FluxSimulator: An R Package to Simulate Isotopomer Distributions in Metabolic Networks

The representation of biochemical knowledge in terms of fluxes (transformation rates) in a metabolic network is often a crucial step in the development of new drugs and efficient bioreactors. Mass spectroscopy (MS) and nuclear magnetic resonance spectroscopy (NMRS) in combination with ^13C labeled substrates are experimental techniques resulting in data that may be used to quantify fluxes in the metabolic network underlying a process. The massive amount of data generated by spectroscopic experiments increasingly requires software which models the dynamics of the underlying biological system. In this work we present an approach to handle isotopomer distributions in metabolic networks using an object-oriented programming approach, implemented using S4 classes in R. The developed package is called FluxSimulator and provides a user friendly interface to specify the topological information of the metabolic network as well as carbon atom transitions in plain text files. The package automatically derives the mathematical representation of the formulated network, and assembles a set of ordinary differential equations (ODEs) describing the change of each isotopomer pool over time. These ODEs are subsequently solved numerically. In a case study FluxSimulator was applied to an example network. Our results indicate that the package is able to reproduce exact changes in isotopomer compositions of the metabolite pools over time at given flux rates.

From thorium phosphate hydrogenphosphate hydrate to β\beta-thorium phosphate diphosphate: Structural evolution to a radwaste storage ceramic

$\beta$-Thorium phosphate diphosphate ($\beta$-TPD), considered as a very promising radwaste storage material, was obtained from thorium phosphate hydrogenphosphate hydrate (TPHPH) precursor through dehydration and hydrogen phosphate condensation. The structures of TPHPH, intermediate $\alpha$-thorium phosphate diphosphate ($\alpha$-TPD) and its hydrate ($\alpha$-TPDH) have been resolved ab initio by Rietveld analysis of their synchrotron diffraction patterns. All were found orthorhombic (space group Cmcm) and similarly composed of [ThPO$_4$]$_4^{4+}$ slabs alternating with disordered layers hosting either [HPO$_4$·H$_2$O]$_2^{4-}$ (TPHPH), [P$_2$O$_7$·2H$_2$O]$^{4-} ($\alpha$-TPDH), or [P$_2O_7$]$^{4-}$($\alpha$-TPD), unlike the 3D structure of$\beta$-TPD. The diphosphate groups of$\alpha$-TPD and$\alpha$-TPDH are strongly bent. The irreversible transition to the final$\beta$-TPD consists in a shearing of the slabs and a reduction of the interslabs cavities that explains the stability of this high-temperature form

Ileal transposition:A non-restrictive bariatric surgical procedure that reduces body fat and increases ingestion-related energy expenditure

Background: Ileal Transposition (IT) was developed as a model to study body weight reduction without the restrictive or malabsorptive aspects of other bariatric surgeries, but the exact mechanisms of the alterations in body weight after IT are not completely understood. Objective: To provide a detailed description of the surgical procedure of IT, and describe its effect on energy balance parameters. Methods: Adult male Lewis rats underwent either IT (IT+) or sham (IT-) surgery. Following surgery body weight and energy intake were monitored. After attaining weight stability (> 30 days), energy expenditure and its components were assessed using indirect calorimetry at a day of fasting, limited intake, and ad libitum intake. At the end of the study body composition analysis was performed. Results: IT+ resulted in transiently reduced energy intake, increased ingestion-related energy expenditure (IEE) and decreased body and adipose tissue weight when compared to IT-. At weight stability, neither energy budget (i.e., energy intake - energy expenditure), nor energy efficiency was different in IT+ rats compared to IT-. Conclusion: Our data show that the primary cause of weight reduction following IT+ is a transient reduction in energy intake. If the increased IEE is related to a higher level of satiety, compensatory feeding to bridge body weight difference between IT+ and IT- rats is less likely to occur

Defect-unbinding and the Bose-glass transition in layered superconductors

The low-field Bose-glass transition temperature in heavy-ion irradiated Bi_2Sr_2CaCu_2O_8+d increases progressively with increasing density of irradiation-induced columnar defects, but saturates for densities in excess of 1.5 x10^9 cm^-2. The maximum Bose-glass temperature corresponds to that above which diffusion of two-dimensional pancake vortices between different vortex lines becomes possible, and above which the ``line-like'' character of vortices is lost. We develop a description of the Bose-glass line that is in excellent quantitative agreement with the experimental line obtained for widely different values of track density and material parameters.Comment: 4 pages, 4 figures, submitted to Phys. Rev. Let

Simulating the physiology of athletes during endurance sports events: modelling human energy conversion and metabolism

The human physiological system is stressed to its limits during endurance sports competition events. We describe a whole body computational model for energy conversion during bicycle racing. About 23 per cent of the metabolic energy is used for muscle work, the rest is converted to heat. We calculated heat transfer by conduction and blood flow inside the body, and heat transfer from the skin by radiation, convection and sweat evaporation, resulting in temperature changes in 25 body compartments. We simulated a mountain time trial to Alpe d'Huez during the Tour de France. To approach the time realized by Lance Armstrong in 2004, very high oxygen uptake must be sustained by the simulated cyclist. Temperature was predicted to reach 39°C in the brain, and 39.7°C in leg muscle. In addition to the macroscopic simulation, we analysed the buffering of bursts of high adenosine triphosphate hydrolysis by creatine kinase during cyclical muscle activity at the biochemical pathway level. To investigate the low oxygen to carbohydrate ratio for the brain, which takes up lactate during exercise, we calculated the flux distribution in cerebral energy metabolism. Computational modelling of the human body, describing heat exchange and energy metabolism, makes simulation of endurance sports events feasible

Supercooling of the disordered vortex lattice in Bi_2Sr_2CaCu_2O_8+d

Time-resolved local induction measurements near to the vortex lattice order-disorder transition in optimally doped Bi$_{2}$Sr$_{2}$CaCu$_{2}$O$_{8+\delta}$ single crystals shows that the high-field, disordered phase can be quenched to fields as low as half the transition field. Over an important range of fields, the electrodynamical behavior of the vortex system is governed by the co-existence of the two phases in the sample. We interpret the results in terms of supercooling of the high-field phase and the possible first order nature of the order-disorder transition at the ``second peak''.Comment: 4 pages, 3 figures. Submitted to Nature, July 10th, 1999; Rejected August 8th for lack of broad interest Submitted to Physical Review Letters September 10th, 199