525 research outputs found
Stochastic Analysis of Dimerization Systems
The process of dimerization, in which two monomers bind to each other and
form a dimer, is common in nature. This process can be modeled using rate
equations, from which the average copy numbers of the reacting monomers and of
the product dimers can then be obtained. However, the rate equations apply only
when these copy numbers are large. In the limit of small copy numbers the
system becomes dominated by fluctuations, which are not accounted for by the
rate equations. In this limit one must use stochastic methods such as direct
integration of the master equation or Monte Carlo simulations. These methods
are computationally intensive and rarely succumb to analytical solutions. Here
we use the recently introduced moment equations which provide a highly
simplified stochastic treatment of the dimerization process. Using this
approach, we obtain an analytical solution for the copy numbers and reaction
rates both under steady state conditions and in the time-dependent case. We
analyze three different dimerization processes: dimerization without
dissociation, dimerization with dissociation and hetero-dimer formation. To
validate the results we compare them with the results obtained from the master
equation in the stochastic limit and with those obtained from the rate
equations in the deterministic limit. Potential applications of the results in
different physical contexts are discussed.Comment: 10 figure
Hard X-ray standing-wave photoemission insights into the structure of an epitaxial Fe/MgO multilayer magnetic tunnel junction
The Fe/MgO magnetic tunnel junction is a classic spintronic system, with current importance technologically and interest for future innovation. The key magnetic properties are linked directly to the structure of hard-to-access buried interfaces, and the Fe and MgO components near the surface are unstable when exposed to air, making a deeper probing, nondestructive, in-situ measurement ideal for this system. We have thus applied hard X-ray photoemission spectroscopy (HXPS) and standing-wave (SW) HXPS in the few kilo-electron-volt energy range to probe the structure of an epitaxially grown MgO/Fe superlattice. The superlattice consists of 9 repeats of MgO grown on Fe by magnetron sputtering on an MgO(001) substrate, with a protective Al2O3 capping layer. We determine through SW-HXPS that 8 of the 9 repeats are similar and ordered, with a period of 33 ± 4 Å, with the minor presence of FeO at the interfaces and a significantly distorted top bilayer with ca. 3 times the oxidation of the lower layers at the top MgO/Fe interface. There is evidence of asymmetrical oxidation on the top and bottom of the Fe layers. We find agreement with dark-field scanning transmission electron microscope (STEM) and X-ray reflectivity measurements. Through the STEM measurements, we confirm an overall epitaxial stack with dislocations and warping at the interfaces of ca. 5 Å. We also note a distinct difference in the top bilayer, especially MgO, with possible Fe inclusions. We thus demonstrate that SW-HXPS can be used to probe deep buried interfaces of novel magnetic devices with few-angstrom precision
Duality, thermodynamics, and the linear programming problem in constraint-based models of metabolism
It is shown that the dual to the linear programming problem that arises in
constraint-based models of metabolism can be given a thermodynamic
interpretation in which the shadow prices are chemical potential analogues, and
the objective is to minimise free energy consumption given a free energy drain
corresponding to growth. The interpretation is distinct from conventional
non-equilibrium thermodynamics, although it does satisfy a minimum entropy
production principle. It can be used to motivate extensions of constraint-based
modelling, for example to microbial ecosystems.Comment: 4 pages, 2 figures, 1 table, RevTeX 4, final accepted versio
Evaluation of rate law approximations in bottom-up kinetic models of metabolism.
