A family of bicistronic vectors to enhance both local and systemic antitumor effects of HSVtk or cytokine expression in a murine melanoma model

The herpes simplex virus-thymidine kinase/ganciclovir (HSVtk/GCV) system produces both direct and immune-mediated tumor cell killing. Here, we compare the efficacy of HSVtk/GCV with cytokines, alone and in combination, on the tumorigenicity and immunogenicity of B16 cells. With respect to single gene modifications, only HSVtk/GCV, or high-level interleukin-2 (IL-2) secretion, completely prevented tumor growth, whereas granulocyte-macrophage colony-stimulating factor (GM-CSF) generated the best levels of long-term systemic protection. To augment both local killing and immune activation, we constructed bicistronic constructs that express HSVtk and a cytokine within the same cell. Co-expression of HSVtk with IL-2 or GM-CSF enhanced the local antitumor activity of any gene alone. In a tumor-prevention model, HSVtk killing, in an environment preprimed with GM-CSF, generated the best long-term immune protection. However, in a short-term therapy model, continued IL-2 expression was most effective against 3-day established tumors. This probably reflects differences in the activities of IL-2 and GM-CSF in generating short-term, nonspecific immune stimulation compared to long-term immunological memory, respectively. As a prelude to in vivo delivery experiments, we also demonstrated that these bicistronic cassettes can be packaged normally into retroviral (5 x 10(5) virus/ml from pooled populations) and adenoviral vectors (5 x 10(9) virus/ml) and function as predicted within virally infected cells. This family of bicistronic vectors can be used to stimulate synergy between suicide and cytokine genes, overcomes the problems of delivering two genes on separate vectors, and should allow easier preparation of vectors for the delivery of multiple genes to patients' tumor cells.     

Needles and pillboxes in anisotropic mediums

We establish a connection between the singularities of dyadic Green functions in biaxial-dielectric media arising from eigenfunction expansions in cylindrical coordinates and general expressions of depolarization dyadics. The results are then extended to general anisotropic-dielectric media     

A novel and simple model of the uptake of organic chemicals by vegetation from air and soil

A novel and simple three-compartment fugacity model has been developed to predict the kinetics and equilibria of the uptake of organic chemicals in herbaceous agricultural plants at various times, including the time of harvest using only readily available input data. The chemical concentration in each of the three plant compartments leaf, stem which includes fruits and seeds, and root) is expressed as a function of both time and chemical concentrations in soil and air. The model was developed using the fugacity concept; however, the final expressions are presented in terms of concentrations in soil and air, equilibrium partition coefficients and a set of transport and transformation half-lives. An illustrative application of the model is presented which describes the uptake of bromacil by a soybean plant under hydroponic conditions. The model, which is believed to give acceptably accurate prediction of the distribution of chemicals among plant tissues, air and soil, may be used for the assessment of exposure to, and risk from contaminants consumed either directly from vegetation or indirectly in natural and agricultural food chains.     

利用无桥式技术提供更高效率的功率因数修正器

国际整流器公司交流转直流应用部门的Ron Brown与Marco Soldano,利用周期控制技术(one-cycle control)来实现更高效率的无桥式功率因数修正器的设计. 最近,无桥式升压型功率因数修正器线路,获得了很多关注的焦点.借助移除传统转换器其输入级的桥式整流器,切换损失可以降低,而使设计者设计出更高的效率.尤有甚者,无桥式的方法可以避免因导通损,而降低效率,这种现象特别是出现在低的输入电压,其根本的原因是二极管整流器的顺向导通压降.最后,无桥式设计具有先天上更简单,需要更少器件的优点.     

Measuring quality of life for patients with terminal illness: the Missoula-VITAS quality of life index

OBJECTIVE: To investigate whether fibronectin fragments (Fn-fs), shown to damage cultured cartilage, can be found in cartilage from patients with osteoarthritis (OA) or rheumatoid arthritis, or can be generated from fibronectin (Fn) within synovial fluids or from Fn in the matrix of cultured cartilage. To also determine whether cartilage or synovial fluid Fn-fs are active and, thus, could contribute to cartilage damage in vivo. METHODS: Fn-fs were immunochemically identified in cartilage extracts from patients with OA or rheumatoid arthritis or in bovine cartilage cultured with IL-1 alpha or in bovine synovial fluids treated with stromelysin-1 (MMP-3). The effect of removal of Fn-fs from OA synovial fluids was tested by passing fluids over an anti-Fn column and adding the resultant fluids to bovine cartilage cultures to measure proteoglycan (PG) degradation. Gelatin-Sepharose purified Fns from bovine plasma, synovial fluid or cartilage were digested with MMP-3 and the Fn-fs tested for degradation of PG in cultured cartilage. RESULTS: Extracts of cartilage from patients with rheumatoid arthritis or with OA contained a range of Fn-fs. Removal of Fn-fs from OA synovial fluids significantly reduced the resultant damage when the fluids were added to cultured cartilage. Addition of IL-1 alpha to cultured cartilage or of MMP-3 to synovial fluids enhanced generation of Fn-fs. Fn-fs, whether derived from bovine plasma or synovial fluid or cartilage Fns, damaged cartilage. CONCLUSIONS: These data demonstrate that although Fn-fs could be generated in vivo within synovial fluids and Fn-fs found in OA synovial fluid may contribute to cartilage damage in vivo, Fn-fs could also be generated within cartilage and amplify cartilage damage. Thus, Fn-fs may be both autocrine and paracrine regulators of cartilage metabolism.     

