664 research outputs found

    The Multifragmentation Freeze--Out Volume in Heavy Ion Collisions

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    The reduced velocity correlation function for fragments from the reaction Fe + Au at 100 A~MeV bombarding energy is investigated using the dynamical--statistical approach QMD+SMM and compared to experimental data to extract the Freeze--Out volume assuming simultaneous multifragmentation.Comment: 8 pages; 3 uuencoded figures available with figures command, LateX, UCRL-J-1157

    The HMGB1/RAGE inflammatory pathway promotes pancreatic tumor growth by regulating mitochondrial bioenergetics

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    Tumor cells require increased adenosine triphosphate (ATP) to support anabolism and proliferation. The precise mechanisms regulating this process in tumor cells are unknown. Here, we show that the receptor for advanced glycation endproducts (RAGE) and one of its primary ligands, high-mobility group box 1 (HMGB1), are required for optimal mitochondrial function within tumors. We found that RAGE is present in the mitochondria of cultured tumor cells as well as primary tumors. RAGE and HMGB1 coordinately enhanced tumor cell mitochondrial complex I activity, ATP production, tumor cell proliferation and migration. Lack of RAGE or inhibition of HMGB1 release diminished ATP production and slowed tumor growth in vitro and in vivo. These findings link, for the first time, the HMGB1-RAGE pathway with changes in bioenergetics. Moreover, our observations provide a novel mechanism within the tumor microenvironment by which necrosis and inflammation promote tumor progression

    Statistical Multifragmentation in Central Au+Au Collisions at 35 MeV/u

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    Multifragment disintegrations, measured for central Au + Au collisions at E/A = 35 MeV, are analyzed with the Statistical Multifragmentation Model. Charge distributions, mean fragment energies, and two-fragment correlation functions are well reproduced by the statistical breakup of a large, diluted and thermalized system slightly above the multifragmentation threshold.Comment: Latex file, 8 pages + 4 postscript figures available upon request from [email protected]

    Charge-Induced Fragmentation of Sodium Clusters

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    The fission of highly charged sodium clusters with fissilities X>1 is studied by {\em ab initio} molecular dynamics. Na_{24}^{4+} is found to undergo predominantly sequential Na_{3}^{+} emission on a time scale of 1 ps, while Na_{24}^{Q+} (5 \leq Q \leq 8) undergoes multifragmentation on a time scale \geq 0.1 ps, with Na^{+} increasingly the dominant fragment as Q increases. All singly-charged fragments Na_{n}^{+} up to size n=6 are observed. The observed fragment spectrum is, within statistical error, independent of the temperature T of the parent cluster for T \leq 1500 K. These findings are consistent with and explain recent trends observed experimentally.Comment: To appear in Physical Review Letter

    Multifragment production in Au+Au at 35 MeV/u

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    Multifragment disintegration has been measured with a high efficiency detection system for the reaction Au+AuAu + Au at E/A=35 MeVE/A = 35\ MeV. From the event shape analysis and the comparison with the predictions of a many-body trajectories calculation the data, for central collisions, are compatible with a fast emission from a unique fragment source.Comment: 9 pages, LaTex file, 4 postscript figures available upon request from [email protected]. - to appear in Phys. Lett.

    A large geometric distortion in the first photointermediate of rhodopsin, determined by double-quantum solid-state NMR

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    Double-quantum magic-angle-spinning NMR experiments were performed on 11,12-C-13(2)-retinylidene-rhodopsin under illumination at low temperature, in order to characterize torsional angle changes at the C11-C12 photoisomerization site. The sample was illuminated in the NMR rotor at low temperature (similar to 120 K) in order to trap the primary photointermediate, bathorhodopsin. The NMR data are consistent with a strong torsional twist of the HCCH moiety at the isomerization site. Although the HCCH torsional twist was determined to be at least 40A degrees, it was not possible to quantify it more closely. The presence of a strong twist is in agreement with previous Raman observations. The energetic implications of this geometric distortion are discussed

    Stepwise-edited, human melanoma models reveal mutations' effect on tumor and microenvironment.

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    Establishing causal relationships between genetic alterations of human cancers and specific phenotypes of malignancy remains a challenge. We sequentially introduced mutations into healthy human melanocytes in up to five genes spanning six commonly disrupted melanoma pathways, forming nine genetically distinct cellular models of melanoma. We connected mutant melanocyte genotypes to malignant cell expression programs in vitro and in vivo, replicative immortality, malignancy, rapid tumor growth, pigmentation, metastasis, and histopathology. Mutations in malignant cells also affected tumor microenvironment composition and cell states. Our melanoma models shared genotype-associated expression programs with patient melanomas, and a deep learning model showed that these models partially recapitulated genotype-associated histopathological features as well. Thus, a progressive series of genome-edited human cancer models can causally connect genotypes carrying multiple mutations to phenotype
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