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111.
Synthesis,Chiral Separation,Absolute Configuration Assignment,and Biological Activity of Enantiomers of Retro‐1 as Potent Inhibitors of Shiga Toxin 下载免费PDF全文
Dr. Hajer Abdelkafi Dr. Aurélien Michau Alexandra Clerget David‐Alexandre Buisson Dr. Ludger Johannes Prof. Daniel Gillet Dr. Julien Barbier Dr. Jean‐Christophe Cintrat 《ChemMedChem》2015,10(7):1153-1156
The Shiga toxin (Stx) family is composed of related protein toxins produced by the bacteria Shigella dysenteriae and certain pathogenic strains of E. coli. No effective therapies for Stx intoxication have been developed yet. However, inhibitors that act on the intracellular trafficking of these toxins may provide new options for the development of therapeutic strategies. This study reports the synthesis, chromatographic separation, and pharmacological evaluation of the two enantiomers of Retro‐1, a compound active against Stx and other such protein toxins. Retro‐1 works by inhibiting retrograde transport of these toxins inside cells. In vitro experiments proved that the configuration of the stereocenter at position 5 is not crucial for the activity of this compound. X‐ray diffraction data revealed (S)‐Retro‐1 to be slightly more active than (R)‐Retro‐1. 相似文献
112.
J. Baron E.M. Bulewicz S. Kandefer M. Pilawska W. ukowski A.N. Hayhurst 《Fuel》2006,85(17-18):2494-2508
Wastes burned in incinerators usually contain polymers, whose combustion can be associated with noxious emissions, unless the conditions are properly selected. This paper investigates how polymers burn in a fluidised bed; in fact, the combustion of a number of polymers, including several types of polyethylene, polystyrene and a polyamide, was studied in a laboratory-size, bubbling, fluidised bed, filled with quartz sand, with no external heating. Pellets of a polymer were mostly thrown into such a bed of sand, fluidised and maintained hot by a fuel-lean mixture of propane, methane or hydrogen in air, which burned soon after entering the bed. In addition, polymers were also used as the only fuel, i.e., added to a hot bed fluidised by only air. Visual observations of burning polymer pellets up to 240 mg were made, as well as video records obtained and the flue gas composition monitored, when the combustor was run at 800–1000 °C with 1.1–2.0 times more O2 than required for complete combustion. It is clear that a polymer burns as if its volatile content were 100%. The polymer pellet first melts at a rate controlled by heat transfer. However, the melt and the gaseous products of thermal decomposition are dispersed, albeit sometimes slowly, in a fluidised bed. Although the high U/Umf of above 10 caused some back-mixing of the gas leaving the bed and the combustion efficiency was high (assessed from O2 consumption and CO2 production), long streaks or plumes of fuel-rich gases (from each polymer pellet) did reach the freeboard, i.e., these plumes burned as transient diffusion flames at a rate controlled by mixing. By increasing the temperature and the residence times of gas in the bed and freeboard, the observed emissions of CO and hydrocarbons could be considerably reduced. The concentrations of NO were low, except when the polymer contained chemically-combined nitrogen, as in a polyamide. It is concluded that bubbling fluidised beds can be good for incinerating polymers, possibly together with other wastes. 相似文献
113.
Ali El Hafidi Bruno Martin Alexandre Loredo Eric Jego 《Mechanical Systems and Signal Processing》2010,24(7):2198-2209
This study is composed of three essential parts. The first part describes an indirect semi-experimental method which is used to reconstruct the excitation force of an operating diesel engine from the acceleration data measured at the mounting points. These internal forces can not be directly measured with force sensors; they have to be derived from the dynamic deformation of the engine support, so a theoretical analysis is carried out to derive the equations for the force re-construction.The second part deals with prevention of low frequency vibration of the powertrain from spreading to the rest of the vehicle. Three uncoupling techniques are used to minimize these vibrations. The first technique reduces the non-diagonal elements of stiffness matrix. The second technique uses the elastic axes decoupling criterion. The third technique uncouple the torque roll axis (TRA) by using the previously determined excitation efforts.In the third part, numerical and experimental results are discussed. The solicitations deducted and the positions of mounts allowing decoupling of the powertrain are presented. 相似文献
114.
