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The trypanosome alternative oxidase (TAO), a mitochondrial enzyme involved in the respiration of the bloodstream form trypomastigotes of Trypanosoma brucei, is a validated drug target against African trypanosomes. Earlier series of TAO inhibitors having a 2,4-dihydroxy-6-methylbenzoic acid scaffold ("head") and a triphenylphosphonium or quinolin-1-ium cation as a mitochondrion-targeting group ("tail") were shown to be nanomolar inhibitors in enzymatic and cellular assays. We investigated here the effect of different mitochondrion-targeting cations and other scaffold modifications on the in vitro activity of this class of inhibitors. Low micromolar range activities were obtained, and the structure-activity relationship studies showed that modulation of the tail region with polar substituents is generally detrimental to the enzymatic and cellular activity of TAO inhibitors.

We investigated a chemical strategy to boost the trypanocidal activity of 2,4-dihydroxybenzoic acid (2,4-DHBA)- and salicylhydroxamic acid (SHAM)-based trypanocides with triphenylphosphonium and quinolinium lipophilic cations (LC). Three series of LC conjugates were synthesized that were active in the submicromolar (5a-d and 10d-f) to low nanomolar (6a-f) range against wild-type and multidrug resistant strains of African trypanosomes (Trypanosoma brucei brucei and T. congolense). This represented an improvement in trypanocidal potency of at least 200-fold, and up to >10 000-fold, compared with that of non-LC-coupled parent compounds 2,4-DHBA and SHAM. Selectivity over human cells was >500 and reached >23 000 for 6e. Mechanistic studies showed that 6e did not inhibit the cell cycle but affected parasite respiration in a dose-dependent manner. Inhibition of trypanosome alternative oxidase and the mitochondrial membrane potential was also studied for selected compounds. We conclude that effective mitochondrial targeting greatly potentiated the activity of these series of compounds.

The detailed understanding of the antineutrino emission from research reactors is mandatory for any high sensitivity experiments either for fundamental or applied neutrino physics, as well as a good control of the gamma and neutron backgrounds induced by the reactor operation. In this article, the antineutrino emission associated to a thermal research reactor: the OSIRIS reactor located in Saclay, France, is computed in a first part. The calculation is performed with the summation method, which sums all the contributions of the beta decay branches of the fission products, coupled for the first time with a complete core model of the OSIRIS reactor core. The MCNP Utility for Reactor Evolution code was used, allowing to take into account the contributions of all beta decayers in-core. This calculation is representative of the isotopic contributions to the antineutrino flux which can be found at research reactors with a standard 19.75\% enrichment in $^{235}$U. In addition, the required off-equilibrium corrections to be applied to converted antineutrino energy spectra of uranium and plutonium isotopes are provided. In a second part, the gamma energy spectrum emitted at the core level is provided and could be used as an input in the simulation of any reactor antineutrino detector installed at such research facilities. Furthermore, a simulation of the core surrounded by the pool and the concrete shielding of the reactor has been developed in order to propagate the emitted gamma rays and neutrons from the core. The origin of these gamma rays and neutrons is discussed and the associated energy spectrum of the photons transported after the concrete walls is displayed., Comment: 14 pages, 11 figures, Data in Appendix A and B (13 pages)

The antineutrino spectra measured in recent experiments at reactors are inconsistent with calculations based on the conversion of integral beta spectra recorded at the ILL reactor. $^{92}$Rb makes the dominant contribution to the reactor spectrum in the 5-8 MeV range but its decay properties are in question. We have studied $^{92}$Rb decay with total absorption spectroscopy. Previously unobserved beta feeding was seen in the 4.5-5.5 region and the GS to GS feeding was found to be 87.5(25)%. The impact on the reactor antineutrino spectra calculated with the summation method is shown and discussed., Comment: 6 pages, 3 figures

