266 research outputs found

    The impact of televised sports on adult nonfiction sports publishing

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    Thyreostats can be used fraudulently to promote a rapid weight increase of breeding animals at low cost. Their severe toxicological effects impose the development of reliable analytical methods to be used in monitoring plans. This work describes an alternative approach to isolate residues of thiouracil, methyl-thiouracil, propyl-thiouracil, phenyl-thiouracil, tapazole and mercaptobenzimidazole from bovine muscle tissue. The developed procedure is based on three steps: i) matrix solid phase dispersion with C18 for the preliminary sample preparation; ii) subcritical water extraction (SWE) at 160°C and 100 bar; iii) clean-up on an Oasis HLB cartridge. The quantitative determination was performed by liquid chromatography-electrospray-tandem mass spectrometry (LC-MS/MS) in dual polarity ionization by using internal standardization. The SWE-LC-MS/MS method was validated according to the identification criteria of the Commission decision 2002/657/EC. The relative recoveries ranged from 72% to 97%; within-lab reproducibility was less than 18%. The decision limit and the detection capability of all analytes were below the recommended concentration, set at 10 µg kg−1, but the validation results demonstrated that this method could only be applied for screening of thiouracil and methyl-thiouracil. Besides the analytical advantages related to the use of water as solvent extraction, the procedure allowed significant removal of lipids, whose detrimental effects on instrumentation and MS sensitivity are well-known

    The effect of bilateral internal thoracic artery harvesting on superficial and deep sternal infection: The role of skeletonization

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    Objective: To determine the relative risk of sternal dehiscence in patients undergoing bilateral internal thoracic artery harvesting and to assess whether and to what extent the technique of artery skeletonization might reduce this risk. Methods: Prospectively collected data on patients undergoing coronary artery bypass operations with at least a single internal thoracic artery were reviewed. The last 450 patients receiving bilateral internal thoracic artery grafts were compared with 450 patients who received a single internal thoracic artery during the same period. The left internal thoracic artery was always harvested in a pedicled fashion. Among patients receiving a bilateral internal thoracic artery, both arteries were harvested in a pedicled fashion in 300 cases, whereas both internal thoracic arteries were skeletonized in the remaining 150 cases. Results: Compared with a single internal thoracic artery, harvesting both internal thoracic arteries either in a skeletonized or in a pedicled fashion increased the chance of deep (1.1% vs 3.3% vs 4.7%; P =. 01) or superficial (4.8% vs 7.8% vs 12%; P =. 002) sternal infection. However, the technique of artery harvesting (odds ratio, 4.1; 95% confidence interval, 1.4-12.1); the presence of peripheral arteriopathy (odds ratio, 3.1; 95% confidence interval, 1.2-8.5), and resternotomy for bleeding (odds ratio, 8.2; 95% confidence interval, 2.0-33.6) were the only independent predictors for deep sternal infection, whereas the technique of artery harvesting (odds ratio, 3.0; 95% confidence interval, 1.6-5.4), female sex (odds ratio, 2.2; 95% confidence interval, 1.2-4.2), and diabetes (odds ratio, 1.7; 95% confidence interval, 1.0-2.9) were the only independent predictors of superficial sternal infection. In diabetic patients, there was no difference in the incidence of deep sternal infection among patients receiving a single internal thoracic artery or double skeletonized internal thoracic arteries (P =. 4). Conclusions: Bilateral internal thoracic artery harvesting carries a higher risk of sternal infection than harvesting a single internal thoracic artery. Skeletonization of both internal thoracic arteries significantly decreases this risk. A strategy of bilateral thoracic artery grafting can also be offered to patients at high risk for wound infection. Copyright © 2005 by The American Association for Thoracic Surgery

    Extracting invariant characteristics of sketch maps: Towards place query-by-sketch

