Atomic jet from SMM1 (FIRS1) in Serpens uncovers non-coeval binary companion

We report on the detection of an atomic jet associated with the protostellar source SMM1 (FIRS1) in Serpens. The jet is revealed in [FeII] and [NeII] line maps observed with Spitzer/IRS, and further confirmed in HiRes IRAC and MIPS images. It is traced very close to SMM1 and peaks at ~5 arcsec" from the source at a position angle of $\sim 125 degrees. In contrast, molecular hydrogen emission becomes prominent at distances > 5" from the protostar and extends at a position angle of 160 degrees. The morphological differences suggest that the atomic emission arises from a companion source, lying in the foreground of the envelope surrounding the embedded protostar SMM1. In addition the molecular and atomic Spitzer maps disentangle the large scale CO (3-2) emission observed in the region into two distinct bipolar outflows, giving further support to a proto-binary source setup. Analysis at the peaks of the [FeII] jet show that emission arises from warm and dense gas (T ~1000 K, n(electron) 10^5 - 10^6 cm^-3). The mass flux of the jet derived independently for the [FeII] and [NeII] lines is 10^7 M(sun)/yr, pointing to a more evolved Class~I/II protostar as the driving source. All existing evidence converge to the conclusion that SMM1 is a non-coeval proto-binary source.Comment: 10 pages, 7 figures, 1 table. Accepted for publication in Astronomy \& Astrophysic

Multitransitional observations of the CS core of L673

A multitransitional study with the BIMA interferometric array was carried out toward the starless core found in the L673 region, in order to study the small-size structure of the cores detected with previous single--dish observations, which provides us with a test of the predictions of the chemical model of Taylor et al. (1996; 1998). We detected emission in the CS (2-1), N2H+ (1-0), and HCO+ (1-0) lines. Several clumps of size ~0.08 pc were found for each line distributed all over the region where previous single-dish emission was found (Morata et al. 1997). Each molecular transition traces differently the clump distribution, although in some cases the detected clumps are coincident. The distribution of the N2H+ emission and the single-dish NH3 emission are coincident and compatible with an origin in the same gas. The large fraction of missing flux measured for the CS (2-1) transition can be explained if the cloud is formed by a clumpy and heterogeneous medium. Four positions were selected to derive the abundance ratios [N2H+/CS] and [HCO+/CS] from the molecular column density determinations, and to compare them with the values predicted by the chemical model. The model was able to explain the interferometric observations, and, in particular, the chemical differentiation of the detected clumps and the coincidence of the NH3 and N2H+ emissions. The lack of HCO+ towards the two selected positions that trace the more evolved clumps cannot be accounted for by the model, but it is possibly due to strong self-absorption. We propose a classification of the studied clumps according to the stage of chemical evolution indicated by the molecular abundances.Comment: 10 pages, 9 figures, accepted for publication in A&

Immunological efficacy of pneumococcal vaccine strategies in HIV-infected adults: a randomized clinical trial

The aim of this study was to compare the immunologic response to a prime-boost immunization strategy combining the 13-valent conjugate pneumococcal vaccine (PCV13) with the 23-valent polysaccharide pneumococcal vaccine (PPSV23) versus the PPSV23 alone in HIV-infected adults. HIV-infected adults were randomized to receive PCV13 at week 0 followed by PPSV23 at week 4 (n=31, prime-boost group) or PPSV23 alone at week 4 (n=33, PPSV23-alone group). Serotype specific IgG geometric mean concentration (GMC) and functional oposonophagocytic (OPA) geometric mean titer (GMT) were compared for 12 pneumococcal serotypes shared by both vaccines at week 8 and week 28. The prime-boost vaccine group were more likely to achieve a ≥2-fold increase in IgG GMC and a GMC \u3e1ug/ml at week 8 (odds ratio (OR) 2.00, 95% confidence interval (CI) 1.46–2.74, p\u3c0.01) and week 28 (OR 1.95, 95% CI 1.40–2.70, p\u3c0.01). Similarly, the prime-boost vaccine group were more likely to achieve a ≥4-fold increase in GMT at week 8 (OR 1.71, 95% CI 1.22–2.39, p\u3c0.01) and week 28 (OR 1.6, 95% CI 1.15–2.3, p\u3c0.01). This study adds to evidence supporting current pneumococcal vaccination recommendations combining the conjugate and polysaccharide pneumococcal vaccines in the United States and Europe for HIV-infected individuals

