Oxidatively truncated docosahexaenoate phospholipids: total synthesis,generation, and Peptide adduction chemistry

The recent immunological detection of extraordinarily high levels of carboxyethylpyrrole (CEP) modifications of proteins from the retinas of individuals with age-related macular degeneration provided presumptive evidence for the involvement of docosahexaenoate-derived oxidatively truncated phospholipids in retinal pathology. To facilitate the in vivo detection and characterization of the chemistry and biological activities of these postulated naturally occurring molecules, a family of oxidatively truncated phospholipids was prepared by total syntheses. Their formation in oxidation reactions of a docosahexaenoate ester of 2-lysophosphatidylcholine (DHA-PC) was also demonstrated. Free radical-induced oxidative cleavage of DHA-PC promoted by myeloperoxidase or copper ions generates similar mixtures of these phospholipids. The most abundant products were 1-palmitoyl-2-succinoyl-sn-glycero-3-phosphatidylcholine (4.7%) and 2-(6-carboxy-4-oxohex-5-enoyl)-1-palmitoyl-sn-glycero-3-phosphatidylcholine (1.7%). Both of these oxidatively truncated phospholipids are homologues of biologically active arachidonate-derived phospholipids. A minor product from DHA-PC, 2-(4-hydroxy-7-oxohept-5-enoyl)-1-palmitoyl-sn-glycero-3-phosphatidylcholine (0.4% yield), reacted with the epsilon-amino group of a peptide lysyl residue to produce a CEP derivative in 0.7% yield. These observations support the previous conclusion, based on immunological evidence, that CEPs are generated by the reaction of an oxidatively truncated phospholipid with proteins in the retina and further indicate that CEP protein modifications probably represent only a tiny fraction of the products generated upon oxidative damage of DHA-PC in photoreceptor disk membranes.     

Optimality conditions in nonconical multiple-objective programming

Previous theoretical work in multiple-objective optimization has focused entirely on vector orders representable by positive cones. Here, we treat multiple-objective problems in which solutions are sought which are maximal (efficient, nondominated) under an order which may be nonconical. Compactness conditions under which maximal solutions exist and bound the remaining alternatives are given. First-order necessary conditions and first-order sufficient conditions for maximality in general normed linear spaces are derived, and a scalarization result is given. A small computational example is also presented. Several previous results are special cases of those given here.     

Nonconical optimality conditions: Some additional results

The purpose of the present note is to provide a somewhat more flexible statement of the sufficiency conditions in Section 4 of Ref. 1 and to give explicit statements of the fundamental necessity and sufficiency results, which were only implicitly presented there. The additional flexibility is obtained by considering local, rather than global, pseudoconcavity requirements.     

Os(VIII)-catalysed oxidation of sulfides by sodium salt of N-chlorobenzenesulfonamide

Catalytic activity of Os(VIII) in the oxidation of some twenty organic sulfides with sodium salt of N-chlorobenzenesulfonamide (CAB) has been investigated in alkaline (pH8.7) t-butanol–water (1:1 v/v) medium. Significant retarding influence of [OH⁻] on the reactivity is exhibited. The catalysed reaction is strongly accelerated in the presence of Hg(II). Imperfections are observed in the linear Hammett relationship in the case of –NO₂ substituents.     

Raman spectroscopic investigation on the microenvironment of the liver tissues of Zebrafish (Danio rerio) due to titanium dioxide exposure

