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61.
Immune and Anticancer Responses Elicited by Fully Synthetic Aberrantly Glycosylated MUC1 Tripartite Vaccines Modified by a TLR2 or TLR9 Agonist
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Dr. Abu‐Baker M. Abdel‐Aal Dr. Vani Lakshminarayanan Dr. Pamela Thompson Nitin Supekar Judy M. Bradley Dr. Margreet A. Wolfert Prof. Dr. Peter A. Cohen Prof. Dr. Sandra J. Gendler Prof. Dr. Geert‐Jan Boons 《Chembiochem : a European journal of chemical biology》2014,15(10):1508-1513
The mucin MUC1 is overexpressed and aberrantly glycosylated by many epithelial cancer cells manifested by truncated O‐linked saccharides. Although tumor‐associated MUC1 has generated considerable attention because of its potential for the development of a therapeutic cancer vaccine, it has been difficult to design constructs that consistently induce cytotoxic T‐lymphocytes (CTLs) and ADCC‐mediating antibodies specific for the tumor form of MUC1. We have designed, chemically synthesized, and immunologically examined vaccine candidates each composed of a glycopeptide derived from MUC1, a promiscuous Thelper peptide, and a TLR2 (Pam3CysSK4) or TLR9 (CpG‐ODN 1826) agonist. It was found that the Pam3CysSK4‐containing compound elicits more potent antigenic and cellular immune responses, resulting in a therapeutic effect in a mouse model of mammary cancer. It is thus shown, for the first time, that the nature of an inbuilt adjuvant of a tripartite vaccine can significantly impact the quality of immune responses elicited against a tumor‐associated glycopeptide. The unique adjuvant properties of Pam3CysSK4, which can reduce the suppressive function of regulatory T cells and enhance the cytotoxicity of tumor‐specific CTLs, are likely responsible for the superior properties of the vaccine candidate 1 . 相似文献
62.
A comparative study of cyclic fatigue damage from Hertzian contacts in silicon carbide ceramics with homogeneous microstructure (fine, equiaxed grains, strong grain boundaries) and heterogeneous microstructure (coarse, contiguous elongate grains, weak interphase boundaries) is presented. Observations of the surface and subsurface damage patterns using optical microscopy reveal fundamentally different cyclic fatigue mechanisns: in the homogeneous material, by slow growth of a well-developed cone crack outside the contact area; in the heterogeneous material, by progressive mechanical degradation within a distributed damage zone below the contact area. Scanning electron micrographs of the latter material show copious fine debris in the damage zone, consistent with a degradation mechanism by frictional attrition by forward-reverse sliding at the weak interphase boundaries. Acoustic emission is recorded during both load and unload half-cycles, confirming hysteresis in the sliding process. Flexure tests indicate initially slight strength losses from the cyclic contact damage in both microstructures, followed by accelerated losses at higher numbers of cycles. The underlying basis for establishing an analytical model of damage accumulation in the heterogeneous microstructure in terms of shear-fault sliding, and for designing micro-structures for optimal properties in fatigue and wear applications, is foreshadowed. 相似文献
63.
Shrinidhi Chandrasekharan Hariharasudhan Palaniswamy Nitin Jain Gracious Ngaile Taylan Altan 《International Journal of Machine Tools and Manufacture》2005,45(4-5):379-388
Lubricants are employed in stamping operations in order to (a) improve the material flow into the die cavity, (b) reduce wear and galling in the die and (c) obtain good surface finish of the part. Process conditions such as high temperatures and pressures could cause the lubricant to fail, thus resulting in galling or tearing of the part, damage to the tooling, and lost production. Therefore, selection of an appropriate lubricant based on the process conditions is important in the stamping industry. Several benchmark tests emulating stamping operations have been developed and are used to evaluate the performance of candidate lubricants. The major drawback of most of these tests is their inability to emulate high contact pressures and sliding velocities, which are crucial parameters for lubricity, especially in the case of high-speed progressive or transfer die operations involving ironing. Moreover, most of these tests are conducted at room temperature, while in reality; the process temperature can reach as high as 200 °C. The ironing tribotest developed at the Engineering Research Center for Net Shape Manufacturing (ERC/NSM) induces high contact pressures and temperatures, thus emulating the conditions in a production environment. Application of the test to screen candidate lubricants for stamping operations involving the ironing process is discussed in this paper. 相似文献
64.
