Metallic Xenon, Molecular Condensates, and Superconductivity

A possibility of explaining the light absorption observed to occur under pressure-induced xenon metallization as due to the transition to the superconducting state is analyzed. The mechanism of the van der Waals bonding is discussed.Comment: LaTeX 2.09 (RevTeX), 4 pages, 4 PostScript figures included in tex

A possible Chandra and Hubble Space Telescope detection of extragalactic WHIM towards PG 1116+215

We have analysed Chandra low energy transmission grating and XMM-Newton Reflection Grating Spectrometer (RGS) spectra towards the z = 0.177 quasar PG 1116+215, a sightline that is rendered particularly interesting by the Hubble Space Telescope (HST) detection of several OVI and HI broad Lyman alpha absorption (BLA) lines that may be associated with the warm-hot intergalactic medium (WHIM). We performed a search for resonance K alpha absorption lines from OVII and OVIII at the redshifts of the detected far-ultraviolet lines. We detected an absorption line in the Chandra spectra at the 5.2 sigma confidence level at wavelengths corresponding to OVIII K alpha at z = 0.0911 +/- 0.0004 +/- 0.0005 (statistical followed by systematic error). This redshift is within 3 sigma of that of an HI broad Lyman alpha of b similar or equal to 130 km s(-1) (corresponding to a temperature of log T(K) similar or equal to 6.1) at z = 0.092 79 +/- 0.000 05. We have also analysed the available XMM-Newton RGS data towards PG 1116+215. Unfortunately, the XMM-Newton data are not suitable to investigate this line because of instrumental features at the wavelengths of interest. At the same redshift, the Chandra and XMM-Newton spectra have OVII K alpha absorption-line features of significance 1.5 sigma and 1.8 sigma, respectively. We also analysed the available Sloan Digital Sky Survey (SDSS) spectroscopic galaxy survey data towards PG 1116+215 in the redshift range of interest. We found evidence for a galaxy filament that intersect the PG 1116+215 sightline and additional galaxy structures that may host WHIM. The HI BLA and the OVIII K alpha absorbers are within a few Mpc of the filament (assuming that redshifts track Hubble flow distances) or consistent with gas accreting on to the filament from either direction relative to the sightline with velocities of a few x 100 km s(-1). The combination of HST, Chandra, XMM-Newton and SDSS data indicates that we have likely detected a multi-temperature WHIM at z similar or equal to 0.091-0.093 towards PG 1116+215. The OVIII Ka absorption line indicates gas at high temperature, log T(K) >= 6.4, with a total column density of the order of log N-H(cm(2)) >= 20 and a baryon overdensity delta(b) similar to 100-1000 for sightline lengths of L = 1-10 Mpc. This detection highlights the importance of BLA absorption lines as possible signposts of high-temperature WHIM filaments

Polycyclic aromatic hydrocarbons as skin carcinogens:Comparison of benzo [a]pyrene, dibenzo[def,p]chrysene and three environmental mixtures in the FVB/N mouse

The polycyclic aromatic hydrocarbon (PAH), benzo[a]pyrene (BaP), was compared to dibenzo[def,p]chrysene (DBC) and combinations of three environmental PAH mixtures (coal tar, diesel particulate and cigarette smoke condensate) using a two stage, FVB/N mouse skin tumor model. DBC (4 nmol) was most potent, reaching 100% tumor incidence with a shorter latency to tumor formation, less than 20 weeks of 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion compared to all other treatments. Multiplicity was 4 times greater than BaP (400 nmol). Both PAHs produced primarily papillomas followed by squamous cell carcinoma and carcinoma in situ. Diesel particulate extract (1 mg SRM 1650b; mix 1) did not differ from toluene controls and failed to elicit a carcinogenic response. Addition of coal tar extract (1 mg SRM 1597a; mix 2) produced a response similar to BaP. Further addition of 2 mg of cigarette smoke condensate (mix 3) did not alter the response with mix 2. PAH-DNA adducts measured in epidermis 12 h post initiation and analyzed by (32)P post- labeling, did not correlate with tumor incidence. PAH- dependent alteration in transcriptome of skin 12 h post initiation was assessed by microarray. Principal component analysis (sum of all treatments) of the 922 significantly altered genes (p<0.05), showed DBC and BaP to cluster distinct from PAH mixtures and each other. BaP and mixtures up-regulated phase 1 and 2 metabolizing enzymes while DBC did not. The carcinogenicity with DBC and two of the mixtures was much greater than would be predicted based on published Relative Potency Factors (RPFs)

Folyóirat vagy gyűjteményes kötet? (Csokonai Diétai Magyar Múzsája)

