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  • 1
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    The role of Compton heating in radiation-regulated accretion on to black holes (2014)
    Oxford University Press
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    Publication Date: 2014-10-18
    Description: We investigate the role of Compton heating in radiation-regulated accretion on to black holes (BHs) from a neutral dense medium using 1D radiation-hydrodynamic simulations. We focus on the relative effects of Compton-heating and photoheating as a function of the spectral slope α, assuming a power-law spectrum in the energy range of 13.6 eV–100 keV. While Compton heating is dominant only close to the BH, it can reduce the accretion rate to 0.1 ( $l \propto \dot{m}^2$ model)–0.01 per cent ( $l \propto \dot{m}$ model) of the Bondi accretion rate when the BH radiation is hard (α ~ 1), where l and $\dot{m}$ are the luminosity and accretion rate normalized by Eddington rates, respectively. The oscillatory behaviour otherwise typically seen in simulations with α 〉 1, become suppressed when α ~ 1 only for the $l \propto \dot{m}$ model. The relative importance of the Compton heating over photoheating decreases and the oscillatory behaviour becomes stronger as the spectrum softens. When the spectrum is soft (α 〉 1.5), photoheating prevails regardless of models making the effect of Compton heating negligible. On the scale of the ionization front, where the gas supply into the Strömgren sphere from large scale is regulated, photoheating dominates. Our simulations show consistent results with the advection-dominated accretion flow ( $l \propto \dot{m}^2$ ) where the accretion is inefficient and the spectrum is hard (α ~ 1).
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 2
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    The effects of AGN feedback and SPH formulation on black hole growth in galaxies (2016)
    Oxford University Press
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    Publication Date: 2016-03-17
    Description: We perform simulations of isolated galaxies and major mergers to investigate the effects on black hole (BH) growth due to variations in active galactic nuclei (AGN) feedback models and different smooth particle hydrodynamic (SPH) solvers. In particular we examine density-SPH versus newer pressure-SPH formulation and their significance relative to minor changes in subgrid AGN feedback prescriptions. The aim is to use these idealized simulations to understand the impact of these effects for large cosmological volume simulations where these models are often adopted. In both isolated galaxies and galaxy mergers, we find that star formation histories are largely insensitive to the choice of SPH schemes whilst BH accretion rate can change. This can result in a factor of 2–3 difference in final BH mass for the two hydrodynamic formulations. However, the differences are much smaller than those obtained even with small changes in the subgrid AGN feedback prescription. In particular, depending on the size of the region and the manner in which the AGN energy is deposited, the star formation rate is suppressed by a factor of 2 in isolated galaxies and the star burst completely quenched during the coalescence of two galaxies. The final BH mass differs by over an order of magnitude by changes in AGN feedback model. Our results indicated that any change in the hydrodynamic formulation is likely subdominant to the effects of changing subgrid physics around the BH, although thermodynamic state and morphology of the gas remnant are also sensitive to the change in hydrodynamic solver.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 3
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    MET is required for the recruitment of anti-tumoural neutrophils (2015)
    Nature Publishing Group (NPG)
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    Publication Date: 2015-05-20
    Description: Mutations or amplification of the MET proto-oncogene are involved in the pathogenesis of several tumours, which rely on the constitutive engagement of this pathway for their growth and survival. However, MET is expressed not only by cancer cells but also by tumour-associated stromal cells, although its precise role in this compartment is not well characterized. Here we show that MET is required for neutrophil chemoattraction and cytotoxicity in response to its ligand hepatocyte growth factor (HGF). Met deletion in mouse neutrophils enhances tumour growth and metastasis. This phenotype correlates with reduced neutrophil infiltration to both the primary tumour and metastatic sites. Similarly, Met is necessary for neutrophil transudation during colitis, skin rash or peritonitis. Mechanistically, Met is induced by tumour-derived tumour necrosis factor (TNF)-alpha or other inflammatory stimuli in both mouse and human neutrophils. This induction is