Use of reduction rate as a quantitative knob for controlling the twin structure and shape of palladium nanocrystals.

PubMed

Wang, Yi; Peng, Hsin-Chieh; Liu, Jingyue; Huang, Cheng Zhi; Xia, Younan

2015-02-11

Kinetic control is a powerful means for maneuvering the twin structure and shape of metal nanocrystals and thus optimizing their performance in a variety of applications. However, there is only a vague understanding of the explicit roles played by reaction kinetics due to the lack of quantitative information about the kinetic parameters. With Pd as an example, here we demonstrate that kinetic parameters, including rate constant and activation energy, can be derived from spectroscopic measurements and then used to calculate the initial reduction rate and further have this parameter quantitatively correlated with the twin structure of a seed and nanocrystal. On a quantitative basis, we were able to determine the ranges of initial reduction rates required for the formation of nanocrystals with a specific twin structure, including single-crystal, multiply twinned, and stacking fault-lined. This work represents a major step forward toward the deterministic syntheses of colloidal noble-metal nanocrystals with specific twin structures and shapes.

Kinetics of Cation and Oxyanion Adsorption and Desorption on Ferrihydrite: Roles of Ferrihydrite Binding Sites and a Unified Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tian, Lei; Shi, Zhenqing; Lu, Yang

Understanding the kinetics of toxic ion reactions with ferrihydrite is crucial for predicting the dynamic behavior of contaminants in soil environments. In this study, the kinetics of As(V), Cr(VI), Cu, and Pb adsorption and desorption on ferrihydrite were investigated with a combination of laboratory macroscopic experiments, microscopic investigation and mechanistic modeling. The rates of As(V), Cr(VI), Cu, and Pb adsorption and desorption on ferrihydrite, as systematically studied using a stirred-flow method, was highly dependent on the reaction pH and metal concentrations and varied significantly among four metals. Spherical aberration-corrected scanning transmission electron microscopy (Cs-STEM) showed, at sub-nano scales, all fourmore » metals were distributed within the ferrihydrite particle aggregates homogeneously after adsorption reactions, with no evidence of surface diffusion-controlled processes. Based on experimental results, we developed a unifying kinetics model for both cation and oxyanion adsorption/desorption on ferrihydrite based on the mechanistic-based equilibrium model CD-MUSIC. Overall, the model described the kinetic results well, and we quantitatively demonstrated how the equilibrium properties of the cation and oxyanion binding to various ferrihydrite sites affected the adsorption and desorption rates. Our results provided a unifying quantitative modeling method for the kinetics of both cation and oxyanion adsorption/desorption on iron minerals.« less

Kinetic Analysis of Rhodamines Efflux Mediated by the Multidrug Resistance Protein (MRP1)

PubMed Central

Saengkhae, Chantarawan; Loetchutinat, Chatchanok; Garnier-Suillerot, Arlette

2003-01-01

Characterization of rhodamine 123 as functional assay for MDR has been primarily focused on P-glycoprotein-mediated MDR. Several studies have suggested that Rh123 is also a substrate for MRP1. However, no quantitative studies of the MRP1-mediated efflux of rhodamines have, up to now, been performed. Measurement of the kinetic characteristics of substrate transport is a powerful approach to enhancing our understanding of their function and mechanism. In the present study, we have used a continuous fluorescence assay with four rhodamine dyes (rhodamine 6G, tetramethylrosamine, tetramethylrhodamine ethyl ester, and tetramethylrhodamine methyl ester) to quantify drug transport by MRP1 in living GLC4/ADR cells. The formation of a substrate concentration gradient was observed. MRP1-mediated transport of rhodamine was glutathione-dependent. The kinetics parameter, ka = VM/km, was very similar for the four rhodamine analogs but ∼10-fold less than the values of the same parameter determined previously for the MRP1-mediated efflux of anthracycline. The findings presented here are the first to show quantitative information about the kinetics parameters for MRP1-mediated efflux of rhodamine dyes. PMID:12944313

Computational modeling approaches to quantitative structure-binding kinetics relationships in drug discovery.

PubMed

De Benedetti, Pier G; Fanelli, Francesca

2018-03-21

Simple comparative correlation analyses and quantitative structure-kinetics relationship (QSKR) models highlight the interplay of kinetic rates and binding affinity as an essential feature in drug design and discovery. The choice of the molecular series, and their structural variations, used in QSKR modeling is fundamental to understanding the mechanistic implications of ligand and/or drug-target binding and/or unbinding processes. Here, we discuss the implications of linear correlations between kinetic rates and binding affinity constants and the relevance of the computational approaches to QSKR modeling. Copyright © 2018 Elsevier Ltd. All rights reserved.

A ten-week biochemistry lab project studying wild-type and mutant bacterial alkaline phosphatase.

PubMed

Witherow, D Scott

2016-11-12

This work describes a 10-week laboratory project studying wild-type and mutant bacterial alkaline phosphatase, in which students purify, quantitate, and perform kinetic assays on wild-type and selected mutants of the enzyme. Students also perform plasmid DNA purification, digestion, and gel analysis. In addition to simply learning important techniques, students acquire novel biochemical data in their kinetic analysis of mutant enzymes. The experiments are designed to build on students' work from week to week in a way that requires them to apply quantitative analysis and reasoning skills, reinforcing traditional textbook biochemical concepts. Students are assessed through lab reports focused on journal style writing, quantitative and conceptual question sheets, and traditional exams. © 2016 by The International Union of Biochemistry and Molecular Biology, 44(6):555-564, 2016. © 2016 The International Union of Biochemistry and Molecular Biology.

Monochloramine disinfection kinetics of Nitrosomonas europaea by propidium monoazide quantitative PCR and Live/Dead BacLight Methods

EPA Science Inventory

Monochloramine disinfection kinetics were determined for the pure culture ammonia-oxidizing bacterium Nitrosomonas europaea (ATCC 19718) by two culture independent methods: (1) LIVE/DEAD® BacLight™ (LD) and (2) propidium monoazide quantitative PCR (PMA-qPCR). Both methods were f...

An Integrated Qualitative and Quantitative Biochemical Model Learning Framework Using Evolutionary Strategy and Simulated Annealing.

PubMed

Wu, Zujian; Pang, Wei; Coghill, George M

2015-01-01

Both qualitative and quantitative model learning frameworks for biochemical systems have been studied in computational systems biology. In this research, after introducing two forms of pre-defined component patterns to represent biochemical models, we propose an integrative qualitative and quantitative modelling framework for inferring biochemical systems. In the proposed framework, interactions between reactants in the candidate models for a target biochemical system are evolved and eventually identified by the application of a qualitative model learning approach with an evolution strategy. Kinetic rates of the models generated from qualitative model learning are then further optimised by employing a quantitative approach with simulated annealing. Experimental results indicate that our proposed integrative framework is feasible to learn the relationships between biochemical reactants qualitatively and to make the model replicate the behaviours of the target system by optimising the kinetic rates quantitatively. Moreover, potential reactants of a target biochemical system can be discovered by hypothesising complex reactants in the synthetic models. Based on the biochemical models learned from the proposed framework, biologists can further perform experimental study in wet laboratory. In this way, natural biochemical systems can be better understood.

Kinetic method for the large-scale analysis of the binding mechanism of histone deacetylase inhibitors.

PubMed

Meyners, Christian; Baud, Matthias G J; Fuchter, Matthew J; Meyer-Almes, Franz-Josef

2014-09-01

Performing kinetic studies on protein ligand interactions provides important information on complex formation and dissociation. Beside kinetic parameters such as association rates and residence times, kinetic experiments also reveal insights into reaction mechanisms. Exploiting intrinsic tryptophan fluorescence a parallelized high-throughput Förster resonance energy transfer (FRET)-based reporter displacement assay with very low protein consumption was developed to enable the large-scale kinetic characterization of the binding of ligands to recombinant human histone deacetylases (HDACs) and a bacterial histone deacetylase-like amidohydrolase (HDAH) from Bordetella/Alcaligenes. For the binding of trichostatin A (TSA), suberoylanilide hydroxamic acid (SAHA), and two other SAHA derivatives to HDAH, two different modes of action, simple one-step binding and a two-step mechanism comprising initial binding and induced fit, were verified. In contrast to HDAH, all compounds bound to human HDAC1, HDAC6, and HDAC8 through a two-step mechanism. A quantitative view on the inhibitor-HDAC systems revealed two types of interaction, fast binding and slow dissociation. We provide arguments for the thesis that the relationship between quantitative kinetic and mechanistic information and chemical structures of compounds will serve as a valuable tool for drug optimization. Copyright © 2014 Elsevier Inc. All rights reserved.

Swelling-induced optical anisotropy of thermoresponsive hydrogels based on poly(2-(2-methoxyethoxy)ethyl methacrylate): deswelling kinetics probed by quantitative Mueller matrix polarimetry.

PubMed

Patil, Nagaraj; Soni, Jalpa; Ghosh, Nirmalya; De, Priyadarsi

2012-11-29

Thermodynamically favored polymer-water interactions below the lower critical solution temperature (LCST) caused swelling-induced optical anisotropy (linear retardance) of thermoresponsive hydrogels based on poly(2-(2-methoxyethoxy)ethyl methacrylate). This was exploited to study the macroscopic deswelling kinetics quantitatively by a generalized polarimetry analysis method, based on measurement of the Mueller matrix and its subsequent inverse analysis via the polar decomposition approach. The derived medium polarization parameters, namely, linear retardance (δ), diattenuation (d), and depolarization coefficient (Δ), of the hydrogels showed interesting differences between the gels prepared by conventional free radical polymerization (FRP) and reversible addition-fragmentation chain transfer polymerization (RAFT) and also between dry and swollen state. The effect of temperature, cross-linking density, and polymerization technique employed to synthesize hydrogel on deswelling kinetics was systematically studied via conventional gravimetry and corroborated further with the corresponding Mueller matrix derived quantitative polarimetry characteristics (δ, d, and Δ). The RAFT gels exhibited higher swelling ratio and swelling-induced optical anisotropy compared to FRP gels and also deswelled faster at 30 °C. On the contrary, at 45 °C, deswelling was significantly retarded for the RAFT gels due to formation of a skin layer, which was confirmed and quantified via the enhanced diattenuation and depolarization parameters.

Quantitative kinetic theory of active matter

NASA Astrophysics Data System (ADS)

Ihle, Thomas; Chou, Yen-Liang

2014-03-01

Models of self-driven agents similar to the Vicsek model [Phys. Rev. Lett. 75 (1995) 1226] are studied by means of kinetic theory. In these models, particles try to align their travel directions with the average direction of their neighbours. At strong alignment a globally ordered state of collective motion forms. An Enskog-like kinetic theory is derived from the exact Chapman-Kolmogorov equation in phase space using Boltzmann's mean-field approximation of molecular chaos. The kinetic equation is solved numerically by a nonlocal Lattice-Boltzmann-like algorithm. Steep soliton-like waves are observed that lead to an abrupt jump of the global order parameter if the noise level is changed. The shape of the wave is shown to follow a novel scaling law and to quantitatively agree within 3 % with agent-based simulations at large particle speeds. This provides a mean-field mechanism to change the second-order character of the flocking transition to first order. Diagrammatic techniques are used to investigate small particle speeds, where the mean-field assumption of Molecular Chaos is invalid and where correlation effects need to be included.

Quantitative collision induced mass spectrometry of substituted piperazines - A correlative analysis between theory and experiment

NASA Astrophysics Data System (ADS)

Ivanova, Bojidarka; Spiteller, Michael

2017-12-01

The present paper deals with quantitative kinetics and thermodynamics of collision induced dissociation (CID) reactions of piperazines under different experimental conditions together with a systematic description of effect of counter-ions on common MS fragment reactions of piperazines; and intra-molecular effect of quaternary cyclization of substituted piperazines yielding to quaternary salts. There are discussed quantitative model equations of rate constants as well as free Gibbs energies of series of m-independent CID fragment processes in GP, which have been evidenced experimentally. Both kinetic and thermodynamic parameters are also predicted by computational density functional theory (DFT) and ab initio both static and dynamic methods. The paper examines validity of Maxwell-Boltzmann distribution to non-Boltzmann CID processes in quantitatively as well. The experiments conducted within the latter framework yield to an excellent correspondence with theoretical quantum chemical modeling. The important property of presented model equations of reaction kinetics is the applicability in predicting unknown and assigning of known mass spectrometric (MS) patterns. The nature of "GP" continuum of CID-MS coupled scheme of measurements with electrospray ionization (ESI) source is discussed, performing parallel computations in gas-phase (GP) and polar continuum at different temperatures and ionic strengths. The effect of pressure is presented. The study contributes significantly to methodological and phenomenological developments of CID-MS and its analytical implementations for quantitative and structural analyses. It also demonstrates great prospective of a complementary application of experimental CID-MS and computational quantum chemistry studying chemical reactivity, among others. To a considerable extend this work underlies the place of computational quantum chemistry to the field of experimental analytical chemistry in particular highlighting the structural analysis.

Quantitative Förster resonance energy transfer analysis for kinetic determinations of SUMO-specific protease.

PubMed

Liu, Yan; Song, Yang; Madahar, Vipul; Liao, Jiayu

2012-03-01

Förster resonance energy transfer (FRET) technology has been widely used in biological and biomedical research, and it is a very powerful tool for elucidating protein interactions in either dynamic or steady state. SUMOylation (the process of SUMO [small ubiquitin-like modifier] conjugation to substrates) is an important posttranslational protein modification with critical roles in multiple biological processes. Conjugating SUMO to substrates requires an enzymatic cascade. Sentrin/SUMO-specific proteases (SENPs) act as an endopeptidase to process the pre-SUMO or as an isopeptidase to deconjugate SUMO from its substrate. To fully understand the roles of SENPs in the SUMOylation cycle, it is critical to understand their kinetics. Here, we report a novel development of a quantitative FRET-based protease assay for SENP1 kinetic parameter determination. The assay is based on the quantitative analysis of the FRET signal from the total fluorescent signal at acceptor emission wavelength, which consists of three components: donor (CyPet-SUMO1) emission, acceptor (YPet) emission, and FRET signal during the digestion process. Subsequently, we developed novel theoretical and experimental procedures to determine the kinetic parameters, k(cat), K(M), and catalytic efficiency (k(cat)/K(M)) of catalytic domain SENP1 toward pre-SUMO1. Importantly, the general principles of this quantitative FRET-based protease kinetic determination can be applied to other proteases. Copyright © 2011 Elsevier Inc. All rights reserved.

A global resource allocation strategy governs growth transition kinetics of Escherichia coli

PubMed Central

Erickson, David W; Schink, Severin J.; Patsalo, Vadim; Williamson, James R.; Gerland, Ulrich; Hwa, Terence

2018-01-01

A grand challenge of systems biology is to predict the kinetic responses of living systems to perturbations starting from the underlying molecular interactions. Changes in the nutrient environment have long been used to study regulation and adaptation phenomena in microorganisms1–3 and they remain a topic of active investigation4–11. Although much is known about the molecular interactions that govern the regulation of key metabolic processes in response to applied perturbations12–17, they are insufficiently quantified for predictive bottom-up modelling. Here we develop a top-down approach, expanding the recently established coarse-grained proteome allocation models15,18–20 from steady-state growth into the kinetic regime. Using only qualitative knowledge of the underlying regulatory processes and imposing the condition of flux balance, we derive a quantitative model of bacterial growth transitions that is independent of inaccessible kinetic parameters. The resulting flux-controlled regulation model accurately predicts the time course of gene expression and biomass accumulation in response to carbon upshifts and downshifts (for example, diauxic shifts) without adjustable parameters. As predicted by the model and validated by quantitative proteomics, cells exhibit suboptimal recovery kinetics in response to nutrient shifts owing to a rigid strategy of protein synthesis allocation, which is not directed towards alleviating specific metabolic bottlenecks. Our approach does not rely on kinetic parameters, and therefore points to a theoretical framework for describing a broad range of such kinetic processes without detailed knowledge of the underlying biochemical reactions. PMID:29072300

Determination of the Effects of Medium Composition on the Monochloramine Disinfection Kinetics of Nitrosomonas europaea by the Propidium Monoazide Quantitative PCR and Live/Dead BacLight Methods

EPA Science Inventory

Various media compositions (phosphate 1-50 mM; ionic strength 2.8-150 meq/L) significantly affected Nitrosomonas europaea monochloramine disinfection kinetics determined by Live/Dead BacLight (LD) and propidium monoazide quantitative PCR (PMA-qPCR) methods (lag coefficient 37-490...

Comparison of three-way and four-way calibration for the real-time quantitative analysis of drug hydrolysis in complex dynamic samples by excitation-emission matrix fluorescence.

PubMed

Yin, Xiao-Li; Gu, Hui-Wen; Liu, Xiao-Lu; Zhang, Shan-Hui; Wu, Hai-Long

2018-03-05

Multiway calibration in combination with spectroscopic technique is an attractive tool for online or real-time monitoring of target analyte(s) in complex samples. However, how to choose a suitable multiway calibration method for the resolution of spectroscopic-kinetic data is a troubling problem in practical application. In this work, for the first time, three-way and four-way fluorescence-kinetic data arrays were generated during the real-time monitoring of the hydrolysis of irinotecan (CPT-11) in human plasma by excitation-emission matrix fluorescence. Alternating normalization-weighted error (ANWE) and alternating penalty trilinear decomposition (APTLD) were used as three-way calibration for the decomposition of the three-way kinetic data array, whereas alternating weighted residual constraint quadrilinear decomposition (AWRCQLD) and alternating penalty quadrilinear decomposition (APQLD) were applied as four-way calibration to the four-way kinetic data array. The quantitative results of the two kinds of calibration models were fully compared from the perspective of predicted real-time concentrations, spiked recoveries of initial concentration, and analytical figures of merit. The comparison study demonstrated that both three-way and four-way calibration models could achieve real-time quantitative analysis of the hydrolysis of CPT-11 in human plasma under certain conditions. However, it was also found that both of them possess some critical advantages and shortcomings during the process of dynamic analysis. The conclusions obtained in this paper can provide some helpful guidance for the reasonable selection of multiway calibration models to achieve the real-time quantitative analysis of target analyte(s) in complex dynamic systems. Copyright © 2017 Elsevier B.V. All rights reserved.

Quantitation of TGF-beta1 mRNA in porcine mesangial cells by comparative kinetic RT/PCR: comparison with ribonuclease protection assay and in situ hybridization.

PubMed

Ceol, M; Forino, M; Gambaro, G; Sauer, U; Schleicher, E D; D'Angelo, A; Anglani, F

2001-01-01

Gene expression can be examined with different techniques including ribonuclease protection assay (RPA), in situ hybridisation (ISH), and quantitative reverse transcription-polymerase chain reaction (RT/PCR). These methods differ considerably in their sensitivity and precision in detecting and quantifying low abundance mRNA. Although there is evidence that RT/PCR can be performed in a quantitative manner, the quantitative capacity of this method is generally underestimated. To demonstrate that the comparative kinetic RT/PCR strategy-which uses a housekeeping gene as internal standard-is a quantitative method to detect significant differences in mRNA levels between different samples, the inhibitory effect of heparin on phorbol 12-myristate 13-acetate (PMA)-induced-TGF-beta1 mRNA expression was evaluated by RT/PCR and RPA, the standard method of mRNA quantification, and the results were compared. The reproducibility of RT/PCR amplification was calculated by comparing the quantity of G3PDH and TGF-beta1 PCR products, generated during the exponential phases, estimated from two different RT/PCR (G3PDH, r = 0.968, P = 0.0000; TGF-beta1, r = 0.966, P = 0.0000). The quantitative capacity of comparative kinetic RT/PCR was demonstrated by comparing the results obtained from RPA and RT/PCR using linear regression analysis. Starting from the same RNA extraction, but using only 1% of the RNA for the RT/PCR compared to RPA, significant correlation was observed (r = 0.984, P = 0.0004). Moreover the morphometric analysis of ISH signal was applied for the semi-quantitative evaluation of the expression and localisation of TGF-beta1 mRNA in the entire cell population. Our results demonstrate the close similarity of the RT/PCR and RPA methods in giving quantitative information on mRNA expression and indicate the possibility to adopt the comparative kinetic RT/PCR as reliable quantitative method of mRNA analysis. Copyright 2001 Wiley-Liss, Inc.

Quantitative proteomics reveals the kinetics of trypsin-catalyzed protein digestion.

PubMed

Pan, Yanbo; Cheng, Kai; Mao, Jiawei; Liu, Fangjie; Liu, Jing; Ye, Mingliang; Zou, Hanfa

2014-10-01

Trypsin is the popular protease to digest proteins into peptides in shotgun proteomics, but few studies have attempted to systematically investigate the kinetics of trypsin-catalyzed protein digestion in proteome samples. In this study, we applied quantitative proteomics via triplex stable isotope dimethyl labeling to investigate the kinetics of trypsin-catalyzed cleavage. It was found that trypsin cleaves the C-terminal to lysine (K) and arginine (R) residues with higher rates for R. And the cleavage sites surrounded by neutral residues could be quickly cut, while those with neighboring charged residues (D/E/K/R) or proline residue (P) could be slowly cut. In a proteome sample, a huge number of proteins with different physical chemical properties coexists. If any type of protein could be preferably digested, then limited digestion could be applied to reduce the sample complexity. However, we found that protein abundance and other physicochemical properties, such as molecular weight (Mw), grand average of hydropathicity (GRAVY), aliphatic index, and isoelectric point (pI) have no notable correlation with digestion priority of proteins.

Determination of the Effects of Medium Composition on the Monochloramine Disinfection Kinetics of Nitrosomonas europaea by the Propidium Monoazide Quantitative PCR and Live/Dead BacLight Methods ▿

PubMed Central

Wahman, David G.; Schrantz, Karen A.; Pressman, Jonathan G.

2010-01-01

Various medium compositions (phosphate, 1 to 50 mM; ionic strength, 2.8 to 150 meq/liter) significantly affected Nitrosomonas europaea monochloramine disinfection kinetics, as determined by the Live/Dead BacLight (LD) and propidium monoazide quantitative PCR (PMA-qPCR) methods (lag coefficient, 37 to 490 [LD] and 91 to 490 [PMA-qPCR] mg·min/liter; Chick-Watson rate constant, 4.0 × 10−3 to 9.3 × 10−3 [LD] and 1.6 × 10−3 to 9.6 × 10−3 [PMA-qPCR] liter/mg·min). Two competing effects may account for the variation in disinfection kinetic parameters: (i) increasing kinetics (disinfection rate constant [k] increased, lag coefficient [b] decreased) with increasing phosphate concentration and (ii) decreasing kinetics (k decreased, b increased) with increasing ionic strength. The results support development of a standard medium for evaluating disinfection kinetics in drinking water. PMID:20952645

Effects of Convective Transport of Solute and Impurities on Defect-Causing Kinetics Instabilities in Protein Crystallization

NASA Technical Reports Server (NTRS)

Vekilov, Peter G.

2002-01-01

The objective of the proposed research is to obtain further insight into the onset and development of the defect-causing instabilities that anise due to the coupling of the bulk transport and nonlinear-interfacial kinetics during growth in the mixed regime, utilizing the reduction of the convective contribution to the bulk transport under microgravity. These studies will build upon the data on the effects of quantitative variations of the forced convection velocity on the averaged and time-dependent kinetic behavior of protein crystal growth systems that have recently been obtained in our laboratory.

Quantitative Investigation of Protein-Nucleic Acid Interactions by Biosensor Surface Plasmon Resonance.

PubMed

Wang, Shuo; Poon, Gregory M K; Wilson, W David

2015-01-01

Biosensor-surface plasmon resonance (SPR) technology has emerged as a powerful label-free approach for the study of nucleic acid interactions in real time. The method provides simultaneous equilibrium and kinetic characterization for biomolecular interactions with low sample requirements and without the need for external probes. A detailed and practical guide for protein-DNA interaction analyses using biosensor-SPR methods is presented. Details of SPR technology and basic fundamentals are described with recommendations on the preparation of the SPR instrument, sensor chips and samples, experimental design, quantitative and qualitative data analyses and presentation. A specific example of the interaction of a transcription factor with DNA is provided with results evaluated by both kinetic and steady-state SPR methods.

Rate Constants and Mechanisms of Protein–Ligand Binding

PubMed Central

Pang, Xiaodong; Zhou, Huan-Xiang

2017-01-01

Whereas protein–ligand binding affinities have long-established prominence, binding rate constants and binding mechanisms have gained increasing attention in recent years. Both new computational methods and new experimental techniques have been developed to characterize the latter properties. It is now realized that binding mechanisms, like binding rate constants, can and should be quantitatively determined. In this review, we summarize studies and synthesize ideas on several topics in the hope of providing a coherent picture of and physical insight into binding kinetics. The topics include microscopic formulation of the kinetic problem and its reduction to simple rate equations; computation of binding rate constants; quantitative determination of binding mechanisms; and elucidation of physical factors that control binding rate constants and mechanisms. PMID:28375732

The Kelvin-Helmholtz instability of boundary-layer plasmas in the kinetic regime

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steinbusch, Benedikt, E-mail: b.steinbusch@fz-juelich.de; Gibbon, Paul, E-mail: p.gibbon@fz-juelich.de; Department of Mathematics, Centre for Mathematical Plasma Astrophysics, Katholieke Universiteit Leuven

2016-05-15

The dynamics of the Kelvin-Helmholtz instability are investigated in the kinetic, high-frequency regime with a novel, two-dimensional, mesh-free tree code. In contrast to earlier studies which focused on specially prepared equilibrium configurations in order to compare with fluid theory, a more naturally occurring plasma-vacuum boundary layer is considered here with relevance to both space plasma and linear plasma devices. Quantitative comparisons of the linear phase are made between the fluid and kinetic models. After establishing the validity of this technique via comparison to linear theory and conventional particle-in-cell simulation for classical benchmark problems, a quantitative analysis of the more complexmore » magnetized plasma-vacuum layer is presented and discussed. It is found that in this scenario, the finite Larmor orbits of the ions result in significant departures from the effective shear velocity and width underlying the instability growth, leading to generally slower development and stronger nonlinear coupling between fast growing short-wavelength modes and longer wavelengths.« less

An adaptive bias - hybrid MD/kMC algorithm for protein folding and aggregation.

PubMed

Peter, Emanuel K; Shea, Joan-Emma

2017-07-05

In this paper, we present a novel hybrid Molecular Dynamics/kinetic Monte Carlo (MD/kMC) algorithm and apply it to protein folding and aggregation in explicit solvent. The new algorithm uses a dynamical definition of biases throughout the MD component of the simulation, normalized in relation to the unbiased forces. The algorithm guarantees sampling of the underlying ensemble in dependency of one average linear coupling factor 〈α〉 τ . We test the validity of the kinetics in simulations of dialanine and compare dihedral transition kinetics with long-time MD-simulations. We find that for low 〈α〉 τ values, kinetics are in good quantitative agreement. In folding simulations of TrpCage and TrpZip4 in explicit solvent, we also find good quantitative agreement with experimental results and prior MD/kMC simulations. Finally, we apply our algorithm to study growth of the Alzheimer Amyloid Aβ 16-22 fibril by monomer addition. We observe two possible binding modes, one at the extremity of the fibril (elongation) and one on the surface of the fibril (lateral growth), on timescales ranging from ns to 8 μs.

Comparison of dynamic contrast-enhanced MRI parameters of breast lesions at 1.5 and 3.0 T: a pilot study

PubMed Central

Pineda, F D; Medved, M; Fan, X; Ivancevic, M K; Abe, H; Shimauchi, A; Newstead, G M

2015-01-01

Objective: To compare dynamic contrast-enhanced (DCE) MRI parameters from scans of breast lesions at 1.5 and 3.0 T. Methods: 11 patients underwent paired MRI examinations in both Philips 1.5 and 3.0 T systems (Best, Netherlands) using a standard clinical fat-suppressed, T1 weighted DCE-MRI protocol, with 70–76 s temporal resolution. Signal intensity vs time curves were fit with an empirical mathematical model to obtain semi-quantitative measures of uptake and washout rates as well as time-to-peak enhancement (TTP). Maximum percent enhancement and signal enhancement ratio (SER) were also measured for each lesion. Percent differences between parameters measured at the two field strengths were compared. Results: TTP and SER parameters measured at 1.5 and 3.0 T were similar; with mean absolute differences of 19% and 22%, respectively. Maximum percent signal enhancement was significantly higher at 3 T than at 1.5 T (p = 0.006). Qualitative assessment showed that image quality was significantly higher at 3 T (p = 0.005). Conclusion: Our results suggest that TTP and SER are more robust to field strength change than other measured kinetic parameters, and therefore measurements of these parameters can be more easily standardized than measurements of other parameters derived from DCE-MRI. Semi-quantitative measures of overall kinetic curve shape showed higher reproducibility than do discrete classification of kinetic curve early and delayed phases in a majority of the cases studied. Advances in knowledge: Qualitative measures of curve shape are not consistent across field strength even when acquisition parameters are standardized. Quantitative measures of overall kinetic curve shape, by contrast, have higher reproducibility. PMID:25785918

A novel robust quantitative Förster resonance energy transfer assay for protease SENP2 kinetics determination against its all natural substrates.

PubMed

Liu, Yan; Shen, Yali; Zheng, Shasha; Liao, Jiayu

2015-12-01

SUMOylation (the process of adding the SUMO [small ubiquitin-like modifier] to substrates) is an important post-translational modification of critical proteins in multiple processes. Sentrin/SUMO-specific proteases (SENPs) act as endopeptidases to process the pre-SUMO or as isopeptidases to deconjugate the SUMO from its substrate. Determining the kinetics of SENPs is important for understanding their activities. Förster resonance energy transfer (FRET) technology has been widely used in biomedical research and is a powerful tool for elucidating protein interactions. In this paper we report a novel quantitative FRET-based protease assay for SENP2 endopeptidase activity that accounts for the self-fluorescent emissions of the donor (CyPet) and the acceptor (YPet). The kinetic parameters, k(cat), K(M), and catalytic efficiency (k(cat)/K(M)) of catalytic domain SENP2 toward pre-SUMO1/2/3, were obtained by this novel design. Although we use SENP2 to demonstrate our method, the general principles of this quantitative FRET-based protease kinetic determination can be readily applied to other proteases.

Oxidation kinetics of Si and SiGe by dry rapid thermal oxidation, in-situ steam generation oxidation and dry furnace oxidation

NASA Astrophysics Data System (ADS)

Rozé, Fabien; Gourhant, Olivier; Blanquet, Elisabeth; Bertin, François; Juhel, Marc; Abbate, Francesco; Pribat, Clément; Duru, Romain

2017-06-01

The fabrication of ultrathin compressively strained SiGe-On-Insulator layers by the condensation technique is likely a key milestone towards low-power and high performances FD-SOI logic devices. However, the SiGe condensation technique still requires challenges to be solved for an optimized use in an industrial environment. SiGe oxidation kinetics, upon which the condensation technique is founded, has still not reached a consensus in spite of various studies which gave insights into the matter. This paper aims to bridge the gaps between these studies by covering various oxidation processes relevant to today's technological needs with a new and quantitative analysis methodology. We thus address oxidation kinetics of SiGe with three Ge concentrations (0%, 10%, and 30%) by means of dry rapid thermal oxidation, in-situ steam generation oxidation, and dry furnace oxidation. Oxide thicknesses in the 50 Å to 150 Å range grown with oxidation temperatures between 850 and 1100 °C were targeted. The present work shows first that for all investigated processes, oxidation follows a parabolic regime even for thin oxides, which indicates a diffusion-limited oxidation regime. We also observe that, for all investigated processes, the SiGe oxidation rate is systematically higher than that of Si. The amplitude of the variation of oxidation kinetics of SiGe with respect to Si is found to be strongly dependent on the process type. Second, a new quantitative analysis methodology of oxidation kinetics is introduced. This methodology allows us to highlight the dependence of oxidation kinetics on the Ge concentration at the oxidation interface, which is modulated by the pile-up mechanism. Our results show that the oxidation rate increases with the Ge concentration at the oxidation interface.

Kinetic quantitation of cerebral PET-FDG studies without concurrent blood sampling: statistical recovery of the arterial input function.

PubMed

O'Sullivan, F; Kirrane, J; Muzi, M; O'Sullivan, J N; Spence, A M; Mankoff, D A; Krohn, K A

2010-03-01

Kinetic quantitation of dynamic positron emission tomography (PET) studies via compartmental modeling usually requires the time-course of the radio-tracer concentration in the arterial blood as an arterial input function (AIF). For human and animal imaging applications, significant practical difficulties are associated with direct arterial sampling and as a result there is substantial interest in alternative methods that require no blood sampling at the time of the study. A fixed population template input function derived from prior experience with directly sampled arterial curves is one possibility. Image-based extraction, including requisite adjustment for spillover and recovery, is another approach. The present work considers a hybrid statistical approach based on a penalty formulation in which the information derived from a priori studies is combined in a Bayesian manner with information contained in the sampled image data in order to obtain an input function estimate. The absolute scaling of the input is achieved by an empirical calibration equation involving the injected dose together with the subject's weight, height and gender. The technique is illustrated in the context of (18)F -Fluorodeoxyglucose (FDG) PET studies in humans. A collection of 79 arterially sampled FDG blood curves are used as a basis for a priori characterization of input function variability, including scaling characteristics. Data from a series of 12 dynamic cerebral FDG PET studies in normal subjects are used to evaluate the performance of the penalty-based AIF estimation technique. The focus of evaluations is on quantitation of FDG kinetics over a set of 10 regional brain structures. As well as the new method, a fixed population template AIF and a direct AIF estimate based on segmentation are also considered. Kinetics analyses resulting from these three AIFs are compared with those resulting from radially sampled AIFs. The proposed penalty-based AIF extraction method is found to achieve significant improvements over the fixed template and the segmentation methods. As well as achieving acceptable kinetic parameter accuracy, the quality of fit of the region of interest (ROI) time-course data based on the extracted AIF, matches results based on arterially sampled AIFs. In comparison, significant deviation in the estimation of FDG flux and degradation in ROI data fit are found with the template and segmentation methods. The proposed AIF extraction method is recommended for practical use.

Determination of cell metabolite VEGF₁₆₅ and dynamic analysis of protein-DNA interactions by combination of microfluidic technique and luminescent switch-on probe.

PubMed

Lin, Xuexia; Leung, Ka-Ho; Lin, Ling; Lin, Luyao; Lin, Sheng; Leung, Chung-Hang; Ma, Dik-Lung; Lin, Jin-Ming

2016-05-15

In this paper, we rationally design a novel G-quadruplex-selective luminescent iridium (III) complex for rapid detection of oligonucleotide and VEGF165 in microfluidics. This new probe is applied as a convenient biosensor for label-free quantitative analysis of VEGF165 protein from cell metabolism, as well as for studying the kinetics of the aptamer-protein interaction combination with a microfluidic platform. As a result, we have successfully established a quantitative analysis of VEGF165 from cell metabolism. Furthermore, based on the principles of hydrodynamic focusing and diffusive mixing, different transient states during kinetics process were monitored and recorded. Thus, the combination of microfluidic technique and G-quadruplex luminescent probe will be potentially applied in the studies of intramolecular interactions and molecule recognition in the future. Copyright © 2015 Elsevier B.V. All rights reserved.

Simulation studies of plasma waves in the electron foreshock - The transition from reactive to kinetic instability

NASA Technical Reports Server (NTRS)

Dum, C. T.

1990-01-01

Particle simulation experiments were used to analyze the electron beam-plasma instability. It is shown that there is a transition from the reactive state of the electron beam-plasma instability to the kinetic instability of Langmuir waves. Quantitative tests, which include an evaluation of the dispersion relation for the evolving non-Maxwellian beam distribution, show that a quasi-linear theory describes the onset of this transition and applies again fully to the kinetic stage. This stage is practically identical to the late stage seen in simulations of plasma waves in the electron foreshock described by Dum (1990).

Stoichiometric and kinetic analysis of extreme halophilic Archaea on various substrates in a corrosion resistant bioreactor.

PubMed

Lorantfy, Bettina; Seyer, Bernhard; Herwig, Christoph

2014-01-25

Extreme halophilic Archaea are extremophile species which can thrive in hypersaline environments of up to 3-5 M sodium chloride concentration. Although their ecology and physiology are widely identified on the microbiological level, little emphasis has been laid on quantitative bioprocess development with extreme halophiles. The goal of this study was to establish, on the one hand, a methodological basis for quantitative bioprocess analysis of extreme halophilic Archaea with an extreme halophilic strain as an example. Firstly, as a novel usage, a corrosion resistant bioreactor setup for extreme halophiles has been implemented. Then, paying special attention to total bioprocess quantification approaches, an indirect method for biomass quantification using on-line process signals was introduced. Subsequently, robust quantitative data evaluation methods for halophiles could be developed, providing defined and controlled cultivation conditions in the bioreactor and therefore obtaining suitable quality of on-line as well as off-line datasets. On the other hand, new physiological results of extreme halophiles in bioreactor have also been obtained based on the quantitative methodological tools. For the first time, quantitative data on stoichiometry and kinetics were collected and evaluated on different carbon sources. The results on various substrates were interpreted, with proposed metabolic mechanisms, by linking to the reported primary carbon metabolism of extreme halophilic Archaea. Moreover, results of chemostat cultures demonstrated that extreme halophilic organisms show Monod-kinetics on different sole carbon sources. A diauxic growth pattern was described on a mixture of substrates in batch cultivations. In addition, the methodologies presented here enable one to characterize the utilized strain Haloferax mediterranei (HFX) as a potential new host organism. Thus, this study offers a strong methodological basis as well as a fundamental physiological assessment for bioreactor quantification of extreme halophiles that can serve as primary knowledge for applications of extreme halophiles in biotechnology. Copyright © 2013 Elsevier B.V. All rights reserved.

Purfication kinetics of beryllium during vacuum induction melting

NASA Technical Reports Server (NTRS)

Mukherjee, J. L.; Gupta, K. P.; Li, C. H.

1972-01-01

The kinetics of evaporation in binary alloys were quantitatively treated. The formalism so developed works well for several systems studied. The kinetics of purification of beryllium was studied through evaporation data actually acquired during vacuum induction melting. Normal evaporation equations are shown to be generally valid and useful for understanding the kinetics of beryllium purification. The normal evaporation analysis has been extended to cover cases of limited liquid diffusion. It was shown that under steady-state evaporation, the solute concentration near the surface may be up to six orders of magnitude different from the bulk concentration. Corrections for limited liquid diffusion are definitely needed for the highly evaporative solute elements, such as Zn, Mg, and Na, for which the computed evaporation times are improved by five orders of magnitude. The commonly observed logarithmic relation between evaporation time and final concentration further supports the validity of the normal evaporation equations.

The sublimation kinetics of GeSe single crystals

NASA Technical Reports Server (NTRS)

Irene, E. A.; Wiedemeier, H.

