45 research outputs found

    Immunotherapy for murine glioma

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    Oncolytic viral immunotherapy is a novel approach to cancer treatment. Viruses can directly kill cancer cells, provide antigens to dendritic cells to stimulate a T cell response, and make cancer cells express genes of immune-enhancing cytokines locally within the tumor microenvironment. We hypothesized that the combination of oncolytic virus with a local stimulus for activating tumor-specific T cells and an anti-immunosuppressant would improve treatment of gliomas. An oncolytic virus encoding IL15Ra-IL15 (the T cell activating stimulus) and the prostaglandin synthesis inhibitor celecoxib (the anti-immunosuppressant) were combined with adoptive transfer of tumor-specific T cells. Two oncolytic poxviruses, vvDD vaccinia virus and myxoma virus, were each engineered to express the fusion protein IL15Ra-IL15 and a fluorescent protein (YFP or tdTomato Red). Viral gene expression (YFP or tdTomato Red) was confirmed in the murine glioma line GL261 in vitro and in vivo. Orthotopic GL261 tumors in immunocompetent C57BL/6J mice were treated with vvDD-IL15Ra-YFP vaccinia virus or vMyx-IL15Ra-tdTr combined with other treatments, including vaccination with GARC-1 peptide (a neoantigen for GL261), rapamycin, celecoxib, and adoptive T cell therapy. We found that vvDD-IL15Ra-YFP and vMyx-IL15Ra-tdTr each infected and killed GL261 cells in vitro. In vivo, NK cells and CD8+ T cells were increased in the tumor due to the expression of IL15Ra-IL15. Each component of a combination treatment contributed to prolonging survival: an oncolytic virus, the IL15Ra-IL15 expressed by the virus, a source of T cells (whether by pre-vaccination or adoptive transfer), and prostaglandin inhibition all synergized to produce total elimination of gliomas in a majority of mice gliomas. vvDD-IL15Ra-YFP occasionally caused ventriculitis-meningitis, but vMyx-IL15Ra-tdTr was safe and effective, causing a strong infiltration of tumor-specific T cells and eliminating gliomas in 83% of treated mice. All these facts suggest that IL15Ra-IL15-armed oncolytic poxviruses provide potent antitumor effects against brain tumors when combined with adoptive T cell therapy, rapamycin and celecoxib and that this combination treatment might be a promising method for human glioma therapy.U of I OnlyAuthor requested U of Illinois access only (OA after 2yrs) in Vireo ETD syste

    An Extended Drucker Yield Criterion to Consider Tension–Compression Asymmetry and Anisotropy on Metallic Materials: Modeling and Verification

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    Pressure sensitive asymmetric Drucker yield criterion is developed to deal with pressure dependent sheet metals for instance steels and aluminum alloys. The sensitivity to pressure is conserved by introducing three-dimensional anisotropic parameters in the first stress invariant; while the third deviatoric stress invariant is remained in odd function form to consider the strength differential effect (SDE). To describe the flow stress directionalities of metallic materials, the Drucker yield function is extended using two transformation matrix consisting of anisotropic parameters. The proposed Drucker yield criterion is utilized to predict the anisotropic yield and plastic deformation of aluminum alloys with weak SDE: AA 2090-T3 with face-centered cubic (FCC) crystal systems and AA 2008-T4 with body-centered cubic (BCC) crystal systems as well as metals with strong SDE: Zirconium clock-rolled plate with hexagonal close packing (HCP) crystal systems. The comparison between the predicted anisotropic behavior and experimental results reveals that the extended anisotropic Drucker yield criterion can precisely model the anisotropy for FCC, BCC and HCP metals. The proposed function is implemented into ABAQUS VUMAT subroutines to describe the four-point bending test which is used to consider the effect of various yield functions and material orientations on deformation behavior. The obtained contours of the cross-section, strain components distribution and also the shift of neutral layer indicate that the extended Drucker yield function can well predict the final geometric configuration of the deformed Zirconium beam

    Research on hot stamping for a typical part of B1500HS boron steel using experiment and numerical simulation methods

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    In the paper, a typical part of B1500HS boron steel was formed using the hot stamping tools, and the effect of austenitization temperature on the microstructure and mechanical properties of B1500HS steel was studied by the experiment and finite element methods. The results show that, the temperature of steel plate has a significant effect on the temperature of hot stamping tools, and the temperature of punch rises at a faster speed than that of die in the hot stamping process. The austenitization temperature and time both have significant effects on the size of martensite, but have not obvious effects on the hardness. The cooling rate of steel plate has a significant effect on the tensile strength when the austenitization temperature is 870 °C. The fracture of sample austenitized at 870 °C or 900 °C is the dimple, the fracture of sample austenitized at 930 °C or 960 °C is the mixture of quasicleavage and dimple

