Polarization and kinematics in Cygnus A

From optical spectropolarimetry of Cygnus A we conclude that the scattering medium in the ionization cones in Cygnus A is moving outward at a speed of 170+-34 km/s, and that the required momentum can be supplied by the radiation pressure of an average quasar. Such a process could produce a structure resembling the observed ionization cones, which are thought to result from shadowing by a circumnuclear dust torus. We detect a polarized red wing in the [O III] emission lines arising from the central kiloparsec of Cygnus A. This wing is consistent with line emission created close to the boundary of the broad-line region.Comment: 5 pages, accepted for publication in MNRAS letter

Gene-modified T cells for adoptive immunotherapy of renal cell cancer maintain transgene-specific immune functions in vivo

Abstract BACKGROUND: We have treated three patients with carboxy-anhydrase-IX (CAIX) positive metastatic renal cell cancer (RCC) by adoptive transfer of autologous T-cells that had been gene-transduced to express a single-chain antibody-G250 chimeric receptor [scFv(G250)], and encountered liver toxicity necessitating adaptation of the treatment protocol. Here, we investigate whether or not the in vivo activity of the infused scFv(G250)(+) T cells is reflected by changes of selected immune parameters measured in peripheral blood. METHODS: ScFv(G250)-chimeric receptor-mediated functions of peripheral blood mononuclear cells (PBMC) obtained from three patients during and after treatment were compared to the same functions of scFv(G250)(+) T lymphocytes prior to infusion, and were correlated with plasma cytokine levels. RESULTS: Prior to infusion, scFv(G250)(+) T lymphocytes showed in vitro high levels of scFv(G250)-chimeric receptor-mediated functions such as killing of CAIX(+) RCC cell lines and cytokine production upon exposure to these cells. High levels of IFN-gamma were produced, whilst production of TNF-alpha, interleukin-4 (IL-4), IL-5 and IL-10 was variable and to lower levels, and that of IL-2 virtually absent. PBMC taken from patients during therapy showed lower levels of in vitro scFv(G250)-receptor-mediated functions as compared to pre-infusion, whilst IFN-gamma was the only detectable cytokine upon in vitro PBMC exposure to CAIX. During treatment, plasma levels of IFN-gamma increased only in the patient with the most prominent liver toxicity. IL-5 plasma levels increased transiently during treatment in all patients, which may have been triggered by the co-administration of IL-2. CONCLUSION: ScFv(G250)-receptor-mediated functions of the scFv(G250)(+) T lymphocytes are, by and large, preserved in vivo upon administration, and may be reflected by fluctuations in plasma IFN-gamma levels

The Missing Luminous Blue Variables and the Bistability Jump

We discuss an interesting feature of the distribution of luminous blue variables on the H-R diagram, and we propose a connection with the bistability jump in the winds of early-type supergiants. There appears to be a deficiency of quiescent LBVs on the S Dor instability strip at luminosities between log L/Lsun = 5.6 and 5.8. The upper boundary, is also where the temperature-dependent S Dor instability strip intersects the bistability jump at about 21,000 K. Due to increased opacity, winds of early-type supergiants are slower and denser on the cool side of the bistability jump, and we postulate that this may trigger optically-thick winds that inhibit quiescent LBVs from residing there. We conduct numerical simulations of radiation-driven winds for a range of temperatures, masses, and velocity laws at log L/Lsun=5.7 to see what effect the bistability jump should have. We find that for relatively low stellar masses the increase in wind density at the bistability jump leads to the formation of a modest to strong pseudo photosphere -- enough to make an early B-type star appear as a yellow hypergiant. Thus, the proposed mechanism will be most relevant for LBVs that are post-red supergiants. Yellow hypergiants like IRC+10420 and rho Cas occupy the same luminosity range as the ``missing'' LBVs, and show apparent temperature variations at constant luminosity. If these yellow hypergiants do eventually become Wolf-Rayet stars, we speculate that they may skip the normal LBV phase, at least as far as their apparent positions on the HR diagram are concerned.Comment: 20 pages, 4 figs, accepted by Ap

Pessary treatment for pelvic organ prolapse and health-related quality of life: a review

