64 research outputs found

    Inductive power transfer for automotive applications: State-of-the-art and future trends

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    The paper discusses the status of the development status of the inductive power transmission for automotive applications. This technology is, in fact, gaining the interest of electric vehicle manufacturers as an effective strategy to improve the market penetration of electric mobility. Starting from the origin of this technology, the paper presents an overview of the current state-of-the-art as well as the current research and industrial projects. Particular attention is devoted to the description of a prototypal system for the dynamic inductive power transmission whose goal is to extend the battery range by a fast partial recharging during the movement of the vehicle

    iNKT Cells Control Mouse Spontaneous Carcinoma Independently of Tumor-Specific Cytotoxic T Cells

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    CD1d-restricted invariant NKT (iNKT) cells are a subset of T lymphocytes endowed with innate effector functions that aid in the establishment of adaptive T and B cell immune responses. iNKT cells have been shown to play a spontaneous protective role against experimental tumors. Yet, the interplay between iNKT and tumor-specific T cells in cancer immune surveillance/editing has never been addressed. The transgenic adenocarcinoma of the mouse prostate (TRAMP) is a realistic model of spontaneous oncogenesis, in which the tumor-specific cytotoxic T cell (CTL) response undergoes full tolerance upon disease progression.We report here that lack of iNKT cells in TRAMP mice resulted in the appearance of more precocious and aggressive tumors that significantly reduced animal survival. TRAMP mice bearing or lacking iNKT cells responded similarly to a tumor-specific vaccination and developed tolerance to a tumor-associated antigen at comparable rate.Hence, our data argue for a critical role of iNKT cells in the immune surveillance of carcinoma that is independent of tumor-specific CTL

    Boosting Interleukin-12 Antitumor Activity and Synergism with Immunotherapy by Targeted Delivery with isoDGR-Tagged Nanogold.

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    AbstractThe clinical use of interleukin‐12 (IL12), a cytokine endowed with potent immunotherapeutic anticancer activity, is limited by systemic toxicity. The hypothesis is addressed that gold nanoparticles tagged with a tumor‐homing peptide containing isoDGR, an αvβ3‐integrin binding motif, can be exploited for delivering IL12 to tumors and improving its therapeutic index. To this aim, gold nanospheres are functionalized with the head‐to‐tail cyclized‐peptide CGisoDGRG (Iso1) and murine IL12. The resulting nanodrug (Iso1/Au/IL12) is monodispersed, stable, and bifunctional in terms of αvβ3 and IL12‐receptor recognition. Low‐dose Iso1/Au/IL12, equivalent to 18–75 pg of IL12, induces antitumor effects in murine models of fibrosarcomas and mammary adenocarcinomas, with no evidence of toxicity. Equivalent doses of Au/IL12 (a nanodrug lacking Iso1) fail to delay tumor growth, whereas 15 000 pg of free IL12 is necessary to achieve similar effects. Iso1/Au/IL12 significantly increases tumor infiltration by innate immune cells, such as NK and iNKT cells, monocytes, and neutrophils. NK cell depletion completely inhibits its antitumor effects. Low‐dose Iso1/Au/IL12 can also increase the therapeutic efficacy of adoptive T‐cell therapy in mice with autochthonous prostate cancer. These findings indicate that coupling IL12 to isoDGR‐tagged nanogold is a valid strategy for enhancing its therapeutic index and sustaining adoptive T‐cell therapy

    11.Hypoxic ventilatory depressionと思われる一症例について(第551回千葉医学会例会・第9回麻酔科例会・第18回千葉麻酔懇話会)

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    FISH analysis on metaphase nuclei (top panel) of cultured cells derived from peripheral blood leukocytes of the proband of family 2 by using BAC probes for 11p15.5-15.4 (RP11-11A9, 3,236,552-3,356,012, green) and 11q22.3 (RP11-179B7, 104,298,339-104,459,797, red). The green signal on both homologues is visible only at chr11p, demonstrating the presence of an in cis duplication and excluding an unbalanced translocation. FISH analysis on interphase nuclei (bottom panel) using the BACs RP11-699D10 (2.9–3.0 Mb, red) and RP11-11A9 (green), hybridizing within the duplication. Note that single and duplicated signals can be seen on the two homologues, respectively. The red-green-green-red order of the duplicated signals indicates that the duplication is inverted. (PDF 52 kb

