Investigation of Antigen-Antibody Interactions of Sulfonamides with a Monoclonal Antibody in a Fluorescence Polarization Immunoassay Using 3D-QSAR Models

A three-dimensional quantitative structure-activity relationship (3D-QSAR) model of sulfonamide analogs binding a monoclonal antibody (MAb(SMR)) produced against sulfamerazine was carried out by Distance Comparison (DISCOtech), comparative molecular field analysis (CoMFA), and comparative molecular similarity indices analysis (CoMSIA). The affinities of the MAb(SMR), expressed as Log(10)IC(50), for 17 sulfonamide analogs were determined by competitive fluorescence polarization immunoassay (FPIA). The results demonstrated that the proposed pharmacophore model containing two hydrogen-bond acceptors, two hydrogen-bond donors and two hydrophobic centers characterized the structural features of the sulfonamides necessary for MAb(SMR) binding. Removal of two outliers from the initial set of 17 sulfonamide analogs improved the predictability of the models. The 3D-QSAR models of 15 sulfonamides based on CoMFA and CoMSIA resulted in q(2) (cv) values of 0.600 and 0.523, and r(2) values of 0.995 and 0.994, respectively, which indicates that both methods have significant predictive capability. Connolly surface analysis, which mainly focused on steric force fields, was performed to complement the results from CoMFA and CoMSIA. This novel study combining FPIA with pharmacophore modeling demonstrates that multidisciplinary research is useful for investigating antigen-antibody interactions and also may provide information required for the design of new haptens.     

The Production of Conjugated α-Linolenic, γ-Linolenic and Stearidonic Acids by Strains of Bifidobacteria and Propionibacteria

Conjugated fatty acids are regularly found in nature and have a history of biogenic activity in animals and humans. A number of these conjugated fatty acids are microbially produced and have been associated with potent anti-carcinogenic, anti-adipogenic, anti-atherosclerotic and anti-diabetogenic activities. Therefore, the identification of novel conjugated fatty acids is highly desirable. In this study, strains of bifidobacteria and propionibacteria previously shown by us and others to display linoleic acid isomerase activity were assessed for their ability to conjugate a range of other unsaturated fatty acids during fermentation. Only four, linoleic, α-linolenic, γ-linolenic and stearidonic acids, were converted to their respective conjugated isomers, conjugated linoleic acid (CLA), conjugated α-linolenic acid (CLNA), conjugated γ-linolenic acid (CGLA) and conjugated stearidonic acid (CSA), each of which contained a conjugated double bond at the 9,11 position. Of the strains assayed, Bifidobacterium breve DPC6330 proved the most effective conjugated fatty acid producer, bio-converting 70% of the linoleic acid to CLA, 90% of the α-linolenic acid to CLNA, 17% of the γ-linolenic acid to CGLA, and 28% of the stearidonic acid to CSA at a substrate concentration of 0.3 mg mL⁻¹. In conclusion, strains of bifidobacteria and propionibacteria can bio-convert linoleic, α-linolenic, γ-linolenic and stearidonic acids to their conjugated isomers via the activity of the enzyme linoleic acid isomerase. These conjugated fatty acids may offer the combined health promoting properties of conjugated fatty acids such as CLA and CLNA, along with those of the unsaturated fatty acids from which they are formed.     

Design, simulation, and testing of a novel hydraulic power take-off system for the Pelamis wave energy converter

The economic viability of a wave energy converter depends largely on its power take-off system. Active control of the power take-off is necessary to maximise power capture across a range of sea-states and can also improve survivability. The high force, low speed regime of wave energy conversion makes it a suitable application for high-pressure hydraulics.This paper describes the hydraulic power take-off system employed in the Pelamis wave energy converter. The process of the system's development is presented, including simulation and laboratory tests at 1/7th and fullscale. Results of efficiency measurements are also presented.     

In situ chemical reduction of Cr(VI) in groundwater using a combination of ferrous sulfate and sodium dithionite: a field investigation

A field study was conducted to evaluate the performance of a ferrous iron based in situ redox zone for the treatment of a dissolved phase Cr(VI) plume at a former industrial site. The ferrous iron based in situ redox zone was created by injecting a blend of 0.2 M ferrous sulfate and 0.2 M sodium dithionite into the path of a dissolved Cr(VI) plume within a shallow medium to fine sand unconfined aquifer formation. Monitoring data collected over a period of 1020 days after more than 100 m of linear groundwater flow through the treatment zone indicated sustained treatment of dissolved phase Cr(VI) from initial concentrations between 4 and 8 mg/L to less than 0.015 mg/L. Sustained treatment is assumed to be primarily due to the reduction of Cr(VI) to Cr(III) by ferrous iron adsorbed to, precipitated on, and/or incorporated into aquifer iron (hydr)oxide solid surfaces within the treatment zone. Precipitated phases likely include FeCO3 and FeS based on saturation index considerations and SEM/EDS analysis. The detection of solid phase sulfites and thiosulfates in aquifer sediments collected from the treatment zone more than 2 years following injection suggests dithionite decomposition products may also play a significant role in the long-term treatment of the dissolved phase Cr(VI).     

