Synthesis of novel DC-SIGN ligands with an alpha-fucosylamide anchor

The dendritic cell-specific intercellular adhesion molecule (ICAM) 3-grabbing nonintegrin (DC-SIGN) is a C-type lectin that appears to perform several different functions. Besides mediating adhesion between dendritic cells and T lymphocytes, DC-SIGN recognizes several pathogens some of which, including HIV, appear to exploit it to invade host organisms. The intriguing diversity of the roles attributed to DC-SIGN and their therapeutic implications have stimulated the search for new ligands that could be used as biological probes and possibly as lead compounds for drug development. The natural ligands of DC-SIGN consist of mannose oligosaccharides or fucose-containing Lewis-type determinants. Using the known 3D structure of the Lewis-x trisaccharide, we have identified some monovalent alpha-fucosylamides that bind to DC-SIGN with inhibitory constants 0.4-0.5 mM, as determined by SPR, and have characterized their interaction with the protein by STD NMR spectroscopy. This work establishes for the first time alpha-fucosylamides as functional mimics of chemically and enzymatically unstable alpha-fucosides and describes interesting candidates for the preparation of multivalent systems able to block the receptor DC-SIGN with high affinity and with potential biomedical applications.     

Monitoring biodegradation of ethene and bioremediation of chlorinated ethenes at a contaminated site using compound-specific isotope analysis (CSIA)

Chlorinated ethenes are commonly found in contaminated groundwater. Remediation strategies focus on transformation processes that will ultimately lead to nontoxic products. A major concern with these strategies is the possibility of incomplete dechlorination and accumulation of toxic daughter products (cis-1,2-dichloroethene (cDCE), vinyl chloride (VC)). Ethene mass balance can be used as a direct indicator to assess the effectiveness of dechlorination. However, the microbial processes that affect ethene are not well characterized and poor mass balance may reflect biotransformation of ethene rather than incomplete dechlorination. Microbial degradation of ethene is commonly observed in aerobic systems but fewer cases have been reported in anaerobic systems. Limited information is available on the isotope enrichment factors associated with these processes. Using compound-specific isotope analysis (CSIA) we determined the enrichment factors associated with microbial degradation of ethene in anaerobic microcosms (ε = -6.7‰ ± 0.4‰, and -4.0‰ ± 0.8‰) from cultures collected from the Twin Lakes wetland area at the Savannah River site in Georgia (United States), and in aerobic microcosms (ε = -3.0‰ ± 0.3‰) from Mycobacterium sp. strain JS60. Under anaerobic and aerobic conditions, CSIA can be used to determine whether biotransformation of ethene is occurring in addition to biodegradation of the chlorinated ethenes. Using δ(13)C values determined for ethene and for chlorinated ethenes at a contaminated field site undergoing bioremediation, this study demonstrates how CSIA of ethene can be used to reduce uncertainty and risk at a site by distinguishing between actual mass balance deficits during reductive dechlorination and apparent lack of mass balance that is related to biotransformation of ethene.     

EFFECT OF A PROPELLER AND GAS DIFFUSION ON BUBBLE NUCLEI DISTRIBUTION IN A LIQUID

A multi-bubble dynamics code accounting for gas diffusion in the liquid and through the bubble wall was developed and used to study the modification of a bubble nuclei population dynamics by a propeller.The propeller flow field was obtained using a Reynolds-Averaged Navier-Stokes(RANS) solver and bubble nuclei populations were propagated in this field.The numerical pro-cedure enabled establishment of the possibility of production behind the propeller of relatively large visible bubbles starting from typical ocean nuclei size distributions.The resulting larger bubbles are seen to cluster in the blade wakes and tip vortices.Parametric investigations of the initial nuclei size distribution,the dissolved gas concentration,and the cavitation number were conducted to ide-ntify their effects on bubble entrainment and the resultant void fractions and bubble distribution modifications downstream from the propeller.Imposed synthetic turbulence-like fluctuations unto the average RANS flow field were also used to study the effect avera-ging in the RANS procedure has on the results.     

