A robust,accurate, sensitive LC–MS/MS method to measure indoxyl sulfate,validated for plasma and kidney cells

Proximal tubular damage is an important prognostic determinant in various chronic kidney diseases (CKDs). Currently available diagnostic methods do not allow for early disease detection and are neither efficient. Indoxyl sulfate (IS) is an endogenous metabolite and protein-bound uremic toxin that is eliminated via renal secretion, but accumulates in plasma during tubular dysfunction. Therefore, it may be suitable as a tubular function marker. To evaluate this, a fast bioanalytical method was developed and validated for IS in various species and a kidney cell line using LC–MS/MS. An isotope-labeled IS potassium salt as an internal standard and acetonitrile (ACN) as a protein precipitant were used for sample pretreatment. The analyte was separated on a Polaris 3 C18-A column by gradient elution using 0.1% formic acid in water and ACN, and detected by negative electrospray ionization in selected reaction monitoring mode. The within-day (≤ 4.0%) and between-day (≤ 4.3%) precisions and accuracies (97.7 to 107.3%) were within the acceptable range. The analyte showed sufficient stability at all conditions investigated. Finally, applying this assay, significantly higher plasma and lower urine concentrations of IS were observed in mice with diabetic nephropathy with tubular damage, which encourages validation toward its use as a biomarker.     

New hybrid Cartesian cut cell/enriched multipoint flux approximation approach for modelling and quantification of structural uncertainties in petroleum reservoirs

Efficient and profitable oil production is subject to make reliable predictions about reservoir performance. However, restricted knowledge about reservoir rock and fluid properties and its geometrical structure calls for history matching in which the reservoir model is calibrated to emulate the field observed history. Such an inverse problem yields multiple history‐matched models, which might result in different predictions of reservoir performance. Uncertainty quantification narrows down the model uncertainties and boosts the model reliability for the forecasts of future reservoir behaviour. Conventional approaches of uncertainty quantification ignore large‐scale uncertainties related to reservoir structure, while structural uncertainties can influence the reservoir forecasts more significantly compared with petrophysical uncertainty. Quantification of structural uncertainty has been usually considered impracticable because of the need for global regridding at each step of history matching process. To resolve this obstacle, we develop an efficient methodology based on Cartesian cut cell method that decouples the model from its representation onto the grid and allows uncertain structures to be varied as a part of history matching process. Reduced numerical accuracy due to cell degeneracies in the vicinity of geological structures is adequately compensated with an enhanced scheme of a class of locally conservative flux continuous methods (extended enriched multipoint flux approximation method or extended EMPFA). The robustness and consistency of the proposed hybrid Cartesian cut cell/extended EMPFA approach are demonstrated in terms of true representation of geological structures influence on flow behaviour. Significant improvements in the quality of reservoir recovery forecasts and reservoir volume estimation are presented for synthetic model of uncertain structures. Copyright © 2015 John Wiley & Sons, Ltd.     

High-pressure behaviour of an X-ray preionized discharge pumped XeCl laser

The output characteristics are described of an X-ray preionized discharge pumped XeCl laser, fed by a low-impedance pulse forming line (PFL), at pressures up to 12 bar. The influence of a multichannel rail gap placed between the PFL and the laser head on the output energy was studied. We found an increase of output energy with increasing pressure up to 8 bar. At higher pressures a saturation behaviour was found. The maximum output energy per unit volume was 6.5 J/l.     

Confocal fluorescence lifetime imaging of free calcium in single cells

Ca²⁺ concentrations in biological cells are widely studied with fluorescent probes. The probes have a high selectivity for free calcium and exhibit marked changes in their photophysical properties upon binding. The differences in the fluorescent lifetime of the probes can now be used as a contrast mechanism for imaging purposes. This technique can be further exploited for the quantitative determination of ion concentrations within the cells. We describe the use of a fast fluorescence lifetime imaging method in combination with a standard confocal laser scanning microscope for the determination of Ca²⁺ concentrations in single rat cardiac myocytes using the intensity probe Calcium Green.     

IMPROVEMENT OF FLUIDIZABILITY OF FINE POWDERS ——A COMPUTER STUDY

Simulations of the gas fluidization of a cohesive powder were performed using the Stokesian Dynamics method and an agglomeration-deagglomeration model to investigate methods of improving the fluidizability of fine powders. Three techniques (a) high gas velocity (b) vibration-assisted fluidization and (c) tapered fluidizer were used in the simulations which provided detailed information on the bed microscopy such as the motion of 1 O0 particles in a fluidizing vessel along with the formation and destruction of cohesive bonds dudng collisions. While all three techniques were found to effectively improve the fluidizability of a strongly cohesive powder, we suggest a combination of high velocity fluidization assisted by extemal vibration of the fluidized bed to minimize entrainment of particles.     