Electrical contact resistance between stainless steel bipolar plate and carbon felt in PEFC: A comprehensive study 总被引:1,自引:0,他引:1
Johan André Laurent Antoni Jean-Pierre Petit Eric De Vito Alexandre Montani 《International Journal of Hydrogen Energy》2009
Bipolar plate represents a key component of Proton Exchange Membrane Fuel Cell (PEFC) with several essential functions, among them the electric connection of elementary cells. Usually made of graphite, this component is studied worldwide in order to develop a commercially viable alternative: different ways have been being investigated, and to date, despite corrosion issues, stainless steel (SS) appears as a good candidate material, but its Electrical Contact Resistance (ECR) can reach unacceptable values when exposed to PEFC environment. This paper offers a comprehensive study of the parameters acting on ECR when using uncoated SS in PEFC: roughness, which influences the surface contact area with carbon baking, bulk composition of the alloy, which influences only partly the nature of passive films, and the composition and structure of passive films, strongly modified by surface treatments and ageing conditions. 相似文献
115.
Alexandre Boucher 《Computers & Geosciences》2009,35(6):1151-1158
Using a complex training image (TI) for the single normal equation simulation (SNESIM) algorithm results in poor simulated realizations since that image contains trends and location specific patterns. By pooling all the TI patterns in a single search tree and not recording the relative locations of those patterns, some critical features of these complex TIs are lost.The search tree partitioning approach subdivides a large TI into imbricated, homogeneous, smaller images, called partition classes. Each of these partition classes has a corresponding search tree that can be utilized by the SNESIM algorithm. These partition classes are obtained by processing the TIs with spatial filters that are pattern sensitive. The resulting filter scores are then clustered into partition classes. All patterns within a partition class are recorded by a search tree; there is one tree per partition class. At each pixel along the simulation path, the partition class is retrieved first and used to select the appropriate search tree. That search tree contains the patterns relevant to that partition class.In practice, the partitioning approach adds flexibility in choosing a TI. TIs that were easier to obtain but traditionally too complex for simulation can now be considered as input to SNESIM. In many cases, it also significantly increases the simulation speed by searching a vector of smaller trees instead of a single large one. A plugin for the SGeMS software is provided. 相似文献
116.
The invasive green alga, Caulerpa taxifolia, that has spread rapidly after its introduction into the Mediterranean and the North American Pacific, reacts to wounding by transforming its major metabolite caulerpenyne (1). This wound-activated reaction involves the transformation of the bis-enol acetate moiety of 1, releasing reactive 1,4-dialdehydes. The ability to perform this transformation is found also in both the noninvasive Mediterranean C. prolifera and the invasive C. racemosa. Trapping experiments, as well as transformation of the model substrate geranyl acetate, suggest that all three investigated Caulerpa spp. rely on esterases that act upon wounding of the algae by subsequently removing the three acetate residues of caulerpenyne. The resulting reactive 1,4-dialdehyde oxytoxin 2 (9) can be identified by liquid chromatography–mass spectrometry and is unstable in the wounded tissue. Caulerpenyne transformation occurs rapidly, and severe tissue damage caused degradation of more than 50% of the stored caulerpenyne within 1 min in all three algae. Prevention of the enzymatic reaction before extraction, by shock freezing the tissue with liquid nitrogen, was used for the determination of the caulerpenyne content in intact algae. It gives about twofold higher values compared to an established methanol extraction protocol. The speed and mechanism of the wound-activated transformation, as well as the caulerpenyne content in intact tissue of invasive and noninvasive Caulerpa spp., are comparable. Thus, this enzymatic , transformation, despite being fast and efficient, is likely not the key for the success of the investigated invasive species. 相似文献
117.
