254 research outputs found

    Polar Actions on Berger Spheres

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    The object of this article is to study a torus action on a so-called Berger sphere. We also make some comments on polar actions on naturally reductive homogeneous spaces. Finally, we prove a rigidity-type theorem for Riemannian manifolds carrying a polar action with a fix point

    In vitro characterization and inhibition of the CXCR4/CXCL12 chemokine axis in human uveal melanoma cell lines

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    <p>Abstract</p> <p>Purpose</p> <p>The CXCR4/CXCL12 chemokine axis may play a critical role in guiding CXCR4+ circulating malignant cells to organ specific locations that actively secrete its ligand CXCL12 (SDF-1) such as bone, brain, liver, and lungs. We sought to characterize the presence of the CXCR4/CXCL12 axis in five uveal melanoma (UM) cell lines in vitro. The ability of TN14003, a synthetic peptide inhibitor that targets the CXCR4 receptor complex, to inhibit this axis was also assessed.</p> <p>Methods</p> <p>Immunocytochemistry was performed against CXCR4 to confirm expression of this chemokine receptor in all five UM cell lines. Flow cytometry was preformed to evaluate CXCR4 cell surface expression on all five UM cell lines. A proliferation assay was also used to test effects TN14003 would have on cellular proliferation. Inhibition of cellular migration by specifically inhibiting the CXCR4/CXCL12 axis with TN14003 was also investigated. The binding efficacy of TN14003 to the CXCR4 receptor was assessed through flow cytometric methods.</p> <p>Results</p> <p>The CXCR4 receptor was present on all five UM cell lines. All five cell lines expressed different relative levels of surface CXCR4. TN14003 did not affect the proliferation of the five cell lines (p > 0.05). All cell lines migrated towards the chemokine CXCL12 at a level greater than the negative control (p < 0.05). All 5 cell lines pre-incubated with TN14003 prevented cellular migration towards chemokine CXCL12 (p < 0.01). TN14003 preferentially binds CXCR4 to native ligand CXCL12.</p> <p>Conclusion</p> <p>Interfering with the CXCR4/CXCL12 axis, using TN14003 was shown to effectively down regulate UM cell migration in vitro. Knowing that UM expresses the CXCR4 receptor, these CXCR4+ cells may be less likely to colonize distant organs that secrete the CXCL12 ligand, if treated with an inhibitor that binds CXCR4. Further studies should be pursued in order to test TN14003 efficacy in vivo.</p

    Equilibration times in numerical simulation of structural glasses: Comparing parallel tempering and conventional molecular dynamics

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    Generation of equilibrium configurations is the major obstacle for numerical investigation of the slow dynamics in supercooled liquid states. The parallel tempering (PT) technique, originally proposed for the numerical equilibration of discrete spin-glass model configurations, has recently been applied in the study of supercooled structural glasses. We present an investigation of the ability of parallel tempering to properly sample the liquid configuration space at different temperatures, by mapping the PT dynamics into the dynamics of the closest local potential energy minima (inherent structures). Comparing the PT equilibration process with the standard molecular dynamics equilibration process we find that the PT does not increase the speed of equilibration of the (slow) configurational degrees of freedom.Comment: 5 pages, 3 figure

    The apparent eta Carinae's long-term evolution and the critical role played by the strengthening of P Cygni absorption lines

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    Over the entire 20th century, Eta Carinae (\ec) has displayed a unique spectrum, which recently has been evolving towards that of a typical LBV. The two competing scenarios to explain such evolution are: (1) a dissipating occulter in front of a stable star or (2) a decreasing mass loss rate of the star. The first mechanism simultaneously explains why the central star appears to be secularly increasing its apparent brightness while its luminosity does not change; why the Homunculus' apparent brightness remains almost constant; and why the spectrum seen in direct light is becoming more similar to that reflected from the Homunculus (and which resembles a typical LBV). The second scenario does not account for these facts and predicts an increase in the terminal speed of the wind, contrary to observations. In this work, we present new data showing that the P Cygni absorption lines are secularly strengthening, which is not the expected behaviour for a decreasing wind-density scenario. CMFGEN modelling of the primary's wind with a small occulter in front agrees with observations. One could argue that invoking a dissipating coronagraphic occulter makes this object even more peculiar than it already appears to be. However, on the contrary, it solves the apparent contradictions between many observations. Moreover, by assigning the long-term behaviour to circumstellar causes and the periodic variations due to binarity, a star more stable after the 1900s than previously thought is revealed, contrary to the earlier paradigm of an unpredictable object.Comment: 17 pages, 12 figures, submitted to MNRA