1975-01-01

The sublimation kinetics of (001) oriented GeSe single crystal platelets was studied by high-temperature mass spectroscopy, quantitative vacuum microbalance techniques, and hot stage optical microscopy. For a mean experimental temperature of 563 K, the activation enthalpy and entropy are found to equal 32.3 kcal/mole and 19.1 eu, respectively. The vaporization coefficient is less than unity for the range of test temperatures, and decreases with increasing temperature. The combined experimental data are correlated by means of a multistep surface adsorption mechanism.

Nucleation and growth in cluster dynamics: A quantitative test of the classical kinetic approach

NASA Astrophysics Data System (ADS)

Gránásy, László; James, Peter F.

2000-12-01

Nucleation and size dependent growth of nanometer sized crystalline particles in glassy media have been studied by numerically solving the Turnbull-Fisher master equations that describe the time evolution of cluster population. Time dependencies of the formation rate and number density are determined for large clusters (built of up to 2×105 formula units, containing 1.8×106 atoms). We demonstrate that the formation rate and number density of such clusters are well approximated by Shneidman's asymptotically exact analytical solution. A quantitative test of the kinetic Turnbull-Fisher model has been performed: Evaluating the kinetic coefficients and interfacial parameters from the transient time and steady-state nucleation rates measured on six stoichiometric oxide glass compositions (lithium-disilicate, barium-disilicate, lithium-diborate, wollastonite, 1:2:3 and 2:1:3 soda-lime-silica glass compositions), we calculated the macroscopic growth rates and compared with experiments. For wollastonite, lithium-diborate and the 1:2:3 soda-lime-silica glass, differences of 2 to 4 orders of magnitude have been observed between theory and experiment. This inadequacy of the microscopic kinetic parameters in describing macroscopic growth cannot be explained by either the curvature effect on the interfacial free energy or the self-consistency correction for the cluster free energy. The origin of the discrepancy is discussed.

Endotoxin Detection in Pharmaceuticals and Medical Devices with Kinetic-QCL, a Kinetic-Quantitative Chromogenic Limulus Amebocyte Lysate Assay.

PubMed

Berzofsky, Ronald N.

1995-01-01

The observation that endotoxin caused gelation in extracts of Limulus amebocytes has been expanded to the development of an in vitro kinetic, quantitative chromogenic LAL assay (Kinetic-QCL) for the detection of endotoxin in aqueous fluids. Within the last 15 years, the use of Limulus amebocyte lysate to detect and control the presence of pyrogenic substances in pharmaceuticals and medical devices has gained wide international acceptance. Both the United States and European Pharmacopoeias contain descriptions of and requirements for the LAL Bacterial Endotoxin Test. Both pharmacopoeias have begun to remove the rabbit pyrogen test requirement in a majority of drug monographs and have substituted endotoxin limits to be determined by LAL. The use of LAL has proved invaluable in controlling the level of endotoxin in finished product. The endotoxin contribution of raw materials and packaging material can be monitored as well. In-process testing at critical production steps can identify additional sources of endotoxin contamination, and depyrogenation processes can be validated by quantitating the degradation of endotoxin challenges. The speed, reproducibility, sensitivity, and economics of the Kinetic-QCL assay, in conjunction with the ppropriate equipment and software, over both the in vivo rabbit pyrogen test and the more traditional LAL gel-clot assay allow a more in-depth approach to the control of endotoxin in pharmaceuticals and medical devices.

What happens in the skin? Integrating skin permeation kinetics into studies of developmental and reproductive toxicity following topical exposure.

PubMed

Dancik, Yuri; Bigliardi, Paul L; Bigliardi-Qi, Mei

2015-12-01

Animal-based developmental and reproductive toxicological studies involving skin exposure rarely incorporate information on skin permeation kinetics. For practical reasons, animal studies cannot investigate the many factors which can affect human skin permeation and systemic uptake kinetics in real-life scenarios. Traditional route-to-route extrapolation is based on the same types of experiments and requires assumptions regarding route similarity. Pharmacokinetic modeling based on skin physiology and structure is the most efficient way to incorporate the variety of intrinsic skin and exposure-dependent parameters occurring in clinical and occupational settings into one framework. Physiologically-based pharmacokinetic models enable the integration of available in vivo, in vitro and in silico data to quantitatively predict the kinetics of uptake at the site of interest, as needed for 21st century toxicology and risk assessment. As demonstrated herein, proper interpretation and integration of these data is a multidisciplinary endeavor requiring toxicological, risk assessment, mathematical, pharmaceutical, biological and dermatological expertise. Copyright © 2015 Elsevier Inc. All rights reserved.

Stress-dependence of kinetic transitions at atomistic defects

NASA Astrophysics Data System (ADS)

Ball, S. L.; Alexander, K. C.; Schuh, C. A.

2018-01-01

The full second-rank activation volume tensors associated with vacancy migration in FCC copper and HCP titanium as well as transition events in the Σ5 (2 1 0) grain boundary in copper are calculated and analyzed. The full tensorial results quantitatively illustrate how the conventional use of an activation volume scalar in atomistic studies of the kinetic processes of complex defects can miss important stress dependencies, in that neither hydrostatic pressure nor deviatoric stress dependencies can be considered alone as dominating the response. The results speak to the importance of anisotropies in the stress-dependence of atomistic kinetics, including crystal structure anisotropy, elastic anisotropy, and defect structure or migration-path anisotropies.

Three-dimensional drift kinetic response of high- β plasmas in the DIII-D tokamak

DOE PAGES

Wang, Zhirui R.; Lanctot, Matthew J.; Liu, Y. Q.; ...

2015-04-07

A quantitative interpretation of the experimentally measured high pressure plasma response to externally applied three-dimensional (3D) magnetic field perturbations, across the no-wall Troyon limit, is achieved. The key to success is the self-consistent inclusion of the drift kinetic resonance effects in numerical modeling using the MARS-K code. This resolves an outstanding issue of ideal magneto-hydrodynamic model, which signi cantly over-predicts the plasma induced field ampli fication near the no-wall limit, as compared to experiments. The self-consistent drift kinetic model leads to quantitative agreement not only for the measured 3D field amplitude and toroidal phase, but also for the measured internalmore » 3D displacement of the plasma.« less

Increased robustness of single-molecule counting with microfluidics, digital isothermal amplification, and a mobile phone versus real-time kinetic measurements.

PubMed

Selck, David A; Karymov, Mikhail A; Sun, Bing; Ismagilov, Rustem F

2013-11-19

Quantitative bioanalytical measurements are commonly performed in a kinetic format and are known to not be robust to perturbation that affects the kinetics itself or the measurement of kinetics. We hypothesized that the same measurements performed in a "digital" (single-molecule) format would show increased robustness to such perturbations. Here, we investigated the robustness of an amplification reaction (reverse-transcription loop-mediated amplification, RT-LAMP) in the context of fluctuations in temperature and time when this reaction is used for quantitative measurements of HIV-1 RNA molecules under limited-resource settings (LRS). The digital format that counts molecules using dRT-LAMP chemistry detected a 2-fold change in concentration of HIV-1 RNA despite a 6 °C temperature variation (p-value = 6.7 × 10(-7)), whereas the traditional kinetic (real-time) format did not (p-value = 0.25). Digital analysis was also robust to a 20 min change in reaction time, to poor imaging conditions obtained with a consumer cell-phone camera, and to automated cloud-based processing of these images (R(2) = 0.9997 vs true counts over a 100-fold dynamic range). Fluorescent output of multiplexed PCR amplification could also be imaged with the cell phone camera using flash as the excitation source. Many nonlinear amplification schemes based on organic, inorganic, and biochemical reactions have been developed, but their robustness is not well understood. This work implies that these chemistries may be significantly more robust in the digital, rather than kinetic, format. It also calls for theoretical studies to predict robustness of these chemistries and, more generally, to design robust reaction architectures. The SlipChip that we used here and other digital microfluidic technologies already exist to enable testing of these predictions. Such work may lead to identification or creation of robust amplification chemistries that enable rapid and precise quantitative molecular measurements under LRS. Furthermore, it may provide more general principles describing robustness of chemical and biological networks in digital formats.

Thermalization of oscillator chains with onsite anharmonicity and comparison with kinetic theory

DOE PAGES

Mendl, Christian B.; Lu, Jianfeng; Lukkarinen, Jani

2016-12-02

We perform microscopic molecular dynamics simulations of particle chains with an onsite anharmonicity to study relaxation of spatially homogeneous states to equilibrium, and directly compare the simulations with the corresponding Boltzmann-Peierls kinetic theory. The Wigner function serves as a common interface between the microscopic and kinetic level. We demonstrate quantitative agreement after an initial transient time interval. In particular, besides energy conservation, we observe the additional quasiconservation of the phonon density, defined via an ensemble average of the related microscopic field variables and exactly conserved by the kinetic equations. On superkinetic time scales, density quasiconservation is lost while energy remainsmore » conserved, and we find evidence for eventual relaxation of the density to its canonical ensemble value. Furthermore, the precise mechanism remains unknown and is not captured by the Boltzmann-Peierls equations.« less

Thermalization of oscillator chains with onsite anharmonicity and comparison with kinetic theory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mendl, Christian B.; Lu, Jianfeng; Lukkarinen, Jani

We perform microscopic molecular dynamics simulations of particle chains with an onsite anharmonicity to study relaxation of spatially homogeneous states to equilibrium, and directly compare the simulations with the corresponding Boltzmann-Peierls kinetic theory. The Wigner function serves as a common interface between the microscopic and kinetic level. We demonstrate quantitative agreement after an initial transient time interval. In particular, besides energy conservation, we observe the additional quasiconservation of the phonon density, defined via an ensemble average of the related microscopic field variables and exactly conserved by the kinetic equations. On superkinetic time scales, density quasiconservation is lost while energy remainsmore » conserved, and we find evidence for eventual relaxation of the density to its canonical ensemble value. Furthermore, the precise mechanism remains unknown and is not captured by the Boltzmann-Peierls equations.« less

Growth Kinetics of Intracellular RNA/Protein Droplets: Signature of a Liquid-Liquid Phase Transition?

NASA Astrophysics Data System (ADS)

Berry, Joel; Weber, Stephanie C.; Vaidya, Nilesh; Zhu, Lian; Haataja, Mikko; Brangwynne, Clifford P.

2015-03-01

Nonmembrane-bound organelles are functional, dynamic assemblies of RNA and/or protein that can self-assemble and disassemble within the cytoplasm or nucleoplasm. The possibility that underlying intracellular phase transitions may drive and mediate the morphological evolution of some membrane-less organelles has been supported by several recent studies. In this talk, results from a collaborative experimental-theoretical study of the growth and dissolution kinetics of nucleoli and extranucleolar droplets (ENDs) in C. elegans embryos will be presented. We have employed Flory-Huggins solution theory, reaction-diffusion kinetics, and quantitative statistical dynamic scaling analysis to characterize the specific growth mechanisms at work. Our findings indicate that both in vivo and in vitro droplet scaling and growth kinetics are consistent with those resulting from an equilibrium liquid-liquid phase transition mediated by passive nonequilibrium growth mechanisms - simultaneous Brownian coalescence and Ostwald ripening. This supports a view in which cells can employ phase transitions to drive structural organization, while utilizing active processes, such as local transcriptional activity, to fine tune the kinetics of these phase transitions in response to given conditions.

A Century of Enzyme Kinetic Analysis, 1913 to 2013

PubMed Central

Johnson, Kenneth A.

2013-01-01

This review traces the history and logical progression of methods for quantitative analysis of enzyme kinetics from the 1913 Michaelis and Menten paper to the application of modern computational methods today. Following a brief review of methods for fitting steady state kinetic data, modern methods are highlighted for fitting full progress curve kinetics based upon numerical integration of rate equations, including a re-analysis of the original Michaelis-Menten full time course kinetic data. Finally, several illustrations of modern transient state kinetic methods of analysis are shown which enable the elucidation of reactions occurring at the active sites of enzymes in order to relate structure and function. PMID:23850893

Kinetics and efficiency of the hydrated electron-induced dehalogenation by the sulfite/UV process.

PubMed

Li, Xuchun; Fang, Jingyun; Liu, Guifang; Zhang, Shujuan; Pan, Bingcai; Ma, Jun

2014-10-01

Hydrated electron (e(aq)(-)), which is listed among the most reactive reducing species, has great potential for removal and detoxification of recalcitrant contaminants. Here we provided quantitative insight into the availability and conversion of e(aq)(-) in a newly developed sulfite/UV process. Using monochloroacetic acid as a simple e(aq)(-)-probe, the e(aq)(-)-induced dehalogenation kinetics in synthetic and surface water was well predicted by the developed models. The models interpreted the complex roles of pH and S(IV), and also revealed the positive effects of UV intensity and temperature quantitatively. Impacts of humic acid, ferrous ion, carbonate/bicarbonate, and surface water matrix were also examined. Despite the retardation of dehalogenation by electron scavengers, the process was effective even in surface water. Efficiency of the process was discussed, and the optimization approaches were proposed. This study is believed to better understand the e(aq)(-)-induced dehalogenation by the sulfite/UV process in a quantitative manner, which is very important for its potential application in water treatment. Copyright © 2014 Elsevier Ltd. All rights reserved.

Quantitatively in Situ Imaging Silver Nanowire Hollowing Kinetics

DOE PAGES

Yu, Le; Yan, Zhongying; Cai, Zhonghou; ...

2016-09-28

We report the in-situ investigation of the morphological evolution of silver nanowires to hollow silver oxide nanotubes using transmission x-ray microscopy (TXM). Complex silver diffusion kinetics and hollowing process via the Kirkendall effect have been captured in real time. Further quantitative x-ray absorption analysis reveals the difference between the longitudinal and radial diffusions. In conclusion, the diffusion coefficient of silver in its oxide nanoshell is, for the first time, calculated to be 1.2 × 10 -13 cm 2/s from the geometrical parameters extracted from the TXM images.

Dimensionality of Motion and Binding Valency Govern Receptor-Ligand Kinetics As Revealed by Agent-Based Modeling.

PubMed

Lehnert, Teresa; Figge, Marc Thilo

2017-01-01

Mathematical modeling and computer simulations have become an integral part of modern biological research. The strength of theoretical approaches is in the simplification of complex biological systems. We here consider the general problem of receptor-ligand binding in the context of antibody-antigen binding. On the one hand, we establish a quantitative mapping between macroscopic binding rates of a deterministic differential equation model and their microscopic equivalents as obtained from simulating the spatiotemporal binding kinetics by stochastic agent-based models. On the other hand, we investigate the impact of various properties of B cell-derived receptors-such as their dimensionality of motion, morphology, and binding valency-on the receptor-ligand binding kinetics. To this end, we implemented an algorithm that simulates antigen binding by B cell-derived receptors with a Y-shaped morphology that can move in different dimensionalities, i.e., either as membrane-anchored receptors or as soluble receptors. The mapping of the macroscopic and microscopic binding rates allowed us to quantitatively compare different agent-based model variants for the different types of B cell-derived receptors. Our results indicate that the dimensionality of motion governs the binding kinetics and that this predominant impact is quantitatively compensated by the bivalency of these receptors.

Dimensionality of Motion and Binding Valency Govern Receptor–Ligand Kinetics As Revealed by Agent-Based Modeling

PubMed Central

Lehnert, Teresa; Figge, Marc Thilo

2017-01-01

Mathematical modeling and computer simulations have become an integral part of modern biological research. The strength of theoretical approaches is in the simplification of complex biological systems. We here consider the general problem of receptor–ligand binding in the context of antibody–antigen binding. On the one hand, we establish a quantitative mapping between macroscopic binding rates of a deterministic differential equation model and their microscopic equivalents as obtained from simulating the spatiotemporal binding kinetics by stochastic agent-based models. On the other hand, we investigate the impact of various properties of B cell-derived receptors—such as their dimensionality of motion, morphology, and binding valency—on the receptor–ligand binding kinetics. To this end, we implemented an algorithm that simulates antigen binding by B cell-derived receptors with a Y-shaped morphology that can move in different dimensionalities, i.e., either as membrane-anchored receptors or as soluble receptors. The mapping of the macroscopic and microscopic binding rates allowed us to quantitatively compare different agent-based model variants for the different types of B cell-derived receptors. Our results indicate that the dimensionality of motion governs the binding kinetics and that this predominant impact is quantitatively compensated by the bivalency of these receptors. PMID:29250071

Quantification of dopamine transporters in the mouse brain using ultra-high resolution single-photon emission tomography.

PubMed

Acton, Paul D; Choi, Seok-Rye; Plössl, Karl; Kung, Hank F

2002-05-01

Functional imaging of small animals, such as mice and rats, using ultra-high resolution positron emission tomography (PET) and single-photon emission tomography (SPET), is becoming a valuable tool for studying animal models of human disease. While several studies have shown the utility of PET imaging in small animals, few have used SPET in real research applications. In this study we aimed to demonstrate the feasibility of using ultra-high resolution SPET in quantitative studies of dopamine transporters (DAT) in the mouse brain. Four healthy ICR male mice were injected with (mean+/-SD) 704+/-154 MBq [(99m)Tc]TRODAT-1, and scanned using an ultra-high resolution SPET system equipped with pinhole collimators (spatial resolution 0.83 mm at 3 cm radius of rotation). Each mouse had two studies, to provide an indication of test-retest reliability. Reference tissue kinetic modeling analysis of the time-activity data in the striatum and cerebellum was used to quantitate the availability of DAT. A simple equilibrium ratio of striatum to cerebellum provided another measure of DAT binding. The SPET imaging results were compared against ex vivo biodistribution data from the striatum and cerebellum. The mean distribution volume ratio (DVR) from the reference tissue kinetic model was 2.17+/-0.34, with a test-retest reliability of 2.63%+/-1.67%. The ratio technique gave similar results (DVR=2.03+/-0.38, test-retest reliability=6.64%+/-3.86%), and the ex vivo analysis gave DVR=2.32+/-0.20. Correlations between the kinetic model and the ratio technique ( R(2)=0.86, P<0.001) and the ex vivo data ( R(2)=0.92, P=0.04) were both excellent. This study demonstrated clearly that ultra-high resolution SPET of small animals is capable of accurate, repeatable, and quantitative measures of DAT binding, and should open up the possibility of further studies of cerebral binding sites in mice using pinhole SPET.

TG study of the Li0.4Fe2.4Zn0.2O4 ferrite synthesis

NASA Astrophysics Data System (ADS)

Lysenko, E. N.; Nikolaev, E. V.; Surzhikov, A. P.

2016-02-01

In this paper, the kinetic analysis of Li-Zn ferrite synthesis was studied using thermogravimetry (TG) method through the simultaneous application of non-linear regression to several measurements run at different heating rates (multivariate non-linear regression). Using TG-curves obtained for the four heating rates and Netzsch Thermokinetics software package, the kinetic models with minimal adjustable parameters were selected to quantitatively describe the reaction of Li-Zn ferrite synthesis. It was shown that the experimental TG-curves clearly suggest a two-step process for the ferrite synthesis and therefore a model-fitting kinetic analysis based on multivariate non-linear regressions was conducted. The complex reaction was described by a two-step reaction scheme consisting of sequential reaction steps. It is established that the best results were obtained using the Yander three-dimensional diffusion model at the first stage and Ginstling-Bronstein model at the second step. The kinetic parameters for lithium-zinc ferrite synthesis reaction were found and discussed.

Quantitative analysis of protein-ligand interactions by NMR.

PubMed

Furukawa, Ayako; Konuma, Tsuyoshi; Yanaka, Saeko; Sugase, Kenji

2016-08-01

Protein-ligand interactions have been commonly studied through static structures of the protein-ligand complex. Recently, however, there has been increasing interest in investigating the dynamics of protein-ligand interactions both for fundamental understanding of the underlying mechanisms and for drug development. NMR is a versatile and powerful tool, especially because it provides site-specific quantitative information. NMR has widely been used to determine the dissociation constant (KD), in particular, for relatively weak interactions. The simplest NMR method is a chemical-shift titration experiment, in which the chemical-shift changes of a protein in response to ligand titration are measured. There are other quantitative NMR methods, but they mostly apply only to interactions in the fast-exchange regime. These methods derive the dissociation constant from population-averaged NMR quantities of the free and bound states of a protein or ligand. In contrast, the recent advent of new relaxation-based experiments, including R2 relaxation dispersion and ZZ-exchange, has enabled us to obtain kinetic information on protein-ligand interactions in the intermediate- and slow-exchange regimes. Based on R2 dispersion or ZZ-exchange, methods that can determine the association rate, kon, dissociation rate, koff, and KD have been developed. In these approaches, R2 dispersion or ZZ-exchange curves are measured for multiple samples with different protein and/or ligand concentration ratios, and the relaxation data are fitted to theoretical kinetic models. It is critical to choose an appropriate kinetic model, such as the two- or three-state exchange model, to derive the correct kinetic information. The R2 dispersion and ZZ-exchange methods are suitable for the analysis of protein-ligand interactions with a micromolar or sub-micromolar dissociation constant but not for very weak interactions, which are typical in very fast exchange. This contrasts with the NMR methods that are used to analyze population-averaged NMR quantities. Essentially, to apply NMR successfully, both the type of experiment and equation to fit the data must be carefully and specifically chosen for the protein-ligand interaction under analysis. In this review, we first explain the exchange regimes and kinetic models of protein-ligand interactions, and then describe the NMR methods that quantitatively analyze these specific interactions. Copyright © 2016 Elsevier B.V. All rights reserved.

Further insights into the kinetics of thermal decomposition during continuous cooling.

PubMed

Liavitskaya, Tatsiana; Guigo, Nathanaël; Sbirrazzuoli, Nicolas; Vyazovkin, Sergey

2017-07-26

Following the previous work (Phys. Chem. Chem. Phys., 2016, 18, 32021), this study continues to investigate the intriguing phenomenon of thermal decomposition during continuous cooling. The phenomenon can be detected and its kinetics can be measured by means of thermogravimetric analysis (TGA). The kinetics of the thermal decomposition of ammonium nitrate (NH 4 NO 3 ), nickel oxalate (NiC 2 O 4 ), and lithium sulfate monohydrate (Li 2 SO 4 ·H 2 O) have been measured upon heating and cooling and analyzed by means of the isoconversional methodology. The results have confirmed the hypothesis that the respective kinetics should be similar for single-step processes (NH 4 NO 3 decomposition) but different for multi-step ones (NiC 2 O 4 decomposition and Li 2 SO 4 ·H 2 O dehydration). It has been discovered that the differences in the kinetics can be either quantitative or qualitative. Physical insights into the nature of the differences have been proposed.

New observations and insights into the morphology and growth kinetics of hydrate films.

PubMed

Li, Sheng-Li; Sun, Chang-Yu; Liu, Bei; Li, Zhi-Yun; Chen, Guang-Jin; Sum, Amadeu K

2014-02-19

The kinetics of film growth of hydrates of methane, ethane, and methane-ethane mixtures were studied by exposing a single gas bubble to water. The morphologies, lateral growth rates, and thicknesses of the hydrate films were measured for various gas compositions and degrees of subcooling. A variety of hydrate film textures was revealed. The kinetics of two-dimensional film growth was inferred from the lateral growth rate and initial thickness of the hydrate film. A clear relationship between the morphology and film growth kinetics was observed. The shape of the hydrate crystals was found to favour heat or mass transfer and favour further growth of the hydrate film. The quantitative results on the kinetics of film growth showed that for a given degree of subcooling, the initial film thicknesses of the double hydrates were larger than that of pure methane or ethane hydrate, whereas the thickest hydrate film and the lowest lateral growth rate occurred when the methane mole fraction was approximately 0.6.

New Observations and Insights into the Morphology and Growth Kinetics of Hydrate Films

PubMed Central

Li, Sheng-Li; Sun, Chang-Yu; Liu, Bei; Li, Zhi-Yun; Chen, Guang-Jin; Sum, Amadeu K.

2014-01-01

The kinetics of film growth of hydrates of methane, ethane, and methane-ethane mixtures were studied by exposing a single gas bubble to water. The morphologies, lateral growth rates, and thicknesses of the hydrate films were measured for various gas compositions and degrees of subcooling. A variety of hydrate film textures was revealed. The kinetics of two-dimensional film growth was inferred from the lateral growth rate and initial thickness of the hydrate film. A clear relationship between the morphology and film growth kinetics was observed. The shape of the hydrate crystals was found to favour heat or mass transfer and favour further growth of the hydrate film. The quantitative results on the kinetics of film growth showed that for a given degree of subcooling, the initial film thicknesses of the double hydrates were larger than that of pure methane or ethane hydrate, whereas the thickest hydrate film and the lowest lateral growth rate occurred when the methane mole fraction was approximately 0.6. PMID:24549241

Supersymmetric quantum mechanics method for the Fokker-Planck equation with applications to protein folding dynamics

NASA Astrophysics Data System (ADS)

Polotto, Franciele; Drigo Filho, Elso; Chahine, Jorge; Oliveira, Ronaldo Junio de

2018-03-01

This work developed analytical methods to explore the kinetics of the time-dependent probability distributions over thermodynamic free energy profiles of protein folding and compared the results with simulation. The Fokker-Planck equation is mapped onto a Schrödinger-type equation due to the well-known solutions of the latter. Through a semi-analytical description, the supersymmetric quantum mechanics formalism is invoked and the time-dependent probability distributions are obtained with numerical calculations by using the variational method. A coarse-grained structure-based model of the two-state protein Tm CSP was simulated at a Cα level of resolution and the thermodynamics and kinetics were fully characterized. Analytical solutions from non-equilibrium conditions were obtained with the simulated double-well free energy potential and kinetic folding times were calculated. It was found that analytical folding time as a function of temperature agrees, quantitatively, with simulations and experiments from the literature of Tm CSP having the well-known 'U' shape of the Chevron Plots. The simple analytical model developed in this study has a potential to be used by theoreticians and experimentalists willing to explore, quantitatively, rates and the kinetic behavior of their system by informing the thermally activated barrier. The theory developed describes a stochastic process and, therefore, can be applied to a variety of biological as well as condensed-phase two-state systems.

A Model for the Estimation of Hepatic Insulin Extraction After a Meal.

PubMed

Piccinini, Francesca; Dalla Man, Chiara; Vella, Adrian; Cobelli, Claudio

2016-09-01

Quantitative assessment of hepatic insulin extraction (HE) after an oral glucose challenge, e.g., a meal, is important to understand the regulation of carbohydrate metabolism. The aim of the current study is to develop a model of system for estimating HE. Nine different models, of increasing complexity, were tested on data of 204 normal subjects, who underwent a mixed meal tolerance test, with frequent measurement of plasma glucose, insulin, and C-peptide concentrations. All these models included a two-compartment model of C-peptide kinetics, an insulin secretion model, a compartmental model of insulin kinetics (with number of compartments ranging from one to three), and different HE descriptions, depending on plasma glucose and insulin. Model performances were compared on the basis of data fit, precision of parameter estimates, and parsimony criteria. The three-compartment model of insulin kinetics, coupled with HE depending on glucose concentration, showed the best fit and a good ability to precisely estimate the parameters. In addition, the model calculates basal and total indices of HE ( HE b and HE tot , respectively), and provides an index of HE sensitivity to glucose ( S G HE ). A new physiologically based HE model has been developed, which allows an improved quantitative description of glucose regulation. The use of the new model provides an in-depth description of insulin kinetics, thus enabling a better understanding of a given subject's metabolic state.

INFLUENCE OF ORGANIC COSOLVENTS ON THE SORPTION KINETICS OF HYDROPHOBIC ORGANIC CHEMICALS

EPA Science Inventory

A quantitative examination of the kinetics of sorption of hydrophobic organic chemicals by soils from mixed solvents reveals that the reverse sorption rate constant (k2) increases log-linearly with increasing volume fraction of organic cosolvent (fc). This relationship was expec...

Mass-transfer limitations for immobilized enzyme-catalyzed kinetic resolution of racemate in a fixed-bed reactor.

PubMed

Xiu, G H; Jiang, L; Li, P

2001-07-05

A mathematical model has been developed for immobilized enzyme-catalyzed kinetic resolution of racemate in a fixed-bed reactor in which the enzyme-catalyzed reaction (the irreversible uni-uni competitive Michaelis-Menten kinetics is chosen as an example) was coupled with intraparticle diffusion, external mass transfer, and axial dispersion. The effects of mass-transfer limitations, competitive inhibition of substrates, deactivation on the enzyme effective enantioselectivity, and the optical purity and yield of the desired product are examined quantitatively over a wide range of parameters using the orthogonal collocation method. For a first-order reaction, an analytical solution is derived from the mathematical model for slab-, cylindrical-, and spherical-enzyme supports. Based on the analytical solution for the steady-state resolution process, a new concise formulation is presented to predict quantitatively the mass-transfer limitations on enzyme effective enantioselectivity and optical purity and yield of the desired product for a continuous steady-state kinetic resolution process in a fixed-bed reactor. Copyright 2001 John Wiley & Sons, Inc.

Kinetic modeling of benzodiazepine receptor binding with PET and high specific activity [(11)C]Iomazenil in healthy human subjects.

PubMed

Bremner, J D; Horti, A; Staib, L H; Zea-Ponce, Y; Soufer, R; Charney, D S; Baldwin, R

2000-01-01

Quantitation of the PET benzodiazepine receptor antagonist, [(11)C]Iomazenil, using low specific activity radioligand was recently described. The purpose of this study was to quantitate benzodiazepine receptor binding in human subjects using PET and high specific activity [(11)C]Iomazenil. Six healthy human subjects underwent PET imaging following a bolus injection of high specific activity (>100 Ci/mmol) [(11)C]iomazenil. Arterial samples were collected at multiple time points after injection for measurement of unmetabolized total and nonprotein-bound parent compound in plasma. Time activity curves of radioligand concentration in brain and plasma were analyzed using two and three compartment model. Kinetic rate constants of transfer of radioligand between plasma, nonspecifically bound brain tissue, and specifically bound brain tissue compartments were fitted to the model. Values for fitted kinetic rate constants were used in the calculation of measures of benzodiazepine receptor binding, including binding potential (the ratio of receptor density to affinity), and product of BP and the fraction of free nonprotein-bound parent compound (V(3)'). Use of the three compartment model improved the goodness of fit in comparison to the two compartment model. Values for kinetic rate constants and measures of benzodiazepine receptor binding, including BP and V(3)', were similar to results obtained with the SPECT radioligand [(123)I]iomazenil, and a prior report with low specific activity [(11)C]Iomazenil. Kinetic modeling using the three compartment model with PET and high specific activity [(11)C]Iomazenil provides a reliable measure of benzodiazepine receptor binding. Synapse 35:68-77, 2000. Published 2000 Wiley-Liss, Inc.

Development and characterization of a dynamic lesion phantom for the quantitative evaluation of dynamic contrast-enhanced MRI.

PubMed

Freed, Melanie; de Zwart, Jacco A; Hariharan, Prasanna; Myers, Matthew R; Badano, Aldo

2011-10-01

To develop a dynamic lesion phantom that is capable of producing physiological kinetic curves representative of those seen in human dynamic contrast-enhanced MRI (DCE-MRI) data. The objective of this phantom is to provide a platform for the quantitative comparison of DCE-MRI protocols to aid in the standardization and optimization of breast DCE-MRI. The dynamic lesion consists of a hollow, plastic mold with inlet and outlet tubes to allow flow of a contrast agent solution through the lesion over time. Border shape of the lesion can be controlled using the lesion mold production method. The configuration of the inlet and outlet tubes was determined using fluid transfer simulations. The total fluid flow rate was determined using x-ray images of the lesion for four different flow rates (0.25, 0.5, 1.0, and 1.5 ml/s) to evaluate the resultant kinetic curve shape and homogeneity of the contrast agent distribution in the dynamic lesion. High spatial and temporal resolution x-ray measurements were used to estimate the true kinetic curve behavior in the dynamic lesion for benign and malignant example curves. DCE-MRI example data were acquired of the dynamic phantom using a clinical protocol. The optimal inlet and outlet tube configuration for the lesion molds was two inlet molds separated by 30° and a single outlet tube directly between the two inlet tubes. X-ray measurements indicated that 1.0 ml/s was an appropriate total fluid flow rate and provided truth for comparison with MRI data of kinetic curves representative of benign and malignant lesions. DCE-MRI data demonstrated the ability of the phantom to produce realistic kinetic curves. The authors have constructed a dynamic lesion phantom, demonstrated its ability to produce physiological kinetic curves, and provided estimations of its true kinetic curve behavior. This lesion phantom provides a tool for the quantitative evaluation of DCE-MRI protocols, which may lead to improved discrimination of breast cancer lesions.

Systematic Construction of Kinetic Models from Genome-Scale Metabolic Networks

PubMed Central

Smallbone, Kieran; Klipp, Edda; Mendes, Pedro; Liebermeister, Wolfram

2013-01-01

The quantitative effects of environmental and genetic perturbations on metabolism can be studied in silico using kinetic models. We present a strategy for large-scale model construction based on a logical layering of data such as reaction fluxes, metabolite concentrations, and kinetic constants. The resulting models contain realistic standard rate laws and plausible parameters, adhere to the laws of thermodynamics, and reproduce a predefined steady state. These features have not been simultaneously achieved by previous workflows. We demonstrate the advantages and limitations of the workflow by translating the yeast consensus metabolic network into a kinetic model. Despite crudely selected data, the model shows realistic control behaviour, a stable dynamic, and realistic response to perturbations in extracellular glucose concentrations. The paper concludes by outlining how new data can continuously be fed into the workflow and how iterative model building can assist in directing experiments. PMID:24324546

Transcriptional bursting is intrinsically caused by interplay between RNA polymerases on DNA

NASA Astrophysics Data System (ADS)

Fujita, Keisuke; Iwaki, Mitsuhiro; Yanagida, Toshio

2016-12-01

Cell-to-cell variability plays a critical role in cellular responses and decision-making in a population, and transcriptional bursting has been broadly studied by experimental and theoretical approaches as the potential source of cell-to-cell variability. Although molecular mechanisms of transcriptional bursting have been proposed, there is little consensus. An unsolved key question is whether transcriptional bursting is intertwined with many transcriptional regulatory factors or is an intrinsic characteristic of RNA polymerase on DNA. Here we design an in vitro single-molecule measurement system to analyse the kinetics of transcriptional bursting. The results indicate that transcriptional bursting is caused by interplay between RNA polymerases on DNA. The kinetics of in vitro transcriptional bursting is quantitatively consistent with the gene-nonspecific kinetics previously observed in noisy gene expression in vivo. Our kinetic analysis based on a cellular automaton model confirms that arrest and rescue by trailing RNA polymerase intrinsically causes transcriptional bursting.

Molecular details of dimerization kinetics reveal negligible populations of transient µ-opioid receptor homodimers at physiological concentrations.

PubMed

Meral, Derya; Provasi, Davide; Prada-Gracia, Diego; Möller, Jan; Marino, Kristen; Lohse, Martin J; Filizola, Marta

2018-05-16

Various experimental and computational techniques have been employed over the past decade to provide structural and thermodynamic insights into G Protein-Coupled Receptor (GPCR) dimerization. Here, we use multiple microsecond-long, coarse-grained, biased and unbiased molecular dynamics simulations (a total of ~4 milliseconds) combined with multi-ensemble Markov state models to elucidate the kinetics of homodimerization of a prototypic GPCR, the µ-opioid receptor (MOR), embedded in a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)/cholesterol lipid bilayer. Analysis of these computations identifies kinetically distinct macrostates comprising several different short-lived dimeric configurations of either inactive or activated MOR. Calculated kinetic rates and fractions of dimers at different MOR concentrations suggest a negligible population of MOR homodimers at physiological concentrations, which is supported by acceptor photobleaching fluorescence resonance energy transfer (FRET) experiments. This study provides a rigorous, quantitative explanation for some conflicting experimental data on GPCR oligomerization.

From kinetic-structure analysis to engineering crystalline fiber networks in soft materials.

PubMed

Wang, Rong-Yao; Wang, Peng; Li, Jing-Liang; Yuan, Bing; Liu, Yu; Li, Li; Liu, Xiang-Yang

2013-03-07

Understanding the role of kinetics in fiber network microstructure formation is of considerable importance in engineering gel materials to achieve their optimized performances/functionalities. In this work, we present a new approach for kinetic-structure analysis for fibrous gel materials. In this method, kinetic data is acquired using a rheology technique and is analyzed in terms of an extended Dickinson model in which the scaling behaviors of dynamic rheological properties in the gelation process are taken into account. It enables us to extract the structural parameter, i.e. the fractal dimension, of a fibrous gel from the dynamic rheological measurement of the gelation process, and to establish the kinetic-structure relationship suitable for both dilute and concentrated gelling systems. In comparison to the fractal analysis method reported in a previous study, our method is advantageous due to its general validity for a wide range of fractal structures of fibrous gels, from a highly compact network of the spherulitic domains to an open fibrous network structure. With such a kinetic-structure analysis, we can gain a quantitative understanding of the role of kinetic control in engineering the microstructure of the fiber network in gel materials.

Kinetic Modeling of Accelerated Stability Testing Enabled by Second Harmonic Generation Microscopy.

PubMed

Song, Zhengtian; Sarkar, Sreya; Vogt, Andrew D; Danzer, Gerald D; Smith, Casey J; Gualtieri, Ellen J; Simpson, Garth J

2018-04-03

The low limits of detection afforded by second harmonic generation (SHG) microscopy coupled with image analysis algorithms enabled quantitative modeling of the temperature-dependent crystallization of active pharmaceutical ingredients (APIs) within amorphous solid dispersions (ASDs). ASDs, in which an API is maintained in an amorphous state within a polymer matrix, are finding increasing use to address solubility limitations of small-molecule APIs. Extensive stability testing is typically performed for ASD characterization, the time frame for which is often dictated by the earliest detectable onset of crystal formation. Here a study of accelerated stability testing on ritonavir, a human immunodeficiency virus (HIV) protease inhibitor, has been conducted. Under the condition for accelerated stability testing at 50 °C/75%RH and 40 °C/75%RH, ritonavir crystallization kinetics from amorphous solid dispersions were monitored by SHG microscopy. SHG microscopy coupled by image analysis yielded limits of detection for ritonavir crystals as low as 10 ppm, which is about 2 orders of magnitude lower than other methods currently available for crystallinity detection in ASDs. The four decade dynamic range of SHG microscopy enabled quantitative modeling with an established (JMAK) kinetic model. From the SHG images, nucleation and crystal growth rates were independently determined.

Update of KDBI: Kinetic Data of Bio-molecular Interaction database

PubMed Central

Kumar, Pankaj; Han, B. C.; Shi, Z.; Jia, J.; Wang, Y. P.; Zhang, Y. T.; Liang, L.; Liu, Q. F.; Ji, Z. L.; Chen, Y. Z.

