Pre-avalanche instabilities in a granular pile

We investigate numerically the transition between static equilibrium and dynamic surface flow of a 2D cohesionless granular system driven by a continuous gravity loading. This transition is characterized by intermittent local dynamic rearrangements and can be described by an order parameter defined as the density of critical contacts, e.g. contacts where the friction is fully mobilized. Analysis of the spatial correlations of critical contacts shows the occurence of ``fluidized'' clusters which exhibit a power-law divergence in size at the approach of the stability limit. The results are compatible with recent models that describe the granular system during the static/dynamic transition as a multi-phase system.Comment: 9 pages, 6 figures, submitted to Phys. Rev. Let

Liver Regeneration after Partial Hepatectomy Is Not Impaired in Mice with Double Deficiency of Myd88 and IFNAR Genes

Liver regeneration is known to occur in mice lacking one or more Toll-like receptors (TLRs) or the adaptor protein MyD88. Though MyD88 is required for signaling by many TLRs, others signal via MyD88-independent pathways, leading to the induction of type I interferons (IFNs). Here, we assessed liver regeneration after partial hepatectomy (PH) in mice lacking both MyD88 and the type I IFN receptor (Myd88-IFNAR double-KO). Approximately 28% of Myd88-IFNAR double-KO mice had gross liver lesions prior to surgery. In mice without lesions, Myd88-IFNAR deficiency abrogated the increase in circulating IL-6 after PH but did not impair hepatocyte BrdU incorporation, mitotic figure counts, or recovery of liver-to-body weight ratios. These results indicate that type I IFNs are not responsible for the preservation of liver regeneration in Myd88-deficient mice, and they also cast doubt on the idea of microbial products being essential triggers of liver regeneration in mice undergoing PH

Molecular crystal approach for pi-conjugated polymers: from PPP Hamiltonian to Holstein model for polaron states

Starting from the $\pi$-electron Pariser-Parr-Pople (PPP) Hamiltonian which includes both strong electron-phonon and electron-electron interactions, we propose some strongly correlated wave functions of increasing quality for the ground state of conjugated polymers. These wavefunctions are built by combining different finite sets of local configurations extended at most over two nearest-neighbour monomers. With this picture, the doped case with one additional particle is expressed in terms of quasi-particle. Thus, the polaron formation problem goes back to the study of a Holstein like model.Comment: 27 pages, 6 eps figs, Revtex; enlarged version. Submitted to Journal of Physics: Condensed Matte

Sorting Nexin 1 Down-Regulation Promotes Colon Tumorigenesis

PURPOSE: Colon cancer is one of the most common human malignancies, yet studies have only begun to identify the multiple mechanisms that underlie the development of this tumor. In this study, we have identified a novel mechanism, dysregulation of endocytic sorting, which promotes colon cancer development. EXPERIMENTAL DESIGN: Immunohistochemical and microarray analyses were done on human colon cancer tissue specimens to determine the levels of one endocytic protein, sorting nexin 1 (SNX1). SW480 cells, a human colon cancer cell line that retains a relatively high level of SNX1 expression, were used to assess the effects of down-regulating this protein by small hairpin RNA. Activation of signal transduction cascades was evaluated in these cells using Western blotting, and multiple functional assays were done. RESULTS: We determined by immunohistochemistry that the level of SNX1 was significantly down-regulated in 75% of human colon cancers. In corroborative studies using microarray analysis, SNX1 message was significantly decreased (log(2) ratio less than -1) for 8 of 19 colon carcinomas. Cell lines with reduced SNX1 levels showed increased proliferation, decreased apoptosis, and decreased susceptibility to anoikis. They also showed increased activation of epidermal growth factor receptor and extracellular signal-regulated kinase 1/2 in response to epidermal growth factor. This increased activation was abolished by inhibition of endocytosis. CONCLUSIONS: These data suggest that loss of SNX1 may play a significant role in the development and aggressiveness of human colon cancer, at least partially through the mechanism of increased signaling from endosomes. Further, these findings suggest that dysregulation of endocytic proteins may represent a new paradigm in the process of carcinogenesis.Fil: Nguyen, Lananh N.. University of Washington; Estados UnidosFil: Holdren, Matthew S.. University of Washington; Estados UnidosFil: Nguyen, Anthony P.. Baylor College of Medicine; Estados UnidosFil: Furuya, Momoko H.. University of Washington; Estados UnidosFil: Bianchini, Michele. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Levy, Estrella Mariel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; ArgentinaFil: Mordoh, Jose. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Liu, Annie. University of Washington; Estados UnidosFil: Guncay, Gabriela D.. University of Washington; Estados UnidosFil: Campbell, Jean S.. University of Washington; Estados UnidosFil: Parks, W. Tony. University of Washington; Estados Unido

Asymptotic behavior of the density of states on a random lattice

We study the diffusion of a particle on a random lattice with fluctuating local connectivity of average value q. This model is a basic description of relaxation processes in random media with geometrical defects. We analyze here the asymptotic behavior of the eigenvalue distribution for the Laplacian operator. We found that the localized states outside the mobility band and observed by Biroli and Monasson (1999, J. Phys. A: Math. Gen. 32 L255), in a previous numerical analysis, are described by saddle point solutions that breaks the rotational symmetry of the main action in the real space. The density of states is characterized asymptotically by a series of peaks with periodicity 1/q.Comment: 11 pages, 2 figure

