3,397 research outputs found

    Structure preserving schemes for mean-field equations of collective behavior

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    In this paper we consider the development of numerical schemes for mean-field equations describing the collective behavior of a large group of interacting agents. The schemes are based on a generalization of the classical Chang-Cooper approach and are capable to preserve the main structural properties of the systems, namely nonnegativity of the solution, physical conservation laws, entropy dissipation and stationary solutions. In particular, the methods here derived are second order accurate in transient regimes whereas they can reach arbitrary accuracy asymptotically for large times. Several examples are reported to show the generality of the approach.Comment: Proceedings of the XVI International Conference on Hyperbolic Problem

    Combinatorial experimental protocols for Erbicin-derived immunoagents and Herceptin

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    Erbicin is a human anti-ErbB2 single-chain antibody fragment with high affinity and selectivity for ErbB2-positive cancer cells. Two anti-ErbB2 immunoconjugates, called Erb-hRNase and Erb-hcAb, have been prepared and found to be selectively cytotoxic on ErbB2-positive cancer cells in vitro and vivo. In Erb-hRNase, Erbicin is linked to a human RNase and in Erb-hcAb it is linked to the key structural and functional regions of a human IgG. Herceptin is an anti-ErbB2 humanised antibody successfully used in the immunotherapy of breast cancer. We report here that the Erbicin-derived immunoagents target on breast cancer cells an ErbB2 epitope different than that of Herceptin. This finding led us to verify the effects of Herceptin on breast cancer cells when it was used in combination with the Erbicin-derived immunoagents. The results indicated that in combination experiments the antitumour action of Herceptin and that of the novel agents were significantly increased in an additive fashion. An inspection of the mechanism of action of Erb-hRNase or Erb-hcAb combined with Herceptin provided evidence that the antibody combinations engendered an increased downregulation of the ErbB2 receptor, and led to an enhanced apoptotic cell death

    A novel fully human antitumour immunoRNase targeting ErbB2-positive tumours

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    BACKGROUND: ErbB2 is an attractive target for immunotherapy, as it is a tyrosine kinase receptor overexpressed on tumour cells of different origin, with a key role in the development of malignancy. Trastuzumab, the only humanised anti-ErbB2 antibody currently used in breast cancer with success, can engender cardiotoxicity and a high fraction of patients is resistant to Trastuzumab treatment. METHODS: A novel human immunoRNase, called anti-ErbB2 human compact antibody-RNase (Erb-hcAb-RNase), made up of the compact anti-ErbB2 antibody Erbicin-human-compact Antibody (Erb-hcAb) and human pancreatic RNase (HP-RNase), has been designed, expressed in mammalian cell cultures and purified. The immunoRNase was then characterised as an enzymatic protein, and tested for its biological actions in vitro and in vivo on ErbB2-positive tumour cells. RESULTS: Erb-hcAb-RNase retains the enzymatic activity of HP-RNase and specifically binds to ErbB2-positive cells with an affinity comparable with that of the parental Erb-hcAb. Moreover, this novel immunoRNase is endowed with an effective and selective antiproliferative action for ErbB2-positive tumour cells both in vitro and in vivo. Its antitumour activity is more potent than that of the parental Erb-hcAb as the novel immunoconjugate has acquired RNase-based cytotoxicity in addition to the inhibitory growth effects, antibody-dependent and complement-dependent cytotoxicity of Erb-hcAb. CONCLUSION: Erb-hcAb-RNase could be a promising candidate for the immunotherapy of ErbB2-positive tumours

    Fractional variational calculus of variable order

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    We study the fundamental problem of the calculus of variations with variable order fractional operators. Fractional integrals are considered in the sense of Riemann-Liouville while derivatives are of Caputo type.Comment: Submitted 26-Sept-2011; accepted 18-Oct-2011; withdrawn by the authors 21-Dec-2011; resubmitted 27-Dec-2011; revised 20-March-2012; accepted 13-April-2012; to 'Advances in Harmonic Analysis and Operator Theory', The Stefan Samko Anniversary Volume (Eds: A. Almeida, L. Castro, F.-O. Speck), Operator Theory: Advances and Applications, Birkh\"auser Verlag (http://www.springer.com/series/4850

    Influence of family and friend smoking on intentions to smoke and smoking-related attitudes and refusal self-efficacy among 9-10 year old children from deprived neighbourhoods: a cross-sectional study.

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    BACKGROUND: Smoking often starts in early adolescence and addiction can occur rapidly. For effective smoking prevention there is a need to identify at risk groups of preadolescent children and whether gender-specific intervention components are necessary. This study aimed to examine associations between mother, father, sibling and friend smoking and cognitive vulnerability to smoking among preadolescent children living in deprived neighbourhoods. METHODS: Cross-sectional data was collected from 9-10 year old children (n =1143; 50.7% girls; 85.6% White British) from 43 primary schools in Merseyside, England. Children completed a questionnaire that assessed their smoking-related behaviour, intentions, attitudes, and refusal self-efficacy, as well as parent, sibling and friend smoking. Data for boys and girls were analysed separately using multilevel linear and logistic regression models, adjusting for individual cognitions and school and deprivation level. RESULTS: Compared to girls, boys had lower non-smoking intentions (P = 0.02), refusal self-efficacy (P = 0.04) and were less likely to agree that smoking is 'definitely' bad for health (P < 0.01). Friend smoking was negatively associated with non-smoking intentions in girls (P < 0.01) and boys (P < 0.01), and with refusal self-efficacy in girls (P < 0.01). Sibling smoking was negatively associated with non-smoking intentions in girls (P < 0.01) but a positive association was found in boys (P = 0.02). Boys who had a smoking friend were less likely to 'definitely' believe that the smoke from other people's cigarettes is harmful (OR 0.57, 95% CI: 0.35 to 0.91, P = 0.02). Further, boys with a smoking friend (OR 0.38, 95% CI: 0.21 to 0.69, P < 0.01) or a smoking sibling (OR 0.45, 95% CI: 0.21 to 0.98) were less likely to 'definitely' believe that smoking is bad for health. CONCLUSION: This study indicates that sibling and friend smoking may represent important influences on 9-10 year old children's cognitive vulnerability toward smoking. Whilst some differential findings by gender were observed, these may not be sufficient to warrant separate prevention interventions. However, further research is needed
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