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91.
    
Protein toxins constitute the main virulence factors of several species of bacteria and have proven to be attractive targets for drug development. Lead candidates that target bacterial toxins range from small molecules to polymeric binders, and act at each of the multiple steps in the process of toxin-mediated pathogenicity. Despite recent and significant advances in the field, a rationally designed drug that targets toxins has yet to reach the market. This Review presents the state of the art in bacterial toxin targeted drug development with a critical consideration of achieved breakthroughs and withstanding challenges. The discussion focuses on A-B-type protein toxins secreted by four species of bacteria, namely Clostridium difficile (toxins A and B), Vibrio cholerae (cholera toxin), enterohemorrhagic Escherichia coli (Shiga toxin), and Bacillus anthracis (anthrax toxin), which are the causative agents of diseases for which treatments need to be improved.  相似文献   
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Highly ordered arrays of single living bacteria were obtained by selective adsorption of bacteria onto chemical patterns with micrometric resolution. The chemically engineered template surfaces were prepared with the combination of microcontact printing process and a simple incubation technique. This methodology can be used for fundamental studies of bacterium's inner mechanisms and sub-cellular organization as well as for interfacing living bacteria with artificial microsystems.  相似文献   
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Modern organometallic methods enable the regioflexible conversion of simple heterocyclic starting materials into families of isomers and congeners. Depending on the choice of the reagent, 1-methyl-5-(trifluoromethyl)pyrazole ( 1 ) undergoes deprotonation and subsequent carboxylation mainly or exclusively at either the 4-position of the heterocycle or at the nitrogen-attached methyl group. Similarly, 1-phenyl-5-(trifluoromethyl)pyrazole ( 5 ) and 3-methyl-1-phenyl-5-(trifluoromethyl)pyrazole ( 8 ) are selectively attacked by lithium diisopropylamide at the heterocyclic 4-position and by butyllithium concomitantly at the 4-position and the ortho position of the phenyl ring. In contrast, metalation of 1-methyl-3-(trifluoromethyl)pyrazole ( 2 ) occurs only at the 5-position, whatever the organometallic or metal amide base. Further sites become accessible to functionalization if bromine is introduced into the heterocyclic or aromatic ring. This has been demonstrated with 4-bromo-1-methyl-5-(trifluoromethyl)pyrazole ( 3 ), 4-bromo-1-methyl-3-(trifluoromethyl)pyrazole ( 4 ), 4-bromo-1-methyl-5-(trifluoromethyl)pyrazole ( 7 ) and 1-(2-bromophenyl)-5-(trifluoromethyl)pyrazole ( 6 ). (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)  相似文献   
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Fission-fragment mass and kinetic energy distributions and their correlations have been measured for 232U and 233U. The results on these uranium isotopes and 235U are compared. The mass peak/valley ratio of 785 ± 68 for 232U is the highest of the three isotopes. The 〈EK〉(μH) distributions show significant differences. The dip ΔEK at symmetry is 16.2 ± 1.0 MeV (232U), 17.0 ± 1.0 MeV (233U) and 20.6 ± 1.1 MeV (235U). In the yields for high-kinetic-energy-selected events, the mass 134 dominates for 233U and 235U, but for 232U it is μH≈144, which dominates. This complete reversal of profiles can be understood in terms of fragment shells.  相似文献   
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Fragment-mass and kinetic-energy distribution measurements for 252Cf(sf) have been extended to the far-out asymmetric low-yield fission region of MH = 190 compared with the existing data that go up to MH ≈ 168. The mass yield Y(m) shows a shoulder for MH ≈ 163 and an important enhancement for MH ? 176. The 〈EK〉(m), σEK(m) and, to a lesser extent, Y(m) distributions show strong and correlated amplitude fluctuations for MH ? 170. These data indicate strong and rapid changes in deformation of the nascent fragments and the coexistence of more than one deformed-shell stabilized scission configuration for the same mass splits. These structures and those present in the relatively high-yield regions are discussed in terms of the static macro-microscopic potential-energy calculations.  相似文献   
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The dynamic behavior of water within two types of ionomer membranes, Nafion and sulfonated polyimide, has been investigated by field-cycling nuclear magnetic relaxation. This technique, applied to materials prepared at different hydration levels, allows the proton motion on a time scale of microseconds to be probed. The NMR longitudinal relaxation rate R(1) measured over three decades of Larmor angular frequencies omega is particularly sensitive to the host-water interactions and thus well-suited to study fluid dynamics in restricted geometries. In the polyimide membranes, we have observed a strong dispersion of R(1)(omega) following closely a 1/square root omega law in a low-frequency range (correlation times from 0.1 to 10 micros). This is indicative of a strong interaction of water with "interfacial" hydrophilic groups of the polymeric matrix (wetting situation). Variations of the relaxation rates with water uptake reveal a two-step hydration process: solvation and formation of disconnected aqueous clusters near polar groups, followed by the formation of a continuous hydrogen bond network. On the contrary, in the Nafion we observed weak variations of R(1)(omega) at low frequencies. This is typical of a nonwetting behavior. At early hydration stages, R(1)(omega) evolves logarithmically, suggesting a confined bidimensional diffusion of protons in the microsecond time range. Such an evolution is lost at higher swelling where a plateau related to three-dimensional diffusion is observed.  相似文献   
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