1,973 research outputs found

    TTC5 is required to prevent apoptosis of acute myeloid leukemia stem cells

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    Using a screening strategy, we identified the tetratricopeptide repeat (TPR) motif protein, Tetratricopeptide repeat domain 5 (TTC5, also known as stress responsive activator of p300 or Strap) as required for the survival of human acute myeloid leukemia (AML) cells. TTC5 is a stress-inducible transcription cofactor known to interact directly with the histone acetyltransferase EP300 to augment the TP53 response. Knockdown (KD) of TTC5 induced apoptosis of both murine and human AML cells, with concomitant loss of clonogenic and leukemia-initiating potential; KD of EP300 elicited a similar phenotype. Consistent with the physical interaction of TTC5 and EP300, the onset of apoptosis following KD of either gene was preceded by reduced expression of BCL2 and increased expression of pro-apoptotic genes. Forced expression of BCL2 blocked apoptosis and partially rescued the clonogenic potential of AML cells following TTC5 KD. KD of both genes also led to the accumulation of MYC, an acetylation target of EP300, and the form of MYC that accumulated exhibited relative hypoacetylation at K148 and K157, residues targeted by EP300. In view of the ability of excess cellular MYC to sensitize cells to apoptosis, our data suggest a model whereby TTC5 and EP300 cooperate to prevent excessive accumulation of MYC in AML cells and their sensitization to cell death. They further reveal a hitherto unappreciated role for TTC5 in leukemic hematopoiesis

    Size and shape analysis of error-prone shape data

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    We consider the problem of comparing sizes and shapes of objects when landmark data are prone to measurement error. We show that naive implementation of ordinary Procrustes analysis that ignores measurement error can compromise inference. To account for measurement error, we propose the conditional score method for matching configurations, which guarantees consistent inference under mild model assumptions. The effects of measurement error on inference from naive Procrustes analysis and the performance of the proposed method are illustrated via simulation and application in three real data examples. Supplementary materials for this article are available online

    PMD20 COST-EFFECTIVENESS ANALYSIS OF A NEW INDEX FOR PROSTATE CANCER DETECTION

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    Nonlinear Modulation of Multi-Dimensional Lattice Waves

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    The equations governing weakly nonlinear modulations of NN-dimensional lattices are considered using a quasi-discrete multiple-scale approach. It is found that the evolution of a short wave packet for a lattice system with cubic and quartic interatomic potentials is governed by generalized Davey-Stewartson (GDS) equations, which include mean motion induced by the oscillatory wave packet through cubic interatomic interaction. The GDS equations derived here are more general than those known in the theory of water waves because of the anisotropy inherent in lattices. Generalized Kadomtsev-Petviashvili equations describing the evolution of long wavelength acoustic modes in two and three dimensional lattices are also presented. Then the modulational instability of a NN-dimensional Stokes lattice wave is discussed based on the NN-dimensional GDS equations obtained. Finally, the one- and two-soliton solutions of two-dimensional GDS equations are provided by means of Hirota's bilinear transformation method.Comment: Submitted to PR

    HuR binding to AU-rich elements present in the 3 ' untranslated region of Classical swine fever virus

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    Background: Classical swine fever virus (CSFV) is the member of the genus Pestivirus under the family Flaviviridae. The 5' untranslated region (UTR) of CSFV contains the IRES, which is a highly structured element that recruits the translation machinery. The 3' UTR is usually the recognition site of the viral replicase to initiate minus-strand RNA synthesis. Adenosine-uridine rich elements (ARE) are instability determinants present in the 3' UTR of short-lived mRNAs. However, the presence of AREs in the 3' UTR of CSFV conserved in all known strains has never been reported. This study inspects a possible role of the ARE in the 3' UTR of CSFV. Results: Using RNA pull-down and LC/MS/MS assays, this study identified at least 32 possible host factors derived from the cytoplasmic extracts of PK-15 cells that bind to the CSFV 3' UTR, one of which is HuR. HuR is known to bind the AREs and protect the mRNA from degradation. Using recombinant GST-HuR, this study demonstrates that HuR binds to the ARE present in the 3' UTR of CSFV in vitro and that the binding ability is conserved in strains irrespective of virulence. Conclusions: This study identified one of the CSFV 3' UTR binding proteins HuR is specifically binding to in the ARE region

    Blow up criterion for compressible nematic liquid crystal flows in dimension three

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    In this paper, we consider the short time strong solution to a simplified hydrodynamic flow modeling the compressible, nematic liquid crystal materials in dimension three. We establish a criterion for possible breakdown of such solutions at finite time in terms of the temporal integral of both the maximum norm of the deformation tensor of velocity gradient and the square of maximum norm of gradient of liquid crystal director field.Comment: 22 page

    Well-posedness of the Ericksen-Leslie system

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    In this paper, we prove the local well-posedness of the Ericksen-Leslie system, and the global well-posednss for small initial data under the physical constrain condition on the Leslie coefficients, which ensures that the energy of the system is dissipated. Instead of the Ginzburg-Landau approximation, we construct an approximate system with the dissipated energy based on a new formulation of the system.Comment: 16 page

    A variational approach to strongly damped wave equations

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    We discuss a Hilbert space method that allows to prove analytical well-posedness of a class of linear strongly damped wave equations. The main technical tool is a perturbation lemma for sesquilinear forms, which seems to be new. In most common linear cases we can furthermore apply a recent result due to Crouzeix--Haase, thus extending several known results and obtaining optimal analyticity angle.Comment: This is an extended version of an article appeared in \emph{Functional Analysis and Evolution Equations -- The G\"unter Lumer Volume}, edited by H. Amann et al., Birkh\"auser, Basel, 2008. In the latest submission to arXiv only some typos have been fixe

    Blowup Criterion for the Compressible Flows with Vacuum States

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    We prove that the maximum norm of the deformation tensor of velocity gradients controls the possible breakdown of smooth(strong) solutions for the 3-dimensional compressible Navier-Stokes equations, which will happen, for example, if the initial density is compactly supported \cite{X1}. More precisely, if a solution of the compressible Navier-Stokes equations is initially regular and loses its regularity at some later time, then the loss of regularity implies the growth without bound of the deformation tensor as the critical time approaches. Our result is the same as Ponce's criterion for 3-dimensional incompressible Euler equations (\cite{po}). Moreover, our method can be generalized to the full Compressible Navier-Stokes system which improve the previous results. In addition, initial vacuum states are allowed in our cases.Comment: 17 page
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