Using in silico models to simulate dual perturbation experiments: procedure development and interpretation of outcomes.

BackgroundA growing number of realistic in silico models of metabolic functions are being formulated and can serve as 'dry lab' platforms to prototype and simulate experiments before they are performed. For example, dual perturbation experiments that vary both genetic and environmental parameters can readily be simulated in silico. Genetic and environmental perturbations were applied to a cell-scale model of the human erythrocyte and subsequently investigated.ResultsThe resulting steady state fluxes and concentrations, as well as dynamic responses to the perturbations were analyzed, yielding two important conclusions: 1) that transporters are informative about the internal states (fluxes and concentrations) of a cell and, 2) that genetic variations can disrupt the natural sequence of dynamic interactions between network components. The former arises from adjustments in energy and redox states, while the latter is a result of shifting time scales in aggregate pool formation of metabolites. These two concepts are illustrated for glucose-6 phosphate dehydrogenase (G6PD) and pyruvate kinase (PK) in the human red blood cell.ConclusionDual perturbation experiments in silico are much more informative for the characterization of functional states than single perturbations. Predictions from an experimentally validated cellular model of metabolism indicate that the measurement of cofactor precursor transport rates can inform the internal state of the cell when the external demands are altered or a causal genetic variation is introduced. Finally, genetic mutations that alter the clinical phenotype may also disrupt the 'natural' time scale hierarchy of interactions in the network

Z^\widehat{Z} at large NN: from curve counts to quantum modularity

Reducing a 6d fivebrane theory on a 3-manifold $Y$ gives a $q$-series 3-manifold invariant $\widehat{Z}(Y)$. We analyse the large-$N$ behaviour of $F_K=\widehat{Z}(M_K)$, where $M_K$ is the complement of a knot $K$ in the 3-sphere, and explore the relationship between an $a$-deformed ($a=q^N$) version of $F_{K}$ and HOMFLY-PT polynomials. On the one hand, in combination with counts of holomorphic annuli on knot complements, this gives an enumerative interpretation of $F_K$ in terms of counts of open holomorphic curves. On the other, it leads to closed form expressions for $a$-deformed $F_K$ for $(2,2p+1)$-torus knots. They suggest a further $t$-deformation based on superpolynomials, which can be used to obtain a $t$-deformation of ADO polynomials, expected to be related to categorification. Moreover, studying how $F_K$ transforms under natural geometric operations on $K$ indicates relations to quantum modularity in a new setting.Comment: 42 pages, 4 figure

Alternative Modes of Financing Higher Education in Nigeria and the Implications for University Governance

Under-funding has been identified as one of the major problems presently facing the university system in most of the African nations, Nigeria inclusive. The study documented both financing and expenditure patterns in the Nigerian universities, and found that most monies, which go on direct teaching, are in fact used for the payment of salaries and entitlements of staff

Fingering convection induced by atomic diffusion in stars: 3D numerical computations and applications to stellar models

Iron-rich layers are known to form in the stellar subsurface through a combination of gravitational settling and radiative levitation. Their presence, nature and detailed structure can affect the excitation process of various stellar pulsation modes, and must therefore be modeled carefully in order to better interpret Kepler asteroseismic data. In this paper, we study the interplay between atomic diffusion and fingering convection in A-type stars, and its role in the establishment and evolution of iron accumulation layers. To do so, we use a combination of three-dimensional idealized numerical simulations of fingering convection, and one-dimensional realistic stellar models. Using the three-dimensional simulations, we first validate the mixing prescription for fingering convection recently proposed by Brown et al. (2013), and identify what system parameters (total mass of iron, iron diffusivity, thermal diffusivity, etc.) play a role in the overall evolution of the layer. We then implement the Brown et al. (2013) prescription in the Toulouse-Geneva Evolution code to study the evolution of the iron abundance profile beneath the stellar surface. We find, as first discussed by Th\'eado et al. (2009), that when the concurrent settling of helium is ignored, this accumulation rapidly causes an inversion in the mean molecular weight profile, which then drives fingering convection. The latter mixes iron with the surrounding material very efficiently, and the resulting iron layer is very weak. However, taking helium settling into account partially stabilizes the iron profile against fingering convection, and a large iron overabundance can accumulate. The opacity also increases significantly as a result, and in some cases ultimately triggers dynamical convection.Comment: 38 pages, 16 figures, submitted to Ap

Comparison of synthetic maps from truncated jet-formation models with YSO jet observations

(abridged) Significant progress has been made in the last years in the understanding of the jet formation mechanism through a combination of numerical simulations and analytical MHD models for outflows characterized by the symmetry of self-similarity. In a previous article we introduced models of truncated jets from disks, i.e. evolved in time numerical simulations based on a radially self-similar MHD solution, but including the effects of a finite radius of the jet-emitting disk and thus the outflow. These models need now to be compared with available observational data. A direct comparison of the results of combined analytical theoretical models and numerical simulations with observations has not been performed as yet. In order to compare our models with observed jet widths inferred from recent optical images taken with HST and AO observations, we use a new set of tools to create emission maps in different forbidden lines, from which we determine the jet width as the FWHM of the emission. It is shown that the untruncated analytical disk outflow solution considered here cannot fit the small jet widths inferred by observations of several jets. Various truncated disk-wind models are examined, whose extracted jet widths range from higher to lower values compared to the observations. Thus we can fit the observed range of jet widths by tuning our models. We conclude that truncation is necessary to reproduce the observed jet widths and our simulations limit the possible range of truncation radii. We infer that the truncation radius, which is the radius on the disk mid-plane where the jet-emitting disk switches to a standard disk, must be between around 0.1 up to about 1 AU in the observed sample for the considered disk-wind solution. One disk-wind simulation with an inner truncation radius at about 0.11 AU also shows potential for reproducing the observations, but a parameter study is needed.Comment: accepted for publication in A & A, 14 pages, 21 figure

Much Ado About Nothing? Comitology as a Feature of EU Policy Implementation and its Effects on the Democratic Arena. IHS Political Science Series: 2001, No. 78

The previously neglected phenomenon of governance by committees has recently received increasing attention in the academic literature. This paper focuses on the consequences of the arrangements prevailing in the committees active in the implementing phase of EU-legislation on the practice of democracy and legitimacy. The so-called "comitology committees" can be seen as a good example of the tension between input- and output-based sources of legitimacy. On the one hand the EP has demanded its increased involvement in this system ever since these committees were established. On the other hand (preliminary) studies have shown that Members of the European Parliament seem to be overwhelmed with the scrutiny or even the filing of draft implementing measures. This gives rise to the question of increasing the legitimacy of committee work and at the same time preserving the "efficiency" of this (presumably) cooperative form of decision making. This phenomenon is illustrated by means of a case study of committees active in the field of health and consumer protection