1,579 research outputs found

    Prenatal origin of childhood AML occurs less frequently than in childhood ALL

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    Background While there is enough convincing evidence in childhood acute lymphoblastic leukemia (ALL), the data on the pre-natal origin in childhood acute myeloid leukemia (AML) are less comprehensive. Our study aimed to screen Guthrie cards (neonatal blood spots) of non-infant childhood AML and ALL patients for the presence of their respective leukemic markers. Methods We analysed Guthrie cards of 12 ALL patients aged 2–6 years using immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements (n = 15) and/or intronic breakpoints of TEL/AML1 fusion gene (n = 3). In AML patients (n = 13, age 1–14 years) PML/RARalpha (n = 4), CBFbeta/MYH11 (n = 3), AML1/ETO (n = 2), MLL/AF6 (n = 1), MLL/AF9 (n = 1) and MLL/AF10 (n = 1) fusion genes and/or internal tandem duplication of FLT3 gene (FLT3/ITD) (n = 2) were used as clonotypic markers. Assay sensitivity determined using serial dilutions of patient DNA into the DNA of a healthy donor allowed us to detect the pre-leukemic clone in Guthrie card providing 1–3 positive cells were present in the neonatal blood spot. Results In 3 patients with ALL (25%) we reproducibly detected their leukemic markers (Ig/TCR n = 2; TEL/AML1 n = 1) in the Guthrie card. We did not find patient-specific molecular markers in any patient with AML. Conclusion In the largest cohort examined so far we used identical approach for the backtracking of non-infant childhood ALL and AML. Our data suggest that either the prenatal origin of AML is less frequent or the load of pre-leukemic cells is significantly lower at birth in AML compared to ALL cases

    Optimizing Human Synovial Fluid Preparation for Two-Dimensional Gel Electrophoresis

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    <p>Abstract</p> <p>Background</p> <p>Proteome analysis is frequently applied in identifying the proteins or biomarkers in knee synovial fluids (SF) that are associated with osteoarthritis and other arthritic disorders. The 2-dimensional gel electrophoresis (2-DE) is the technique of choice in these studies. Disease biomarkers usually appear in low concentrations and may be masked by high abundant proteins. Therefore, the main aim of this study was to find the most suitable sample preparation method that can optimize the expression of proteins on 2-DE gels that can be used to develop a reference proteome picture for non-osteoarthritic knee synovial fluid samples. Proteome pictures obtained from osteoarthritic knee synovial fluids can then be compared with the reference proteome pictures obtained in this study to assist us in identifying the disease biomarkers more correctly.</p> <p>Results</p> <p>The proteomic tool of 2-DE with immobilized pH gradients was applied in this study. A total of 12 2-DE gel images were constructed from SF samples that were free of osteoarthritis. In these samples, 3 were not treated with any sample preparation methods, 3 were treated with acetone, 3 were treated with 2-DE Clean-Up Kit, and 3 were treated with the combination of acetone and 2-D Clean-Up Kit prior to 2-DE analysis. Gel images were analyzed using the PDQuest Basic 8.0.1 Analytical software. Protein spots that were of interest were excised from the gels and sent for identification by mass spectrometry. Total SF total protein concentration was calculated to be 21.98 ± 0.86 mg/mL. The untreated SF samples were detected to have 456 ± 33 protein spots on 2-DE gel images. Acetone treated SF samples were detected to have 320 ± 28 protein spots, 2-D Clean-Up Kit treated SF samples were detected to have 413 ± 31 protein spots, and the combined treatment method of acetone and 2-D Clean-Up Kit was detected to have 278 ± 26 protein spots 2-DE gel images. SF samples treated with 2-D Clean-Up Kit revealed clearer presentation of the isoforms and increased intensities of the less abundant proteins of haptoglobin, apolipoprotein A-IV, prostaglandin-D synthase, alpha-1B-glycoprotein, and alpha-2-HS-glycoprotein on 2-DE gel images as compared with untreated SF samples and SF samples treated with acetone.</p> <p>Conclusions</p> <p>The acetone precipitation method and the combined treatment effect of acetone and 2-DE Clean-Up Kit are not preferred in preparing SF samples for 2-DE analysis as both protein intensities and numbers decrease significantly. On the other hand, 2-D Clean-Up Kit treated SF samples revealed clearer isoforms and higher intensities for the less abundant proteins of haptoglobin, apolipoprotein A-IV, prostaglandin-D synthase, alpha-1B-glycoprotein, and alpha-2-HS-glycoprotein on 2-DE gels. As a result, it is recommended that SF samples should be treated with protein clean up products such as 2-D Clean-Up Kit first before conducting proteomic research in searching for the relevant biomarkers associated with knee osteoarthritis.</p

