810 research outputs found

    MTSS1 is a critical epigenetically regulated tumor suppressor in CML

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    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

    Search for the Supersymmetric Partner of the Top-Quark in ppˉp \bar{p} Collisions at s=1.8TeV\sqrt{s} = 1.8 {\rm TeV}

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    We report on a search for the supersymmetric partner of the top quark (stop) produced in ttˉt \bar{t} events using 110pb1110 {\rm pb}^{-1} of ppˉp \bar{p} collisions at s=1.8TeV\sqrt{s} = 1.8 {\rm TeV} recorded with the Collider Detector at Fermilab. In the case of a light stop squark, the decay of the top quark into stop plus the lightest supersymmetric particle (LSP) could have a significant branching ratio. The observed events are consistent with Standard Model ttˉt \bar{t} production and decay. Hence, we set limits on the branching ratio of the top quark decaying into stop plus LSP, excluding branching ratios above 45% for a LSP mass up to 40 {\rm GeV/c}2^{2}.Comment: 11 pages, 4 figure

    Measurement of the Associated γ+μ±\gamma + \mu^\pm Production Cross Section in ppˉp \bar p Collisions at s=1.8\sqrt{s} = 1.8 TeV

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    We present the first measurement of associated direct photon + muon production in hadronic collisions, from a sample of 1.8 TeV ppˉp \bar p collisions recorded with the Collider Detector at Fermilab. Quantum chromodynamics (QCD) predicts that these events are primarily from the Compton scattering process cgcγcg \to c\gamma, with the final state charm quark producing a muon. Hence this measurement is sensitive to the charm quark content of the proton. The measured cross section of 29±9pb129\pm 9 pb^{-1} is compared to a leading-order QCD parton shower model as well as a next-to-leading-order QCD calculation.Comment: 12 pages, 4 figures Added more detailed description of muon background estimat

    Policy shifts and Markov-switching in financial markets

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    Veränderungen der Rahmenbedingungen auf Finanzmärkten müssen von ökonomischen und ökonometrischen Modellen sinnvoll erfasst werden. Diese Dissertation beschäftigt sich mit der Zinsdynamik im Vorfeld einer Währungsunion. Auf diese Dynamik aufbauend werden Optionen auf Nullkuponanleihen bewertet. Wird die veränderte Dynamik nicht beachtet kann es zum Teil zu erheblichen Fehlbewertungen kommen wie in einer Monte-Carlo Studie gezeigt wird. Ferner wird ein Markov-Switching GARCH-Modell entwickelt, welches verschiedene GARCH Variationen in den einzelnen Regimen zulässt. So sind erstmals auch Wechsel der Spezifikation in den einzelnen Regimen, wie z.B. EGARCH-GARCH Modelle möglich. Diese neue Modellklasse wird genutzt, um die Auswirkungen des Verbots ungedeckter Leerverkäufe auf ausgewählte Aktien zu untersuchen

    Measurement of the B0 anti-B0 oscillation frequency using l- D*+ pairs and lepton flavor tags

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    The oscillation frequency Delta-md of B0 anti-B0 mixing is measured using the partially reconstructed semileptonic decay anti-B0 -> l- nubar D*+ X. The data sample was collected with the CDF detector at the Fermilab Tevatron collider during 1992 - 1995 by triggering on the existence of two lepton candidates in an event, and corresponds to about 110 pb-1 of pbar p collisions at sqrt(s) = 1.8 TeV. We estimate the proper decay time of the anti-B0 meson from the measured decay length and reconstructed momentum of the l- D*+ system. The charge of the lepton in the final state identifies the flavor of the anti-B0 meson at its decay. The second lepton in the event is used to infer the flavor of the anti-B0 meson at production. We measure the oscillation frequency to be Delta-md = 0.516 +/- 0.099 +0.029 -0.035 ps-1, where the first uncertainty is statistical and the second is systematic.Comment: 30 pages, 7 figures. Submitted to Physical Review

