Tracing circumnuclear dense gas in H2O maser galaxies

A sample of 30 H2O extra-galactic maser galaxies with their published HCN(J=1-0) and HCO+(J=1-0) observations has been compiled to investigate the dense gas correlation with H2O maser emission. Our sample number exceeds the size of the previous HCN samples studied so far by a factor of three, and it is the first study on the possible relation with the dense gas tracer HCO+. We find a strong correlation between normalized H2O maser emission luminosity (LH2O\LCO) and normalized HCO+ line luminosity (LHCO+\LCO). Moreover, a weak correlation has been found between LH2O\LCO and normalized HCN line luminosity (LHCN\LCO). The sample is also studied after excluding Luminous and Ultraluminous infrared galaxy (U)LIRG sources, and the mentioned correlations are noticeably stronger. We show that 'Dense gas' fractions as obtained from HCN and HCO+ molecules tightly correlate with maser emission, especially for galaxies with normal IR luminosity(LIR< 10^11Lsun) and we show that HCO+ is a better 'dense gas' tracer than HCN. Further systematic studies of these dense gas tracers with higher transition level lines are vital to probe megamaser physical conditions and to accurately determining how maser emission interrelates with the dense gas

Vibrational modes in nanocrystalline iron under high pressure

The phonon density of states (DOS) of nanocrystalline 57Fe was measured using nuclear resonant inelastic x-ray scattering (NRIXS) at pressures up to 28 GPa in a diamond anvil cell. The nanocrystalline material exhibited an enhancement in its DOS at low energies by a factor of 2.2. This enhancement persisted throughout the entire pressure range, although it was reduced to about 1.7 after decompression. The low-energy regions of the spectra were fitted to the function AEn, giving values of n close to 2 for both the bulk control sample and the nanocrystalline material, indicative of nearly three-dimensional vibrational dynamics. At higher energies, the van Hove singularities observed in both samples were coincident in energy and remained so at all pressures, indicating that the forces conjugate to the normal coordinates of the nanocrystalline materials are similar to the interatomic potentials of bulk crystals

Turning T cells On: Epigenetically Enhanced Expression of Effector T-cell Costimulatory Molecules on Irradiated Human Tumor Cells

Background: Sub-lethal doses of radiation can alter the phenotype of target tissue by modulating gene expression and making tumor cells more susceptible to T-cell-mediated immune attack. We have previously shown that sublethal tumor cell irradiation enhances killing of colorectal carcinoma cells by tumor-specific cytotoxic T cells by unknown mechanisms. Recent data from our lab indicates that irradiation of tumor cells results in the upregulation of OX40L and 41BBL, and that T cells incubated with irradiated tumor cells displayed improved CTL survival, activation and effector activity. The objective of this current study was to determine the mechanism of enhanced OX40L and 41BBL expression in human colorectal tumor cells. Methods: Two colorectal carcinoma cell lines, HCT116 and SW620, were examined for changes in the expression of 41BBL and OX40L in response to inhibition of histone deacetylases (using TSA) and DNA methyltransferases (using 5-Aza-2′-deoxycytidine) to evaluate if epigenetic mechanisms of gene expression can modulate these genes. Tumor cells were treated with radiation, TSA, or 5-Aza-dC, and subsequently evaluated for changes in gene expression using RT-qPCR and flow cytometry. Moreover, we assessed levels of histone acetylation at the 41BBL promoter using chromatin immunoprecipitation assays in irradiated HCT116 cells. Results: Our data indicate that expression of 41BBL and OX40L can indeed be epigenetically regulated, as inhibition of histone deacetylases and of DNA methyltransferases results in increased OX40L and 41BBL mRNA and protein expression. Treatment of tumor cells with TSA enhanced the expression of these genes more than treatment with 5-Aza-dC, and co-incubation of T cells with TSA-treated tumor cells enhanced T-cell survival and activation, similar to radiation. Furthermore, chromatin immunoprecipitation experiments revealed significantly increased histone H3 acetylation of 41BBL promoters specifically following irradiation. Conclusions: Full understanding of specific mechanisms of immunogenic modulation (altered expression of immune relevant genes) of irradiated tumor cells will be required to determine how to best utilize radiation as a tool to enhance cancer immunotherapy approaches. Overall, our results suggest that radiation can be used to make human tumors more immunogenic through epigenetic modulation of genes stimulatory to effector T-cells. Keywords: External beam radiation, Immunogenic modulation, CTLs, Epigenetic, Effector co-stimulation