instrumental for neutrophil transmigration across an activated endothelium and for inducible nitric oxide synthase production upon HGF stimulation. Consequently, HGF/MET-dependent nitric oxide release by neutrophils promotes cancer cell killing, which abates tumour growth and metastasis. After systemic administration of a MET kinase inhibitor, we prove that the therapeutic benefit of MET targeting in cancer cells is partly countered by the pro-tumoural effect arising from MET blockade in neutrophils. Our work identifies an unprecedented role of MET in neutrophils, suggests a potential 'Achilles' heel' of MET-targeted therapies in cancer, and supports the rationale for evaluating anti-MET drugs in certain inflammatory diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4594765/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4594765/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Finisguerra, Veronica -- Di Conza, Giusy -- Di Matteo, Mario -- Serneels, Jens -- Costa, Sandra -- Thompson, A A Roger -- Wauters, Els -- Walmsley, Sarah -- Prenen, Hans -- Granot, Zvi -- Casazza, Andrea -- Mazzone, Massimiliano -- 098516/Wellcome Trust/United Kingdom -- 308459/European Research Council/International -- G0802255/Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2015 Jun 18;522(7556):349-53. doi: 10.1038/nature14407. Epub 2015 May 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, VIB, Leuven B3000, Belgium [2] Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, Department of Oncology, KU Leuven, Leuven B3000, Belgium. ; 1] Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, VIB, Leuven B3000, Belgium [2] Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, Department of Oncology, KU Leuven, Leuven B3000, Belgium [3] Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, 4710-057 Braga, Portugal [4] ICVS/3B's - PT Government Associate Laboratory, 4710-057 Braga/Guimaraes, Portugal. ; Department of Infection and Immunity, University of Sheffield, Sheffield S10 2RX, UK. ; 1] Respiratory Division, University Hospital Gasthuisberg, Leuven B3000, Belgium [2] Laboratory of Translational Genetics, Vesalius Research Center, VIB, Leuven B3000, Belgium [3] Laboratory of Translational Genetics, Vesalius Research Center, Department of Oncology, KU Leuven, Leuven B3000, Belgium. ; Digestive Oncology Unit, University Hospital Gasthuisberg, Department of Oncology, KU Leuven, Leuven B3000, Belgium. ; Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University, Jerusalem 91120, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25985180" target="_blank"〉PubMed〈/a〉
    Keywords: Aged ; Animals ; Antineoplastic Agents/*adverse effects/*pharmacology ; Disease Models, Animal ; Disease Progression ; Female ; Gene Deletion ; Hepatocyte Growth Factor ; Humans ; Inflammation/immunology/pathology ; Male ; Mice ; Middle Aged ; Neoplasm Metastasis ; Neoplasms/drug therapy/*immunology/*metabolism/pathology ; Neutrophils/drug effects/*immunology/secretion ; Nitric Oxide/secretion ; Proto-Oncogene Proteins c-met/antagonists & ; inhibitors/deficiency/genetics/*metabolism ; Solubility ; Transendothelial and Transepithelial Migration ; Tumor Necrosis Factor-alpha/metabolism ; Xenograft Model Antitumor Assays
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 4
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    NMR Analysis of Nucleophosmin/G-quadruplex Interaction [Molecular Bases of Disease] (2012)
    The American Society for Biochemistry and Molecular Biology (ASBMB)
    Details
    Publication Date: 2012-08-04
    Description: Nucleophosmin (NPM1) is a nucleocytoplasmic shuttling protein, mainly localized at nucleoli, that plays a key role in several cellular functions, including ribosome maturation and export, centrosome duplication, and response to stress stimuli. More than 50 mutations at the terminal exon of the NPM1 gene have been identified so far in acute myeloid leukemia; the mutated proteins are aberrantly and stably localized in the cytoplasm due to high destabilization of the NPM1 C-terminal domain and the appearance of a new nuclear export signal. We have shown previously that the 70-residue NPM1 C-terminal domain (NPM1-C70) is able to bind with high affinity a specific region at the c-MYC gene promoter characterized by parallel G-quadruplex structure. Here we present the solution structure of the NPM1-C70 domain and NMR analysis of its interaction with a c-MYC-derived G-quadruplex. These data were used to calculate an experimentally restrained molecular docking model for the complex. The NPM1-C70 terminal three-helix bundle binds the G-quadruplex DNA at the interface between helices H1 and H2 through electrostatic interactions with the G-quadruplex phosphate backbone. Furthermore, we show that the 17-residue lysine-rich sequence at the N terminus of the three-helix bundle is disordered and, although necessary, does not participate directly in the contact surface in the complex.
