Quantitation and characterization of glutathionyl haemoglobin as an oxidative stress marker in chronic renal failure by mass spectrometry

Objectives: Glutathionyl haemoglobin (GS-Hb) belonging to the class of glutathionylated proteins has been investigated as a possible marker of oxidative stress in different chronic diseases. The purpose of this study was to examine whether glutathionyl haemoglobin can serve as an oxidative stress marker in non-diabetic chronic renal failure patients on different renal replacement therapies (RRT) through its quantitation, and characterization of the specific binding site of glutathione in haemoglobin molecule by mass spectrometric analysis. Design and methods: The study group consisted of non-diabetic chronic renal failure patients on renal replacement therapy (RRT): hemodialysis (HD), continuous ambulatory peritoneal dialysis (CAPD) and renal allograft transplant (Txp) patients. Haemoglobin samples of these subjects were analyzed by liquid chromatography electrospray ionization mass spectrometry for GS-Hb quantitation. Characterization of GS-Hb was done by tandem mass spectrometry. Levels of erythrocyte glutathione (GSH) and lipid peroxidation (as thiobarbituric acid reacting substances) were measured spectrophotometrically, while glycated baernoglobin (HbA1c) was measured by HPLC. Results: GS-Hb levels were markedly elevated in the dialysis group and marginally in the transplant group as compared to the controls. GS-Hb levels correlated positively with lipid peroxidation and negatively with the erythrocyte glutathione levels in RRT groups indicating enhanced oxidative stress. De novo sequencing of the chymotryptic fragment of GS-Hb established that glutathione is attached to Cys-93 of the beta globin chain. Mass spectrometric quantitation of total glycated haemoglobin showed good agreement with HbA1c estimation by conventional HPLC method. Conclusions: Glutathionyl haemoglobin can serve as a clinical marker of oxidative stress in chronic debilitating therapies like RRT. Mass spectrometry provides a reliable analytical tool for quantitation and residue level characterization of different post-translational modifications of haemoglobin. (c) 2007 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

A water model study of the flow asymmetry inside a continuous slab casting mold

The work studies the extent of asymmetric flow in water models of continuous casting molds of two different configurations. In the molds where fluid is discharged through multiple holes at the bottom, the flow pattern in the lower portion depends on the size of the lower two recirculating domains. If they reach the mold bottom, the flow pattern in the lower portion is symmetrical about the central plane; otherwise, it is asymmetrical. On the other hand, in the molds where the fluid is discharged through the entire mold cross section, the flow pattern is always asymmetrical if the aspect ratio is 1:6.25 or more. The fluid jet swirls while emerging through the nozzle. The interaction of the swirling Jets with the wide sidewalls of the mold gives rise to asymmetrical flow inside the mold. In the molds with lower aspect ratios, where the jets do not touch the wide side walls, the flow pattern is symmetrical about the central plane.

Structure and properties of two component hydrogels comprising lithocholic acid and organic amines

We demonstrate the aptitude of supramolecular hydrogel formation using simple bile acid such as lithocholic acid in aqueous solution in the presence of various dimeric or oligomeric amines. By variation of the choice of the amines in such mixtures the gelation properties could be modulated. However, the replacement of lithocholic acid (LCA) by cholic acid or deoxycholic acid resulted in no hydrogel formation. FT-IR studies confirm that the carboxylate and ammonium residues of the two components are involved in the salt (ion-pair) formation. This promotes further assembly of the components reinforced by a continuous hydrogen bonded network leading to gelation. Electron microscopy shows the morphology of the internal organization of gels of two component systems which also depends significantly on the amine part. Variation of the amine component from the simple 1,2-ethanediamine (EDA) to oligomeric amines in such gels of lithocholic acid changes the morphology of the assembly from long one-dimensional nanotubes to three-dimensional complex structures. Single crystal X-ray diffraction analysis with one of the amine-LCA complexes suggested the motif of fiber formation where the amines interact with the carboxylate and hydroxyl moieties through electrostatic forces and hydrogen bonding. From small angle neutron scattering study, it becomes clear that the weak gel from LCA-EDA shows scattering oscillation due to the presence of non-interacting nanotubules while for gels of LCA with oligomeric amines the individual fibers come together to form complex three-dimensional organizations of higher length scale. The rheological properties of this class of two component system provide clear evidence that the flow behavior can be modulated varying the acid-amine ratio.