To improve response time of a Web site, one replicates the site on multiple servers. The effectiveness of a replicated server system will depend on how the incoming requests are distributed among replicas. A large number of load‐balancing strategies for Web server systems have been proposed. In this paper we describe a testbed that can be used to evaluate the performance of different load‐balancing strategies. The testbed uses a general architecture which allows different load‐balancing approaches to be supported easily. It emulates a typical World Wide Web scenario and allows variable load generation and performance measurement. We have performed some preliminary experiments to measure the performance of a few policies for load balancing using this testbed. Copyright © 2003 John Wiley & Sons, Ltd. 相似文献
65.
Nitin R. Anturkar James O. Wilkes Tasos C. Papanastasiou 《Polymer Engineering and Science》1993,33(23):1532-1539
In industrial coextrusion operations, multiple layers are frequently brought in contact with each other at different temperatures to “match” viscosities and to reduce interfacial instability. Here, a linear stability analysis of multilayer plane Poiseuille flow is carried out for real, specific polymer melts in terms of process parameters, such as temperatures and flow rates. However, heat transfer across the layers is neglected as a first approximation. Previously, it was observed that below a certain Reynolds number and above a certain relaxation time, the flow-rate ratio (or the depth ratio), above which the flow is stable to all wavelengths, can be estimated by the long-wavelength asymptotic analysis (1,3). The Reynolds numbers for the industrial flows are smaller, and the relaxation times are larger than the corresponding critical values by several orders of magnitude. Therefore, the critical stability parameters can be estimated in the present study for industrial cases using the asymptotic stability analysis at long wavelengths. Although a large number of earlier parametric studies of model fluids indicate the influence of various theological parameters, only the viscosity stratification plays an important role in the interfacial instability within the operating range of industrial coextrusion processes. 相似文献
66.
M. Dhakad Amish G. Joshi S. Rayalu P. Tanwar J. K. Bassin R. Kumar S. Lokhande J. Subrt T. Mitsuhashi Nitin Labhsetwar 《Topics in Catalysis》2009,52(13-20):2070-2075
Alumina supported Co–K–Mo based mixed metal oxide type catalytic materials have been prepared by co-impregnation. These catalysts show excellent activity for carbon as well as diesel soot oxidation, which could be due to the redox properties of Mo and Co as well as to a synergistic effect of molybdenum, cobalt, and K contents. The catalyst containing 5 wt% molybdenum shows a lowering of carbon oxidation by about 190 °C under loose contact conditions as compared to the non-catalyzed reaction, as well as to bare alumina. Characterization studies suggest a composite nature of these materials, while thermal stability investigations confirm the stable nature. The selected catalyst has been studied by XPS, however, it is difficult to conclude which are the important factors contributing to the catalytic activity. It appears to be a synergistic effect of Co, K, and Mo components as these catalysts show much improved activity as compared to the individual components in supported and unsupported forms. 相似文献
67.
This study represents the application of nanozeolite NaX (NZX) synthesized by hydrothermal treatment without addition of any expensive structure directing agent for the highly effectual adsorption of biochanin A from aqueous solution. The characteristics and surface morphology of NZX were determined using FT-IR, SEM, TEM, BET, and XRD. The adsorption performance of NZX was analyzed at different conditions such as temperature, pH, contact time, adsorbent dose, and initial adsorbate concentration. The adsorption mechanism was well verified by pseudo-second-order kinetic and Redlich–Peterson isotherm models. The thermodynamic parameters revealed that the removal process was exothermic and spontaneous. 相似文献
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70.
Sharma Nitin Kumar Kannan Rangasayee Li Leijun Anderson Neil Rashid Muhammad Collins Laurie Poplawsky Jonathan D. Unocic Raymond 《Metallurgical and Materials Transactions A》2021,52(9):3788-3798
Metallurgical and Materials Transactions A - The bondline of electric-resistance-welded (ERW) linepipe steel, often etched white (i.e., ferrite) in optical microscopy, is generally believed to be... 相似文献