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Objective. Leukocyte traffic from the blood to the joints is crucial in the pathogenesis of arthritis. A bifunctional endothelial cell-surface glycoprotein, AOC3 (amine oxidase, copper-containing 3; also known as vascular adhesion protein 1), has both adhesive and enzymatic properties. We undertook this study to determine the contribution of AOC3 and its oxidase activity to leukocyte trafficking into inflamed joints in vivo.Methods. We used gene-modified animals, molecular modeling, an AOC3 enzyme inhibitor, oxidase assays, and arthritis models (adjuvant-induced arthritis [AIA] in rats and anti-type II collagen antibodyinduced arthritis in mice) to dissect the importance of AOC3 in vivo.Results. The AOC3 inhibitor fitted well with a covalent binding mode into the active site of the AOC3 crystal structure. It selectively blocked the oxidase activity of AOC3 in enzyme assays. Intraperitoneal and oral administration of the AOC3 inhibitor significantly ameliorated rat AIA. In anti-type II collagen antibodyinduced arthritis in mice, the AOC3 inhibitor also improved the outcome of the joint inflammation. The acute semicarbazide-sensitive amine oxidase blockade by the inhibitor had even more pronounced effects than genetic deletion of AOC3. Enzymatic analyses showed that the inhibitor also blocked 2 other structurally very closely related AOCs, but not any of more than 100 other enzymes tested.Conclusion. These are the first data to demonstrate that the enzymatic activity of the atypical endothelial adhesion molecule AOC3, and possibly that of other closely related ecto-oxidases, is crucial for leukocyte exit from the vessels in inflamed joints in vivo.
Objective. Leukocyte traffic from the blood to the joints is crucial in the pathogenesis of arthritis. A bifunctional endothelial cell-surface glycoprotein, AOC3 (amine oxidase, copper-containing 3; also known as vascular adhesion protein 1), has both adhesive and enzymatic properties. We undertook this study to determine the contribution of AOC3 and its oxidase activity to leukocyte trafficking into inflamed joints in vivo.Methods. We used gene-modified animals, molecular modeling, an AOC3 enzyme inhibitor, oxidase assays, and arthritis models (adjuvant-induced arthritis [AIA] in rats and anti-type II collagen antibodyinduced arthritis in mice) to dissect the importance of AOC3 in vivo.Results. The AOC3 inhibitor fitted well with a covalent binding mode into the active site of the AOC3 crystal structure. It selectively blocked the oxidase activity of AOC3 in enzyme assays. Intraperitoneal and oral administration of the AOC3 inhibitor significantly ameliorated rat AIA. In anti-type II collagen antibodyinduced arthritis in mice, the AOC3 inhibitor also improved the outcome of the joint inflammation. The acute semicarbazide-sensitive amine oxidase blockade by the inhibitor had even more pronounced effects than genetic deletion of AOC3. Enzymatic analyses showed that the inhibitor also blocked 2 other structurally very closely related AOCs, but not any of more than 100 other enzymes tested.Conclusion. These are the first data to demonstrate that the enzymatic activity of the atypical endothelial adhesion molecule AOC3, and possibly that of other closely related ecto-oxidases, is crucial for leukocyte exit from the vessels in inflamed joints in vivo.
Current approaches to the citation analysis of scientific publications are outlined. Science Citation Index, Impact Factor, Immediacy Index, and the selection procedure for Essential Science Indicators-a relatively new citation analysis tool-are described. The new citation evaluation tool has yet not been discussed adequately by mechanicians
Slug impact is considered a potential risk for pressurized water reactors in the event of a severe accident. The German team of FZK investigates this issue through the reduced-scale experiments BERDA, whose goal is to quantify the maximum mechanical energy that the upper head of a PWR is able to withstand. As these tests are performed with a material different from the one that would intervene in a real accident, the French team of CEA studies the influence of the slug material with the SKIPPY mock-ups. In order to understand better the impact process, relevant theoretical study has been conducted with the EUROPLEXUS code Keywords: composition and shape of slugs, slug impact, upper head of pressurized water reactor, mechanical energy, experimental investigation, simulation 1. Introduction. Over the last years, the international scientific journal International Applied Mechanics has published review articles on applications of engineering mechanics [1,6,7,10,15,21,27], offering in this way the specificity of modern solutions to problems in engineering to the circle of specialists in mechanics and related fields.To guarantee high standards of safety for the nuclear reactors, different kinds of accidents are studied. Among the severe accidents postulated (accidents with a probability of occurrence lower than 10 -6 ), in-vessel steam explosions are studied for Pressurized Water nuclear Reactors (PWRs) [22][23][24]. Part of the reactor core is supposed to have molten and fallen into the lower head of the reactor. The contact between the hot molten material (called corium) and the cold water leads to violent evaporation of the water, thus causing a steam explosion. In case of a very energetic explosion, part of the molten material can be accelerated as a liquid slug towards the upper head of the reactor pressure vessel.The slug impact concerns both the upward acceleration of the corium slug and its crash against the upper head of the vessel. In some cases, the head may fail and fragments can be hurled against the concrete containment. If the missiles endanger the containment integrity, this process can lead to a release of radioactive products to the atmosphere. This kind of accident is generally called an α-mode accident [8,9,18].In Europe, slug impact is mainly studied by the German and French research centers FZK and CEA-Saclay. FKZ aims at the quantification of the maximum mechanical energy that the upper head can be able to withstand without failing. The investigation work is largely based on the German mock-ups BERDA, consisting in the simulation of a slug impact on reduced-scale replicas of the upper part of the reactor pressure vessel.As the BERDA tests are performed with a material different from corium because of the difficulties introduced by radioactive material handling, the influence of the slug material is investigated with the French mock-ups SKIPPY.In order to deepen the understanding of the impact process and to extrapolate the experimental results to other combinations of parameters, relevant theoret...
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