2,129 research outputs found

    Nonresonant searches for axion-like particles in vector boson scattering processes at the LHC

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    We propose a new search for Axion-Like Particles (ALPs), targeting Vector Boson Scattering (VBS) processes at the LHC. We consider nonresonant ALP-mediated VBS, where the ALP participates as an off-shell mediator. This process occurs whenever the ALP is too light to be produced resonantly, and it takes advantage of the derivative nature of ALP interactions with the electroweak Standard Model bosons. We study the production of ZZ, Zγ, W ±γ, W ±Z and W ±W ± pairs with large diboson invariant masses in association with two jets. Working in a gauge-invariant framework, upper limits on ALP couplings to electroweak bosons are obtained from a reinterpretation of Run 2 public CMS VBS analyses. The constraints inferred on ALP couplings to ZZ, Zγ and W ±W ± pairs are very competitive for ALP masses up to 100 GeV. They have the advantage of being independent of the ALP coupling to gluons and of the ALP decay width. Simple projections for LHC Run 3 and HL-LHC are also calculated, demonstrating the power of future dedicated analyses at ATLAS and CMS

    Predicting circulating biomarker response and its impact on the survival of advanced melanoma patients treated with adjuvant therapy

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    Advanced melanoma remains a disease with poor prognosis. Several serologic markers have been investigated to help monitoring and prognostication, but to date only lactate dehydrogenase (LDH) has been validated as a standard prognostic factor biomarker for this disease by the American Joint Committee on Cancer. In this work, we built a semi-mechanistic model to explore the relationship between the time course of several circulating biomarkers and overall or progression free survival in advanced melanoma patients treated with adjuvant high-dose interferon-[Formula: see text]. Additionally, due to the adverse interferon tolerability, a semi-mechanistic model describing the side effects of the treatment in the absolute neutrophil counts is proposed in order to simultaneously analyze the benefits and toxic effects of this treatment. The results of our analysis suggest that the relative change from baseline of LDH was the most significant predictor of the overall survival of the patients. Unfortunately, there was no significant difference in the proportion of patients with elevated serum biomarkers between the patients who recurred and those who remained free of disease. Still, we believe that the modelling framework presented in this work of circulating biomarkers and adverse effects could constitute an additional strategy for disease monitoring in advance melanoma patients

    The Influence of Age on the Dynamic Relationship Between End-Tidal Sevoflurane Concentrations and Bispectral Index

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    BACKGROUND: Age is an important determinant of the pharmacokinetic profile of inhaled anesthetics. The influence of age on the dynamic profile of sevoflurane's effect has not been well described. We performed this study to characterize the influence of age and other covariates on the dynamic relationship between sevoflurane end-tidal concentration (C(ET)) and its effect measured by bispectral index (BIS). METHODS: Fifty patients, aged 3-71 yr, scheduled for minor surgery were prospectively studied. The BIS and sevoflurane C(ET) were continuously measured during the study period. During maintenance of anesthesia and after stable BIS values of 60-65 were obtained, the inspired concentration of sevoflurane was increased to 5 vol % for 5 min or until BIS <40 and then decreased. The dynamic relationship between sevoflurane C(ET) and its effect as measured by BIS during this transition period were modeled with an inhibitory E(max) model using a population pharmacokinetic-pharmacodynamic approach with NONMEM V. A predictive check method was used to validate the final model. RESULTS: The sensitivity to sevoflurane's effect as measured by BIS expressed in the C(50) [steady-state C(ET) eliciting half of maximum response (I(max))] increased with age. The speed of change of sevoflurane's effect, expressed as the effect-site equilibration half-life (t(1/2) k(e0)), increased at older ages. The predictive check analysis confirmed the adequacy of the model. CONCLUSIONS: Age significantly affects the dynamic relationship between sevoflurane C(ET) and its effect measured with BIS

    Application of different methods to formulate PEG-liposomes of oxaliplatin: Evaluation in vitro and in vivo

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    In this work the film method (FM), reverse-phase evaporation (REV) and the heating method (HM) were applied to prepare PEG-coated liposomes of oxaliplatin with natural neutral and cationic lipids, respectively. The formulations developed with the three methods, showed similar physicochemical characteristics, except in the loading of oxaliplatin, which was statistically lower (P<0.05) using the HM. The incorporation of a semi-synthetic lipid in the formulation developed by FM, provided liposomes with a particle size of 115 nm associated to the lowest polydispersity index and the highest drug loading, 35%, compared to the other two lipids, suggesting an increase of the membrane stability. That stability was also evaluated according to the presence of cholesterol, the impact of the temperature, and the application of different cryoprotectans during the lyophilization. The results indicated long-term stability of the developed formulation, because after its intravenous in-vivo administration to HT-29 tumor bearing mice was able to induce an inhibition of tumor growth statistically higher (P < 0.05) than the inhibition caused by the free drug. In conclusion, the FM was the simplest method in comparison with REV and HM to develop in vivo stable and efficient PEG-coated liposomes of oxaliplatin with a loading higher than those reported for REV