A hydrodynamical study of the flow in renal tubules

The hydrodynamical problem of flow in proximal renal tubule is investigated by considering axisymmetric flow of a viscous, incompressible fluid through a long narrow tube of varying cross-section with reabsorption at the wall. Two cases for reabsorption have been studied (i) when the bulk flow,Q, decays exponentially with the axial distancex, and (ii) whenQ is an arbitrary function ofx such thatQ-Q 0 can be expressed as a Fourier integral (whereQ 0 is the flux atx=0). The analytic expressions for flow variables have been obtained by applying perturbation method in terms of wall parameter ε. The effects of ε on pressure drop across the tube, radial velocity and wall shear have been studied in the case of exponentially decaying bulk flow and it has been found that the results are in agreement with the existing ones for the renal tubules.

Optimal maintenance and replacement via a semi-Markov decision model

Optimal bang-coast maintenance policies for a machine, subject to failure, are considered. The approach utilizes a semi-Markov model for the system. A simplified model for modifying the probability of machine failure with maintenance is employed. A numerical example is presented to illustrate the procedure and results.

A Team of Continuous-Action Learning Automata for Noise-Tolerant Learning of Half-Spaces

Learning automata are adaptive decision making devices that are found useful in a variety of machine learning and pattern recognition applications. Although most learning automata methods deal with the case of finitely many actions for the automaton, there are also models of continuous-action-set learning automata (CALA). A team of such CALA can be useful in stochastic optimization problems where one has access only to noise-corrupted values of the objective function. In this paper, we present a novel formulation for noise-tolerant learning of linear classifiers using a CALA team. We consider the general case of nonuniform noise, where the probability that the class label of an example is wrong may be a function of the feature vector of the example. The objective is to learn the underlying separating hyperplane given only such noisy examples. We present an algorithm employing a team of CALA and prove, under some conditions on the class conditional densities, that the algorithm achieves noise-tolerant learning as long as the probability of wrong label for any example is less than 0.5. We also present some empirical results to illustrate the effectiveness of the algorithm.

Continuous Distribution Kinetics for Photopolymerization of Alkyl Methacrylates

The photopolymerization of methyl,ethyl,butyl, and hexyl methacrylates in solution was studied. The effect of initial initiator and monomer concentrations on the time evolution of polymer concentration (M) over bar (n) and PDI was examined. The reversible chain addition and beta-scission, and primary radical termination steps were included in the mechanism along with the classical steps. The rate equations were derived using continuous distribution kinetics and solved numerically to fit the experimental data. The regressed rate coefficients compared well with the literature data. The model predicted the instantaneous increase in (M) over bar (n) and PDI to steady state values. The rate coefficients exhibited a linear increase with the size of alkyl chain of the alkyl methacrylates.

Continuous-Flow Surface Aeration Systems

An aeration process in ail activated sludge plant is a continuous-flow system. In this system, there is a steady input flow (flow from the primary clarifier or settling tank with some part from the secondary clarifier or secondary settling tank) and output flow connection to the secondary clarifier or settling tank. The experimental and numerical results obtained through batch systems can not be relied on and applied for the designing of a continuous aeration tank. In order to scale up laboratory results for field application, it is imperative to know the geometric parameters of a continuous system. Geometric parameters have a greater influence on the mass transfer process of surface aeration systems. The present work establishes the optimal geometric configuration of a continuous-flow surface aeration system. It is found that the maintenance of these optimal geometric parameters systems result in maximum aeration efficiency. By maintaining the obtained optimal geometric parameters, further experiments are conducted in continuous-flow surface aerators with three different sizes in order to develop design curves correlating the oxygen transfer coefficient and power number with the rotor speed. The design methodology to implement the presently developed optimal geometric parameters and correlation equations for field application is discussed.

Replacement of water on a steel substrate by a surrounding oil reservoir

With an objective to replace a water droplet from a steel surface by oil we study here the impact of injecting a hydrophilic/lipophilic surfactant into the droplet or into the surrounding oil reservoir. Contact angle goniometery, Grazing angle FTIR spectroscopy and Atomic force microscopy are used to record the oil/water interfacial tension, surface energetics of the substrate under the oil and water phases as well as the corresponding physical states of the substrates. Such energetics reflect the rate at which the excess surfactant molecules accumulate at the water/oil interface and desorb into the phases. The molecules diffuse into the substrate from the phases and build up specific molecular configurations which, with the interfacial tension, control the non-equilibrium progress of and the equilibrium status of the contact line. The study shows that the most efficient replacement of water by the surrounding oil happens when a surfactant is sparingly soluble in the supplier oil phase and highly soluble in the recipient water phase.