    General Gauge Mediation at the Weak Scale

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    We completely characterize General Gauge Mediation (GGM) at the weak scale by solving all IR constraints over the full parameter space. This is made possible through a combination of numerical and analytical methods, based on a set of algebraic relations among the IR soft masses derived from the GGM boundary conditions in the UV. We show how tensions between just a few constraints determine the boundaries of the parameter space: electroweak symmetry breaking (EWSB), the Higgs mass, slepton tachyons, and left-handed stop/sbottom tachyons. While these constraints allow the left-handed squarks to be arbitrarily light, they place strong lower bounds on all of the right-handed squarks. Meanwhile, light EW superpartners are generic throughout much of the parameter space. This is especially the case at lower messenger scales, where a positive threshold correction to mhm_h coming from light Higgsinos and winos is essential in order to satisfy the Higgs mass constraint.Comment: 43 pages, 20 figures, mathematica package included in the sourc

    A Complete Model of Low-Scale Gauge Mediation

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    Recent signs of a Standard Model-like Higgs at 125 GeV point towards large A-terms in the MSSM. This presents special challenges for gauge mediation, which by itself predicts vanishing A-terms at the messenger scale. In this paper, we review the general problems that arise when extending gauge mediation to achieve large A-terms, and the mechanisms that exist to overcome them. Using these mechanisms, we construct weakly-coupled models of low-scale gauge mediation with extended Higgs-messenger couplings that generate large A-terms at the messenger scale and viable mu/B_mu-terms. Our models are simple, economical, and complete realizations of supersymmetry at the weak scale.Comment: 33 pages; v2: refs added, minor change

    Pseudomoduli Dark Matter and Quiver Gauge Theories

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    We investigate supersymmetric models for dark matter which is represented by pseudomoduli in weakly coupled hidden sectors. We propose a scheme to add a dark matter sector to quiver gauge theories with metastable supersymmetry breaking. We discuss the embedding of such scheme in string theory and we describe the dark matter sector in terms of D7 flavour branes. We explore the phenomenology in various regions of the parameters.Comment: 24 pages, 12 figures, JHEP3.cl

    Simplified R-Symmetry Breaking and Low-Scale Gauge Mediation

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    We argue that some of the difficulties in constructing realistic models of low-scale gauge mediation are artifacts of the narrow set of models that have been studied. In particular, much attention has been payed to the scenario in which the Goldstino superfield in an O'Raifeartaigh model is responsible for both supersymmetry breaking and R-symmetry breaking. In such models, the competing problems of generating sufficiently massive gauginos while preserving an acceptably light gravitino can be quite challenging. We show that by sharing the burdens of breaking supersymmetry and R-symmetry with a second field, these problems are easily solved even within the O'Raifeartaigh framework. We present explicit models realizing minimal gauge mediation with a gravitino mass in the eV range that are both calculable and falsifiable.Comment: 31 pages, 4 figures, references added, minor change

    Cosmological vacuum selection and metastable susy breaking

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    We study gauge mediation in a wide class of O'Raifeartaigh type models where supersymmetry breaking metastable vacuum is created by gravity and/or quantum corrections. We examine their thermal evolution in the early universe and the conditions under which the susy breaking vacuum can be selected. It is demonstrated that thermalization typically makes the metastable supersymmetry breaking cosmologically disfavoured but this is not always the case. Initial conditions with the spurion displaced from the symmetric thermal minimum and a small coupling to the messenger sector can result in the realization of the susy breaking vacuum even if the reheating temperature is high. We show that this can be achieved without jeopardizing the low energy phenomenology. In addition, we have found that deforming the models by a supersymmetric mass term for messengers in such a way that the susy breaking minimum and the susy preserving minima are all far away from the origin does not change the conclusions. The basic observations are expected to hold also in the case of models with an anomalous U(1) group.Comment: 28 pages, 4 figures, plain Latex, journal versio

    Light Stop NLSPs at the Tevatron and LHC

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    How light can the stop be given current experimental constraints? Can it still be lighter than the top? In this paper, we study this and related questions in the context of gauge-mediated supersymmetry breaking, where a stop NLSP decays into a W, b and gravitino. Focusing on the case of prompt decays, we simulate several existing Tevatron and LHC analyses that would be sensitive to this scenario, and find that they allow the stop to be as light as 150 GeV, mostly due to the large top production background. With more data, the existing LHC analyses will be able to push the limit up to at least 180 GeV. We hope this work will motivate more dedicated experimental searches for this simple scenario, in which, for most purposes, the only free parameters are the stop mass and lifetime.Comment: 31 pages, 11 figures; v2: added minor clarifications and reference

    Prompt Decays of General Neutralino NLSPs at the Tevatron

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    Recent theoretical developments have shown that gauge mediation has a much larger parameter space of possible spectra and mixings than previously considered. Motivated by this, we explore the collider phenomenology of gauge mediation models where a general neutralino is the lightest MSSM superpartner (the NLSP), focusing on the potential reach from existing and future Tevatron searches. Promptly decaying general neutralino NLSPs can give rise to final states involving missing energy plus photons, Zs, Ws and/or Higgses. We survey the final states and determine those where the Tevatron should have the most sensitivity. We then estimate the reach of existing Tevatron searches in these final states and discuss new searches (or optimizations of existing ones) that should improve the reach. Finally we comment on the potential for discovery at the LHC.Comment: 41 pages, minor changes, added refs and discussion of previous literatur
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