Surface enhanced Raman spectroscopy for characterization of structural characteristics of carbon chains in alpha1-acid glycoprotein and pseudoglycoproteins]

Surface-enhanced Raman scattering (SERS) spectroscopy was used to study the structure of carbohydrate chains in glycosylated forms of alpha 1-acid glycoprotein (AGP) and in pseudoglycoproteins obtained by transferring the carbohydrate chains of AGP to a polyacrylamide carrier. It was found that AGP-D glycoform and pseudoglycoproteins containing three or more glycans per molecule, which possess high immunomodulating activity, have a specific spatial organization of carbohydrate chains. This organization is maintained by the interaction of neighboring glycans with each other and does not depend on the nature of the carrier (whether it is polypeptide or polyacrylamide).     

Effect of cerebral ischaemia on the cerebrovascular and cardiovascular response to haemorrhage

Reports studying the combination of low blood pressure and cerebral ischaemia are few, and it remains to be determined how cerebral circulatory insufficiency modifies the cerebral perfusion and the central haemodynamic response to blood loss. We hypothesised that occlusion of arteries to the brain modifies the cerebrovascular and cardiovascular responses to blood loss. Continuous measurements of the cerebral microcirculation with laser Doppler microprobes in the cerebral cortex were performed in anaesthetised pigs during cerebral ischaemia and haemorrhagic hypotension. The response to rapid bleeding (25% of the blood volume) was recorded during normal conditions and during cerebral ischaemia induced by bilateral occlusion of the common carotid arteries. During normal conditions haemorrhage caused insignificant decreases in cerebral microcirculation. Haemorrhage during bilateral carotid artery occlusion, however, caused significantly greater changes in cerebral microcirculation and a greater posthaemorrhagic increase in cerebrovascular resistance shortly after the blood loss. Haemorrhage during bilateral carotid artery occlusion also caused greater reductions in cardiac output and arterial pressure than similar blood loss caused during normal conditions. This study showed a disproportionate decrease in cerebral blood flow with haemorrhage during bilateral carotid occlusion, caused by an immediate increase in cerebrovascular resistance. The results suggest that even a moderate blood loss in patients with impaired cerebral circulation could be dangerous, because normal compensatory mechanisms to haemorrhage are impaired.     

Assuring quality in extramural studies: the perceptions of practitioners

This paper presents the results of a questionnaire completed by 331 UK veterinary practitioners which focused on the quality assurance of extramural studies. The questionnaire considered the attributes of practitioners as extramural teachers and the suitability of host practices for extramural studies, the students' evaluation of their quality, and the role of the veterinary schools. The questionnaire identified two broad roles for the practitioner, first, as teacher and, secondly, as professional role model, and there was strong support for students being allowed to evaluate their role as teacher. The findings are discussed in relation to aspects of good practice associated with quality assurance, and in relation to the need to develop stronger links between the schools and the veterinary profession.     

Stimulus classes in matching to sample and sequence production: the emergence of numeric relations

We investigated interrelationships among stimulus classes established in matching-to-sample and sequence-production tasks. The analysis focused on the matching and sequencing of quantities, numerals, and arbitrary forms in two individuals with mental retardation. The basic protocol involved: (a) establishing both matching and sequencing performances with some stimuli, (b) training sequencing with a new set of stimuli and assessing whether new matching performances emerged, and (c) training matching with a new set of stimuli and assessing whether new sequencing emerged. The results showed that sequence training did not readily lead to new matching performances, unlike prior research with college students. In contrast, training in matching to sample yielded emergent sequence production; these data support prior studies involving children and adults without developmental disabilities. The results extend prior stimulus class research and suggest an important role for stimulus control processes in the production of generative numeric performances.     

Current situation and control strategies for resurgence of diphtheria in newly independent states of the former Soviet Union

Since 1990, an epidemic of diphtheria has spread throughout the newly independent states of the former Soviet Union, and by 1995 a total of 47 808 cases were reported. During the early stages of the epidemic, adequate control measures were not taken and vaccine was in short supply; possible contributing factors to the spread of the epidemic are the presence of highly susceptible child and adult populations, socioeconomic instability, population movement, and a deteriorating health infrastructure. Although WHO views the epidemic as an International public-health emergency and, together with UNICEF and the International Red Cross, has formulated a strategy to combat the epidemic, the necessary funds have not been made fully available. Current vaccination recommendations also need to be reviewed to ensure that population immunity will be adequate to prevent any resurgence of diphtheria in Europe and North America.