Role of Chiral Two-Body Currents in

A direct measurement of the decay width of the excited 0_{1}^{+} state of ^{6}Li using the relative self-absorption technique is reported. Our value of Γ_{γ,0_{1}^{+}→1_{1}^{+}}=8.17(14)_{stat.}(11)_{syst.} eV provides sufficiently low experimental uncertainties to test modern theories of nuclear forces. The corresponding transition rate is compared to the results of ab initio calculations based on chiral effective field theory that take into account contributions to the magnetic dipole operator beyond leading order. This enables a precision test of the impact of two-body currents that enter at next-to-leading order.

Analytical interatomic bond-order potential for simulations of oxygen defects in iron.

We present an analytical bond-order potential for the Fe-O system, capable of reproducing the basic properties of wüstite as well as the energetics of oxygen impurities in [Formula: see text]-iron. The potential predicts binding energies of various small oxygen-vacancy clusters in [Formula: see text]-iron in good agreement with density functional theory results, and is therefore suitable for simulations of oxygen-based defects in iron. We apply the potential in simulations of the stability and structure of Fe/FeO interfaces and FeO precipitates in iron, and observe that the shape of FeO precipitates can change due to formation of well-defined Fe/FeO interfaces. The interface with crystalline Fe also ensures that the precipitates never become fully amorphous, no matter how small they are.

Molecular-dynamics study of the density scaling of inert gas condensation.

The initial stages of vapor condensation of Ge in the presence of a cold Ar atmosphere were studied by molecular-dynamics simulations. The state variables of interest included the densities of condensing vapor and gas, the density of clusters, and the average cluster size, while the temperatures of the vapor and the clusters were separately monitored with time. Three condensation processes were explicitly identified: nucleation, monomeric growth, and cluster aggregation. Our principal finding is that both the average cluster size and the number of clusters scale with the linear dimension of the computation cell, L, and Ln, with the scaling parameter n approximately 4, corresponding to a reaction order of nu approximately 2.33. This small value of n is explained by an unexpected nucleation path involving the formation of Ge dimers via two-body collisions.

Mechanisms of radiation-induced viscous flow: role of point defects.

Mechanisms of radiation-induced flow in amorphous solids have been investigated using molecular dynamics computer simulations. It is shown for a model glass system, CuTi, that the radiation-induced flow is independent of recoil energy between 100 eV and 10 keV when compared on the basis of defect production and that there is a threshold energy for flow of approximately 10 eV. Injection of interstitial- and vacancylike defects induces the same amount of flow as the recoil events, indicating that point-defect-like entities mediate the flow process, even at 10 K. Comparisons of these results with experiments and thermal spike models are made.

Carbohydrate metabolism in Dictyostelium discoideum: I. Model construction.

A model of the transitional changes which occur in fluxes and metabolite concentrations during the course of differentiation of Dictyostelium discoideum is constructed, based on extensive experimental data collected from D. discoideum. Input to the model includes metabolite compartmentation and fluxes, determined by radiotracer analyses, and enzyme mechanisms and constants. This transition model reproduced experimentally measured changes in metabolite concentrations over the last 15 hr of differentiation. The real test of a mathematical model is its ability to correctly predict the effects of an altered environment or a mutation. This model demonstrates that ability. Constraints on model parameters are also examined, and many of the altered parameters result in a model which is unable to reproduce experimental data. These results imply that the model represents many aspects of metabolism in vivo and will provide a means of examining rate-limiting events during differentiation and aging of this organism.

Carbohydrate metabolism in Dictyostelium discoideum: II. Systems' analysis.

A transition model of carbohydrate metabolism during differentiation of Dictyostelium discoideum was described in Wright & Albe (1994, J. theor. Biol. 168, 231-241). From this base model, two steady-state models are derived in which concentration and flux are consistent with culmination (600 min) or young sorocarp (700 min) stages of development. These steady-state models are analyzed using metabolic control theory (MCT), and the summation property is met for metabolites, individual flux rates, and overall flux control coefficients. The MCT analyses show that flux control differs between the two stages. At culmination, cellulose synthetase is the major control point for overall pathway flux (C = 0.86) whereas at young sorocarp, glycogen phosphorylase is the major control point (C = 0.89). This is a reflection of the increased competition between the endproduct synthases, which are used to define overall pathway flux. Thus the specific metabolic state of the cells is important in assessing control distribution. The significance of this work in understanding the mechanisms controlling biochemical differentiation is discussed and related to the work of others in the field. For example, mutant analysis can reveal which enzymes are essential to differentiation (most are) but cannot reveal which enzymes are unique and/or rate-controlling.

