606 research outputs found

    Performance-based durability design of reinforced concrete structures with stainless steel bars

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    Stainless steel reinforcement can be a suitable option for the achievement of the durability target forreinforced concrete structures exposed to aggressive chloride bearing environments. To quantitatively assessthe benefits of using stainless steel bars, performance-based design models can be applied. However,although these models could, in principle, be used for the design with stainless steel bars, at the momentthey do not provide any specific indication for the design with this type of bars particularly the critical chloridethreshold values. This paper reports results of an experimental work aimed at evaluating the statisticaldistribution of the critical chloride threshold in concrete of low nickel duplex stainless steel (type 1.4362)reinforcement. Results of the potentiostatic polarisation tests showed that the statistical distribution ofthe chloride threshold may be fitted by a Beta probability distribution function that can be used as inputparameter in performance-based models for structures exposed in atmospheric condition and to temperatemarine environments

    Genetic algorithm against cancer,”

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    Abstract. We present an evolutionary approach to the search for effective vaccination schedules using mathematical computerized model as a fitness evaluator. Our study is based on our previous model that simulates the Cancer -Immune System competition activated by a tumor vaccine. The model reproduces pre-clinical results obtained for an immunoprevention cancer vaccine (Triplex) for mammary carcinoma on HER-2/neu mice. A complete prevention of mammary carcinoma was obtained in vivo using a Chronic vaccination schedule. Our genetic algorithm found complete immunoprevention with a much lighter vaccination schedule. The number of injections required is roughly one third of those used in Chronic schedule

    Effect of electroosmotic flow of aqueous suspension of nanosilica on the properties of carbonated concrete

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    The paper investigates the possibility to use electroosmosis to transport nanosilica (NS) particles inside carbonated concrete, in order to exert a filler effect and enhance its durability performance. This method aims to extending possible beneficial effects of NS to existing reinforced concrete structures, where the presence of a carbonated layer of concrete is very likely. Injection tests were performed with electrochemical cells on carbonated concrete discs with water/cement (w/c) ratios of 0.50, 0.55 and 0.65, using a NS aqueous suspension at the anode. The results indicated that a flow did occur through the concrete disc and it was directed from the anode towards the cathode. A linear relationship between flux and applied voltage gradient was obtained, which is typical of electroosmotic phenomena. The bulk properties of concrete, such as density, water absorption and sorptivity, were not affected by the injection tests, whilst electrical resistivity increased indicating a mild ‘sealing’ effect on the surface. Also microstructural analyses highlighted the local presence of NS that decreased the local porosity close to the surface

    List of requirements on formalisms and selection of appropriate tools

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    This deliverable reports on the activities for the set-up of the modelling environments for the evaluation activities of WP5. To this objective, it reports on the identified modelling peculiarities of the electric power infrastructure and the information infrastructures and of their interdependencies, recalls the tools that have been considered and concentrates on the tools that are, and will be, used in the project: DrawNET, DEEM and EPSys which have been developed before and during the project by the partners, and M\uf6bius and PRISM, developed respectively at the University of Illinois at Urbana Champaign and at the University of Birmingham (and recently at the University of Oxford)

    Modeling the competition between lung metastases and the immune system using agents

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    <p>Abstract</p> <p>Background</p> <p>The Triplex cell vaccine is a cancer cellular vaccine that can prevent almost completely the mammary tumor onset in HER-2/neu transgenic mice. In a translational perspective, the activity of the Triplex vaccine was also investigated against lung metastases showing that the vaccine is an effective treatment also for the cure of metastases. A future human application of the Triplex vaccine should take into account several aspects of biological behavior of the involved entities to improve the efficacy of therapeutic treatment and to try to predict, for example, the outcomes of longer experiments in order to move faster towards clinical phase I trials. To help to address this problem, MetastaSim, a hybrid Agent Based - ODE model for the simulation of the vaccine-elicited immune system response against lung metastases in mice is presented. The model is used as in silico wet-lab. As a first application MetastaSim is used to find protocols capable of maximizing the total number of prevented metastases, minimizing the number of vaccine administrations.</p> <p>Results</p> <p>The model shows that it is possible to obtain "in silico" a 45% reduction in the number of vaccinations. The analysis of the results further suggests that any optimal protocol for preventing lung metastases formation should be composed by an initial massive vaccine dosage followed by few vaccine recalls.</p> <p>Conclusions</p> <p>Such a reduction may represent an important result from the point of view of translational medicine to humans, since a downsizing of the number of vaccinations is usually advisable in order to minimize undesirable effects. The suggested vaccination strategy also represents a notable outcome. Even if this strategy is commonly used for many infectious diseases such as tetanus and hepatitis-B, it can be in fact considered as a relevant result in the field of cancer-vaccines immunotherapy. These results can be then used and verified in future "in vivo" experiments, and their outcome can be used to further improve and refine the model.</p