    Advanced Phase Change Materials from Natural Perspectives: Structural Design and Functional Applications

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    Abstract Phase change materials have garnered extensive interest in heat harvesting and utilization owing to their high energy storage density and isothermal phase transition. Nevertheless, inherent leakage problems and low heat storage efficiencies hinder their widespread utilization. Nature has served as a great source of inspiration for addressing these challenges. Natural strategies are proposed to achieve advanced thermal energy management systems, and breakthroughs are made in recent years. This review focuses on recent advances in the structural design and functions of phase change materials from a natural perspective. By highlighting the structure–function relationship, advanced applications including human motion, medicine, and intelligent thermal management devices are discussed in detail. Finally, the views on the remaining challenges and future prospects are also provided, that is, phase change materials are advancing around the biomimicry design spiral

    Cytokine Gene Vaccine Therapy for Treatment of a Brain Tumor

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    A glioma is a malignant brain tumor with a poor prognosis. Attempts at the surgical removal of the tumor are the first approach, but additional treatment strategies, including radiation therapy and systemic or local chemotherapy, are necessary. Furthermore, the treatments are often associated with significant adverse side effects. Normal and malignant cells generally have antigenic differences, and this is the rationale for clinical immunotherapeutic strategies. Cytokines such as IL-15 or IL-2, which stimulate an anti-tumor immune response, have been shown to have a particularly high potential for use in immunotherapy against various tumors. In this review, treatments with either a poxvirus, genetically engineered to secrete IL-15, or allogeneic fibroblasts, transfected with tumor DNA and engineered to secrete IL-2, are shown to be effective strategies in extending the survival of mice with malignant brain tumors upon intracerebral injection of the treatment cells. Future studies with these treatment strategies in patients with intracerebral tumors are urgently needed

    Hydrophilic Modification of Multi-Walled Carbon Nanotube for Building Photonic Crystals with Enhanced Color Visibility and Mechanical Strength

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    Low color visibility and poor mechanical strength of polystyrene (PS) photonic crystal films have been the main shortcomings for the potential applications in paints or displays. This paper presents a simple method to fabricate PS/MWCNTs (multi-walled carbon nanotubes) composite photonic crystal films with enhanced color visibility and mechanical strength. First, MWCNTs was modified through radical addition reaction by aniline 2,5-double sulfonic acid diazonium salt to generate hydrophilic surface and good water dispersity. Then the MWCNTs dispersion was blended with PS emulsion to form homogeneous PS/MWCNTs emulsion mixtures and fabricate composite films through thermal-assisted method. The obtained films exhibit high color visibility under natural light and improved mechanical strength owing to the light-adsorption property and crosslinking effect of MWCNTs. The utilization of MWCNTs in improving the properties of photonic crystals is significant for various applications, such as in paints and displays

    Research on hot stamping for a typical part of B1500HS boron steel using experiment and numerical simulation methods

    No full text
    In the paper, a typical part of B1500HS boron steel was formed using the hot stamping tools, and the effect of austenitization temperature on the microstructure and mechanical properties of B1500HS steel was studied by the experiment and finite element methods. The results show that, the temperature of steel plate has a significant effect on the temperature of hot stamping tools, and the temperature of punch rises at a faster speed than that of die in the hot stamping process. The austenitization temperature and time both have significant effects on the size of martensite, but have not obvious effects on the hardness. The cooling rate of steel plate has a significant effect on the tensile strength when the austenitization temperature is 870 °C. The fracture of sample austenitized at 870 °C or 900 °C is the dimple, the fracture of sample austenitized at 930 °C or 960 °C is the mixture of quasicleavage and dimple

    Synthesis of Novel Reactive Disperse Silicon-Containing Dyes and Their Coloring Properties on Silicone Rubbers

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    Novel red and purple reactive disperse silicon-containing dyes were designed and synthesized using p-nitroaniline and 6-bromo-2,4-dinitro-aniline as diazonium components, the first condensation product of cyanuric chloride and 3-(N,N-diethyl)amino-aniline as coupling component, and 3-aminopropylmethoxydimethylsilane, 3-aminopropylmethyldimethoxysilane, and 3-aminopropyltrimethoxysilane as silicone reactive agents. These dyes were characterized by UV-Vis, 1H-NMR, FT-IR, and MS. The obtained reactive disperse silicon-containing dyes were used to color silicone rubbers and the color fastness of the dyes were evaluated. The dry/wet rubbing and washing fastnesses of these dyes all reached 4–5 grade and the sublimation fastness was also above 4 grade, indicating outstanding performance in terms of color fastness. Such colored silicone rubbers showed bright and rich colors without affecting its static mechanical properties
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