2009-01-01

Knowledge of the kinetics of biomolecular interactions is important for facilitating the study of cellular processes and underlying molecular events, and is essential for quantitative study and simulation of biological systems. Kinetic Data of Bio-molecular Interaction database (KDBI) has been developed to provide information about experimentally determined kinetic data of protein–protein, protein–nucleic acid, protein–ligand, nucleic acid–ligand binding or reaction events described in the literature. To accommodate increasing demand for studying and simulating biological systems, numerous improvements and updates have been made to KDBI, including new ways to access data by pathway and molecule names, data file in System Biology Markup Language format, more efficient search engine, access to published parameter sets of simulation models of 63 pathways, and 2.3-fold increase of data (19 263 entries of 10 532 distinctive biomolecular binding and 11 954 interaction events, involving 2635 proteins/protein complexes, 847 nucleic acids, 1603 small molecules and 45 multi-step processes). KDBI is publically available at http://bidd.nus.edu.sg/group/kdbi/kdbi.asp. PMID:18971255

Advances in Studies of Electrode Kinetics and Mass Transport in AMTEC Cells (abstract)

NASA Technical Reports Server (NTRS)

Williams, R. M.; Jeffries-Nakamura, B.; Ryan, M. A.; Underwood, M. L.; Kisor, A.; O'Connor, D.; Kikkert, S.

1993-01-01

Previous work reported from JPL has included characterization of electrode kinetics and alkali atom transport from electrodes including Mo, W, WRh(sub x), WPt(sub x)(Mn), in sodium AMTEC cells and vapor exposure cells, and Mo in potassium vapor exposure cells. These studies were generally performed in cells with small area electrodes (about 1 to 5 cm(sup 2)), and device geometry had little effect on transport. Alkali diffusion coefficients through these electrodes have been characterized, and approximate surface diffusion coefficients derived in cases of activated transport. A basic model of electrode kinetic at the alkali metal vapor/porous metal electrode/alkali beta'-alumina solid electrolyte three phase boundary has been proposed which accounts for electrochemical reaction rates with a collision frequency near the three phase boundary and tunneling from the porous electrode partially covered with adsorbed alkali metal atoms. The small electrode effect in AMTEC cells has been discussed in several papers, but quantitative investigations have described only the overall effect and the important contribution of electrolyte resistance. The quantitative characterization of transport losses in cells with large area electrodes has been limited to simulations of large area electrode effects, or characterization of transport losses from large area electrodes with significant longitudinal temperature gradients. This paper describes new investigations of electrochemical kinetics and transport, particularily with WPt(sub 3.5) electrodes, including the influence of electrode size on the mass transport loss in the AMTEC cell. These electrodes possess excellent sodium transport properties making verification of device limitations on transport much more readily attained.

Connecting the Kinetics and Energy Landscape of tRNA Translocation on the Ribosome

PubMed Central

Whitford, Paul C.; Blanchard, Scott C.; Cate, Jamie H. D.; Sanbonmatsu, Karissa Y.

2013-01-01

Functional rearrangements in biomolecular assemblies result from diffusion across an underlying energy landscape. While bulk kinetic measurements rely on discrete state-like approximations to the energy landscape, single-molecule methods can project the free energy onto specific coordinates. With measures of the diffusion, one may establish a quantitative bridge between state-like kinetic measurements and the continuous energy landscape. We used an all-atom molecular dynamics simulation of the 70S ribosome (2.1 million atoms; 1.3 microseconds) to provide this bridge for specific conformational events associated with the process of tRNA translocation. Starting from a pre-translocation configuration, we identified sets of residues that collectively undergo rotary rearrangements implicated in ribosome function. Estimates of the diffusion coefficients along these collective coordinates for translocation were then used to interconvert between experimental rates and measures of the energy landscape. This analysis, in conjunction with previously reported experimental rates of translocation, provides an upper-bound estimate of the free-energy barriers associated with translocation. While this analysis was performed for a particular kinetic scheme of translocation, the quantitative framework is general and may be applied to energetic and kinetic descriptions that include any number of intermediates and transition states. PMID:23555233

Connecting the kinetics and energy landscape of tRNA translocation on the ribosome.

PubMed

Whitford, Paul C; Blanchard, Scott C; Cate, Jamie H D; Sanbonmatsu, Karissa Y

2013-01-01

Functional rearrangements in biomolecular assemblies result from diffusion across an underlying energy landscape. While bulk kinetic measurements rely on discrete state-like approximations to the energy landscape, single-molecule methods can project the free energy onto specific coordinates. With measures of the diffusion, one may establish a quantitative bridge between state-like kinetic measurements and the continuous energy landscape. We used an all-atom molecular dynamics simulation of the 70S ribosome (2.1 million atoms; 1.3 microseconds) to provide this bridge for specific conformational events associated with the process of tRNA translocation. Starting from a pre-translocation configuration, we identified sets of residues that collectively undergo rotary rearrangements implicated in ribosome function. Estimates of the diffusion coefficients along these collective coordinates for translocation were then used to interconvert between experimental rates and measures of the energy landscape. This analysis, in conjunction with previously reported experimental rates of translocation, provides an upper-bound estimate of the free-energy barriers associated with translocation. While this analysis was performed for a particular kinetic scheme of translocation, the quantitative framework is general and may be applied to energetic and kinetic descriptions that include any number of intermediates and transition states.

qPIPSA: Relating enzymatic kinetic parameters and interaction fields

PubMed Central

Gabdoulline, Razif R; Stein, Matthias; Wade, Rebecca C

2007-01-01

Background The simulation of metabolic networks in quantitative systems biology requires the assignment of enzymatic kinetic parameters. Experimentally determined values are often not available and therefore computational methods to estimate these parameters are needed. It is possible to use the three-dimensional structure of an enzyme to perform simulations of a reaction and derive kinetic parameters. However, this is computationally demanding and requires detailed knowledge of the enzyme mechanism. We have therefore sought to develop a general, simple and computationally efficient procedure to relate protein structural information to enzymatic kinetic parameters that allows consistency between the kinetic and structural information to be checked and estimation of kinetic constants for structurally and mechanistically similar enzymes. Results We describe qPIPSA: quantitative Protein Interaction Property Similarity Analysis. In this analysis, molecular interaction fields, for example, electrostatic potentials, are computed from the enzyme structures. Differences in molecular interaction fields between enzymes are then related to the ratios of their kinetic parameters. This procedure can be used to estimate unknown kinetic parameters when enzyme structural information is available and kinetic parameters have been measured for related enzymes or were obtained under different conditions. The detailed interaction of the enzyme with substrate or cofactors is not modeled and is assumed to be similar for all the proteins compared. The protein structure modeling protocol employed ensures that differences between models reflect genuine differences between the protein sequences, rather than random fluctuations in protein structure. Conclusion Provided that the experimental conditions and the protein structural models refer to the same protein state or conformation, correlations between interaction fields and kinetic parameters can be established for sets of related enzymes. Outliers may arise due to variation in the importance of different contributions to the kinetic parameters, such as protein stability and conformational changes. The qPIPSA approach can assist in the validation as well as estimation of kinetic parameters, and provide insights into enzyme mechanism. PMID:17919319

A Ten-Week Biochemistry Lab Project Studying Wild-Type and Mutant Bacterial Alkaline Phosphatase

ERIC Educational Resources Information Center

Witherow, D. Scott

2016-01-01

This work describes a 10-week laboratory project studying wild-type and mutant bacterial alkaline phosphatase, in which students purify, quantitate, and perform kinetic assays on wild-type and selected mutants of the enzyme. Students also perform plasmid DNA purification, digestion, and gel analysis. In addition to simply learning important…

Quantitative fluorescence loss in photobleaching for analysis of protein transport and aggregation

PubMed Central

2012-01-01

Background Fluorescence loss in photobleaching (FLIP) is a widely used imaging technique, which provides information about protein dynamics in various cellular regions. In FLIP, a small cellular region is repeatedly illuminated by an intense laser pulse, while images are taken with reduced laser power with a time lag between the bleaches. Despite its popularity, tools are lacking for quantitative analysis of FLIP experiments. Typically, the user defines regions of interest (ROIs) for further analysis which is subjective and does not allow for comparing different cells and experimental settings. Results We present two complementary methods to detect and quantify protein transport and aggregation in living cells from FLIP image series. In the first approach, a stretched exponential (StrExp) function is fitted to fluorescence loss (FL) inside and outside the bleached region. We show by reaction–diffusion simulations, that the StrExp function can describe both, binding/barrier–limited and diffusion-limited FL kinetics. By pixel-wise regression of that function to FL kinetics of enhanced green fluorescent protein (eGFP), we determined in a user-unbiased manner from which cellular regions eGFP can be replenished in the bleached area. Spatial variation in the parameters calculated from the StrExp function allow for detecting diffusion barriers for eGFP in the nucleus and cytoplasm of living cells. Polyglutamine (polyQ) disease proteins like mutant huntingtin (mtHtt) can form large aggregates called inclusion bodies (IB’s). The second method combines single particle tracking with multi-compartment modelling of FL kinetics in moving IB’s to determine exchange rates of eGFP-tagged mtHtt protein (eGFP-mtHtt) between aggregates and the cytoplasm. This method is self-calibrating since it relates the FL inside and outside the bleached regions. It makes it therefore possible to compare release kinetics of eGFP-mtHtt between different cells and experiments. Conclusions We present two complementary methods for quantitative analysis of FLIP experiments in living cells. They provide spatial maps of exchange dynamics and absolute binding parameters of fluorescent molecules to moving intracellular entities, respectively. Our methods should be of great value for quantitative studies of intracellular transport. PMID:23148417

Experimental and Theoretical Studies of Atmosphereic Inorganic Chlorine Chemistry

NASA Technical Reports Server (NTRS)

Sander, Stanley P.; Friedl, Randall R.

1993-01-01

Over the last five years substantial progress has been made in defining the realm of new chlorine chemistry in the polar stratosphere. Application of existing experimental techniques to potentially important chlorine-containing compounds has yielded quantitative kinetic and spectroscopic data as well as qualitative mechanistic insights into the relevant reactions.

A comparison of quantitative methods for clinical imaging with hyperpolarized (13)C-pyruvate.

PubMed

Daniels, Charlie J; McLean, Mary A; Schulte, Rolf F; Robb, Fraser J; Gill, Andrew B; McGlashan, Nicholas; Graves, Martin J; Schwaiger, Markus; Lomas, David J; Brindle, Kevin M; Gallagher, Ferdia A

2016-04-01

Dissolution dynamic nuclear polarization (DNP) enables the metabolism of hyperpolarized (13)C-labelled molecules, such as the conversion of [1-(13)C]pyruvate to [1-(13)C]lactate, to be dynamically and non-invasively imaged in tissue. Imaging of this exchange reaction in animal models has been shown to detect early treatment response and correlate with tumour grade. The first human DNP study has recently been completed, and, for widespread clinical translation, simple and reliable methods are necessary to accurately probe the reaction in patients. However, there is currently no consensus on the most appropriate method to quantify this exchange reaction. In this study, an in vitro system was used to compare several kinetic models, as well as simple model-free methods. Experiments were performed using a clinical hyperpolarizer, a human 3 T MR system, and spectroscopic imaging sequences. The quantitative methods were compared in vivo by using subcutaneous breast tumours in rats to examine the effect of pyruvate inflow. The two-way kinetic model was the most accurate method for characterizing the exchange reaction in vitro, and the incorporation of a Heaviside step inflow profile was best able to describe the in vivo data. The lactate time-to-peak and the lactate-to-pyruvate area under the curve ratio were simple model-free approaches that accurately represented the full reaction, with the time-to-peak method performing indistinguishably from the best kinetic model. Finally, extracting data from a single pixel was a robust and reliable surrogate of the whole region of interest. This work has identified appropriate quantitative methods for future work in the analysis of human hyperpolarized (13)C data. © 2016 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.

Kinetics analysis and quantitative calculations for the successive radioactive decay process

NASA Astrophysics Data System (ADS)

Zhou, Zhiping; Yan, Deyue; Zhao, Yuliang; Chai, Zhifang

2015-01-01

The general radioactive decay kinetics equations with branching were developed and the analytical solutions were derived by Laplace transform method. The time dependence of all the nuclide concentrations can be easily obtained by applying the equations to any known radioactive decay series. Taking the example of thorium radioactive decay series, the concentration evolution over time of various nuclide members in the family has been given by the quantitative numerical calculations with a computer. The method can be applied to the quantitative prediction and analysis for the daughter nuclides in the successive decay with branching of the complicated radioactive processes, such as the natural radioactive decay series, nuclear reactor, nuclear waste disposal, nuclear spallation, synthesis and identification of superheavy nuclides, radioactive ion beam physics and chemistry, etc.

Novel mathematic models for quantitative transitivity of quality-markers in extraction process of the Buyanghuanwu decoction.

PubMed

Zhang, Yu-Tian; Xiao, Mei-Feng; Deng, Kai-Wen; Yang, Yan-Tao; Zhou, Yi-Qun; Zhou, Jin; He, Fu-Yuan; Liu, Wen-Long

2018-06-01

Nowadays, to research and formulate an efficiency extraction system for Chinese herbal medicine, scientists have always been facing a great challenge for quality management, so that the transitivity of Q-markers in quantitative analysis of TCM was proposed by Prof. Liu recently. In order to improve the quality of extraction from raw medicinal materials for clinical preparations, a series of integrated mathematic models for transitivity of Q-markers in quantitative analysis of TCM were established. Buyanghuanwu decoction (BYHWD) was a commonly TCMs prescription, which was used to prevent and treat the ischemic heart and brain diseases. In this paper, we selected BYHWD as an extraction experimental subject to study the quantitative transitivity of TCM. Based on theory of Fick's Rule and Noyes-Whitney equation, novel kinetic models were established for extraction of active components. Meanwhile, fitting out kinetic equations of extracted models and then calculating the inherent parameters in material piece and Q-marker quantitative transfer coefficients, which were considered as indexes to evaluate transitivity of Q-markers in quantitative analysis of the extraction process of BYHWD. HPLC was applied to screen and analyze the potential Q-markers in the extraction process. Fick's Rule and Noyes-Whitney equation were adopted for mathematically modeling extraction process. Kinetic parameters were fitted and calculated by the Statistical Program for Social Sciences 20.0 software. The transferable efficiency was described and evaluated by potential Q-markers transfer trajectory via transitivity availability AUC, extraction ratio P, and decomposition ratio D respectively. The Q-marker was identified with AUC, P, D. Astragaloside IV, laetrile, paeoniflorin, and ferulic acid were studied as potential Q-markers from BYHWD. The relative technologic parameters were presented by mathematic models, which could adequately illustrate the inherent properties of raw materials preparation and affection of Q-markers transitivity in equilibrium processing. AUC, P, D for potential Q-markers of AST-IV, laetrile, paeoniflorin, and FA were obtained, with the results of 289.9 mAu s, 46.24%, 22.35%; 1730 mAu s, 84.48%, 1.963%; 5600 mAu s, 70.22%, 0.4752%; 7810 mAu s, 24.29%, 4.235%, respectively. The results showed that the suitable Q-markers were laetrile and paeoniflorin in our study, which exhibited acceptable traceability and transitivity in the extraction process of TCMs. Therefore, these novel mathematic models might be developed as a new standard to control TCMs quality process from raw medicinal materials to product manufacturing. Copyright © 2018 Elsevier GmbH. All rights reserved.

A century of enzyme kinetic analysis, 1913 to 2013.

PubMed

Johnson, Kenneth A

2013-09-02

This review traces the history and logical progression of methods for quantitative analysis of enzyme kinetics from the 1913 Michaelis and Menten paper to the application of modern computational methods today. Following a brief review of methods for fitting steady state kinetic data, modern methods are highlighted for fitting full progress curve kinetics based upon numerical integration of rate equations, including a re-analysis of the original Michaelis-Menten full time course kinetic data. Finally, several illustrations of modern transient state kinetic methods of analysis are shown which enable the elucidation of reactions occurring at the active sites of enzymes in order to relate structure and function. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Quantitative Connection Between Ensemble Thermodynamics and Single-Molecule Kinetics: A Case Study Using Cryo-EM and smFRET Investigations of the Ribosome

PubMed Central

Frank, Joachim; Gonzalez, Ruben L.

2015-01-01

At equilibrium, thermodynamic and kinetic information can be extracted from biomolecular energy landscapes by many techniques. However, while static, ensemble techniques yield thermodynamic data, often only dynamic, single-molecule techniques can yield the kinetic data that describes transition-state energy barriers. Here we present a generalized framework based upon dwell-time distributions that can be used to connect such static, ensemble techniques with dynamic, single-molecule techniques, and thus characterize energy landscapes to greater resolutions. We demonstrate the utility of this framework by applying it to cryogenic electron microscopy and single-molecule fluorescence resonance energy transfer studies of the bacterial ribosomal pretranslocation complex. Among other benefits, application of this framework to these data explains why two transient, intermediate conformations of the pretranslocation complex, which are observed in a cryogenic electron microscopy study, may not be observed in several single-molecule fluorescence resonance energy transfer studies. PMID:25785884

Quantitative Connection between Ensemble Thermodynamics and Single-Molecule Kinetics: A Case Study Using Cryogenic Electron Microscopy and Single-Molecule Fluorescence Resonance Energy Transfer Investigations of the Ribosome.

PubMed

Thompson, Colin D Kinz; Sharma, Ajeet K; Frank, Joachim; Gonzalez, Ruben L; Chowdhury, Debashish

2015-08-27

At equilibrium, thermodynamic and kinetic information can be extracted from biomolecular energy landscapes by many techniques. However, while static, ensemble techniques yield thermodynamic data, often only dynamic, single-molecule techniques can yield the kinetic data that describe transition-state energy barriers. Here we present a generalized framework based upon dwell-time distributions that can be used to connect such static, ensemble techniques with dynamic, single-molecule techniques, and thus characterize energy landscapes to greater resolutions. We demonstrate the utility of this framework by applying it to cryogenic electron microscopy (cryo-EM) and single-molecule fluorescence resonance energy transfer (smFRET) studies of the bacterial ribosomal pre-translocation complex. Among other benefits, application of this framework to these data explains why two transient, intermediate conformations of the pre-translocation complex, which are observed in a cryo-EM study, may not be observed in several smFRET studies.

Invasion-wave-induced first-order phase transition in systems of active particles.

PubMed

Ihle, Thomas

2013-10-01

An instability near the transition to collective motion of self-propelled particles is studied numerically by Enskog-like kinetic theory. While hydrodynamics breaks down, the kinetic approach leads to steep solitonlike waves. These supersonic waves show hysteresis and lead to an abrupt jump of the global order parameter if the noise level is changed. Thus they provide a mean-field mechanism to change the second-order character of the phase transition to first order. The shape of the wave is shown to follow a scaling law and to quantitatively agree with agent-based simulations.

QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS FOR CHEMICAL REDUCTIONS OF ORGANIC CONTAMINANTS

EPA Science Inventory

Sufficient kinetic data on abiotic reduction reactions involving organic contaminants are now available that quantitative structure-activity relationships (QSARs) for these reactions can be developed. Over 50 QSARs have been reported, most in just the last few years, and they ar...

Use of Ambient Ionization High-Resolution Mass Spectrometry for the Kinetic Analysis of Organic Surface Reactions.

PubMed

Sen, Rickdeb; Escorihuela, Jorge; Smulders, Maarten M J; Zuilhof, Han

2016-04-12

In contrast to homogeneous systems, studying the kinetics of organic reactions on solid surfaces remains a difficult task due to the limited availability of appropriate analysis techniques that are general, high-throughput, and capable of offering quantitative, structural surface information. Here, we demonstrate how direct analysis in real time mass spectrometry (DART-MS) complies with above considerations and can be used for determining interfacial kinetic parameters. The presented approach is based on the use of a MS tag that--in principle--allows application to other reactions. To show the potential of DART-MS, we selected the widely applied strain-promoted alkyne-azide cycloaddition (SPAAC) as a model reaction to elucidate the effects of the nanoenvironment on the interfacial reaction rate.

Principles of quantitation of viral loads using nucleic acid sequence-based amplification in combination with homogeneous detection using molecular beacons.

PubMed

Weusten, Jos J A M; Carpay, Wim M; Oosterlaken, Tom A M; van Zuijlen, Martien C A; van de Wiel, Paul A

2002-03-15

For quantitative NASBA-based viral load assays using homogeneous detection with molecular beacons, such as the NucliSens EasyQ HIV-1 assay, a quantitation algorithm is required. During the amplification process there is a constant growth in the concentration of amplicons to which the beacon can bind while generating a fluorescence signal. The overall fluorescence curve contains kinetic information on both amplicon formation and beacon binding, but only the former is relevant for quantitation. In the current paper, mathematical modeling of the relevant processes is used to develop an equation describing the fluorescence curve as a function of the amplification time and the relevant kinetic parameters. This equation allows reconstruction of RNA formation, which is characterized by an exponential increase in concentrations as long as the primer concentrations are not rate limiting and by linear growth over time after the primer pool is depleted. During the linear growth phase, the actual quantitation is based on assessing the amplicon formation rate from the viral RNA relative to that from a fixed amount of calibrator RNA. The quantitation procedure has been successfully applied in the NucliSens EasyQ HIV-1 assay.

Influence of quasi-specific sites on kinetics of target DNA search by a sequence-specific DNA-binding protein.

PubMed

Kemme, Catherine A; Esadze, Alexandre; Iwahara, Junji

2015-11-10

Functions of transcription factors require formation of specific complexes at particular sites in cis-regulatory elements of genes. However, chromosomal DNA contains numerous sites that are similar to the target sequences recognized by transcription factors. The influence of such "quasi-specific" sites on functions of the transcription factors is not well understood at present by experimental means. In this work, using fluorescence methods, we have investigated the influence of quasi-specific DNA sites on the efficiency of target location by the zinc finger DNA-binding domain of the inducible transcription factor Egr-1, which recognizes a 9 bp sequence. By stopped-flow assays, we measured the kinetics of Egr-1's association with a target site on 143 bp DNA in the presence of various competitor DNAs, including nonspecific and quasi-specific sites. The presence of quasi-specific sites on competitor DNA significantly decelerated the target association by the Egr-1 protein. The impact of the quasi-specific sites depended strongly on their affinity, their concentration, and the degree of their binding to the protein. To quantitatively describe the kinetic impact of the quasi-specific sites, we derived an analytical form of the apparent kinetic rate constant for the target association and used it for fitting to the experimental data. Our kinetic data with calf thymus DNA as a competitor suggested that there are millions of high-affinity quasi-specific sites for Egr-1 among the 3 billion bp of genomic DNA. This study quantitatively demonstrates that naturally abundant quasi-specific sites on DNA can considerably impede the target search processes of sequence-specific DNA-binding proteins.

Influence of Quasi-Specific Sites on Kinetics of Target DNA Search by a Sequence-Specific DNA-Binding Protein

PubMed Central

2015-01-01

Functions of transcription factors require formation of specific complexes at particular sites in cis-regulatory elements of genes. However, chromosomal DNA contains numerous sites that are similar to the target sequences recognized by transcription factors. The influence of such “quasi-specific” sites on functions of the transcription factors is not well understood at present by experimental means. In this work, using fluorescence methods, we have investigated the influence of quasi-specific DNA sites on the efficiency of target location by the zinc finger DNA-binding domain of the inducible transcription factor Egr-1, which recognizes a 9 bp sequence. By stopped-flow assays, we measured the kinetics of Egr-1’s association with a target site on 143 bp DNA in the presence of various competitor DNAs, including nonspecific and quasi-specific sites. The presence of quasi-specific sites on competitor DNA significantly decelerated the target association by the Egr-1 protein. The impact of the quasi-specific sites depended strongly on their affinity, their concentration, and the degree of their binding to the protein. To quantitatively describe the kinetic impact of the quasi-specific sites, we derived an analytical form of the apparent kinetic rate constant for the target association and used it for fitting to the experimental data. Our kinetic data with calf thymus DNA as a competitor suggested that there are millions of high-affinity quasi-specific sites for Egr-1 among the 3 billion bp of genomic DNA. This study quantitatively demonstrates that naturally abundant quasi-specific sites on DNA can considerably impede the target search processes of sequence-specific DNA-binding proteins. PMID:26502071

Kinetic theory of Lennard-Jones fluids

NASA Astrophysics Data System (ADS)

Leegwater, Jan A.

1991-12-01

A kinetic theory that describes the time evolution of a fluid consisting of Lennard-Jones particles at all densities is proposed. The kinetic equation assumes binary collisions, but takes into account the finite time duration of a collision. Furthermore, it is an extension of a kinetic equation for the square well fluid as well as the hard sphere Enskog theory. In the low density limit, the Boltzmann theory is obtained. It is shown that the proposed theory obeys all the conservation laws. The exchange of potential and kinetic energies is studied and it is shown that at high density this is a fast process. The dominant mechanism for energy exchange is found to be collisions at the strongly repulsive part of the potential that are disturbed by third particles. The kinetic equation is also used to calculate the Green-Kubo integrands for shear viscosity and heat conductivity. The major structures found in molecular dynamics simulations are reproduced at intermediate densities quantitatively and at high density semiquantitatively. It is found that at high density, not only correlated collisions have to be taken into account, but that even the concept of collisions in the sense of sudden changes in the velocity is no longer useful.

Kinetic Studies and Product Characterization during the Basic Hydrolysis of Glyceryl Nitrate Esters

DTIC Science & Technology

1979-08-01

elaborate instrumentation, which was considered too time consuming and costly to construct for this study. 25 The quantitative estimation of the calcium...0.6 [ l-exp(- Kfc ) 1 Figure 21. Formation of N03~ during hydrolysis of 1-MNG in aqueous Ca(0H)2 solution at 25°C (See Tables 2 and 8) 6 5

Kinetic Model of Growth of Arthropoda Populations

NASA Astrophysics Data System (ADS)

Ershov, Yu. A.; Kuznetsov, M. A.

2018-05-01

Kinetic equations were derived for calculating the growth of crustacean populations ( Crustacea) based on the biological growth model suggested earlier using shrimp ( Caridea) populations as an example. The development cycle of successive stages for populations can be represented in the form of quasi-chemical equations. The kinetic equations that describe the development cycle of crustaceans allow quantitative prediction of the development of populations depending on conditions. In contrast to extrapolation-simulation models, in the developed kinetic model of biological growth the kinetic parameters are the experimental characteristics of population growth. Verification and parametric identification of the developed model on the basis of the experimental data showed agreement with experiment within the error of the measurement technique.

[Analysis of hydrodynamics parameters of runoff erosion and sediment-yielding on unpaved road].

PubMed

Huang, Peng-Fei; Wang, Wen-Long; Luo, Ting; Wang, Zhen; Wang, Zheng-Li; Li, Ren

2013-02-01

By the method of field runoff washout experiment, a simulation study was conducted on the relationships between the soil detachment rate and the hydrodynamic parameters on unpaved road, and the related quantitative formulas were established. Under the conditions of different flow discharges and road gradients, the averaged soil detachment rate increased with increasing flow discharge and road gradient, and the relationships between them could be described by a power function. As compared with road gradient, flow discharge had greater effects on the soil detachment rate. The soil detachment rate had a power relation with water flow velocity and runoff kinetic energy, and the runoff kinetic energy was of importance to the soil detachment rate. The soil detachment rate was linearly correlated with the unit runoff kinetic energy. The averaged soil erodibility was 0.120 g m-1.J-F-1, and the averaged critical unit runoff kinetic energy was 2.875 g.m-1.J-1. Flow discharge, road gradient, and unit runoff kinetic energy could be used to accurately describe the soil erosion process and calculate the soil erosion rate on unpaved road.

A quantitative analysis of aerosols inside an armored vehicle perforated by a kinetic energy penetrator containing tungsten, nickel, and cobalt.

PubMed

Gold, Kenneth; Cheng, Yung Sung; Holmes, Thomas D

2007-04-01

These tests were conducted to develop a database that could be used to assess risks to soldiers from exposure to aerosolized metallic particulates when the crew compartment of an Abrams tank is perforated by a kinetic energy penetrator. Quantitative data are reported for aerosols produced by kinetic energy penetrators containing tungsten, nickel, and cobalt. The following are addressed: (1) concentrations and rates of particle settling inside the vehicle, (2) particle size distribution, (3) inhalable and respirable particulates, (4) distribution of aerosol particles by mass, and (5) particle shapes. The scenario described in this report simulates a rare occurrence. The lessons learned, however, highlight a requirement for developing protocols for analyses of metals in body fluids and urine as soon as practical, and also for implementing targeted postdeployment medical surveillance programs that monitor both body burden for respired metals and pulmonary function.

New insight in quantitative analysis of vascular permeability during immune reaction (Conference Presentation)

NASA Astrophysics Data System (ADS)

Kalchenko, Vyacheslav; Molodij, Guillaume; Kuznetsov, Yuri; Smolyakov, Yuri; Israeli, David; Meglinski, Igor; Harmelin, Alon

2016-03-01

The use of fluorescence imaging of vascular permeability becomes a golden standard for assessing the inflammation process during experimental immune response in vivo. The use of the optical fluorescence imaging provides a very useful and simple tool to reach this purpose. The motivation comes from the necessity of a robust and simple quantification and data presentation of inflammation based on a vascular permeability. Changes of the fluorescent intensity, as a function of time is a widely accepted method to assess the vascular permeability during inflammation related to the immune response. In the present study we propose to bring a new dimension by applying a more sophisticated approach to the analysis of vascular reaction by using a quantitative analysis based on methods derived from astronomical observations, in particular by using a space-time Fourier filtering analysis followed by a polynomial orthogonal modes decomposition. We demonstrate that temporal evolution of the fluorescent intensity observed at certain pixels correlates quantitatively to the blood flow circulation at normal conditions. The approach allows to determine the regions of permeability and monitor both the fast kinetics related to the contrast material distribution in the circulatory system and slow kinetics associated with extravasation of the contrast material. Thus, we introduce a simple and convenient method for fast quantitative visualization of the leakage related to the inflammatory (immune) reaction in vivo.

Quantitative Analysis of Microstructural Constituents in Welded Transformation-Induced-Plasticity Steels

NASA Astrophysics Data System (ADS)

Amirthalingam, M.; Hermans, M. J. M.; Zhao, L.; Richardson, I. M.

2010-02-01

A quantitative analysis of retained austenite and nonmetallic inclusions in gas tungsten arc (GTA)-welded aluminum-containing transformation-induced-plasticity (TRIP) steels is presented. The amount of retained austenite in the heat-affected and fusion zones of welded aluminum-containing TRIP steel with different base metal austenite fractions has been measured by magnetic saturation measurements, to study the effect of weld thermal cycles on the stabilization of austenite. It is found that for base metals containing 3 to 14 pct of austenite, 4 to 13 pct of austenite is found in the heat-affected zones and 6 to 10 pct in the fusion zones. The decomposition kinetics of retained austenite in the base metal and welded samples was also studied by thermomagnetic measurements. The decomposition kinetics of the austenite in the fusion zone is found to be slower compared to that in the base metal. Thermomagnetic measurements indicated the formation of ferromagnetic ɛ carbides above 290 °C and paramagnetic η( ɛ') transient iron carbides at approximately 400 °C due to the decomposition of austenite during heating.

Emergence of HGF/SF-Induced Coordinated Cellular Motility

PubMed Central

Zaritsky, Assaf; Natan, Sari; Ben-Jacob, Eshel; Tsarfaty, Ilan

2012-01-01

Collective cell migration plays a major role in embryonic morphogenesis, tissue remodeling, wound repair and cancer invasion. Despite many decades of extensive investigations, only few analytical tools have been developed to enhance the biological understanding of this important phenomenon. Here we present a novel quantitative approach to analyze long term kinetics of bright field time-lapse wound healing. Fully-automated spatiotemporal measures and visualization of cells' motility and implicit morphology were proven to be sound, repetitive and highly informative compared to single-cell tracking analysis. We study cellular collective migration induced by tyrosine kinase-growth factor signaling (Met-Hepatocyte Growth Factor/Scatter Factor (HGF/SF)). Our quantitative approach is applied to demonstrate that collective migration of the adenocarcinoma cell lines is characterized by simple morpho-kinetics. HGF/SF induces complex morpho-kinetic coordinated collective migration: cells at the front move faster and are more spread than those further away from the wound edge. As the wound heals, distant cells gradually accelerate and enhance spread and elongation –resembling the epithelial to mesenchymal transition (EMT), and then the cells become more spread and maintain higher velocity than cells located closer to the wound. Finally, upon wound closure, front cells halt, shrink and round up (resembling mesenchymal to epithelial transition (MET) phenotype) while distant cells undergo the same process gradually. Met inhibition experiments further validate that Met signaling dramatically alters the morpho-kinetic dynamics of the healing wound. Machine-learning classification was applied to demonstrate the generalization of our findings, revealing even subtle changes in motility patterns induced by Met-inhibition. It is concluded that activation of Met-signaling induces an elaborated model in which cells lead a coordinated increased motility along with gradual differentiation-based collective cell motility dynamics. Our quantitative phenotypes may guide future investigation on the molecular and cellular mechanisms of tyrosine kinase-induced coordinate cell motility and morphogenesis in metastasis. PMID:22970283

Neurobiological model of stimulated dopamine neurotransmission to interpret fast-scan cyclic voltammetry data.

PubMed

Harun, Rashed; Grassi, Christine M; Munoz, Miranda J; Torres, Gonzalo E; Wagner, Amy K

2015-03-02

Fast-scan cyclic voltammetry (FSCV) is an electrochemical method that can assess real-time in vivo dopamine (DA) concentration changes to study the kinetics of DA neurotransmission. Electrical stimulation of dopaminergic (DAergic) pathways can elicit FSCV DA responses that largely reflect a balance of DA release and reuptake. Interpretation of these evoked DA responses requires a framework to discern the contribution of DA release and reuptake. The current, widely implemented interpretive framework for doing so is the Michaelis-Menten (M-M) model, which is grounded on two assumptions- (1) DA release rate is constant during stimulation, and (2) DA reuptake occurs through dopamine transporters (DAT) in a manner consistent with M-M enzyme kinetics. Though the M-M model can simulate evoked DA responses that rise convexly, response types that predominate in the ventral striatum, the M-M model cannot simulate dorsal striatal responses that rise concavely. Based on current neurotransmission principles and experimental FSCV data, we developed a novel, quantitative, neurobiological framework to interpret DA responses that assumes DA release decreases exponentially during stimulation and continues post-stimulation at a diminishing rate. Our model also incorporates dynamic M-M kinetics to describe DA reuptake as a process of decreasing reuptake efficiency. We demonstrate that this quantitative, neurobiological model is an extension of the traditional M-M model that can simulate heterogeneous regional DA responses following manipulation of stimulation duration, frequency, and DA pharmacology. The proposed model can advance our interpretive framework for future in vivo FSCV studies examining regional DA kinetics and their alteration by disease and DA pharmacology. Copyright © 2015 Elsevier B.V. All rights reserved.

Single-Molecule Imaging of an in Vitro-Evolved RNA Aptamer Reveals Homogeneous Ligand Binding Kinetics

PubMed Central

2009-01-01

Many studies of RNA folding and catalysis have revealed conformational heterogeneity, metastable folding intermediates, and long-lived states with distinct catalytic activities. We have developed a single-molecule imaging approach for investigating the functional heterogeneity of in vitro-evolved RNA aptamers. Monitoring the association of fluorescently labeled ligands with individual RNA aptamer molecules has allowed us to record binding events over the course of multiple days, thus providing sufficient statistics to quantitatively define the kinetic properties at the single-molecule level. The ligand binding kinetics of the highly optimized RNA aptamer studied here displays a remarkable degree of uniformity and lack of memory. Such homogeneous behavior is quite different from the heterogeneity seen in previous single-molecule studies of naturally derived RNA and protein enzymes. The single-molecule methods we describe may be of use in analyzing the distribution of functional molecules in heterogeneous evolving populations or even in unselected samples of random sequences. PMID:19572753

Machine learning-based kinetic modeling: a robust and reproducible solution for quantitative analysis of dynamic PET data

NASA Astrophysics Data System (ADS)

Pan, Leyun; Cheng, Caixia; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

2017-05-01

A variety of compartment models are used for the quantitative analysis of dynamic positron emission tomography (PET) data. Traditionally, these models use an iterative fitting (IF) method to find the least squares between the measured and calculated values over time, which may encounter some problems such as the overfitting of model parameters and a lack of reproducibility, especially when handling noisy data or error data. In this paper, a machine learning (ML) based kinetic modeling method is introduced, which can fully utilize a historical reference database to build a moderate kinetic model directly dealing with noisy data but not trying to smooth the noise in the image. Also, due to the database, the presented method is capable of automatically adjusting the models using a multi-thread grid parameter searching technique. Furthermore, a candidate competition concept is proposed to combine the advantages of the ML and IF modeling methods, which could find a balance between fitting to historical data and to the unseen target curve. The machine learning based method provides a robust and reproducible solution that is user-independent for VOI-based and pixel-wise quantitative analysis of dynamic PET data.

Quantitative modeling of the reaction/diffusion kinetics of two-chemistry photopolymers

NASA Astrophysics Data System (ADS)

Kowalski, Benjamin Andrew

Optically driven diffusion in photopolymers is an appealing material platform for a broad range of applications, in which the recorded refractive index patterns serve either as images (e.g. data storage, display holography) or as optical elements (e.g. custom GRIN components, integrated optical devices). A quantitative understanding of the reaction/diffusion kinetics is difficult to obtain directly, but is nevertheless necessary in order to fully exploit the wide array of design freedoms in these materials. A general strategy for characterizing these kinetics is proposed, in which key processes are decoupled and independently measured. This strategy enables prediction of a material's potential refractive index change, solely on the basis of its chemical components. The degree to which a material does not reach this potential reveals the fraction of monomer that has participated in unwanted reactions, reducing spatial resolution and dynamic range. This approach is demonstrated for a model material similar to commercial media, achieving quantitative predictions of index response over three orders of exposure dose (~1 to ~103 mJ cm-2) and three orders of feature size (0.35 to 500 microns). The resulting insights enable guided, rational design of new material formulations with demonstrated performance improvement.

Effects of combined pressure and temperature on enzymes related to quality of fruits and vegetables: from kinetic information to process engineering aspects.

PubMed

Ludikhuyze, L; Van Loey, A; Indrawati; Smout, C; Hendrickx, M

2003-01-01

Throughout the last decade, high pressure technology has been shown to offer great potential to the food processing and preservation industry in delivering safe and high quality products. Implementation of this new technology will be largely facilitated when a scientific basis to assess quantitatively the impact of high pressure processes on food safety and quality becomes available. Besides, quantitative data on the effects of pressure and temperature on safety and quality aspects of foods are indispensable for design and evaluation of optimal high pressure processes, i.e., processes resulting in maximal quality retention within the constraints of the required reduction of microbial load and enzyme activity. Indeed it has to be stressed that new technologies should deliver, apart from the promised quality improvement, an equivalent or preferably enhanced level of safety. The present paper will give an overview from a quantitative point of view of the combined effects of pressure and temperature on enzymes related to quality of fruits and vegetables. Complete kinetic characterization of the inactivation of the individual enzymes will be discussed, as well as the use of integrated kinetic information in process engineering.

