Commentary: Using the convection-dispersion model and transit time density functions in the analysis of organ distribution kinetics

The convection-dispersion model and its extended form have been used to describe solute disposition in organs and to predict hepatic availabilities. A range of empirical transit-time density functions has also been used for a similar purpose. The use of the dispersion model with mixed boundary conditions and transit-time density functions has been queried recently by Hisaka and Sugiyanaa in this journal. We suggest that, consistent with soil science and chemical engineering literature, the mixed boundary conditions are appropriate providing concentrations are defined in terms of flux to ensure continuity at the boundaries and mass balance. It is suggested that the use of the inverse Gaussian or other functions as empirical transit-time densities is independent of any boundary condition consideration. The mixed boundary condition solutions of the convection-dispersion model are the easiest to use when linear kinetics applies. In contrast, the closed conditions are easier to apply in a numerical analysis of nonlinear disposition of solutes in organs. We therefore argue that the use of hepatic elimination models should be based on pragmatic considerations, giving emphasis to using the simplest or easiest solution that will give a sufficiently accurate prediction of hepatic pharmacokinetics for a particular application. (C) 2000 Wiley-Liss Inc. and the American Pharmaceutical Association J Pharm Sci 89:1579-1586, 2000.

Analysis of multicomponent adsorption kinetics on activated carbon

An integrated mathematical model for the kinetics of multicomponent adsorption on microporous carbon was developed. Transport in this bidisperse solid is represented by balance equations in the macropore and micropore phases, in which gas-phase diffusion dominates the mass transfer in the macropores, with the phenomenological diffusivities represented by the generalized Maxwell-Stefan (GMS) formulation. Viscous flow also contributes to the macropore fluxes and is included in the MS expressions. Diffusion of the adsorbed phase controls the mass transfer in the micro ore phase, p which is also described in a similar way by the MS method. The adsorption isotherms are represented by a new heterogeneous modified vacancy solution theory formulation of adsorption, which has proved to be a robust method for adsorption on activated carbons. The model is applied to the coadsorption and codesorption of C2H6 and C3H8 on Ajax and Norit carbon, as well as the displacement on Ajax carbon. The effect of the viscous flow in the macropore phase is not significant for the cases studied. The model accurately predicts the overshoot behavior and rollup of C2H6 during coadsorption. The prediction for the heavier compound C3H8 is always satisfactory, though at higher C3H8 mole fraction, the overshoot extent of C2H6 is overpredicted, possibly due to neglect of heat effects.

Kinetics of martensitic transitions in Cu-Al-Mn under thermal cycling: Analysis at multiple length scales

In this paper we study the evolution of the kinetic features of the martensitic transition in a Cu-Al-Mn single crystal under thermal cycling. The use of several experimental techniques including optical microscopy, calorimetry, and acoustic emission, has enabled us to perform an analysis at multiple scales. In particular, we have focused on the analysis of avalanche events (associated with the nucleation and growth of martensitic domains), which occur during the transition. There are significant differences between the kinetics at large and small length scales. On the one hand, at small length scales, small avalanche events tend to sum to give new larger events in subsequent loops. On the other hand, at large length scales the large domains tend to split into smaller ones on thermal cycling. We suggest that such different behavior is the necessary ingredient that leads the system to the final critical state corresponding to a power-law distribution of avalanches.

Animal manure phosphorus characterization by sequential chemical fractionation, release kinetics and 31P-NMR analysis

Phosphate release kinetics from manures are of global interest because sustainable plant nutrition with phosphate will be a major concern in the future. Although information on the bioavailability and chemical composition of P present in manure used as fertilizer are important to understand its dynamics in the soil, such studies are still scarce. Therefore, P extraction was evaluated in this study by sequential chemical fractionation, desorption with anion-cation exchange resin and 31P nuclear magnetic resonance (31P-NMR) spectroscopy to assess the P forms in three different dry manure types (i.e. poultry, cattle and swine manure). All three methods showed that the P forms in poultry, cattle and swine dry manures are mostly inorganic and highly bioavailable. The estimated P pools showed that organic and recalcitrant P forms were negligible and highly dependent on the Ca:P ratio in manures. The results obtained here showed that the extraction of P with these three different methods allows a better understanding and complete characterization of the P pools present in the manures.

