395 research outputs found

    Discrete exterior calculus (DEC) for the surface Navier-Stokes equation

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    We consider a numerical approach for the incompressible surface Navier-Stokes equation. The approach is based on the covariant form and uses discrete exterior calculus (DEC) in space and a semi-implicit discretization in time. The discretization is described in detail and related to finite difference schemes on staggered grids in flat space for which we demonstrate second order convergence. We compare computational results with a vorticity-stream function approach for surfaces with genus 0 and demonstrate the interplay between topology, geometry and flow properties. Our discretization also allows to handle harmonic vector fields, which we demonstrate on a torus.Comment: 21 pages, 9 figure

    Ferromagnetism and suppression of metallic clusters in Fe implanted ZnO - a phenomenon related to defects?

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    We investigated ZnO(0001) single crystals annealed in high vacuum with respect to their magnetic properties and cluster formation tendency after implant-doping with Fe. While metallic Fe cluster formation is suppressed, no evidence for the relevance of the Fe magnetic moment for the observed ferromagnetism was found. The latter along with the cluster suppression is discussed with respect to defects in the ZnO host matrix, since the crystalline quality of the substrates was lowered due to the preparation as observed by x-ray diffraction.Comment: 20 pages, 6 figure

    The Small GTPase RhoA Localizes to the Nucleus and Is Activated by Net1 and DNA Damage Signals

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    Rho GTPases control many cellular processes, including cell survival, gene expression and migration. Rho proteins reside mainly in the cytosol and are targeted to the plasma membrane (PM) upon specific activation by guanine nucleotide exchange factors (GEFs). Accordingly, most GEFs are also cytosolic or associated with the PM. However, Net1, a RhoA-specific GEF predominantly localizes to the cell nucleus at steady-state. Nuclear localization for Net1 has been seen as a mechanism for sequestering the GEF away from RhoA, effectively rendering the protein inactive. However, considering the prominence of nuclear Net1 and the fact that a biological stimulus that promotes Net1 translocation out the nucleus to the cytosol has yet to be discovered, we hypothesized that Net1 might have a previously unidentified function in the nucleus of cells.Using an affinity precipitation method to pulldown the active form of Rho GEFs from different cellular fractions, we show here that nuclear Net1 does in fact exist in an active form, contrary to previous expectations. We further demonstrate that a fraction of RhoA resides in the nucleus, and can also be found in a GTP-bound active form and that Net1 plays a role in the activation of nuclear RhoA. In addition, we show that ionizing radiation (IR) specifically promotes the activation of the nuclear pool of RhoA in a Net1-dependent manner, while the cytoplasmic activity remains unchanged. Surprisingly, irradiating isolated nuclei alone also increases nuclear RhoA activity via Net1, suggesting that all the signals required for IR-induced nuclear RhoA signaling are contained within the nucleus.These results demonstrate the existence of a functional Net1/RhoA signaling pathway within the nucleus of the cell and implicate them in the DNA damage response

    Analysis of expression profiles of MAGE-A antigens in oral squamous cell carcinoma cell lines

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    <p>Abstract</p> <p>Background</p> <p>The immunological response to solid tumours is insufficient. Therefore, tumour specific antigens have been explored to facilitate the activation of the immune system. The cancer/testis antigen class of MAGE-A antigens is a possible target for vaccination. Their differential expression profiles also modulate the course of the cancer disease and its response to antineoplastic drugs.</p> <p>Methods</p> <p>The expression profiles of MAGE-A2, -A3, -A4, -A6 and -A10 in five own oral squamous cell carcinoma cell lines were characterised by rt-PCR, qrt-PCR and immunocytochemistry with a global MAGE-A antibody (57B) and compared with those of an adult keratinocyte cell line (NHEK).</p> <p>Results</p> <p>All tumour cell lines expressed MAGE-A antigens. The antigens were expressed in groups with different preferences. The predominant antigens expressed were MAGE-A2, -A3 and -A6. MAGE-A10 was not expressed in the cell lines tested. The MAGE-A gene products detected in the adult keratinocyte cell line NHEK were used as a reference.</p> <p>Conclusion</p> <p>MAGE-A antigens are expressed in oral squamous cell carcinomas. The expression profiles measured facilitate distinct examinations in forthcoming studies on responses to antineoplastic drugs or radiation therapy. MAGE-A antigens are still an interesting aim for immunotherapy.</p

    The XMM Cluster Survey: the interplay between the brightest cluster galaxy and the intracluster medium via AGN feedback

