GD3/proteosome vaccines induce consistent IgM antibodies against the ganglioside GD3

The gangliosides of melanoma and other tumours of neuroectodermal origin are suitable targets for immune intervention with tumour vaccines. The optimal vaccines in current use contain ganglioside plus bacillus Calmette-Guérin and induce considerable morbidity. We have screened a variety of new adjuvants in the mouse, and describe one antigen-delivery system, proteosomes, which is especially effective. Highly hydrophobic Neisserial outer membrane proteins (OMP) form multimolecular liposome-like vesicular structures termed proteosomes which can readily incorporate amphiphilic molecules such as GD3 ganglioside. The optimal GD3/proteosome vaccine formulation for induction of GD3 antibodies in the mouse is determined. Interestingly, the use of potent immunological adjuvants in addition to proteosomes augments the IgM and IgG antibody titres against OMP in these vaccines but GD3 antibody titres are unaffected. The application of proteosomes to enhance the immune response to GD3 extends the concept of the proteosome immunopotentiating system from lipopeptides to amphipathic carbohydrate epitopes such as cell-surface gangliosides. The demonstrated safety of meningococcal OMP in humans and the data in mice presented here suggest that proteosome vaccines have potential for augmenting the immunogenicity of amphipathic tumour antigens in humans.     

An attempt to compare the performance of bioscrubbers and biotrickling filters for degradation of ethyl acetate in gas streams

This study presents a comparison of the efficiency of a bioscrubber and a biotrickling filter (BTF) for the removal of ethyl acetate (EA) vapour from a waste gas stream, under the same operating conditions. The maximum EA elimination capacity achieved in the bioscrubber was 550 g m^?3 h^?1 with removal efficiency higher than 96%. For higher EA loadings the bioscrubber was oxygen limited, which caused incomplete EA biodegradation. When pure oxygen was fed to the bioscrubber at a rate of 0.02 L min^?1, the bioscrubber recovered and could treat higher EA loadings without any oxygen limitation. The BTF achieved EA elimination capacity of 600 g m^?3 h^?1 with removal efficiency higher than 97% and the dissolved oxygen concentration remained substantially higher than in the bioscrubber. However, severe channelling and blockage of the spray nozzle occurred due to the excessive biomass growth. Overall, the bioscrubber system was easier to operate and control than the BTF, while an enhancement of the oxygen mass transfer in the bioscrubber could potentially increase its performance by up to three times. Copyright © 2005 Society of Chemical Industry     

Room-temperature deformation and stress-induced phase transformation of laves phases in Fe-10 At. Pct Zr alloy

The microstructure within particles of the Laves phase Fe₂Zr in a two-phase Fe-10 at. pct Zr alloy after compression was investigated using X-ray diffraction and electron microscopy. Stressinduced phase transformation between C36 and C15 structures was found to be a major deformation mode for the Laves phase. Twinning and stacking faults were also found within C15 regions. Phase transformation models based on partial dislocations are discussed.     

Isolation of a novel Helicobacter species, Helicobacter cholecystus sp. nov., from the gallbladders of Syrian hamsters with cholangiofibrosis and centrilobular pancreatitis

A filamentous, gram-negative, motile bacterium with a single polar sheathed flagellum was isolated from gallbladders of hamsters with cholangiofibrosis and centrilobular pancreatitis. Bacteria grew under microaerophilic conditions at 37 and 42 degrees C, were oxidase, catalase, arginine aminopeptidase, and L-arginine arylamidase positive, reduced nitrate to nitrite, were resistant to cephalothin, and exhibited intermediate susceptibility to nalidixic acid. Sequence analysis of the 16S rRNA gene indicated that the bacterium was a novel member of the Helicobacter genus, most closely related to Helicobacter pametensis. We propose to name this bacterium Helicobacter cholecystus. In epidemiologic studies, isolation of H. cholecystus correlated strongly with the presence of cholangiofibrosis and centrilobular pancreatitis; however, further studies are needed to define the role of this bacterium in pathogenesis.     

Ganglioside vaccines with emphasis on GM2

OBJECTIVE: To investigate the impact of an educational intervention on knowledge and anxiety level of women scheduled for colposcopy after an abnormal Papanicolaou (Pap) test. DESIGN: Experimental, randomized controlled study. SETTING: An inner-city medical school. PARTICIPANTS: The final sample consisted of 58 women in the intervention group and 55 women in the control group. Exclusion criteria included any previous colposcopy. INTERVENTIONS: The women in the intervention group received in the mail, approximately 1 week before their appointment, a one-page handout about colposcopy. The control group received no mailed handout. After arriving for the visit, women were asked to participate in the study and then were interviewed. MAIN OUTCOME MEASURES: Knowledge of reason for visit and knowledge of colposcopy as measured by content analysis of interview; and anxiety as measured by the Spielberger State/Trait Anxiety Inventory. RESULTS: Women in the intervention group demonstrated significantly more knowledge about the reason for their visit and about colposcopy than did the other women. No significant difference in mean anxiety score was found between the groups. CONCLUSIONS: The intervention increased knowledge about colposcopy for this population. Because patient education is an essential nursing function, these results are encouraging. This intervention can be replicated by nurses in other settings. Further research is necessary to understand how nurses can best help women alleviate anxiety before colposcopy.     