Kinetics of martensitic transitions in Cu-Al-Mn under thermal cycling: Analysis at multiple length scales

In this paper we study the evolution of the kinetic features of the martensitic transition in a Cu-Al-Mn single crystal under thermal cycling. The use of several experimental techniques including optical microscopy, calorimetry, and acoustic emission, has enabled us to perform an analysis at multiple scales. In particular, we have focused on the analysis of avalanche events (associated with the nucleation and growth of martensitic domains), which occur during the transition. There are significant differences between the kinetics at large and small length scales. On the one hand, at small length scales, small avalanche events tend to sum to give new larger events in subsequent loops. On the other hand, at large length scales the large domains tend to split into smaller ones on thermal cycling. We suggest that such different behavior is the necessary ingredient that leads the system to the final critical state corresponding to a power-law distribution of avalanches.

A comparison of two time-domain analysis procedures in the determination of VO2 kinetics by pseudorandom binary sequence exercise testing

The purpose of this study was to apply and compare two time-domain analysis procedures in the determination of oxygen uptake (VO2) kinetics in response to a pseudorandom binary sequence (PRBS) exercise test. PRBS exercise tests have typically been analysed in the frequency domain. However, the complex interpretation of frequency responses may have limited the application of this procedure in both sporting and clinical contexts, where a single time measurement would facilitate subject comparison. The relative potential of both a mean response time (MRT) and a peak cross-correlation time (PCCT) was investigated. This study was divided into two parts: a test-retest reliability study (part A), in which 10 healthy male subjects completed two identical PRBS exercise tests, and a comparison of the VO2 kinetics of 12 elite endurance runners (ER) and 12 elite sprinters (SR; part B). In part A, 95% limits of agreement were calculated for comparison between MRT and PCCT. The results of part A showed no significant difference between test and retest as assessed by MRT [mean (SD) 42.2 (4.2) s and 43.8 (6.9) s] or by PCCT [21.8 (3.7) s and 22.7 (4.5) s]. Measurement error (%) was lower for MRT in comparison with PCCT (16% and 25%, respectively). In part B of the study, the VO2 kinetics of ER were significantly faster than those of SR, as assessed by MRT [33.4 (3.4) s and 39.9 (7.1) s, respectively; P<0.01] and PCCT [20.9 (3.8) s and 24.8 (4.5) s; P < 0.05]. It is possible that either analysis procedure could provide a single test measurement Of VO2 kinetics; however, the greater reliability of the MRT data suggests that this method has more potential for development in the assessment Of VO2 kinetics by PRBS exercise testing.

Dielectric thermal analysis as a tool for quantitative-evaluation of the viscosity and the kinetics of epoxy resin cure

Dielectric thermal analysis has been proved as a valuable tool for monitoring the epoxy curing process and the related rheological properties in the fabrication of polymer-matrix composite materials. This technique also has the potential to be applied in the monitoring of magnet impregnation processes as well as in quality control. In this work we present the quantitative evaluation of the viscosity changing and the curing kinetics for a commercial Stycast epoxy resin system at different temperatures through the impedance analysis. The results showed correlation between the real component of the complex impedance and the isothermal reaction extent. Comparing the dielectric analysis result with the viscosity measured by rotational rheometer we observed a similar behavior reported for dynamic mechanic analysis. The results comparison have shown that the kinetics parameters obtained from DSC and DETA analysis showed different sensitivities related to the characteristics of curing stages. We concluded that the dielectric thermal analysis should be applied in quantitative evaluation of cure kinetics.

