The essential signature of a massive starburst in a distant galaxy

Observations of carbon monoxide (CO) emission in high redshift (z>2) galaxies indicate the presence of large amounts of molecular gas. Many of these galaxies contain an active galactic nucleus (AGN) powered by accretion of gas onto a supermassive black hole, and a key question is whether their extremely high infrared luminosities result from the AGN, or from bursts of massive star formation (associated with the molecular gas), or both. In the Milky Way, high-mass stars form in the dense cores of interstellar molecular clouds; gas densities are n(H2)>105 cm-3 in the cores. Recent surveys show that virtually all galactic sites of high-mass star formation have similarly high densities. The bulk of the cloud material traced by CO observations is at a much lower density. In galaxies in the local Universe, the HCN(J=1-0) line is an effective tracer of the high-density molecular gas. Here we report observations of HCN emission in the early Universe from the infrared luminous 'Cloverleaf' quasar (at a redshift z=2.5579). The HCN line luminosity indicates the presence of 10 billion solar masses of very dense gas, an essential feature of an immense starburst that contributes, together with the AGN it harbors, to its high infrared luminosity.Comment: PDF pape

In vitro and in vivo gene transfer to pulmonary cells mediated by cationic liposomes

Cationic liposomes have been proposed as alternative to adenovirus in the treatment of cystic fibrosis lung disease. Therefore, we have investigated the efficiency of two lipid mixtures in mediating gene transfer in in vitro and in vivo models. The cationic lipid DOTMA (N-(1-(2,3(dioleyloxy)propyl)-n,n,n-trimethylammoniumchloride) and DOGS (dioctadecylamidoglycylspermine) were used in combination with the neutral lipid DOPE (dioleoylphosphatidylethanolamine). The relative transfection efficiencies of the two cationic liposomes were tested using the bacterial β-galactosidase (lacZ) and the firefly luciferase genes. Gene expression was detected in both cell lines and primary culture of rhesus monkey airway epithelium after transfection with plasmid DNA complexed with DOGS/DOPE or DOTMA/DOPE. Transfection efficiency of both types of lipids was higher in the mouse fibroblast 3T3 cell line as compared to human carcinoma A549 cells and primary epithelial cultures. Administration of DNA-liposome complexes via intratracheal instillation resulted in expression of the lacZ and luciferase marker gene in the mouse airways. In vivo transfection mediated by both types of liposomes were proven to be far less efficient than adenovirus treatment

Atomic carbon at redshift ~2.5

Using the IRAM 30m telescope we detected the lower fine structure line of neutral carbon towards three high--redshift sources: IRAS FSC10214 (z=2.3), SMMJ14011+0252 (z=2.5) and H1413+117 (Cloverleaf quasar, z=2.5). SMMJ14011+0252 is the first high--redshift, non--AGN source in which CI has been detected. The CI(1-0) line from FSC10214 is almost an order of magnitude weaker than previously claimed, while our detection in the Cloverleaf is in good agreement with earlier observations. The CI(1-0) linewidths are similar to the CO widths, indicating that both lines trace similar regions of molecular gas on galactic scales. Derived CI masses for all three objects are of order few 10^7 solar masses and the implied CI(1-0)/CO(3-2) line luminosity ratio is about 0.2. This number is similar to values found in local galaxies. We derive a CI abundance of 5x10^{-5} which implies significant metal enrichment of the cold molecular gas at redshifts 2.5 (age of the universe 2.7 Gyr). We conclude that the physical properties of systems at large lookback times are similar to today's starburst/AGN environments.Comment: 4 pages, 2 figures; accepted by A&

The Evolution of Interstellar Medium Mass Probed by Dust Emission: ALMA Observations at z = 0.3-2

The use of submillimeter dust continuum emission to probe the mass of interstellar dust and gas in galaxies is empirically calibrated using samples of local star-forming galaxies, Planck observations of the Milky Way, and high-redshift submillimeter galaxies. All of these objects suggest a similar calibration, strongly supporting the view that the Rayleigh-Jeans tail of the dust emission can be used as an accurate and very fast probe of the interstellar medium (ISM) in galaxies. We present ALMA Cycle 0 observations of the Band 7 (350 GHz) dust emission in 107 galaxies from z = 0.2 to 2.5. Three samples of galaxies with a total of 101 galaxies were stellar-mass-selected from COSMOS to have M* ≃ 10^(11) M☉: 37 at z ~ 0.4, 33 at z ~ 0.9, and 31 at z = 2. A fourth sample with six infrared-luminous galaxies at z = 2 was observed for comparison with the purely mass-selected samples. From the fluxes detected in the stacked images for each sample, we find that the ISM content has decreased by a factor ~6 from 1 to 2 × 10^(10) M☉ at both z = 2 and 0.9 down to ~2 × 10^9 M☉ at z = 0.4. The infrared-luminous sample at z = 2 shows a further ~4 times increase in M_(ISM) compared with the equivalent non-infrared-bright sample at the same redshift. The gas mass fractions are ~2% ± 0.5%, 12% ± 3%, 14% ± 2%, and 53% ± 3% for the four subsamples (z = 0.4, 0.9, and 2 and infrared-bright galaxies)

Isolated limb perfusion for local gene delivery: efficient and targeted adenovirus-mediated gene transfer into soft tissue sarcomas

