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Maria Buuales Maria Cristina Ballesteros-Briones Manuela Gonzalez-Aparicio Sandra Hervas-Stubbs Eva Martisova Uxua Mancheo Ana Ricobaraza Sara Lumbreras Cristian Smerdou Ruben Hernandez-Alcoceba 《International journal of molecular sciences》2021,22(8)
Immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy in a growing number of malignancies. However, overcoming primary or secondary resistances is difficult due to pharmacokinetics issues and side effects associated with high systemic exposure. Local or regional expression of monoclonal antibodies (mAbs) using gene therapy vectors can alleviate this problem. In this work, we describe a high-capacity adenoviral vector (HCA-EFZP-aPDL1) equipped with a mifepristone-inducible system for the controlled expression of an anti-programmed death ligand 1 (PD-L1) blocking antibody. The vector was tested in an immune-competent mouse model of colorectal cancer based on implantation of MC38 cells. A single local administration of HCA-EFZP-aPDL1 in subcutaneous lesions led to a significant reduction in tumor growth with minimal release of the antibody in the circulation. When the vector was tested in a more stringent setting (rapidly progressing peritoneal carcinomatosis), the antitumor effect was marginal even in combination with other immune-stimulatory agents such as polyinosinic-polycytidylic acid (pI:C), blocking mAbs for T cell immunoglobulin, mucin-domain containing-3 (TIM-3) or agonistic mAbs for 4-1BB (CD137). In contrast, macrophage depletion by clodronate liposomes enhanced the efficacy of HCA-EFZP-aPDL1. These results highlight the importance of addressing macrophage-associated immunoregulatory mechanisms to overcome resistance to ICIs in the context of colorectal cancer. 相似文献
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Gas hold-up, mixing intensity of dispersion characterised by exchange flows between adjacent impellers and a volumetric mass transfer coefficient are presented for 18 impeller configurations in triple-impeller vessel of inner diameter . Rushton Turbines, six Pitched Blade impellers pumping down and hydrofoil impellers Techmix 335 (Techmix co., Czech republic) pumping up or down and their combinations were used. aqueous solution was used as a liquid phase, which represents non-coalescent batches. Gas hold-ups and volumetric mass transfer coefficients are presented for individual configurations as functions of specific power dissipated and superficial gas velocity. The regression of the mass transfer coefficients shows large standard deviation (30%). The power number included to the regression to express the impeller configuration effect did not improve the standard deviation significantly (23%). The impeller configurations with low power number (less than unity) provide higher dispersion mixing intensities, while the impeller configurations with high power number provide better mass transfer performance. 相似文献
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Poly(p-tert-butoxycarbonyloxystyrene): a convenient precursor to p-hydroxystyrene resins 总被引:1,自引:0,他引:1
An efficient synthetic route to pure, high molecular weight poly(p-hydroxystyrene) is reported. The route involves synthesis of a new monomer, p-tert-butoxycarbonyloxystyrene, polymerization by radical initiation or by cationic initiation in liquid SO2, followed by thermolysis or acidolysis of the tert-butoxycarbonyl protecting group. Porous, crosslinked resin beads containing the nucleophilic, phenol pendant group have been prepared in a similar fashion from the precursor terpolymer of p-tert-butoxycarbonyloxystyrene, styrene and divinylbenzene. The utility of this resin for solid-phase synthesis has been demonstrated. 相似文献
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Conium maculatum, a Eurasian weed naturalized in North America, contains high concentrations of piperidine alkaloids that act as chemical defenses against herbivores. C. maculatum was largely free from herbivory in the United States, until approximately 30 yr ago, when it was reassociated via accidental introduction with a monophagous European herbivore, the oecophorid caterpillar Agonopterix alstroemeriana. At present, A. alstroemeriana is found in a continuum of reassociation time and intensities with C. maculatum across the continent; in the Pacific Northwest, A. alstroemeriana can cause severe damage, resulting in some cases in complete defoliation. Studies in biological control and invasion biology have yet to determine whether plants reassociated with a significant herbivore from the area of indigeneity increase their chemical defense investment in areas of introduction. In this study, we compared three locations in the United States (New York, Washington, and Illinois) where C. maculatum experiences different levels of herbivory by A. alstroemeriana to determine the association between the intensity of the interaction, as measured by damage, and chemical defense production. Total alkaloid production in C. maculatum was positively correlated with A. alstroemeriana herbivory levels: plants from New York and Washington, with higher herbivory levels, invested two and four times more N to alkaloid synthesis than did plants from Illinois. Individual plants with lower concentrations of alkaloids from a single location in Illinois experienced more damage by A. alstroemeriana, indicative of a preference on the part of the insect for plants with less chemical defense. These results suggest that A. alstroemeriana may act either as a selective agent or inducing agent for C. maculatum and increase its toxicity in its introduced range. 相似文献
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Natural rubber vulcanizates of two formulations, with sulfur/N-cyclohexyl-2-benzothiazolesulfenamide (CBS) and tetramethylthiuram disulfide (TMTD), respectively, were analyzed by pyrolysis gas chromatography. A sulfur-selective flame-photometric detector was utilized. The main pyrolysis products were identified as CS2 and some thiophenes. The yields of the pyrolysis products from the two types of rubber were very different. The yields also varied with the curing time of the rubbers. 相似文献
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Beatriz Miranda Eva Díaz Salvador Ordez Fernando V. Díez 《Catalysis communications》2006,7(12):945-949
The performance of 0.5% Ru/Al2O3 for the deep oxidation of trichloroethene (1000–2500 ppmV, WHSV = 55 h−1) in air was studied in this work. Experiments were carried out both at dry and wet (20,000 ppmV of H2O) conditions. Catalytic performance was studied in terms of activity and selectivity for the different reaction products (CO2, HCl, Cl2, C2Cl4, CCl4 and CHCl3). Both the activity and the selectivity for total combustion are higher than other catalysts suggested in the literature for this process (especially Pd and Pt).The main organic by-products are CCl4 and CHCl3, whereas in all the other catalysts tested in the literature, tetrachloroethene is the main organic by-product. This fact suggests that the mechanism of the combustion reaction, involving a double-bond scission, is essentially specific for this catalyst.Kinetic data was fit to a pseudo-first order kinetic expression, providing fairly good fit. 相似文献
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Sufficient conditions for stability and stabilization of networked control systems with uncertainties and nonlinearities 下载免费PDF全文
In this paper, we consider the problem of robust stability and stabilization for networked control systems (NCS) with uncertain/nonlinear dynamics AUTHOR: Please check that authors and their affiliations are correct. in which the network‐induced delays are time‐varying and bounded. Based on some recent achievements, a relatively simple Lyapunov–Krasovskii functional is proposed to derive sufficient conditions both for analysis and synthesis of NCS in the form of LMIs depending on the delay bounds. The effectiveness of the proposed method is illustrated by several benchmark examples available in the literature. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
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