Spin-trapping and Human Neutrophils: Limits of detection of hydroxyl radical

Using the spin trap, 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) and an excess of dimethyl sulfoxide, we previously reported that in the absence of an exogenous iron catalyst, human neutrophils will not generate hydroxyl radical, manifested as the catalyse-inhibitable methyl radical spin-trapped adduct, 2,2,5-trimethyl-1-pyrrolidinyloxy (DMPO-CH3) (Britigan, B.E., Rosen, G.M., Chai, Y., and Cohen, M.S. (1986) J. Biol. Chem. 261, 4426-4431). However, superoxide destroys the preformed hydroxyl radical spin-trapped adduct, 2,2-dimethyl-5-hydroxy-1-pyrrolidinyloxy (DMPO-OH), and DMPO-CH3. The present study was undertaken to better resolve the limits of sensitivity of the spin-trapping method. Photolytically generated DMPO-CH3 and DMPO-OH slowly decomposed in the presence of a low flux (1 μM/min) of enzymatically (xanthine/xanthine oxidase)-generated superoxide, but more rapid decomposition of these adducts occurred with higher superoxide flux (5 μM/min). Inclusion of cysteine markedly increased the rate of DMPO-OH and DMPO-CH3 decomposition, masking the effects of superoxide alone. The addition of varying concentrations of superoxide dismutase did not lead to increased formation of DMPO-OH or DMPO-CH3, as should have occurred if these adducts were being destroyed by superoxide. As a positive control, we employed an iron-supplemented system with phorbol 12-myristate 13-acetate-stimulated neutrophils or xanthine/xanthine oxidase to generate DMPO-CH3. Addition of superoxide dismutase increased the magnitude of DMPO-CH3, primarily by increasing the rate of hydrogen peroxide formation, and to a lesser extent by prolonging the half-life of DMPO-CH3. Although spin-trapped adducts can be destroyed by a high concentration of superoxide, or by lower concentrations of superoxide in the presence of thiol-containing compounds, our results demonstrate that such decomposition does not interfere with the ability of the spin-trapping method to detect hydroxyl radical generated by human neutrophils. These data do not support the capacity of neutrophils to generate hydroxyl radical in the absence of an exogenous Haber-Weiss catalyst

CEO pay, shareholder returns, and accounting profits

We assess the impact on CEO pay (including salary, cash bonus, and benefits in kind) of changes in both accounting and shareholder returns in 99 British companies in the years 1972-89. After correcting for heterogeneity biases inherent in the standard specifications of the problem, we find a strong positive relationship between CEO pay and within-company changes in shareholder returns, and no statistically significant relationship between CEO pay and within-company changes in accounting returns. Differences between firms in long-term average profitability do appear to have a substantial effect on CEO pay, while differences between firms in shareholder returns add nothing to the within-firm pay dynamics.These findings call into question the rationale for explicitly share-based incentive schemes

Stimulated human neutrophils limit iron-catalyzed hydroxyl radical formation as detected by spin-trapping techniques

Neutrophils stimulated with phorbol myristate acetate (PMA) in the presence of the spin trap 5,5-dimethyl-1-pyrroline 1-oxide (DMPO), dimethyl sulfoxide, and diethylenetriaminepentaacetic acid (DETAPAC) fail to generate hydroxyl radical (.OH), detected as the methyl spin-trapped adduct of DMPO (2,2,5-trimethyl-1-pyrrolidinyloxyl, DMPO-CH3), unless ferric salts (Fe3+) are also added (Britigan, B.E., Rosen, G.M., Chai, Y., and Cohen, M.S. (1986) J. Biol. Chem. 261, 4426-4431). Even then, .OH formation wanes in spite of ongoing superoxide (O2̇-) production. In contrast, ferric salt supplementation of a hypoxanthine/xanthine oxidase O2̇- generating system containing DETAPAC produces continual .OH, suggesting that neutrophils limit the formation of this free radical. To evaluate this hypothesis, neutrophil cytoplasts (largely devoid of granules but able to generate O2̇-) were stimulated with PMA in the presence of Fe3+, DETAPAC, dimethyl sulfoxide, and DMPO. This resulted in continual production of DMPO-CH3. In the presence of dimethyl sulfoxide, HL-60 (promyelocytic) cells differentiate into cells similar in morphology and O2̇- generating capacity to neutrophils. However, their granules lack the iron-binding protein lactoferrin (LF). Ferric salt supplementation of HL-60 cells stimulated with PMA yielded an EPR spectrum similar to cytoplasts. Supernatant obtained following PMA-induced neutrophil degranulation (which releases LF extracellularly) suppressed DMPO-CH3 formation by the hypoxanthine/xanthine oxidase/Fe3+/DETAPAC system. Anti-LF antibody, but not anti-transferrin antibody, prevented stimulated neutrophil supernatant inhibition of hypoxanthine/xanthine oxidase/Fe3+/DETAPAC-mediated .OH formation. Similarly, neutrophils stimulated with PMA in the presence of Fe3+, DETAPAC, and anti-LF antibody (but not anti-transferrin antibody) demonstrated continual formation of .OH. Neutrophil degranulation of LF limits Fe3+-catalyzed .OH formation which in vivo could protect tissue from possible .OH-mediated injury

