while in the I band the star brightened by $\simeq 0.4$ mag during the last 17 years. Although the non-detection of large photometric variability leads us to use the prefix `candidate' in the classification of MN112, we remind that the long-term photometric stability is not unusual for genuine LBVs and that the brightness of P Cygni remains relatively stable during the last three centuries.Comment: 6 pages, 3 figures, accepted to MNRA

Spitzer Sage Survey of the Large Magellanic Cloud. III. Star Formation and ~1000 New Candidate Young Stellar Objects

We present ~1000 new candidate Young Stellar Objects (YSOs) in the Large Magellanic Cloud selected from Spitzer Space Telescope data, as part of the Surveying the Agents of a Galaxy's Evolution (SAGE) Legacy program. The YSOs, detected by their excess infrared (IR) emission, represent early stages of evolution, still surrounded by disks and/or infalling envelopes. Previously, fewer than 20 such YSOs were known. The candidate YSOs were selected from the SAGE Point Source Catalog from regions of color-magnitude space least confused with other IR-bright populations. The YSOs are biased toward intermediate- to high-mass and young evolutionary stages, because these overlap less with galaxies and evolved stars in color-magnitude space. The YSOs are highly correlated spatially with atomic and molecular gas, and are preferentially located in the shells and bubbles created by massive stars inside. They are more clustered than generic point sources, as expected if star formation occurs in filamentary clouds or shells. We applied a more stringent color-magnitude selection to produce a subset of "high-probability" YSO candidates. We fitted the spectral-energy distributions (SEDs) of this subset and derived physical properties for those that were well fitted. The total mass of these well-fitted YSOs is ~2900 M_☉ and the total luminosity is ~2.1 × 10^6 L_☉ . By extrapolating the mass function with a standard initial mass function and integrating, we calculate a current star-formation rate of ~0.06 M_☉ yr^(–1), which is at the low end of estimates based on total ultraviolet and IR flux from the galaxy (~0.05 – 0.25 M_☉ yr^(–1)), consistent with the expectation that our current YSO list is incomplete. Follow-up spectroscopy and further data mining will better separate the different IR-bright populations and likely increase the estimated number of YSOs. The full YSO list is available as electronic tables, and the SEDs are available as an electronic figure for further use by the scientific community

Spitzer SAGE survey of the Large Magellanic Cloud II: Evolved Stars and Infrared Color Magnitude Diagrams

Color-magnitude diagrams (CMDs) are presented for the Spitzer SAGE (Surveying the Agents of a Galaxy's Evolution) survey of the Large Magellanic Cloud (LMC). IRAC and MIPS 24 um epoch one data are presented. These data represent the deepest, widest mid-infrared CMDs of their kind ever produced in the LMC. Combined with the 2MASS survey, the diagrams are used to delineate the evolved stellar populations in the Large Magellanic Cloud as well as Galactic foreground and extragalactic background populations. Some 32000 evolved stars brighter than the tip of the red giant branch are identified. Of these, approximately 17500 are classified as oxygen-rich, 7000 carbon-rich, and another 1200 as ``extreme'' asymptotic giant branch (AGB) stars. Brighter members of the latter group have been called ``obscured'' AGB stars in the literature owing to their dusty circumstellar envelopes. A large number (1200) of luminous oxygen--rich AGB stars/M supergiants are also identified. Finally, there is strong evidence from the 24 um MIPS channel that previously unexplored, lower luminosity oxygen-rich AGB stars contribute significantly to the mass loss budget of the LMC (1200 such sources are identified).Comment: LaTex, 31 pages, 10 figures. Accepted for publication in the Astronomical Journa

A Spectroscopic Survey of WNL Stars in the LMC: General Properties and Binary Status

We report the results of an intense, spectroscopic survey of all 41 late-type, nitrogen-rich Wolf-Rayet (WR) stars in the Large Magellanic Cloud (LMC) observable with ground-based telescopes. This survey concludes the decade-long effort of the Montr\'eal Massive Star Group to monitor every known WR star in the Magellanic Clouds except for the 6 crowded WNL stars in R136, which will be discussed elsewhere. The focus of our survey was to monitor the so-called WNL stars for radial-velocity (RV) variability in order to identify the short- to intermediate-period (P \la 200 days) binaries among them. Our results are in line with results of previous studies of other WR subtypes, and show that the binary frequency among LMC WNL stars is statistically consistent with that of WNL stars in the Milky Way. We have identified four previously unknown binaries, bringing the total number of known WNL binaries in the LMC to nine. Since it is very likely that none but one of the binaries are classical, helium-burning WNL stars, but rather superluminous, hence extremely massive, hydrogen-burning objects, our study has dramatically increased the number of known binaries harbouring such objects, and thus paved the way to determine their masses through model-independent, Keplerian orbits. It is expected that some of the stars in our binaries will be among the most massive known. With the binary status of each WR star now known, we also studied the photometric and X-ray properties of our program stars using archival MACHO photometry as well as Chandra and ROSAT data. We find that one of our presumably single WNL stars is among the X-ray brightest WR sources known. We also identify a binary candidate from its RV variability and X-ray luminosity which harbours the most luminous WR star known in the Local Group.Comment: 25 pages, 11 figures; accepted for MNRA

STEP: the VST survey of the SMC and the Magellanic Bridge - I : Overview and first results

STEP (the SMC in Time: Evolution of a Prototype interacting late-type dwarf galaxy) is a Guaranteed Time Observation survey being performed at the VST (the ESO VLT Survey Telescope). STEP will image an area of 74 sq. deg. covering the main body of the Small Magellanic Cloud (32 sq. deg.), the Bridge that connects it to the Large Magellanic Cloud (30 sq. deg.) and a small part of the Magellanic Stream (2 sq. deg.). Our g, r, i, Hα photometry is able to resolve individual stars down to magnitudes well below the main-sequence turn-off of the oldest populations. In this first paper, we describe the observing strategy, the photometric techniques and the upcoming data products of the survey. We also present preliminary results for the first two fields for which data acquisition is completed, including some detailed analysis of the two stellar clusters IC 1624 and NGC 419.Peer reviewedFinal Accepted Versio