    Print ISSN: 0021-9258
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
    Published by The American Society for Biochemistry and Molecular Biology (ASBMB)
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  • 5
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    Rayleigh-Taylor instability of ionization front around black holes (2013)
    Oxford University Press
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    Publication Date: 2013-12-23
    Description: We examine the role of ionizing radiation emitted from black holes (BHs) in suppressing the growth of the Rayleigh–Taylor instability (RTI) across the ionization front (I-front) that forms when the gas fuelling the BH is neutral. We use radiation-hydrodynamic simulations to show that the RTI is suppressed for non-accelerating fronts on all scales resolved in our simulations. A necessary condition for the stability of the I-front is that the radius of the Strömgren sphere is larger than the Bondi radius. When this condition is violated, the I-front collapses producing an accretion luminosity burst. Transient growth of the RTI occurs only during the accretion burst when the effective acceleration in the frame of reference of the I-front increases significantly due to the rapid expansion of the Strömgren sphere.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 6
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    Monsters in the dark: predictions for luminous galaxies in the early Universe from the BLUETIDES simulation (2016)
    Oxford University Press
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    Publication Date: 2016-06-15
    Description: Using deep Hubble and Spitzer observations Oesch et al. have identified a bright ( M UV –22) star-forming galaxy candidate at z 11. The presence of GN- z 11 implies a number density ~10 –6 Mpc –3 , roughly an order of magnitude higher than the expected value based on extrapolations from lower redshift. Using the unprecedented volume and high resolution of the B lue T ides cosmological hydrodynamical simulation, we study the population of luminous rare objects at z 〉 10. The luminosity function in B lue T ides implies an enhanced number of massive galaxies, consistent with the observation of GN- z 11. We find about 30 galaxies at M UV –22 at z = 11 in the B lue T ides volume, including a few objects about 1.5 mag brighter. The probability of observing GN- z 11 in the volume probed by Oesch et al. is ~13 per cent. The predicted properties of the rare bright galaxies at z = 11 in B lue T ides closely match those inferred from the observations of GN- z 11. B lue T ides predicts a negligible contribution from faint AGN in the observed SED. The enormous increase in volume surveyed by WFIRST will provide observations of ~1000 galaxies with M UV 〈 –22 beyond z = 11 out to z = 13.5.
    Print ISSN: 1745-3925
    Electronic ISSN: 1745-3933
    Topics: Physics
    Published by Oxford University Press
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  • 7
    Electronic Resource
    Electronic Resource
    Superoxide, nitric oxide, peroxynitrite and cytokine combinations all cause functional impairment and morphological changes in rat islets of Langerhans and insulin secreting cell lines, but dictate cell death by different mechanisms (1997)
    Springer
    Apoptosis 2 (1997), S. 164-177 
    Details
    ISSN: 1573-675X
    Keywords: Apoptosis ; beta cells ; cytokines ; Islets of Langerhans ; nitric oxide ; peroxynitrite ; superoxide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We have shown that nitric oxide treatment for 30–90 min causes inhibition of insulin secretion, DNA damage and disturbs sub-cellular organization in rat and human islets of Langerhans and HIT-T15 cells. Here rat islets and beta-cell lines were treated with various free radical generating systems S-nitrosoglutathione (nitric oxide), xanthine oxidase plus hypoxanthine (reactive oxygen species), 3-morpholinosydnonimine (nitric oxide, super-oxide, peroxynitrite, hydrogen peroxide) and peroxynitrite and their effects over 4 h to 3 days compared with those of the cytokine combination interleukin-1β, tumour necrosis factor-α and interferon-γ. End points examined were de novo protein synthesis, cellular reducing capacity, morphological changes and apoptosis by acridine orange cytochemistry, DNA gel electrophoresis and electron microscopy. Treatment (24–72 h) with nitric oxide, superoxide, peroxynitrite or combined cytokines differentially decreased redox function and inhibited protein synthesis in rat islets of Langerhans and in insulin-containing cell lines; cytokine effects were arginine and nitric oxide dependent. Peroxynitrite gave rare apoptosis in HIT-T15 cells and superoxide gave none in any cell type, but caused the most beta cell-specific damage in islets. S-nitroso-glutathione was the most effective agent at causing DNA laddering or chromatin margination characteristic of apoptotic cell death in insulin-containing cells. Cytokine-induced apoptosis was observed specifically in islet beta cells, combined cytokine effects on islet function and death most resembled those of the mixed radical donor SIN-1.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026412414666
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  • 8
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    On the transmission of waves at discrete frequencies from the solar wind to the magnetosphere and ground: a case study. (2015)
    Wiley-Blackwell
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    Publication Date: 2015-10-14
    Description: We analyze a case event in which several fluctuations at discrete frequencies ( f ≈1.3-1.5, ≈3.3-3.6, ≈4.4-4.6, ≈5.9-6.2 mHz; i. e. close to the “CMS” frequencies) were observed in the magnetosphere, after the impact of a sharp shock wave that, in the interplanetary medium, was followed by intense fluctuations in the solar wind parameters. The comparison between interplanetary, geosynchronous and ground-based observations revealed that, following the SI, magnetospheric modes at the same discrete frequencies were detected at geostationary orbit by spacecraft located in the morning and the dawn sector, and, ubiquitously, at ground-based stations: all of them revealed a one-to-one correspondence with those ultimately identified in the high velocity stream following the shock wave. It reveals that the occurrence of such global modes is directly related to the transmission of external fluctuations and the observed geomagnetic fluctuations might be interpreted as the ground magnetic response to magnetospheric compressional modes forced by oscillations of the solar wind pressure at the same frequencies. By contrast, we did not find any evidence for magnetospheric oscillations possibly related to other mechanisms such as the velocity shear, the impact of the shock wave itself, etc.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley-Blackwell on behalf of American Geophysical Union (AGU).
