Cofactor regeneration by a soluble pyridine nucleotide transhydrogenase for biological production of hydromorphone

We have applied the soluble pyridine nucleotide transhydrogenase of Pseudomonas fluorescens to a cell-free system for the regeneration of the nicotinamide cofactors NAD and NADP in the biological production of the important semisynthetic opiate drug hydromorphone. The original recombinant whole-cell system suffered from cofactor depletion resulting from the action of an NADP(+)-dependent morphine dehydrogenase and an NADH-dependent morphinone reductase. By applying a soluble pyridine nucleotide transhydrogenase, which can transfer reducing equivalents between NAD and NADP, we demonstrate with a cell-free system that efficient cofactor cycling in the presence of catalytic amounts of cofactors occurs, resulting in high yields of hydromorphone. The ratio of morphine dehydrogenase, morphinone reductase, and soluble pyridine nucleotide transhydrogenase is critical for diminishing the production of the unwanted by-product dihydromorphine and for optimum hydromorphone yields. Application of the soluble pyridine nucleotide transhydrogenase to the whole-cell system resulted in an improved biocatalyst with an extended lifetime. These results demonstrate the usefulness of the soluble pyridine nucleotide transhydrogenase and its wider application as a tool in metabolic engineering and biocatalysis

Hydrogen Dissociation and Diffusion on Ni and Ti -doped Mg(0001) Surfaces

It is well known, both theoretically and experimentally, that alloying MgH$_2$ with transition elements can significantly improve the thermodynamic and kinetic properties for H$_2$ desorption, as well as the H$_2$ intake by Mg bulk. Here we present a density functional theory investigation of hydrogen dissociation and surface diffusion over Ni-doped surface, and compare the findings to previously investigated Ti-doped Mg(0001) and pure Mg(0001) surfaces. Our results show that the energy barrier for hydrogen dissociation on the pure Mg(0001) surface is high, while it is small/null when Ni/Ti are added to the surface as dopants. We find that the binding energy of the two H atoms near the dissociation site is high on Ti, effectively impeding diffusion away from the Ti site. By contrast, we find that on Ni the energy barrier for diffusion is much reduced. Therefore, although both Ti and Ni promote H$_2$ dissociation, only Ni appears to be a good catalyst for Mg hydrogenation, allowing diffusion away from the catalytic sites. Experimental results corroborate these theoretical findings, i.e. faster hydrogenation of the Ni doped Mg sample as opposed to the reference Mg or Ti doped Mg.Comment: 17 pages, 15 figures, to appear in Journal of Chemical Physic

Parasitism, Adult Emergence, Sex Ratio, and Size of \u3ci\u3eAphidius Colemani\u3c/i\u3e (Hymenoptera: Aphidiidae) on Several Aphid Species

Aphidius colemani Viereck parasitizes several economically important aphid pests of small grain crops including the greenbug, Schizaphis graminum and the Russian wheat aphid, Diuraphis noxia. The ability of A. colemani to switch from S. graminum to several species of aphids common to agricultural and associated non-agricultural ecosystems in the Great Plains, and the effects of host-change on several biological parameters that influence population growth rate were determined. Female A. colemani parasitized and developed to adulthood in nine of 14 aphid species to which they were exposed in the laboratory. All small grain feeding aphids except Sipha flava were parasi­tized. Two sunflower feeding species (Aphis nerii and A. helianthi) and two crucifer feeding species (Lipaphis erysimi and Brevicoryne brassicae) were parasitized, as was the cotton aphid. Aphis gossypii. The average percentage of aphids parasitized differed significantly among host aphid species. as did the percentage of parasitoids surviving from the mummy to the adult stage and the time required for immature development. The sex ratio of adults that enclosed from the various hosts did not differ significantly among species. Dry weights of adult parasitoids differed significantly among host species. Adults from S. graminum weighed most (0.054 mg) while those emerging from A. helianthi weighed least (0.020 mg). Results are discussed in terms of strategies for classical biological control of aphid pests of cereals

Negative cognition, affect, metacognition and dimensions of paranoia in people at ultra-high risk of psychosis: a multi-level modelling analysis

Background: Paranoia is one of the commonest symptoms of psychosis but has rarely been studied in a population at risk of developing psychosis. Based on existing theoretical models, including the proposed distinction between ‘poor me’ and ‘bad me’ paranoia, we aimed to test specific predictions about associations between negative cognition, metacognitive beliefs and negative emotions and paranoid ideation and the belief that persecution is deserved (deservedness). Method: We used data from 117 participants from the Early Detection and Intervention Evaluation for people at risk of psychosis (EDIE-2) trial of cognitive–behaviour therapy, comparing them with samples of psychiatric in-patients and healthy students from a previous study. Multi-level modelling was utilized to examine predictors of both paranoia and deservedness, with post-hoc planned comparisons conducted to test whether person-level predictor variables were associated differentially with paranoia or with deservedness. Results: Our sample of at-risk mental state participants was not as paranoid, but reported higher levels of ‘bad-me’ deservedness, compared with psychiatric in-patients. We found several predictors of paranoia and deservedness. Negative beliefs about self were related to deservedness but not paranoia, whereas negative beliefs about others were positively related to paranoia but negatively with deservedness. Both depression and negative metacognitive beliefs about paranoid thinking were specifically related to paranoia but not deservedness. Conclusions: This study provides evidence for the role of negative cognition, metacognition and negative affect in the development of paranoid beliefs, which has implications for psychological interventions and our understanding of psychosis