Evidence for transient clumps and gas chemical evolution in the CS core of L673

We present FCRAO maps as well as combined BIMA and FCRAO maps of the high density molecular emission towards the CS core in the L673 region. With the FCRAO telescope, we mapped the emission in the CS(2-1), C34S(2-1), HCO+(1-0), and H13CO+(1-0) lines. The high density molecular emission, which arises from a filamentary structure oriented in the NW-SE direction, shows clear morphological differences for each molecule. We find that HCO+ has an extremely high optical depth, and that the H13CO+ emission is well correlated with submm sources. The BIMA and FCRAO combined maps recover emission from a lot of other structure which was previously undetected or only marginally detected, and show an overall aspect of a filamentary structure connecting several intense clumps. We found a total 15 clumps in our combined data cube, all of them resolved by our angular resolution, with diameters in the 0.03-0.09 pc range. We find a clear segregation between the northern and southern region of the map: the northern section shows the less chemically evolved gas and less massive but more numerous clumps, while the southern region is dominated by the largest and most massive clump, and contains the more evolved gas, as traced by emission of late-time molecules. We find that the derived clump masses are below the virial mass, and that the clumps masses become closer to the virial mass when they get bigger and more massive. This supports the idea that these clumps must be transient, and only the more massive ones have a chance to last long enough to form stars. The clumps we detect are probably in an earlier evolutionary stage than the ``starless cores'' reported recently in the literature. Only the most massive one has properties similar to a ``starless core''.Comment: 12 pages, 8 figures, accepted for publication in Astronomy & Astrophysics; minor revisions after language editin

OH emission from warm and dense gas in the Orion Bar PDR

As part of a far-infrared (FIR) spectral scan with Herschel/PACS, we present the first detection of the hydroxyl radical (OH) towards the Orion Bar photodissociation region (PDR). Five OH rotational Lambda-doublets involving energy levels out to E_u/k~511 K have been detected (at ~65, ~79, ~84, ~119 and ~163um). The total intensity of the OH lines is I(OH)~5x10^-4 erg s^-1 cm^-2 sr^-1. The observed emission of rotationally excited OH lines is extended and correlates well with the high-J CO and CH^+ J=3-2 line emission (but apparently not with water vapour), pointing towards a common origin. Nonlocal, non-LTE radiative transfer models including excitation by the ambient FIR radiation field suggest that OH arises in a small filling factor component of warm (Tk~160-220 K) and dense (n_H~10^{6-7} cm^-3) gas with source-averaged OH column densities of ~10^15 cm^-2. High density and temperature photochemical models predict such enhanced OH columns at low depths (A_V<1) and small spatial scales (~10^15 cm), where OH formation is driven by gas-phase endothermic reactions of atomic oxygen with molecular hydrogen. We interpret the extended OH emission as coming from unresolved structures exposed to far-ultraviolet (FUV) radiation near the Bar edge (photoevaporating clumps or filaments) and not from the lower density "interclump" medium. Photodissociation leads to OH/H2O abundance ratios (>1) much higher than those expected in equally warm regions without enhanced FUV radiation fields.Comment: Accepted for publication in A&A Letters. Figure B.2. is bitmapped to lower resolutio