Systems analysis of the tricarboxylic acid cycle in Dictyostelium discoideum. I. The basis for model construction.

A steady-state model of the tricarboxylic acid cycle was constructed using a dynamic systems analysis computer program, METASIM. The model was based on radioactive tracer analyses which provided flux relationships and compartmented metabolite concentrations. Ten of the enzymes modeled were purified and characterized from Dictyostelium discoideum. Although experimentally determined enzyme mechanisms and constants were used in the model, Vmax values were found to be unreliable, i.e. they did not reflect enzyme activity in vivo. This value was therefore calculated as the only unknown in each enzyme kinetic equation and called Vvivo, to distinguish it from Vmax determined in vitro.

Systems analysis of the tricarboxylic acid cycle in Dictyostelium discoideum. II. Control analysis.

A steady-state computer model of the tricarboxylic cycle in Dictyostelium discoideum was analyzed using metabolic control theory. The steady state had variations of less than 0.04% over the last half of the simulation for both metabolite concentrations and fluxes. Metabolite and flux control coefficients were determined by varying enzymatic activities within 2% of their initial values and simulating the responses of metabolite concentrations and fluxes to these changes. Under these conditions, summation properties were met for most metabolite and all flux control coefficients. Maximum flux control coefficients were found for succinate dehydrogenase (0.35), malic enzyme (0.24), and malate dehydrogenase (-0.18). Comparable control was found for the reaction supplying pyruvate (0.14) and for the sum of the input amino acids (0.43), which serve as an energy source for D. discoideum. The time-dependent processes by which a new steady state was established were examined after increasing malic enzyme or malate dehydrogenase activities. This provided a method for an analysis of the mechanisms by which the observed control coefficients were generated. In addition, the effects of increasing the stimuli within 5-20% of the original enzyme activity were examined. Under these conditions, more typical of experimental stimuli and measurable responses, the metabolic model failed to return to steady state, and thus summation properties were not met. Whether "true" steady states ever occur or whether metabolic control theory can be applied in vivo is discussed.

Cellular concentrations of enzymes and their substrates.

The activity of crude and pure enzyme preparations as well as the molecular weight of these enzymes were obtained from the literature for several organisms. From these data enzyme concentrations were calculated and compared to the concentration(s) of their substrates in the same organism. The data are expressed as molar ratios of metabolite concentration to enzyme site concentration. Of the 140 ratios calculated, 88% were one or greater, indicating that in general substrates exceed their cognate enzyme concentrations. Of the 17 cases where enzyme exceeds metabolite concentration, 16 were in glycolysis. The data in general justify the use of enzyme kinetic mechanisms determined in vitro in the construction of dynamic models which simulate in vivo metabolism.

Purification and characterization of the 2-oxoglutarate dehydrogenase complex from Dictyostelium discoideum.

The 2-oxoglutarate dehydrogenase complex was isolated from the cellular slime mould, Dictyostelium discoideum, and purified 113-fold. The enzyme exhibited Michaelis-Menten kinetics and the Km values for 2-oxoglutarate, CoA, and NAD were 1.0 mM, 0.002 mM, and 0.07 mM, respectively. The Ki value for succinyl-CoA was determined to be 0.004 mM and the Ki for NADH was 0.018 mM. AMP had positive effects whereas ATP had negative effects on the enzyme activity. The kinetic constants determined in this study and the reaction mechanism suggested can now be incorporated into a transition model of the tricarboxylic acid cycle during differentiation of D. discoideum.

Protein kinases of the human placental microvillous membrane. Their potential role in intrasyncytial communication.

Protein phosphorylation has been shown to alter various plasma membrane functions. To investigate the role of phosphorylation in human placental trophoblast, microvillous membrane vesicles were incubated with [gamma-32-P]ATP and the phosphorylation of endogenous and exogenous protein substrates was measured. The microvillous membrane was shown to possess both adenosine 3',5'-cyclic monophosphate (cAMP)-independent and cAMP-dependent kinases. Both endogenous proteins and exogenous proteins were phosphorylated and these processes were enhanced by the presence of Triton or the ionophore alamethicin. The phosphorylation of histone and of endogenous peptides of molecular weights (MW) 147 000, 97 000 and 53 000 was increased by the addition of cAMP. cAMP stimulation required the presence of Triton or alamethicin. The cAMP-dependent kinases are apparently located at the internal (cytoplasmic) surface of the membrane. This location would allow stimulation by cAMP produced by the basal (fetal-facing) plasma membrane. cAMP-stimulated protein phosphorylation may serve as a means of communication between the syncytial plasma membranes facing the fetal and maternal surfaces.