    New results on the hadronic vacuum polarization to the muon g-2

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    Results on the lowest-order hadronic vacuum polarization contribution to the muon magnetic anomaly are presented. They are based on the latest published experimental data used as input to the dispersion integral. Thus recent results on tau to nutau pi pi0 decays from Belle and on e+ e- annihilation to pi+ pi- from BABAR and KLOE are included. The new data, together with improved isospin-breaking corrections for tau decays, result into a much better consistency among the different results. A discrepancy between the Standard Model prediction and the direct g-2 measurement is found at the level of 3 sigma.Comment: proceedings of the PhiPsi09 conference, Oct. 13-16, 2009, Beijing, Chin

    Contributions of semi-hadronic states Pγ;Sγ,π+π−γP\gamma;S\gamma, \pi^+\pi^-\gamma to amm of muon, in frames of Nambu-Jona-Lasinio model

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    We calculate the contribution of semi-hadronic states with pseudoscalar P=π0,ηP=\pi^0, \eta and scalar (σ\sigma(550))meson accompanied with real photon as an intermediate state of a heavy photon to the anomalous magnetic moment of muon. We consider the intermediate states with π0\pi_0 and σ\sigma as a hadrons in frames of Nambu-Jona-Lasinio model. The contribution of π0γ\pi_0\gamma state is in agreement with results obtained in previous theoretical considerations as well as with experimental data aμπ0γ≈4.5×10−10a_\mu^{\pi_0\gamma}\approx 4.5 \times 10^{-10}, besides we estimate aμηγ=0.7×10−10,aμσγ∼1.5×10−11,aμπ+π−γ∼3.2×10−10.a_{\mu}^{\eta\gamma}=0.7 \times 10^{-10}, a_{\mu}^{\sigma\gamma} \sim 1.5 \times 10^{-11}, a_{\mu}^{\pi^+\pi^-\gamma} \sim 3.2 \times 10^{-10}. We discass as well the LbL mechanism with aμlbl=10.5⋅10−10.a_{\mu}^{lbl}=10.5 \cdot 10^{-10}.Comment: 6 pages, 2 figure

    A systems pharmacology model for inflammatory bowel disease

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    Motivation The literature on complex diseases is abundant but not always quantitative. This is particularly so for Inflammatory Bowel Disease (IBD), where many molecular pathways are qualitatively well described but this information cannot be used in traditional quantitative mathematical models employed in drug development. We propose the elaboration and validation of a logic network for IBD able to capture the information available in the literature that will facilitate the identification/validation of therapeutic targets. Results In this article, we propose a logic model for Inflammatory Bowel Disease (IBD) which consists of 43 nodes and 298 qualitative interactions. The model presented is able to describe the pathogenic mechanisms of the disorder and qualitatively describes the characteristic chronic inflammation. A perturbation analysis performed on the IBD network indicates that the model is robust. Also, as described in clinical trials, a simulation of anti-TNFα, anti-IL2 and Granulocyte and Monocyte Apheresis showed a decrease in the Metalloproteinases node (MMPs), which means a decrease in tissue damage. In contrast, as clinical trials have demonstrated, a simulation of anti-IL17 and anti-IFNγ or IL10 overexpression therapy did not show any major change in MMPs expression, as corresponds to a failed therapy. The model proved to be a promising in silico tool for the evaluation of potential therapeutic targets, the identification of new IBD biomarkers, the integration of IBD polymorphisms to anticipate responders and non-responders and can be reduced and transformed in quantitative model/s

    Neutralino Dark Matter in Mirage Mediation

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    We study the phenomenology of neutralino dark matter (DM) in mirage mediation scenario of supersymmetry breaking which results from the moduli stabilization in some string/brane models. Depending upon the model parameters, especially the anomaly to modulus mediation ratio determined by the moduli stabilization mechanism, the nature of the lightest supersymmetric particle (LSP) changes from Bino-like neutralino to Higgsino-like one via Bino-Higgsino mixing region. For the Bino-like LSP, the standard thermal production mechanism can give a right amount of relic DM density through the stop/stau-neutralino coannihilation or the pseudo-scalar Higgs resonance process. We also examine the prospect of direct and indirect DM detection in various parameter regions of mirage mediation. Neutralino DM in galactic halo might be detected by near future direct detection experiments in the case of Bino-Higgsino mixed LSP. The gamma ray flux from Galactic Center might be detectable also if the DM density profile takes a cuspy shape.Comment: One reference adde
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