Random matrix analysis of complex networks

We study complex networks under random matrix theory (RMT) framework. Using nearest-neighbor and next-nearest-neighbor spacing distributions we analyze the eigenvalues of adjacency matrix of various model networks, namely, random, scale-free and small-world networks. These distributions follow Gaussian orthogonal ensemble statistic of RMT. To probe long-range correlations in the eigenvalues we study spectral rigidity via $\Delta_3$ statistic of RMT as well. It follows RMT prediction of linear behavior in semi-logarithmic scale with slope being $\sim 1/\pi^2$. Random and scale-free networks follow RMT prediction for very large scale. Small-world network follows it for sufficiently large scale, but much less than the random and scale-free networks.Comment: accepted in Phys. Rev. E (replaced with the final version

Artificial Brains and Hybrid Minds

The paper develops two related thought experiments exploring variations on an ‘animat’ theme. Animats are hybrid devices with both artificial and biological components. Traditionally, ‘components’ have been construed in concrete terms, as physical parts or constituent material structures. Many fascinating issues arise within this context of hybrid physical organization. However, within the context of functional/computational theories of mentality, demarcations based purely on material structure are unduly narrow. It is abstract functional structure which does the key work in characterizing the respective ‘components’ of thinking systems, while the ‘stuff’ of material implementation is of secondary importance. Thus the paper extends the received animat paradigm, and investigates some intriguing consequences of expanding the conception of bio-machine hybrids to include abstract functional and semantic structure. In particular, the thought experiments consider cases of mind-machine merger where there is no physical Brain-Machine Interface: indeed, the material human body and brain have been removed from the picture altogether. The first experiment illustrates some intrinsic theoretical difficulties in attempting to replicate the human mind in an alternative material medium, while the second reveals some deep conceptual problems in attempting to create a form of truly Artificial General Intelligence

Population, sexual and reproductive health, rights and sustainable development: forging a common agenda.

This article suggests that sexual and reproductive health and rights activists seeking to influence the post-2015 international development paradigm must work with sustainable development advocates concerned with a range of issues, including climate change, environmental issues, and food and water security, and that a way of building bridges with these communities is to demonstrate how sexual and reproductive health and rights are relevant for these issues. An understanding of population dynamics, including urbanization and migration, as well as population growth, can help to clarify these links. This article therefore suggests that whether or not sexual and reproductive health and rights activists can overcome resistance to discussing "population", become more knowledgeable about other sustainable development issues, and work with others in those fields to advance the global sustainable development agenda are crucial questions for the coming months. The article also contends that it is possible to care about population dynamics (including ageing and problems faced by countries with a high proportion of young people) and care about human rights at the same time. It expresses concern that, if sexual and reproductive health and rights advocates do not participate in the population dynamics discourse, the field will be left free for those for whom respecting and protecting rights may be less of a priority

Special Theory of Relativity through the Doppler Effect

We present the special theory of relativity taking the Doppler effect as the starting point, and derive several of its main effects, such as time dilation, length contraction, addition of velocities, and the mass-energy relation, and assuming energy and momentum conservation, we discuss how to introduce the 4-momentum in a natural way. We also use the Doppler effect to explain the "twin paradox", and its version on a cylinder. As a by-product we discuss Bell's spaceship paradox, and the Lorentz transformation for arbitrary velocities in one dimension.Comment: 20 pages, 1 figur

Statistical Theory of Parity Nonconservation in Compound Nuclei

We present the first application of statistical spectroscopy to study the root-mean-square value of the parity nonconserving (PNC) interaction matrix element M determined experimentally by scattering longitudinally polarized neutrons from compound nuclei. Our effective PNC interaction consists of a standard two-body meson-exchange piece and a doorway term to account for spin-flip excitations. Strength functions are calculated using realistic single-particle energies and a residual strong interaction adjusted to fit the experimental density of states for the targets, ^{238} U for A\sim 230 and ^{104,105,106,108} Pd for A\sim 100. Using the standard Desplanques, Donoghue, and Holstein estimates of the weak PNC meson-nucleon coupling constants, we find that M is about a factor of 3 smaller than the experimental value for ^{238} U and about a factor of 1.7 smaller for Pd. The significance of this result for refining the empirical determination of the weak coupling constants is discussed.Comment: Latex file, no Fig