Machine learning-based kinetic modeling: a robust and reproducible solution for quantitative analysis of dynamic PET data.

PubMed

Pan, Leyun; Cheng, Caixia; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

2017-05-07

A variety of compartment models are used for the quantitative analysis of dynamic positron emission tomography (PET) data. Traditionally, these models use an iterative fitting (IF) method to find the least squares between the measured and calculated values over time, which may encounter some problems such as the overfitting of model parameters and a lack of reproducibility, especially when handling noisy data or error data. In this paper, a machine learning (ML) based kinetic modeling method is introduced, which can fully utilize a historical reference database to build a moderate kinetic model directly dealing with noisy data but not trying to smooth the noise in the image. Also, due to the database, the presented method is capable of automatically adjusting the models using a multi-thread grid parameter searching technique. Furthermore, a candidate competition concept is proposed to combine the advantages of the ML and IF modeling methods, which could find a balance between fitting to historical data and to the unseen target curve. The machine learning based method provides a robust and reproducible solution that is user-independent for VOI-based and pixel-wise quantitative analysis of dynamic PET data.

Methods for Kinetic and Thermodynamic Analysis of Aminoacyl-tRNA Synthetases

PubMed Central

Francklyn, Christopher S.; First, Eric A.; Perona, John J.; Hou, Ya-Ming

2008-01-01

The accuracy of protein synthesis relies on the ability of aminoacyl-tRNA synthetases (aaRSs) to discriminate among true and near cognate substrates. To date, analysis of aaRSs function, including identification of residues of aaRS participating in amino acid and tRNA discrimination, has largely relied on the steady state kinetic pyrophosphate exchange and aminoacylation assays. Pre-steady state kinetic studies investigating a more limited set of aaRS systems have also been undertaken to assess the energetic contributions of individual enzyme-substrate interactions, particularly in the adenylation half reaction. More recently, a renewed interest in the use of rapid kinetics approaches for aaRSs has led to their application to several new aaRS systems, resulting in the identification of mechanistic differences that distinguish the two structurally distinct aaRS classes. Here, we review the techniques for thermodynamic and kinetic analysis of aaRS function. Following a brief survey of methods for the preparation of materials and for steady state kinetic analysis, this review will describe pre-steady state kinetic methods employing rapid quench and stopped-flow fluorescence for analysis of the activation and aminoacyl transfer reactions. Application of these methods to any aaRS system allows the investigator to derive detailed kinetic mechanisms for the activation and aminoacyl transfer reactions, permitting issues of substrate specificity, stereochemical mechanism, and inhibitor interaction to be addressed in a rigorous and quantitative fashion. PMID:18241792

Gradual Ordering in Red Abalone Nacre

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gilbert, P. U. P. A.; Metzler, Rebecca A.; Zhou, Dong

2008-09-03

Red abalone (Haliotis rufescens) nacre is a layered composite biomineral that contains crystalline aragonite tablets confined by organic layers. Nacre is intensely studied because its biologically controlled microarchitecture gives rise to remarkable strength and toughness, but the mechanisms leading to its formation are not well understood. Here we present synchrotron spectromicroscopy experiments revealing that stacks of aragonite tablet crystals in nacre are misoriented with respect to each other. Quantitative measurements of crystal orientation, tablet size, and tablet stacking direction show that orientational ordering occurs not abruptly but gradually over a distance of 50 {micro}m. Several lines of evidence indicate thatmore » different crystal orientations imply different tablet growth rates during nacre formation. A theoretical model based on kinetic and gradual selection of the fastest growth rates produces results in qualitative and quantitative agreement with the experimental data and therefore demonstrates that ordering in nacre is a result of crystal growth kinetics and competition either in addition or to the exclusion of templation by acidic proteins as previously assumed. As in other natural evolving kinetic systems, selection of the fastest-growing stacks of tablets occurs gradually in space and time. These results suggest that the self-ordering of the mineral phase, which may occur completely independently of biological or organic-molecule control, is fundamental in nacre formation.« less

Kinetic analyses of vasculogenesis inform mechanistic studies

PubMed Central

Winfree, Seth; Chu, Chenghao; Tu, Wanzhu; Blue, Emily K.; Gohn, Cassandra R.; Dunn, Kenneth W.

2017-01-01

Vasculogenesis is a complex process by which endothelial stem and progenitor cells undergo de novo vessel formation. Quantitative assessment of vasculogenesis is a central readout of endothelial progenitor cell functionality. However, current assays lack kinetic measurements. To address this issue, new approaches were developed to quantitatively assess in vitro endothelial colony-forming cell (ECFC) network formation in real time. Eight parameters of network structure were quantified using novel Kinetic Analysis of Vasculogenesis (KAV) software. KAV assessment of structure complexity identified two phases of network formation. This observation guided the development of additional vasculogenic readouts. A tissue cytometry approach was established to quantify the frequency and localization of dividing ECFCs. Additionally, Fiji TrackMate was used to quantify ECFC displacement and speed at the single-cell level during network formation. These novel approaches were then implemented to identify how intrauterine exposure to maternal diabetes mellitus (DM) impairs fetal ECFC vasculogenesis. Fetal ECFCs exposed to maternal DM form fewer initial network structures, which are not stable over time. Correlation analyses demonstrated that ECFC samples with greater division in branches form fewer closed network structures. Additionally, reductions in average ECFC movement over time decrease structural connectivity. Identification of these novel phenotypes utilizing the newly established methodologies provides evidence for the cellular mechanisms contributing to aberrant ECFC vasculogenesis. PMID:28100488

Development and characterization of a dynamic lesion phantom for the quantitative evaluation of dynamic contrast-enhanced MRI

PubMed Central

Freed, Melanie; de Zwart, Jacco A.; Hariharan, Prasanna; R. Myers, Matthew; Badano, Aldo

2011-01-01

Purpose: To develop a dynamic lesion phantom that is capable of producing physiological kinetic curves representative of those seen in human dynamic contrast-enhanced MRI (DCE-MRI) data. The objective of this phantom is to provide a platform for the quantitative comparison of DCE-MRI protocols to aid in the standardization and optimization of breast DCE-MRI. Methods: The dynamic lesion consists of a hollow, plastic mold with inlet and outlet tubes to allow flow of a contrast agent solution through the lesion over time. Border shape of the lesion can be controlled using the lesion mold production method. The configuration of the inlet and outlet tubes was determined using fluid transfer simulations. The total fluid flow rate was determined using x-ray images of the lesion for four different flow rates (0.25, 0.5, 1.0, and 1.5 ml∕s) to evaluate the resultant kinetic curve shape and homogeneity of the contrast agent distribution in the dynamic lesion. High spatial and temporal resolution x-ray measurements were used to estimate the true kinetic curve behavior in the dynamic lesion for benign and malignant example curves. DCE-MRI example data were acquired of the dynamic phantom using a clinical protocol. Results: The optimal inlet and outlet tube configuration for the lesion molds was two inlet molds separated by 30° and a single outlet tube directly between the two inlet tubes. X-ray measurements indicated that 1.0 ml∕s was an appropriate total fluid flow rate and provided truth for comparison with MRI data of kinetic curves representative of benign and malignant lesions. DCE-MRI data demonstrated the ability of the phantom to produce realistic kinetic curves. Conclusions: The authors have constructed a dynamic lesion phantom, demonstrated its ability to produce physiological kinetic curves, and provided estimations of its true kinetic curve behavior. This lesion phantom provides a tool for the quantitative evaluation of DCE-MRI protocols, which may lead to improved discrimination of breast cancer lesions. PMID:21992378

Multiresponse kinetic modelling of Maillard reaction and caramelisation in a heated glucose/wheat flour system.

PubMed

Kocadağlı, Tolgahan; Gökmen, Vural

2016-11-15

The study describes the kinetics of the formation and degradation of α-dicarbonyl compounds in glucose/wheat flour system heated under low moisture conditions. Changes in the concentrations of glucose, fructose, individual free amino acids, lysine and arginine residues, glucosone, 1-deoxyglucosone, 3-deoxyglucosone, 3,4-dideoxyglucosone, 5-hydroxymethyl-2-furfural, glyoxal, methylglyoxal and diacetyl concentrations were determined to form a multiresponse kinetic model for isomerisation and degradation reactions of glucose. Degradation of Amadori product mainly produced 1-deoxyglucosone. Formation of 3-deoxyglucosone proceeded directly from glucose and also Amadori product degradation. Glyoxal formation was predominant from glucosone while methylglyoxal and diacetyl originated from 1-deoxyglucosone. Formation of 5-hydroxymethyl-2-furfural from fructose was found to be a key step. Multi-response kinetic modelling of Maillard reaction and caramelisation simultaneously indicated quantitatively predominant parallel and consecutive pathways and rate limiting steps by estimating the reaction rate constants. Copyright © 2016 Elsevier Ltd. All rights reserved.

Kinetics of heavy metal adsorption and desorption in soil: Developing a unified model based on chemical speciation

NASA Astrophysics Data System (ADS)

Peng, Lanfang; Liu, Paiyu; Feng, Xionghan; Wang, Zimeng; Cheng, Tao; Liang, Yuzhen; Lin, Zhang; Shi, Zhenqing

2018-03-01

Predicting the kinetics of heavy metal adsorption and desorption in soil requires consideration of multiple heterogeneous soil binding sites and variations of reaction chemistry conditions. Although chemical speciation models have been developed for predicting the equilibrium of metal adsorption on soil organic matter (SOM) and important mineral phases (e.g. Fe and Al (hydr)oxides), there is still a lack of modeling tools for predicting the kinetics of metal adsorption and desorption reactions in soil. In this study, we developed a unified model for the kinetics of heavy metal adsorption and desorption in soil based on the equilibrium models WHAM 7 and CD-MUSIC, which specifically consider metal kinetic reactions with multiple binding sites of SOM and soil minerals simultaneously. For each specific binding site, metal adsorption and desorption rate coefficients were constrained by the local equilibrium partition coefficients predicted by WHAM 7 or CD-MUSIC, and, for each metal, the desorption rate coefficients of various binding sites were constrained by their metal binding constants with those sites. The model had only one fitting parameter for each soil binding phase, and all other parameters were derived from WHAM 7 and CD-MUSIC. A stirred-flow method was used to study the kinetics of Cd, Cu, Ni, Pb, and Zn adsorption and desorption in multiple soils under various pH and metal concentrations, and the model successfully reproduced most of the kinetic data. We quantitatively elucidated the significance of different soil components and important soil binding sites during the adsorption and desorption kinetic processes. Our model has provided a theoretical framework to predict metal adsorption and desorption kinetics, which can be further used to predict the dynamic behavior of heavy metals in soil under various natural conditions by coupling other important soil processes.

Textural kinetics: a novel dynamic contrast-enhanced (DCE)-MRI feature for breast lesion classification.

PubMed

Agner, Shannon C; Soman, Salil; Libfeld, Edward; McDonald, Margie; Thomas, Kathleen; Englander, Sarah; Rosen, Mark A; Chin, Deanna; Nosher, John; Madabhushi, Anant

2011-06-01

Dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) of the breast has emerged as an adjunct imaging tool to conventional X-ray mammography due to its high detection sensitivity. Despite the increasing use of breast DCE-MRI, specificity in distinguishing malignant from benign breast lesions is low, and interobserver variability in lesion classification is high. The novel contribution of this paper is in the definition of a new DCE-MRI descriptor that we call textural kinetics, which attempts to capture spatiotemporal changes in breast lesion texture in order to distinguish malignant from benign lesions. We qualitatively and quantitatively demonstrated on 41 breast DCE-MRI studies that textural kinetic features outperform signal intensity kinetics and lesion morphology features in distinguishing benign from malignant lesions. A probabilistic boosting tree (PBT) classifier in conjunction with textural kinetic descriptors yielded an accuracy of 90%, sensitivity of 95%, specificity of 82%, and an area under the curve (AUC) of 0.92. Graph embedding, used for qualitative visualization of a low-dimensional representation of the data, showed the best separation between benign and malignant lesions when using textural kinetic features. The PBT classifier results and trends were also corroborated via a support vector machine classifier which showed that textural kinetic features outperformed the morphological, static texture, and signal intensity kinetics descriptors. When textural kinetic attributes were combined with morphologic descriptors, the resulting PBT classifier yielded 89% accuracy, 99% sensitivity, 76% specificity, and an AUC of 0.91.

Kinetic Titration Series with Biolayer Interferometry

PubMed Central

Frenzel, Daniel; Willbold, Dieter

2014-01-01

Biolayer interferometry is a method to analyze protein interactions in real-time. In this study, we illustrate the usefulness to quantitatively analyze high affinity protein ligand interactions employing a kinetic titration series for characterizing the interactions between two pairs of interaction patterns, in particular immunoglobulin G and protein G B1 as well as scFv IC16 and amyloid beta (1–42). Kinetic titration series are commonly used in surface plasmon resonance and involve sequential injections of analyte over a desired concentration range on a single ligand coated sensor chip without waiting for complete dissociation between the injections. We show that applying this method to biolayer interferometry is straightforward and i) circumvents problems in data evaluation caused by unavoidable sensor differences, ii) saves resources and iii) increases throughput if screening a multitude of different analyte/ligand combinations. PMID:25229647

Kinetic titration series with biolayer interferometry.

PubMed

Frenzel, Daniel; Willbold, Dieter

2014-01-01

Biolayer interferometry is a method to analyze protein interactions in real-time. In this study, we illustrate the usefulness to quantitatively analyze high affinity protein ligand interactions employing a kinetic titration series for characterizing the interactions between two pairs of interaction patterns, in particular immunoglobulin G and protein G B1 as well as scFv IC16 and amyloid beta (1-42). Kinetic titration series are commonly used in surface plasmon resonance and involve sequential injections of analyte over a desired concentration range on a single ligand coated sensor chip without waiting for complete dissociation between the injections. We show that applying this method to biolayer interferometry is straightforward and i) circumvents problems in data evaluation caused by unavoidable sensor differences, ii) saves resources and iii) increases throughput if screening a multitude of different analyte/ligand combinations.

The Role of Endocytosis during Morphogenetic Signaling

PubMed Central

Gonzalez-Gaitan, Marcos; Jülicher, Frank

2014-01-01

Morphogens are signaling molecules that are secreted by a localized source and spread in a target tissue where they are involved in the regulation of growth and patterning. Both the activity of morphogenetic signaling and the kinetics of ligand spreading in a tissue depend on endocytosis and intracellular trafficking. Here, we review quantitative approaches to study how large-scale morphogen profiles and signals emerge in a tissue from cellular trafficking processes and endocytic pathways. Starting from the kinetics of endosomal networks, we discuss the role of cellular trafficking and receptor dynamics in the formation of morphogen gradients. These morphogen gradients scale during growth, which implies that overall tissue size influences cellular trafficking kinetics. Finally, we discuss how such morphogen profiles can be used to control tissue growth. We emphasize the role of theory in efforts to bridge between scales. PMID:24984777

Ivestigation of the Interface Kinetic Effects on Dendritic Growth in a Pure Undercooled Melt

NASA Astrophysics Data System (ADS)

Lee, Youngyih; Rappel, Wouter-Jan; Karma, Alain

1997-03-01

The non-equilibrium kinetics of the solid-liquid interface is known to strongly influence the growth rate and morphology of dendrites in undercooled melts. In metallic systems, kinetic effects are usually considered relevant only at high undercooling, while in some transparent organic materials, like pivalic acid (PVA), kinetic effects already seem to influence dendritic growth at low undercooling. We investigate quantitatively the effect of isotropic and anisotropic kinetics on dendritic growth in a pure undercooled melt in two and three dimensions using a standard boundary integral approach. Our numerical results are interpreted with the help of a simple dimensional criterion which predicts the critical undercooling at which the transition from surface energy dominated growth to interface kinetics dominated growth takes place. Finally, our calculations are used to estimate the kinetic coefficient of pure Nickel and PVA using a fit to the experimentally observed growth rates.

Quantitative methods for evaluating the efficacy of thalamic deep brain stimulation in patients with essential tremor.

PubMed

Wastensson, Gunilla; Holmberg, Björn; Johnels, Bo; Barregard, Lars

2013-01-01

Deep brain stimulation (DBS) of the thalamus is a safe and efficient method for treatment of disabling tremor in patient with essential tremor (ET). However, successful tremor suppression after surgery requires careful selection of stimulus parameters. Our aim was to examine the possible use of certain quantitative methods for evaluating the efficacy of thalamic DBS in ET patients in clinical practice, and to compare these methods with traditional clinical tests. We examined 22 patients using the Essential Tremor Rating Scale (ETRS) and quantitative assessment of tremor with the stimulator both activated and deactivated. We used an accelerometer (CATSYS tremor Pen) for quantitative measurement of postural tremor, and a eurythmokinesimeter (EKM) to evaluate kinetic tremor in a rapid pointing task. The efficacy of DBS on tremor suppression was prominent irrespective of the method used. The agreement between clinical rating of postural tremor and tremor intensity as measured by the CATSYS tremor pen was relatively high (rs = 0.74). The agreement between kinetic tremor as assessed by the ETRS and the main outcome variable from the EKM test was low (rs = 0.34). The lack of agreement indicates that the EKM test is not comparable with the clinical test. Quantitative methods, such as the CATSYS tremor pen, could be a useful complement to clinical tremor assessment in evaluating the efficacy of DBS in clinical practice. Future studies should evaluate the precision of these methods and long-term impact on tremor suppression, activities of daily living (ADL) function and quality of life.

New techniques for positron emission tomography in the study of human neurological disorders

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuhl, D.E.

1993-01-01

This progress report describes accomplishments of four programs. The four programs are entitled (1) Faster,simpler processing of positron-computing precursors: New physicochemical approaches, (2) Novel solid phase reagents and methods to improve radiosynthesis and isotope production, (3) Quantitative evaluation of the extraction of information from PET images, and (4) Optimization of tracer kinetic methods for radioligand studies in PET.

Nuclear apoptotic volume decrease in individual cells: Confocal microscopy imaging and kinetic modeling.

PubMed

Khalo, Irina V; Konokhova, Anastasiya I; Orlova, Darya Y; Trusov, Konstantin V; Yurkin, Maxim A; Bartova, Eva; Kozubek, Stanislav; Maltsev, Valeri P; Chernyshev, Andrei V

2018-05-30

The dynamics of nuclear morphology changes during apoptosis remains poorly investigated and understood. Using 3D time-lapse confocal microscopy we performed a study of early-stage apoptotic nuclear morphological changes induced by etoposide in single living HepG2 cells. These observations provide a definitive evidence that nuclear apoptotic volume decrease (AVD) is occurring simultaneously with peripheral chromatin condensation (so called "apoptotic ring"). In order to describe quantitatively the dynamics of nuclear morphological changes in the early stage of apoptosis we suggest a general molecular kinetic model, which fits well the obtained experimental data in our study. Results of this work may clarify molecular mechanisms of nuclear morphology changes during apoptosis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Kinetics of N-Glycan Release from Human Immunoglobulin G (IgG) by PNGase F: All Glycans Are Not Created Equal.

PubMed

Huang, Yining; Orlando, Ron

2017-12-01

The biologic activity of IgG molecules is modulated by its crystallizable fragment N-glycosylation, and thus, the analysis of IgG glycosylation is critical. A standard approach to analyze glycosylation of IgGs involves the release of the N-glycans by the enzyme peptide N-glycosidase F, which cleaves the linkage between the asparagine residue and innermost N-acetylglucosamine (GlcNAc) of all N-glycans except those containing a 3-linked fucose attached to the reducing terminal GlcNAc residue. The importance of obtaining complete glycan release for accurate quantitation led us to investigate the kinetics of this de-glycosylation reaction for IgG glycopeptides and to determine the effect of glycan structure and amino acid sequence on the rate of glycan release from glycopeptides of IgGs. This study revealed that the slight differences in amino acid sequences did not lead to a statistically different deglycosylation rate. However, statistically significant differences in the deglycosylation rate constants were observed between glycopeptides differing only in glycan structure ( i.e. , nonfucosylated, fucosylated, bisecting-GlcNAc, sialylated, etc .). For example, a single sialic acid residue was found to decrease the rate by a factor of 3. Similar reductions in rate were associated with the presence of a bisecting-GlcNAc. We predict the differences in release kinetics can lead to significant quantitative variations of the glycosylation study of IgGs.

Quantitative tests of a reconstitution model for RNA folding thermodynamics and kinetics.

PubMed

Bisaria, Namita; Greenfeld, Max; Limouse, Charles; Mabuchi, Hideo; Herschlag, Daniel

2017-09-12

Decades of study of the architecture and function of structured RNAs have led to the perspective that RNA tertiary structure is modular, made of locally stable domains that retain their structure across RNAs. We formalize a hypothesis inspired by this modularity-that RNA folding thermodynamics and kinetics can be quantitatively predicted from separable energetic contributions of the individual components of a complex RNA. This reconstitution hypothesis considers RNA tertiary folding in terms of ΔG align , the probability of aligning tertiary contact partners, and ΔG tert , the favorable energetic contribution from the formation of tertiary contacts in an aligned state. This hypothesis predicts that changes in the alignment of tertiary contacts from different connecting helices and junctions (ΔG HJH ) or from changes in the electrostatic environment (ΔG +/- ) will not affect the energetic perturbation from a mutation in a tertiary contact (ΔΔG tert ). Consistent with these predictions, single-molecule FRET measurements of folding of model RNAs revealed constant ΔΔG tert values for mutations in a tertiary contact embedded in different structural contexts and under different electrostatic conditions. The kinetic effects of these mutations provide further support for modular behavior of RNA elements and suggest that tertiary mutations may be used to identify rate-limiting steps and dissect folding and assembly pathways for complex RNAs. Overall, our model and results are foundational for a predictive understanding of RNA folding that will allow manipulation of RNA folding thermodynamics and kinetics. Conversely, the approaches herein can identify cases where an independent, additive model cannot be applied and so require additional investigation.

Quantitative correlations between collision induced dissociation mass spectrometry coupled with electrospray ionization or atmospheric pressure chemical ionization mass spectrometry - Experiment and theory

NASA Astrophysics Data System (ADS)

Ivanova, Bojidarka; Spiteller, Michael

2018-04-01

The problematic that we consider in this paper treats the quantitative correlation model equations between experimental kinetic and thermodynamic parameters of coupled electrospray ionization (ESI) mass spectrometry (MS) or atmospheric pressure chemical ionization (APCI) mass spectrometry with collision induced dissociation mass spectrometry, accounting for the fact that the physical phenomena and mechanisms of ESI- and APCI-ion formation are completely different. There are described forty two fragment reactions of three analytes under independent ESI- and APCI-measurements. The developed new quantitative models allow us to study correlatively the reaction kinetics and thermodynamics using the methods of mass spectrometry, which complementary application with the methods of the quantum chemistry provide 3D structural information of the analytes. Both static and dynamic quantum chemical computations are carried out. The object of analyses are [2,3-dimethyl-4-(4-methyl-benzoyl)-2,3-di-p-tolyl-cyclobutyl]-p-tolyl-methanone (1) and the polycyclic aromatic hydrocarbons derivatives of dibenzoperylen (2) and tetrabenzo [a,c,fg,op]naphthacene (3), respectively. As far as (1) is known to be a product of [2π+2π] cycloaddition reactions of chalcone (1,3-di-p-tolyl-propenone), however producing cyclic derivatives with different stereo selectivity, so that the study provide crucial data about the capability of mass spectrometry to provide determine the stereo selectivity of the analytes. This work also first provides quantitative treatment of the relations '3D molecular/electronic structures'-'quantum chemical diffusion coefficient'-'mass spectrometric diffusion coefficient', thus extending the capability of the mass spectrometry for determination of the exact 3D structure of the analytes using independent measurements and computations of the diffusion coefficients. The determination of the experimental diffusion parameters is carried out within the 'current monitoring method' evaluating the translation diffusion of charged analytes, while the theoretical modelling of MS ions and computations of theoretical diffusion coefficients are based on the Arrhenius type behavior of the charged species under ESI- and APCI-conditions. Although the study provide certain sound considerations for the quantitative relations between the reaction kinetic-thermodynamics and 3D structure of the analytes together with correlations between 3D molecular/electronic structures-quantum chemical diffusion coefficient-mass spectrometric diffusion coefficient, which contribute significantly to the structural analytical chemistry, the results have importance to other areas such as organic synthesis and catalysis as well.

Real-Time Enzyme Kinetics by Quantitative NMR Spectroscopy and Determination of the Michaelis-Menten Constant Using the Lambert-W Function

ERIC Educational Resources Information Center

Her, Cheenou; Alonzo, Aaron P.; Vang, Justin Y.; Torres, Ernesto; Krishnan, V. V.

2015-01-01

Enzyme kinetics is an essential part of a chemistry curriculum, especially for students interested in biomedical research or in health care fields. Though the concept is routinely performed in undergraduate chemistry/biochemistry classrooms using other spectroscopic methods, we provide an optimized approach that uses a real-time monitoring of the…

Oxidative dissolution of silver nanoparticles: A new theoretical approach.

PubMed

Adamczyk, Zbigniew; Oćwieja, Magdalena; Mrowiec, Halina; Walas, Stanisław; Lupa, Dawid

2016-05-01

A general model of an oxidative dissolution of silver particle suspensions was developed that rigorously considers the bulk and surface solute transport. A two-step surface reaction scheme was proposed that comprises the formation of the silver oxide phase by direct oxidation and the acidic dissolution of this phase leading to silver ion release. By considering this, a complete set of equations is formulated describing oxygen and silver ion transport to and from particles' surfaces. These equations are solved in some limiting cases of nanoparticle dissolution in dilute suspensions. The obtained kinetic equations were used for the interpretation of experimental data pertinent to the dissolution kinetics of citrate-stabilized silver nanoparticles. In these kinetic measurements the role of pH and bulk suspension concentration was quantitatively evaluated by using the atomic absorption spectrometry (AAS). It was shown that the theoretical model adequately reflects the main features of the experimental results, especially the significant increase in the dissolution rate for lower pH. Also the presence of two kinetic regimes was quantitatively explained in terms of the decrease in the coverage of the fast dissolving oxide layer. The overall silver dissolution rate constants characterizing these two regimes were determined. Copyright © 2015 Elsevier Inc. All rights reserved.

Tuning Precursor Reactivity toward Nanometer-Size Control in Palladium Nanoparticles Studied by in Situ Small Angle X-ray Scattering

DOE PAGES

Wu, Liheng; Lian, Huada; Willis, Joshua J.; ...

2018-01-03

Synthesis of monodisperse nanoparticles (NPs) with precisely controlled size is critical for understanding their size-dependent properties. Although significant synthetic developments have been achieved, it is still challenging to synthesize well-defined NPs in a predictive way due to a lack of in-depth mechanistic understanding of reaction kinetics. Here we use synchrotron-based small-angle X-ray scattering (SAXS) to monitor in situ the formation of palladium (Pd) NPs through thermal decomposition of Pd–TOP (TOP: trioctylphosphine) complex via the “heat-up” method. We systematically study the effects of different ligands, including oleylamine, TOP, and oleic acid, on the formation kinetics of Pd NPs. Through quantitative analysismore » of the real-time SAXS data, we are able to obtain a detailed picture of the size, size distribution, and concentration of Pd NPs during the syntheses, and these results show that different ligands strongly affect the precursor reactivity. We find that oleylamine does not change the reactivity of the Pd–TOP complex but promote the formation of nuclei due to strong ligand–NP binding. On the other hand, TOP and oleic acid substantially change the precursor reactivity over more than an order of magnitude, which controls the nucleation kinetics and determines the final particle size. A theoretical model is used to demonstrate that the nucleation and growth kinetics are dependent on both precursor reactivity and ligand–NP binding affinity, thus providing a framework to explain the synthesis process and the effect of the reaction conditions. Quantitative understanding of the impacts of different ligands enables the successful synthesis of a series of monodisperse Pd NPs in the broad size range from 3 to 11 nm with nanometer-size control, which serve as a model system to study their size-dependent catalytic properties. Furthermore, the in situ SAXS probing can be readily extended to other functional NPs to greatly advance their synthetic design.« less

Tuning Precursor Reactivity toward Nanometer-Size Control in Palladium Nanoparticles Studied by in Situ Small Angle X-ray Scattering

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Liheng; Lian, Huada; Willis, Joshua J.

Synthesis of monodisperse nanoparticles (NPs) with precisely controlled size is critical for understanding their size-dependent properties. Although significant synthetic developments have been achieved, it is still challenging to synthesize well-defined NPs in a predictive way due to a lack of in-depth mechanistic understanding of reaction kinetics. Here we use synchrotron-based small-angle X-ray scattering (SAXS) to monitor in situ the formation of palladium (Pd) NPs through thermal decomposition of Pd–TOP (TOP: trioctylphosphine) complex via the “heat-up” method. We systematically study the effects of different ligands, including oleylamine, TOP, and oleic acid, on the formation kinetics of Pd NPs. Through quantitative analysismore » of the real-time SAXS data, we are able to obtain a detailed picture of the size, size distribution, and concentration of Pd NPs during the syntheses, and these results show that different ligands strongly affect the precursor reactivity. We find that oleylamine does not change the reactivity of the Pd–TOP complex but promote the formation of nuclei due to strong ligand–NP binding. On the other hand, TOP and oleic acid substantially change the precursor reactivity over more than an order of magnitude, which controls the nucleation kinetics and determines the final particle size. A theoretical model is used to demonstrate that the nucleation and growth kinetics are dependent on both precursor reactivity and ligand–NP binding affinity, thus providing a framework to explain the synthesis process and the effect of the reaction conditions. Quantitative understanding of the impacts of different ligands enables the successful synthesis of a series of monodisperse Pd NPs in the broad size range from 3 to 11 nm with nanometer-size control, which serve as a model system to study their size-dependent catalytic properties. Furthermore, the in situ SAXS probing can be readily extended to other functional NPs to greatly advance their synthetic design.« less

Comparative Inactivation of Murine Norovirus, Human Adenovirus, and Human JC Polyomavirus by Chlorine in Seawater

PubMed Central

de Abreu Corrêa, Adriana; Carratala, Anna; Barardi, Celia Regina Monte; Calvo, Miquel; Bofill-Mas, Sílvia

2012-01-01

Viruses excreted by humans affect the commercial and recreational use of coastal water. Shellfish produced in contaminated waters have been linked to many episodes and outbreaks of viral gastroenteritis, as well as other food-borne diseases worldwide. The risk can be reduced by appropriate treatment following harvesting and by depuration. The kinetics of inactivation of murine norovirus 1 and human adenovirus 2 in natural and artificial seawater by free available chlorine was studied by quantifying genomic copies (GC) using quantitative PCR and infectious viral particles (PFU). Human JC polyomavirus Mad4 kinetics were evaluated by quantitative PCR. DNase or RNase were used to eliminate free genomes and assess potential viral infectivity when molecular detection was performed. At 30 min of assay, human adenovirus 2 showed 2.6- and 2.7-log10 GC reductions and a 2.3- and 2.4-log10 PFU reductions in natural and artificial seawater, respectively, and infectious viral particles were still observed at the end of the assay. When DNase was used prior to the nucleic acid extraction the kinetic of inactivation obtained by quantitative PCR was statistically equivalent to the one observed by infectivity assays. For murine norovirus 1, 2.5, and 3.5-log10 GC reductions were observed in natural and artificial seawater, respectively, while no viruses remained infectious after 30 min of contact with chlorine. Regarding JC polyomavirus Mad4, 1.5- and 1.1-log10 GC reductions were observed after 30 min of contact time. No infectivity assays were conducted for this virus. The results obtained provide data that might be applicable to seawater used in shellfish depuration. PMID:22773637

Kinetic analysis on precursors for iturin A production from Bacillus amyloliquefaciens BPD1.

PubMed

Wu, Jiun-Yan; Liao, Jen-Hung; Shieh, Chwen-Jen; Hsieh, Feng-Chia; Liu, Yung-Chuan

2018-06-12

In this study, the precursor effect for iturin A production was quantitatively analyzed. A strain identified as Bacillus amyloliquefaciens BPD1 (Ba-BPD1) was selected due to its ability to produce iturin A. The enhancement of iturin A production in a submerged culture was tested using various additives, including palmitic acid, oils, and complex amino acids. Among these, complex amino acids triggered the highest yield at 559 mg/L. The respective amino acids that contribute to the structure of iturin A were used as precursors. In fact, it was found that the addition of l-proline, l-glutamine, l-asparagine and l-serine could improve iturin A yield in the defined medium. However, during the kinetic analysis, all the amino acids exhibited a lower saturation level than l-serine, which exhibited a high saturation level at 1.2% resulting in an iturin A yield of 914 mg/L. In contrast, a negative effect was observed following the addition of l-tyrosine. To analyze the kinetic behavior of l-serine, three kinetic models were adopted: the kinetic order equation, the Langmuir kinetic equation, and a modified logistic equation. The regression results showed that the modified logistic model was the best fit for the kinetic behavior of l-serine as the major precursor, which could be further referred to the biosynthesis pathway of iturin A. Among the proposed processes for iturin A production, this study achieved the highest iturin A levels as a result of the addition of precursors. Copyright © 2018 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Thermal degradation kinetics of all-trans and cis-carotenoids in a light-induced model system.

PubMed

Xiao, Ya-Dong; Huang, Wu-Yang; Li, Da-Jing; Song, Jiang-Feng; Liu, Chun-Quan; Wei, Qiu-Yu; Zhang, Min; Yang, Qiu-Ming

2018-01-15

Thermal degradation kinetics of lutein, zeaxanthin, β-cryptoxanthin, β-carotene was studied at 25, 35, and 45°C in a model system. Qualitative and quantitative analyses of all-trans- and cis-carotenoids were conducted using HPLC-DAD-MS technologies. Kinetic and thermodynamic parameters were calculated by non-linear regression. A total of 29 geometrical isomers and four oxidation products were detected, including all-trans-, keto compounds, mono-cis- and di-cis-isomers. Degradations of all-trans-lutein, zeaxanthin, β-cryptoxanthin, and β-carotene were described by a first-order kinetic model, with the order of rate constants as k β -carotene >k β -cryptoxanthin >k lutein >k zeaxanthin . Activation energies of zeaxanthin, lutein, β-cryptoxanthin, and β-carotene were 65.6, 38.9, 33.9, and 8.6kJ/moL, respectively. cis-carotenoids also followed with the first-order kinetic model, but they did not show a defined sequence of degradation rate constants and activation energies at different temperatures. A possible degradation pathway of four carotenoids was identified to better understand the mechanism of carotenoid degradation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Quantification of Protein-Induced Membrane Remodeling Kinetics In Vitro with Lipid Multilayer Gratings

PubMed Central

Lowry, Troy W.; Hariri, Hanaa; Prommapan, Plengchart; Kusi-Appiah, Aubrey; Vafai, Nicholas; Bienkiewicz, Ewa A.; Van Winkle, David H.; Stagg, Scott M.

2016-01-01

The dynamic self-organization of lipids in biological systems is a highly regulated process that enables the compartmentalization of living systems at micro- and nanoscopic scales. Consequently, quantitative methods for assaying the kinetics of supramolecular remodeling such as vesicle formation from planar lipid bilayers or multilayers are needed to understand cellular self-organization. Here, a new nanotechnology-based method for quantitative measurements of lipid–protein interactions is presented and its suitability for quantifying the membrane binding, inflation, and budding activity of the membrane-remodeling protein Sar1 is demonstrated. Lipid multilayer gratings are printed onto surfaces using nanointaglio and exposed to Sar1, resulting in the inflation of lipid multilayers into unilamellar structures, which can be observed in a label-free manner by monitoring the diffracted light. Local variations in lipid multilayer volume on the surface is used to vary substrate availability in a microarray format. A quantitative model is developed that allows quantification of binding affinity (KD) and kinetics (kon and koff). Importantly, this assay is uniquely capable of quantifying membrane remodeling. Upon Sar1-induced inflation of single bilayers from surface supported multilayers, the semicylindrical grating lines are observed to remodel into semispherical buds when a critical radius of curvature is reached. PMID:26649649

Development of an electron paramagnetic resonance methodology for studying the photo-generation of reactive species in semiconductor nano-particle assembled films

NASA Astrophysics Data System (ADS)

Twardoch, Marek; Messai, Youcef; Vileno, Bertrand; Hoarau, Yannick; Mekki, Djamel E.; Felix, Olivier; Turek, Philippe; Weiss, Jean; Decher, Gero; Martel, David

2018-06-01

An experimental approach involving electron paramagnetic resonance is proposed for studying photo-generated reactive species in semiconductor nano-particle-based films deposited on the internal wall of glass capillaries. This methodology is applied here to nano-TiO2 and allows a semi-quantitative analysis of the kinetic evolutions of radical production using a spin scavenger probe.

New techniques for positron emission tomography in the study of human neurological disorders. Progress report, June 1990--June 1993

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuhl, D.E.

1993-06-01

This progress report describes accomplishments of four programs. The four programs are entitled (1) Faster,simpler processing of positron-computing precursors: New physicochemical approaches, (2) Novel solid phase reagents and methods to improve radiosynthesis and isotope production, (3) Quantitative evaluation of the extraction of information from PET images, and (4) Optimization of tracer kinetic methods for radioligand studies in PET.

Quantitatively and Kinetically Identifying Binding Motifs of Amelogenin Proteins to Mineral Crystals Through Biochemical and Spectroscopic Assays

PubMed Central

Zhu, Li; Hwang, Peter; Witkowska, H. Ewa; Liu, Haichuan; Li, Wu

2014-01-01

Tooth enamel is the hardest tissue in vertebrate animals. Consisting of millions of carbonated hydroxyapatite crystals, this highly mineralized tissue develops from a protein matrix in which amelogenin is the predominant component. The enamel matrix proteins are eventually and completely degraded and removed by proteinases to form mineral-enriched tooth enamel. Identification of the apatite-binding motifs in amelogenin is critical for understanding the amelogenin–crystal interactions and amelogenin–proteinases interactions during tooth enamel biomineralization. A stepwise strategy is introduced to kinetically and quantitatively identify the crystal-binding motifs in amelogenin, including a peptide screening assay, a competitive adsorption assay, and a kinetic-binding assay using amelogenin and gene-engineered amelogenin mutants. A modified enzyme-linked immunosorbent assay on crystal surfaces is also applied to compare binding amounts of amelogenin and its mutants on different planes of apatite crystals. We describe the detailed protocols for these assays and provide the considerations for these experiments in this chapter. PMID:24188774

Quantitative Evaluation of the Total Magnetic Moments of Colloidal Magnetic Nanoparticles: A Kinetics-based Method.