Analysis of the kinetics of phase and amplitude gratings recorded in azopolymer films

In this work we use a stabilized holographic technique to study both refractive index and absorption gratings recorded in thin films made of Disperse Red 1 (DR1) embedded in an organic polymer matrix (PMMA) deposited on glass substrate. Gratings are recorded by linearly polarized illumination with the interference pattern of two crossing beams. One of the beams is phase modulated and the interference signals between the transmitted and diffracted waves are detected by a tuned lock-in amplifier. The technique allows measuring separately changes of the refractive index and the absorption coefficient during the course of the photoreaction process. The time evolution of the diffraction efficiencies during recording has shown bi-exponential kinetics for both gratings. © 2008 American Institute of Physics.

Evaluation of Decomposition Kinetics of Poly (Ether-Ether-Ketone) by Thermogravimetric Analysis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Corrosion kinetics and topography analysis of Ti-6Al-4V alloy subjected to different mouthwash solutions

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Microarray based real-time analysis of nucleic acid hybridization kinetics and thermodynamics

Ziel dieser Dissertation ist die experimentelle Charakterisierung und quantitative Beschreibung der Hybridisierung von komplementären Nukleinsäuresträngen mit oberflächengebundenen Fängermolekülen für die Entwicklung von integrierten Biosensoren. Im Gegensatz zu lösungsbasierten Verfahren ist mit Microarray Substraten die Untersuchung vieler Nukleinsäurekombinationen parallel möglich. Als biologisch relevantes Evaluierungssystem wurde das in Eukaryoten universell exprimierte Actin Gen aus unterschiedlichen Pflanzenspezies verwendet. Dieses Testsystem ermöglicht es, nahe verwandte Pflanzenarten auf Grund von geringen Unterschieden in der Gen-Sequenz (SNPs) zu charakterisieren. Aufbauend auf dieses gut studierte Modell eines House-Keeping Genes wurde ein umfassendes Microarray System, bestehend aus kurzen und langen Oligonukleotiden (mit eingebauten LNA-Molekülen), cDNAs sowie DNA und RNA Targets realisiert. Damit konnte ein für online Messung optimiertes Testsystem mit hohen Signalstärken entwickelt werden. Basierend auf den Ergebnissen wurde der gesamte Signalpfad von Nukleinsärekonzentration bis zum digitalen Wert modelliert. Die aus der Entwicklung und den Experimenten gewonnen Erkenntnisse über die Kinetik und Thermodynamik von Hybridisierung sind in drei Publikationen zusammengefasst die das Rückgrat dieser Dissertation bilden. Die erste Publikation beschreibt die Verbesserung der Reproduzierbarkeit und Spezifizität von Microarray Ergebnissen durch online Messung von Kinetik und Thermodynamik gegenüber endpunktbasierten Messungen mit Standard Microarrays. Für die Auswertung der riesigen Datenmengen wurden zwei Algorithmen entwickelt, eine reaktionskinetische Modellierung der Isothermen und ein auf der Fermi-Dirac Statistik beruhende Beschreibung des Schmelzüberganges. Diese Algorithmen werden in der zweiten Publikation beschrieben. Durch die Realisierung von gleichen Sequenzen in den chemisch unterschiedlichen Nukleinsäuren (DNA, RNA und LNA) ist es möglich, definierte Unterschiede in der Konformation des Riboserings und der C5-Methylgruppe der Pyrimidine zu untersuchen. Die kompetitive Wechselwirkung dieser unterschiedlichen Nukleinsäuren gleicher Sequenz und die Auswirkungen auf Kinetik und Thermodynamik ist das Thema der dritten Publikation. Neben der molekularbiologischen und technologischen Entwicklung im Bereich der Sensorik von Hybridisierungsreaktionen oberflächengebundener Nukleinsäuremolekülen, der automatisierten Auswertung und Modellierung der anfallenden Datenmengen und der damit verbundenen besseren quantitativen Beschreibung von Kinetik und Thermodynamik dieser Reaktionen tragen die Ergebnisse zum besseren Verständnis der physikalisch-chemischen Struktur des elementarsten biologischen Moleküls und seiner nach wie vor nicht vollständig verstandenen Spezifizität bei.

