57 research outputs found

    Improved W boson mass measurement with the D0 detector

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    We have measured the W boson mass using the D0 detector and a data sample of 82 pb^-1 from the Tevatron collider. This measurement used W -> e nu decays, where the electron is close to a boundary of a central electromagnetic calorimeter module. Such 'edge' electrons have not been used in any previous D0 analysis, and represent a 14% increase in the W boson sample size. For these electrons, new response and resolution parameters are determined, and revised backgrounds and underlying event energy flow measurements are made. When the current measurement is combined with previous D0 W boson mass measurements, we obtain M_W = 80.483 +/- 0.084 GeV. The 8% improvement from the previous D0 measurement is primarily due to the improved determination of the response parameters for non-edge electrons using the sample of Z bosons with non-edge and edge electrons.Comment: submitted to Phys. Rev. D; 20 pages, 18 figures, 9 table

    Lack of SMARCB1 expression characterizes a subset of human and murine peripheral T-cell lymphomas.

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    Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous group of malignancies with poor outcome. Here, we identify a subgroup, PTCL-NOS <sup>SMARCB1-</sup> , which is characterized by the lack of the SMARCB1 protein and occurs more frequently in young patients. Human and murine PTCL-NOS <sup>SMARCB1-</sup> show similar DNA methylation profiles, with hypermethylation of T-cell-related genes and hypomethylation of genes involved in myeloid development. Single-cell analyses of human and murine tumors revealed a rich and complex network of interactions between tumor cells and an immunosuppressive and exhausted tumor microenvironment (TME). In a drug screen, we identified histone deacetylase inhibitors (HDACi) as a class of drugs effective against PTCL-NOS <sup>Smarcb1-</sup> . In vivo treatment of mouse tumors with SAHA, a pan-HDACi, triggered remodeling of the TME, promoting replenishment of lymphoid compartments and reversal of the exhaustion phenotype. These results provide a rationale for further exploration of HDACi combination therapies targeting PTCL-NOS <sup>SMARCB1-</sup> within the TME

    Patterns, predictors and prognostic relevance of high-grade hematotoxicity after temozolomide or temozolomide-lomustine in the CeTeG/NOA-09 trial

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    PURPOSE: In the randomized phase III trial CeTeG/NOA-09, temozolomide (TMZ)/lomustine (CCNU) combination therapy was superior to TMZ in newly diagnosed MGMT methylated glioblastoma, albeit reporting more frequent hematotoxicity. Here, we analyze high grade hematotoxicity and its prognostic relevance in the trial population. METHODS: Descriptive and comparative analysis of hematotoxicity adverse events ≥ grade 3 (HAE) according to the Common Terminology of Clinical Adverse Events, version 4.0 was performed. The association of HAE with survival was assessed in a landmark analysis. Logistic regression analysis was performed to predict HAE during the concomitant phase of chemotherapy. RESULTS: HAE occurred in 36.4% and 28.6% of patients under CCNU/TMZ and TMZ treatment, respectively. The median onset of the first HAE was during concomitant chemotherapy (i.e. first CCNU/TMZ course or daily TMZ therapy), and 42.9% of patients with HAE receiving further courses experienced repeat HAE. Median HAE duration was similar between treatment arms (CCNU/TMZ 11.5; TMZ 13 days). Chemotherapy was more often discontinued due to HAE in CCNU/TMZ than in TMZ (19.7 vs. 6.3%, p = 0.036). The occurrence of HAE was not associated with survival differences (p = 0.76). Regression analysis confirmed older age (OR 1.08) and female sex (OR 2.47), but not treatment arm, as predictors of HAE. CONCLUSION: Older age and female sex are associated with higher incidence of HAE. Although occurrence of HAE was not associated with shorter survival, reliable prediction of patients at risk might be beneficial to allow optimal management of therapy and allocation of supportive measures. TRIAL REGISTRATION: NCT01149109

    The Biochemical and Cellular Basis for Nutraceutical Strategies to Attenuate Neurodegeneration in Parkinson’s Disease