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    In geography, invariant aspects of sketches are essential to study because they reflect the human perception of real-world places. A person's perception of a place can be ex-pressed in sketches. In this article, we quantitatively and qualitatively analyzed the characteristics of single objects and characteristics among objects in sketches and the real world to find reliable invariants that can be used to establish references/correspondences between sketch and world in a matching process. These characteristics include category, shape, name, and relative size of each object. Moreover, quantity and spatial relationships—such as topological, or-dering, and location relationships—among all objects are also analyzed to assess consistency between sketched and actual places. The approach presented in this study extracts the reliable invariants for query-by-sketch and prioritizes their relevance for a sketch-map matching process

    Comparative one-month safety and effectiveness of five leading new-generation devices for transcatheter aortic valve implantation

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    Transcatheter aortic valve implantation (TAVI) for aortic stenosis is becoming an appealing alternative to surgical aortic valve replacement in high-risk patients and to medical therapy for inoperable ones. Several new-generation TAVI devices have been recently introduced, but comparative analyses are lacking. We aimed to compare 1-month outcomes associated with such five leading new-generation TAVI devices exploiting data collected in the prospective observational RISPEVA (Registro Italiano GISE sull’impianto di Valvola Aortica Percutanea) Study. We queried the dataset of the ongoing RISPEVA study to retrieve baseline, procedural and 1-month outcome details of patients undergoing TAVI with Acurate, Evolut, Portico, Lotus, and Sapien3. Analysis was based on unadjusted and propensity score-adjusted methods. We included 1976 patients, 234 (11.8%) treated with Acurate, 703 (35.6%) with Evolut, 151 (7.6%) with Lotus, 347 (17.6%) with Portico, and 541 (27.4%) with Sapien3. Unadjusted analysis for baseline features highlighted several significant differences, and other discrepancies were found for procedural features. Despite these differences, device and procedural success were similarly high (ranging from 98.0% to 99.4%, p > 0.05). However, procedural valve migration appeared more common with Acurate (p = 0.007), and major bleeding with Sapien3 (p = 0.002). Unadjusted analysis for 1-month outcomes also highlighted significant differences in the composite of death, stroke, myocardial infarction, major vascular complication, major bleeding, or renal failure (favoring Portico, p < 0.001), major vascular complications (favoring Lotus, p < 0.001), renal failure (favoring Portico, p = 0.035), and permanent pacemaker implantation (favoring Acurate, p < 0.001). Propensity score-adjusted analyses showed lower rates of major adverse events with Evolut and Portico (p < 0.05), major vascular complications with Lotus and Portico (p < 0.05), renal failure with Sapien3 (p < 0.05) and permanent pacemaker implantation with Acurate (p < 0.05). In conclusion, new-generation TAVI devices have different profiles of early comparative safety and efficacy. These findings should be taken into account for individualized decision making and patient management

    A RasGAP SH3 Peptide Aptamer Inhibits RasGAP-Aurora Interaction and Induces Caspase-Independent Tumor Cell Death

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    The Ras GTPase-activating protein RasGAP catalyzes the conversion of active GTP-bound Ras into inactive GDP-bound Ras. However, RasGAP also acts as a positive effector of Ras and exerts an anti-apoptotic activity that is independent of its GAP function and that involves its SH3 (Src homology) domain. We used a combinatorial peptide aptamer approach to select a collection of RasGAP SH3 specific ligands. We mapped the peptide aptamer binding sites by performing yeast two-hybrid mating assays against a panel of RasGAP SH3 mutants. We examined the biological activity of a peptide aptamer targeting a pocket delineated by residues D295/7, L313 and W317. This aptamer shows a caspase-independent cytotoxic activity on tumor cell lines. It disrupts the interaction between RasGAP and Aurora B kinase. This work identifies the above-mentioned pocket as an interesting therapeutic target to pursue and points its cognate peptide aptamer as a promising guide to discover RasGAP small-molecule drug candidates

