534 research outputs found

    Hadronic mass and q^2 moments of charmless semileptonic B decay distributions

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    We report OPE predictions for hadronic mass and q^2 moments in inclusive semileptonic B decays without charm, taking into account experimental cuts on the charged lepton energy and on the hadronic invariant mass, and address the related theoretical uncertainty.Comment: 16 pages, 1 figure; v3: we have corrected a mistake in the code that produced the numerical results; tables replaced, small changes in the tex

    Cabozantinib in neuroendocrine tumours: tackling drug activity and resistance mechanisms

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    Neuroendocrine tumors (NETs) are highly vascularized malignancies in which angiogenesis may entail cell proliferation and survival. Among the emerging compounds with antivascular properties, cabozantinib (CAB) appeared promising. We analyzed the antitumor activity of CAB against NETs utilizing in vitro and in vivo models. For cell cultures, we used BON-1, NCI-H727 and NCI-H720 cell lines. Cell viability was assessed by manual count coupled with quantification of cell death, performed through fluorescence-activated cell sorting analysis as propidium iodide exclusion assay. In addition, we investigated the modulation of the antiapoptotic myeloid cell leukemia 1 protein under CAB exposure, as a putative adaptive pro-survival mechanism, and compared the responses with sunitinib. The activity of CAB was also tested in mouse and zebrafish xenograft tumor models. Cabozantinib showed a dose-dependent and time-dependent effect on cell viability and proliferation in human NET cultures, besides a halting of cell cycle progression for endoduplication, never reported for other tyrosine kinase inhibitors. In a transplantable zebrafish model, CAB drastically inhibited NET-induced angiogenesis and migration of implanted cells through the embryo body. CAB showed encouraging activity in NETs, both in vitro and in vivo models. On this basis, we envisage future research to further investigate along these promising lines

    Responses of peripheral blood mononucleated cells from non-celiac gluten sensitive patients to various cereal sources

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    Non-celiac gluten sensitivity (NCGS) is still an undefined syndrome whose triggering mechanisms remain unsettled. This study aimed to clarify how cultured peripheral blood mononucleated cells (PBMC) obtained from NCGS patients responded to contact with wheat proteins. Results demonstrated that wheat protein induced an overactivation of the proinflammatory chemokine CXCL10 in PBMC from NCGS patients, and that the overactivation level depends on the cereal source from which proteins are obtained. CXCL10 is able to decrease the transepithelial resistance of monolayers of normal colonocytes (NCM 460) by diminishing the mRNA expression of cadherin-1 (CDH1) and tight junction protein 2 (TJP2), two primary components of the tight junction strands. Thus, CXCL10 overactivation is one of the mechanisms triggered by wheat proteins in PBMC obtained from NCGS patients. This mechanism is activated to a greater extent by proteins from modern with respect to those extracted from ancient wheat genotypes

    Spitzer-IRS high resolution spectroscopic survey of the 12 micron Seyfert galaxies: II. Results for the Complete Dataset

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    We present the Spitzer 10-37um IRS high resolution (R~600) spectroscopic survey of the Seyfert galaxies of the 12 micron Galaxy Sample. The new spectra of 61 galaxies, with those already published, gives us a total of 91 12micron Seyfert galaxies observed, out of 112. We use an improved AGN classification for Seyfert galaxies: instead of the type 1 and 2 classes, we use the spectropolarimetric data to divide them into "AGN 1" and "AGN 2", where AGN 1's include all broad-line objects, including the Seyfert 2's showing hidden broad lines in polarized light, while AGN 2's contains only Seyferts with no detectable broad lines at all. We present various mid-IR observables and we find that these properties characterize the AGN 1's objects as a single family, with strongly AGN-dominated spectra. In contrast, the AGN 2's can be divided in two groups, the first one with properties similar to the AGN 1's and the second similar to the non-Seyfert galaxies, such as LINERs or starburst galaxies. We computed a semianalytical model to estimate the AGN and the starburst contributions to the mid-IR galaxy emission at 19um. We find that AGN 1 have an AGN contribution >73% and AGN 2 >45% of their total emission at 19um. The detection of [NeV] lines is an almost perfect signature of energy production by an AGN. We present mean spectra of the various AGN categories. We derive the first local luminosity functions for the mid-infrared lines and the PAH feature. No statistical difference is found in the space densities for Seyfert 1's and 2's, nor for the new classes of AGN 1's and 2's. The global output of accretion-powered galactic nuclei in the local universe is derived from the correlation between [NeV] line and the nonstellar IR continuum luminosity.Comment: Accepted in The Astrophysical Journal Part 1 on November 15, 2009. 58 page