    Identification of Novel Pax8 Targets in FRTL-5 Thyroid Cells by Gene Silencing and Expression Microarray Analysis

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    The differentiation program of thyroid follicular cells (TFCs), by far the most abundant cell population of the thyroid gland, relies on the interplay between sequence-specific transcription factors and transcriptional coregulators with the basal transcriptional machinery of the cell. However, the molecular mechanisms leading to the fully differentiated thyrocyte are still the object of intense study. The transcription factor Pax8, a member of the Paired-box gene family, has been demonstrated to be a critical regulator required for proper development and differentiation of thyroid follicular cells. Despite being Pax8 well-characterized with respect to its role in regulating genes involved in thyroid differentiation, genomics approaches aiming at the identification of additional Pax8 targets are lacking and the biological pathways controlled by this transcription factor are largely unknown.To identify unique downstream targets of Pax8, we investigated the genome-wide effect of Pax8 silencing comparing the transcriptome of silenced versus normal differentiated FRTL-5 thyroid cells. In total, 2815 genes were found modulated 72 h after Pax8 RNAi, induced or repressed. Genes previously reported to be regulated by Pax8 in FRTL-5 cells were confirmed. In addition, novel targets genes involved in functional processes such as DNA replication, anion transport, kinase activity, apoptosis and cellular processes were newly identified. Transcriptome analysis highlighted that Pax8 is a key molecule for thyroid morphogenesis and differentiation.This is the first large-scale study aimed at the identification of new genes regulated by Pax8, a master regulator of thyroid development and differentiation. The biological pathways and target genes controlled by Pax8 will have considerable importance to understand thyroid disease progression as well as to set up novel therapeutic strategies

    biological properties of hsc scientific basis for hsct

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    Hematopoiesis—from the Greek term for "blood making"—is the adaptive process by which mature and functional blood cells are continuously replaced over the entire lifetime of an individual. Erythrocytes, platelets, and the various subsets of leukocytes all have finite although different life spans. As a consequence, the daily production of red blood cells, platelets, and neutrophils in homeostatic conditions amount to more than 300 billion cells

    The Making of the NEAM Tsunami Hazard Model 2018 (NEAMTHM18)

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    The NEAM Tsunami Hazard Model 2018 (NEAMTHM18) is a probabilistic hazard model for tsunamis generated by earthquakes. It covers the coastlines of the North-eastern Atlantic, the Mediterranean, and connected seas (NEAM). NEAMTHM18 was designed as a three-phase project. The first two phases were dedicated to the model development and hazard calculations, following a formalized decision-making process based on a multiple-expert protocol. The third phase was dedicated to documentation and dissemination. The hazard assessment workflow was structured in Steps and Levels. There are four Steps: Step-1) probabilistic earthquake model; Step-2) tsunami generation and modeling in deep water; Step-3) shoaling and inundation; Step-4) hazard aggregation and uncertainty quantification. Each Step includes a different number of Levels. Level-0 always describes the input data; the other Levels describe the intermediate results needed to proceed from one Step to another. Alternative datasets and models were considered in the implementation. The epistemic hazard uncertainty was quantified through an ensemble modeling technique accounting for alternative models’ weights and yielding a distribution of hazard curves represented by the mean and various percentiles. Hazard curves were calculated at 2,343 Points of Interest (POI) distributed at an average spacing of ∼20 km. Precalculated probability maps for five maximum inundation heights (MIH) and hazard intensity maps for five average return periods (ARP) were produced from hazard curves. In the entire NEAM Region, MIHs of several meters are rare but not impossible. Considering a 2% probability of exceedance in 50 years (ARP≈2,475 years), the POIs with MIH >5 m are fewer than 1% and are all in the Mediterranean on Libya, Egypt, Cyprus, and Greece coasts. In the North-East Atlantic, POIs with MIH >3 m are on the coasts of Mauritania and Gulf of Cadiz. Overall, 30% of the POIs have MIH >1 m. NEAMTHM18 results and documentation are available through the TSUMAPS-NEAM project website (http://www.tsumaps-neam.eu/), featuring an interactive web mapper. Although the NEAMTHM18 cannot substitute in-depth analyses at local scales, it represents the first action to start local and more detailed hazard and risk assessments and contributes to designing evacuation maps for tsunami early warning.publishedVersio
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