PubMed

Liu, Haiyi; Sun, Jianfei; Wang, Haoyao; Wang, Peng; Song, Lina; Li, Yang; Chen, Bo; Zhang, Yu; Gu, Ning

2015-06-08

A kinetics-based method is proposed to quantitatively characterize the collective magnetization of colloidal magnetic nanoparticles. The method is based on the relationship between the magnetic force on a colloidal droplet and the movement of the droplet under a gradient magnetic field. Through computational analysis of the kinetic parameters, such as displacement, velocity, and acceleration, the magnetization of colloidal magnetic nanoparticles can be calculated. In our experiments, the values measured by using our method exhibited a better linear correlation with magnetothermal heating, than those obtained by using a vibrating sample magnetometer and magnetic balance. This finding indicates that this method may be more suitable to evaluate the collective magnetism of colloidal magnetic nanoparticles under low magnetic fields than the commonly used methods. Accurate evaluation of the magnetic properties of colloidal nanoparticles is of great importance for the standardization of magnetic nanomaterials and for their practical application in biomedicine. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Photochemistry and Transmission Pump-Probe Spectroscopy of 2-Azidobiphenyls in Aqueous Nanocrystalline Suspensions: Simplified Kinetics in Crystalline Solids.

PubMed

Chung, Tim S; Ayitou, Anoklase J-L; Park, Jin H; Breslin, Vanessa M; Garcia-Garibay, Miguel A

2017-04-20

Aqueous nanocrystalline suspensions provide a simple and efficient medium for performing transmission spectroscopy measurements in the solid state. In this Letter we describe the use of laser flash photolysis methods to analyze the photochemistry of 2-azidobiphenyl and several aryl-substituted derivatives. We show that all the crystalline compounds analyzed in this study transform quantitatively into carbazole products via a crystal-to-crystal reconstructive phase transition. While the initial steps of the reaction cannot be followed within the time resolution of our instrument (ca. 8 ns), we detected the primary isocarbazole photoproducts and analyzed the kinetics of their formal 1,5-H shift reactions, which take place in time scales that range from a few nanoseconds to several microseconds. It is worth noting that the high reaction selectivity observed in the crystalline state translates into a clean and simple kinetic process compared to that in solution.

Quantitative Studies on the Propagation and Extinction of Near-Limit Premixed Flames Under Normal and Microgravity

NASA Technical Reports Server (NTRS)

Dong, Y.; Spedding, G. R.; Egolfopoulos, F. N.; Miller, F. J.

2003-01-01

The main objective of this research is to introduce accurate fluid mechanics measurements diagnostics in the 2.2-s drop tower for the determination of the detailed flow-field at the states of extinction. These results are important as they can then be compared with confidence with detailed numerical simulations so that important insight is provided into near-limit phenomena that are controlled by not well-understood kinetics and thermal radiation processes. Past qualitative studies did enhance our general understanding on the subject. However, quantitative studies are essential for the validation of existing models that subsequently be used to describe near-limit phenomena that can initiate catastrophic events in micro- and/or reduced gravity environments.

Structure elucidation and degradation kinetic study of Ofloxacin using surface enhanced Raman spectroscopy

NASA Astrophysics Data System (ADS)

El-Zahry, Marwa R.; Lendl, Bernhard

2018-03-01

A simple, fast and sensitive surface enhanced Raman spectroscopy (SERS) method for quantitative determination of fluoroquinolone antibiotic Ofloxacin (OFX) is presented. Also the stability behavior of OFX was investigated by monitoring the SERS spectra of OFX after various degradation processes. Acidic, basic and oxidative force degradation processes were applied at different time intervals. The forced degradation conditions were conducted and followed using SERS method utilizing silver nanoparticles (Ag NPs) as a SERS substrate. The Ag NPs colloids were prepared by reduction of silver nitrate using polyethyelene glycol (PEG) as a reducing and stabilizing agent. Validation tests were done in accordance with International Conference on Harmonization (ICH) guidelines. The calibration curve with a correlation coefficient (R = 0.9992) was constructed as a relationship between the concentration range of OFX (100-500 ng/ml) and SERS intensity at 1394 cm- 1 band. LOD and LOQ values were calculated and found to be 23.5 ng/ml and 72.6 ng/ml, respectively. The developed method was applied successfully for quantitation of OFX in different pharmaceutical dosage forms. Kinetic parameters were calculated including rate constant of the degradation of the studied antibiotic.

Ice recrystallization kinetics in the presence of synthetic antifreeze glycoprotein analogues using the framework of LSW theory.

PubMed

Budke, C; Heggemann, C; Koch, M; Sewald, N; Koop, T

2009-03-05

The Ostwald ripening of polycrystalline ice in aqueous sucrose solutions was investigated experimentally. The kinetics of this ice recrystallization process was studied at temperatures between -6 and -10 degrees C and varying ice volume fractions. Using the theory of Lifshitz, Slyozov, and Wagner (LSW), the diffusion-limited rate constant for ice recrystallization was determined. Also, the effects of synthetic analogues of natural antifreeze glycoproteins (AFGP) were studied. These analogues synAFGPmi (i = 3-5) contained monosaccharide side groups instead of disaccharide side groups that occur in natural AFGP. In order to account for the inhibition effect of the synAFGPmi, we have modified classical LSW theory, allowing for the derivation of inhibition rate constants. It was found that the investigated synAFGPmi inhibit ice recrystallization at concentrations down to approximately 3 microg mL(-1) or, equivalently, approximately 1 micromol L(-1) for the largest synAFGPmi investigated: synAFGPm5. Hence, our new method is capable of quantitatively assessing the efficiency of very similar AFGP with a sensitivity that is at least 2 orders of magnitude larger than that typical for quantitative thermal hysteresis measurements.

Comparison of the performance of tracer kinetic model-driven registration for dynamic contrast enhanced MRI using different models of contrast enhancement.

PubMed

Buonaccorsi, Giovanni A; Roberts, Caleb; Cheung, Sue; Watson, Yvonne; O'Connor, James P B; Davies, Karen; Jackson, Alan; Jayson, Gordon C; Parker, Geoff J M

2006-09-01

The quantitative analysis of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) data is subject to model fitting errors caused by motion during the time-series data acquisition. However, the time-varying features that occur as a result of contrast enhancement can confound motion correction techniques based on conventional registration similarity measures. We have therefore developed a heuristic, locally controlled tracer kinetic model-driven registration procedure, in which the model accounts for contrast enhancement, and applied it to the registration of abdominal DCE-MRI data at high temporal resolution. Using severely motion-corrupted data sets that had been excluded from analysis in a clinical trial of an antiangiogenic agent, we compared the results obtained when using different models to drive the tracer kinetic model-driven registration with those obtained when using a conventional registration against the time series mean image volume. Using tracer kinetic model-driven registration, it was possible to improve model fitting by reducing the sum of squared errors but the improvement was only realized when using a model that adequately described the features of the time series data. The registration against the time series mean significantly distorted the time series data, as did tracer kinetic model-driven registration using a simpler model of contrast enhancement. When an appropriate model is used, tracer kinetic model-driven registration influences motion-corrupted model fit parameter estimates and provides significant improvements in localization in three-dimensional parameter maps. This has positive implications for the use of quantitative DCE-MRI for example in clinical trials of antiangiogenic or antivascular agents.

Design and characterization of a prototype enzyme microreactor: quantification of immobilized transketolase kinetics.

PubMed

Matosevic, S; Lye, G J; Baganz, F

2010-01-01

In this work, we describe the design of an immobilized enzyme microreactor (IEMR) for use in transketolase (TK) bioconversion process characterization. The prototype microreactor is based on a 200-microm ID fused silica capillary for quantitative kinetic analysis. The concept is based on the reversible immobilization of His(6)-tagged enzymes via Ni-NTA linkage to surface derivatized silica. For the initial microreactor design, the mode of operation is a stop-flow analysis which promotes higher degrees of conversion. Kinetics for the immobilized TK-catalysed synthesis of L-erythrulose from substrates glycolaldehyde (GA) and hydroxypyruvate (HPA) were evaluated based on a Michaelis-Menten model. Results show that the TK kinetic parameters in the IEMR (V(max(app)) = 0.1 +/- 0.02 mmol min(-1), K(m(app)) = 26 +/- 4 mM) are comparable with those measured in free solution. Furthermore, the k(cat) for the microreactor of 4.1 x 10(5) s(-1) was close to the value for the bioconversion in free solution. This is attributed to the controlled orientation and monolayer surface coverage of the His(6)-immobilized TK. Furthermore, we show quantitative elution of the immobilized TK and the regeneration and reuse of the derivatized capillary over five cycles. The ability to quantify kinetic parameters of engineered enzymes at this scale has benefits for the rapid and parallel evaluation of evolved enzyme libraries for synthetic biology applications and for the generation of kinetic models to aid bioconversion process design and bioreactor selection as a more efficient alternative to previously established microwell-based systems for TK bioprocess characterization.

Evidence for a Shared Mechanism in the Formation of Urea-Induced Kinetic and Equilibrium Intermediates of Horse Apomyoglobin from Ultrarapid Mixing Experiments.

PubMed

Mizukami, Takuya; Abe, Yukiko; Maki, Kosuke

2015-01-01

In this study, the equivalence of the kinetic mechanisms of the formation of urea-induced kinetic folding intermediates and non-native equilibrium states was investigated in apomyoglobin. Despite having similar structural properties, equilibrium and kinetic intermediates accumulate under different conditions and via different mechanisms, and it remains unknown whether their formation involves shared or distinct kinetic mechanisms. To investigate the potential mechanisms of formation, the refolding and unfolding kinetics of horse apomyoglobin were measured by continuous- and stopped-flow fluorescence over a time range from approximately 100 μs to 10 s, along with equilibrium unfolding transitions, as a function of urea concentration at pH 6.0 and 8°C. The formation of a kinetic intermediate was observed over a wider range of urea concentrations (0-2.2 M) than the formation of the native state (0-1.6 M). Additionally, the kinetic intermediate remained populated as the predominant equilibrium state under conditions where the native and unfolded states were unstable (at ~0.7-2 M urea). A continuous shift from the kinetic to the equilibrium intermediate was observed as urea concentrations increased from 0 M to ~2 M, which indicates that these states share a common kinetic folding mechanism. This finding supports the conclusion that these intermediates are equivalent. Our results in turn suggest that the regions of the protein that resist denaturant perturbations form during the earlier stages of folding, which further supports the structural equivalence of transient and equilibrium intermediates. An additional folding intermediate accumulated within ~140 μs of refolding and an unfolding intermediate accumulated in <1 ms of unfolding. Finally, by using quantitative modeling, we showed that a five-state sequential scheme appropriately describes the folding mechanism of horse apomyoglobin.

Kinetic signature of fractal-like filament networks formed by orientational linear epitaxy.

PubMed

Hwang, Wonmuk; Eryilmaz, Esma

2014-07-11

We study a broad class of epitaxial assembly of filament networks on lattice surfaces. Over time, a scale-free behavior emerges with a 2.5-3 power-law exponent in filament length distribution. Partitioning between the power-law and exponential behaviors in a network can be used to find the stage and kinetic parameters of the assembly process. To analyze real-world networks, we develop a computer program that measures the network architecture in experimental images. Application to triaxial networks of collagen fibrils shows quantitative agreement with our model. Our unifying approach can be used for characterizing and controlling the network formation that is observed across biological and nonbiological systems.

Structures of glycans bound to receptors from saturation transfer difference (STD) NMR spectroscopy: quantitative analysis by using CORCEMA-ST.

PubMed

Enríquez-Navas, Pedro M; Guzzi, Cinzia; Muñoz-García, Juan C; Nieto, Pedro M; Angulo, Jesús

2015-01-01

Glycan-receptor interactions are of fundamental relevance for a large number of biological processes, and their kinetics properties (medium/weak binding affinities) make them appropriated to be studied by ligand observed NMR techniques, among which saturation transfer difference (STD) NMR spectroscopy has been shown to be a very robust and powerful approach. The quantitative analysis of the results from a STD NMR study of a glycan-receptor interaction is essential to be able to translate the resulting spectral intensities into a 3D molecular model of the complex. This chapter describes how to carry out such a quantitative analysis by means of the Complete Relaxation and Conformational Exchange Matrix Approach for STD NMR (CORCEMA-ST), in general terms, and an example of a previous work on an antibody-glycan interaction is also shown.

Cold Incineration of Chlorophenols in Aqueous Solution by Advanced Electrochemical Process Electro-Fenton. Effect of Number and Position of Chlorine Atoms on the Degradation Kinetics

NASA Astrophysics Data System (ADS)

Oturan, Nihal; Panizza, Marco; Oturan, Mehmet A.

2009-09-01

This study reports the kinetics of the degradation of several chlorophenols (CPs), such as monochlorophenols (2-chlorophenol and 4-chlorophenol), dichlorophenols (2,4-dichlorophenol and 2,6- dichlorophenol), trichlorophenols (2,3,5- trichlorophenol and 2,4,5-trichlorophenol), 2,3,5,6-tetrachlorophenol, and pentachlorophenol, by the electro-Fenton process using a carbon felt cathode and a Pt anode. The effect of number and the position of the chlorine atoms in the aromatic ring on the oxidative degradation rate was evaluated and discussed. The oxidation reaction of all the CPs with hydroxyl radicals evidenced a pseudo-first-order kinetics and the rate constant decreased with increasing the number of chlorine atoms. The absolute rate constant of second-order reaction kinetics between CPs and •OH was determined by the competition kinetics method in the range of (3.56-7.75) × 109 M-1 s-1 and follows the same sequence of the apparent rate constants. The mineralization of several CPs and of a mixture of all CPs under study was monitored by the total organic carbon (TOC) removal and the chlorine release during mineralization was followed by ion chromatography. Our results demonstrated that more chlorinated phenols are more difficult to mineralize; however for all the tested CPs, almost quantitative release of chloride ions was obtained after 6 h of treatment.

Kinetic Analysis of Amylase Using Quantitative Benedict's and Iodine Starch Reagents

ERIC Educational Resources Information Center

Cochran, Beverly; Lunday, Deborah; Miskevich, Frank

2008-01-01

Quantitative analysis of carbohydrates is a fundamental analytical tool used in many aspects of biology and chemistry. We have adapted a technique developed by Mathews et al. using an inexpensive scanner and open-source image analysis software to quantify amylase activity using both the breakdown of starch and the appearance of glucose. Breakdown…

Kinetics of microwave assisted extraction of pectin from Balinese orange peel using Pseudo-homogeneous model

NASA Astrophysics Data System (ADS)

Megawati, Wulansarie, Ria; Faiz, Merisa Bestari; Adi, Susatyo; Sammadikun, Waliyuddin

2018-03-01

The objective of this work was to study the homogeneous kinetics of pectin extraction of Balinese orange peel conducted using Microwave Assisted Extraction (MAE). The experimental data showed that the power increases (180 to 600 W), so that the extraction yield of pectin also increases (12.2 to 30.6 % w/w). Moreover, the extraction time is longer (10, 15, and 20 min) the yield of pectin increases (8.8, 20.2, and 40.5). At time after of 20 min (25 and 30 min), the yield starts to decrease (36.6 and 22.9). This phenomena shows pectin degradation. Therefore, pectin extraction is a series reaction, i.e. extraction and degradation. The calculation result showed that pseudo series homogeneous model can quantitatively describe the extraction kinetics. The kinetic constants can be expressed by Arrhenius equation with the frequency factors of 1.58 × 105 and 2.29 × 105 1/min, while the activation energies are 64,350 and 56,571 J/mole for extraction and degradation, respectively.

Effect of Prior Athermal Martensite on the Isothermal Transformation Kinetics Below M s in a Low-C High-Si Steel

NASA Astrophysics Data System (ADS)

Navarro-López, A.; Sietsma, J.; Santofimia, M. J.

2016-03-01

Thermomechanical processing of Advanced Multiphase High Strength Steels often includes isothermal treatments around the martensite start temperature ( M s). It has been reported that the presence of martensite formed prior to these isothermal treatments accelerates the kinetics of the subsequent transformation. This kinetic effect is commonly attributed to the creation of potential nucleation sites at martensite-austenite interfaces. The aim of this study is to determine qualitatively and quantitatively the effect of a small volume fraction of martensite on the nucleation kinetics of the subsequent transformation. For this purpose, dilatometry experiments were performed at different temperatures above and below the M s temperature for athermal martensite in a low-carbon high-silicon steel. Microstructural analysis led to the identification of the isothermal decomposition product formed above and below M s as bainitic ferrite. The analysis of the transformation processes demonstrated that the initial stage of formation of bainitic ferrite at heat treatments below M s is at least two orders of magnitude faster than above M s due to the presence of martensite.

Evaluation of the recrystallization kinetics of hot-melt extruded polymeric solid dispersions using an improved Avrami equation

PubMed Central

Feng, Xin; Ye, Xingyou; Park, Jun-Bom; Lu, Wenli; Morott, Joe; Beissner, Brad; Lian, Zhuoyang John; Pinto, Elanor; Bi, Vivian; Porter, Stu; Durig, Tom; Majumdar, Soumyajit; Repka, Michael A.

2017-01-01

The recrystallization of an amorphous drug in a solid dispersion system could lead to a loss in the drug solubility and bioavailability. The primary objective of the current research was to use an improved kinetic model to evaluate the recrystallization kinetics of amorphous structures and to further understand the factors influencing the physical stability of amorphous solid dispersions. Amorphous solid dispersions of fenofibrate with different molecular weights of hydroxypropylcellulose, HPC (Klucel™ LF, EF, ELF) were prepared utilizing hot-melt extrusion technology. Differential scanning calorimetry was utilized to quantitatively analyze the extent of recrystallization in the samples stored at different temperatures and relative humidity (RH) conditions. The experimental data were fitted into the improved kinetics model of a modified Avrami equation to calculate the recrystallization rate constants. Klucel LF, the largest molecular weight among the HPCs used, demonstrated the greatest inhibition of fenofibrate recrystallization. Additionally, the recrystallization rate (k) decreased with increasing polymer content, however exponentially increased with higher temperature. Also k increased linearly rather than exponentially over the range of RH studied. PMID:25224341

Evaluation of the recrystallization kinetics of hot-melt extruded polymeric solid dispersions using an improved Avrami equation.

PubMed

Feng, Xin; Ye, Xingyou; Park, Jun-Bom; Lu, Wenli; Morott, Joe; Beissner, Brad; Lian, Zhuoyang John; Pinto, Elanor; Bi, Vivian; Porter, Stu; Durig, Tom; Majumdar, Soumyajit; Repka, Michael A

2015-01-01

The recrystallization of an amorphous drug in a solid dispersion system could lead to a loss in the drug solubility and bioavailability. The primary objective of the current research was to use an improved kinetic model to evaluate the recrystallization kinetics of amorphous structures and to further understand the factors influencing the physical stability of amorphous solid dispersions. Amorphous solid dispersions of fenofibrate with different molecular weights of hydroxypropylcellulose, HPC (Klucel™ LF, EF, ELF) were prepared utilizing hot-melt extrusion technology. Differential scanning calorimetry was utilized to quantitatively analyze the extent of recrystallization in the samples stored at different temperatures and relative humidity (RH) conditions. The experimental data were fitted into the improved kinetics model of a modified Avrami equation to calculate the recrystallization rate constants. Klucel LF, the largest molecular weight among the HPCs used, demonstrated the greatest inhibition of fenofibrate recrystallization. Additionally, the recrystallization rate (k) decreased with increasing polymer content, however exponentially increased with higher temperature. Also k increased linearly rather than exponentially over the range of RH studied.

Toward a Better Quantitative Understanding of Polar Stratospheric Ozone Loss

NASA Technical Reports Server (NTRS)

Frieler, K.; Rex, M.; Salawitch, R. J.; Canty, T.; Streibel, M.; Stimpfle, R. M.; Pfeilsticker, K.; Dorf, M.; Weisenstein, D. K.; Godin-Beekmann, S.

2006-01-01

Previous studies have shown that observed large O3 loss rates in cold Arctic Januaries cannot be explained with current understanding of the loss processes, recommended reaction kinetics, and standard assumptions about total stratospheric chlorine and bromine. Studies based on data collected during recent field campaigns suggest faster rates of photolysis and thermal decomposition of ClOOCl and higher stratospheric bromine concentrations than previously assumed. We show that a model accounting for these kinetic changes and higher levels of BrO can largely resolve the January Arctic O3 loss problem and closely reproduces observed Arctic O3 loss while being consistent with observed levels of ClO and ClOOCl. The model also suggests that bromine catalyzed O3 loss is more important relative to chlorine catalyzed loss than previously thought.

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

During this time period, at WVU, we tried several methods to eliminate problems related to condensation of heavier products when reduced Mo-Ni-K/C materials were used as catalysts. We then resumed our kinetic study on the reduced Mo-Ni-K/C catalysts. We have also obtained same preliminary results in our attempts to analyze quantitatively the temperature-programmed reduction (TPR) spectra for C-supported Mo-based catalysts. We have completed the kinetic study for the sulfided Co-K-MoS /C catalyst. We have compared the results of methanol synthesis 2 using the membrane reactor with those using a simple plug-flow reactor. At UCC, the complete characterization of selected catalystsmore » has been completed. The results suggest that catalyst pretreatment under different reducing conditions yield different surface compositions and thus different catalytic reactivities.« less

Measurements and Modeling of Nitric Oxide Formation in Counterflow, Premixed CH4/O2/N2 Flames

NASA Technical Reports Server (NTRS)

Thomsen, D. Douglas; Laurendeau, Normand M.

2000-01-01

Laser-induced fluorescence (LIF) measurements of NO concentration in a variety of CH4/O2/N2 flames are used to evaluate the chemical kinetics of NO formation. The analysis begins with previous measurements in flat, laminar, premixed CH4/O2/N2 flames stabilized on a water-cooled McKenna burner at pressures ranging from 1 to 14.6 atm, equivalence ratios from 0.5 to 1.6, and volumetric nitrogen/oxygen dilution ratios of 2.2, 3.1 and 3.76. These measured results are compared to predictions to determine the capabilities and limitations of the comprehensive kinetic mechanism developed by the Gas Research Institute (GRI), version 2.11. The model is shown to predict well the qualitative trends of NO formation in lean-premixed flames, while quantitatively underpredicting NO concentration by 30-50%. For rich flames, the model is unable to even qualitatively match the experimental results. These flames were found to be limited by low temperatures and an inability to separate the flame from the burner surface. In response to these limitations, a counterflow burner was designed for use in opposed premixed flame studies. A new LIF calibration technique was developed and applied to obtain quantitative measurements of NO concentration in laminar, counterflow premixed, CH4/O2/N2 flames at pressures ranging from 1 to 5.1 atm, equivalence ratios of 0.6 to 1.5, and an N2/O2 dilution ratio of 3.76. The counterflow premixed flame measurements are combined with measurements in burner-stabilized premixed flames and counterflow diffusion flames to build a comprehensive database for analysis of the GRI kinetic mechanism. Pathways, quantitative reaction path and sensitivity analyses are applied to the GRI mechanism for these flame conditions. The prompt NO mechanism is found to severely underpredict the amount of NO formed in rich premixed and nitrogen-diluted diffusion flames. This underprediction is traced to uncertainties in the CH kinetics as well as in the nitrogen oxidation chemistry. Suggestions are made which significantly improve the predictive capability of the GRI mechanism in near-stoichiometric, rich, premixed flames and in atmospheric-pressure, diffusion flames. However, the modified reaction mechanism is unable to model the formation of NO in ultra-rich, premixed or in high-pressure, nonpremixed flames, thus indicating the need for additional study under these conditions.

Quantitative analysis of small molecule-nucleic acid interactions with a biosensor surface and surface plasmon resonance detection.

PubMed

Liu, Yang; Wilson, W David

2010-01-01

Surface plasmon resonance (SPR) technology with biosensor surfaces has become a widely-used tool for the study of nucleic acid interactions without any labeling requirements. The method provides simultaneous kinetic and equilibrium characterization of the interactions of biomolecules as well as small molecule-biopolymer binding. SPR monitors molecular interactions in real time and provides significant advantages over optical or calorimetic methods for systems with strong binding coupled to small spectroscopic signals and/or reaction heats. A detailed and practical guide for nucleic acid interaction analysis using SPR-biosensor methods is presented. Details of the SPR technology and basic fundamentals are described with recommendations on the preparation of the SPR instrument, sensor chips, and samples, as well as extensive information on experimental design, quantitative and qualitative data analysis and presentation. A specific example of the interaction of a minor-groove-binding agent with DNA is evaluated by both kinetic and steady-state SPR methods to illustrate the technique. Since the molecules that bind cooperatively to specific DNA sequences are attractive for many applications, a cooperative small molecule-DNA interaction is also presented.

Second-order advantage obtained from standard addition first-order instrumental data and multivariate curve resolution-alternating least squares. Calculation of the feasible bands of results.

PubMed

Mohseni, Naimeh; Bahram, Morteza; Olivieri, Alejandro C

2014-03-25

In order to achieve the second-order advantage, second-order data per sample is usually required, e.g., kinetic-spectrophotometric data. In this study, instead of monitoring the time evolution of spectra (and collecting the kinetic-spectrophotometric data) replicate spectra are used to build a virtual second order data. This data matrix (replicate mode×λ) is rank deficient. Augmentation of these data with standard addition data [or standard sample(s)] will break the rank deficiency, making the quantification of the analyte of interest possible. The MCR-ALS algorithm was applied for the resolution and quantitation of the analyte in both simulated and experimental data sets. In order to evaluate the rotational ambiguity in the retrieved solutions, the MCR-BANDS algorithm was employed. It has been shown that the reliability of the quantitative results significantly depends on the amount of spectral overlap in the spectral region of occurrence of the compound of interest and the remaining constituent(s). Copyright © 2013 Elsevier B.V. All rights reserved.

Coagulation monitoring based on blood elastic measurement using optical coherence tomography

NASA Astrophysics Data System (ADS)

Xu, Xiangqun; Zhu, Jiang; Chen, Zhongping

2017-02-01

Blood coagulation monitoring is important to diagnose hematological diseases and cardiovascular diseases and to predict the risk of bleeding and excessive clotting. In this study, we developed a system to dynamically monitor blood coagulation and quantitatively determine the coagulation function by blood elastic measurement. When blood forms a clot from a liquid, ultrasonic force induces a shear wave, which is detected by optical coherence tomography (OCT). The coagulation of porcine whole blood recalcified by calcium chloride is assessed using the metrics of reaction time, clot formation kinetics and maximum shear modulus. The OCE system can noninvasively monitor the blood coagulation and quantitatively determine the coagulation function.

Kinetic Modeling Sheds Light on the Mode of Action of Recombinant Factor VIIa on Thrombin Generation

DTIC Science & Technology

2011-01-01

Regular Article Kinetic modeling sheds light on the mode of action of recombinant factor VIIa on thrombin generation Alexander Y. Mitrophanov...its effects on the quantitative parameters of thrombin generation. For recombinant activated factor VII (rFVIIa) ― a promising hemostasis-inducing...modulate thrombin production , it is necessary to identify rFVIIa-induced effects that are compatible with the available biochemical knowledge about

Integrated stoichiometric, thermodynamic and kinetic modelling of steady state metabolism

PubMed Central

Fleming, R.M.T.; Thiele, I.; Provan, G.; Nasheuer, H.P.

2010-01-01

The quantitative analysis of biochemical reactions and metabolites is at frontier of biological sciences. The recent availability of high-throughput technology data sets in biology has paved the way for new modelling approaches at various levels of complexity including the metabolome of a cell or an organism. Understanding the metabolism of a single cell and multi-cell organism will provide the knowledge for the rational design of growth conditions to produce commercially valuable reagents in biotechnology. Here, we demonstrate how equations representing steady state mass conservation, energy conservation, the second law of thermodynamics, and reversible enzyme kinetics can be formulated as a single system of linear equalities and inequalities, in addition to linear equalities on exponential variables. Even though the feasible set is non-convex, the reformulation is exact and amenable to large-scale numerical analysis, a prerequisite for computationally feasible genome scale modelling. Integrating flux, concentration and kinetic variables in a unified constraint-based formulation is aimed at increasing the quantitative predictive capacity of flux balance analysis. Incorporation of experimental and theoretical bounds on thermodynamic and kinetic variables ensures that the predicted steady state fluxes are both thermodynamically and biochemically feasible. The resulting in silico predictions are tested against fluxomic data for central metabolism in E. coli and compare favourably with in silico prediction by flux balance analysis. PMID:20230840

Quantitative diffusion and swelling kinetic measurements using large-angle interferometric refractometry.

PubMed

Saunders, John E; Chen, Hao; Brauer, Chris; Clayton, McGregor; Chen, Weijian; Barnes, Jack A; Loock, Hans-Peter

2015-12-07

The uptake and release of sorbates into films and coatings is typically accompanied by changes of the films' refractive index and thickness. We provide a comprehensive model to calculate the concentration of the sorbate from the average refractive index and the film thickness, and validate the model experimentally. The mass fraction of the analyte partitioned into a film is described quantitatively by the Lorentz-Lorenz equation and the Clausius-Mosotti equation. To validate the model, the uptake kinetics of water and other solvents into SU-8 films (d = 40-45 μm) were explored. Large-angle interferometric refractometry measurements can be used to characterize films that are between 15 μm to 150 μm thick and, Fourier analysis, is used to determine independently the thickness, the average refractive index and the refractive index at the film-substrate interface at one-second time intervals. From these values the mass fraction of water in SU-8 was calculated. The kinetics were best described by two independent uptake processes having different rates. Each process followed one-dimensional Fickian diffusion kinetics with diffusion coefficients for water into SU-8 photoresist film of 5.67 × 10(-9) cm(2) s(-1) and 61.2 × 10(-9) cm(2) s(-1).

Predicting Ki67% expression from DCE-MR images of breast tumors using textural kinetic features in tumor habitats

NASA Astrophysics Data System (ADS)

Chaudhury, Baishali; Zhou, Mu; Farhidzadeh, Hamidreza; Goldgof, Dmitry B.; Hall, Lawrence O.; Gatenby, Robert A.; Gillies, Robert J.; Weinfurtner, Robert J.; Drukteinis, Jennifer S.

2016-03-01

The use of Ki67% expression, a cell proliferation marker, as a predictive and prognostic factor has been widely studied in the literature. Yet its usefulness is limited due to inconsistent cut off scores for Ki67% expression, subjective differences in its assessment in various studies, and spatial variation in expression, which makes it difficult to reproduce as a reliable independent prognostic factor. Previous studies have shown that there are significant spatial variations in Ki67% expression, which may limit its clinical prognostic utility after core biopsy. These variations are most evident when examining the periphery of the tumor vs. the core. To date, prediction of Ki67% expression from quantitative image analysis of DCE-MRI is very limited. This work presents a novel computer aided diagnosis framework to use textural kinetics to (i) predict the ratio of periphery Ki67% expression to core Ki67% expression, and (ii) predict Ki67% expression from individual tumor habitats. The pilot cohort consists of T1 weighted fat saturated DCE-MR images from 17 patients. Support vector regression with a radial basis function was used for predicting the Ki67% expression and ratios. The initial results show that texture features from individual tumor habitats are more predictive of the Ki67% expression ratio and spatial Ki67% expression than features from the whole tumor. The Ki67% expression ratio could be predicted with a root mean square error (RMSE) of 1.67%. Quantitative image analysis of DCE-MRI using textural kinetic habitats, has the potential to be used as a non-invasive method for predicting Ki67 percentage and ratio, thus more accurately reporting high KI-67 expression for patient prognosis.

Simultaneous Quantification of Viral Antigen Expression Kinetics Using Data-Independent (DIA) Mass Spectrometry*

PubMed Central

Croft, Nathan P.; de Verteuil, Danielle A.; Smith, Stewart A.; Wong, Yik Chun; Schittenhelm, Ralf B.; Tscharke, David C.; Purcell, Anthony W.

2015-01-01

The generation of antigen-specific reagents is a significant bottleneck in the study of complex pathogens that express many hundreds to thousands of different proteins or to emerging or new strains of viruses that display potential pandemic qualities and therefore require rapid investigation. In these instances the development of antibodies for example can be prohibitively expensive to cover the full pathogen proteome, or the lead time may be unacceptably long in urgent cases where new highly pathogenic viral strains may emerge. Because genomic information on such pathogens can be rapidly acquired this opens up avenues using mass spectrometric approaches to study pathogen antigen expression, host responses and for screening the utility of therapeutics. In particular, data-independent acquisition (DIA) modalities on high-resolution mass spectrometers generate spectral information on all components of a complex sample providing depth of coverage hitherto only seen in genomic deep sequencing. The spectral information generated by DIA can be iteratively interrogated for potentially any protein of interest providing both evidence of protein expression and quantitation. Here we apply a solely DIA mass spectrometry based methodology to profile the viral antigen expression in cells infected with vaccinia virus up to 9 h post infection without the need for antigen specific antibodies or other reagents. We demonstrate deep coverage of the vaccinia virus proteome using a SWATH-MS acquisition approach, extracting quantitative kinetics of 100 virus proteins within a single experiment. The results highlight the complexity of vaccinia protein expression, complementing what is known at the transcriptomic level, and provide a valuable resource and technique for future studies of viral infection and replication kinetics. Furthermore, they highlight the utility of DIA and mass spectrometry in the dissection of host-pathogen interactions. PMID:25755296

Minimal Model of Quantum Kinetic Clusters for the Energy-Transfer Network of a Light-Harvesting Protein Complex.

PubMed

Wu, Jianlan; Tang, Zhoufei; Gong, Zhihao; Cao, Jianshu; Mukamel, Shaul

2015-04-02

The energy absorbed in a light-harvesting protein complex is often transferred collectively through aggregated chromophore clusters. For population evolution of chromophores, the time-integrated effective rate matrix allows us to construct quantum kinetic clusters quantitatively and determine the reduced cluster-cluster transfer rates systematically, thus defining a minimal model of energy-transfer kinetics. For Fenna-Matthews-Olson (FMO) and light-havrvesting complex II (LCHII) monomers, quantum Markovian kinetics of clusters can accurately reproduce the overall energy-transfer process in the long-time scale. The dominant energy-transfer pathways are identified in the picture of aggregated clusters. The chromophores distributed extensively in various clusters can assist a fast and long-range energy transfer.

Quantitative studies of kinetic effects in direct- and indirect-drive Inertial Confinement Fusion implosions

NASA Astrophysics Data System (ADS)

Rinderknecht, Hans

2013-10-01

A comprehensive set of experiments using shock-driven implosions has been conducted to quantitatively study kinetic effects by exploring deviations from hydrodynamic behavior in plasmas relevant to inertial confinement fusion (ICF). Two types of targets were imploded at OMEGA to create ~10 keV, ~1022 cm-3 plasmas with conditions comparable to the incipient hotspot in ignition designs: thin-glass targets filled with mixtures of D2 and 3He gas; and thin deuterated-plastic shells filled with 3He. In the thin-glass experiments, the gas pressure was varied from 1 to 25 atm to scan the ion-mean-free path in the plasma at shock burn. The observed nuclear yields and temperatures deviated more strongly from hydrodynamic predictions as the ion-mean-free path increased to the order of the plasma size. This result provides the first direct experimental evidence how kinetic effects impact yields and ion temperature. The ratio of D to 3He was also varied while maintaining the fuel mass density. As the D fraction was reduced, the DD and D3He fusion products displayed an anomalous yield reduction. Separation of the D and 3He ion species across the strong (Mach ~10) shock-front will be discussed as the likely cause of this result. Finally, thin-CD shells filled with 3He produced significantly more D3He-protons when imploded than is explained by hydrodynamic mix models. This result suggests a kinetic form of mix dominates at the strongly-shocked shell-gas interface. This work was performed in collaboration with C. Li, M. Rosenberg, A. Zylstra, H. Sio, M. Gatu Johnson, F. Séguin, J. Frenje, and R. Petrasso (MIT), V. Glebov, C. Stoeckl, J. Delettrez, and C. Sangster (LLE), J. Pino, P. Amendt, C. Bellei, and S. Wilks (LLNL), G. Kagan, N. Hoffmann and K. Molvig (LANL), and A. Nikroo (GA) and was supported in part by the NLUF, FSC/UR, U.S. DOE, LLNL and LLE.

Hydrogen measurement during steam oxidation using coupled thermogravimetric analysis and quadrupole mass spectrometry

DOE PAGES

Parkison, Adam J.; Nelson, Andrew Thomas

2016-01-11

An analytical technique is presented with the goal of measuring reaction kinetics during steam oxidation reactions for three cases in which obtaining kinetics information often requires a prohibitive amount of time and cost. The technique presented relies on coupling thermogravimetric analysis (TGA) with a quantitative hydrogen measurement technique using quadrupole mass spectrometry (QMS). The first case considered is in differentiating between the kinetics of steam oxidation reactions and those for simultaneously reacting gaseous impurities such as nitrogen or oxygen. The second case allows one to independently measure the kinetics of oxide and hydride formation for systems in which both ofmore » these reactions are known to take place during steam oxidation. The third case deals with measuring the kinetics of formation for competing volatile and non-volatile oxides during certain steam oxidation reactions. In order to meet the requirements of the coupled technique, a methodology is presented which attempts to provide quantitative measurement of hydrogen generation using QMS in the presence of an interfering fragmentation species, namely water vapor. This is achieved such that all calibrations and corrections are performed during the TGA baseline and steam oxidation programs, making system operation virtually identical to standard TGA. Benchmarking results showed a relative error in hydrogen measurement of 5.7–8.4% following the application of a correction factor. Lastly, suggestions are made for possible improvements to the presented technique so that it may be better applied to the three cases presented.« less

Hydrogen measurement during steam oxidation using coupled thermogravimetric analysis and quadrupole mass spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parkison, Adam J.; Nelson, Andrew Thomas

An analytical technique is presented with the goal of measuring reaction kinetics during steam oxidation reactions for three cases in which obtaining kinetics information often requires a prohibitive amount of time and cost. The technique presented relies on coupling thermogravimetric analysis (TGA) with a quantitative hydrogen measurement technique using quadrupole mass spectrometry (QMS). The first case considered is in differentiating between the kinetics of steam oxidation reactions and those for simultaneously reacting gaseous impurities such as nitrogen or oxygen. The second case allows one to independently measure the kinetics of oxide and hydride formation for systems in which both ofmore » these reactions are known to take place during steam oxidation. The third case deals with measuring the kinetics of formation for competing volatile and non-volatile oxides during certain steam oxidation reactions. In order to meet the requirements of the coupled technique, a methodology is presented which attempts to provide quantitative measurement of hydrogen generation using QMS in the presence of an interfering fragmentation species, namely water vapor. This is achieved such that all calibrations and corrections are performed during the TGA baseline and steam oxidation programs, making system operation virtually identical to standard TGA. Benchmarking results showed a relative error in hydrogen measurement of 5.7–8.4% following the application of a correction factor. Lastly, suggestions are made for possible improvements to the presented technique so that it may be better applied to the three cases presented.« less

Chemical Carcinogen-Induced Changes in tRNA Metabolism in Human Cells.