The antineutrino spectra measured in recent experiments at reactors are inconsistent with calculations based on the conversion of integral beta spectra recorded at the ILL reactor. $^{92}$Rb makes the dominant contribution to the reactor spectrum in the 5-8 MeV range but its decay properties are in question. We have studied $^{92}$Rb decay with total absorption spectroscopy. Previously unobserved beta feeding was seen in the 4.5-5.5 region and the GS to GS feeding was found to be 87.5(25)%. The impact on the reactor antineutrino spectra calculated with the summation method is shown and discussed., Comment: 6 pages, 3 figures

The modeling test was successful in finding out the mechanism causing the sediment resuspension in the vicinity of the cutter head and confirming the effect of preventing the sediment resuspension by a cutter cover. However, many problems still exist that have to be solved before the cutter cover can be used practically. Further studies are needed on the structure of the cutter cover, operation of dredge, etc., from various angles so that a test can be conducted on an actual dredge in the future., This article is from 'Management of Bottom Sediments Containing Toxic Substances, Proceedings of the U.S./Japan Experts Meeting (8th) Held at Tokyo, Japan on 8-10 November 1982,' AD-A149 291, p434-441.

Discontinuities in the rock are assumed to be represented by elliptic-plate-cracks. Two crack cases are analysed, one is open crack, and the other is closed crack. The effective elastic moduli of material with random oriented cracks are analysed by using the self consistent method., Discontinuities in the rock are assumed to be represented by elliptic-plate-cracks. Two crack cases are analysed, one is open crack, and the other is closed crack. The effective elastic moduli of material with random oriented cracks are analysed by using the self consistent method.

A stress/strain relationship of the elastic body which contains many cracks is theoretically analysed in consideration of the mechanical interaction of cracks. The equivalent volume defect (EVD) is determined by the length and the orientation of each crack, and the effective elastic compliance of the body is expressed as a function of the EVD and the intrinsic elastic moduli of the body. A numerical procedure for finite element analysis based on EVD is also presented., A stress/strain relationship of the elastic body which contains many cracks is theoretically analysed in consideration of the mechanical interaction of cracks. The equivalent volume defect (EVD) is determined by the length and the orientation of each crack, and the effective elastic compliance of the body is expressed as a function of the EVD and the intrinsic elastic moduli of the body. A numerical procedure for finite element analysis based on EVD is also presented.

The deformation of an elastic body which contains a single closed crack is analysed in consideration of frictional sliding on the crack surface. The equivalent volume defect for a closed crack is expressed as a function of the crack length, the crack orientation, the frictional coefficient on the crack surface and the applied stress. The method gives a good approximation for deformability of the materials which contain closed, open, or open and closed cracks., The deformation of an elastic body which contains a single closed crack is analysed in consideration of frictional sliding on the crack surface. The equivalent volume defect for a closed crack is expressed as a function of the crack length, the crack orientation, the frictional coefficient on the crack surface and the applied stress. The method gives a good approximation for deformability of the materials which contain closed, open, or open and closed cracks.

The improvement of the accuracy of DDM analysis on the crack problem and the applicability of DDM to the stress analysis of the jointed rock are discussed., The improvement of the accuracy of DDM analysis on the crack problem and the applicability of DDM to the stress analysis of the jointed rock are discussed.

Four kinds of granite specimens with different crack concentrations were employed in experiments. Modal analysis, hydrostatic compression test, and observation of cracks on the polished surface of specimens were carried out. By analysing these results, the crack density and the intrinsic elastic moduli of the specimen were evaluated and the theoretical values of effective elastic moduli were calculated in two cases. The tangential elastic moduli of the specimen were measured as a function of the applied stress by unaxial compression test. The maximum and minimum values of elastic moduli obtained experimentally were compared with the theoretical values. Reasonable agreement was obtained., Four kinds of granite specimens with different crack concentrations were employed in experiments. Modal analysis, hydrostatic compression test, and observation of cracks on the polished surface of specimens were carried out. By analysing these results, the crack density and the intrinsic elastic moduli of the specimen were evaluated and the theoretical values of effective elastic moduli were calculated in two cases. The tangential elastic moduli of the specimen were measured as a function of the applied stress by unaxial compression test. The maximum and minimum values of elastic moduli obtained experimentally were compared with the theoretical values. Reasonable agreement was obtained.