Salmeterol compared with slow-release terbutaline in nocturnal asthma. A multicenter, randomized, double-blind, double-dummy, sequential clinical trial. French Multicenter Study Group

The aim of the multicenter, randomized, double-blind, double-dummy, parallel-group clinical trial with a 2-week treatment period was to compare the efficacy and safety of salmeterol (50 micrograms twice daily) with slow-release (SR) terbutaline (5 mg orally, twice daily) in nocturnal asthma. A total of 159 asthmatic adults (FEV, 50-90% of predicted value; sex ratio: 0.87) with at least two nocturnal awakenings during a 7-d run-in period was included in the study. Patients were centrally randomized with a national computer network (Minitel). The main variable (number of awakening-free nights during the last week of treatment) was analyzed according to a sequential method with the one-sided triangular test. The number of awakening-free nights (+/- SD) was significantly higher in the salmeterol group: 5.3 +/- 2.4 vs 4.6 +/- 2.3 (P = 0.006). Salmeterol was significantly more effective than SR-terbutaline in the following factors: number of patients without any awakening during the last week of treatment (50% vs 27%, P = 0.003), mean morning PEF (351 +/- 109 l/min-1 vs 332 +/- 105 l/min-1, P = 0.04), PEF diurnal variation 6 +/- 10% vs 11 +/- 12%, P = 0.01), overall assessment of efficacy by the patient and the investigator (P = 0.001 and 0.005, respectively), and daily rescue salbutamol intakes (P = 0.004). In the salmeterol group, significantly fewer patients reported adverse events (16% vs 29%, P = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)     

Electrochemical oxidation of hydrophobic compounds in aqueous micellar solutions and oil-in-water emulsions

The electrochemical oxidation of ferrocene (Fc) and tetrathiofulvalene (TTF) has been investigated in micelles and dodecane-in-water emulsions in order to compare the diffusional process involved in these systems. It is found that the diffusion coefficients of Fc and TTF, determined from the observed limiting currents at the rotating disc electrode, are governed by the solubilization equilibrium of the neutral substrates which are predominantly solubilized in the micelle or oil-droplet phase. In the emulsion, the cyclic voltammograms show that the current is controlled also by the rate constants of the substrate partition, which depend on the size of the emulsion droplets. The determination of the diffusion coefficients of Fc⁺ and TTF⁺, produced in situ by controlled potential electrolysis, showed that, except in SDS micellar solutions, the monocation radicals are solubilized mainly in the aqueous phase. As a result, the diffusion coefficients of the species involved in the redox system are different. In the case of TTF, the above results have a great influence upon the second oxidation step TTF⁺ → TTF²⁺. Indeed, the homogeneous solution reaction between TTF and the electrogenerated dication TTF²⁺ leads to the monocation TTF⁺ which diffuses more rapidly than its parent molecule TTF. The ratios of the two waves in cyclic and rotating disc electrode voltammetry show that the enhancement of the second wave depends mainly on the difference between the diffusion coefficients of TTF and TTF⁺ and that the nature of the solution or the size of the disperse phase has little influence upon the reaction rate of the homogeneous solution reaction.     

Hydrogen isotopic enrichment: an indicator of biodegradation at a petroleum hydrocarbon contaminated field site

Compound-specific carbon and hydrogen isotope analysis was used to investigate biodegradation of benzene and ethylbenzene in contaminated groundwater at Dow Benelux BV industrial site. delta13C values for dissolved benzene and ethylbenzene in downgradient samples were enriched by up to 2+/-0.5 per thousand, in 13C, compared to the delta13C value of the source area samples. delta2H values for dissolved benzene and ethylbenzene in downgradient samples exhibited larger isotopic enrichments of up to 27+/-5 per thousand for benzene and up to 50+/-5 per thousand for ethylbenzene relative to the source area. The observed carbon and hydrogen isotopic fractionation in downgradient samples provides evidence of biodegradation of both benzene and ethylbenzene within the study area at Dow Benelux BV. The estimated extents of biodegradation of benzene derived from carbon and hydrogen isotopic compositions for each sample are in agreement, supporting the conclusion that biodegradation is the primary control on the observed differences in carbon and hydrogen isotope values. Combined carbon and hydrogen isotope analyses provides the ability to compare biodegradation in the field based on two different parameters, and hence provides a stronger basis for assessment of biodegradation of petroleum hydrocarbon contaminants.     

