156 research outputs found
MTSS1 is a critical epigenetically regulated tumor suppressor in CML
Chronic myeloid leukemia (CML) is driven by malignant stem cells that can persist despite therapy. We have identified Metastasis suppressor 1 (Mtss1/MIM) to be downregulated in hematopoietic stem and progenitor cells from leukemic transgenic SCLtTA/Bcr-Abl mice and in patients with CML at diagnosis, and Mtss1 was restored when patients achieved complete remission. Forced expression of Mtss1 decreased clonogenic capacity and motility of murine myeloid progenitor cells and reduced tumor growth. Viral transduction of Mtss1 into lineage depleted SCLtTA/Bcr-Abl bone marrow cells decreased leukemic cell burden in recipients, and leukemogenesis was reduced upon injection of Mtss1 overexpressing murine myeloid 32D cells. Tyrosine kinase inhibitor (TKI) therapy and reversion of Bcr-Abl expression increased Mtss1 expression but failed to restore it to control levels. CML patient samples revealed higher DNA methylation of specific Mtss1 promoter CpG sites that contain binding sites for Kaiso and Rest transcription factors. In summary, we identified a novel tumor suppressor in CML stem cells that is downregulated by both Bcr-Abl kinase-dependent and -independent mechanisms. Restored Mtss1 expression markedly inhibits primitive leukemic cell biology in vivo, providing a therapeutic rationale for the Bcr-Abl-Mtss1 axis to target TKI resistant CML stem cells in patients
Off-Forward Parton Distributions
Recently, there have been some interesting developments involving off-forward
parton distributions of the nucleon, deeply virtual Compton scattering, and
hard diffractive vector-meson production. These developments are triggered by
the realization that the off-forward distributions contain information about
the internal spin structure of the nucleon and that diffractive
electroproduction of vector mesons depends on these unconventional
distributions. This paper gives a brief overview of the recent developments
Proof of Factorization for Deeply Virtual Compton Scattering in QCD
We show that factorization holds for the deeply virtual Compton scattering
amplitude in QCD, up to power suppressed terms, to all orders in perturbation
theory. Furthermore, we show that the virtuality of the produced photon does
not influence the general theorem.Comment: 14 pages, Revtex, postscript figures. Improved treatement of
"endpoint/breakpoint" regions. Corrected references to earlier wor
Nonforward Parton Distributions
Applications of perturbative QCD to deeply virtual Compton scattering and
hard exclusive electroproduction processes require a generalization of usual
parton distributions for the case when long-distance information is accumulated
in nonforward matrix elements of quark and gluon light-cone operators.
We describe two types of nonperturbative functions parametrizing such matrix
elements: double distributions F(x,y;t) and nonforward distribution functions
F_\zeta (X;t), discuss their spectral properties, evolution equations which
they satisfy, basic uses and general aspects of factorization for hard
exclusive processes.Comment: Final version, to be published in Phys.Rev.
Hadron Production in Diffractive Deep-Inelastic Scattering
Characteristics of hadron production in diffractive deep-inelastic
positron-proton scattering are studied using data collected in 1994 by the H1
experiment at HERA. The following distributions are measured in the
centre-of-mass frame of the photon dissociation system: the hadronic energy
flow, the Feynman-x (x_F) variable for charged particles, the squared
transverse momentum of charged particles (p_T^{*2}), and the mean p_T^{*2} as a
function of x_F. These distributions are compared with results in the gamma^* p
centre-of-mass frame from inclusive deep-inelastic scattering in the
fixed-target experiment EMC, and also with the predictions of several Monte
Carlo calculations. The data are consistent with a picture in which the
partonic structure of the diffractive exchange is dominated at low Q^2 by hard
gluons.Comment: 16 pages, 6 figures, submitted to Phys. Lett.
Measurement of D* Meson Cross Sections at HERA and Determination of the Gluon Density in the Proton using NLO QCD
With the H1 detector at the ep collider HERA, D* meson production cross
sections have been measured in deep inelastic scattering with four-momentum
transfers Q^2>2 GeV2 and in photoproduction at energies around W(gamma p)~ 88
GeV and 194 GeV. Next-to-Leading Order QCD calculations are found to describe
the differential cross sections within theoretical and experimental
uncertainties. Using these calculations, the NLO gluon momentum distribution in
the proton, x_g g(x_g), has been extracted in the momentum fraction range
7.5x10^{-4}< x_g <4x10^{-2} at average scales mu^2 =25 to 50 GeV2. The gluon
momentum fraction x_g has been obtained from the measured kinematics of the
scattered electron and the D* meson in the final state. The results compare
well with the gluon distribution obtained from the analysis of scaling
violations of the proton structure function F_2.Comment: 27 pages, 9 figures, 2 tables, submitted to Nucl. Phys.
Low Q^2 Jet Production at HERA and Virtual Photon Structure
The transition between photoproduction and deep-inelastic scattering is
investigated in jet production at the HERA ep collider, using data collected by
the H1 experiment. Measurements of the differential inclusive jet
cross-sections dsigep/dEt* and dsigmep/deta*, where Et* and eta* are the
transverse energy and the pseudorapidity of the jets in the virtual
photon-proton centre of mass frame, are presented for 0 < Q2 < 49 GeV2 and 0.3
< y < 0.6. The interpretation of the results in terms of the structure of the
virtual photon is discussed. The data are best described by QCD calculations
which include a partonic structure of the virtual photon that evolves with Q2.Comment: 20 pages, 5 Figure
A Search for Selectrons and Squarks at HERA
Data from electron-proton collisions at a center-of-mass energy of 300 GeV
are used for a search for selectrons and squarks within the framework of the
minimal supersymmetric model. The decays of selectrons and squarks into the
lightest supersymmetric particle lead to final states with an electron and
hadrons accompanied by large missing energy and transverse momentum. No signal
is found and new bounds on the existence of these particles are derived. At 95%
confidence level the excluded region extends to 65 GeV for selectron and squark
masses, and to 40 GeV for the mass of the lightest supersymmetric particle.Comment: 13 pages, latex, 6 Figure
One-Loop Corrections and All Order Factorization In Deeply Virtual Compton Scattering
We calculate the one-loop corrections to a general off-forward deeply-virtual
Compton process at leading twist for both parton helicity-dependent and
independent cases. We show that the infrared divergences can be factorized
entirely into off-forward parton distributions, even when one of the two
photons is onshell. We argue that this property persists to all orders in
perturbation theory. We obtain the next-to-leading order Wilson coefficients
for the general leading-twist expansion of the product of two electromagnetic
currents in the \overline{\rm MS} scheme.Comment: Replaced with the version submitted to Phys. Rev.
The Spin Structure of the Nucleon
We present an overview of recent experimental and theoretical advances in our
understanding of the spin structure of protons and neutrons.Comment: 84 pages, 29 figure
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