Staling in Starch Bread: the Effect of Gluten Additions on Specific Loaf Volume and Firming Rate

Hypotheses on the role of gluten in bread staling range from gluten having an anti-firming effect, or no effect on firming, to gluten-starch interactions being essential for bread firming. To test these hypotheses, the firming rate of starch bread made from protein-free synthetic flour was compared with that of starch-gluten breads made from synthetic flours containing 1–15% gluten (Fig. 1). Only loaves of similar specific loaf volume and crumb moisture content were compared to eliminate these parameters as variables that might influence firming rate. The starch breads clearly increased in firmness up to six days, indicating that gluten was not essential to the firming process, starch alone causing bread to firm with time. The starch-10% gluten breads and starch-15% gluten breads had very similar specific loaf volumes, moisture contents and firming rates to that of the starch breads. This indicates that protein possibly has some role in firming, because if only starch has a role in firming then adding gluten would effectively dilute the starch and reduce the rate of firming. We propose that increasing bread firmness results from glucan chains of partially leached amylose and amylo-pectin attached to swollen starch granules forming hydrogen bonds with other starch granules and, to a smaller extent, with gluten fibrils.     

Advance directives: the price of life

Advance directives support the concepts of patient autonomy and resource allocation. Promotion of advance directives by nurse managers according to the suggested paradigm should be an economic and policy priority.     

High-performance liquid chromatography of amino acids, peptides and proteins. CXXXIX. Impact of operating parameters in large-scale chromatography of proteins

Large-scale chromatography has been playing an important role in downstream treatment processing in biotechnology. In order to improve the productivity, the throughput of the chromatographic equipment was often increased by increasing the flow-rate and/or by increasing the column sample loading. This paper reports the results of a study on the impact of these and other operating parameters in affinity and ion-exchange chromatographic columns when used for protein purification. A sectional model was developed to predict protein adsorption processes in a packed column. The formulations of this mathematical model are presented in the Appendix. The present study was carried out with computer simulation based on this model and using data obtained from laboratory-scale columns. This model can simulate both the adsorption and washing stages of the protein purification process for both porous and non-porous particles. The effects of changing operating parameters were simulated and contour plots were generated for the easy identification of these effects. It was shown that both flow-rate and column loading can have a considerable impact on the processing rate and the yield of the column. As for the column capacity utilization, the impact of changing flow-rate is not significant at column loading of less than 80% in the test case. It was suggest that the present investigation provides a systematic predictive strategy which will greatly reduce the need for expensive, labour-intensive and time-consuming experimental work during process scale-up.     

Origins of comorbidity between conduct and affective disorders

OBJECTIVE: This analysis used methods of structural equation modeling to assess the extent to which comorbidity between conduct and affective disorders could be explained by (1) common or correlated causal factors that influenced both outcomes or (2) reciprocal causation between these conditions. METHOD: Data were obtained during the course of a 16-year longitudinal study of a birth cohort of New Zealand children. The data analyzed comprised measures of conduct and affective disorders at ages 15 and 16 years and data on a series of antecedent childhood factors. RESULTS: Structural equation modeling suggested that a substantial component of the comorbidity between conduct and affective disorders arose because the risk factors associated with the development of conduct disorders in teenagers overlapped and were correlated with the risk factors for adolescent affective disorders; of the shared variance between conduct disorder and affective disorders, more than two thirds was explained by common risk factors. These conclusions were replicated using diagnostically scored measures and methods of categorical data analysis. Model extensions suggested an absence of direct causal pathways between conduct and affective disorders. CONCLUSIONS: A substantial amount of the correlation and comorbidity between conduct and affective disorders arises because the risk factors and life pathways that predispose adolescents to one outcome are also associated with the risk factors and life pathways that predispose adolescents to the other outcome. Nonetheless, even after control for common causal factors, there was evidence of some unexplained comorbidity between conduct and affective disorders.     

Clinical perspectives on seabather's eruption, also known as 'sea lice'

Seabather's eruption is usually a benign clinical syndrome that resolves spontaneously, although severe symptoms and long-term sequelae have been identified. Recent research has implicated the larvae of a jellyfish, Linuche unguiculata, as the cause of this syndrome; confirmation by serological and experimental studies is pending. Clinical signs and symptoms are consistent with this etiology. Outbreaks occur when jellyfish larvae are transported to shore by ocean currents. Treatment is symptomatic and involves use of antihistamines and steroids.     

Productive and persistent infection of human thymic epithelial cells in vitro with HIV-1

Clostridium sporogenes was isolated from rabbits with antibiotic-associated hemorrhagic diarrhea, then its hemorrhagic toxin was purified from the supernatant by means of hydrophobic interaction chromatography, hydroxyapatite chromatography, and gel filtration. The purified toxin's hemorrhagic activity was completely inhibited by EDTA, but not by PMSF or ovomucoid; and fully restored by the addition of such divalent cations as Zn2+, Ca2+ and Mg2+. The purified toxin did not hydrolyze azocasein, or type I or II collagens. But the purified toxin did hydrolyze type III and IV collagens, and also gelatins prepared from type I, II, III and IV collagens. It appears, therefore that C. sporogenes's toxin is a collagenase that hydrolyzes type III and IV collagens, which are major constituents of the tunica intima and media of blood vessels. And that fact suggests that hemorrhage caused by the toxin depend on its collagenase activity.