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11.
Patients who undergo transplantation with haploidentical "three-loci" mismatched T-cell-depleted bone marrow (BM) are at high risk for graft failure. To overcome the host-versus-graft barrier, we increased the size of the graft inoculum, which has been shown to be a major factor in controlling both immune rejection and stem cell competition in murine models. Seventeen patients (mean age, 23.2 years; range, 6 to 51 years) with end-stage chemoresistant leukemia were received transplants of a combination of BM with recombinant human granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells from HLA-haploidentical "three-loci" incompatible family members. The average concentration of colony-forming unit-granulocyte-macrophage in the final inoculum was sevenfold to 10-fold greater than that found in BM alone. The sole graft-versus-host disease (GVHD) prophylaxis consisted of T-cell depletion of the graft by the soybean agglutination and E-rosetting technique. The conditioning regimen included total body irradiation in a single fraction at a fast dose rate, antithymocyte globulin, cyclophosphamide and thiotepa to provide both immunosuppression and myeloablation. One patient rejected the graft and the other 16 had early and sustained full donor-type engraftment. One patient who received a much greater quantity of T lymphocytes than any other patient died from grade IV acute GVHD. There were no other cases of GVHD > or = grade II. Nine patients died from transplant-related toxicity, 2 relapsed, and 6 patients are alive and event-free at a median follow-up of 230 days (range, 100 to 485 days). Our results show that a highly immunosuppressive and myeloablative conditioning followed by transplantation of a large number of stem cells depleted of T lymphocytes by soybean agglutination and E-rosetting technique has made transplantation of three HLA-antigen disparate grafts possible, with only rare cases of GVHD.  相似文献   
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Breast cancer is the most frequent cancer in women worldwide and late diagnosis often adversely affects the prognosis of the disease. Radiotherapy is commonly used to treat breast cancer, reducing the risk of recurrence after surgery. However, the eradication of radioresistant cancer cells, including cancer stem cells, remains the main challenge of radiotherapy. Recently, lipid droplets (LDs) have been proposed as functional markers of cancer stem cells, also being involved in increased cell tumorigenicity. LD biogenesis is a multistep process requiring various enzymes, including Diacylglycerol acyltransferase 2 (DGAT2). In this context, we evaluated the effect of PF-06424439, a selective DGAT2 inhibitor, on MCF7 breast cancer cells exposed to X-rays. Our results demonstrated that 72 h of PF-06424439 treatment reduced LD content and inhibited cell migration, without affecting cell proliferation. Interestingly, PF-06424439 pre-treatment followed by radiation was able to enhance radiosensitivity of MCF7 cells. In addition, the combined treatment negatively interfered with lipid metabolism-related genes, as well as with EMT gene expression, and modulated the expression of typical markers associated with the CSC-like phenotype. These findings suggest that PF-06424439 pre-treatment coupled to X-ray exposure might potentiate breast cancer cell radiosensitivity and potentially improve the radiotherapy effectiveness.  相似文献   
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In addition to triggering the activation of B- or T-cell antigen receptors, the binding of a ligand to its receptor at the cell surface can sometimes determine the physiological outcome of interactions between antigen-presenting cells, T and B lymphocytes. The protein SLAM (also known as CDw150), which is present on the surface of B and T cells, forms such a receptor-ligand pair as it is a self-ligand. We now show that a T-cell-specific, SLAM-associated protein (SAP), which contains an SH2 domain and a short tall, acts as an inhibitor by blocking recruitment of the SH2-domain-containing signal-transduction molecule SHP-2 to a docking site in the SLAM cytoplasmic region. The gene encoding SAP maps to the same area of the X chromosome as the locus for X-linked lymphoproliferative disease (XLP) and we found mutations in the SAP gene in three XLP patients. Absence of the inhibitor SAP in XLP patients affects T/B-cell interactions induced by SLAM, leading to an inability to control B-cell proliferation caused by Epstein-Barr virus infections.  相似文献   
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Mismatched haploidentical bone marrow transplantations from a related donor have been the topic of clinical and laboratory research for more than 20 years. During that time, new treatment strategies have been designed based on animal experiments, and, since our group introduced the megadose inoculum which combines T-cell-depleted bone marrow cells with a large number of granulocyte colony-stimulating factor-mobilized peripheral blood stem cells and a more intensive conditioning regimen, have done much to overcome the problems of graft-versus-host disease and graft rejection. As most patients have a full haplotype mismatched relative available, this technique means that a far greater number of patients with hematologic malignancies can be offered a T-cell-depleted transplantation as curative therapy.  相似文献   