Efficient integration of stiff kinetics with phase change detection for reactive reservoir processes

We propose the use of implicit one-step Explicit Singly Diagonal Implicit Runge–Kutta (ESDIRK) methods for integration of the stiff kinetics in reactive, compositional and thermal processes that are solved using operator-splitting type approaches. To facilitate the algorithmic development we construct a virtual kinetic cell model. The model serves both as a tool for the development and testing of tailored solvers as well as a testbed for studying the interactions between chemical kinetics and phase behavior. As case study, two chemical kinetics models with 6 and 14 components, respectively, are implemented for in situ combustion, a thermal oil recovery process. Through benchmark studies using the 14 component reaction model the new ESDIRK solvers are shown to improve computational speed when compared to the widely used multi-step BDF methods DASSL and LSODE. Phase changes are known to cause convergence problems for the integration method. We propose an algorithm for detection and location of phase changes based on discrete event system theory. Experiments show that the algorithm improves the robustness of the integration process near phase boundaries by lowering the number convergence and error test failures by more than 50% compared to direct integration without the new algorithm.     

Robust Multi-D Transport Schemes with Reduced Grid Orientation Effects

In this paper we investigate truly multi-D upwind schemes for simulating adverse mobility ratio displacements in porous media. Due to an underlying physical instability at the simulation scale, numerical results are highly sensitive to discretization errors and hence the orientation of the underlying computational grid. We use modified equations analysis to predict preferred flow angles on structured grids for several popular methods and present a conservative, multi-D framework for designing positive upwind schemes for general velocity fields. After placing the common schemes in this framework, we go on to develop a novel scheme with “minimal” constant transverse (cross-wind) diffusion. Results for miscible gas injection into homogeneous and heterogeneous media demonstrate that truly multi-D schemes, and in particular our new scheme, greatly reduce grid orientation effects and numerical biasing as compared to dimensional upwinding.     

Probing the Different Life Stages of a Fluid Catalytic Cracking Particle with Integrated Laser and Electron Microscopy

While cycling through a fluid catalytic cracking (FCC) unit, the structure and performance of FCC catalyst particles are severely affected. In this study, we set out to characterize the damage to commercial equilibrium catalyst particles, further denoted as ECat samples, and map the different pathways involved in their deactivation in a practical unit. The degradation was studied on a structural and a functional level. Transmission electron microscopy (TEM) of ECat samples revealed several structural features; including zeolite crystals that were partly or fully severed, mesoporous, macroporous, and/or amorphous. These defects were then correlated to structural features observed in FCC particles that were treated with different levels of hydrothermal deactivation. This allowed us not only to identify which features observed in ECat samples were a result of hydrothermal deactivation, but also to determine the severity of treatments resulting in these defects. For functional characterization of the ECat sample, the Brønsted acidity within individual FCC particles was studied by a selective fluorescent probe reaction with 4‐fluorostyrene. Integrated laser and electron microscopy (iLEM) allowed correlating this Brønsted acidity to structural features by combining a fluorescence and a transmission electron microscope in a single set‐up. Together, these analyses allowed us to postulate a plausible model for the degradation of zeolite crystals in FCC particles in the ECat sample. Furthermore, the distribution of the various deactivation processes within particles of different ages was studied. A rim of completely deactivated zeolites surrounding each particle in the ECat sample was identified by using iLEM. These zeolites, which were never observed in fresh or steam‐deactivated samples, contained clots of dense structures. The structures are proposed to be carbonaceous deposits formed during the cracking process, and seem resistant towards burning off during catalyst regeneration.     

A Ninhydrin‐Type Urea Sorbent for the Development of a Wearable Artificial Kidney

The aim of this study is to develop polymeric chemisorbents with a high density of ninhydrin groups, able to covalently bind urea under physiological conditions and thus potentially suitable for use in a wearable artificial kidney. Macroporous beads are prepared by suspension polymerization of 5‐vinyl‐1‐indanone (vinylindanone) using a 90:10 (v/v) mixture of toluene and nitrobenzene as a porogen. The indanone groups are subsequently oxidized in a one‐step procedure into ninhydrin groups. Their urea absorption kinetics are evaluated under both static and dynamic conditions at 37 °C in simulated dialysate (urea in phosphate buffered saline). Under static conditions and at a 1:1 molar ratio of ninhydrin: urea the sorbent beads remove ≈0.6–0.7 mmol g^?1 and under dynamic conditions and at a 2:1 molar excess of ninhydrin ≈0.6 mmol urea g^?1 sorbent in 8 h at 37 °C, which is a step toward a wearable artificial kidney.