Leading coordinate analysis of reaction pathways in proton chain transfer: Application to a two-proton transfer model for the green fluorescent protein

The ‘leading coordinate’ approach to computing an approximate reaction pathway, with subsequent determination of the true minimum energy profile, is applied to a two-proton chain transfer model based on the chromophore and its surrounding moieties within the green fluorescent protein (GFP). Using an ab initio quantum chemical method, a number of different relaxed energy profiles are found for several plausible guesses at leading coordinates. The results obtained for different trial leading coordinates are rationalized through the calculation of a two-dimensional relaxed potential energy surface (PES) for the system. Analysis of the 2-D relaxed PES reveals that two of the trial pathways are entirely spurious, while two others contain useful information and can be used to furnish starting points for successful saddle-point searches. Implications for selection of trial leading coordinates in this class of proton chain transfer reactions are discussed, and a simple diagnostic function is proposed for revealing whether or not a relaxed pathway based on a trial leading coordinate is likely to furnish useful information.

Measurement of strain and strain rate by echocardiography - Ready for prime time?

Strain and strain rate (SR) are measures of deformation that are basic descriptors of both the nature and the function of cardiac tissue. These properties may now be measured using either Doppler or two-dimensional ultrasound techniques. Although these measurements are feasible in routine clinical echocardiography, their acquisition and analysis nonetheless presents a number of technical challenges and complexities. Echocardiographic strain and SR imaging has been applied to the assessment of resting ventricular function, the assessment of myocardial viability using low-dose dobutamine infusion, and stress testing for ischemia. Resting function assessment has been applied in both the left and the fight ventricles, and may prove particularly valuable for identifying myocardial diseases and following up the treatment response. Although the evidence base is limited, SR imaging seems to be feasible and effective for the assessment of myocardial viability. The use of the technique for the detection of ischemia during stress echocardiography is technically challenging and likely to evolve further. The clinical availability of strain and SR measurement may offer a solution to the ongoing need for quantification of regional and global cardiac function. Nonetheless, these techniques are susceptible to artifact, and further technical development is necessary.

From point defects to plate tectonic faults

Understanding and explaining emergent constitutive laws in the multi-scale evolution from point defects, dislocations and two-dimensional defects to plate tectonic scales is an arduous challenge in condensed matter physics. The Earth appears to be the only planet known to have developed stable plate tectonics as a means to get rid of its heat. The emergence of plate tectonics out of mantle convection appears to rely intrinsically on the capacity to form extremely weak faults in the top 100 km of the planet. These faults have a memory of at least several hundred millions of years, yet they appear to rely on the effects of water on line defects. This important phenomenon was first discovered in laboratory and dubbed ``hydrolytic weakening''. At the large scale it explains cycles of co-located resurgence of plate generation and consumption (the Wilson cycle), but the exact physics underlying the process itself and the enormous spanning of scales still remains unclear. We present an attempt to use the multi-scale non-equilibrium thermodynamic energy evolution inside the deforming lithosphere to move phenomenological laws to laws derived from basic scaling quantities, develop self-consistent weakening laws at lithospheric scale and give a fully coupled deformation-weakening constitutive framework. At meso- to plate scale we encounter in a stepwise manner three basic domains governed by the diffusion/reaction time scales of grain growth, thermal diffusion and finally water mobility through point defects in the crystalline lattice. The latter process governs the planetary scale and controls the stability of its heat transfer mode.

The presence of ascorbate induces expression of brain derived neurotrophic factor in SH-SY5Y neuroblastoma cells after peroxide insult, which is associated with increased survival

Oxidative stress and free radical production have been implicated in Alzheimer's disease, where low levels of the antioxidant vitamin C (ascorbate) have been shown to be associated with the disease. In this study, neuroblastoma SH-SY5Y cells were treated with hydrogen peroxide in the presence of ascorbate in order to elucidate the me0chanism(s) of protection against oxidative stress afforded by ascorbate. Protein oxidation, glutathione levels, cell viability and the effects on the proteome and its oxidized counterpart were monitored. SH-SY5Y cells treated with ascorbate prior to co-incubation with peroxide showed increased viability in comparison to cells treated with peroxide alone. This dual treatment also caused an increase in protein carbonyl content and a decrease in glutathione levels within the cells. Proteins, extracted from SH-SY5Y cells that were treated with either ascorbate or peroxide alone or with ascorbate prior to peroxide, were separated by two-dimensional gel electrophoresis and analyzed for oxidation. Co-incubation for 24 hours decreased the number of oxidised proteins (e.g. acyl CoA oxidase 3) and induced brain derived neurotrophic factor (BDNF) expression. Enhanced expression of BDNF may contribute to the protective effects of ascorbate against oxidative stress in neuronal cells.