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Mono-material in the manufacturing of oil-based plastic bottles has been so far not considered because of the poor flexibility of polyethylene terephthalate (PET). The undercuts of PET caps (i.e., the threads of the screw caps) would be torn-off during the ejection step of the injection/compression molding processes that are commonly used to fabricate them. In this respect, the present work deals with the design and development of innovative biodegradable polyester-based blends with high flexibility, intended for the manufacturing of screw-cap, being this element the most critical in the implementation of the complete bottle. The blend is based on polylactic acid and it is tailored for injection molding of tamper-evident screw plastic caps by the addition of another biodegradable polyester, that is, polybutylene adipate-co-terephthalate. The effect of the addition of a barrier agent, polyvinyl alcohol, on the overall behavior of the blends was also studied in the perspective of the implementation of caps featuring barrier properties against water vapor and oxygen. The same material could be, however, easily tailored for the fabrication of the bottle body and printed label to get to the mono-material bottle. Twin-screw corotating extrusion of the compound, injection molding of the plastic material for the fabrication of the screw caps, and evaluation of the thermophysical and mechanical properties of the screw caps are hereinafter discussed. The biodegradable polyester-based blends are found to be suitable for injection molding of the tamper-evident screw caps, exhibiting adequate flexibility during ejection from the mold. The screw caps can also boast appreciable mechanical strength and impact resistance as well as good thermal stability.  相似文献   
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The present work is aimed at developing innovative solutions to enhance mechanical and physical properties of Poly(Lactic) Acid (PLA) blends, specifically designed for melt processing applications. Attention is drawn on dimensional accuracy and stability of PLA-based components manufactured by injection molding. PLA belongs to the class of bioplastic materials, entirely relying on renewable resources. It is a semi-crystalline linear aliphatic polyester, highly prone to recrystallize in harsh temperature conditions that can arise during transportation or storage of injection-molded components. Recrystallization is known to cause shrinkage of polymeric materials and, consequently, a marked warpage of components produced from them, causing scraps or parts that do not conform to the functional requirements. In this context, the experimental investigation deals with the effect of increasing amounts of micro-lamellar talc in PLA and Poly(butylene) Succinate Co-Adipate (PBSA) blends. In particular, the role of talc aliquot on dimensional accuracy and stability of injection-molded coffee capsules manufactured by PLA/PBSA blends is studied, with emphasis on the key role of recrystallization. For that purpose, commercial grade PLA and PBSA are compounded with micro-lamellar talc and several processing additives by a twin screw co-rotating extruder. The resulting compound is reprocessed to form coffee capsules by injection molding. Characterization tests include Differential Scanning Calorimetry (DSC), Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) spectroscopy and Field Emission Gun Scanning Electron Microscopy (FEG – SEM). Measurements of the characteristic dimensions of the molded components reveals the effect of increasing amounts of talc in PLA/PBSA blends on dimensional accuracy and stability properties of coffee capsules. Brewing tests allowed to identify the formulations that can ensure the utmost geometrical accuracy of the coffee capsules and their suitability for brewing in instant coffee machine. Based on experimental evidences, lowest shrinkage and improved stability are found on components manufactured by polymeric blends that involve the highest amount of talc.  相似文献   
18.
“Row nucleated lamellar” structures are formed when highly crystalline polymers are melt-extruded and recrystallized under high stress. Polyethylene (PE) and polypropylene (PP) films with row lamellar structures have been utilized to produce microporous membranes. Birefringence measurements of melt-extruded PE films show that improved film orientation can be achieved by annealing, extruding at higher speed, and using higher molecular weight polymers. Images from scanning tunneling, atomic force, and field emission scanning electron microscopy (STM, AFM, and FESEM) clearly show the lamellar structures in the melt-extruded PE and PP films. Microscopy results also show that surface lamellar textures are more pronounced with thicker lamellae and are better aligned along the extrusion direction after annealing. X-ray diffraction results show that the increase in film orientation can be attributed to increased lamellar perfection and orientation during annealing and also to better crystallite alignment along the machine direction with higher extrusion speed or with higher molecular weight. High-resolution capabilities of STM, AFM, and FESEM prove to be very effective tools in elucidating lamellar structures in polymeric membrane precursors and can be used as an aid in establishing structure–process–property relationships in making microporous membranes. © 1994 John Wiley & Sons, Inc.  相似文献   
19.
Use of high-temperature superconducting (HTS) windings may soon turn power transformers into compact high-performers on good terms with the environment. The potential for HTS transformers is being examined in major design and hardware development programs by several teams of engineers and scientists worldwide. The team to which the authors belong is led by Waukesha Electric Systems. The Waukesha-led team has conducted a series of reference designs concentrating mostly on a 30-MVA, 138-kV/13.8-kV transformer rating. This rating is representative of a medium power transformer class foreseen as comprising about half of all US power transformer sales in the next two decades. Two of these designed are compared with a 30-MVA conventional oil-filled transformer typical of this class. Each uses a different commercially successful and reliable type of refrigeration. Since reliable operation is paramount, both transformers are designed to have a several-day on-board refrigeration reserve that lets them operate continuously with no interruption of service to customers  相似文献   
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