OBJECTIVE: To evaluate the potential of isolated limb perfusion (ILP) for efficient and tumor-specific adenovirus-mediated gene transfer in sarcoma-bearing rats. SUMMARY BACKGROUND DATA: A major concern in adenovirus-mediated gene therapy in cancer is the transfer of genes to organs other than the tumor, especially organs with a rapid cell turnover. Adjustment of the vector delivery route might be an option creating tumor specificity in therapeutic gene expression. METHODS: Rat hind limb sarcomas (5-10 mm) were transfected with recombinant adenoviruses. Intratumoral luciferase expression after ILP was compared with systemic administration, regional infusion, or intratumoral injection using a similar dose of adenoviruses carrying the luciferase marker gene. Localization studies using lacZ as a marker gene were performed to evaluate the intratumoral distribution of transfected cells after both ILP and intratumoral injection. RESULTS: Intratumoral luciferase activity after ILP or intratumoral administration was significantly higher compared with regional infusion or systemic administration. After ILP, luciferase gene expression was minimal in extratumoral organs, whether outside or inside the isolated circuit. Localization studies demonstrated that transfection was confined to tumor cells lying along the needle track after intratumoral injection, whereas after ILP, lacZ expression was found in viable tumor cells and in the tumor-associated vasculature. CONCLUSIONS: Using ILP, efficient and tumor-specific gene transfection can be achieved. The ILP technique might be useful for the delivery of recombinant adenoviruses carrying therapeutic gene constructs to enhance tumor control

Melphalan 140mg/m2 or 200mg/m2 for autologous transplantation in myeloma: results from the Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study. A report by the EBMT Chronic Malignancies Working Party

Melphalan at a dose of 200mg/m2 is standard conditioning prior to autologous haematopoietic stem cell transplantation for multiple myeloma, but a dose of 140mg/m2 is often used in clinical practice in patients perceived to be at risk of excess toxicity. To determine if melphalan 200 and melphalan 140 are equally effective and tolerable in clinically relevant patient subgroups we analysed 1964 first single autologous transplantation episodes using a series of Cox proportional-hazards models. Overall survival, progression-free survival, cumulative incidence of relapse, non-relapse mortality, haematopoietic recovery and second primary malignancy rates were not significantly different between the melphalan 140 (n=245) and melphalan 200 (n=1719) groups. Multivariable subgroup analysis showed that disease status at transplantation interacted with overall survival, progression-free survival, and cumulative incidence of relapse, with a significant advantage associated with melphalan 200 in patients transplanted in less than partial response (adjusted hazard ratios for melphalan 200 versus melphalan 140: 0.5, 0.54, and 0.56). In contrast, transplantation in very good partial or complete response significantly favoured melphalan 140 for overall survival (adjusted hazard ratio: 2.02). Age, renal function, prior proteasome inhibitor treatment, gender, or Karnofsky score did not interact with overall/progression-free survival or relapse rate in the melphalan dose groups. There were no significant survival or relapse rate differences between melphalan 200 and melphalan 140 patients with high-risk or standard-risk chromosomal abnormalities. In conclusion, remission status at the time of transplantation may favour melphalan 200 or melphalan 140 for key transplant outcomes (NCT01362972)

Hydrogen-like nitrogen radio line from hot interstellar and warm-hot intergalactic gas

Hyperfine structure lines of highly-charged ions may open a new window in observations of hot rarefied astrophysical plasmas. In this paper we discuss spectral lines of isotopes and ions abundant at temperatures 10^5-10^7 K, characteristic for warm-hot intergalactic medium, hot interstellar medium, starburst galaxies, their superwinds and young supernova remnants. Observations of these lines will allow to study bulk and turbulent motions of the observed target and will broaden the information about the gas ionization state, chemical and isotopic composition. The most prospective is the line of the major nitrogen isotope having wavelength 5.65 mm (Sunyaev and Churazov 1084). Wavelength of this line is well-suited for observation of objects at z=0.15-0.6 when it is redshifted to 6.5-9 mm spectral band widely-used in ground-based radio observations, and, for example, for z>=1.3, when the line can be observed in 1.3 cm band and at lower frequencies. Modern and future radio telescopes and interferometers are able to observe the absorption by 14-N VII in the warm-hot intergalactic medium at redshifts above z=0.15 in spectra of brightest mm-band sources. Sub-millimeter emission lines of several most abundant isotopes having hyperfine splitting might also be detected in spectra of young supernova remnants.Comment: 12 pages, 5 figures, accepted by Astronomy Letters; v3: details added; error fixe

PIP5KIβ Selectively Modulates Apical Endocytosis in Polarized Renal Epithelial Cells

Localized synthesis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] at clathrin coated pits (CCPs) is crucial for the recruitment of adaptors and other components of the internalization machinery, as well as for regulating actin dynamics during endocytosis. PtdIns(4,5)P2 is synthesized from phosphatidylinositol 4-phosphate by any of three phosphatidylinositol 5-kinase type I (PIP5KI) isoforms (α, β or γ). PIP5KIβ localizes almost exclusively to the apical surface in polarized mouse cortical collecting duct cells, whereas the other isoforms have a less polarized membrane distribution. We therefore investigated the role of PIP5KI isoforms in endocytosis at the apical and basolateral domains. Endocytosis at the apical surface is known to occur more slowly than at the basolateral surface. Apical endocytosis was selectively stimulated by overexpression of PIP5KIβ whereas the other isoforms had no effect on either apical or basolateral internalization. We found no difference in the affinity for PtdIns(4,5)P2-containing liposomes of the PtdIns(4,5)P2 binding domains of epsin and Dab2, consistent with a generic effect of elevated PtdIns(4,5)P2 on apical endocytosis. Additionally, using apical total internal reflection fluorescence imaging and electron microscopy we found that cells overexpressing PIP5KIβ have fewer apical CCPs but more internalized coated structures than control cells, consistent with enhanced maturation of apical CCPs. Together, our results suggest that synthesis of PtdIns(4,5)P2 mediated by PIP5KIβ is rate limiting for apical but not basolateral endocytosis in polarized kidney cells. PtdIns(4,5)P2 may be required to overcome specific structural constraints that limit the efficiency of apical endocytosis. © 2013 Szalinski et al