A principled approach to interactive hierarchical non-linear visualization of high-dimensional data

Hierarchical visualization systems are desirable because a single two-dimensional visualization plot may not be sufficient to capture all of the interesting aspects of complex high-dimensional data sets. We extend an existing locally linear hierarchical visualization system PhiVis [1] in several directions: bf(1) we allow for em non-linear projection manifolds (the basic building block is the Generative Topographic Mapping -- GTM), bf(2) we introduce a general formulation of hierarchical probabilistic models consisting of local probabilistic models organized in a hierarchical tree, bf(3) we describe folding patterns of low-dimensional projection manifold in high-dimensional data space by computing and visualizing the manifold's local directional curvatures. Quantities such as magnification factors [3] and directional curvatures are helpful for understanding the layout of the nonlinear projection manifold in the data space and for further refinement of the hierarchical visualization plot. Like PhiVis, our system is statistically principled and is built interactively in a top-down fashion using the EM algorithm. We demonstrate the visualization system principle of the approach on a complex 12-dimensional data set and mention possible applications in the pharmaceutical industry.

Quantitative risk assessment of groundwater quality utilizing GIS technology and coupled groundwater models

The thesis presents a two-dimensional Risk Assessment Method (RAM) where the assessment of risk to the groundwater resources incorporates both the quantification of the probability of the occurrence of contaminant source terms, as well as the assessment of the resultant impacts. The approach emphasizes the need for a greater dependency on the potential pollution sources, rather than the traditional approach where assessment is based mainly on the intrinsic geo-hydrologic parameters. The risk is calculated using Monte Carlo simulation methods whereby random pollution events were generated to the same distribution as historically occurring events or a priori potential probability distribution. Integrated mathematical models then simulate contaminant concentrations at the predefined monitoring points within the aquifer. The spatial and temporal distributions of the concentrations were calculated from repeated realisations, and the number of times when a user defined concentration magnitude was exceeded is quantified as a risk. The method was setup by integrating MODFLOW-2000, MT3DMS and a FORTRAN coded risk model, and automated, using a DOS batch processing file. GIS software was employed in producing the input files and for the presentation of the results. The functionalities of the method, as well as its sensitivities to the model grid sizes, contaminant loading rates, length of stress periods, and the historical frequencies of occurrence of pollution events were evaluated using hypothetical scenarios and a case study. Chloride-related pollution sources were compiled and used as indicative potential contaminant sources for the case study. At any active model cell, if a random generated number is less than the probability of pollution occurrence, then the risk model will generate synthetic contaminant source term as an input into the transport model. The results of the applications of the method are presented in the form of tables, graphs and spatial maps. Varying the model grid sizes indicates no significant effects on the simulated groundwater head. The simulated frequency of daily occurrence of pollution incidents is also independent of the model dimensions. However, the simulated total contaminant mass generated within the aquifer, and the associated volumetric numerical error appear to increase with the increasing grid sizes. Also, the migration of contaminant plume advances faster with the coarse grid sizes as compared to the finer grid sizes. The number of daily contaminant source terms generated and consequently the total mass of contaminant within the aquifer increases in a non linear proportion to the increasing frequency of occurrence of pollution events. The risk of pollution from a number of sources all occurring by chance together was evaluated, and quantitatively presented as risk maps. This capability to combine the risk to a groundwater feature from numerous potential sources of pollution proved to be a great asset to the method, and a large benefit over the contemporary risk and vulnerability methods.

Three-dimensional magnetic resonance imaging of the phakic crystalline lens during accommodation

To quantify changes in crystalline lens curvature, thickness, equatorial diameter, surface area, and volume during accommodation using a novel two-dimensional magnetic resonance imaging (MRI) paradigm to generate a complete three-dimensional crystalline lens surface model.

Two-axis temperature-insensitive accelerometer based on multicore fiber Bragg gratings

We report a compact two-dimensional accelerometer based upon a simple fiber cantilever constructed from a short length of multicore optical fiber. Two-axis measurement is demonstrated up to 3 kHz. Differential measurement between fiber Bragg gratings written in the multicore fiber provides temperature- insensitive measurements.

Investigation of two-wave mixing in arbitrary oriented sillenite crystals

A generalized systematic description of the Two-Wave Mixing (TWM) process in sillenite crystals allowing for arbitrary orientation of the grating vector is presented. An analytical expression for the TWM gain is obtained for the special case of plane waves in a thin crystal (|g|d«1) with large optical activity (|g|/?«1, g is the coupling constant, ? the rotatory power, d the crystal thickness). Using a two-dimensional formulation the scope of the nonlinear equations describing TWM can be extended to finite beams in arbitrary geometries and to any crystal parameters. Two promising applications of this formulation are proposed. The polarization dependence of the TWM gain is used for the flattening of Gaussian beam profiles without expanding them. The dependence of the TWM gain on the interaction length is used for the determination of the crystal orientation. Experiments carried out on Bi12GeO20 crystals of a non-standard cut are in good agreement with the results of modelling.