Pessaries have been used to treat women with pelvic organ prolapse (POP) since the beginning of recorded history. This review aims to assess the effect of pessary treatment on the disease-specific, health-related quality of life in women with pelvic organ prolapse. After a Medline search using the Mesh term ‘pessary’ and critical appraisal, 41 articles were selected and used in this review. Pessaries are widely used to treat pelvic organ prolapse. It is minimally invasive and appears to be safe. Although there is evidence that the use of pessaries in the treatment of pelvic organ prolapse is effective in alleviating symptoms and that patient satisfaction is high, the follow-up in many published papers is short, and the use of validated urogynaecological questionnaires is limited. Comparison with surgical treatment of pelvic organ prolapse is rare and not assessed in a randomised controlled trial

Translocation and de novo synthesis of eicosapentaenoic acid (EPA) during nitrogen starvation in Nannochloropsis gaditana

The microalga Nannochloropsis gaditana is known for accumulating fatty acids, including the commercially interesting eicosapentaenoic acid (EPA) within the polar lipids (PL) and neutral lipids (NL). During microalgal growth EPA is mainly present in the PL. Upon nitrogen starvation N. gaditana accumulates large amounts of TAG in lipid bodies. The neutral lipid fraction will mainly consist of triacylglycerol (TAG). When expressed per total cell dry weight, the NL-localized EPA increased while the PL-localized EPA decreased, suggesting that EPA is translocated from the PL into the NL lipids during nitrogen starvation. Here, we elucidated the origin of EPA in NL of N. gaditana by firstly growing this microalga under optimal growth conditions with 13CO2 as the sole carbon source followed by nitrogen starvation with 12CO2 as the sole carbon source. By measuring both 12C and 13C fatty acid isotope species in time, the de novo synthesized fatty acids and the already present fatty acids can be distinguished. For the first time, we proved that actual translocation of EPA from the PL into the NL occurs during nitrogen starvation of N. gaditana. Next to being translocated, EPA was synthesized de novo in both PL and NL during nitrogen starvation. EPA was made by carbon reshuffling within the cell as well. EPA was the main fatty acid translocated, suggesting that the enzyme responsible for fatty acid translocation has a high specificity for EPA.publishedVersio

T Cell Maturation Stage Prior to and During GMP Processing Informs on CAR T Cell Expansion in Patients

textabstractAutologous T cells were genetically modified to express a chimeric antigen receptor (CAR) directed toward carboxy-anhydrase-IX (CAIX) and used to treat patients with CAIX-positive metastatic renal cell carcinoma. In this study, we questioned whether the T cell maturation stage in the pre-infusion product affected CAIX CAR expression and function in vitro as well as in vivo CAR T cell numbers and expansion. During the 14 days expansion of CAR T cells prior to administration, we observed shifts from a predominant CD4 to a CD8 T cell phenotype and from a significant fraction of naïve to central effector T cells. Surface expression of the CAR was equally distributed among different T cell subsets and T cell maturation stages. During T cell culture days 14-18 (which covered patient treatment days 1-5), T cells demonstrated a decline in CAR expression level per cell irrespective of T cell maturation stage, although the proportion of CAR-positive T cells and CAR-mediated T cell effector functions remained similar for both CD4 and CD8 T cell populations. Notably, patients with a higher fraction of naïve CD8 T cells at baseline (prior to genetic modification) or central effector CD8 T cells at 2 weeks of CAR T cell culture demonstrated a higher fold expansion and absolute numbers of circulating CAR T cells at 1 month after start of therapy. We conclude that the T cell maturation stage prior to and during CAR T cell expansion culture is related to in vivo CAR T cell expansion

Numerical Modeling of Eta Carinae Bipolar Outflows

In this paper, we present two-dimensional gas dynamic simulations of the formation and evolution of the eta-Car bipolar outflows. Adopting the interacting nonspherical winds model, we have carried out high-resolution numerical simulations, which include explicitly computed time-dependent radiative cooling, for different possible scenarios of the colliding winds. In our simulations, we consider different degrees of non-spherical symmetry for the pre-outburst wind and the great eruption of the 1840s presented by the eta-Car wind. From these models, we obtain important differences in the shape and kinematical properties of the Homunculus structure. In particular, we find an appropriate combination of the wind parameters (that control the degree of non-spherical symmetry) and obtain numerical experiments that best match both the observed morphology and the expansion velocity of the eta-Car bipolar shell. In addition, our numerical simulations show the formation of a bipolar nebula embedded within the Homunculus (the little Homunculus) developed from a secondary eruptive event suffered by the star in the 1890s, and also the development of tenuous, high velocity ejections in the equatorial region that result from the impact of the eruptive wind of the 1840s with the pre-outburst wind and that could explain some of the high speed features observed in the equatorial ejecta. The models were, however, unable to produce equatorial ejections associated to the second eruptive event.Comment: 33 pages, 9 figures, accepted by the Astrophysical Journa

