596 research outputs found

    Modulation of the CD8+-T-cell response by CD4+ CD25+ regulatory T cells in patients with Hepatitis B virus infection

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    CD4+ CD25+ regulatory T cells have been shown to maintain peripheral tolerance against self and foreign antigens. In this study we analyzed the effect of circulating CD4+ CD25+ T cells on CD8+-T-cell responses of patients with chronic and resolved hepatitis B virus (HBV) infection. We demonstrated that circulating CD4+ CD25+ T cells modulate the function and expansion of HBV-specific CD8+ cells ex vivo in all patients, regardless of whether they have chronic or resolved HBV infection. The possible role of CD4+ CD25+ T cells in the pathogenesis of chronic HBV infection is not supported by these data. However, these results might have implications for optimizing future immunotherapeutic approaches to HBV treatment

    On the reserve price in all-pay auctions with complete information and lobbying games

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    We show that the seller’s optimal reserve price in an all-pay auction with complete information is higher than in a standard auction. We use our results to re-consider some findings of the literature that models lobbying games as all-pay auctions. In particular, we show that the so-called Exclusion Principle appears to rely crucially on the implicit assumption of a “weak” (in terms of bargaining power) seller, and does not hold if she regards bidders’ valuations as iid according to a monotonic hazard rate. Our preliminary results for the case of independent but asymmetric bidders make it even more suspicious.all-pay auctions; reserve price; economic theory of lobbying

    A note on the Exclusion Principle

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    According to the so-called Exclusion Principle (introduced by Baye et alii, 1993), it might be profitable for the seller to reduce the number of fully-informed potential bidders in an all-pay auction. We show that it does not apply if the seller regards the bidders’ private valuations as belonging to the class of identical and independent distributions with a monotonic hazard rate.all-pay auctions; Exclusion Principle; monotonic hazard rate; economic theory of lobbying

    Optimization of the manufacturing process to minimize porosity in a CW614N brass sealing cap

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    Porosity easily forms during the manufacturing process of the CW614N alloy, a leaded brass widely used in engineering applications. These porosity issues, often undetected until components are in use, can arise during the casting phase due to gas entrapment or shrinkage cavities, or during extrusion as a consequence of suboptimal parameters, such as temperature and speed. An example of this type of defect was found in a sealing cap made of CW614N brass that failed in an industrial machine, causing a dangerous butane gas leakage at room temperature under atmospheric pressure. Chemical composition analyses were performed to confirm compliance of the failed component with the standard. Metallographic characterizations, including both optical and stereo microscopy and scanning electron microscopy coupled with energy dispersive spectroscopy, were conducted on the failed component to assess its microstructure. Additionally, chemical and microscopy investigations were performed on cast billets and extruded bars produced at varying extrusion speeds (10 mm/s, 25 mm/s, 40 mm/s) and temperatures (620 °C, 670 °C, 720 °C) to understand the causes of the defect and identify extrusion parameters able to minimize it. It was found that the failure can be attributed to the pores’ formation due to the hot tearing phenomenon arising during the extrusion process. Moreover, increasing the extrusion temperature from 620 °C to 720 °C at a speed of 25 mm/s or 40 mm/s significantly reduces the total porosity area in the extruded bars

    Pasquarosa

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    L'attività della pittrice Pasquarosa Bertoletti (1896-1973) fino al 1920 e i suoi rapporti con Federigo Tozzi

    Outcomes in the emergency endovascular repair of blunt thoracic aortic injuries

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    Abstract Thoracic aorta blunt injury (BAI) is a highly lethal lesion. A large number of victims die before obtaining emergency care. Thoracic endovascular aneurysm repair (TEVAR) is a less invasive method compared with open surgery and may change protocols for BAI treatment. This retrospective study was developed to evaluate the potential issues about thoracic endografting in the management of these patients. Twenty-seven patients with a BAI underwent aortic stent grafting. Intervention was preceded by the treatment of more urgent associated lesions in nine cases. In-hospital mortality was 7.4%. No paraplegia or ischemic complications developed because of the coverage of the left subclavian artery. In one case (3.2%), a type I endoleak was detected, proximal endograft infolding in two cases (7.4%) and endograft distal migration in further two cases were detected during follow-up (6-110 months). Thoracic endovascular aneurysm repair of BAI showed encouraging results in terms of perioperative mortality and morbidity. Concerns still remain about the potential mid- and long-term complications in younger patients

    Separation and characterisation of beta2-microglobulin folding conformers by ion-exchange liquid chromatography and ion-exchange liquid chromatography-mass spectrometry

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    In this work we present for the first time the use of ion-exchange liquid chromatography to separate the native form and a partially structured intermediate of the folding of the amyloidogenic protein beta2-microglobulin. Using a strong anion-exchange column that accounts for the differences in charge exposure of the two conformers, a LC-UV method is initially optimised in terms of mobile phase pH, composition and temperature. The preferred mobile phase conditions that afford useful information were found to be 35 mM ammonium formate, pH 7.4 at 25°C. The dynamic equilibrium of the two species is demonstrated upon increasing the concentration of acetonitrile in the protein sample. Then, the chromatographic method is transferred to MS detection and the respective charge state distributions of the separated conformers are identified. The LC-MS results demonstrate that one of the conformers is partially unfolded, compared with the native and more compact species. The correspondence with previous results obtained in free solution by capillary electrophoresis suggest that strong ion exchange LC-MS does not alter beta2-microglobulin conformation and maintains the dynamic equilibrium already observed between the native protein and its folding intermediate

    Covalent modification of beta2-microglobulin induced by reactive carbonyl species : high resolution mass spectrometric studies

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    Beta2-microglobulin (β2m) is responsible for dialysis related amyloidosis (DRA), a destructive osteoarticular disease that affects patients undergoing long-term hemodialysis. Physicochemical and immunochemical analyses showed that one of the constituents of DRA aggregates is an acidic form of β2m, which is generated through covalent modifications induced by reactive carbonyl species (RCS) and glucose. The resulting advanced lipoxidation and glycoxidation end products (ALEs and AGEs) have been detected in long-lived β2m amyloid deposits, mainly by immunoistochemistry.[1] On these evidences we here use high resolution MS to investigate the β2m non-enzymatic glycation and carbonylation, as induced by the main RCS.[2] The identification of post-translational modifications was carried out by direct infusion analysis of the intact protein (top-down proteomics) and NanoLC-ESI-MS/MS analysis of the chymotryptic digest (bottom-up proteomics). After 24 hours of incubation of recombinant β2m with RCS, we are able to identify covalent adducts for dialdehydes (glyoxal and methylglyoxal) occurring on Arg4. Neither cross-links/polymerization events nor adducts for α,β-unsatured compounds were observed. On these bases the optimized methods were used for the same characterization and semi-quantitative analysis of purified and commercial urinary β2m. The obtained results give a deeper insight on the covalently modified β2m and RCS as potential drug targets in DRA and inflammation
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