Analysis of human cytochrome P450 3A4 cooperativity: Construction and characterization of a site-directed mutant that displays hyperbolic steroid hydroxylation kinetics

Cytochrome P450 3A4 is generally considered to be the most important human drug-metabolizing enzyme and is known to catalyze the oxidation of a number of substrates in a cooperative manner. An allosteric mechanism is usually invoked to explain the cooperativity. Based on a structure–activity study from another laboratory using various effector–substrate combinations and on our own studies using site-directed mutagenesis and computer modeling of P450 3A4, the most likely location of effector binding is in the active site along with the substrate. Our study was designed to test this hypothesis by replacing residues Leu-211 and Asp-214 with the larger Phe and Glu, respectively. These residues were predicted to constitute a portion of the effector binding site, and the substitutions were designed to mimic the action of the effector by reducing the size of the active site. The L211F/D214E double mutant displayed an increased rate of testosterone and progesterone 6β-hydroxylation at low substrate concentrations and a decreased level of heterotropic stimulation elicited by α-naphthoflavone. Kinetic analyses of the double mutant revealed the absence of homotropic cooperativity with either steroid substrate. At low substrate concentrations the steroid 6β-hydroxylase activity of the wild-type enzyme was stimulated by a second steroid, whereas L211F/D214E displayed simple substrate inhibition. To analyze L211F/D214E at a more mechanistic level, spectral binding studies were carried out. Testosterone binding by the wild-type enzyme displayed homotropic cooperativity, whereas substrate binding by L211F/D214E displayed hyperbolic behavior.

Effects of Hypoxia on 13NH4+ Fluxes in Rice Roots1 : Kinetics and Compartmental Analysis

Techniques of compartmental (efflux) and kinetic influx analyses with the radiotracer 13NH4+ were used to examine the adaptation to hypoxia (15, 35, and 50% O2 saturation) of root N uptake and metabolism in 3-week-old hydroponically grown rice (Oryza sativa L., cv IR72) seedlings. A time-dependence study of NH4+ influx into rice roots after onset of hypoxia (15% O2) revealed an initial increase in the first 1 to 2.5 h after treatment imposition, followed by a decline to less than 50% of influx in control plants by 4 d. Efflux analyses conducted 0, 1, 3, and 5 d after the treatment confirmed this adaptation pattern of NH4+ uptake. Half-lives for NH4+ exchange with subcellular compartments, cytoplasmic NH4+ concentrations, and efflux (as percentage of influx) were unaffected by hypoxia. However, significant differences were observed in the relative amounts of N allocated to NH4+ assimilation and the vacuole versus translocation to the shoot. Kinetic experiments conducted at 100, 50, 35, and 15% O2 saturation showed no significant change in the Km value for NH4+ uptake with varying O2 supply. However, Vmax was 42% higher than controls at 50% O2 saturation, unchanged at 35%, and 10% lower than controls at 15% O2. The significance of these flux adaptations is discussed.

Effects of nitrogen sources on the nitrate assimilation in Haloferax mediterranei: growth kinetics and transcriptomic analysis

The haloarchaeon Haloferax mediterranei is able to grow in a defined culture media not only in the presence of inorganic nitrogen salt but also with amino acid as the sole nitrogen source. Assimilatory nitrate and nitrite reductases, respectively, catalyze the first and second reactions. The genes involved in this process are nasA, which encodes nitrate reductase and is found within the operon nasABC, and nasD, which encodes nitrite reductase. These genes are subjected to transcriptional regulation, being repressed in the presence of ammonium and induced with either nitrate or nitrite. This type of regulation has also been described when the amino acids are used as nitrogen source in the minimal media. Furthermore, it has been observed that the microorganism growth depends on nitrogen source, obtaining the lowest growth rate in the presence of nitrate and aspartate. In this paper, we present the results of a comparative study of microorganism growth and transcriptomic analysis of the operon nasABC and gene nasD in different nitrogen sources. The results are the first ever produced in relation to amino acids as nitrogen sources within the Halobacteriaceae family.