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  • 9
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    Tumour-educated circulating monocytes are powerful candidate biomarkers for diagnosis and disease follow-up of colorectal cancer (2016)
    BMJ Publishing Group
    In: Gut
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    Publication Date: 2016-05-11
    Description: Objective Cancer immunology is a growing field of research whose aim is to develop innovative therapies and diagnostic tests. Starting from the hypothesis that immune cells promptly respond to harmful stimuli, we used peripheral blood monocytes in order to characterise a distinct gene expression profile and to evaluate its potential as a candidate diagnostic biomarker in patients with colorectal cancer (CRC), a still unmet clinical need. Design We performed a case-control study including 360 peripheral blood monocyte samples from four European oncological centres and defined a gene expression profile specific to CRC. The robustness of the genetic profile and disease specificity were assessed in an independent setting. Results This screen returned 43 putative diagnostic markers, which we refined and validated in the confirmative multicentric analysis to 23 genes with outstanding diagnostic accuracy (area under the curve (AUC)=0.99 (0.99 to 1.00), Se=100.0% (100.0% to 100.0%), Sp=92.9% (78.6% to 100.0%) in multiple-gene receiver operating characteristic analysis). The diagnostic accuracy was robustly maintained in prospectively collected independent samples (AUC=0.95 (0.85 to 1.00), Se=92.6% (81.5% to 100.0%), Sp=92.3% (76.9% to 100.0%). This monocyte signature was expressed at early disease onset, remained robust over the course of disease progression, and was specific for the monocytic fraction of mononuclear cells. The gene modulation was induced specifically by soluble factors derived from transformed colon epithelium in comparison to normal colon or other cancer histotypes. Moreover, expression changes were plastic and reversible, as they were abrogated upon withdrawal of these tumour-released factors. Consistently, the modified set of genes reverted to normal expression upon curative treatment and was specific for CRC. Conclusions Our study is the first to demonstrate monocyte plasticity in response to tumour-released soluble factors. The identified distinct signature in tumour-educated monocytes might be used as a candidate biomarker in CRC diagnosis and harbours the potential for disease follow-up and therapeutic monitoring.
    Keywords: Colon cancer
    Print ISSN: 0017-5749
    Electronic ISSN: 1468-3288
    Topics: Medicine
    Published by BMJ Publishing Group
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  • 10
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    Magnetic anisotropy and orbital ordering in ${\mathrm{Ca}}_{2}{\mathrm{RuO}}_{4}$ (2018)
    American Physical Society (APS)
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    Publication Date: 2018-09-26
    Description: Author(s): D. G. Porter, V. Granata, F. Forte, S. Di Matteo, M. Cuoco, R. Fittipaldi, A. Vecchione, and A. Bombardi We review the magnetic and orbital ordered states in Ca 2 RuO 4 by performing resonant elastic x-ray scattering (REXS) at the Ru L 2 , 3 edges. In principle, the point symmetry at Ru sites does not constrain the direction of the magnetic moment below T N . However early measurements reported the ordered mom... [Phys. Rev. B 98, 125142] Published Tue Sep 25, 2018
    Keywords: Electronic structure and strongly correlated systems
    Print ISSN: 1098-0121
    Electronic ISSN: 1095-3795
    Topics: Physics
    Published by American Physical Society (APS)
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