831 research outputs found

    Different canonical formulations of Einstein's theory of gravity

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    We describe the four most famous versions of the classical canonical formalism in the Einstein theory of gravity: the Arnovitt-Deser-Misner formalism, the Faddeev-Popov formalism, the tetrad formalism in the usual form, and the tetrad formalism in the form best suited for constructing the loop theory of gravity, which is now being developed. We present the canonical transformations relating these formalisms. The paper is written mainly for pedagogical purposes.Comment: LaTeX, 18 pages, some misprints in formulas (131)-(134) are correcte

    Authentic Films as a Tool for the Development of Sociocultural Competence

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    The article is devoted to the problem of foreign language teaching with the help of authentic films and TV series. Some effective ways of using such tools are discussed in the article

    Authentic Films as a Tool for the Development of Sociocultural Competence

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    The article is devoted to the problem of foreign language teaching with the help of authentic films and TV series. Some effective ways of using such tools are discussed in the article

    Obesity and the Risk for a Hematological Malignancy: Leukemia, Lymphoma, or Myeloma

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    Studies on obesity and the risk for hematological malignancies are reviewed. The paper includes a discussion of the metabolic effects of obesity and their possible role in linking increased body fat to neoplasia

    Inhibition of phosphatidylinositol 3-kinase dephosphorylates BAD and promotes apoptosis in myeloid leukemias

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    : The phosphatidylinositol 3-kinase (PI3K)/AKT protein kinase pathway is involved in cell growth, proliferation, and apoptosis. The functional activation of PI3K/AKT provides survival signals and blockade of this pathway may facilitate cell death. Downstream targets of PI3K-AKT include the proapoptotic protein BAD, caspase-9, NF-kappaB, and Forkhead. We have previously reported that BAD is constitutively phosphorylated in primary acute myeloid leukemia (AML) cells, a post-transcriptional modification, which inactivates its proapoptotic function. In this study, we tested the hypothesis that the inhibition of PI3K by LY294002 results in the dephosphorylation of AKT and BAD, and thus promote leukemia cell apoptosis. We investigated the effects of LY294002 in megakaryocytic leukemia-derived MO7E cells, primary AML and normal bone marrow progenitor cells. In MO7E cells, LY294002 reduced AKT kinase activity, induced dephosphorylation of AKT and BAD, and increased apoptosis. Concomitant inhibition of mitogen-activated protein kinase signaling or combination with all-trans retinoic acid further enhanced apoptosis of leukemic cells. In primary AML samples, clonogenic cell growth was significantly reduced. Normal hematopoietic progenitors were less affected, suggesting preferential targeting of leukemia cells. In conclusion, the data suggest that the inhibition of the PI3K/AKT signaling pathway restores apoptosis in AML and may be explored as a novel target for molecular therapeutics in AML

    Gravitation and Duality Symmetry

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    By generalizing the Hodge dual operator to the case of soldered bundles, and working in the context of the teleparallel equivalent of general relativity, an analysis of the duality symmetry in gravitation is performed. Although the basic conclusion is that, at least in the general case, gravitation is not dual symmetric, there is a particular theory in which this symmetry shows up. It is a self dual (or anti-self dual) teleparallel gravity in which, due to the fact that it does not contribute to the interaction of fermions with gravitation, the purely tensor part of torsion is assumed to vanish. The ensuing fermionic gravitational interaction is found to be chiral. Since duality is intimately related to renormalizability, this theory may eventually be more amenable to renormalization than teleparallel gravity or general relativity.Comment: 7 pages, no figures. Version 2: minor presentation changes, references added. Accepted for publication in Int. J. Mod. Phys.

    Quantitative single cell determination of ERK phosphorylation and regulation in relapsed and refractory primary acute myeloid leukemia