    COVID-19-related challenges in dental education: experiences from Australia, Brazil, and the USA

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    Aim: To describe the management of dental education in three dental schools during the COVID-19 crisis. Methods: Adopted strategies in the Federal University of Paraíba (UFPB), Brazil, University of Pittsburgh (UP), USA, and Griffith University (GU), Australia were detailed. Results: In the UFPB, all on-site teaching was suspended, and resources for distance learning set up as a supplementary semester to be available as face to face classes later. A protocol for clinical care followed safety measures recommended by Brazilian official health institutions. The adequacy of the physical structure, human resources, and personal protective equipment (PPE) acquisition for the return to clinical activities are currently under discussion. In the UP, learning activities were shifted to virtual teaching using lecture recordings and live sections. All elective patients care was postponed. Urgent dental cases were discussed via teledentistry. The physical layout of the dental clinics and pre-clinical laboratories were changed, allowing a safe distance between students. In the GU, all clinical and pre-clinical activities were cancelled, and theoretical activities were maintained online for all students. Several clinically based scenarios where created and delivered in the format of online problem-based learning. The reception area was redesigned, ensuring social distancing. Safety measures follow the Australia Dental Association. Conclusions: Dealing with dental education depends on the stage of the epidemic and the characteristics of each country

    Search for New Particles Decaying to Dijets at CDF

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    We have used 106 pb^-1 of data collected with the Collider Detector at Fermilab to search for new particles decaying to dijets. We exclude at the 95% confidence level models containing the following new particles: axigluons and flavor universal colorons with mass between 200 and 980 GeV/c, excited quarks with mass between 80 and 570 GeV/c^2 and between 580 and 760 GeV/c^2, color octet technirhos with mass between 260 and 480 GeV/c^2, W' bosons with mass between 300 and 420 GeV/c^2, and E_6 diquarks with mass between 290 and 420 GeV/c^2.Comment: 18 pages, 4 figures, 1 table. Submitted to Physical Review D Rapid Communications. Postscript file of paper is also available at http://www-cdf.fnal.gov/physics/pub97/cdf3276_dijet_search_prd_rc.p

    Measurement of Dijet Angular Distributions at CDF

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    We have used 106 pb^-1 of data collected in proton-antiproton collisions at sqrt(s)=1.8 TeV by the Collider Detector at Fermilab to measure jet angular distributions in events with two jets in the final state. The angular distributions agree with next to leading order (NLO) predictions of Quantum Chromodynamics (QCD) in all dijet invariant mass regions. The data exclude at 95% confidence level (CL) a model of quark substructure in which only up and down quarks are composite and the contact interaction scale is Lambda_ud(+) < 1.6 TeV or Lambda_ud(-) < 1.4 TeV. For a model in which all quarks are composite the excluded regions are Lambda(+) < 1.8 TeV and Lambda(-) < 1. 6 TeV.Comment: 16 pages, 2 figures, 2 tables, LaTex, using epsf.sty. Submitted to Physical Review Letters on September 17, 1996. Postscript file of full paper available at http://www-cdf.fnal.gov/physics/pub96/cdf3773_dijet_angle_prl.p

    Disability and Political Representation: Analysing the Obstacles to Elected Office in the UK

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    Around 1 in 6 Europeans are disabled, yet there are few self-declared disabled politicians. Despite scholarly and political interest in the under-representation of various social groups, little attention has been paid to disabled people. This article identifies and analyses the barriers to elected office faced by disabled people by drawing upon interviews with 51 candidates and elected politicians in the UK. It reveals barriers which occur throughout the political recruitment process, from initial participation to selection and the election campaign. They broadly fall into (1) a lack of accessibility, including the built environment and documents; (2) a lack of resources to make events and activities accessible; and (3) ableism, including openly expressed prejudices but also a lack of awareness and willingness to make processes inclusive. While people with different impairments encounter some distinct barriers, all of them have similar experiences of obstacles and exclusion which go beyond those faced by people from other under-represented groups seeking elected office
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