Nanofiltration for the recovery of caustic cleaning-in-place solutions: robustness towards large variations of composition

In the dairy industry re-use and multi-use cleaning-in-place (CIP) systems are operated by circulating chemicals and water without taking the equipment apart. The solutions, which become polluted due to the removal of fouling compounds, are drained periodically when they are considered to be too polluted. This work shows the large variations in composition (pollution, surface tension, etc) of the industrial caustic solutions coming from milk standardization and pasteurization plant CIP throughout their life time (7 days) and from 1 week to another. The work is also intended to show how nanofiltration (1 kg mol(-1) molecular weight cut-off) was robust and performed well, with good recovery of caustic solutions, even when faced with large variations of solutions composition: high caustic yield, permeation flux (J) in the range 42-110 l h(-1) m(-2), average chemical oxygen demand (COD) reduction equal to 0.58 and low surface tension change. Equations have been established for the prediction of J as a function of initial membrane hydraulic resistance (Rm) caustic concentration, volume reduction ratio (VRR) and initial soluble COD. When VRR increased, both J and pollution retention decreased despite the increase in irreversible fouling induced by the increase of soluble pollution concentration in retentate. The higher the initial soluble COD, the sharper the decrease in J vs. VRR. Since irreversible fouling was usually small (0.1-3.4 x 10(13) m(-1), that is to say of the same order of magnitude as Rm), the membrane cleaning could be efficiently performed by using single phase sodium hypochlorite alternately with a more expensive acid-base cleaning sequence. The obtained permeate was a clear regenerated cleaning solution with low soluble COD (0.2-3.5 g/l) and surface tension (56-30 mJ m(-2)) which could be successfully exploited owing to its cleaning potential.     

A parametric investigation on seat/occupant contact forces and their relationship with initially perceived discomfort using a configurable seat

The present work investigates the contact forces between sitters and seat as well as their correlations with perceived discomfort. Twelve different economy class aeroplane seat configurations were simulated using a multi-adjustable experimental seat by varying seat pan and backrest angles, as well as seat pan compressed surface. Eighteen males and 18 females, selected by their body mass index and stature, tested these configurations for two sitting postures. Perceived discomfort was significantly affected by seat parameters and posture and correlated both with normal force distribution on the seat-pan surface and with normal forces at the lumbar and head supports. Lower discomfort ratings were obtained for more evenly distributed normal forces on the seat pan. Shear force at the seat pan surface was at its lowest when sitters were allowed to self-select their seat-pan angle, supporting that a shear force should be reduced but not zeroed to improve seating comfort.

Practitioner Summary: The effects of seat-pan and backrest angle, anthropometric dimensions and sitting posture on contact forces and perceived discomfort were investigated using a multi-adjustable experimental seat. In addition to preferred seat profile parameters, the present work provides quantitative guidelines on contact force requirement for improving seating comfort.     

Values of the mass transfer coefficient of the linear driving force model for VOC adsorption on activated carbons

Modelling of activated carbon cartridges is essential in personal protective equipments against toxic gases in order to know the duration of protection. The linear driving force model seems to be more adapted than the actual Wheeler–Jonas model because it has more physical significance. The difficulty is that the mass transfer coefficient can not be calculated a priori. Values of the LDF mass transfer coefficient are disseminated in the literature and thus there is no overview of the range and variations with different adsorbents, adsorbates and concentrations. The object of this paper is thus twofold: obtaining values of the mass transfer coefficient at different concentrations and adsorbates in order to have a comprehensive view of variations and appreciating the validity of the LDF constant pattern model.     

Distinctive arsenic(V) trapping modes by magnetite nanoparticles induced by different sorption processes

Arsenic sorption onto iron oxide spinels such as magnetite may contribute to arsenic immobilization at redox fronts in soils, sediments, and aquifers, as well as in putative remediation and water treatment technologies. We have investigated As(V) speciation resulting from different sorption processes on magnetite nanoparticles, including both adsorption and precipitation, using X-ray absorption fine structure (XAFS) spectroscopy and transmission electron microscopy (TEM). XAFS results suggest that AsO(4) tetrahedra form predominantly inner-sphere bidentate corner-sharing ((2)C) complexes and outer-sphere complexes on magnetite in the adsorption experiments. In the precipitation experiments, an increasing fraction of AsO(4) tetrahedra appears to be incorporated in clusters having a magnetite-like local structure with increasing As loading, the remaining fraction of As being adsorbed at the surface of magnetite particles. In the sample with the highest As loading (15.7 μmol/m(2)) XAFS data indicate that As(V) is fully incorporated in such clusters. Such processes help to explain the significantly higher arsenic uptake in precipitation samples compared to those generated in adsorption experiments. In addition, for the precipitation samples, TEM observations indicate the formation of amorphous coatings and small (~3 nm) nanoparticles associated with larger (~20-40 nm) magnetite nanoparticles, which are absent in the adsorption samples. These results suggest that As(V) could form complexes at the surfaces of the small nanoparticles and could be progressively incorporated in their structure with increasing As loading. These results provide some of the fundamental knowledge about As(V)-magnetite interactions that is essential for developing effective water treatment technologies for arsenic.