DTIC Science & Technology

1981-11-01

the resolution and quantitation of modified ucleosides in the urine of cancer patients would not be particularly useful for the cell culture studies...Comparison of nucleic acid catabolism by normal human fibroblasts and fibroblasts transformed with methylazoxymethyl alcohol ( MAMA ),an activated...catabolite in long-term, pulse-chase experiments. However, the kinetics of catabolism differed, in that only the MAMA -transformed cells had generated

PET brain kinetics studies of 11C-ITMM and 11C-ITDM,radioprobes for metabotropic glutamate receptor type 1, in a nonhuman primate

PubMed Central

Yamasaki, Tomoteru; Maeda, Jun; Fujinaga, Masayuki; Nagai, Yuji; Hatori, Akiko; Yui, Joji; Xie, Lin; Nengaki, Nobuki; Zhang, Ming-Rong

2014-01-01

The metabotropic glutamate receptor type 1 (mGluR1) is a novel target protein for the development of new drugs against central nervous system disorders. Recently, we have developed 11C-labeled PET probes 11C-ITMM and 11C-ITDM, which demonstrate similar profiles, for imaging of mGluR1. In the present study, we compared 11C-ITMM and 11C-ITDM PET imaging and quantitative analysis in the monkey brain. Respective PET images showed similar distribution of uptake in the cerebellum, thalamus, and cingulate cortex. Slightly higher uptake was detected with 11C-ITDM than with 11C-ITMM. For the kinetic analysis using the two-tissue compartment model (2-TCM), the distribution volume (VT) in the cerebellum, an mGluR1-rich region in the brain, was 2.5 mL∙cm-3 for 11C-ITMM and 3.6 mL∙cm-3 for 11C-ITDM. By contrast, the VT in the pons, a region with negligible mGluR1 expression, was similarly low for both radiopharmaceuticals. Based on these results, we performed noninvasive PET quantitative analysis with general reference tissue models using the time-activity curve of the pons as a reference region. We confirmed the relationship and differences between the reference tissue models and 2-TCM using correlational scatter plots and Bland-Altman plots analyses. Although the scattergrams of both radiopharmaceuticals showed over- or underestimations of reference tissue model-based the binding potentials against 2-TCM, there were no significant differences between the two kinetic analysis models. In conclusion, we first demonstrated the potentials of 11C-ITMM and 11C-ITDM for noninvasive PET quantitative analysis using reference tissue models. In addition, our findings suggest that 11C-ITDM may be superior to 11C-ITMM as a PET probe for imaging of mGluR1, because regional VT values in PET with 11C-ITDM were higher than those of 11C-ITMM. Clinical studies of 11C-ITDM in humans will be necessary in the future. PMID:24795840

PET brain kinetics studies of (11)C-ITMM and (11)C-ITDM,radioprobes for metabotropic glutamate receptor type 1, in a nonhuman primate.

PubMed

Yamasaki, Tomoteru; Maeda, Jun; Fujinaga, Masayuki; Nagai, Yuji; Hatori, Akiko; Yui, Joji; Xie, Lin; Nengaki, Nobuki; Zhang, Ming-Rong

2014-01-01

The metabotropic glutamate receptor type 1 (mGluR1) is a novel target protein for the development of new drugs against central nervous system disorders. Recently, we have developed (11)C-labeled PET probes (11)C-ITMM and (11)C-ITDM, which demonstrate similar profiles, for imaging of mGluR1. In the present study, we compared (11)C-ITMM and (11)C-ITDM PET imaging and quantitative analysis in the monkey brain. Respective PET images showed similar distribution of uptake in the cerebellum, thalamus, and cingulate cortex. Slightly higher uptake was detected with (11)C-ITDM than with (11)C-ITMM. For the kinetic analysis using the two-tissue compartment model (2-TCM), the distribution volume (VT) in the cerebellum, an mGluR1-rich region in the brain, was 2.5 mL∙cm(-3) for (11)C-ITMM and 3.6 mL∙cm(-3) for (11)C-ITDM. By contrast, the VT in the pons, a region with negligible mGluR1 expression, was similarly low for both radiopharmaceuticals. Based on these results, we performed noninvasive PET quantitative analysis with general reference tissue models using the time-activity curve of the pons as a reference region. We confirmed the relationship and differences between the reference tissue models and 2-TCM using correlational scatter plots and Bland-Altman plots analyses. Although the scattergrams of both radiopharmaceuticals showed over- or underestimations of reference tissue model-based the binding potentials against 2-TCM, there were no significant differences between the two kinetic analysis models. In conclusion, we first demonstrated the potentials of (11)C-ITMM and (11)C-ITDM for noninvasive PET quantitative analysis using reference tissue models. In addition, our findings suggest that (11)C-ITDM may be superior to (11)C-ITMM as a PET probe for imaging of mGluR1, because regional VT values in PET with (11)C-ITDM were higher than those of (11)C-ITMM. Clinical studies of (11)C-ITDM in humans will be necessary in the future.

Kinetic Defects Induced by Melittin in Model Lipid Membranes: A Solution Atomic Force Microscopy Study.

PubMed

Pan, Jianjun; Khadka, Nawal K

2016-05-26

Quantitative characterization of membrane defects (pores) is important for elucidating the molecular basis of many membrane-active peptides. We study kinetic defects induced by melittin in vesicular and planar lipid bilayers. Fluorescence spectroscopy measurements indicate that melittin induces time-dependent calcein leakage. Solution atomic force microscopy (AFM) is used to visualize melittin-induced membrane defects. After initial equilibration, the most probable defect radius is ∼3.8 nm in 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC) bilayers. Unexpectedly, defects become larger with longer incubation, accompanied by substantial shape transformation. The initial defect radius is ∼4.7 nm in 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) bilayers. Addition of 30 mol % cholesterol to DOPC bilayers suppresses defect kinetics, although the inhibitory impact is negated by longer incubation. Overall, the kinetic rate of defect development follows DLPC > DOPC > DOPC/cholesterol. Kinetic defects are also observed when anionic lipids are present. Based on the observation that defects can occupy as large as 40% of the bilayer surface, we propose a kinetic defect growth model. We also study the effect of melittin on the phase behavior of DOPC/egg-sphingomyelin/cholesterol bilayers. We find that melittin initially suppresses or eliminates liquid-ordered (Lo) domains; Lo domains gradually emerge and become the dominant species with longer incubation; and defects in phase-coexisting bilayers have a most probable radius of ∼5 nm and are exclusively localized in the liquid-disordered (Ld) phase. Our experimental data highlight that melittin-induced membrane defects are not static; conversely, spontaneous defect growth is intrinsically associated with membrane permeabilization exerted by melittin.

Hydrogen Donor-Acceptor Fluctuations from Kinetic Isotope Effects: A Phenomenological Model

PubMed Central

Roston, Daniel; Cheatum, Christopher M.; Kohen, Amnon

2012-01-01

Kinetic isotope effects (KIEs) and their temperature dependence can probe the structural and dynamic nature of enzyme-catalyzed proton or hydride transfers. The molecular interpretation of their temperature dependence requires expensive and specialized QM/MM calculations to provide a quantitative molecular understanding. Currently available phenomenological models use a non-adiabatic assumption that is not appropriate for most hydride and proton-transfer reactions, while others require more parameters than the experimental data justify. Here we propose a phenomenological interpretation of KIEs based on a simple method to quantitatively link the size and temperature dependence of KIEs to a conformational distribution of the catalyzed reaction. The present model assumes adiabatic hydrogen tunneling, and by fitting experimental KIE data, the model yields a population distribution for fluctuations of the distance between donor and acceptor atoms. Fits to data from a variety of proton and hydride transfers catalyzed by enzymes and their mutants, as well as non-enzymatic reactions, reveal that steeply temperature-dependent KIEs indicate the presence of at least two distinct conformational populations, each with different kinetic behaviors. We present the results of these calculations for several published cases and discuss how the predictions of the calculations might be experimentally tested. The current analysis does not replace molecular quantum mechanics/molecular mechanics (QM/MM) investigations, but it provides a fast and accessible way to quantitatively interpret KIEs in the context of a Marcus-like model. PMID:22857146

A New Kinetic Spectrophotometric Method for the Quantitation of Amorolfine.

PubMed

Soto, César; Poza, Cristian; Contreras, David; Yáñez, Jorge; Nacaratte, Fallon; Toral, M Inés

2017-01-01

Amorolfine (AOF) is a compound with fungicide activity based on the dual inhibition of growth of the fungal cell membrane, the biosynthesis and accumulation of sterols, and the reduction of ergosterol. In this work a sensitive kinetic and spectrophotometric method for the AOF quantitation based on the AOF oxidation by means of KMnO 4 at 30 min (fixed time), pH alkaline, and ionic strength controlled was developed. Measurements of changes in absorbance at 610 nm were used as criterion of the oxidation progress. In order to maximize the sensitivity, different experimental reaction parameters were carefully studied via factorial screening and optimized by multivariate method. The linearity, intraday, and interday assay precision and accuracy were determined. The absorbance-concentration plot corresponding to tap water spiked samples was rectilinear, over the range of 7.56 × 10 -6 -3.22 × 10 -5  mol L -1 , with detection and quantitation limits of 2.49 × 10 -6  mol L -1 and 7.56 × 10 -6  mol L -1 , respectively. The proposed method was successfully validated for the application of the determination of the drug in the spiked tap water samples and the percentage recoveries were 94.0-105.0%. The method is simple and does not require expensive instruments or complicated extraction steps of the reaction product.

Quantitative study of bundle size effect on thermal conductivity of single-walled carbon nanotubes

NASA Astrophysics Data System (ADS)

Feng, Ya; Inoue, Taiki; An, Hua; Xiang, Rong; Chiashi, Shohei; Maruyama, Shigeo

2018-05-01

Compared with isolated single-walled carbon nanotubes (SWNTs), thermal conductivity is greatly impeded in SWNT bundles; however, the measurement of the bundle size effect is difficult. In this study, the number of SWNTs in a bundle was determined based on the transferred horizontally aligned SWNTs on a suspended micro-thermometer to quantitatively study the effect of the bundle size on thermal conductivity. Increasing the bundle size significantly degraded the thermal conductivity. For isolated SWNTs, thermal conductivity was approximately 5000 ± 1000 W m-1 K-1 at room temperature, three times larger than that of the four-SWNT bundle. The logarithmical deterioration of thermal conductivity resulting from the increased bundle size can be attributed to the increased scattering rate with neighboring SWNTs based on the kinetic theory.

Quantitative studies of sulphate conjugation by isolated rat liver cells using [35S]sulphate.

PubMed

Dawson, J; Knowles, R G; Pogson, C I

1991-06-21

We have developed a simple, rapid and sensitive method for the study of sulphate conjugation in isolated liver cells based on the incorporation of 35S from [35S]sulphate. Excess [35S]sulphate is removed by a barium precipitation procedure, leaving [35S]sulphate conjugates in solution. We have used this method to examine the kinetics of sulphation of N-acetyl-p-aminophenol (acetaminophen), 4-nitrophenol and 1-naphthol in isolated rat liver cells. The efficiency of recovery of the sulphate conjugates was greater than 86%. The method is applicable to the quantitative study of sulphate conjugation of any substrate which forms a sulphate conjugate that is soluble in the presence of barium, without the need for standards or radiolabelled sulphate acceptors.

Quantitative Functional Imaging Using Dynamic Positron Computed Tomography and Rapid Parameter Estimation Techniques

NASA Astrophysics Data System (ADS)

Koeppe, Robert Allen

Positron computed tomography (PCT) is a diagnostic imaging technique that provides both three dimensional imaging capability and quantitative measurements of local tissue radioactivity concentrations in vivo. This allows the development of non-invasive methods that employ the principles of tracer kinetics for determining physiological properties such as mass specific blood flow, tissue pH, and rates of substrate transport or utilization. A physiologically based, two-compartment tracer kinetic model was derived to mathematically describe the exchange of a radioindicator between blood and tissue. The model was adapted for use with dynamic sequences of data acquired with a positron tomograph. Rapid estimation techniques were implemented to produce functional images of the model parameters by analyzing each individual pixel sequence of the image data. A detailed analysis of the performance characteristics of three different parameter estimation schemes was performed. The analysis included examination of errors caused by statistical uncertainties in the measured data, errors in the timing of the data, and errors caused by violation of various assumptions of the tracer kinetic model. Two specific radioindicators were investigated. ('18)F -fluoromethane, an inert freely diffusible gas, was used for local quantitative determinations of both cerebral blood flow and tissue:blood partition coefficient. A method was developed that did not require direct sampling of arterial blood for the absolute scaling of flow values. The arterial input concentration time course was obtained by assuming that the alveolar or end-tidal expired breath radioactivity concentration is proportional to the arterial blood concentration. The scale of the input function was obtained from a series of venous blood concentration measurements. The method of absolute scaling using venous samples was validated in four studies, performed on normal volunteers, in which directly measured arterial concentrations were compared to those predicted from the expired air and venous blood samples. The glucose analog ('18)F-3-deoxy-3-fluoro-D -glucose (3-FDG) was used for quantitating the membrane transport rate of glucose. The measured data indicated that the phosphorylation rate of 3-FDG was low enough to allow accurate estimation of the transport rate using a two compartment model.

MASCOT2, a Lander to Characterize the Target of an Asteroid Kinetic Impactor Deflection Test (AIM) Mission

NASA Astrophysics Data System (ADS)

Biele, J.; Ulamec, S.; Krause, C.; Cozzoni, B.; Lange, C.; Grundmann, J. T.; Grimm, C.; Ho, T.-M.; Herique, A.; Plettemeier, D.; Grott, M.; Auster, H.-U.; Hercik, D.; Carnelli, I.; Galvez, A.; Philippe, C.; Küppers, M.; Grieger, B.; Gil Fernandez, J.; Grygorczuk, J.

2017-09-01

In the course of the AIDA/AIM mission studies [1,2] a lander, MASCOT2, has been studied to be deployed on the moon of the binary Near-Earth Asteroid system, (65803) Didymos. The AIDA technology demonstration mission, composed of a kinetic impactor, DART, and an observing spacecraft, AIM, has been designed to deliver vital data to determine the momentum transfer efficiency of the kinetic impact and key physical properties of the target asteroid. This will enable derivation of the impact response of the object as a function of its physical properties, a crucial quantitative point besides the qualitative proof that the asteroid has been deflected at all. A landed asset on the target asteroid greatly supports analyzing its dynamical state, mass, geophysical properties, surface and subsurface structure. The lander's main instrument is a bistatic, low frequency radar (LFR) [3a,b] to sound the interior structure of the asteroid. It is supported by a camera (MasCAM) [4], a radiometer (MARA)[5], an accelerometer (DACC [9]), and, optionally regarding the science case, also a magnetometer (MasMAG)[6].

Kinetic study on non-thermal volumetric plasma decay in the early afterglow of air discharge generated by a short pulse microwave or laser

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Wei, E-mail: yangwei861212@126.com; Zhou, Qianhong; Dong, Zhiwei

This paper reports a kinetic study on non-thermal plasma decay in the early afterglow of air discharge generated by short pulse microwave or laser. A global self-consistent model is based on the particle balance of complex plasma chemistry, electron energy equation, and gas thermal balance equation. Electron-ion Coulomb collision is included in the steady state Boltzmann equation solver to accurately describe the electron mobility and other transport coefficients. The model is used to simulate the afterglow of microsecond to nanosecond pulse microwave discharge in N{sub 2}, O{sub 2}, and air, as well as femtosecond laser filament discharge in dry andmore » humid air. The simulated results for electron density decay are in quantitative agreement with the available measured ones. The evolution of plasma decay under an external electric field is also investigated, and the effect of gas heating is considered. The underlying mechanism of plasma density decay is unveiled through the above kinetic modeling.« less

Nonclassical Kinetics of Clonal yet Heterogeneous Enzymes.

PubMed

Park, Seong Jun; Song, Sanggeun; Jeong, In-Chun; Koh, Hye Ran; Kim, Ji-Hyun; Sung, Jaeyoung

2017-07-06

Enzyme-to-enzyme variation in the catalytic rate is ubiquitous among single enzymes created from the same genetic information, which persists over the lifetimes of living cells. Despite advances in single-enzyme technologies, the lack of an enzyme reaction model accounting for the heterogeneous activity of single enzymes has hindered a quantitative understanding of the nonclassical stochastic outcome of single enzyme systems. Here we present a new statistical kinetics and exactly solvable models for clonal yet heterogeneous enzymes with possibly nonergodic state dynamics and state-dependent reactivity, which enable a quantitative understanding of modern single-enzyme experimental results for the mean and fluctuation in the number of product molecules created by single enzymes. We also propose a new experimental measure of the heterogeneity and nonergodicity for a system of enzymes.

Control of DNA strand displacement kinetics using toehold exchange.

PubMed

Zhang, David Yu; Winfree, Erik

2009-12-02

DNA is increasingly being used as the engineering material of choice for the construction of nanoscale circuits, structures, and motors. Many of these enzyme-free constructions function by DNA strand displacement reactions. The kinetics of strand displacement can be modulated by toeholds, short single-stranded segments of DNA that colocalize reactant DNA molecules. Recently, the toehold exchange process was introduced as a method for designing fast and reversible strand displacement reactions. Here, we characterize the kinetics of DNA toehold exchange and model it as a three-step process. This model is simple and quantitatively predicts the kinetics of 85 different strand displacement reactions from the DNA sequences. Furthermore, we use toehold exchange to construct a simple catalytic reaction. This work improves the understanding of the kinetics of nucleic acid reactions and will be useful in the rational design of dynamic DNA and RNA circuits and nanodevices.

Kinetics of Poliovirus Shedding following Oral Vaccination as Measured by Quantitative Reverse Transcription-PCR versus Culture

PubMed Central

Begum, Sharmin; Uddin, Md Jashim; Platts-Mills, James A.; Liu, Jie; Kirkpatrick, Beth D.; Chowdhury, Anwarul H.; Jamil, Khondoker M.; Haque, Rashidul; Petri, William A.; Houpt, Eric R.

2014-01-01

Amid polio eradication efforts, detection of oral polio vaccine (OPV) virus in stool samples can provide information about rates of mucosal immunity and allow estimation of the poliovirus reservoir. We developed a multiplex one-step quantitative reverse transcription-PCR (qRT-PCR) assay for detection of OPV Sabin strains 1, 2, and 3 directly in stool samples with an external control to normalize samples for viral quantity and compared its performance with that of viral culture. We applied the assay to samples from infants in Dhaka, Bangladesh, after the administration of trivalent OPV (tOPV) at weeks 14 and 52 of life (on days 0 [pre-OPV], +4, +11, +18, and +25 relative to vaccination). When 1,350 stool samples were tested, the sensitivity and specificity of the quantitative PCR (qPCR) assay were 89 and 91% compared with culture. A quantitative relationship between culture+/qPCR+ and culture−/qPCR+ stool samples was observed. The kinetics of shedding revealed by qPCR and culture were similar. qPCR quantitative cutoffs based on the day +11 or +18 stool samples could be used to identify the culture-positive shedders, as well as the long-duration or high-frequency shedders. Interestingly, qPCR revealed that a small minority (7%) of infants contributed the vast majority (93 to 100%) of the total estimated viral excretion across all subtypes at each time point. This qPCR assay for OPV can simply and quantitatively detect all three Sabin strains directly in stool samples to approximate shedding both qualitatively and quantitatively. PMID:25378579

Fission-fragment total kinetic energy and mass yields for neutron-induced fission of 235U and 238U with En =200 keV - 30 MeV

NASA Astrophysics Data System (ADS)

Duke, D. L.; Tovesson, F.; Brys, T.; Geppert-Kleinrath, V.; Hambsch, F.-J.; Laptev, A.; Meharchand, R.; Manning, B.; Mayorov, D.; Meierbachtol, K.; Mosby, S.; Perdue, B.; Richman, D.; Shields, D.; Vidali, M.

2017-09-01

The average Total Kinetic Energy (TKE) release and fission-fragment yields in neutron-induced fission of 235U and 238U was measured using a Frisch-gridded ionization chamber. These observables are important nuclear data quantites that are relevant to applications and for informing the next generation of fission models. The measurements were performed a the Los Alamos Neutron Science Center and cover En = 200 keV - 30 MeV. The double-energy (2E) method was used to determine the fission-fragment yields and two methods of correcting for prompt-neutron emission were explored. The results of this study are correlated mass and TKE data.

Folding and unfolding single RNA molecules under tension

PubMed Central

Woodside, Michael T; García-García, Cuauhtémoc; Block, Steven M

2010-01-01

Single-molecule force spectroscopy constitutes a powerful method for probing RNA folding: it allows the kinetic, energetic, and structural properties of intermediate and transition states to be determined quantitatively, yielding new insights into folding pathways and energy landscapes. Recent advances in experimental and theoretical methods, including fluctuation theorems, kinetic theories, novel force clamps, and ultrastable instruments, have opened new avenues for study. These tools have been used to probe folding in simple model systems, for example, RNA and DNA hairpins. Knowledge gained from such systems is helping to build our understanding of more complex RNA structures composed of multiple elements, as well as how nucleic acids interact with proteins involved in key cellular activities, such as transcription and translation. PMID:18786653

Spectroscopic and DFT Study of RhIII Chloro Complex Transformation in Alkaline Solutions.

PubMed

Vasilchenko, Danila B; Berdyugin, Semen N; Korenev, Sergey V; O'Kennedy, Sean; Gerber, Wilhelmus J

2017-09-05

The hydrolysis of [RhCl 6 ] 3- in NaOH-water solutions was studied by spectrophotometric methods. The reaction proceeds via successive substitution of chloride with hydroxide to quantitatively form [Rh(OH) 6 ] 3- . Ligand substitution kinetics was studied in an aqueous 0.434-1.085 M NaOH matrix in the temperature range 5.5-15.3 °C. Transformation of [RhCl 6 ] 3- into [RhCl 5 (OH)] 3- was found to be the rate-determining step with activation parameters of ΔH † = 105 ± 4 kJ mol -1 and ΔS † = 59 ± 10 J K -1 mol -1 . The coordinated hydroxo ligand(s) induces rapid ligand substitution to form [Rh(OH) 6 ] 3- . By simulating ligand substitution as a dissociative mechanism, using density functional theory (DFT), we can now explain the relatively fast and slow kinetics of chloride substitution in basic and acidic matrices, respectively. Moreover, the DFT calculated activation energies corroborated experimental data that the kinetic stereochemical sequence of [RhCl 6 ] 3- hydrolysis in an acidic solution proceeds as [RhCl 6 ] 3- → [RhCl 5 (H 2 O)] 2- → cis-[RhCl 4 (H 2 O) 2 ] - . However, DFT calculations predict in a basic solution the trans route of substitution [RhCl 6 ] 3- → [RhCl 5 (OH)] 3- → trans-[RhCl 4 (OH) 2 ] 3- is kinetically favored.

Degradation Kinetics Study of Alogliptin Benzoate in Alkaline Medium by Validated Stability-Indicating HPTLC Method.

PubMed

Bodiwala, Kunjan Bharatkumar; Shah, Shailesh; Thakor, Jeenal; Marolia, Bhavin; Prajapati, Pintu

2016-11-01

A rapid, sensitive, and stability-indicating high-performance thin-layer chromatographic method was developed and validated to study degradation kinetics of Alogliptin benzoate (ALG) in an alkaline medium. ALG was degraded under acidic, alkaline, oxidative, and thermal stress conditions. The degraded samples were chromatographed on silica gel 60F254-TLC plates, developed using a quaternary-solvent system (chloroform-methanol-ethyl acetate-triethyl amine, 9+1+1+0.5, v/v/v/v), and scanned at 278 nm. The developed method was validated per International Conference on Harmonization guidelines using validation parameters such as specificity, linearity and range, precision, accuracy, LOD, and LOQ. The linearity range for ALG was 100-500 ng/band (correlation coefficient = 0.9997) with an average recovery of 99.47%. The LOD and LOQ for ALG were 9.8 and 32.7 ng/band, respectively. The developed method was successfully applied for the quantitative estimation of ALG in its synthetic mixture with common excipients. Degradation kinetics of ALG in an alkaline medium was studied by degrading it under three different temperatures and three different concentrations of alkali. Degradation of ALG in the alkaline medium was found to follow first-order kinetics. Contour plots have been generated to predict degradation rate constant, half-life, and shelf life of ALG in various combinations of temperature and concentration of alkali using Design Expert software.

Kinetic study of hydrolysis of coconut fiber into glucose

NASA Astrophysics Data System (ADS)

Muhaimin, Sudiono, Sri

2017-03-01

Kinetic study of hydrolysis of coconut fiber into glucose has been done. The aim of this research was to study of the effect of time and temperature to the glucose as the result of the conversion of coconut fiber. The various temperature of the hydrolysis process were 30 °C, 48 °C, 72 °C and 95 °C and the various time of the hydrolysis process were 0, 15, 30, 60, 120, 180, 240, 300 minutes. A quantitative analysis was done by measured the concentration of the glucose as the result of the conversion of coconut fiber. The result showed that the rate constant from the various temperature were 3.10-4 minute-1; 8.10-4 minutees-1; 84.10-4 minute-1, and 205.10-4 minute-1, and the energy activation was 7,69. 103 kJ/mol.

Quantifying the Effect of Stress on Sn Whisker Nucleation Kinetics

NASA Astrophysics Data System (ADS)

Chason, Eric; Vasquez, Justin; Pei, Fei; Jain, Nupur; Hitt, Andrew

2018-01-01

Although Sn whiskers have been studied extensively, there is still a need to understand the driving forces behind whisker nucleation and growth. Many studies point to the role of stress, but confirming this requires a quantitative comparison between controlled stress and the resulting whisker evolution. Recent experimental studies applied stress to a Sn layer via thermal cycling and simultaneously monitored the evolution of the temperature, stress and number of nuclei. In this work, we analyze these nucleation kinetics in terms of classical nucleation theory to relate the observed behavior to underlying mechanisms including a stress dependent activation energy and a temperature and stress-dependent whisker growth rate. Non-linear least squares fitting of the data taken at different temperatures and strain rates to the model shows that the results can be understood in terms of stress decreasing the barrier for whisker nucleation.

Evaluation of Lacrimation Characteristics in Clinically Normal New Zealand White Rabbits by Using the Schirmer Tear Test I

PubMed Central

Whittaker, Alexandra L; Williams, David L

2015-01-01

Rabbits are a common animal model in eye research and in safety testing of novel chemical agents. In addition, ocular disease is a routine presentation in clinical practice. However, few studies have quantitatively examined lacrimation kinetics in this species. This study used a noninvasive method of tear measurement (the Schirmer tear test, STT) to quantify values for basal and reflex tearing and to determine the kinetic nature of tear production in 76 New Zealand white rabbits. We obtained a value of 7.58 ± 2.3 mm/min for the standard 1-min STT. Calculated values for mean residual tear volume and reflex tear flow were 1.95 µL and 0.035 µL/s, respectively. In addition, this study provides preliminary evidence for an interaction effect between eyes given that higher STT values were obtained from the second eye tested. PMID:26632789

Hyperthyroidism stimulates mitochondrial proton leak and ATP turnover in rat hepatocytes but does not change the overall kinetics of substrate oxidation reactions.

PubMed

Harper, M E; Brand, M D

1994-08-01

Thyroid hormones have well-known effects on oxidative phosphorylation, but there is little quantitative information on their important sites of action. We have used top-down elasticity analysis, an extension of metabolic control analysis, to identify the sites of action of thyroid hormones on oxidative phosphorylation in rat hepatocytes. We divided the oxidative phosphorylation system into three blocks of reactions: the substrate oxidation subsystem, the phosphorylating subsystem, and the mitochondrial proton leak subsystem and have identified those blocks of reactions whose kinetics are significantly changed by hyperthyroidism. Our results show significant effects on the kinetics of the proton leak and the phosphorylating subsystems. Quantitative analyses revealed that 43% of the increase in resting respiration rate in hyperthyroid hepatocytes compared with euthyroid hepatocytes was due to differences in the proton leak and 59% was due to differences in the activity of the phosphorylating subsystem. There were no significant effects on the substrate oxidation subsystem. Changes in nonmitochondrial oxygen consumption accounted for -2% of the change in respiration rate. Top-down control analysis revealed that the distribution of control over the rates of mitochondrial oxygen consumption, ATP synthesis and consumption, and proton leak and over mitochondrial membrane potential (delta psi m) was similar in hepatocytes from hyperthyroid and littermate-paired euthyroid controls. The results of this study include the first complete top-down elasticity and control analyses of oxidative phosphorylation in hepatocytes from hyperthyroid rats.

Whole-body PET parametric imaging employing direct 4D nested reconstruction and a generalized non-linear Patlak model

NASA Astrophysics Data System (ADS)

Karakatsanis, Nicolas A.; Rahmim, Arman

2014-03-01

Graphical analysis is employed in the research setting to provide quantitative estimation of PET tracer kinetics from dynamic images at a single bed. Recently, we proposed a multi-bed dynamic acquisition framework enabling clinically feasible whole-body parametric PET imaging by employing post-reconstruction parameter estimation. In addition, by incorporating linear Patlak modeling within the system matrix, we enabled direct 4D reconstruction in order to effectively circumvent noise amplification in dynamic whole-body imaging. However, direct 4D Patlak reconstruction exhibits a relatively slow convergence due to the presence of non-sparse spatial correlations in temporal kinetic analysis. In addition, the standard Patlak model does not account for reversible uptake, thus underestimating the influx rate Ki. We have developed a novel whole-body PET parametric reconstruction framework in the STIR platform, a widely employed open-source reconstruction toolkit, a) enabling accelerated convergence of direct 4D multi-bed reconstruction, by employing a nested algorithm to decouple the temporal parameter estimation from the spatial image update process, and b) enhancing the quantitative performance particularly in regions with reversible uptake, by pursuing a non-linear generalized Patlak 4D nested reconstruction algorithm. A set of published kinetic parameters and the XCAT phantom were employed for the simulation of dynamic multi-bed acquisitions. Quantitative analysis on the Ki images demonstrated considerable acceleration in the convergence of the nested 4D whole-body Patlak algorithm. In addition, our simulated and patient whole-body data in the postreconstruction domain indicated the quantitative benefits of our extended generalized Patlak 4D nested reconstruction for tumor diagnosis and treatment response monitoring.

Modeling and Classification of Kinetic Patterns of Dynamic Metabolic Biomarkers in Physical Activity

PubMed Central

Breit, Marc; Netzer, Michael

2015-01-01

The objectives of this work were the classification of dynamic metabolic biomarker candidates and the modeling and characterization of kinetic regulatory mechanisms in human metabolism with response to external perturbations by physical activity. Longitudinal metabolic concentration data of 47 individuals from 4 different groups were examined, obtained from a cycle ergometry cohort study. In total, 110 metabolites (within the classes of acylcarnitines, amino acids, and sugars) were measured through a targeted metabolomics approach, combining tandem mass spectrometry (MS/MS) with the concept of stable isotope dilution (SID) for metabolite quantitation. Biomarker candidates were selected by combined analysis of maximum fold changes (MFCs) in concentrations and P-values resulting from statistical hypothesis testing. Characteristic kinetic signatures were identified through a mathematical modeling approach utilizing polynomial fitting. Modeled kinetic signatures were analyzed for groups with similar behavior by applying hierarchical cluster analysis. Kinetic shape templates were characterized, defining different forms of basic kinetic response patterns, such as sustained, early, late, and other forms, that can be used for metabolite classification. Acetylcarnitine (C2), showing a late response pattern and having the highest values in MFC and statistical significance, was classified as late marker and ranked as strong predictor (MFC = 1.97, P < 0.001). In the class of amino acids, highest values were shown for alanine (MFC = 1.42, P < 0.001), classified as late marker and strong predictor. Glucose yields a delayed response pattern, similar to a hockey stick function, being classified as delayed marker and ranked as moderate predictor (MFC = 1.32, P < 0.001). These findings coincide with existing knowledge on central metabolic pathways affected in exercise physiology, such as β-oxidation of fatty acids, glycolysis, and glycogenolysis. The presented modeling approach demonstrates high potential for dynamic biomarker identification and the investigation of kinetic mechanisms in disease or pharmacodynamics studies using MS data from longitudinal cohort studies. PMID:26317529

Computational model, method, and system for kinetically-tailoring multi-drug chemotherapy for individuals

DOEpatents

Gardner, Shea Nicole

2007-10-23

A method and system for tailoring treatment regimens to individual patients with diseased cells exhibiting evolution of resistance to such treatments. A mathematical model is provided which models rates of population change of proliferating and quiescent diseased cells using cell kinetics and evolution of resistance of the diseased cells, and pharmacokinetic and pharmacodynamic models. Cell kinetic parameters are obtained from an individual patient and applied to the mathematical model to solve for a plurality of treatment regimens, each having a quantitative efficacy value associated therewith. A treatment regimen may then be selected from the plurlaity of treatment options based on the efficacy value.

Practical Modeling Concepts for Connective Tissue Stem Cell and Progenitor Compartment Kinetics

PubMed Central

2003-01-01

Stem cell activation and development is central to skeletal development, maintenance, and repair, as it is for all tissues. However, an integrated model of stem cell proliferation, differentiation, and transit between functional compartments has yet to evolve. In this paper, the authors review current concepts in stem cell biology and progenitor cell growth and differentiation kinetics in the context of bone formation. A cell-based modeling strategy is developed and offered as a tool for conceptual and quantitative exploration of the key kinetic variables and possible organizational hierarchies in bone tissue development and remodeling, as well as in tissue engineering strategies for bone repair. PMID:12975533

[The accuracy of rapid equilibrium assumption in steady-state enzyme kinetics is the function of equilibrium segment structure and properties].

PubMed

Vrzheshch, P V

2015-01-01

Quantitative evaluation of the accuracy of the rapid equilibrium assumption in the steady-state enzyme kinetics was obtained for an arbitrary mechanism of an enzyme-catalyzed reaction. This evaluation depends only on the structure and properties of the equilibrium segment, but doesn't depend on the structure and properties of the rest (stationary part) of the kinetic scheme. The smaller the values of the edges leaving equilibrium segment in relation to values of the edges within the equilibrium segment, the higher the accuracy of determination of intermediate concentrations and reaction velocity in a case of the rapid equilibrium assumption.

Kinetic Profiling of Catalytic Organic Reactions as a Mechanistic Tool.

PubMed

Blackmond, Donna G

2015-09-02

The use of modern kinetic tools to obtain virtually continuous reaction progress data over the course of a catalytic reaction opens up a vista that provides mechanistic insights into both simple and complex catalytic networks. Reaction profiles offer a rate/concentration scan that tells the story of a batch reaction time course in a qualitative "fingerprinting" manner as well as in quantitative detail. Reaction progress experiments may be mathematically designed to elucidate catalytic rate laws from only a fraction of the number of experiments required in classical kinetic measurements. The information gained from kinetic profiles provides clues to direct further mechanistic analysis by other approaches. Examples from a variety of catalytic reactions spanning two decades of the author's work help to delineate nuances on a central mechanistic theme.

Relationship of Interplanetary Shock Micro and Macro Characteristics: A Wind Study

NASA Technical Reports Server (NTRS)

Szabo, Adam; Koval, A

2008-01-01

The non-linear least squared MHD fitting technique of Szabo 11 9941 has been recently further refined to provide realistic confidence regions for interplanetary shock normal directions and speeds. Analyzing Wind observed interplanetary shocks from 1995 to 200 1, macro characteristics such as shock strength, Theta Bn and Mach numbers can be compared to the details of shock micro or kinetic structures. The now commonly available very high time resolution (1 1 or 22 vectors/sec) Wind magnetic field data allows the precise characterization of shock kinetic structures, such as the size of the foot, ramp, overshoot and the duration of damped oscillations on either side of the shock. Detailed comparison of the shock micro and macro characteristics will be given. This enables the elucidation of shock kinetic features, relevant for particle energization processes, for observations where high time resolution data is not available. Moreover, establishing a quantitative relationship between the shock micro and macro structures will improve the confidence level of shock fitting techniques during disturbed solar wind conditions.

New Combustion Regimes and Kinetic Studies of Plasma Assisted Combustion

DTIC Science & Technology

2012-11-01

IR Faraday Rotational Spectroscopy Method to quantify HO2 29 30 Brian Brumfield, Wenting Sun, Gerard Wysock, and Yinguang Ju, submitted...to JACS, 2012 7.1 μm Mid infra-red Faraday Rotation Spectroscopy (FRS), 1396 cm-1 Quantitative HO2 Measurement (very challenging!): 2L + 1...paramagnetic species Polarization rotation detection Linearly-polarized laser light 610 Hz oscillating magnetic field 125 Gauss rms Sub-ppm level

Biological evolution of replicator systems: towards a quantitative approach.

PubMed

Martin, Osmel; Horvath, J E

2013-04-01

The aim of this work is to study the features of a simple replicator chemical model of the relation between kinetic stability and entropy production under the action of external perturbations. We quantitatively explore the different paths leading to evolution in a toy model where two independent replicators compete for the same substrate. To do that, the same scenario described originally by Pross (J Phys Org Chem 17:312-316, 2004) is revised and new criteria to define the kinetic stability are proposed. Our results suggest that fast replicator populations are continually favored by the effects of strong stochastic environmental fluctuations capable to determine the global population, the former assumed to be the only acting evolution force. We demonstrate that the process is continually driven by strong perturbations only, and that population crashes may be useful proxies for these catastrophic environmental fluctuations. As expected, such behavior is particularly enhanced under very large scale perturbations, suggesting a likely dynamical footprint in the recovery patterns of new species after mass extinction events in the Earth's geological past. Furthermore, the hypothesis that natural selection always favors the faster processes may give theoretical support to different studies that claim the applicability of maximum principles like the Maximum Metabolic Flux (MMF) or Maximum Entropy Productions Principle (MEPP), seen as the main goal of biological evolution.

Theoretical derivation of anodizing current and comparison between fitted curves and measured curves under different conditions.