BACKGROUND: The complex interplay between viral replication and host immune response during infection remains poorly understood. While many viruses are known to employ anti-immune strategies to facilitate their replication, highly pathogenic virus infections can also cause an excessive immune response that exacerbates, rather than reduces pathogenicity. To investigate this dichotomy in severe acute respiratory syndrome coronavirus (SARS-CoV), we developed a transcriptional network model of SARS-CoV infection in mice and used the model to prioritize candidate regulatory targets for further investigation. RESULTS: We validated our predictions in 18 different knockout (KO) mouse strains, showing that network topology provides significant predictive power to identify genes that are important for viral infection. We identified a novel player in the immune response to virus infection, Kepi, an inhibitory subunit of the protein phosphatase 1 (PP1) complex, which protects against SARS-CoV pathogenesis. We also found that receptors for the proinflammatory cytokine tumor necrosis factor alpha (TNFα) promote pathogenesis, presumably through excessive inflammation. CONCLUSIONS: The current study provides validation of network modeling approaches for identifying important players in virus infection pathogenesis, and a step forward in understanding the host response to an important infectious disease. The results presented here suggest the role of Kepi in the host response to SARS-CoV, as well as inflammatory activity driving pathogenesis through TNFα signaling in SARS-CoV infections. Though we have reported the utility of this approach in bacterial and cell culture studies previously, this is the first comprehensive study to confirm that network topology can be used to predict phenotypes in mice with experimental validation

To be or not to be: the case of the hot WHIM absorption in the blazar PKS 2155-304 sight line

The cosmological missing baryons at z 5.5 K) phase of the warm hot intergalactic medium (WHIM). While the hot WHIM is hard to detect due to its high ionisation level, the warm (T ≲ 105.5 K) phase of the WHIM has been very robustly detected in the far-ultraviolet (FUV) band. We adopted the assumption that the hot and warm WHIM phases are co-located and therefore used the FUV-detected warm WHIM as a tracer for the cosmologically interesting hot WHIM. We performed an X-ray follow-up in the sight line of the blazar PKS 2155-304 at the redshifts where previous FUV measurements of O VI, Si IV, and broad Lyman-alpha (BLA) absorption have indicated the existence of the warm WHIM. We looked for the O VII Heα and O VIII Lyα absorption lines, the most likely hot WHIM tracers. Despite the very large exposure time (≈1 Ms), the Reflection Grating Spectrometer unit 1 (RGS1) on-board XMM-Newton data yielded no significant detection which corresponds to upper limits of log N(O VII(cm-2)) ≤ 14.5-15.2 and log N(O VIII(cm-2)) ≤ 14.5-15.2. An analysis of the data obtained with the combination of the Low Energy Transmission Grating (LETG) and the High Resolution Camera (HRC) on-board Chandra yielded consistent results. However, the data obtained with the LETG, combined with the Advanced CCD Imaging Spectrometer (ACIS) lead to the detection of an feature resembling an absorption line at λ ≈ 20 Å at simple one-parameter confidence level of 3.7σ, consistent with several earlier LETG/ACIS reports. Given the high statistical quality of the RGS1 data, the possibility of RGS1 accidentally missing the true line at λ ̃ 20 Å is very low: 0.006%. Neglecting this, the LETG/ACIS detection can be interpreted as Lyα transition of O VIII at one of the redshifts (z ≈ 0.054) of FUV-detected warm WHIM. Given the very convincing X-ray spectral evidence for and against the existence of the λ ̃ 20 Å feature, we cannot conclude whether or not it is a true astrophysical absorption line. Considering cosmological simulations, the probability of the LETG/ACIS λ ̃ 20 Å feature being due to the astrophysical O VIII absorber co-located with the FUV-detected O VI absorber is at the very low level of ≲0.1%. We cannot completely rule out the very unlikely possibility that the LETG/ACIS 20 Å feature is due to a transient event located close to the blazar. </p

To be or not to be : the case of the hot WHIM absorption in the blazar PKS 2155-304 sight line

The cosmological missing baryons at z <1 most likely hide in the hot (T greater than or similar to 10(5.5) K) phase of the warm hot intergalactic medium (WHIM). While the hot WHIM is hard to detect due to its high ionisation level, the warm (T less than or similar to 10(5.5) K) phase of the WHIM has been very robustly detected in the far-ultraviolet (FUV) band. We adopted the assumption that the hot and warm WHIM phases are co-located and therefore used the FUV-detected warm WHIM as a tracer for the cosmologically interesting hot WHIM. We performed an X-ray follow-up in the sight line of the blazar PKS 2155-304 at the redshifts where previous FUV measurements of O VI, Si IV, and broad Lyman-alpha (BLA) absorption have indicated the existence of the warm WHIM. We looked for the O VII Hc alpha and O VIII Ly alpha absorption lines, the most likely hot WHIM tracers. Despite the very large exposure time (approximate to 1 Ms), the Reflection Grating Spectrometer unit 1 (RGS1) on-board XMM-Newton data yielded no significant detection which corresponds to upper limits of log N(O VII (cm(-2)))Peer reviewe