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    Future therapeutic intervention that could effectively decelerate the rate of degeneration within the substantia nigra pars compacta (SNc) could add years of mobility and reduce morbidity associated with Parkinson’s disease (PD). Neurodegenerative decline associated with PD is distinguished by extensive damage to SNc dopaminergic (DAergic) neurons and decay of the striatal tract. While genetic mutations or environmental toxins can precipitate pathology, progressive degenerative succession involves a gradual decline in DA neurotransmission/synaptic uptake, impaired oxidative glucose consumption, a rise in striatal lactate and chronic inflammation. Nutraceuticals play a fundamental role in energy metabolism and signaling transduction pathways that control neurotransmission and inflammation. However, the use of nutritional supplements to slow the progression of PD has met with considerable challenge and has thus far proven unsuccessful. This review re-examines precipitating factors and insults involved in PD and how nutraceuticals can affect each of these biological targets. Discussed are disease dynamics (Sections 1 and 2) and natural substances, vitamins and minerals that could impact disease processes (Section 3). Topics include nutritional influences on α-synuclein aggregation, ubiquitin proteasome function, mTOR signaling/lysosomal-autophagy, energy failure, faulty catecholamine trafficking, DA oxidation, synthesis of toxic DA-quinones, o-semiquinones, benzothiazolines, hyperhomocyseinemia, methylation, inflammation and irreversible oxidation of neuromelanin. In summary, it is clear that future research will be required to consider the multi-faceted nature of this disease and re-examine how and why the use of nutritional multi-vitamin-mineral and plant-based combinations could be used to slow the progression of PD, if possible

    Limits on Anomalous WWgamma and WWZ Couplings from WW/WZ->enujj Production

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    Limits on anomalous WWgamma and WWZ couplings are presented from a study of WW/WZ->enujj events in ppbar collisions at sqrt{s}=1.8 TeV. Results from the analysis of data collected using the D0 detector during the 1993-1995 Tevatron collider run at Fermilab are combined with those of an earlier study from the 1992-1993 run. A fit to the transverse momentum spectrum of the W boson yields direct limits on anomalous WWgamma and WWZ couplings. With the assumption that the WWgamma and WWZ couplings are equal, we obtain -0.34< lambda < 0.36 (with Delta kappa=0) and -0.43< Delta kappa < 0.59 (with lambda=0) at the 95 confidence level for a form-factor scale Lambda=2.0 TeV.Comment: 37 pages, 13 figures, submitted to Phys. Rev.

    The economic well-being of nations is associated with positive daily situational experiences

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    People in economically advantaged nations tend to evaluate their life as more positive overall and report greater well-being than people in less advantaged nations. But how does positivity manifest in the daily life experiences of individuals around the world? The present study asked 15,244 college students from 62 nations, in 42 languages, to describe a situation they experienced the previous day using the Riverside Situational Q-sort (RSQ). Using expert ratings, the overall positivity of each situation was calculated for both nations and individuals. The positivity of the average situation in each nation was strongly related to the economic development of the nation as measured by the Human Development Index (HDI). For individuals’ daily experiences, the economic status of their nation also predicted the positivity of their experience, even more than their family socioeconomic status. Further analyses revealed the specific characteristics of the average situations for higher HDI nations that make their experiences more positive. Higher HDI was associated with situational experiences involving humor, socializing with others, and the potential to express emotions and fantasies. Lower HDI was associated with an increase in the presence of threats, blame, and hostility, as well as situational experiences consisting of family, religion, and money. Despite the increase in a few negative situational characteristics in lower HDI countries, the overall average experience still ranged from neutral to slightly positive, rather than negative, suggesting that greater HDI may not necessarily increase positive experiences but rather decrease negative experiences. The results illustrate how national economic status influences the lives of individuals even within a single instance of daily life, with large and powerful consequences when accumulated across individuals within each nation

    Crowded visual search in children with normal vision and children with visual impairment

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    Contains fulltext : 123733.pdf (publisher's version ) (Open Access)This study investigates the influence of oculomotor control, crowding, and attentional factors on visual search in children with normal vision ([NV], n = 11), children with visual impairment without nystagmus ([VI−nys], n = 11), and children with VI with accompanying nystagmus ([VI+nys], n = 26). Exclusion criteria for children with VI were: multiple impairments and visual acuity poorer than 20/400 or better than 20/50. Three search conditions were presented: a row with homogeneous distractors, a matrix with homogeneous distractors, and a matrix with heterogeneous distractors. Element spacing was manipulated in 5 steps from 2 to 32 minutes of arc. Symbols were sized 2 times the threshold acuity to guarantee visibility for the VI groups. During simple row and matrix search with homogeneous distractors children in the VI+nys group were less accurate than children with NV at smaller spacings. Group differences were even more pronounced during matrix search with heterogeneous distractors. Search times were longer in children with VI compared to children with NV. The more extended impairments during serial search reveal greater dependence on oculomotor control during serial compared to parallel search.10 p
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