Water and ammonia abundances in S140 with the Odin satellite

We have used the Odin satellite to obtain strip maps of the ground-state rotational transitions of ortho-water and ortho-ammonia, as well as CO(5-4) and 13CO(5-4) across the PDR, and H218O in the central position. A physi-chemical inhomogeneous PDR model was used to compute the temperature and abundance distributions for water, ammonia and CO. A multi-zone escape probability method then calculated the level populations and intensity distributions. These results are compared to a homogeneous model computed with an enhanced version of the RADEX code. H2O, NH3 and 13CO show emission from an extended PDR with a narrow line width of ~3 kms. Like CO, the water line profile is dominated by outflow emission, however, mainly in the red wing. The PDR model suggests that the water emission mainly arises from the surfaces of optically thick, high density clumps with n(H2)>10^6 cm^-3 and a clump water abundance, with respect to H2, of 5x10^-8. The mean water abundance in the PDR is 5x10^-9, and between ~2x10^-8 -- 2x10^-7 in the outflow derived from a simple two-level approximation. Ammonia is also observed in the extended clumpy PDR, likely from the same high density and warm clumps as water. The average ammonia abundance is about the same as for water: 4x10^-9 and 8x10^-9 given by the PDR model and RADEX, respectively. The similarity of water and ammonia PDR emission is also seen in the almost identical line profiles observed close to the bright rim. Around the central position, ammonia also shows some outflow emission although weaker than water in the red wing. Predictions of the H2O(110-101) and (111-000) antenna temperatures across the PDR are estimated with our PDR model for the forthcoming observations with the Herschel Space Observatory.Comment: 13 pages, 14 figures, 10 tables. Accepted for publication in Astronomy & Astrophysics 14 November 200

Airway inflammatory markers in individuals with cystic fibrosis and non-cystic fibrosis bronchiectasis.

Bronchiectasis is an airway disease characterized by thickening of the bronchial wall, chronic inflammation , and destruction of affected bronchi. Underlying etiologies include severe pulmonary infection and cystic fibrosis (CF); however, in a substantial number of patients with non-CF-related bronchiectasis (NCFB), no cause is found. The increasing armamentarium of therapies now available to combat disease in CF is in stark contrast to the limited tools employed in NCFB. Our study aimed to evaluate similarities and differences in airway inflammatory markers in patients with NCFB and CF, and to suggest potential common treatment options. The results of this study show that NCFB bronchoalveolar lavage fluid samples possessed significantly increased NE activity and elevated levels of matrix metalloproteinases 2 (MMP-2) and MMP-9 compared to healthy controls (P \u3c 0.01); however, the levels detected were lower than in CF (P \u3c 0.01). Interleukin-8 (IL-8) concentrations were significantly elevated in NCFB and CF compared to controls (P \u3c 0.05), but in contrast, negligible levels of IL-18 were detected in both NCFB and CF. Analogous concentrations of IL-10 and IL-4 measured in NCFB and CF were statistically elevated above the healthy control values (P \u3c 0.05 and P \u3c 0.01, respectively). These results indicate high levels of important proinflammatory markers in both NCFB and CF and support the use of appropriate anti-inflammatory therapies already employed in the treatment of CF bronchiectasis in NCFB

Young starless cores embedded in the magnetically dominated Pipe Nebula

The Pipe Nebula is a massive, nearby dark molecular cloud with a low star-formation efficiency which makes it a good laboratory to study the very early stages of the star formation process. The Pipe Nebula is largely filamentary, and appears to be threaded by a uniform magnetic field at scales of few parsecs, perpendicular to its main axis. The field is only locally perturbed in a few regions, such as the only active cluster forming core B59. The aim of this study is to investigate primordial conditions in low-mass pre-stellar cores and how they relate to the local magnetic field in the cloud. We used the IRAM 30-m telescope to carry out a continuum and molecular survey at 3 and 1 mm of early- and late-time molecules toward four selected starless cores inside the Pipe Nebula. We found that the dust continuum emission maps trace better the densest regions than previous 2MASS extinction maps, while 2MASS extinction maps trace better the diffuse gas. The properties of the cores derived from dust emission show average radii of ~0.09 pc, densities of ~1.3x10^5 cm^-3, and core masses of ~2.5 M_sun. Our results confirm that the Pipe Nebula starless cores studied are in a very early evolutionary stage, and present a very young chemistry with different properties that allow us to propose an evolutionary sequence. All of the cores present early-time molecular emission, with CS detections toward all the sample. Two of them, Cores 40 and 109, present strong late-time molecular emission. There seems to be a correlation between the chemical evolutionary stage of the cores and the local magnetic properties that suggests that the evolution of the cores is ruled by a local competition between the magnetic energy and other mechanisms, such as turbulence.Comment: Accepted for publication in ApJ. 15 pages, 5 figures, 9 table