Release of Severe Acute Respiratory Syndrome Coronavirus Nuclear Import Block Enhances Host Transcription in Human Lung Cells

The severe acute respiratory syndrome coronavirus accessory protein ORF6 antagonizes interferon signaling by blocking karyopherin-mediated nuclear import processes. Viral nuclear import antagonists, expressed by several highly pathogenic RNA viruses, likely mediate pleiotropic effects on host gene expression, presumably interfering with transcription factors, cytokines, hormones, and/or signaling cascades that occur in response to infection. By bioinformatic and systems biology approaches, we evaluated the impact of nuclear import antagonism on host expression networks by using human lung epithelial cells infected with either wild-type virus or a mutant that does not express ORF6 protein. Microarray analysis revealed significant changes in differential gene expression, with approximately twice as many upregulated genes in the mutant virus samples by 48 h postinfection, despite identical viral titers. Our data demonstrated that ORF6 protein expression attenuates the activity of numerous karyopherin-dependent host transcription factors (VDR, CREB1, SMAD4, p53, EpasI, and Oct3/4) that are critical for establishing antiviral responses and regulating key host responses during virus infection. Results were confirmed by proteomic and chromatin immunoprecipitation assay analyses and in parallel microarray studies using infected primary human airway epithelial cell cultures. The data strongly support the hypothesis that viral antagonists of nuclear import actively manipulate host responses in specific hierarchical patterns, contributing to the viral pathogenic potential in vivo. Importantly, these studies and modeling approaches not only provide templates for evaluating virus antagonism of nuclear import processes but also can reveal candidate cellular genes and pathways that may significantly influence disease outcomes following severe acute respiratory syndrome coronavirus infection in vivo

Engineering HIV-Resistant Human CD4+ T Cells with CXCR4-Specific Zinc-Finger Nucleases

HIV-1 entry requires the cell surface expression of CD4 and either the CCR5 or CXCR4 coreceptors on host cells. Individuals homozygous for the ccr5Δ32 polymorphism do not express CCR5 and are protected from infection by CCR5-tropic (R5) virus strains. As an approach to inactivating CCR5, we introduced CCR5-specific zinc-finger nucleases into human CD4+ T cells prior to adoptive transfer, but the need to protect cells from virus strains that use CXCR4 (X4) in place of or in addition to CCR5 (R5X4) remains. Here we describe engineering a pair of zinc finger nucleases that, when introduced into human T cells, efficiently disrupt cxcr4 by cleavage and error-prone non-homologous DNA end-joining. The resulting cells proliferated normally and were resistant to infection by X4-tropic HIV-1 strains. CXCR4 could also be inactivated in ccr5Δ32 CD4+ T cells, and we show that such cells were resistant to all strains of HIV-1 tested. Loss of CXCR4 also provided protection from X4 HIV-1 in a humanized mouse model, though this protection was lost over time due to the emergence of R5-tropic viral mutants. These data suggest that CXCR4-specific ZFNs may prove useful in establishing resistance to CXCR4-tropic HIV for autologous transplant in HIV-infected individuals

QSO Absorption Systems Detected in Ne VIII: High-Metallicity Clouds with a Large Effective Cross Section

Using high resolution, high signal-to-noise ultraviolet spectra of the z = 0.9754 quasar PG1148+549 obtained with the Cosmic Origins Spectrograph (COS) on the Hubble Space Telescope, we study the physical conditions and abundances of NeVIII+OVI absorption line systems at z(abs) =0.68381, 0.70152, 0.72478. In addition to NeVIII and OVI, absorption lines from multiple ionization stages of oxygen (OII, OIII, OIV) are detected and are well-aligned with the more highly ionized species. We show that these absorbers are multiphase systems including hot gas (T ~ 10^{5.7} K) that produces NeVIII and OVI, and the gas metallicity of the cool phase ranges from Z = 0.3 Z_{solar} to supersolar. The cool (~10^{4} K) phases have densities n_{H} ~ 10^{-4} cm^{-3} and small sizes (< 4kpc); these cool clouds are likely to expand and dissipate, and the NeVIII may be within a transition layer between the cool gas and a surrounding, much hotter medium. The NeVIII redshift density, dN/dz = 7^{+7}_{-3}, requires a large number of these clouds for every L > 0.1L* galaxy and a large effective absorption cross section (>~ 100 kpc), and indeed, we find a star forming ~L* galaxy at the redshift of the z(abs)=0.72478 system, at an impact parameter of 217 kpc. Multiphase absorbers like these NeVIII systems are likely to be an important reservoir of baryons and metals in the circumgalactic media of galaxies.Comment: Final published version (Astrophysical Journal