Nano titanium dioxide (nTiO₂), generally considered to be toxicologically inert, is manufactured in large quantities and extensively applied in consumer products. The small size and large surface area endow them with an active group or intrinsic toxicity. Advances in instrumentation are making Raman spectroscopy the tool of choice for an increasing number of (bio) chemical applications. One of the great advantages of this technique is its ability to provide information on the concentration, structure and interaction of biochemical molecules in their microenvironments within intact cells and tissues, non-destructively. Zebrafish (Danio rerio), one of the most important vertebrate model organisms used in developmental biology, are increasingly used in biomedical research, particularly as a model of human disease. In the present work, an attempt is made to study the effect of titanium dioxide, both nano and bulk, on the microenvironment of the liver tissues of Zebrafish using FT-Raman spectroscopy. The results of the present study suggest that TiO₂ exposure demonstrate a marked influence on the microenvironments of the liver tissues of Zebrafish. A shift to a higher wavenumber and an increase in the intensity of the band at ∼1087 cm⁻¹ in the TiO₂ exposed tissues suggest that some of the conformational changes resulting from the alkali recovery process takes place due to TiO₂ exposure. The decreased intensity ratio (I₃₂₂₀/I₃₄₀₀) observed in the titanium-exposed tissues suggests a decreased water domain size, which could be interpreted in terms of weaker hydrogen-bonded molecular species of water in the TiO₂ exposed tissues. The observed shift of COO⁻ bands to higher frequencies shows the disruption of salt bridges as a result of a change in the oppositely charged partners and due to the enhanced random coil conformation. The variation in the intensity ratio of the tyrosyl doublet (I₈₅₈/I₈₂₅) indicates variation in the hydrogen bonding of the phenolic hydroxyl group due to TiO₂ exposure. The results further suggest that the microenvironments are greatly altered due to titanium nano exposure when compared to titanium bulk. In conclusion, the results indicate that FT-Raman spectroscopy might be a useful tool for rapid assessment of nano particle biological interactions.     

High-pressure crystal chemistry of scheelite-type tungstates and molybdates

Unit-cell parameters and crystal structures of CaWO₄(scheelite) and CaMoO₄ (powellite) have been determined at several pressures to 5 8 GPa, and unit-cell parameters of PbMoO₄ (wulfemte), PbWO₄ (stolzite) and CdMoO₄ have been measured at pressures to 6 0 GPa All five tetragonal scheelite-type compounds compress anisotropically, with the (itc) axis 1 2 to 1 9 times more compressible than a. In both CaWO₄ and CaMoO₄ the cation tetrahedra (with W⁶⁺ or Mo⁶⁺) behave as rigid structural elements with no observed cation-oxygen compression (W-O and Mo-O bond compression < 0001 GPa^?1) Compression of the eight-coordinated calcium polyhedron, on the other hand, is comparable to bulk compression of the compounds (Ca-O bond compression = 0005 ± 0 001 GPa^?1) Amsotropies in the pressure response of the calcium polyhedron, which is more compressible parallel to c than perpendicular to c, result in the amsotropic unit-cell compression Bulk moduli of the five compounds (with K' assumed to be 4) are CaWO₄ (68 ± 9 GPa), CaMoO₄ (81 5 ± 0 7 GPa), PbWO₄ (64 ± 2 GPa), PbMoO₄ (64 ± 2 GPa), and CdMoO₄ (104 ± 2 GPa) No reversible transitions to the monoclinic (fergusomte) distortion of scheelite were observed in these compounds Pressure-volume data for PbWO₄, however, display strong positive curvature (K'_calc) = 23 ± 2) up to about 5 GPa, at which pressure crystals appear to undergo a first-order phase transition The relatively large curvature may be a premonitory effect pnor to a reconstructive transition Structural changes in these compounds with increasing pressure are qualitatively similar to changes that result from isobanc cooling or substitution of a smaller cation in the eight-coordinated site.     

A Continuous-Risk Decision Analysis of Total Hip Replacement

Stochastic trees are stochastic processes, such as continuous-time Markov chains, which may be represented using tree diagrams. Continuous-risk utility assessment is a methodology that differs from standard assessment protocols by offering choices between alternatives which are not ‘sure’ things, thus enabling more realistic and familiar assessment scenarios to be posed. In this paper we develop, using information from the medical literature, stochastic tree models of the total hip replacement decision alternatives facing a patient with advanced osteoarthritis of the hip. We describe a decision analytic approach to the problem which uses continuous-risk utility assessment, and present empirical assessment results. We explore the sensitivity of the subjects' treatment recommendations to changes in model parameters and elicited preference values, offering insights into the variety of patient risk attitudes and preferences about functional well-being and the robustness of the total hip replacement decision to them.