    Timely DNA Vaccine Combined with Systemic IL-12 Prevents Parotid Carcinomas before a Dominant-Negative p53 Makes Their Growth Independent of HER-2/neu Expression

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    Double transgenic mice overespressing the transforming rat HER-2/neu oncogene and the mutated p53, with both deminant-negative and a gain-of-function properties, display early aggressive and metastasizing parotid tumors. Multiple acinar and ductal hyperplasia foci overexpressing the HER-2/neu gene product are evident at wk 5 and progress to poorly differentiated carcinoma by wk 7. Mice die before wk 18 with invasive carcinomas and multiple metastases that no longer express HER-2/neu. A combination of repeated electroporations of plasmids coding for the extracellular and transmembrane domains of the rat HER-2/neu receptor with systemic IL-12 administrations started when the parotids that present diffuse hyperplasia protected all female and 50% of the male mice until the close of the experiment at wk 40. This combined treatment began when multifocal in situ - carcinomas that were already present cured 33% of the females and 25 % of the males. The most prominent immunologic features associated with the antitumor protection were the production of high titers of anti-HER-2/neu Abs and the nonappearance of cell-mediated cytotoxic reactivity. In conclusion, anti-HER-2/neu vaccination combined with systemic IL-12 control parotid carcinomas as far as p53 mutation makes their growth independent of HER-2/neu expression

    A better immune reaction to Erbb-2 tumors is elicited in mice by DNA vaccines encoding rat/human chimeric proteins.

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    The Erbb-2 (neu in rat and Her-2 in humans) tyrosine kinase receptor is an oncoantigen (i.e., a tumor- associated molecule directly involved in cancer progression). Because oncoantigens are self-tolerated mole- cules, to trigger a response circumventing tolerance, we generated two plasmids (RHuT and HuRT) coding for chimeric neu-Her-2 extracellular and transmembrane proteins that are expressed on the cell membrane of the transfected cells and recognized by monoclonal antibodies reacting against neu and Her-2. RHuT encodes a protein in which the 410 NH2-terminal residues are from the neu extracellular domain and the remaining residues from Her-2. Almost symmetrically, HuRT encodes for a protein in which the 390 NH2-terminal resi- dues are from Her-2 and the remainder from neu. The ability of RHuT and HuRT to elicit a protective response to neu and Her-2 in wild-type mice and in transgenic mice tolerant to neu and Her-2 proteins was compared with that of plasmids coding for the fully rat or fully human extracellular and transmembrane domains of the Erbb-2 receptor. In most cases, RHuT and HuRT elicited a stronger response, although this chimeric benefit is markedly modulated by the location of the heterologous moiety in the protein coded by the plasmid, the immune tolerance of the responding mouse, and the kind of Erbb-2 orthologue on the targeted tumor

    Cure of mammary carcinomas in Her-2 transgenic mice through sequential stimulation of innate (neoadjuvant interleukin-12) and adaptive (DNA vaccine electroporation) immunity.

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    Purpose: Whereas neoadjuvant therapy is emerging as a treatment option in early primary breast cancer, no data are available on the use of antiangiogenic and immunomodulatory agents in a neoadjuvant setting. In a model of Her-2 spontaneous mammary cancer, we investigated the efficacy of neoadjuvant interleukin 12 (IL-12) followed by ‘‘immune-surgery’’ of the residual tumor. Experimental Design: Female BALB/c mice transgenic for the rat Her-2 oncogene inexorably develop invasive carcinomas in all their mammary glands by the 23rd week of age. Mice with multifocal in situ carcinomas received four weekly i.p. injections of 100 ng IL-12 followed by a 3-week rest. This course was given four times. A few mice additionally received DNA plasmids encoding portions of the Her-2 receptor electroporated through transcutaneous electric pulses. Results: The protection elicited by IL-12 in combination with two DNA vaccine electroporations kept 63% of mice tumor-free. Complete protection of all 1-year-old mice was achieved when IL-12-treated mice received four vaccine electroporations. Pathologic findings, in vitro tests, and the results from immunization of both IFN-; andimmunoglobulin gene knockout transgenic mice and of adoptive transfer experiments all show that IL-12 augments the B- and T-cell response elicited by vaccination and slightly decreases the number of regulatory T cells. In addition, IL-12 strongly inhibits tumor angiogenesis. Conclusions: In Her-2 transgenic mice, IL-12 impairs tumor progression and triggers innate immunity so markedly that DNA vaccination becomes effective at late points in time when it is ineffective on its own
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