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    : We investigated the constitutive activation of the MEK/ERK pathway in acute myelogenous leukemia (AML) via a flow cytometric technique to quantitate expression of phosphorylated ERK (p-ERK). A total of 42 AML samples (16 newly diagnosed, 26 relapsed/refractory) were analyzed. Normal bone marrow CD34+ cells (n = 10) had little or no expression of p-ERK, while G-CSF-mobilized CD34+ cells exhibited enhanced p-ERK levels. Markedly elevated p-ERK levels were found in 83.3% of the AML samples, with no differences observed between the newly diagnosed and relapsed/refractory samples. Treatment with a MEK inhibitor resulted in significantly decreased p-ERK levels in both the newly diagnosed and relapsed/refractory samples, which was associated with growth arrest, but not apoptosis induction. In summary, we defined conditions for the analysis of MAPK signaling in primary AML samples. Normal CD34+ cells expressed very low levels of p-ERK, and increased p-ERK levels were found in normal G-CSF-stimulated circulating CD34+ cells. Constitutively high p-ERK levels observed in the majority of AML samples suggest deregulation of this pathway that appears to be independent of disease status. The ability of ERK inhibition to promote growth arrest rather than apoptosis suggests that clinical trials of MEK/ERK inhibitors may be more effective when combined with chemotherapy

    Triterpenoids Display Single Agent Anti-tumor Activity in a Transgenic Mouse Model of Chronic Lymphocytic Leukemia and Small B Cell Lymphoma

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    The synthetic triterpenoid 2-Cyano-3,12-Dioxooleana-1,9-Dien-28-Oic Acid (CDDO) and derivatives display anti-tumor activity against a variety of cultured tumor cell lines and in mouse xenografts. In this report, we have studied the effects of CDDO and its imidazolide derivative (CDDO-Im) on chronic lymphocytic leukemia (CLL), using patients' CLL cells and a mouse model of CLL and small B cell lymphoma (SBL).CDDO and CDDO-Im efficiently induced apoptosis of malignant human and mouse B-cells ex vivo, although CDDO-Im was over 10-fold more potent than CDDO. Treating mice with CLL/SBL with liposome-formulated CDDO or CDDO-Im resulted in significant reductions of B cells in blood, spleen and lung. CDDO-Im was shown to be more potent than CDDO, while treatment with empty liposomes had no impact on disease. CDDO-Im treatment initially resulted in an increase of circulating B cells, which correlates with a reduction in resident lymphocytes in spleen, and lungs, suggesting that CDDO-Im induces mobilization of tumor cells from lymphoid organs and infiltrated tissues into the circulation. Analysis of blood cells recovered from treated mice also showed that CDDO-Im is a potent inducer of tumor cells death in vivo. Furthermore, CDDO-Im efficiently eradicated mouse CLL/SBL cells but had little effect on the viability of normal B and T cells in vivo.The presented data demonstrate that triterpenoids CDDO and CDDO-Im reduce leukemia and lymphoma burden in vivo in a transgenic mouse model of CLL/SBL, and support the clinical testing of CDDO-based synthetic triterpenoids in patients with CLL

    Therapeutic targeting of the MEK/MAPK signal transduction module in acute myeloid leukemia

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    : The mitogen-activated protein kinase (MAPK) pathway regulates growth and survival of many cell types, and its constitutive activation has been implicated in the pathogenesis of a variety of malignancies. In this study we demonstrate that small-molecule MEK inhibitors (PD98059 and PD184352) profoundly impair cell growth and survival of acute myeloid leukemia (AML) cell lines and primary samples with constitutive MAPK activation. These agents abrogate the clonogenicity of leukemic cells but have minimal effects on normal hematopoietic progenitors. MEK blockade also results in sensitization to spontaneous and drug-induced apoptosis. At a molecular level, these effects correlate with modulation of the expression of cyclin-dependent kinase inhibitors (p27(Kip1) and p21(Waf1/CIP1)) and antiapoptotic proteins of the inhibitor of apoptosis proteins (IAP) and Bcl-2 families. Interruption of constitutive MEK/MAPK signaling therefore represents a promising therapeutic strategy in AML

    Gauge field theory for Poincar\'{e}-Weyl group

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    On the basis of the general principles of a gauge field theory the gauge theory for the Poincar\'{e}-Weyl group is constructed. It is shown that tetrads are not true gauge fields, but represent functions from true gauge fields: Lorentzian, translational and dilatational ones. The equations of gauge fields which sources are an energy-momentum tensor, orbital and spin momemta, and also a dilatational current of an external field are obtained. A new direct interaction of the Lorentzian gauge field with the orbital momentum of an external field appears, which describes some new effects. Geometrical interpretation of the theory is developed and it is shown that as a result of localization of the Poincar\'{e}-Weyl group spacetime becomes a Weyl-Cartan space. Also the geometrical interpretation of a dilaton field as a component of the metric tensor of a tangent space in Weyl-Cartan geometry is proposed.Comment: LaTex, 27 pages, no figure
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