Tissue-type plasminogen activator variants with domain duplications and rearrangements

The interactions between tPA domains that are important forcatalysis are poorly understood. We have probed the functionof interdomain interactions by generating tPA variants in whichdomains are duplicated or rearranged. The proteins were expressedin a transient mammalian expression system and tested in vitrofor their ability to activate plasminogen, induce fibrinolysisand bind to a forming fibrin clot. Duplication of the heavychain domains of tPA produced enzymatically active tPA variants,many of which demonstrated similar in vitro amidolytic and fibrinolyticactivity and similar fibrin affinity to the parent molecule.Zymographic analysis of the domain duplication tPA variantsshowed one major active species for each variant. Selectionof the residues duplicated and the interdomain spacing werefound to be critical considerations in the design of tPA variantswith duplicated domains. We also rearranged the domains of tPAsuch that kringle 1 replaced the second kringle domain and viceversa. An analysis of these variants indicates that the firstkringle domain can confer fibrin affinity to a tPA variant andfunction in place of kringle 2. Therefore, in wild-type tPA,the functions of kringle 1 and kringle 2 must be dependent partiallyon their orientation within the heavy chain of the protein.The functional autonomy of the heavy and light chains of tPAis demonstrated by the activity of a tPA variant in which theorder of the heavy and light chains was reversed.     

Evaluation of trend localization with multi-variate visualizations

Multi-valued data sets are increasingly common, with the number of dimensions growing. A number of multi-variate visualization techniques have been presented to display such data. However, evaluating the utility of such techniques for general data sets remains difficult. Thus most techniques are studied on only one data set. Another criticism that could be levied against previous evaluations of multi-variate visualizations is that the task doesn't require the presence of multiple variables. At the same time, the taxonomy of tasks that users may perform visually is extensive. We designed a task, trend localization, that required comparison of multiple data values in a multi-variate visualization. We then conducted a user study with this task, evaluating five multivariate visualization techniques from the literature (Brush Strokes, Data-Driven Spots, Oriented Slivers, Color Blending, Dimensional Stacking) and juxtaposed grayscale maps. We report the results and discuss the implications for both the techniques and the task.     

Multidimensional visual representations for underwater environmental uncertainty

We investigate how to represent the resulting multivariate information and multidimensional uncertainty by developing and applying candidate visual techniques. Although good techniques exist for visualizing many data types, less progress has been made on how to display uncertainty and multivariate information - this is especially true as the dimensionality rises. At this time, our primary focus is to develop the statistical characterizations for the environmental uncertainty (described only briefly in this article) and to develop a visual method for each characterization. The mariner community needs enhanced characterizations of environmental uncertainty now, but the accuracy of the characterizations is still not sufficient, and therefore formal user evaluations cannot take place at this point in development. We received feedback on the applicability of our techniques from domain experts. We used this in conjunction with previous results to compile a set of development guidelines.     

Regional difference in insulin inhibition of non-esterified fatty acid release from human adipocytes: relation to insulin receptor phosphorylation and intracellular signalling through the insulin receptor substrate-1 pathway

Increased mobilization of non-esterified fatty acids (NEFA) from visceral as opposed to peripheral fat depots can lead to metabolic disturbances because of the direct portal link between visceral fat and the liver. Compared with peripheral fat, visceral fat shows a decreased response to insulin. The mechanisms behind these site variations were investigated by comparing insulin action on NEFA metabolism with insulin receptor signal transduction through the insulin receptor substrate-1 (IRS-1) pathway in omental (visceral) and subcutaneous human fat obtained during elective surgery. Insulin inhibited lipolysis and stimulated NEFA re-esterification. This was counteracted by wortmannin, an inhibitor of phosphaditylinositol (PI) 3-kinase. The effects of insulin on antilipolysis and NEFA re-esterification were greatly reduced in omental fat cells. Insulin receptor binding capacity, mRNA and protein expression did not differ between the cell types. Insulin was four times more effective in stimulating tyrosine phosphorylation of the insulin receptor in subcutaneous fat cells (p < 0.001). Similarly, insulin was two to three times more effective in stimulating tyrosine phosphorylation of IRS-1 in subcutaneous fat cells (p < 0.01). This finding could be explained by finding that IRS-1 protein expression was reduced by 50 +/- 8% in omental fat cells (p < 0.01). In omental fat cells, maximum insulin-stimulated association of the p85 kDa subunit of PI 3-kinase to phosphotyrosine proteins and phosphotyrosine associated PI 3-kinase activity were both reduced by 50% (p < 0.05 or better). Thus, the ability of insulin to induce antilipolysis and stimulate NEFA re-esterification is reduced in visceral adipocytes. This reduction can be explained by reduced insulin receptor autophosphorylation and signal transduction through an IRS-1 associated PI 3-kinase pathway in visceral adipocytes.