Synthesis, Evaluation and Structural Studies of Antiproliferative Tubulin-targeting Azetidin-2-ones

A series of azetidin-2-ones substituted at positions 2, 3 and 4 of the azetidinone ring scaffold were synthesised and evaluated for antiproliferative, cytotoxic and tubulin binding activity. In these compounds, the cis double bond of the vascular targeting agent combretastatin A-4 is replaced with the azetidinone ring in order to enhance the antiproliferative effects displayed by combretastatin A-4 and prevent the cis/trans isomerization that is associated with inactivation of combretastatin A-4. The series of azetidinones was synthetically accessible via the Staudinger and Reformatsky reactions. Of a diverse range of heterocyclic derivatives, 3-(2-thienyl) analogue 28 and 3-(3-thienyl) analogue 29 displayed the highest potency in human MCF-7 breast cancer cells with IC50 values of 7nM and 10nM respectively, comparable to combretastatin A-4. Compounds from this series also exhibited potent activity in MDA-MB-231 breast cancer cells and in the NCI60 cell line panel. No significant toxicity was observed in normal murine breast epithelial cells. The presence of larger, bulkier groups at the 3-position, for example 3-naphthyl derivative 21 and 3-benzothienyl derivative 26, resulted in relatively lower antiproliferative activity in the micromolar range. Tubulin-binding studies of 28 (IC50=1.37μM) confirmed that the molecular target of this series of compounds is tubulin. These novel 3-(thienyl) β-lactam antiproliferative agents are useful scaffolds for the development of tubulin-targeting drugs

The effect of the decoy molecule PA401 on CXCL8 levels in bronchoalveolar lavage fluid of patients with cystic fibrosis.

BACKGROUND: The chemokine interleukin-8 (CXCL8) is a key mediator of inflammation in airways of patients with cystic fibrosis (CF). Glycosaminoglycans (GAGs) possess the ability to influence the chemokine profile of the CF lung by binding CXCL8 and protecting it from proteolytic degradation. CXCL8 is maintained in an active state by this glycan interaction thus increasing infiltration of immune cells such as neutrophils into the lungs. As the CXCL8-based decoy PA401 displays no chemotactic activity, yet demonstrates glycan binding affinity, the aim of this study was to investigate the anti-inflammatory effect of PA401 on CXCL8 levels, and activity, in CF airway samples in vitro. METHODS: Bronchoalveolar lavage fluid (BALF) was collected from patients with CF homozygous for the ΔF508 mutation (n=13). CXCL8 in CF BALF pre and post exposure to PA401 was quantified by ELISA. Western blot analysis was used to determine PA401 degradation in CF BALF. The ex vivo chemotactic activity of purified neutrophils in response to CF airway secretions was evaluated post exposure to PA401 by use of a Boyden chamber-based motility assay. RESULTS: Exposure of CF BALF to increasing concentrations of PA401 (50-1000pg/ml) over a time course of 2-12h in vitro, significantly reduced the level of detectable CXCL8 (P CONCLUSION: PA401 can disrupt CXCL8:GAG complexes, rendering the chemokine susceptible to proteolytic degradation. Clinical application of a CXCL8 decoy, such as PA401, may serve to decrease the inflammatory burden in the CF lung in vivo