Using the measures of initial reaction rate, a kinetic-photometric method is developed that uses the reaction of Diquat with H2O2 in basic medium. The reaction rate is very high and therefore the stopped-flow mixing technique is required in order to make kinetic measurements. The reaction rate is obtained in 20 s after the reactants are mixed and it allows the simple application of the method proposed to the routine analyses. The sensitivity of the method is very high being the detection limit 0.44 microgmL(-1) and the application range between 1 and 16 microgmL(-1). The time of measure per sample is 90s. The proposed kinetic-photometric method has been applied to the direct determination of this compound in river water, in the water of laundry of the olives, and in a commercial product. The results are very acceptable. 相似文献
118.
Alexandre Yakovlev Luciano Lavagno Alberto Sangiovanni-Vincentelli 《Formal Methods in System Design》1996,9(3):139-188
Characterization of the behavior of an asynchronous system depending on the delay of components and wires is a major task facing designers. Some of these delays are outside the designer's control, and in practice may have to be assumed unbounded. The existing literature offers a number of analysis and specification models, but lacks a unified framework to verify directly if the circuit specification admits a correct implementation under these hypotheses.Our aim is to fill exactly this gap, offering both low-level (analysis-oriented) and high-level (specification-oriented) models for asynchronous circuits and the environment where they operate, together with strong equivalence results between the properties at the two levels. One interesting side result is the precise characterization of classical static and dynamic hazards in terms of our model. Consequently the designer can check the specification and directly decide if the behavior of any implementation will depend, e.g., on the delays of the signals described by such specification.We also outline a design methodology based on our models, pointing out how they can be used to select appropriate high and low-level models depending on the desired characteristics of the system. 相似文献
119.
In Bacillus transformation, sexual isolation is known to be an exponential function of the sequence divergence between donor and recipient. Here, we have investigated the mechanism under which sequence divergence results in sexual isolation. We tested the effect of mismatch repair by comparing a wild-type strain and an isogenic mismatch-repair mutant for the relationship between sexual isolation and sequence divergence. Mismatch repair was shown to contribute to sexual isolation but was responsible for only a small fraction of the sexual isolation observed. Another possible mechanism of sexual isolation is that more divergent recipient and donor DNA strands have greater difficulty forming a heteroduplex because a region of perfect identity between donor and recipient is required for initiation of the heteroduplex. A mathematical model showed that this heteroduplex-resistance mechanism yields an exponential relationship between sexual isolation and sequence divergence. Moreover, this model yields an estimate of the size of the region of perfect identity that is comparable to independent estimates for Escherichia coli. For these reasons, and because all other mechanisms of sexual isolation may be ruled out, we conclude that resistance to heteroduplex formation is predominantly responsible for the exponential relationship between sexual isolation and sequence divergence in Bacillus transformation. 相似文献
120.
EE Mancilla F De Luca JA Uyeda FS Czerwiec J Baron 《Canadian Metallurgical Quarterly》1998,139(6):2900-2904
In vivo, fibroblast growth factor-2 (FGF-2) inhibits longitudinal bone growth. Similarly, activating FGF receptor 3 mutations impair growth in achondroplasia and thanatophoric dysplasia. To investigate the underlying mechanisms, we chose a fetal rat metatarsal organ culture system that would maintain growth plate histological architecture. Addition of FGF-2 to the serum-free medium inhibited longitudinal growth. We next assessed each major component of longitudinal growth: proliferation, cellular hypertrophy, and cartilage matrix synthesis. Surprisingly, FGF-2 stimulated proliferation, as assessed by [3H]thymidine incorporation. However, autoradiographic studies demonstrated that this increased proliferation occurred only in the perichondrium, whereas decreased labeling was seen in the proliferative and epiphyseal chondrocytes. FGF-2 also caused a marked decrease in the number of hypertrophic chondrocytes. To assess cartilage matrix synthesis, we measured 35SO4 incorporation into newly synthesized glycosaminoglycans. Low concentrations (10 ng/ml) of FGF-2 stimulated cartilage matrix production, but high concentrations (1000 ng/ml) inhibited matrix production. We conclude that FGF-2 inhibits longitudinal bone growth by three mechanisms: decreased growth plate chondrocyte proliferation, decreased cellular hypertrophy, and, at high concentrations, decreased cartilage matrix production. These effects may explain the impaired growth seen in patients with achondroplasia and related skeletal dysplasias. 相似文献