BackgroundThe mechanistic description of enzyme kinetics in a dynamic model of metabolism requires specifying the numerical values of a large number of kinetic parameters. The parameterization challenge is often addressed through the use of simplifying approximations to form reaction rate laws with reduced numbers of parameters. Whether such simplified models can reproduce dynamic characteristics of the full system is an important question.ResultsIn this work, we compared the local transient response properties of dynamic models constructed using rate laws with varying levels of approximation. These approximate rate laws were: 1) a Michaelis-Menten rate law with measured enzyme parameters, 2) a Michaelis-Menten rate law with approximated parameters, using the convenience kinetics convention, 3) a thermodynamic rate law resulting from a metabolite saturation assumption, and 4) a pure chemical reaction mass action rate law that removes the role of the enzyme from the reaction kinetics. We utilized in vivo data for the human red blood cell to compare the effect of rate law choices against the backdrop of physiological flux and concentration differences. We found that the Michaelis-Menten rate law with measured enzyme parameters yields an excellent approximation of the full system dynamics, while other assumptions cause greater discrepancies in system dynamic behavior. However, iteratively replacing mechanistic rate laws with approximations resulted in a model that retains a high correlation with the true model behavior. Investigating this consistency, we determined that the order of magnitude differences among fluxes and concentrations in the network were greatly influential on the network dynamics. We further identified reaction features such as thermodynamic reversibility, high substrate concentration, and lack of allosteric regulation, which make certain reactions more suitable for rate law approximations.ConclusionsOverall, our work generally supports the use of approximate rate laws when building large scale kinetic models, due to the key role that physiologically meaningful flux and concentration ranges play in determining network dynamics. However, we also showed that detailed mechanistic models show a clear benefit in prediction accuracy when data is available. The work here should help to provide guidance to future kinetic modeling efforts on the choice of rate law and parameterization approaches
Oesophageal symptoms are common and associated with other functional gastrointestinal disorders (FGIDs) in an English-speaking Western population
mean age 46.7 years) were available for analysis. Symptom prevalence was 8.1% for globus, 6.5% for heartburn, 4.5% for dysphagia and 5.2% for chest pain, and 17.0% reported at least one oesophageal symptom. Oesophageal symptoms were independently associated with younger age, female gender, previous abdominal surgery and the presence of other functional GI disorders. Reporting oesophageal symptoms was associated with reduced quality of life. Conclusion: Oesophageal symptoms are common in the general population and important predictors include other functional GI disorders, age and gender. Oesophageal symptoms are associated with poorer quality of life.Background: The prevalence and frequency of oesophageal symptoms suggestive of a functional oesophageal disorder according to the Rome IV criteria are unknown. Objective: We aimed to describe the prevalence and risk factors for oesophageal symptoms compatible with functional oesophageal disorders in the general population. Methods: Data were analysed from a population-based online survey of 6300 individuals aged ≥ 18 years in the USA, UK and Canada with equal demographic proportions across countries. Questions included the Rome IV diagnostic questionnaire, demographics, medication, somatization, quality of life, and organic gastrointestinal (GI) disease. Multivariate analysis was used to identify factors independently related to oesophageal symptoms. Results: Data from 5177 participants (47.8% femal
Purifying Selection in Deeply Conserved Human Enhancers Is More Consistent than in Coding Sequences
(c) 2014 De Silva et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Motility response to colonic distention is increased in postinfectious irritable bowel syndrome (PI-IBS)
Acute intestinal infection leads to persistent intestinal smooth muscle hypercontractility and pain hypersensitivity after resolution of the infection in animal models. We investigated whether post-infectious irritable bowel syndrome (PI-IBS) is associated with abnormalities in phasic contractions of the colon, smooth muscle tone and pain sensitivity compared to non-PI-IBS (NI-IBS) or healthy controls (HC)
Self-organized Vortex State in Two-dimensional Dictyostelium Dynamics
We present results of experiments on the dynamics of Dictyostelium discoideum
in a novel set-up which constraints cell motion to a plane. After aggregation,
the amoebae collect into round ''pancake" structures in which the cells rotate
around the center of the pancake. This vortex state persists for many hours and
we have explicitly verified that the motion is not due to rotating waves of
cAMP. To provide an alternative mechanism for the self-organization of the
Dictyostelium cells, we have developed a new model of the dynamics of
self-propelled deformable objects. In this model, we show that cohesive energy
between the cells, together with a coupling between the self-generated
propulsive force and the cell's configuration produces a self-organized vortex
state. The angular velocity profiles of the experiment and of the model are
qualitatively similar. The mechanism for self-organization reported here can
possibly explain similar vortex states in other biological systems.Comment: submitted to PRL; revised version dated 3/8/9
- …