A study of the expanding envelope of Nova V1974 Cyg 1992 based on IUE high resolution spectroscopy

We have carried out a detailed analysis of the IUE archival high resolution spectra of the classical nova V1974 Cyg 1992. In addition to the P Cygni and emission lines, two shortward shifted absorption systems are present. Evidence is given that these absorptions originate in two separate expanding shells, outside the wind layers where the emission lines are formed. The outer main shell, containing most of the matter ejected at outburst, produces the so-called ``principal absorption line system'', and the inner faster moving second shell produces the so-called ``diffuse--enhanced absorption line system''. The outflow velocity of the two shells increases exponentially with time reaching a value of about 1750 km/s and 2900 km/s, respectively. We suggest that the acceleration of the shells is the result of increasing line-radiation pressure due to the UV-brightening of the star as the effective radius decreases. Around day 60 the second shell has overtaken the slower moving principal system shell, and merged with it. This explains: the sudden disappearance of the diffuse line system near that date, the upward jump of 240 km/s in velocity of the principal system and the first detection of hard X-ray emission on day 63. This velocity jump indicates that the main shell is about 4 times more massive than the second shell. The deceleration suffered by the diffuse-enhanced system after the shock provides a shock temperature of about 1.6 KeV, in fairly good agreement with the temperature of the observed hard X-ray emission.Comment: 19 pages, 11 figure

The Baltimore and Utrecht models for cluster dissolution

The analysis of the age distributions of star cluster samples of different galaxies has resulted in two very different empirical models for the dissolution of star clusters: the Baltimore model and the Utrecht model. I describe these two models and their differences. The Baltimore model implies that the dissolution of star clusters is mass independent and that about 90% of the clusters are destroyed each age dex, up to an age of about a Gyr, after which point mass-dependent dissolution from two-body relaxation becomes the dominant mechanism. In the Utrecht model, cluster dissolution occurs in three stages: (i) mass-independent infant mortality due to the expulsion of gas up to about 10 Myr; (ii) a phase of slow dynamical evolution with strong evolutionary fading of the clusters lasting up to about a Gyr; and (iii) a phase dominated by mass dependent-dissolution, as predicted by dynamical models. I describe the cluster age distributions for mass-limited and magnitude-limited cluster samples for both models. I refrain from judging the correctness of these models.Comment: 3 pages, 1 figure, to appear in "Young Massive Star Clusters - Initial Conditions and Environment", 2008, Astrophysics and Space Science, Eds. E. Perez, R. de Grijs and R.M. Gonzalez Delgad

Starvation Induces Phase-Specific Changes in the Proteome of Mouse Small Intestine

Food deprivation results in metabolic, structural, and functional changes in the small intestine that influences gut mucosal integrity, epithelial cell proliferation, mucin synthesis, and other processes. The underlying mechanisms are still unclear, which lead to the study of molecular effects of short-term and long-term starvation in the intestine of mice. A comparative proteomics approach, combining two-dimensional gel electrophoresis with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, was used to identify intestinal proteins whose expression is changed under different starvation conditions (0, 12, 24, and 72 h). In total, the expression levels of 80 protein spots changed significantly between the different groups. The results demonstrate that after 12 h of starvation, mainly proteins involved in glycolysis and energy metabolism show decreased expression levels. Starvation for 24 h results in a down-regulation of proteins involved in protein synthesis and amino acid metabolism. Simultaneously, proteins with a protective role, e.g., reg I and II, glutathione peroxidase 3, and carbonic anhydrase 3, are clearly up-regulated. The last starvation phase (72 h) is characterized by increased ezrin expression, which may enhance villus morphogenesis critical for survival. Together, these results provide novel insights in the intestinal starvation response and may contribute to improved nutritional support during conditions characterized by malnutrition