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.     

Transparent optical packet switching: network architecture anddemonstrators in the KEOPS project

This paper reviews the work carried out in the ACTS KEOPS (Keys to Optical Packet Switching) project, describing the results obtained to date. The main objective of the project is the definition, development, and assessment of optical packet switching and routing networks, capable of providing transparency to the payload bit rate, using optical packets of fixed duration and low bit rate headers in order to enable easier processing at the network/node interfaces. The feasibility of the KEOPS concept is assessed by modeling, laboratory experiments, and testbed implementation of optical packet switching nodes and network/node interfacing blocks, including a fully equipped demonstrator. The demonstration relies on advanced optoelectronic components, developed within the project, which are described     

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).     

Origins of adolescents' ideal self: An intergenerational perspective.

The present longitudinal study traced the ideal self of 120 adolescents to the ideals that parents hold for themselves and for their children. Ideals were assessed using Q sorts for personality attributes and life goals. After permutation analysis was used to control for random similarity, moderate parent-child ideal-self similarity was evident. Three intermediate transmission steps accounted for this intergenerational similarity: (a) transfer of parents' ideal self to ideals for their children, (b) children's perception, and (c) acceptance of these parental ideals. The last 2 processes related to parenting practices, with parental warmth augmenting parent-child concordance and restrictiveness reducing it. Compared with boys' ideal self, that of girls was more similar to the ideals that parents hold for their children and for themselves. Analyses of patterns over time suggested a growth of ideal-self stability across adolescence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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.     

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.     

Colorectal surgery using a biofragmentable anastomotic ring

To compare the efficacy of the biofragmentable anastomotic ring (Valtrac-BAR, Davis and Geck, Medical Device Division, Danbury, CT, USA) with conventional anastomotic techniques, 30 patients who underwent colorectal surgery from August 1993 to March 1995 were retrospectively studied. The use of the BAR was also compared with conventional techniques including hand-sewn sutures in 30 patients and an end-to-end anastomosis (EEA) stapler in 24 patients. There were 17 men and 13 women in the BAR group with ages ranging from 37 to 80 years, 18 men and 12 women in the hand-sewn group with ages ranging from 41 to 82 years and 14 men and 10 women in the EEA group with ages ranging from 38 to 72 years. Surgical indications included: 25 colon cancers and five rectal cancers in the BAR group; 27 colon cancers and three rectal cancers in the hand-sewn group; and six colon cancers and 18 rectal cancers in the EEA group. There was no conversion to other anastomotic methods. Most of the patients tolerated a low-residual diet from the fifth post-operative day. No clinical leakage or stricture was noted. Only seven patients were aware of the passage of BAR fragments. The mean hospital stay was 14.1 days. There were no significant differences among these techniques in the return of bowel function, the incidence of surgical complications, including anastomotic leakage, or the length of hospitalization. BAR anastomosis was more time efficient than conventional techniques. Our results confirmed that BAR was an ideal sutureless alternative for anastomosis in colorectal surgery.