    STRASSE: A Silicon Tracker for Quasi-free Scattering Measurements at the RIBF

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    STRASSE (Silicon Tracker for RAdioactive nuclei Studies at SAMURAI Experiments) is a new detection system under construction for quasi-free scattering (QFS) measurements at 200-250 MeV/nucleon at the RIBF facility of the RIKEN Nishina Center. It consists of a charged-particle silicon tracker coupled with a dedicated thick liquid hydrogen target (up to 150-mm long) in a compact geometry to fit inside large scintillator or germanium arrays. Its design was optimized for two types of studies using QFS: missing-mass measurements and in-flight prompt γ\gamma-ray spectroscopy. This article describes (i) the resolution requirements needed to go beyond the sensitivity of existing systems for these two types of measurements, (ii) the conceptual design of the system using detailed simulations of the setup and (iii) its complete technical implementation and challenges. The final tracker aims at a sub-mm reaction vertex resolution and is expected to reach a missing-mass resolution below 2 MeV in σ\sigma for (p,2p)(p,2p) reactions when combined with the CsI(Na) CATANA array.Comment: 25 pages, 29 figure

    Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3

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    Missense mutations in the CIAS1 gene cause three autoinflammatory disorders: familial cold autoinflammatory syndrome, Muckle-Wells syndrome and neonatal-onset multiple-system inflammatory disease(1). Cryopyrin (also called Nalp3), the product of CIAS1, is a member of the NOD-LRR protein family that has been linked to the activation of intracellular host defence signalling pathways(2,3). Cryopyrin forms a multi-protein complex termed 'the inflammasome', which contains the apoptosis-associated speck-like protein (ASC) and caspase-1, and promotes caspase-1 activation and processing of pro-interleukin (IL)-1 beta (ref. 4). Here we show the effect of cryopyrin deficiency on inflammasome function and immune responses. Cryopyrin and ASC are essential for caspase-1 activation and IL-1 beta and IL-18 production in response to bacterial RNA and the imidazoquinoline compounds R837 and R848. In contrast, secretion of tumour-necrosis factor-alpha and IL-6, as well as activation of NF-kappa B and mitogen-activated protein kinases (MAPKs) were unaffected by cryopyrin deficiency. Furthermore, we show that Toll-like receptors and cryopyrin control the secretion of IL-1 beta and IL-18 through different intracellular pathways. These results reveal a critical role for cryopyrin in host defence through bacterial RNA-mediated activation of caspase-1, and provide insights regarding the pathogenesis of autoinflammatory syndromes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62569/1/nature04517.pd

    Toll-Like Receptor Agonists Synergize with CD40L to Induce Either Proliferation or Plasma Cell Differentiation of Mouse B Cells

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    In a classical dogma, pathogens are sensed (via recognition of Pathogen Associated Molecular Patterns (PAMPs)) by innate immune cells that in turn activate adaptive immune cells. However, recent data showed that TLRs (Toll Like Receptors), the most characterized class of Pattern Recognition Receptors, are also expressed by adaptive immune B cells. B cells play an important role in protective immunity essentially by differentiating into antibody-secreting cells (ASC). This differentiation requires at least two signals: the recognition of an antigen by the B cell specific receptor (BCR) and a T cell co-stimulatory signal provided mainly by CD154/CD40L acting on CD40. In order to better understand interactions of innate and adaptive B cell stimulatory signals, we evaluated the outcome of combinations of TLRs, BCR and/or CD40 stimulation. For this purpose, mouse spleen B cells were activated with synthetic TLR agonists, recombinant mouse CD40L and agonist anti-BCR antibodies. As expected, TLR agonists induced mouse B cell proliferation and activation or differentiation into ASC. Interestingly, addition of CD40 signal to TLR agonists stimulated either B cell proliferation and activation (TLR3, TLR4, and TLR9) or differentiation into ASC (TLR1/2, TLR2/6, TLR4 and TLR7). Addition of a BCR signal to CD40L and either TLR3 or TLR9 agonists did not induce differentiation into ASC, which could be interpreted as an entrance into the memory pathway. In conclusion, our results suggest that PAMPs synergize with signals from adaptive immunity to regulate B lymphocyte fate during humoral immune response
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