Isotropic compression of mixtures of hard and soft spheres

The compaction behaviour of powders with soft and hard components is of particular interest to the paint processing industry. Unfortunately, at the present time, very little is known about the internal mechanisms within such systems and therefore suitable tests are required to help in the interpretative process. The TRUBAL, Distinct Element Method (D.E.M.) program was the method of investigation used in this study. Steel (hard) and rubber (soft) particles were used in the randomly-generated, binary assemblies because they provided a sharp contrast in physical properties. For reasons of simplicity, isotropic compression of two-dimensional assemblies was also initially considered. The assemblies were first subject to quasi-static compaction, in order to define their behaviour under equilibrium conditions. The stress-strain behaviour of the assemblies under such conditions was found to be adequately described by a second-order polynomial expansion. The structural evolution of the simulation assemblies was also similar to that observed for real powder systems. Further simulation tests were carried out to investigate the effects of particle size on the compaction behaviour of the two-dimensional, binary assemblies. Later work focused on the quasi-static compaction behaviour of three-dimensional assemblies, because they represented more realistic particle systems. The compaction behaviour of the assemblies during the simulation experiments was considered in terms of percolation theory concepts, as well as more familiar macroscopic and microstructural parameters. Percolation theory, which is based on ideas from statistical physics, has been found to be useful in the interpretation of the mechanical behaviour of simple, elastic lattices. However, from the evidence of this study, percolation theory is also able to offer a useful insight into the compaction behaviour of more realistic particle assemblies.

Interacting nonequilibrium systems with two temperatures

We investigate a simplified model of two fully connected magnetic systems maintained at different temperatures by virtue of being connected to two independent thermal baths while simultaneously being interconnected with each other. Using generating functional analysis, commonly used in statistical mechanics, we find exactly soluble expressions for their individual magnetization that define a two-dimensional nonlinear map, the equations of which have the same form as those obtained for densely connected equilibrium systems. Steady states correspond to the fixed points of this map, separating the parameter space into a rich set of nonequilibrium phases that we analyze in asymptotically high and low (nonequilibrium) temperature limits. The theoretical formalism is shown to revert to the classical nonequilibrium steady state problem for two interacting systems with a nonzero heat transfer between them that catalyzes a phase transition between ambient nonequilibrium states. © 2013 American Physical Society.

Investigation of two-wave mixing in arbitrary oriented sillenite crystals

A generalized systematic description of the Two-Wave Mixing (TWM) process in sillenite crystals allowing for arbitrary orientation of the grating vector is presented. An analytical expression for the TWM gain is obtained for the special case of plane waves in a thin crystal (|g|d«1) with large optical activity (|g|/?«1, g is the coupling constant, ? the rotatory power, d the crystal thickness). Using a two-dimensional formulation the scope of the nonlinear equations describing TWM can be extended to finite beams in arbitrary geometries and to any crystal parameters. Two promising applications of this formulation are proposed. The polarization dependence of the TWM gain is used for the flattening of Gaussian beam profiles without expanding them. The dependence of the TWM gain on the interaction length is used for the determination of the crystal orientation. Experiments carried out on Bi12GeO20 crystals of a non-standard cut are in good agreement with the results of modelling.

CFD and bubble column reactors:simulation and experiment

The simulation of two-phase flow in bubble columns using commercially available software fromFluent Incorporated is presented here. Data from a bubble column with a ratio of height to thecolumn diameter of 5 : 1 are compared with simulations and experimental results for time-averaged velocity and Reynolds stress proles are used to validate transient, two-dimensional simulations.The models are based on multiphase biological reactors with applications in the food industry. An example case of the mass transfer of oxygen through the liquid phase is also presented.

Linear stability of flow past two circular cylinders in a side-by-side arrangement

The linear stability of flow past two circular cylinders in a side-by-side arrangement is investigated theoretically, numerically and experimentally under the assumption of a two-dimensional flow field, in order to explore the origin of in-phase and antiphase oscillatory flows. Steady symmetric flow is realized at a small Reynolds number, but becomes unstable above a critical Reynolds number though the solution corresponding to the flow still satisfies the basic equations irrespective of the magnitude of the Reynolds number. We obtained the solution numerically and investigated its linear stability. We found that there are two kinds of unstable modes, i.e., antisymmetric and symmetric modes, which lead to in-phase and antiphase oscillatory flows, respectively. We determined the critical Reynolds numbers for the two modes and evaluated the critical distance at which the most unstable disturbance changes from the antisymmetric to the symmetric mode, or vice versa. ©2005 The Physical Society of Japan.