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    Using a sample of 123 X‐ray clusters and groups drawn from the XMM Cluster Survey first data release, we investigate the interplay between the brightest cluster galaxy (BCG), its black hole and the intracluster/group medium (ICM). It appears that for groups and clusters with a BCG likely to host significant active galactic nuclei (AGN) feedback, gas cooling dominates in those with T X > 2 keV while AGN feedback dominates below. This may be understood through the subunity exponent found in the scaling relation we derive between the BCG mass and cluster mass over the halo mass range 10 13 < M 500 < 10 15  M ⊙ and the lack of correlation between radio luminosity and cluster mass, such that BCG AGN in groups can have relatively more energetic influence on the ICM. The L X – T X relation for systems with the most massive BCGs, or those with BCGs co‐located with the peak of the ICM emission, is steeper than that for those with the least massive and most offset, which instead follows self‐similarity. This is evidence that a combination of central gas cooling and powerful, well fuelled AGN causes the departure of the ICM from pure gravitational heating, with the steepened relation crossing self‐similarity at T X = 2 keV. Importantly, regardless of their black hole mass, BCGs are more likely to host radio‐loud AGN if they are in a massive cluster ( T X ≳ 2 keV) and again co‐located with an effective fuel supply of dense, cooling gas. This demonstrates that the most massive black holes appear to know more about their host cluster than they do about their host galaxy. The results lead us to propose a physically motivated, empirical definition of ‘cluster’ and ‘group’, delineated at 2 keV.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91324/1/j.1365-2966.2012.20764.x.pd

    The dynamic architecture of the metabolic switch in Streptomyces coelicolor

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    [EN] Background: During the lifetime of a fermenter culture, the soil bacterium S. coelicolor undergoes a major metabolic switch from exponential growth to antibiotic production. We have studied gene expression patterns during this switch, using a specifically designed Affymetrix genechip and a high-resolution time-series of fermenter-grown samples.Results: Surprisingly, we find that the metabolic switch actually consists of multiple finely orchestrated switching events. Strongly coherent clusters of genes show drastic changes in gene expression already many hours before the classically defined transition phase where the switch from primary to secondary metabolism was expected. The main switch in gene expression takes only 2 hours, and changes in antibiotic biosynthesis genes are delayed relative to the metabolic rearrangements. Furthermore, global variation in morphogenesis genes indicates an involvement of cell differentiation pathways in the decision phase leading up to the commitment to antibiotic biosynthesis.Conclusions: Our study provides the first detailed insights into the complex sequence of early regulatory events during and preceding the major metabolic switch in S. coelicolor, which will form the starting point for future attempts at engineering antibiotic production in a biotechnological settingSIWe are very grateful to Mervyn Bibb for his generous support with the Affymetrix custom microarray design. We acknowledge the excellent technical help of K. Klein, S. Poths, M. Walter, A. Øverby and E. Hansen. This project was supported by grants of the ERA-NET SySMO Project [GEN2006-27745-E/SYS]: (P-UK-01-11-3i) and the Research Council of Norway [project no. 181840/I30

    Photocytotoxicity of mTHPC (Temoporfin) Loaded Polymeric Micelles Mediated by Lipase Catalyzed Degradation

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    Purpose. To study the in vitro photocytotoxicity and cellular uptake of biodegradable polymeric micelles loaded with the photosensitizer mTHPC, including the effect of lipase-catalyzed micelle degradation. Methods. Micelles of mPEG750-b-oligo(ɛ-caprolactone)5 (mPEG750-b-OCL5) with a hydroxyl (OH), benzoyl (Bz) or naphthoyl (Np) end group were formed and loaded with mTHPC by the film hydration method. The cellular uptake of the loaded micelles, and their photocytotoxicity on human neck squamous carcinoma cells in the absence and presence of lipase were compared with free and liposomal mTHPC (Fospeg ®). Results. Micelles composed of mPEG750-b-OCL5 with benzoyl and naphtoyl end groups had the highest loading capacity up to 30 % (w/w), likely due to π–π interactions between the aromatic end group and the photosensitizer. MTHPC-loaded benzoylated micelles (0.5 mg/mL polymer) did not display photocytotoxicity or any mTHPC-uptake by the cells, in contrast to free and liposomal mTHPC. After dilution of the micelles below the critical aggregation concentration (CAC), or after micelle degradation by lipase, photocytotoxicity and cellular uptake of mTHPC were restored. Conclusion. The high loading capacity of the micelles, the high stability of mTHPC-loaded micelles above the CAC, and the lipase-induced release of the photosensitizer makes these micelles very promising carriers for photodynamic therapy in vivo. KEY WORDS: drug release; enzymatic degradation; meta-tetra(hydroxyphenyl)chlorin (mTHPC); photodynamic therapy (PDT); polymeric micelles
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