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Treating neuroinflammation-related injuries and disorders through manipulation of neuroinflammation functions is being heralded as a new therapeutic strategy. In this study, a novel pectic galactan (PG) polysaccharide based gene therapy approach is developed for targeting reactive gliosis in neuroinflammation. Galectin-3 (Gal-3) is a cell protein with a high affinity to β-galactoside sugars and is highly expressed in reactive gliosis. Since PG carries galactans, it can target reactive gliosis via specific carbohydrate interaction between galactan and Gal-3 on the cell membrane, and therefore can be utilized as a carrier for delivering genes to these cells. The carrier is synthesized by modifying quaternary ammonium groups on the PG. The resulting quaternized PG (QPG) is found to form complexes with plasmid DNA with a mean diameter of 100 nm and have the characteristics required for targeted gene therapy. The complexes efficiently condense large amounts of plasmid per particle and successfully bind to Gal-3. The in vivo study shows that the complexes are biocompatible and safe for administration and can selectively transfect reactive glial cells of an induced cortical lesion. The results confirm that this PG-based delivery system is a promising platform for targeting Gal-3 overexpressing neuroinflammation cells for treating neuroinflammation-related injuries and neurodegenerative diseases.  相似文献   
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CAR (Chimeric Antigen Receptor) T cells have demonstrated clinical success for the treatment of multiple lymphomas and leukaemias, but not for various solid tumours, despite promising data from murine models. Lower effective CAR T-cell delivery rates to human solid tumours compared to haematological malignancies in humans and solid tumours in mice might partially explain these divergent outcomes. We used anatomical and physiological data for human and rodent circulatory systems to calculate the typical perfusion of healthy and tumour tissues, and estimated the upper limits of immune cell delivery rates across different organs, tumour types and species. Estimated maximum delivery rates were up to 10 000-fold greater in mice than humans yet reported CAR T-cell doses are typically only 10–100-fold lower in mice, suggesting that the effective delivery rates of CAR T cells into tumours in clinical trials are far lower than in corresponding mouse models. Estimated delivery rates were found to be consistent with published positron emission tomography data. Results suggest that higher effective human doses may be needed to drive efficacy comparable to mouse solid tumour models, and that lower doses should be tested in mice. We posit that quantitation of species and organ-specific delivery and homing of engineered T cells will be key to unlocking their potential for solid tumours.  相似文献   
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A cohort of 2nd-grade students provided comparisons of academic and social competence based on school retention/promotion decisions. Sample groups were (a) retained, (b) at risk for retention, (c) special education, and (d) promoted. Findings suggested most children with academic deficiencies are identified by schools early and are sorted into educational treatments differing in intensity that represent a continuum of competence. The authors provide empirical evidence counter to the assumptions that retained students have the requisite ability to catch up and have more problem behaviors than other low-achieving students. The relevance of high-stakes test scores for promotion/retention decisions and the parallels between schools' implementation of retention policy and implementation of regulations for identifying children with disabilities are included in the discussion. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
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A series of studies of top European and other firms has revealed patterns of design management associated with commercial success. Firms that invest resources and professional expertise in product and industrial design in traditional and new industries have been commercially more successful than firms that pay less attention to these aspects of design. As an industry matures there is a shift in emphasis from design associated with technological innovation, to designs supporting technical improvements, and then to supporting user needs, fashion and product variants. These issues are illustrated through the history of the evolution of the bicycle.  相似文献   
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Cured samples of a nitrogen-containing acetylene-terminated resin, N,N′-(1,3-phenylene-dimethylidene)bis(3-ethynylaniline), have been heated at 10°C/min up to 900°C in a pyroprobe attached to a gas chromatograph/mass spectrometer (GC/MS). Analysis of the volatiles evolved during heating identified both gases and higher boiling compounds. The major higher boiling compounds are benzene, toluene, xylene, aniline, benzonitrile, m-methylaniline, and m-methylbenzonitrile; the gases include ammonia, methane, and traces of carbon dioxide. Correlations between sample temperature and the evolution of each of these compounds have been made. The onset of all volatile formation occurs between 450 and 500°C. The higher boiling volatiles peak, then end by approximately 700°C, while the gases peak then fall off but are still being evolved at 900°C. Average weight loss measurements of 13.6% at 700°C and 15.7% at 900°C agree with previously published thermogravimetric analysis (TGA) data. © 1993 John Wiley & Sons, Inc.  相似文献   
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A historical review of licensing among industrial/organizational (I/O) psychologists demonstrates that the American Psychological Association (APA) policy on such licensing is inconsistent. Arguments for and against licensure for this group are presented. Job analysis and APA data are drawn upon to show that few I/O activities may pose the personal risk that would seem to require the protection of a license. Alternatives are discussed for changes in present APA policy and state licensing requirements. (16 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
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This paper attempts to broaden the analysis of the technology transfer phenomenon by refocusing research attention on the level of performance assessment of technology transfer projects. An holistic evaluation framework based on the considerations of an extended Project Life Cycle model is proposed to overcome some of the shortcomings of conventional approaches to project evaluation. This also reinforces the need for open systems thinking in assessing and managing risk of technology transfer projects. The discussion is based on two case studies which articulate the experiences with two integrated mechanisms of technology transfer used in Algeria from 1965 to 1990: turnkey and “product-in-hand”. The aim is to gain a better understanding of the processes of technology transfer and to contribute to the improvement of associated managerial practices in developing economies.  相似文献   
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Many advanced document systems provide a formatting mechanism called ‘style sheets’ Style sheets provide a great deal of flexibility in describing a document's format, and allow easy maintenance of different house styles for a collection of documents. In this paper, we describe the basics of general style sheet systems, argue that successful document interchange must include the exchange of style sheet information, and evaluate ODA's style mechanism against this requirement.  相似文献   
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