Spin state and moment of inertia of Venus

Fundamental properties of the planet Venus, such as its internal mass distribution and variations in length of day, have remained unknown. We used Earth-based observations of radar speckles tied to the rotation of Venus obtained in 2006-2020 to measure its spin axis orientation, spin precession rate, moment of inertia, and length-of-day variations. Venus is tilted by 2.6392 $\pm$ 0.0008 degrees ($1\sigma$) with respect to its orbital plane. The spin axis precesses at a rate of 44.58 $\pm$ 3.3 arcseconds per year ($1\sigma$), which gives a normalized moment of inertia of 0.337 $\pm$ 0.024 and yields a rough estimate of the size of the core. The average sidereal day on Venus in the 2006-2020 interval is 243.0226 $\pm$ 0.0013 Earth days ($1\sigma$). The spin period of the solid planet exhibits variations of 61 ppm ($\sim$20 minutes) with a possible diurnal or semidiurnal forcing. The length-of-day variations imply that changes in atmospheric angular momentum of at least $\sim$4% are transferred to the solid planet.Comment: 20 pages, 7 figures, supplementary information. Submitted to Nature Astronomy on October 14, 202

Extracellular Matrix Dynamics in Hepatocarcinogenesis: a Comparative Proteomics Study of PDGFC Transgenic and Pten Null Mouse Models

We are reporting qualitative and quantitative changes of the extracellular matrix (ECM) and associated receptor proteomes, occurring during the transition from liver fibrosis and steatohepatitis to hepatocellular carcinoma (HCC). We compared two mouse models relevant to human HCC: PDGFC transgenic (Tg) and Pten null mice, models of disease progression from fibrosis and steatohepatitis to HCC. Using mass spectrometry, we identified in the liver of both models proteins for 26 collagen-encoding genes, providing the first evidence of expression at the protein level for 16 collagens. We also identified post-transcriptional protein variants for six collagens and lysine hydroxylation modifications for 14 collagens. Tumor-associated collagen proteomes were similar in both models with increased expression of collagens type IV, VI, VII, X, XIV, XV, XVI, and XVIII. Splice variants for Col4a2, Col6a2, Col6a3 were co-upregulated while only the short form of Col18a1 increased in the tumors. We also identified tumor specific increases of nidogen 1, decorin, perlecan, and of six laminin subunits. The changes in these non-collagenous ECM proteins were similar in both models with the exception of laminin β3, detected specifically in the Pten null tumors. Pdgfa and Pdgfc mRNA expression was increased in the Pten null liver, a possible mechanism for the similarity in ECM composition observed in the tumors of both models. In contrast and besides the strong up-regulation of integrin α5 protein observed in the liver tumors of both models, the expression of the six other integrins identified was specific to each model, with integrins α2b, α3, α6, and β1 up-regulated in Pten null tumors and integrins α8 and β5 up-regulated in the PDGFC Tg tumors. In conclusion, HCC–associated ECM proteins and ECM–integrin networks, common or specific to HCC subtypes, were identified, providing a unique foundation to using ECM composition for HCC classification, diagnosis, prevention, or treatment

Sorafenib sensitizes hepatocellular carcinoma cells to physiological apoptotic stimuli

Sorafenib increases survival rate of patients with advanced hepatocellular carcinoma (HCC). The mechanism underlying this effect is not completely understood. In this work we have analyzed the effects of sorafenib on autocrine proliferation and survival of different human HCC cell lines. Our results indicate that sorafenib in vitro counteracts autocrine growth of different tumor cells (Hep3B, HepG2, PLC-PRF-5, SK-Hep1). Arrest in S/G2/M cell cycle phases were observed coincident with cyclin D1 down-regulation. However, sorafenib's main anti-tumor activity seems to occur through cell death induction which correlated with caspase activation, increase in the percentage of hypodiploid cells, activation of BAX and BAK and cytochrome c release from mitochondria to cytosol. In addition, we observed a rise in mRNA and protein levels of the pro-apoptotic BH3-domain only PUMA and BIM, as well as decreased protein levels of the anti-apoptotic MCL1 and survivin. PUMA targeting knock-down, by using specific siRNAs, inhibited sorafenib-induced apoptotic features. Moreover, we obtained evidence suggesting that sorafenib also sensitizes HCC cells to the apoptotic activity of transforming growth factor-beta (TGF-beta) through the intrinsic pathway and to tumor necrosis factor-a (TNF) through the extrinsic pathway. Interestingly, sensitization to sorafenib-induced apoptosis is characteristic of liver tumor cells, since untransformed hepatocytes did not respond to sorafenib inducing apoptosis, either alone or in combination with TGF-beta or TNF. Indeed, sorafenib effectiveness in delaying HCC late progression might be partly related to a selectively sensitization of HCC cells to apoptosis by disrupting autocrine signals that protect them from adverse conditions and pro-apoptotic physiological cytokines. J. Cell. Physiol. 227: 1319-1325, 2012. (C) 2011 Wiley Periodicals, Inc

The Physicist's Guide to the Orchestra

An experimental study of strings, woodwinds (organ pipe, flute, clarinet, saxophone and recorder), and the voice was undertaken to illustrate the basic principles of sound production in music instruments. The setup used is simple and consists of common laboratory equipment. Although the canonical examples (standing wave on a string, in an open and closed pipe) are easily reproduced, they fail to explain the majority of the measurements. The reasons for these deviations are outlined and discussed.Comment: 11 pages, 10 figures (jpg files). Submitted to European Journal of Physic