    Comparing long-acting antipsychotic discontinuation rates under ordinary clinical circumstances: a survival analysis from an observational, pragmatic study

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    Background: Recent guidelines suggested a wider use of long-acting injectable antipsychotics (LAI) than previously, but naturalistic data on the consequences of LAI use in terms of discontinuation rates and associated factors are still sparse, making it hard for clinicians to be informed on plausible treatment courses. Objective: Our objective was to assess, under real-world clinical circumstances, LAI discontinuation rates over a period of 12 months after a first prescription, reasons for discontinuation, and associated factors. Methods: The STAR Network 'Depot Study' was a naturalistic, multicentre, observational prospective study that enrolled subjects initiating a LAI without restrictions on diagnosis, clinical severity or setting. Participants from 32 Italian centres were assessed at baseline and at 6 and 12 months of follow-up. Psychopathology, drug attitude and treatment adherence were measured using the Brief Psychiatric Rating Scale, the Drug Attitude Inventory and the Kemp scale, respectively. Results: The study followed 394 participants for 12 months. The overall discontinuation rate at 12 months was 39.3% (95% confidence interval [CI] 34.4-44.3), with paliperidone LAI being the least discontinued LAI (33.9%; 95% CI 25.3-43.5) and olanzapine LAI the most discontinued (62.5%; 95% CI 35.4-84.8). The most frequent reason for discontinuation was onset of adverse events (32.9%; 95% CI 25.6-40.9) followed by participant refusal of the medication (20.6%; 95% CI 14.6-27.9). Medication adherence at baseline was negatively associated with discontinuation risk (hazard ratio [HR] 0.853; 95% CI 0.742-0.981; p = 0.026), whereas being prescribed olanzapine LAI was associated with increased discontinuation risk compared with being prescribed paliperidone LAI (HR 2.156; 95% CI 1.003-4.634; p = 0.049). Conclusions: Clinicians should be aware that LAI discontinuation is a frequent occurrence. LAI choice should be carefully discussed with the patient, taking into account individual characteristics and possible obstacles related to the practicalities of each formulation

    The Chandra XBootes Survey - III: Optical and Near-IR Counterparts

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    The XBootes Survey is a 5-ks Chandra survey of the Bootes Field of the NOAO Deep Wide-Field Survey (NDWFS). This survey is unique in that it is the largest (9.3 deg^2), contiguous region imaged in X-ray with complementary deep optical and near-IR observations. We present a catalog of the optical counterparts to the 3,213 X-ray point sources detected in the XBootes survey. Using a Bayesian identification scheme, we successfully identified optical counterparts for 98% of the X-ray point sources. The optical colors suggest that the optically detected galaxies are a combination of z<1 massive early-type galaxies and bluer star-forming galaxies whose optical AGN emission is faint or obscured, whereas the majority of the optically detected point sources are likely quasars over a large redshift range. Our large area, X-ray bright, optically deep survey enables us to select a large sub-sample of sources (773) with high X-ray to optical flux ratios (f_x/f_o>10). These objects are likely high redshift and/or dust obscured AGN. These sources have generally harder X-ray spectra than sources with 0.1<f_x/f_o<10. Of the 73 X-ray sources with no optical counterpart in the NDWFS catalog, 47 are truly optically blank down to R~25.5 (the average 50% completeness limit of the NDWFS R-band catalogs). These sources are also likely to be high redshift and/or dust obscured AGN.Comment: 19 pages, 13 figures, ApJ accepted. Catalog can be found at: http://www.noao.edu/noao/noaodeep or ftp://archive.noao.edu/pub/catalogs/xbootes
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