Characterization of a novel Hodgkin cell-line, HD-MyZ, HD-Myr, with myelomonocytic features mimicking Hodgkin's disease in severe combined immunodeficient mice

A novel Hodgkin cell line, designated HD-MyZ, was established from the pleural effusion of a 29-yr-old patient with Hodgkin's disease (HD) of nodular sclerosing type. The majority of cells grow adherently and display typical morphological characteristics of Reed-Sternberg (RS) and Hodgkin (H) cells, i.e., large multi- and mononucleated cells with prominent nucleoli. Immunofluorescence analysis revealed a myelomonocytoid immunophenotype (expression of CD13 and CD68, and lack of lymphoid markers). HD-MyZ cells strongly expressed restin, a recently described intermediate filament-associated protein, the expression of which is restricted to H cells, RS cells, and in vitro cultivated peripheral blood monocytes. In addition mRNA expression of c-fms (colony-stimulating factor 1 receptor) could be induced in HD-MyZ cells by phorbol myristate acetate (PMA) stimulation. Southern blot analysis did not detect rearrangement of T cell receptor beta and immunoglobulin H loci, thus demonstrating the lack of lymphoid commitment. HD-MyZ cells were also devoid of Epstein-Barr virus genomes. HD-MyZ cells constitutively express mRNAs for interleukin 1 alpha (IL-1 alpha), IL-1 beta, IL-5, IL-6, IL-7, IL-8, IL-10, IL-1 receptor (type I), and IL-6 receptor. Stimulation of cells with PMA increased mRNA expression as well as the secretion of IL-1 beta, IL-6, and IL-8, and induced the de novo expression of IL-8 receptors. Xenotransplantation into severe combined immunodeficient (SCID) mice by intravenous or subcutaneous inoculation led to development of disseminated tumors with infiltrative and destructive growth. In addition lymphadenopathy, pleural effusion, and infiltration of spleen were observed. Morphological and immunological analysis of tumor cells revealed the same features as HD-MyZ cells. This cell line might be an important tool for understanding the pathogenesis and biology of HD. In addition the SCID mice model might prove helpful in developing new therapeutic strategies

Blocking of transcription factor E2F/DP by dominant-negative mutants in a normal breast epithelial cell line efficiently inhibits apoptosis and induces tumor growth in scid mice

The transcription factor E2F is regulated during the cell cycle through interactions with the product of the retinoblastoma susceptibility gene and related proteins. It is thought that E2F-mediated gene regulation at the G1/S boundary and during S phase may be one of the rate-limiting steps in cell proliferation. It was reported that in vivo overexpression of E2F-1 in fibroblasts induces S phase entry and leads to apoptosis. This observation suggests that E2F plays a role in both cell cycle regulation and apoptosis. To further understand the role of E2F in cell cycle progression, cell death, and tumor development, we have blocked endogenous E2F activity in HBL-100 cells, derived from nonmalignant human breast epithelium, using dominant-negative mutants under the control of a tetracycline-dependent expression system. We have shown here that induction of dominant-negative mutants led to strong downregulation of transiently transfected E2F-dependent chloramphenicol acetyl transferase reporter constructs and of endogenous c-myc, which has been described as a target gene of the transcription factor E2F/DP. In addition, we have shown that blocking of E2F could efficiently protect from apoptosis induced by serum starvation within a period of 10 d, whereas control cells started to die after 24 h. Surprisingly, blocking of E2F did not alter the rate of proliferation or of DNA synthesis of these cells; this finding indicates that cell-cycle progression could be driven in an E2F-independent manner. In addition, we have been able to show that blocking of endogenous E2F in HBL-100 cells led to rapid induction of tumor growth in severe combined immunodeficiency mice. No tumor growth could be observed in mice that received mock-transfected clones or tetracycline to block expression of the E2F mutant constructs in vivo. Thus, it appears that E2F has a potential tumor-suppressive function under certain circumstances. Furthermore, we provide evidence that dysregulation of apoptosis may be an important step in tumorigenesis

Supersymmetric AdS_3, AdS_2 and Bubble Solutions

We present new supersymmetric AdS_3 solutions of type IIB supergravity and AdS_2 solutions of D=11 supergravity. The former are dual to conformal field theories in two dimensions with N=(0,2) supersymmetry while the latter are dual to conformal quantum mechanics with two supercharges. Our construction also includes AdS_2 solutions of D=11 supergravity that have non-compact internal spaces which are dual to three-dimensional N=2 superconformal field theories coupled to point-like defects. We also present some new bubble-type solutions, corresponding to BPS states in conformal theories, that preserve four supersymmetries.Comment: v2: 33 pages, published version in JHE

North American Influence on Tropospheric Ozone and the Effects of Recent Emission Reductions: Constraints from ICARTT Observations