    822 Local radiotherapy synergizes with tumor-specific TCR redirected T cells in the rejection of prostate cancer

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    Background Adoptive T cell therapy (ACT) has become a promising option for cancer patients. While tumor-infiltrating lymphocytes were initially exploited as a source of tumor reactive lymphocytes, T cells genetically redirected to the tumor by TCR/CAR gene transfer are now in clinical validation. In the case of solid tumors, unfavorable immunosuppressive microenvironments remain recognized barriers to therapeutic efficacy. We have recently reported that the therapeutic activity of ACT against poorly immunogenic and indolent prostate cancer is improved by the concurrent targeting of the tumor stroma by mean of T cells redirected to an ubiquitously expressed minor histocompatibility antigen or a tumor vessel targeted TNF derivative. We have now taken the concept further and hypothesized that local radiotherapy (RT), might also synergize with ACT by promoting lymphocyte endothelial transmigration and tumor recognition, and ultimately favor abscopal effects. Methods We investigated the combination of local RT and ACT in TRAMP (Transgenic Adenocarcinoma of the Mouse Prostate) mice and in mice bearing subcutaneous B16/B16-OVA (MO4) or TRAMP-C2/TRAMP-C2-OVA tumors. Local RT was delivered by X-RAD SmART (the Small Animal Radiation Therapy) microirradiator in single dose or hypo-fractioned regimens. ACT consisted of T cells engineered with tumor-specific TCRs. Immunogenic consequences were analyzed by Real-Time PCR, and flow cytometry (FACS) analyses. Prostate tumor debulking was evaluated by histological analyses. Results We found that local hypofractionated RT and ACT, while individually inefficacious in controlling tumor growth, concurred to the debulking of advanced prostate adenocarcinoma when used in combination in treating TRAMP mice. Mechanistically, exposing isolated tumor cells, or the TRAMP mouse prostate to hypo-fractionated RT regimens induced stronger type-I interferon (IFN-I) responses, when compared to single high dose. Acutely, hypofractionated RT promoted better immune tumor infiltration, among which TCR redirected effector cells. Conclusions Data support feasibility and efficacy of combining hypo-fractionated local RT with ACT in the form of TCR engineered T cells to promote prostate cancer recognition and eradication. Tumor debulking was observed in the absence of treatment-related toxicity. Systemic recirculation of TCR redirected T cells was observed. We are now investigating therapeutic effects at distal (metastatic) sites. Acknowledgements The authors acknowledge the support of the Italian Association for Cancer Research (AIRC) Ethics Approval The studies involving animals were approved by The Institutional Ethical Committee (IACUC#999)

    Gregorio Agdollo

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    Biografia di Gregorio Agdollo (Isfahan 1707 - Venezia 1787), mercante armeno residente a Venezia e collezionista d'arte

    Currents Passing Through the Human Body: The Numerical Viewpoint

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    In the case of direct or indirect contact with electrically energized parts, an electric current circulates through the body. When the magnitude and duration of the current through the heart exceed the ventricular fibrillation thresholds, the cardiac muscle starts uncoordinated contractions, greatly jeopardizing the life of the subject. Technical standards on electrical installations describe the protective measures against direct and indirect contact necessary to minimize the probability of inception of ventricular fibrillation. Safety considerations are based on experiments made in the past on animals, but the extrapolation of results to human beings is complex and rather questionable. The purpose of this study is to analyze the body factors that affect the distribution of currents passing through the human body with virtual anatomical models. A set of 16 models of individuals is used to simulate different electric contacts. The use of virtual models of a diverse population (i.e., eight males and eight females, ten adults and six children) provides a statistical support to the results. The obtained heart-current factors, are compared with values present in the literature. This paper provides a novel viewpoint on the problem, and supports the ongoing research activity and efforts to improve the electrical safety of persons

    Currents flowing through the human body: the numerical viewpoint

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    In case of direct or indirect contact with electrically energized parts, an electric current circulates through the body. When the magnitude and duration of the current through the heart exceed the ventricular fibrillation thresholds, the cardiac muscle starts uncoordinated contractions, greatly jeopardizing the life of the subject. Technical standards on electrical installations describe the protective measures against direct and indirect contact necessary to minimize the probability of inception of ventricular fibrillation. Safety considerations are based on experiments made in the past on animals, but the extrapolation of results to human beings is complex and rather questionable. The purpose of this study is to analyze the body factors that affect the distribution of currents passing through the human body with virtual anatomical models. A set of sixteen models of individuals is used to simulate different electric contacts. The use of virtual models of a diverse population (i.e. eight males and eight females, ten adults and six children) provides a statistical support to the results. The obtained heart-current factors, which take into account the current frequency, are compared with values present in literature. This paper provides a novel viewpoint on the problem, and supports the ongoing research activity and efforts to improve the electrical safety of persons
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