PubMed

Chong, Bin; Yu, Dongliang; Jin, Rong; Wang, Yang; Li, Dongdong; Song, Ye; Gao, Mingqi; Zhu, Xufei

2015-04-10

Anodic TiO2 nanotubes have been studied extensively for many years. However, the growth kinetics still remains unclear. The systematic study of the current transient under constant anodizing voltage has not been mentioned in the original literature. Here, a derivation and its corresponding theoretical formula are proposed to overcome this challenge. In this paper, the theoretical expressions for the time dependent ionic current and electronic current are derived to explore the anodizing process of Ti. The anodizing current-time curves under different anodizing voltages and different temperatures are experimentally investigated in the anodization of Ti. Furthermore, the quantitative relationship between the thickness of the barrier layer and anodizing time, and the relationships between the ionic/electronic current and temperatures are proposed in this paper. All of the current-transient plots can be fitted consistently by the proposed theoretical expressions. Additionally, it is the first time that the coefficient A of the exponential relationship (ionic current j(ion) = A exp(BE)) has been determined under various temperatures and voltages. And the results indicate that as temperature and voltage increase, ionic current and electronic current both increase. The temperature has a larger effect on electronic current than ionic current. These results can promote the research of kinetics from a qualitative to quantitative level.

Biological Evolution of Replicator Systems: Towards a Quantitative Approach

NASA Astrophysics Data System (ADS)

Martin, Osmel; Horvath, J. E.

2013-04-01

The aim of this work is to study the features of a simple replicator chemical model of the relation between kinetic stability and entropy production under the action of external perturbations. We quantitatively explore the different paths leading to evolution in a toy model where two independent replicators compete for the same substrate. To do that, the same scenario described originally by Pross (J Phys Org Chem 17:312-316, 2004) is revised and new criteria to define the kinetic stability are proposed. Our results suggest that fast replicator populations are continually favored by the effects of strong stochastic environmental fluctuations capable to determine the global population, the former assumed to be the only acting evolution force. We demonstrate that the process is continually driven by strong perturbations only, and that population crashes may be useful proxies for these catastrophic environmental fluctuations. As expected, such behavior is particularly enhanced under very large scale perturbations, suggesting a likely dynamical footprint in the recovery patterns of new species after mass extinction events in the Earth's geological past. Furthermore, the hypothesis that natural selection always favors the faster processes may give theoretical support to different studies that claim the applicability of maximum principles like the Maximum Metabolic Flux (MMF) or Maximum Entropy Productions Principle (MEPP), seen as the main goal of biological evolution.

Theoretical derivation of anodizing current and comparison between fitted curves and measured curves under different conditions

NASA Astrophysics Data System (ADS)

Chong, Bin; Yu, Dongliang; Jin, Rong; Wang, Yang; Li, Dongdong; Song, Ye; Gao, Mingqi; Zhu, Xufei

2015-04-01

Anodic TiO2 nanotubes have been studied extensively for many years. However, the growth kinetics still remains unclear. The systematic study of the current transient under constant anodizing voltage has not been mentioned in the original literature. Here, a derivation and its corresponding theoretical formula are proposed to overcome this challenge. In this paper, the theoretical expressions for the time dependent ionic current and electronic current are derived to explore the anodizing process of Ti. The anodizing current-time curves under different anodizing voltages and different temperatures are experimentally investigated in the anodization of Ti. Furthermore, the quantitative relationship between the thickness of the barrier layer and anodizing time, and the relationships between the ionic/electronic current and temperatures are proposed in this paper. All of the current-transient plots can be fitted consistently by the proposed theoretical expressions. Additionally, it is the first time that the coefficient A of the exponential relationship (ionic current jion = A exp(BE)) has been determined under various temperatures and voltages. And the results indicate that as temperature and voltage increase, ionic current and electronic current both increase. The temperature has a larger effect on electronic current than ionic current. These results can promote the research of kinetics from a qualitative to quantitative level.

New techniques for positron emission tomography in the study of human neurological disorders

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuhl, D.E.

1992-07-01

The general goals of the physics and kinetic modeling projects are to: (1) improve the quantitative information extractable from PET images, and (2) develop, implement and optimize tracer kinetic models for new PET neurotransmitter/receptor ligands aided by computer simulations. Work towards improving PET quantification has included projects evaluating: (1) iterative reconstruction algorithms using supplemental boundary information, (2) automated registration of dynamic PET emission and transmission data using sinogram edge detection, and (3) automated registration of multiple subjects to a common coordinate system, including the use of non-linear warping methods. Simulation routines have been developed providing more accurate representation of datamore » generated from neurotransmitter/receptor studies. Routines consider data generated from complex compartmental models, high or low specific activity administrations, non-specific binding, pre- or post-injection of cold or competing ligands, temporal resolution of the data, and radiolabeled metabolites. Computer simulations and human PET studies have been performed to optimize kinetic models for four new neurotransmitter/receptor ligands, [{sup 11}C]TRB (muscarinic), [{sup 11}C]flumazenil (benzodiazepine), [{sup 18}F]GBR12909, (dopamine), and [{sup 11}C]NMPB (muscarinic).« less

New techniques for positron emission tomography in the study of human neurological disorders

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuhl, D.E.

1992-01-01

The general goals of the physics and kinetic modeling projects are to: (1) improve the quantitative information extractable from PET images, and (2) develop, implement and optimize tracer kinetic models for new PET neurotransmitter/receptor ligands aided by computer simulations. Work towards improving PET quantification has included projects evaluating: (1) iterative reconstruction algorithms using supplemental boundary information, (2) automated registration of dynamic PET emission and transmission data using sinogram edge detection, and (3) automated registration of multiple subjects to a common coordinate system, including the use of non-linear warping methods. Simulation routines have been developed providing more accurate representation of datamore » generated from neurotransmitter/receptor studies. Routines consider data generated from complex compartmental models, high or low specific activity administrations, non-specific binding, pre- or post-injection of cold or competing ligands, temporal resolution of the data, and radiolabeled metabolites. Computer simulations and human PET studies have been performed to optimize kinetic models for four new neurotransmitter/receptor ligands, ({sup 11}C)TRB (muscarinic), ({sup 11}C)flumazenil (benzodiazepine), ({sup 18}F)GBR12909, (dopamine), and ({sup 11}C)NMPB (muscarinic).« less

Spatiotemporal dynamics of DNA repair proteins following laser microbeam induced DNA damage – When is a DSB not a DSB?☆

PubMed Central

Reynolds, Pamela; Botchway, Stanley W.; Parker, Anthony W.; O’Neill, Peter

2013-01-01

The formation of DNA lesions poses a constant threat to cellular stability. Repair of endogenously and exogenously produced lesions has therefore been extensively studied, although the spatiotemporal dynamics of the repair processes has yet to be fully understood. One of the most recent advances to study the kinetics of DNA repair has been the development of laser microbeams to induce and visualize recruitment and loss of repair proteins to base damage in live mammalian cells. However, a number of studies have produced contradictory results that are likely caused by the different laser systems used reflecting in part the wavelength dependence of the damage induced. Additionally, the repair kinetics of laser microbeam induced DNA lesions have generally lacked consideration of the structural and chemical complexity of the DNA damage sites, which are known to greatly influence their reparability. In this review, we highlight the key considerations when embarking on laser microbeam experiments and interpreting the real time data from laser microbeam irradiations. We compare the repair kinetics from live cell imaging with biochemical and direct quantitative cellular measurements for DNA repair. PMID:23688615

Mathematics of quantitative kinetic PCR and the application of standard curves.

PubMed

Rutledge, R G; Côté, C

2003-08-15

Fluorescent monitoring of DNA amplification is the basis of real-time PCR, from which target DNA concentration can be determined from the fractional cycle at which a threshold amount of amplicon DNA is produced. Absolute quantification can be achieved using a standard curve constructed by amplifying known amounts of target DNA. In this study, the mathematics of quantitative PCR are examined in detail, from which several fundamental aspects of the threshold method and the application of standard curves are illustrated. The construction of five replicate standard curves for two pairs of nested primers was used to examine the reproducibility and degree of quantitative variation using SYBER Green I fluorescence. Based upon this analysis the application of a single, well- constructed standard curve could provide an estimated precision of +/-6-21%, depending on the number of cycles required to reach threshold. A simplified method for absolute quantification is also proposed, in which quantitative scale is determined by DNA mass at threshold.

Understanding the oriented-attachment growth of nanocrystals from an energy point of view: a review

NASA Astrophysics Data System (ADS)

Lv, Weiqiang; He, Weidong; Wang, Xiaoning; Niu, Yinghua; Cao, Huanqi; Dickerson, James H.; Wang, Zhiguo

2014-02-01

Since Penn et al. first discovered the oriented attachment growth of crystals, the oriented attachment mechanism has now become a major research focus in the crystal field, and extensive efforts have been carried out over the past decade to systematically investigate the growth mechanism and the statistical kinetic models. However, most of the work mainly focuses on the experimental results on the oriented attachment growth. In contrast to the previous reviews, our review provides an overview of the recent theoretical advances in oriented attachment kinetics combined with experimental evidences. After a brief introduction to the van der Waals interaction and Coulombic interaction in a colloidal system, the correlation between the kinetic models of oriented attachment growth and the interactions is then our focus. The impact of in situ experimental observation techniques on the study of oriented attachment growth is examined with insightful examples. In addition, the advances in theoretical simulations mainly investigating the thermodynamic origin of these interactions at the atomic level are reviewed. This review seeks to understand the oriented attachment crystal growth from a kinetic point of view and provide a quantitative methodology to rationally design an oriented attachment system with pre-evaluated crystal growth parameters.

Probing specific molecular processes and intermediates by time-resolved Fourier transform infrared spectroscopy: application to the bacteriorhodopsin photocycle.

PubMed

Lórenz-Fonfría, Víctor A; Kandori, Hideki; Padrós, Esteve

2011-06-23

We present a general approach for probing the kinetics of specific molecular processes in proteins by time-resolved Fourier transform infrared (IR) spectroscopy. Using bacteriorhodopsin (bR) as a model we demonstrate that by appropriately monitoring some selected IR bands it is possible obtaining the kinetics of the most important events occurring in the photocycle, namely changes in the chromophore and the protein backbone conformation, and changes in the protonation state of the key residues implicated in the proton transfers. Besides confirming widely accepted views of the bR photocycle, our analysis also sheds light into some disputed issues: the degree of retinal torsion in the L intermediate to respect the ground state; the possibility of a proton transfer from Asp85 to Asp212; the relationship between the protonation/deprotonation of Asp85 and the proton release complex; and the timing of the protein backbone dynamics. By providing a direct way to estimate the kinetics of photocycle intermediates the present approach opens new prospects for a robust quantitative kinetic analysis of the bR photocycle, which could also benefit the study of other proteins involved in photosynthesis, in phototaxis, or in respiratory chains.

Relationships between PEMFC Cathode Kinetic Losses and Contaminants’ Dipole Moment and Adsorption Energy on Pt

DOE PAGES

St-Pierre, Jean; Zhai, Yunfeng; Ge, Junjie

2016-01-05

A database summarizing the effects of 21 contaminants on the performance of proton exchange membrane fuel cells (PEMFCs) was used to examine relationships between cathode kinetic losses and contaminant physicochemical parameters. Impedance spectroscopy data were employed to obtain oxygen reduction kinetic resistances by fitting data in the 10-158 Hz range to a simplified equivalent circuit. The contaminant dipole moment and the adsorption energy of the contaminant on a Pt surface were chosen as parameters. Dipole moments did not correlate with dimensionless cathode kinetic resistances. In contrast, adsorption energies were quantitatively and linearly correlated with minimum dimensionless cathode kinetic resistances. Contaminantsmore » influence the oxygen reduction for contaminant adsorption energies smaller than -24.5 kJ mol -1, a value near the high limit of the adsorption energy of O 2 on Pt. Dimensionless cathode kinetic resistances linearly increase with decreasing O 2 adsorption energies below -24.5 kJ mol -1. Measured total cell voltage losses are mostly larger than the cathode kinetic losses calculated from kinetic resistance changes, which indicates the existence of other sources of performance degradation. Modifications to the experimental procedure are proposed to ensure that data are comparable on a similar basis and improve the correlation between contaminant adsorption energy and kinetic cell voltage losses.« less

Relationships between PEMFC Cathode Kinetic Losses and Contaminants’ Dipole Moment and Adsorption Energy on Pt

DOE Office of Scientific and Technical Information (OSTI.GOV)

St-Pierre, Jean; Zhai, Yunfeng; Ge, Junjie

A database summarizing the effects of 21 contaminants on the performance of proton exchange membrane fuel cells (PEMFCs) was used to examine relationships between cathode kinetic losses and contaminant physicochemical parameters. Impedance spectroscopy data were employed to obtain oxygen reduction kinetic resistances by fitting data in the 10-158 Hz range to a simplified equivalent circuit. The contaminant dipole moment and the adsorption energy of the contaminant on a Pt surface were chosen as parameters. Dipole moments did not correlate with dimensionless cathode kinetic resistances. In contrast, adsorption energies were quantitatively and linearly correlated with minimum dimensionless cathode kinetic resistances. Contaminantsmore » influence the oxygen reduction for contaminant adsorption energies smaller than -24.5 kJ mol -1, a value near the high limit of the adsorption energy of O 2 on Pt. Dimensionless cathode kinetic resistances linearly increase with decreasing O 2 adsorption energies below -24.5 kJ mol -1. Measured total cell voltage losses are mostly larger than the cathode kinetic losses calculated from kinetic resistance changes, which indicates the existence of other sources of performance degradation. Modifications to the experimental procedure are proposed to ensure that data are comparable on a similar basis and improve the correlation between contaminant adsorption energy and kinetic cell voltage losses.« less

Evidence for a Shared Mechanism in the Formation of Urea-Induced Kinetic and Equilibrium Intermediates of Horse Apomyoglobin from Ultrarapid Mixing Experiments

PubMed Central

Mizukami, Takuya; Abe, Yukiko; Maki, Kosuke

2015-01-01

In this study, the equivalence of the kinetic mechanisms of the formation of urea-induced kinetic folding intermediates and non-native equilibrium states was investigated in apomyoglobin. Despite having similar structural properties, equilibrium and kinetic intermediates accumulate under different conditions and via different mechanisms, and it remains unknown whether their formation involves shared or distinct kinetic mechanisms. To investigate the potential mechanisms of formation, the refolding and unfolding kinetics of horse apomyoglobin were measured by continuous- and stopped-flow fluorescence over a time range from approximately 100 μs to 10 s, along with equilibrium unfolding transitions, as a function of urea concentration at pH 6.0 and 8°C. The formation of a kinetic intermediate was observed over a wider range of urea concentrations (0–2.2 M) than the formation of the native state (0–1.6 M). Additionally, the kinetic intermediate remained populated as the predominant equilibrium state under conditions where the native and unfolded states were unstable (at ~0.7–2 M urea). A continuous shift from the kinetic to the equilibrium intermediate was observed as urea concentrations increased from 0 M to ~2 M, which indicates that these states share a common kinetic folding mechanism. This finding supports the conclusion that these intermediates are equivalent. Our results in turn suggest that the regions of the protein that resist denaturant perturbations form during the earlier stages of folding, which further supports the structural equivalence of transient and equilibrium intermediates. An additional folding intermediate accumulated within ~140 μs of refolding and an unfolding intermediate accumulated in <1 ms of unfolding. Finally, by using quantitative modeling, we showed that a five-state sequential scheme appropriately describes the folding mechanism of horse apomyoglobin. PMID:26244984

Kinetic Methods for Understanding Linker Exchange in Metal-Organic Frameworks

NASA Astrophysics Data System (ADS)

Morabito, Joseph V.

Exchange reactions have enabled a new level of control in the rational, stepwise preparation of metal-organic framework (MOF) materials. However, their full potential is limited by a lack of understanding of the molecular mechanisms by which they occur. This dissertation describes our efforts to understand this important class of reactions in two parts. The first reports our use of a linker exchange process to encapsulate guest molecules larger than the limiting pore aperture of the MOF. The concept is demonstrated, along with evidence for guest encapsulation and its relation to a dissociative linker exchange process. The second part describes our development of the first quantitative kinetic method for studying MOF linker exchange reactions and our application of this method to understand the solvent dependence of the reaction of ZIF-8 with imidazole. This project involved the collection of the largest set of rate data available on any MOF linker exchange reaction. The combination of this dataset with small molecule encapsulation experiments allowed us to formulate a mechanistic model that could account for all the observed kinetic and structural data. By comparison with the kinetic behavior of complexes in solution, we were able to fit the kinetic behavior of ZIF-8 into the broader family of coordination compounds. Aside from the specific use that our kinetic data may have in predicting the reactivity of ZIF linker exchange, we hope that the conceptual bridges made between MOFs and related metal?organic compounds can help reveal underlying patterns in behavior and advance the field.

Evaluation of the kinetic energy of the torso by magneto-inertial measurement unit during the sit-to-stand movement.

PubMed

Lepetit, Kevin; Ben Mansour, Khalil; Boudaoud, Sofiane; Kinugawa-Bourron, Kiyoka; Marin, Frédéric

2018-01-23

Sit-to-stand tests are used in geriatrics as a qualitative issue in order to evaluate motor control and stability. In terms of measured indicators, it is traditionally the duration of the task that is reported, however it appears that the use of the kinetic energy as a new quantitative criterion allows getting a better understanding of musculoskeletal deficits of elderly subjects. The aim of this study was to determine the feasibility to obtain the measure of kinetic energy using magneto-inertial measurement units (MIMU) during sit-to-stand movements at various paces. 26 healthy subjects contributed to this investigation. Measured results were compared to a marker-based motion capture using the correlation coefficient and the normalized root mean square error (nRMSE). nRMSE were below 10% and correlation coefficients were over 0.97. In addition, errors on the mean kinetic energy were also investigated using Bland-Altman 95% limits of agreement (0.63 J-0.77 J), RMSE (0.29 J-0.38 J) and correlation coefficient (0.96-0.98). The results obtained highlighted that the method based on MIMU data could be an alternative to optoelectronic data acquisition to assess the kinetic energy of the torso during the sit-to-stand test, suggesting this method as being a promising alternative to determine kinetic energy during the sit-to-stand movement. Copyright © 2017 Elsevier Ltd. All rights reserved.

Physics and chemistry of antimicrobial behavior of ion-exchanged silver in glass.

PubMed

Borrelli, N F; Senaratne, W; Wei, Y; Petzold, O

2015-02-04

The results of a comprehensive study involving the antimicrobial activity in a silver ion-exchanged glass are presented. The study includes the glass composition, the method of incorporating silver into the glass, the effective concentration of the silver available at the glass surface, and the effect of the ambient environment. A quantitative kinetic model that includes the above factors in predicting the antimicrobial activity is proposed. Finally, experimental data demonstrating antibacterial activity against Staphylococcus aureus with correlation to the predicted model is shown.

Dynamic hysteresis behaviors in the kinetic Ising system on triangular lattice

NASA Astrophysics Data System (ADS)

Kantar, Ersin; Ertaş, Mehmet

2018-04-01

We studied dynamic hysteresis behaviors of the spin-1 Blume-Capel (BC) model in a triangular lattice by means of the effective-field theory (EFT) with correlations and using Glauber-type stochastic dynamics. The effects of the exchange interaction (J), crystal field (D), temperature (T) and oscillating frequency (w) on the hysteresis behaviors of the BC model in a triangular lattice are investigated in detail. Results are compared with some other dynamic studies and quantitatively good agreement is found.

Evaluation of simulation-based scatter correction for 3-D PET cardiac imaging

NASA Astrophysics Data System (ADS)

Watson, C. C.; Newport, D.; Casey, M. E.; deKemp, R. A.; Beanlands, R. S.; Schmand, M.

1997-02-01

Quantitative imaging of the human thorax poses one of the most difficult challenges for three-dimensional (3-D) (septaless) positron emission tomography (PET), due to the strong attenuation of the annihilation radiation and the large contribution of scattered photons to the data. In [/sup 18/F] fluorodeoxyglucose (FDG) studies of the heart with the patient's arms in the field of view, the contribution of scattered events can exceed 50% of the total detected coincidences. Accurate correction for this scatter component is necessary for meaningful quantitative image analysis and tracer kinetic modeling. For this reason, the authors have implemented a single-scatter simulation technique for scatter correction in positron volume imaging. Here, they describe this algorithm and present scatter correction results from human and chest phantom studies.

Some fundamental questions concerning the kinetic theory of electrons in molecular gases and the e H2 vibrational cross section controversy

NASA Astrophysics Data System (ADS)

Robson, R. E.; White, R. D.; Morrison, Michael A.

2003-10-01

We commence a fundamental re-examination of the kinetic theory of charged particle swarms in molecular gases, focusing on collisional excitation of molecular rotational and ro-vibrational states by electrons. Modern day analysis of electron swarms has been based upon the kinetic equation of Wang-Chang et al, which simply treats all processes as scalar energy excitations, and ignores angular momentum conservation and the vector dynamics associated with rotational excitation. It is pointed out that there is no alternative, more exact kinetic equation readily available for electrons which enables one to directly ascertain the degree of error introduced by this approximation. Thus in this preliminary study, we approach the problem indirectly, from the standpoint of the neutral molecules, using the Waldmann-Snider quantum kinetic equation, and insist that an electron-molecule collision must look the same from the perspective of both electron and molecule. We give a formula for quantitatively assessing the importance of scalar versus vectorial treatments of rotational excitation by looking at the post-collisional 'echo' produced by an electron swarm as it passes through the gas. It is then pointed out that in order to remedy any deficiency, it will be necessary to introduce a kinetic collisional operator non-local in space to properly account for angular momentum conservation, as has long been established in the literature. This is a major exercise and given the preliminary nature of this study, we consider the inclusion of such effects from a formal point of view only. In particular we show how non-local effects lead to a spatially dependent 'source' term in the equation of continuity, and hence to corrections for both drift velocity and diffusion coefficients. The magnitude of these corrections has yet to be established.

Kinetic Parameters of Efflux of Penicillins by the Multidrug Efflux Transporter AcrAB-TolC of Escherichia coli▿

PubMed Central

Lim, Siew Ping; Nikaido, Hiroshi

2010-01-01

The multidrug efflux transporter AcrAB-TolC is known to pump out a diverse range of antibiotics, including β-lactams. However, the kinetic constants of the efflux process, needed for the quantitative understanding of resistance, were not available until those accompanying the efflux of some cephalosporins were recently determined by combining efflux with the hydrolysis of drugs by the periplasmic β-lactamase. In the present study we extended this approach to the study of a wide range of penicillins, from ampicillin and penicillin V to ureidopenicillins and isoxazolylpenicillins, by combining efflux with hydrolysis with the OXA-7 penicillinase. We found that the penicillins had a much stronger apparent affinity to AcrB and higher maximum rates of efflux than the cephalosporins. All penicillins showed strong positive cooperativity kinetics for export. The kinetic constants obtained were validated, as the MICs theoretically predicted on the basis of efflux and hydrolysis kinetics were remarkably similar to the observed MICs (except for the isoxazolylpenicillins). Surprisingly, however, the efflux kinetics of cloxacillin, for example, whose MIC decreased 512-fold in Escherichia coli upon the genetic deletion of the acrB gene, were quite similar to those of ampicillin, whose MIC decreased only 2-fold with the same treatment. Analysis of this phenomenon showed that the extensive decrease in the MIC for the acrB mutant is primarily due to the low permeation of the drug and that comparison of the MICs between the parent and the acrB strains is a very poor measure of the ability of AcrB to pump a drug out. PMID:20160052

Quantitative analysis of immobilized penicillinase using enzyme-modified AlGaN/GaN field-effect transistors.

PubMed

Müntze, Gesche Mareike; Baur, Barbara; Schäfer, Wladimir; Sasse, Alexander; Howgate, John; Röth, Kai; Eickhoff, Martin

2015-02-15

Penicillinase-modified AlGaN/GaN field-effect transistors (PenFETs) are utilized to systematically investigate the covalently immobilized enzyme penicillinase under different experimental conditions. We demonstrate quantitative evaluation of covalently immobilized penicillinase layers on pH-sensitive field-effect transistors (FETs) using an analytical kinetic PenFET model. This kinetic model is explicitly suited for devices with thin enzyme layers that are not diffusion-limited, as it is the case for the PenFETs discussed here. By means of the kinetic model it was possible to extract the Michaelis constant of covalently immobilized penicillinase as well as relative transport coefficients of the different species associated with the enzymatic reaction which, exempli gratia, give information about the permeability of the enzymatic layer. Based on this analysis we quantify the reproducibility and the stability of the analyzed PenFETs over the course of 33 days as well as the influence of pH and buffer concentration on the properties of the enzymatic layer. Thereby the stability measurements reveal a Michalis constant KM of (67 ± 13)μM while the chronological development of the relative transport coefficients suggests a detachment of physisorbed penicillinase during the first two weeks since production. Our results show that AlGaN/GaN PenFETs prepared by covalent immobilization of a penicillinase enzyme layer present a powerful tool for quantitative analysis of enzyme functionality. Copyright © 2014 Elsevier B.V. All rights reserved.

AntiJen: a quantitative immunology database integrating functional, thermodynamic, kinetic, biophysical, and cellular data

PubMed Central

Toseland, Christopher P; Clayton, Debra J; McSparron, Helen; Hemsley, Shelley L; Blythe, Martin J; Paine, Kelly; Doytchinova, Irini A; Guan, Pingping; Hattotuwagama, Channa K; Flower, Darren R

2005-01-01

AntiJen is a database system focused on the integration of kinetic, thermodynamic, functional, and cellular data within the context of immunology and vaccinology. Compared to its progenitor JenPep, the interface has been completely rewritten and redesigned and now offers a wider variety of search methods, including a nucleotide and a peptide BLAST search. In terms of data archived, AntiJen has a richer and more complete breadth, depth, and scope, and this has seen the database increase to over 31,000 entries. AntiJen provides the most complete and up-to-date dataset of its kind. While AntiJen v2.0 retains a focus on both T cell and B cell epitopes, its greatest novelty is the archiving of continuous quantitative data on a variety of immunological molecular interactions. This includes thermodynamic and kinetic measures of peptide binding to TAP and the Major Histocompatibility Complex (MHC), peptide-MHC complexes binding to T cell receptors, antibodies binding to protein antigens and general immunological protein-protein interactions. The database also contains quantitative specificity data from position-specific peptide libraries and biophysical data, in the form of diffusion co-efficients and cell surface copy numbers, on MHCs and other immunological molecules. The uses of AntiJen include the design of vaccines and diagnostics, such as tetramers, and other laboratory reagents, as well as helping parameterize the bioinformatic or mathematical in silico modeling of the immune system. The database is accessible from the URL: . PMID:16305757

Dynamic and quantitative assessment of blood coagulation using optical coherence elastography

PubMed Central

Xu, Xiangqun; Zhu, Jiang; Chen, Zhongping

2016-01-01

Reliable clot diagnostic systems are needed for directing treatment in a broad spectrum of cardiovascular diseases and coagulopathy. Here, we report on non-contact measurement of elastic modulus for dynamic and quantitative assessment of whole blood coagulation using acoustic radiation force orthogonal excitation optical coherence elastography (ARFOE-OCE). In this system, acoustic radiation force (ARF) is produced by a remote ultrasonic transducer, and a shear wave induced by ARF excitation is detected by the optical coherence tomography (OCT) system. During porcine whole blood coagulation, changes in the elastic property of the clots increase the shear modulus of the sample, altering the propagating velocity of the shear wave. Consequently, dynamic blood coagulation status can be measured quantitatively by relating the velocity of the shear wave with clinically relevant coagulation metrics, including reaction time, clot formation kinetics and maximum shear modulus. The results show that the ARFOE-OCE is sensitive to the clot formation kinetics and can differentiate the elastic properties of the recalcified porcine whole blood, blood added with kaolin as an activator, and blood spiked with fibrinogen. PMID:27090437

Dynamic and quantitative assessment of blood coagulation using optical coherence elastography

NASA Astrophysics Data System (ADS)

Xu, Xiangqun; Zhu, Jiang; Chen, Zhongping

2016-04-01

Reliable clot diagnostic systems are needed for directing treatment in a broad spectrum of cardiovascular diseases and coagulopathy. Here, we report on non-contact measurement of elastic modulus for dynamic and quantitative assessment of whole blood coagulation using acoustic radiation force orthogonal excitation optical coherence elastography (ARFOE-OCE). In this system, acoustic radiation force (ARF) is produced by a remote ultrasonic transducer, and a shear wave induced by ARF excitation is detected by the optical coherence tomography (OCT) system. During porcine whole blood coagulation, changes in the elastic property of the clots increase the shear modulus of the sample, altering the propagating velocity of the shear wave. Consequently, dynamic blood coagulation status can be measured quantitatively by relating the velocity of the shear wave with clinically relevant coagulation metrics, including reaction time, clot formation kinetics and maximum shear modulus. The results show that the ARFOE-OCE is sensitive to the clot formation kinetics and can differentiate the elastic properties of the recalcified porcine whole blood, blood added with kaolin as an activator, and blood spiked with fibrinogen.

Simulation of the M13 life cycle I: Assembly of a genetically-structured deterministic chemical kinetic simulation.

PubMed

Smeal, Steven W; Schmitt, Margaret A; Pereira, Ronnie Rodrigues; Prasad, Ashok; Fisk, John D

2017-01-01

To expand the quantitative, systems level understanding and foster the expansion of the biotechnological applications of the filamentous bacteriophage M13, we have unified the accumulated quantitative information on M13 biology into a genetically-structured, experimentally-based computational simulation of the entire phage life cycle. The deterministic chemical kinetic simulation explicitly includes the molecular details of DNA replication, mRNA transcription, protein translation and particle assembly, as well as the competing protein-protein and protein-nucleic acid interactions that control the timing and extent of phage production. The simulation reproduces the holistic behavior of M13, closely matching experimentally reported values of the intracellular levels of phage species and the timing of events in the M13 life cycle. The computational model provides a quantitative description of phage biology, highlights gaps in the present understanding of M13, and offers a framework for exploring alternative mechanisms of regulation in the context of the complete M13 life cycle. Copyright © 2016 Elsevier Inc. All rights reserved.

Kinetics and Quantitative Structure—Activity Relationship Study on the Degradation Reaction from Perfluorooctanoic Acid to Trifluoroacetic Acid

PubMed Central

Gong, Chen; Sun, Xiaomin; Zhang, Chenxi; Zhang, Xue; Niu, Junfeng

2014-01-01

Investigation of the degradation kinetics of perfluorooctanoic acid (PFOA) has been carried out to calculate rate constants of the main elementary reactions using the multichannel Rice-Ramsperger-Kassel-Marcus theory and canonical variational transition state theory with small-curvature tunneling correction over a temperature range of 200~500 K. The Arrhenius equations of rate constants of elementary reactions are fitted. The decarboxylation is role step in the degradation mechanism of PFOA. For the perfluorinated carboxylic acids from perfluorooctanoic acid to trifluoroacetic acid, the quantitative structure–activity relationship of the decarboxylation was analyzed with the genetic function approximation method and the structure–activity model was constructed. The main parameters governing rate constants of the decarboxylation reaction from the eight-carbon chain to the two-carbon chain were obtained. As the structure–activity model shows, the bond length and energy of C1–C2 (RC1–C2 and EC1–C2) are positively correlated to rate constants, while the volume (V), the energy difference between EHOMO and ELUMO (ΔE), and the net atomic charges on atom C2 (QC2) are negatively correlated. PMID:25196516

Understanding ligninase-mediated reactions of endocrine disrupting chemicals in water: reaction rates and quantitative structure-activity relationships.

PubMed

Mao, Liang; Colosi, Lisa M; Gao, Shixiang; Huang, Qingguo

2011-07-15

We have verified in our previous work that lignin peroxidase (LiP) mediates effective removal of selected natural and synthetic estrogens. The efficiency of these reactions was greatly enhanced in the presence of veratryl alcohol (VA), a chemical that is produced along with LiP by certain white rot fungi, for example, Phanerochaete chrysosporium. In this study, we systematically evaluated the kinetic behaviors of LiP-mediated reactions for six endocrine disrupting compounds (EDCs), that is, steroid estrogens and their structural analogs, in both the presence and absence of VA. Resulting kinetic parameters were then correlated with structural features of LiP/substrate binding complexes, as quantified using molecular simulation, to create quantitative structure-activity relationship (QSAR) equations. These equations suggest that binding distance between a substrate's phenolic proton and δN of HIS47's imidazole ring plays an important role in modulating substrate reactivity toward LiP in both the presence and absence of VA. This information provides insight into an important enzymatic reaction process that occurs in the natural environment affecting EDC transformation, a process that may be used in engineered systems to achieve EDC removal from water.

Pattern, growth, and aging in aggregation kinetics of a Vicsek-like active matter model

NASA Astrophysics Data System (ADS)

Das, Subir K.

2017-01-01

Via molecular dynamics simulations, we study kinetics in a Vicsek-like phase-separating active matter model. Quantitative results, for isotropic bicontinuous pattern, are presented on the structure, growth, and aging. These are obtained via the two-point equal-time density-density correlation function, the average domain length, and the two-time density autocorrelation function. Both the correlation functions exhibit basic scaling properties, implying self-similarity in the pattern dynamics, for which the average domain size exhibits a power-law growth in time. The equal-time correlation has a short distance behavior that provides reasonable agreement between the corresponding structure factor tail and the Porod law. The autocorrelation decay is a power-law in the average domain size. Apart from these basic similarities, the overall quantitative behavior of the above-mentioned observables is found to be vastly different from those of the corresponding passive limit of the model which also undergoes phase separation. The functional forms of these have been quantified. An exceptionally rapid growth in the active system occurs due to fast coherent motion of the particles, mean-squared-displacements of which exhibit multiple scaling regimes, including a long time ballistic one.

Calcium tracer kinetics show decreased irreversible flow to bone in glucocorticoid treated patients.

PubMed

Goans, R E; Weiss, G H; Abrams, S A; Perez, M D; Yergey, A L

1995-06-01

Osteopenia resulting from pharmacologic doses of glucocorticoids is well known. Previously, there has been no satisfactory quantitative model describing the kinetics of calcium flow in subjects on chronic steroid use. A mathematical model of calcium isotope interaction with bone is described and applied to determine an estimate of kinetic parameters characterizing these changes. Calcium tracer dilution kinetics after a bolus injection of 42Ca were measured in 14 subjects with juvenile dermatomyositis, 6 on prednisone regimens and 8 on treatment regimens without prednisone. Irreversible tracer loss from plasma bone is found to be significantly reduced (P = 0.043) in the glucocorticoid-treated patients compared with patients on nonsteroid regimens. Reversible flow to bone is noted to be similar in the two groups. These results suggest a direct effect of glucocorticoids on osteoblast function.

Modeling of scale-dependent bacterial growth by chemical kinetics approach.

PubMed

Martínez, Haydee; Sánchez, Joaquín; Cruz, José-Manuel; Ayala, Guadalupe; Rivera, Marco; Buhse, Thomas

2014-01-01

We applied the so-called chemical kinetics approach to complex bacterial growth patterns that were dependent on the liquid-surface-area-to-volume ratio (SA/V) of the bacterial cultures. The kinetic modeling was based on current experimental knowledge in terms of autocatalytic bacterial growth, its inhibition by the metabolite CO2, and the relief of inhibition through the physical escape of the inhibitor. The model quantitatively reproduces kinetic data of SA/V-dependent bacterial growth and can discriminate between differences in the growth dynamics of enteropathogenic E. coli, E. coli JM83, and Salmonella typhimurium on one hand and Vibrio cholerae on the other hand. Furthermore, the data fitting procedures allowed predictions about the velocities of the involved key processes and the potential behavior in an open-flow bacterial chemostat, revealing an oscillatory approach to the stationary states.

The Human Terrain System: Operationally Relevant Social Science Research in Iraq and Afghanistan

DTIC Science & Technology

2015-12-01

my own studies; I have learned from them that scholarship is, indeed, a collective enterprise. Dr. Martin Bayly, Dr. Aliki Karapliagou, Andrea Coles...Division Colonel Martin Schweitzer’s initial positive assessment of AF1 in October 2007 (quoted by The New York Times) credited the team with re- ducing... Martin Schweitzer’s claim in congressional testimony concerning the quantitative reduction in kinetic activity. In February 2008, after

On the mode-coupling treatment of collective density fluctuations for quantum liquids: para-hydrogen and normal liquid helium.

PubMed

Kletenik-Edelman, Orly; Reichman, David R; Rabani, Eran

2011-01-28

A novel quantum mode coupling theory combined with a kinetic approach is developed for the description of collective density fluctuations in quantum liquids characterized by Boltzmann statistics. Three mode-coupling approximations are presented and applied to study the dynamic response of para-hydrogen near the triple point and normal liquid helium above the λ-transition. The theory is compared with experimental results and to the exact imaginary time data generated by path integral Monte Carlo simulations. While for liquid para-hydrogen the combination of kinetic and quantum mode-coupling theory provides semi-quantitative results for both short and long time dynamics, it fails for normal liquid helium. A discussion of this failure based on the ideal gas limit is presented.

Study of the temperature dependent immuno-reaction kinetics for the bio-functionalized magnetic nanoparticle assay of bio-markers of colorectal cancer

NASA Astrophysics Data System (ADS)

Yang, S. Y.; Chang, J. F.; Chen, T. C.; Yang, C. C.; Ho, C. S.

2014-01-01

By conjugating antibodies on magnetic nanoparticles, target antigens can be quantitatively detected by measuring the magnetic signals of the magnetic nanoparticles due to their association with target antigens. This method of detection is called magnetically labeled immunoassay. The assay characteristics of magnetically labeled immunoassay have been reported widely. However, the immuno-reaction kinetics of magnetically labeled immunoassay has not been studied. In this work, the reaction rates between magnetic nanoparticles and target antigens are measured at various temperatures. It is found that the temperature dependent reaction rate obeys Arrhenius's equation, which shows the collision frequency and activation energy for the immuno-reaction between antibody-functionalized magnetic nanoparticles and target antigens. The carcinoembryonic antigen, which is a regular blood bio-marker for in-vitro diagnosis of colorectal cancer, is used as a target antigen for the example.

Final Report: Molecular mechanisms and kinetics of microbial anaerobic nitrate-dependent U(IV) and Fe(II) oxidation

DOE Office of Scientific and Technical Information (OSTI.GOV)

O'Day, Peggy A.; Asta, Maria P.; Kanematsu, Masakazu

2015-02-27

In this project, we combined molecular genetic, spectroscopic, and microscopic techniques with kinetic and reactive transport studies to describe and quantify biotic and abiotic mechanisms underlying anaerobic, nitrate-dependent U(IV) and Fe(II) oxidation, which influences the long-term efficacy of in situ reductive immobilization of uranium at DOE sites. In these studies, Thiobacillus denitrificans, an autotrophic bacterium that catalyzes anaerobic U(IV) and Fe(II) oxidation, was used to examine coupled oxidation-reduction processes under either biotic (enzymatic) or abiotic conditions in batch and column experiments with biogenically produced UIVO2(s). Synthesis and quantitative analysis of coupled chemical and transport processes were done with the reactivemore » transport modeling code Crunchflow. Research focused on identifying the primary redox proteins that catalyze metal oxidation, environmental factors that influence protein expression, and molecular-scale geochemical factors that control the rates of biotic and abiotic oxidation.« less

Kinetic characterisation of primer mismatches in allele-specific PCR: a quantitative assessment.