We use observations from the International Consortium for Atmospheric Research on Transport and Transformation (ICARTT) campaign over eastern North America in summer 2004, interpreted with a global 3‐D model of tropospheric chemistry (GEOS‐Chem), to improve and update estimates of North American influence on global tropospheric ozone and the effect of recent U.S. anthropogenic reductions on surface ozone pollution. We find that the 50% decrease in U.S. stationary NOx sources since 1999 has decreased mean U.S. boundary layer ozone concentrations by 6–8 ppbv in the southeast and 4–6 ppbv in the Midwest. The observed dO3/dCO molar enhancement ratio in the U.S. boundary layer during ICARTT was 0.46 mol mol−1, larger than the range of 0.3–0.4 from studies in the early 1990s, possibly reflecting the decrease in the NOx/CO emission ratio as well as an increase in the ozone production efficiency per unit NOx. North American NOx emissions during summer 2004 as constrained by the ICARTT observations (0.72 Tg N fossil fuel, 0.11 Tg N biomass burning, 0.28 Tg N lightning for 1 July to 15 August) enhanced the hemispheric tropospheric ozone burden by 12.4%, with comparable contributions from fossil fuel and lightning (5–6%), but only 1% from biomass burning emissions despite 2004 being a record fire year over Alaska and western Canada.Earth and Planetary Science

QCD vacuum structure in strong magnetic fields

We study the response of the QCD vacuum to strong magnetic fields, using a potential model for the quark-antiquark interaction. We find that production of spin-polarized u-ubar pairs is energetically favorable for fields B > B_crit \sim 10 GeV^2. We contrast the resulting u-ubar condensate with the quark condensate which is present at zero magnetic field, and we estimate the corresponding magnetization as a function of B.Comment: 16 pages, LaTeX, 3 eps figures. v2: references added. v3: fixed typ

Coulomb Energy, Remnant Symmetry, and the Phases of Non-Abelian Gauge Theories

We show that the confining property of the one-gluon propagator, in Coulomb gauge, is linked to the unbroken realization of a remnant gauge symmetry which exists in this gauge. An order parameter for the remnant gauge symmetry is introduced, and its behavior is investigated in a variety of models via numerical simulations. We find that the color-Coulomb potential, associated with the gluon propagator, grows linearly with distance both in the confined and - surprisingly - in the high-temperature deconfined phase of pure Yang-Mills theory. We also find a remnant symmetry-breaking transition in SU(2) gauge-Higgs theory which completely isolates the Higgs from the (pseudo)confinement region of the phase diagram. This transition exists despite the absence, pointed out long ago by Fradkin and Shenker, of a genuine thermodynamic phase transition separating the two regions.Comment: 18 pages, 19 figures, revtex

Biogenic Versus Anthropogenic Sources of CO in the United States

Aircraft observations of carbon monoxide (CO) from the ICARTT campaign over the eastern United States in summer 2004 (July 1–August 15), interpreted with a global 3-D model of tropospheric chemistry (GEOS-Chem), show that the national anthropogenic emission inventory from the U.S. Environmental Protection Agency (93 Tg CO y−1) is too high by 60% in summer. Our best estimate of the CO anthropogenic source for the ICARTT period is 6.4 Tg CO, including 4.6 Tg from direct emission and 1.8 Tg CO from oxidation of anthropogenic volatile organic compounds (VOCs). The biogenic CO source for the same period from the oxidation of isoprene and other biogenic VOCs is 8.3 Tg CO, and is independently constrained by ICARTT observations of formaldehyde (HCHO). Anthropogenic emissions of CO in the U.S. have decreased to the point that they are now lower than the biogenic source in summer.Earth and Planetary SciencesEngineering and Applied Science

Adenomatose Pulmonaire ovine: transmission experimental£ aux agneaux au moyen de cellules en culture et d'homogenats de cellules

Studies on the transmission of jaagsiekte (ovine pulmonary adenomatosis) both by sub inoculation of cells of known sex and by cell homogenates into male and female lambs are reported. The results obtained indicate a thymocyte-dependent rejection of male cells in female recipients in contrast to the successful transplantation of male cells in male animals and female cells in both sexes. This suggests the presence of a surface antigen determined by the Y-chromosome in the tumour cells. A second mechanism of transmission, dependent on the transformation of the recipient's cells, was demonstrated by 2 cases of heterologous transplantation and confirmed by inoculation of cellular homogenatesThe articles have been scanned in colour with a HP Scanjet 5590; 300dpi. Adobe Acrobat XI Pro was used to OCR the text and also for the merging and conversion to the final presentation PDF-format

From Fake Supergravity to Superstars

The fake supergravity method is applied to 5-dimensional asymptotically AdS spacetimes containing gravity coupled to a real scalar and an abelian gauge field. The motivation is to obtain bulk solutions with R x S^3 symmetry in order to explore the AdS/CFT correspondence when the boundary gauge theory is on R x S^3. A fake supergravity action, invariant under local supersymmetry through linear order in fermion fields, is obtained. The gauge field makes things more restrictive than in previous applications of fake supergravity which allowed quite general scalar potentials. Here the superpotential must take the form W(\phi) ~ exp(-k\phi) + c exp(2\phi/(3k)), and the only freedom is the choice of the constant k. The fermion transformation rules of fake supergravity lead to fake Killing spinor equations. From their integrability conditions, we obtain first order differential equations which we solve analytically to find singular electrically charged solutions of the Lagrangian field equations. A Schwarzschild mass term can be added to produce a horizon which shields the singularity. The solutions, which include "superstars", turn out to be known in the literature. We compute their holographic parameters.Comment: 42 pages, 3 figure