Simultaneous material selection and geometry design of statically determinate trusses using continuous optimization

In this work, we explore simultaneous geometry design and material selection for statically determinate trusses by posing it as a continuous optimization problem. The underlying principles of our approach are structural optimization and Ashby’s procedure for material selection from a database. For simplicity and ease of initial implementation, only static loads are considered in this work with the intent of maximum stiffness, minimum weight/cost, and safety against failure. Safety of tensile and compression members in the truss is treated differently to prevent yield and buckling failures, respectively. Geometry variables such as lengths and orientations of members are taken to be the design variables in an assumed layout. Areas of cross-section of the members are determined to satisfy the failure constraints in each member. Along the lines of Ashby’s material indices, a new design index is derived for trusses. The design index helps in choosing the most suitable material for any geometry of the truss. Using the design index, both the design space and the material database are searched simultaneously using gradient-based optimization algorithms. The important feature of our approach is that the formulated optimization problem is continuous, although the material selection from a database is an inherently discrete problem. A few illustrative examples are included. It is observed that the method is capable of determining the optimal topology in addition to optimal geometry when the assumed layout contains more links than are necessary for optimality.

Rendering stiffer walls: a hybrid haptic system using continuous and discrete time feedback

Instability in conventional haptic rendering destroys the perception of rigid objects in virtual environments. Inherent limitations in the conventional haptic loop restrict the maximum stiffness that can be rendered. In this paper we present a method to render virtual walls that are much stiffer than those achieved by conventional techniques. By removing the conventional digital haptic loop and replacing it with a part-continuous and part-discrete time hybrid haptic loop, we were able to render stiffer walls. The control loop is implemented as a combinational logic circuit on an field-programmable gate array. We compared the performance of the conventional haptic loop and our hybrid haptic loop on the same haptic device, and present mathematical analysis to show the limit of stability of our device. Our hybrid method removes the computer-intensive haptic loop from the CPU-this can free a significant amount of resources that can be used for other purposes such as graphical rendering and physics modeling. It is our hope that, in the future, similar designs will lead to a haptics processing unit (HPU).

Analysis of continuous beams—a three dimensional elasticity solution

A three dimensional elasticity solution for the analysis of beams continuous over an infinite number of equally spaced supports has been given. The beam has been subjected to normal tractions on its two opposite faces and these loads are identical over each span. The other two faces are traction free. Numerical results have been given for different cases when the beam is loaded on its bottom face. The results obtained have been compared with the results of two dimensional elasticity solution.

Characterization of a continuous CO2 laser-welded Fe-Cu dissimilar couple

Continuous CO2 laser welding of an Fe-Cu dissimilar couple in a butt-weld geometry at different process conditions is studied. The process conditions are varied to identify and characterize the microstructural features that are independent of the welding mode. The study presents a characterization of the microstructure and mechanical properties of the welds. Detailed microstructural analysis of the weld/base-metal interface shows features that are different on the two sides of the weld. The iron side can grow into the weld with a local change in length scale, whereas the interface on the copper side indicates a barrier to growth. The interface is jagged, and a banded microstructure consisting of iron-rich layers could be observed next to the weld/Cu interface. The observations suggest that solidification initiates inside the melt, where iron and copper are mixed due to convective flow. The transmission electron microscopy (TEM) of the weld region also indicates the occasional presence of droplets of iron and copper. The microstructural observations are rationalized using arguments drawn from a thermodynamic analysis of the Fe-Cu system.

A novel approach for large-scale polypeptide folding based on elastic networks using continuous optimization

We present a new computationally efficient method for large-scale polypeptide folding using coarse-grained elastic networks and gradient-based continuous optimization techniques. The folding is governed by minimization of energy based on Miyazawa–Jernigan contact potentials. Using this method we are able to substantially reduce the computation time on ordinary desktop computers for simulation of polypeptide folding starting from a fully unfolded state. We compare our results with available native state structures from Protein Data Bank (PDB) for a few de-novo proteins and two natural proteins, Ubiquitin and Lysozyme. Based on our simulations we are able to draw the energy landscape for a small de-novo protein, Chignolin. We also use two well known protein structure prediction software, MODELLER and GROMACS to compare our results. In the end, we show how a modification of normal elastic network model can lead to higher accuracy and lower time required for simulation.