Interchanging Functionality Among Homologous Elongation Factors Using Signatures of Heterotachy

Numerous models of molecular evolution have been formulated to describe the forces that shape sequence divergence among homologous proteins. These models have greatly enhanced our understanding of evolutionary processes. Rarely are such models empirically tested in the laboratory, and even more rare, are such models exploited to generate novel molecules useful for synthetic biology. Here, we experimentally demonstrate that the heterotachy model of evolution captures signatures of functional divergence among homologous elongation factors (EFs) between bacterial EF-Tu and eukaryotic eEF1A. These EFs are GTPases that participate in protein translation by presenting aminoacylated-tRNAs to the ribosome. Upon release from the ribosome, the EFs are recharged by nucleotide exchange factors EF-Ts in bacteria or eEF1B in eukaryotes. The two nucleotide exchange factors perform analogous functions despite not being homologous proteins. The heterotachy model was used to identify a set of sites in eEF1A/EF-Tu associated with eEF1B binding in eukaryotes and another reciprocal set associated with EF-Ts binding in bacteria. Introduction of bacterial EF-Tu residues at these sites into eEF1A protein efficiently disrupted binding of cognate eEF1B as well as endowed eEF1A with the novel ability to bind bacterial EF-Ts. We further demonstrate that eEF1A variants, unlike yeast wild-type, can function in a reconstituted in vitro bacterial translation system. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00239-013-9540-9) contains supplementary material, which is available to authorized users

Cover coefficient-based multi-document summarization

In this paper we present a generic, language independent multi-document summarization system forming extracts using the cover coefficient concept. Cover Coefficient-based Summarizer (CCS) uses similarity between sentences to determine representative sentences. Experiments indicate that CCS is an efficient algorithm that is able to generate quality summaries online. © Springer-Verlag Berlin Heidelberg 2009

Planetary migration in evolving planetesimals discs

In the current paper, we further improved the model for the migration of planets introduced in Del Popolo et al. (2001) and extended to time-dependent planetesimal accretion disks in Del Popolo and Eksi (2002). In the current study, the assumption of Del Popolo and Eksi (2002), that the surface density in planetesimals is proportional to that of gas, is released. In order to obtain the evolution of planetesimal density, we use a method developed in Stepinski and Valageas (1997) which is able to simultaneously follow the evolution of gas and solid particles for up to 10^7 yrs. Then, the disk model is coupled to migration model introduced in Del Popolo et al. (2001) in order to obtain the migration rate of the planet in the planetesimal. We find that the properties of solids known to exist in protoplanetary systems, together with reasonable density profiles for the disk, lead to a characteristic radius in the range 0.03-0.2 AU for the final semi-major axis of the giant planet.Comment: IJMP A in prin

Combination Treatment with Sublethal Ionizing Radiation and the Proteasome Inhibitor, Bortezomib, Enhances Death-Receptor Mediated Apoptosis and Anti-Tumor Immune Attack

Sub-lethal doses of radiation can modulate gene expression, making tumor cells more susceptible to T-cell-mediated immune attack. Proteasome inhibitors demonstrate broad anti-tumor activity in clinical and pre-clinical cancer models. Here, we use a combination treatment of proteasome inhibition and irradiation to further induce immunomodulation of tumor cells that could enhance tumor-specific immune responses. We investigate the effects of the 26S proteasome inhibitor, bortezomib, alone or in combination with radiotherapy, on the expression of immunogenic genes in normal colon and colorectal cancer cell lines. We examined cells for changes in the expression of several death receptors (DR4, DR5 and Fas) commonly used by T cells for killing of target cells. Our results indicate that the combination treatment resulted in increased cell surface expression of death receptors by increasing their transcript levels. The combination treatment further increases the sensitivity of carcinoma cells to apoptosis through FAS and TRAIL receptors but does not change the sensitivity of normal non-malignant epithelial cells. Furthermore, the combination treatment significantly enhances tumor cell killing by tumor specific CD8+ T cells. This study suggests that combining radiotherapy and proteasome inhibition may simultaneously enhance tumor immunogenicity and the induction of antitumor immunity by enhancing tumor-specific T-cell activity