Towards Autopoietic Computing

A key challenge in modern computing is to develop systems that address complex, dynamic problems in a scalable and efficient way, because the increasing complexity of software makes designing and maintaining efficient and flexible systems increasingly difficult. Biological systems are thought to possess robust, scalable processing paradigms that can automatically manage complex, dynamic problem spaces, possessing several properties that may be useful in computer systems. The biological properties of self-organisation, self-replication, self-management, and scalability are addressed in an interesting way by autopoiesis, a descriptive theory of the cell founded on the concept of a system's circular organisation to define its boundary with its environment. In this paper, therefore, we review the main concepts of autopoiesis and then discuss how they could be related to fundamental concepts and theories of computation. The paper is conceptual in nature and the emphasis is on the review of other people's work in this area as part of a longer-term strategy to develop a formal theory of autopoietic computing.Comment: 10 Pages, 3 figure

WLIMES, The Wandering LIMES: Towards a Theoretical Framework for Wandering Logic Intelligence Memory Evolutive Systems

This paper compares two complementary theories, Simeonov’s Wandering Logic Intelligence and Ehresmann’s & Vanbremeersch’s Memory Evolutive Systems, in view of developing a common framework for the study of multiscale complex systems such as living systems. It begins by a brief summary of WLI and MES, then analyzes their resemblances and differences. Finally, the article provides an outlook for a future research

The Orbital Period of the Pre-Cataclysmic Binary RE 2013+400 and a Study of the Atmosphere of the DAO White Dwarf Primary

Several pre-cataclysmic binaries, comprising a hot white dwarf with a red dwarf companion, have been discovered as a result of the optical identification of EUV sources from the ROSAT all-sky survey. The optical spectra have the steep blue continuum and Balmer absorption typical of a hot white dwarf, but there are bright, narrow emission lines of H I (and sometimes He I and Ca II) superimposed. An intense campaign of follow-up observations has been devoted to these binary systems. So far, only RE 2013+400 has exhibited any measurable changes in the radial velocities of the emission components, from which it is possible to estimate that the binary period is 0.71 d. A clear He II 4886-Å absorption feature is detected, which indicates that, like most PCBs with white dwarfs hotter than 40 000 K, the white dwarf is a hydrogen-helium hybrid star (DAO). A combined analysis of the optical, UV and EUV/X-ray data suggests that the atmospheric He abundance is higher in the optical line-forming region of the white dwarf photosphere than in the region where the EUV/X-ray flux is formed. This is an interesting result, in the light of the recent optical study of a sample of DAO white dwarfs by Bergeron et al., if representative of DAO white dwarfs in general

Exact Hypersurface-Homogeneous Solutions in Cosmology and Astrophysics

A framework is introduced which explains the existence and similarities of most exact solutions of the Einstein equations with a wide range of sources for the class of hypersurface-homogeneous spacetimes which admit a Hamiltonian formulation. This class includes the spatially homogeneous cosmological models and the astrophysically interesting static spherically symmetric models as well as the stationary cylindrically symmetric models. The framework involves methods for finding and exploiting hidden symmetries and invariant submanifolds of the Hamiltonian formulation of the field equations. It unifies, simplifies and extends most known work on hypersurface-homogeneous exact solutions. It is shown that the same framework is also relevant to gravitational theories with a similar structure, like Brans-Dicke or higher-dimensional theories.Comment: 41 pages, REVTEX/LaTeX 2.09 file (don't use LaTeX2e !!!) Accepted for publication in Phys. Rev.