PubMed

Waterfall, Christy M; Eisenthal, Robert; Cobb, Benjamin D

2002-12-20

A novel method of estimating the kinetic parameters of Taq DNA polymerase during rapid cycle PCR is presented. A model was constructed using a simplified sigmoid function to represent substrate accumulation during PCR in combination with the general equation describing high substrate inhibition for Michaelis-Menten enzymes. The PCR progress curve was viewed as a series of independent reactions where initial rates were accurately measured for each cycle. Kinetic parameters were obtained for allele-specific PCR (AS-PCR) amplification to examine the effect of mismatches on amplification. A high degree of correlation was obtained providing evidence of substrate inhibition as a major cause of the plateau phase that occurs in the later cycles of PCR.

Pixel-based approach to assess contrast-enhanced ultrasound kinetics parameters for differential diagnosis of rheumatoid arthritis.

PubMed

Rizzo, Gaia; Raffeiner, Bernd; Coran, Alessandro; Ciprian, Luca; Fiocco, Ugo; Botsios, Costantino; Stramare, Roberto; Grisan, Enrico

2015-07-01

Inflammatory rheumatic diseases are the leading causes of disability and constitute a frequent medical disorder, leading to inability to work, high comorbidity, and increased mortality. The standard for diagnosing and differentiating arthritis is based on clinical examination, laboratory exams, and imaging findings, such as synovitis, bone edema, or joint erosions. Contrast-enhanced ultrasound (CEUS) examination of the small joints is emerging as a sensitive tool for assessing vascularization and disease activity. Quantitative assessment is mostly performed at the region of interest level, where the mean intensity curve is fitted with an exponential function. We showed that using a more physiologically motivated perfusion curve, and by estimating the kinetic parameters separately pixel by pixel, the quantitative information gathered is able to more effectively characterize the different perfusion patterns. In particular, we demonstrated that a random forest classifier based on pixelwise quantification of the kinetic contrast agent perfusion features can discriminate rheumatoid arthritis from different arthritis forms (psoriatic arthritis, spondyloarthritis, and arthritis in connective tissue disease) with an average accuracy of 97%. On the contrary, clinical evaluation (DAS28), semiquantitative CEUS assessment, serological markers, or region-based parameters do not allow such a high diagnostic accuracy.

Pixel-based approach to assess contrast-enhanced ultrasound kinetics parameters for differential diagnosis of rheumatoid arthritis

PubMed Central

Rizzo, Gaia; Raffeiner, Bernd; Coran, Alessandro; Ciprian, Luca; Fiocco, Ugo; Botsios, Costantino; Stramare, Roberto; Grisan, Enrico

2015-01-01

Abstract. Inflammatory rheumatic diseases are the leading causes of disability and constitute a frequent medical disorder, leading to inability to work, high comorbidity, and increased mortality. The standard for diagnosing and differentiating arthritis is based on clinical examination, laboratory exams, and imaging findings, such as synovitis, bone edema, or joint erosions. Contrast-enhanced ultrasound (CEUS) examination of the small joints is emerging as a sensitive tool for assessing vascularization and disease activity. Quantitative assessment is mostly performed at the region of interest level, where the mean intensity curve is fitted with an exponential function. We showed that using a more physiologically motivated perfusion curve, and by estimating the kinetic parameters separately pixel by pixel, the quantitative information gathered is able to more effectively characterize the different perfusion patterns. In particular, we demonstrated that a random forest classifier based on pixelwise quantification of the kinetic contrast agent perfusion features can discriminate rheumatoid arthritis from different arthritis forms (psoriatic arthritis, spondyloarthritis, and arthritis in connective tissue disease) with an average accuracy of 97%. On the contrary, clinical evaluation (DAS28), semiquantitative CEUS assessment, serological markers, or region-based parameters do not allow such a high diagnostic accuracy. PMID:27014713

Modeling of kinetic, ionospheric and auroral contributions to the 557.7-nm nightglow

NASA Astrophysics Data System (ADS)

Campbell, L.; Brunger, M. J.

2010-11-01

Emission of 557.7-nm radiation from the Earth's upper atmosphere is produced by kinetic, ionospheric and auroral excitation of oxygen atoms. The mechanisms and hence the relative contributions of these three sources are not fully understood. A ground-based mid-latitude recording of the 557.7-nm emissions over the previous solar cycle facilitates a comparison of measurements with theoretical predictions. In this paper the predicted kinetic and ionospheric contributions are simulated and compared with the observations. Semi-quantitative agreement is found between the kinetic contribution and the observations, particularly in the presence of annual, semi-annual and solar cycle variations. An observed enhancement in the emissions in the years following solar maximum is not predicted by the kinetic model. However, correlation analysis reveals a component in the observed values that is related to the auroral hemispheric power. When this extra component is included, a better fit to the pre-midnight observations over the full solar cycle is found.

Influence of thermodynamically unfavorable secondary structures on DNA hybridization kinetics

PubMed Central

Hata, Hiroaki; Kitajima, Tetsuro

2018-01-01

Abstract Nucleic acid secondary structure plays an important role in nucleic acid–nucleic acid recognition/hybridization processes, and is also a vital consideration in DNA nanotechnology. Although the influence of stable secondary structures on hybridization kinetics has been characterized, unstable secondary structures, which show positive ΔG° with self-folding, can also form, and their effects have not been systematically investigated. Such thermodynamically unfavorable secondary structures should not be ignored in DNA hybridization kinetics, especially under isothermal conditions. Here, we report that positive ΔG° secondary structures can change the hybridization rate by two-orders of magnitude, despite the fact that their hybridization obeyed second-order reaction kinetics. The temperature dependence of hybridization rates showed non-Arrhenius behavior; thus, their hybridization is considered to be nucleation limited. We derived a model describing how ΔG° positive secondary structures affect hybridization kinetics in stopped-flow experiments with 47 pairs of oligonucleotides. The calculated hybridization rates, which were based on the model, quantitatively agreed with the experimental rate constant. PMID:29220504

Solidification kinetics of a Cu-Zr alloy: ground-based and microgravity experiments

NASA Astrophysics Data System (ADS)

Galenko, P. K.; Hanke, R.; Paul, P.; Koch, S.; Rettenmayr, M.; Gegner, J.; Herlach, D. M.; Dreier, W.; Kharanzhevski, E. V.

2017-04-01

Experimental and theoretical results obtained in the MULTIPHAS-project (ESA-European Space Agency and DLR-German Aerospace Center) are critically discussed regarding solidification kinetics of congruently melting and glass forming Cu50Zr50 alloy samples. The samples are investigated during solidification using a containerless technique in the Electromagnetic Levitation Facility [1]. Applying elaborated methodologies for ground-based and microgravity experimental investigations [2], the kinetics of primary dendritic solidification is quantitatively evaluated. Electromagnetic Levitator in microgravity (parabolic flights and on board of the International Space Station) and Electrostatic Levitator on Ground are employed. The solidification kinetics is determined using a high-speed camera and applying two evaluation methods: “Frame by Frame” (FFM) and “First Frame - Last Frame” (FLM). In the theoretical interpretation of the solidification experiments, special attention is given to the behavior of the cluster structure in Cu50Zr50 samples with the increase of undercooling. Experimental results on solidification kinetics are interpreted using a theoretical model of diffusion controlled dendrite growth.

Simulation of the effects of sub-breakdown electric fields on the chemical kinetics in nonpremixed counterflow methane/air flames

NASA Astrophysics Data System (ADS)

Belhi, Memdouh; Im, Hong; Computational Reacting Flows Laboratory, Clean Combustion Research Center Team

2017-11-01

The effects of an electric field on the combustion kinetics in nonpremixed counterflow methane/air flames were investigated via one-dimensional numerical simulations. A classical fluid model coupling Poison's equation with transport equations for combustion species and electric field-induced particles was used. A methane-air reaction mechanism accounting for the natural ionization in flames was combined with a set of reactions that describe the formation of active particles induced by the electric field. Kinetic parameters for electron-impact reactions and transport coefficients of electrons were modeled as functions of reduced electric field via solutions to the Boltzmann kinetic equation using the BOLSIG code. Mobility of ions was computed based on the (n,6,4) and coulomb interaction potentials, while the diffusion coefficient was approximated from the mobility using Einstein relation. Contributions of electron dissociation, excitation and ionization processes were characterized quantitatively. An analysis to identify the plasma regime where the electric field can alter the combustion kinetic was proposed.

Kinetic characterization of bile salt transport by human NTCP (SLC10A1).

PubMed

Jani, Márton; Beéry, Erzsébet; Heslop, Teresa; Tóth, Beáta; Jagota, Bhavana; Kis, Emese; Kevin Park, B; Krajcsi, Peter; Weaver, Richard J

2018-02-01

The transport of bile acids facilitated by NTCP is an important factor in establishing bile flow. In this study, we examine the kinetics associated with human NTCP-dependent transport of two quantitatively important bile acids comprising the human bile acid pool, chenodeoxycholic acid and glycine-chenodeoxycholate, and secondary bile salt, 3-sulfo-glycolithocholate of potential toxicological significance. The study employed human NTCP overexpressing Chinese Hamster Ovary cells and results compared with taurocholate, a prototypical bile salt commonly used in transporter studies. GCDC and 3S-GLC but not CDCA were transported by NTCP. The efficient uptake of GCDC, TCA and 3S-GLC by NTCP enabled the determination of kinetics. GCDC displayed a lower K M (0.569±0.318μM) than TCA (6.44±3.83μM) and 3S-GLC (3.78±1.17μM). The apparent CL int value for GCDC was 20-fold greater (153±53μl/mg protein/min) than the apparent CL int for TCA (6.92±4.72μl/mg protein/min) and apparent CL int for 3S-GLC (8.05±1.33μl/mg protein/min). These kinetic results provide important complementary data on the substrate selectivity and specificity of NTCP to transport bile acids. NTCP transports GCDC with greater efficiency than TCA and has the same efficacy for 3S-GLC and TCA. Copyright © 2017. Published by Elsevier Ltd.

Abnormal early diastolic intraventricular flow 'kinetic energy index' assessed by vector flow mapping in patients with elevated filling pressure.

PubMed

Nogami, Yoshie; Ishizu, Tomoko; Atsumi, Akiko; Yamamoto, Masayoshi; Kawamura, Ryo; Seo, Yoshihiro; Aonuma, Kazutaka

2013-03-01

Recently developed vector flow mapping (VFM) enables evaluation of local flow dynamics without angle dependency. This study used VFM to evaluate quantitatively the index of intraventricular haemodynamic kinetic energy in patients with left ventricular (LV) diastolic dysfunction and to compare those with normal subjects. We studied 25 patients with estimated high left atrial (LA) pressure (pseudonormal: PN group) and 36 normal subjects (control group). Left ventricle was divided into basal, mid, and apical segments. Intraventricular haemodynamic energy was evaluated in the dimension of speed, and it was defined as the kinetic energy index. We calculated this index and created time-energy index curves. The time interval from electrocardiogram (ECG) R wave to peak index was measured, and time differences of the peak index between basal and other segments were defined as ΔT-mid and ΔT-apex. In both groups, early diastolic peak kinetic energy index in mid and apical segments was significantly lower than that in the basal segment. Time to peak index did not differ in apex, mid, and basal segments in the control group but was significantly longer in the apex than that in the basal segment in the PN group. ΔT-mid and ΔT-apex were significantly larger in the PN group than the control group. Multiple regression analysis showed sphericity index, E/E' to be significant independent variables determining ΔT apex. Retarded apical kinetic energy fluid dynamics were detected using VFM and were closely associated with LV spherical remodelling in patients with high LA pressure.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aghaei, Faranak; Tan, Maxine; Liu, Hong

Purpose: To identify a new clinical marker based on quantitative kinetic image features analysis and assess its feasibility to predict tumor response to neoadjuvant chemotherapy. Methods: The authors assembled a dataset involving breast MR images acquired from 68 cancer patients before undergoing neoadjuvant chemotherapy. Among them, 25 patients had complete response (CR) and 43 had partial and nonresponse (NR) to chemotherapy based on the response evaluation criteria in solid tumors. The authors developed a computer-aided detection scheme to segment breast areas and tumors depicted on the breast MR images and computed a total of 39 kinetic image features from bothmore » tumor and background parenchymal enhancement regions. The authors then applied and tested two approaches to classify between CR and NR cases. The first one analyzed each individual feature and applied a simple feature fusion method that combines classification results from multiple features. The second approach tested an attribute selected classifier that integrates an artificial neural network (ANN) with a wrapper subset evaluator, which was optimized using a leave-one-case-out validation method. Results: In the pool of 39 features, 10 yielded relatively higher classification performance with the areas under receiver operating characteristic curves (AUCs) ranging from 0.61 to 0.78 to classify between CR and NR cases. Using a feature fusion method, the maximum AUC = 0.85 ± 0.05. Using the ANN-based classifier, AUC value significantly increased to 0.96 ± 0.03 (p < 0.01). Conclusions: This study demonstrated that quantitative analysis of kinetic image features computed from breast MR images acquired prechemotherapy has potential to generate a useful clinical marker in predicting tumor response to chemotherapy.« less

Differential equation methods for simulation of GFP kinetics in non-steady state experiments.

PubMed

Phair, Robert D

2018-03-15

Genetically encoded fluorescent proteins, combined with fluorescence microscopy, are widely used in cell biology to collect kinetic data on intracellular trafficking. Methods for extraction of quantitative information from these data are based on the mathematics of diffusion and tracer kinetics. Current methods, although useful and powerful, depend on the assumption that the cellular system being studied is in a steady state, that is, the assumption that all the molecular concentrations and fluxes are constant for the duration of the experiment. Here, we derive new tracer kinetic analytical methods for non-steady state biological systems by constructing mechanistic nonlinear differential equation models of the underlying cell biological processes and linking them to a separate set of differential equations governing the kinetics of the fluorescent tracer. Linking the two sets of equations is based on a new application of the fundamental tracer principle of indistinguishability and, unlike current methods, supports correct dependence of tracer kinetics on cellular dynamics. This approach thus provides a general mathematical framework for applications of GFP fluorescence microscopy (including photobleaching [FRAP, FLIP] and photoactivation to frequently encountered experimental protocols involving physiological or pharmacological perturbations (e.g., growth factors, neurotransmitters, acute knockouts, inhibitors, hormones, cytokines, and metabolites) that initiate mechanistically informative intracellular transients. When a new steady state is achieved, these methods automatically reduce to classical steady state tracer kinetic analysis. © 2018 Phair. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Gender differences in joint biomechanics during walking: normative study in young adults.

PubMed

Kerrigan, D C; Todd, M K; Della Croce, U

1998-01-01

The effect of gender on specific joint biomechanics during gait has been largely unexplored. Given the perceived, subjective, and temporal differences in walking between genders, we hypothesized that quantitative analysis would reveal specific gender differences in joint biomechanics as well. Sagittal kinematic (joint motion) and kinetic (joint torque and power) data from the lower limbs during walking were collected and analyzed in 99 young adult subjects (49 females), aged 20 to 40 years, using an optoelectronic motion analysis and force platform system. Kinetic data were normalized for both height and weight. Female and male data were compared graphically and statistically to assess differences in all major peak joint kinematic and kinetic values. Females had significantly greater hip flexion and less knee extension before initial contact, greater knee flexion moment in pre-swing, and greater peak mechanical joint power absorption at the knee in pre-swing (P < 0.0019 for each parameter). Other differences were noted (P < 0.05) that were not statistically significant when accounting for multiple comparisons. These gender differences may provide new insights into walking dynamics and may be important for both clinical and research studies in motivating the development of separate biomechanical reference databases for males and females.

Stochastic mechano-chemical kinetics of molecular motors: A multidisciplinary enterprise from a physicist’s perspective

NASA Astrophysics Data System (ADS)

Chowdhury, Debashish

2013-08-01

A molecular motor is made of either a single macromolecule or a macromolecular complex. Just like their macroscopic counterparts, molecular motors “transduce” input energy into mechanical work. All the nano-motors considered here operate under isothermal conditions far from equilibrium. Moreover, one of the possible mechanisms of energy transduction, called Brownian ratchet, does not even have any macroscopic counterpart. But, molecular motor is not synonymous with Brownian ratchet; a large number of molecular motors execute a noisy power stroke, rather than operating as Brownian ratchet. We review not only the structural design and stochastic kinetics of individual single motors, but also their coordination, cooperation and competition as well as the assembly of multi-module motors in various intracellular kinetic processes. Although all the motors considered here execute mechanical movements, efficiency and power output are not necessarily good measures of performance of some motors. Among the intracellular nano-motors, we consider the porters, sliders and rowers, pistons and hooks, exporters, importers, packers and movers as well as those that also synthesize, manipulate and degrade “macromolecules of life”. We review mostly the quantitative models for the kinetics of these motors. We also describe several of those motor-driven intracellular stochastic processes for which quantitative models are yet to be developed. In part I, we discuss mainly the methodology and the generic models of various important classes of molecular motors. In part II, we review many specific examples emphasizing the unity of the basic mechanisms as well as diversity of operations arising from the differences in their detailed structure and kinetics. Multi-disciplinary research is presented here from the perspective of physicists.

Monochloramine Disinfection Kinetics of Nitrosomonas europaea by Propidium Monoazide Quantitative PCR and Live/Dead BacLight Methods▿

PubMed Central

Wahman, David G.; Wulfeck-Kleier, Karen A.; Pressman, Jonathan G.

2009-01-01

Monochloramine disinfection kinetics were determined for the pure-culture ammonia-oxidizing bacterium Nitrosomonas europaea (ATCC 19718) by two culture-independent methods, namely, Live/Dead BacLight (LD) and propidium monoazide quantitative PCR (PMA-qPCR). Both methods were first verified with mixtures of heat-killed (nonviable) and non-heat-killed (viable) cells before a series of batch disinfection experiments with stationary-phase cultures (batch grown for 7 days) at pH 8.0, 25°C, and 5, 10, and 20 mg Cl2/liter monochloramine. Two data sets were generated based on the viability method used, either (i) LD or (ii) PMA-qPCR. These two data sets were used to estimate kinetic parameters for the delayed Chick-Watson disinfection model through a Bayesian analysis implemented in WinBUGS. This analysis provided parameter estimates of 490 mg Cl2-min/liter for the lag coefficient (b) and 1.6 × 10−3 to 4.0 × 10−3 liter/mg Cl2-min for the Chick-Watson disinfection rate constant (k). While estimates of b were similar for both data sets, the LD data set resulted in a greater k estimate than that obtained with the PMA-qPCR data set, implying that the PMA-qPCR viability measure was more conservative than LD. For N. europaea, the lag phase was not previously reported for culture-independent methods and may have implications for nitrification in drinking water distribution systems. This is the first published application of a PMA-qPCR method for disinfection kinetic model parameter estimation as well as its application to N. europaea or monochloramine. Ultimately, this PMA-qPCR method will allow evaluation of monochloramine disinfection kinetics for mixed-culture bacteria in drinking water distribution systems. PMID:19561179

Optimization of time-course experiments for kinetic model discrimination.

PubMed

Lages, Nuno F; Cordeiro, Carlos; Sousa Silva, Marta; Ponces Freire, Ana; Ferreira, António E N

2012-01-01

Systems biology relies heavily on the construction of quantitative models of biochemical networks. These models must have predictive power to help unveiling the underlying molecular mechanisms of cellular physiology, but it is also paramount that they are consistent with the data resulting from key experiments. Often, it is possible to find several models that describe the data equally well, but provide significantly different quantitative predictions regarding particular variables of the network. In those cases, one is faced with a problem of model discrimination, the procedure of rejecting inappropriate models from a set of candidates in order to elect one as the best model to use for prediction.In this work, a method is proposed to optimize the design of enzyme kinetic assays with the goal of selecting a model among a set of candidates. We focus on models with systems of ordinary differential equations as the underlying mathematical description. The method provides a design where an extension of the Kullback-Leibler distance, computed over the time courses predicted by the models, is maximized. Given the asymmetric nature this measure, a generalized differential evolution algorithm for multi-objective optimization problems was used.The kinetics of yeast glyoxalase I (EC 4.4.1.5) was chosen as a difficult test case to evaluate the method. Although a single-substrate kinetic model is usually considered, a two-substrate mechanism has also been proposed for this enzyme. We designed an experiment capable of discriminating between the two models by optimizing the initial substrate concentrations of glyoxalase I, in the presence of the subsequent pathway enzyme, glyoxalase II (EC 3.1.2.6). This discriminatory experiment was conducted in the laboratory and the results indicate a two-substrate mechanism for the kinetics of yeast glyoxalase I.

Improved accuracy of quantitative parameter estimates in dynamic contrast-enhanced CT study with low temporal resolution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Sun Mo, E-mail: Sunmo.Kim@rmp.uhn.on.ca; Haider, Masoom A.; Jaffray, David A.

Purpose: A previously proposed method to reduce radiation dose to patient in dynamic contrast-enhanced (DCE) CT is enhanced by principal component analysis (PCA) filtering which improves the signal-to-noise ratio (SNR) of time-concentration curves in the DCE-CT study. The efficacy of the combined method to maintain the accuracy of kinetic parameter estimates at low temporal resolution is investigated with pixel-by-pixel kinetic analysis of DCE-CT data. Methods: The method is based on DCE-CT scanning performed with low temporal resolution to reduce the radiation dose to the patient. The arterial input function (AIF) with high temporal resolution can be generated with a coarselymore » sampled AIF through a previously published method of AIF estimation. To increase the SNR of time-concentration curves (tissue curves), first, a region-of-interest is segmented into squares composed of 3 × 3 pixels in size. Subsequently, the PCA filtering combined with a fraction of residual information criterion is applied to all the segmented squares for further improvement of their SNRs. The proposed method was applied to each DCE-CT data set of a cohort of 14 patients at varying levels of down-sampling. The kinetic analyses using the modified Tofts’ model and singular value decomposition method, then, were carried out for each of the down-sampling schemes between the intervals from 2 to 15 s. The results were compared with analyses done with the measured data in high temporal resolution (i.e., original scanning frequency) as the reference. Results: The patients’ AIFs were estimated to high accuracy based on the 11 orthonormal bases of arterial impulse responses established in the previous paper. In addition, noise in the images was effectively reduced by using five principal components of the tissue curves for filtering. Kinetic analyses using the proposed method showed superior results compared to those with down-sampling alone; they were able to maintain the accuracy in the quantitative histogram parameters of volume transfer constant [standard deviation (SD), 98th percentile, and range], rate constant (SD), blood volume fraction (mean, SD, 98th percentile, and range), and blood flow (mean, SD, median, 98th percentile, and range) for sampling intervals between 10 and 15 s. Conclusions: The proposed method of PCA filtering combined with the AIF estimation technique allows low frequency scanning for DCE-CT study to reduce patient radiation dose. The results indicate that the method is useful in pixel-by-pixel kinetic analysis of DCE-CT data for patients with cervical cancer.« less

Quantitative production of compound I from a cytochrome P450 enzyme at low temperatures. Kinetics, activation parameters, and kinetic isotope effects for oxidation of benzyl alcohol.

PubMed

Wang, Qin; Sheng, Xin; Horner, John H; Newcomb, Martin

2009-08-05

Cytochrome P450 enzymes are commonly thought to oxidize substrates via an iron(IV)-oxo porphyrin radical cation transient termed Compound I, but kinetic studies of P450 Compounds I are essentially nonexistent. We report production of Compound I from cytochrome P450 119 (CYP119) in high conversion from the corresponding Compound II species at low temperatures in buffer mixtures containing 50% glycerol by photolysis with 365 nm light from a pulsed lamp. Compound I was studied as a reagent in oxidations of benzyl alcohol and its benzylic mono- and dideuterio isotopomers. Pseudo-first-order rate constants obtained at -50 degrees C with concentrations of substrates between 1.0 and 6.0 mM displayed saturation kinetics that gave binding constants for the substrate in the Compound I species (K(bind)) and first-order rate constants for the oxidation reactions (k(ox)). Representative results are K(bind) = 214 M(-1) and k(ox) = 0.48 s(-1) for oxidation of benzyl alcohol. For the dideuterated substrate C(6)H(5)CD(2)OH, kinetics were studied between -50 and -25 degrees C, and a van't Hoff plot for complexation and an Arrhenius plot for the oxidation reaction were constructed. The H/D kinetic isotope effects (KIEs) at -50 degrees C were resolved into a large primary KIE (P = 11.9) and a small, inverse secondary KIE (S = 0.96). Comparison of values extrapolated to 22 degrees C of both the rate constant for oxidation of C(6)H(5)CD(2)OH and the KIE for the nondeuterated and dideuterated substrates to values obtained previously in laser flash photolysis experiments suggested that tunneling could be a significant component of the total rate constant at -50 degrees C.

The significance of intergranular diffusion to the mechanisms and kinetics of porphyroblast crystallization

NASA Astrophysics Data System (ADS)

Carlson, William D.

1989-09-01

The spatial disposition, compositional zoning profiles, and size distributions of garnet crystals in 11 specimens of pelitic schist from the Picuris Range of New Mexico (USA) demonstrate that the kinetics of intergranular diffusion controlled the nucleation and growth mechanisms of porphyroblasts in these rocks. An ordered disposition of garnet centers and a significant correlation between crystal radius and near-neighbor distances manifest suppressed nucleation of new crystals in diffusionally depleted zones surrounding pre-existing crystals. Compositional zoning profiles require diffusionally controlled growth, the rate of which increases exponentially as temperature increases with time; an acceleration factor for growth rate can be estimated from a comparison of compositional profiles for crystals of different sizes in each specimen. Crystal size distributions are interpreted as the result of nucleation rates that accelerate exponentially with increasing temperature early in the crystallization process, but decline in the later stages because of suppression effects in the vicinity of earlier-formed nuclei. Simulations of porphyroblast crystallization, based upon thermally accelerated diffusionally influenced nucleation kinetics and diffusionally controlled growth kinetics, quantitatively replicate textural relations in the rocks. The simulations employ only two variable parameters, which are evaluated by fitting of crystal size distributions. Both have physical significance. The first is an acceleration factor for nucleation, with a magnitude reflecting the prograde increase during the nucleation interval of the chemical affinity for the reaction in undepleted regions of the rock. The second is a measure of the relative sizes of the porphyroblast and the diffusionally depleted zone surrounding it. Crystal size distributions for the Picuris Range garnets correspond very closely to those in the literature from a variety of other localities for garnet and other minerals. The same kinetic model accounts quantitatively for crystal size distributions of porphyroblastic garnet, phlogopite, sphene, and pyroxene in rocks from both regional and contact metamorphic occurrences. These commonalities indicate that intergranular diffusion may be the dominant kinetic factor in the crystallization of porphyroblasts in a wide variety of metamorphic environments.

Three-dimensional drift kinetic response of high-β plasmas in the DIII-D tokamak.

PubMed

Wang, Z R; Lanctot, M J; Liu, Y Q; Park, J-K; Menard, J E

2015-04-10

A quantitative interpretation of the experimentally measured high-pressure plasma response to externally applied three-dimensional (3D) magnetic field perturbations, across the no-wall Troyon β limit, is achieved. The self-consistent inclusion of the drift kinetic effects in magnetohydrodynamic (MHD) modeling [Y. Q. Liu et al., Phys. Plasmas 15, 112503 (2008)] successfully resolves an outstanding issue of the ideal MHD model, which significantly overpredicts the plasma-induced field amplification near the no-wall limit, as compared to experiments. The model leads to quantitative agreement not only for the measured field amplitude and toroidal phase but also for the measured internal 3D displacement of the plasma. The results can be important to the prediction of the reliable plasma behavior in advanced fusion devices, such as ITER [K. Ikeda, Nucl. Fusion 47, S1 (2007)].

Stepwise kinetic equilibrium models of quantitative polymerase chain reaction.

PubMed

Cobbs, Gary

2012-08-16

Numerous models for use in interpreting quantitative PCR (qPCR) data are present in recent literature. The most commonly used models assume the amplification in qPCR is exponential and fit an exponential model with a constant rate of increase to a select part of the curve. Kinetic theory may be used to model the annealing phase and does not assume constant efficiency of amplification. Mechanistic models describing the annealing phase with kinetic theory offer the most potential for accurate interpretation of qPCR data. Even so, they have not been thoroughly investigated and are rarely used for interpretation of qPCR data. New results for kinetic modeling of qPCR are presented. Two models are presented in which the efficiency of amplification is based on equilibrium solutions for the annealing phase of the qPCR process. Model 1 assumes annealing of complementary targets strands and annealing of target and primers are both reversible reactions and reach a dynamic equilibrium. Model 2 assumes all annealing reactions are nonreversible and equilibrium is static. Both models include the effect of primer concentration during the annealing phase. Analytic formulae are given for the equilibrium values of all single and double stranded molecules at the end of the annealing step. The equilibrium values are then used in a stepwise method to describe the whole qPCR process. Rate constants of kinetic models are the same for solutions that are identical except for possibly having different initial target concentrations. Analysis of qPCR curves from such solutions are thus analyzed by simultaneous non-linear curve fitting with the same rate constant values applying to all curves and each curve having a unique value for initial target concentration. The models were fit to two data sets for which the true initial target concentrations are known. Both models give better fit to observed qPCR data than other kinetic models present in the literature. They also give better estimates of initial target concentration. Model 1 was found to be slightly more robust than model 2 giving better estimates of initial target concentration when estimation of parameters was done for qPCR curves with very different initial target concentration. Both models may be used to estimate the initial absolute concentration of target sequence when a standard curve is not available. It is argued that the kinetic approach to modeling and interpreting quantitative PCR data has the potential to give more precise estimates of the true initial target concentrations than other methods currently used for analysis of qPCR data. The two models presented here give a unified model of the qPCR process in that they explain the shape of the qPCR curve for a wide variety of initial target concentrations.

Folding kinetics of WW domains with the united residue force field for bridging microscopic motions and experimental measurements

PubMed Central

Zhou, Rui; Maisuradze, Gia G.; Suñol, David; Todorovski, Toni; Macias, Maria J.; Xiao, Yi; Scheraga, Harold A.; Czaplewski, Cezary; Liwo, Adam

2014-01-01

To demonstrate the utility of the coarse-grained united-residue (UNRES) force field to compare experimental and computed kinetic data for folding proteins, we have performed long-time millisecond-timescale canonical Langevin molecular dynamics simulations of the triple β-strand from the Formin binding protein 28 WW domain and six nonnatural variants, using UNRES. The results have been compared with available experimental data in both a qualitative and a quantitative manner. Complexities of the folding pathways, which cannot be determined experimentally, were revealed. The folding mechanisms obtained from the simulated folding kinetics are in agreement with experimental results, with a few discrepancies for which we have accounted. The origins of single- and double-exponential kinetics and their correlations with two- and three-state folding scenarios are shown to be related to the relative barrier heights between the various states. The rate constants obtained from time profiles of the fractions of the native, intermediate, and unfolded structures, and the kinetic equations fitted to them, correlate with the experimental values; however, they are about three orders of magnitude larger than the experimental ones for most of the systems. These differences are in agreement with the timescale extension derived by scaling down the friction of water and averaging out the fast degrees of freedom when passing from all-atom to a coarse-grained representation. Our results indicate that the UNRES force field can provide accurate predictions of folding kinetics of these WW domains, often used as models for the study of the mechanisms of proein folding. PMID:25489078

Folding kinetics of WW domains with the united residue force field for bridging microscopic motions and experimental measurements.

PubMed

Zhou, Rui; Maisuradze, Gia G; Suñol, David; Todorovski, Toni; Macias, Maria J; Xiao, Yi; Scheraga, Harold A; Czaplewski, Cezary; Liwo, Adam

2014-12-23

To demonstrate the utility of the coarse-grained united-residue (UNRES) force field to compare experimental and computed kinetic data for folding proteins, we have performed long-time millisecond-timescale canonical Langevin molecular dynamics simulations of the triple β-strand from the Formin binding protein 28 WW domain and six nonnatural variants, using UNRES. The results have been compared with available experimental data in both a qualitative and a quantitative manner. Complexities of the folding pathways, which cannot be determined experimentally, were revealed. The folding mechanisms obtained from the simulated folding kinetics are in agreement with experimental results, with a few discrepancies for which we have accounted. The origins of single- and double-exponential kinetics and their correlations with two- and three-state folding scenarios are shown to be related to the relative barrier heights between the various states. The rate constants obtained from time profiles of the fractions of the native, intermediate, and unfolded structures, and the kinetic equations fitted to them, correlate with the experimental values; however, they are about three orders of magnitude larger than the experimental ones for most of the systems. These differences are in agreement with the timescale extension derived by scaling down the friction of water and averaging out the fast degrees of freedom when passing from all-atom to a coarse-grained representation. Our results indicate that the UNRES force field can provide accurate predictions of folding kinetics of these WW domains, often used as models for the study of the mechanisms of proein folding.

Solar Wind Turbulent Cascade from MHD to Sub-ion Scales: Large-size 3D Hybrid Particle-in-cell Simulations

NASA Astrophysics Data System (ADS)

Franci, Luca; Landi, Simone; Verdini, Andrea; Matteini, Lorenzo; Hellinger, Petr

2018-01-01

Properties of the turbulent cascade from fluid to kinetic scales in collisionless plasmas are investigated by means of large-size 3D hybrid (fluid electrons, kinetic protons) particle-in-cell simulations. Initially isotropic Alfvénic fluctuations rapidly develop a strongly anisotropic turbulent cascade, mainly in the direction perpendicular to the ambient magnetic field. The omnidirectional magnetic field spectrum shows a double power-law behavior over almost two decades in wavenumber, with a Kolmogorov-like index at large scales, a spectral break around ion scales, and a steepening at sub-ion scales. Power laws are also observed in the spectra of the ion bulk velocity, density, and electric field, at both magnetohydrodynamic (MHD) and kinetic scales. Despite the complex structure, the omnidirectional spectra of all fields at ion and sub-ion scales are in remarkable quantitative agreement with those of a 2D simulation with similar physical parameters. This provides a partial, a posteriori validation of the 2D approximation at kinetic scales. Conversely, at MHD scales, the spectra of the density and of the velocity (and, consequently, of the electric field) exhibit differences between the 2D and 3D cases. Although they can be partly ascribed to the lower spatial resolution, the main reason is likely the larger importance of compressible effects in the full 3D geometry. Our findings are also in remarkable quantitative agreement with solar wind observations.

Improved kinetic neoclassical transport calculation for a low-collisionality QH-mode pedestal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Battaglia, D. J.; Burrell, K. H.; Chang, C. S.

The role of neoclassical, anomalous and neutral transport to the overall H-mode pedestal and scrape-off layer (SOL) structure in an ELM-free QH-mode discharge on DIII-D is explored using XGC0, a 5D full-f multi-species particle-in-cell drift-kinetic solver with self-consistent neutral recycling and sheath potentials. The work in this paper builds on previous work aimed at achieving quantitative agreement between the flux-driven simulation and the experimental electron density, impurity density and orthogonal measurements of impurity temperature and flow profiles. Improved quantitative agreement is achieved by performing the calculations with a more realistic electron mass, larger neutral density and including finite-Larmor-radius corrections self-consistentlymore » in the drift-kinetic motion of the particles. Consequently, the simulations provide stronger evidence that the radial electric field (E r) in the pedestal is primarily established by the required balance between the loss of high-energy tail main ions against a pinch of colder main ions and impurities. The kinetic loss of a small population of ions carrying a large proportion of energy and momentum leads to a separation of the particle and energy transport rates and introduces a source of intrinsic edge torque. Ion orbit loss and finite orbit width effects drive the energy distributions away from Maxwellian, and describe the anisotropy, poloidal asymmetry and local minimum near the separatrix observed in the T i profile.« less

Improved kinetic neoclassical transport calculation for a low-collisionality QH-mode pedestal

DOE PAGES

Battaglia, D. J.; Burrell, K. H.; Chang, C. S.; ...

2016-07-15

The role of neoclassical, anomalous and neutral transport to the overall H-mode pedestal and scrape-off layer (SOL) structure in an ELM-free QH-mode discharge on DIII-D is explored using XGC0, a 5D full-f multi-species particle-in-cell drift-kinetic solver with self-consistent neutral recycling and sheath potentials. The work in this paper builds on previous work aimed at achieving quantitative agreement between the flux-driven simulation and the experimental electron density, impurity density and orthogonal measurements of impurity temperature and flow profiles. Improved quantitative agreement is achieved by performing the calculations with a more realistic electron mass, larger neutral density and including finite-Larmor-radius corrections self-consistentlymore » in the drift-kinetic motion of the particles. Consequently, the simulations provide stronger evidence that the radial electric field (E r) in the pedestal is primarily established by the required balance between the loss of high-energy tail main ions against a pinch of colder main ions and impurities. The kinetic loss of a small population of ions carrying a large proportion of energy and momentum leads to a separation of the particle and energy transport rates and introduces a source of intrinsic edge torque. Ion orbit loss and finite orbit width effects drive the energy distributions away from Maxwellian, and describe the anisotropy, poloidal asymmetry and local minimum near the separatrix observed in the T i profile.« less

Fast Metabolic Response to Drug Intervention through Analysis on a Miniaturized, Highly Integrated Molecular Imaging System

PubMed Central

Wang, Jun; Hwang, Kiwook; Braas, Daniel; Dooraghi, Alex; Nathanson, David; Campbell, Dean O.; Gu, Yuchao; Sandberg, Troy; Mischel, Paul; Radu, Caius; Chatziioannou, Arion F.; Phelps, Michael E.; Christofk, Heather; Heath, James R.

2014-01-01

We report on a radiopharmaceutical imaging platform designed to capture the kinetics of cellular responses to drugs. Methods A portable in vitro molecular imaging system, comprised of a microchip and a beta-particle imaging camera, permits routine cell-based radioassays on small number of either suspension or adherent cells. We investigate the response kinetics of model lymphoma and glioblastoma cancer cell lines to [18F]fluorodeoxyglucose ([18F]FDG) uptake following drug exposure. Those responses are correlated with kinetic changes in the cell cycle, or with changes in receptor-tyrosine kinase signaling. Results The platform enables radioassays directly on multiple cell types, and yields results comparable to conventional approaches, but uses smaller sample sizes, permits a higher level of quantitation, and doesn’t require cell lysis. Conclusion The kinetic analysis enabled by the platform provides a rapid (~1 hour) drug screening assay. PMID:23978446

Nonlinear Acoustical Assessment of Precipitate Nucleation

NASA Technical Reports Server (NTRS)

Cantrell, John H.; Yost, William T.

2004-01-01

The purpose of the present work is to show that measurements of the acoustic nonlinearity parameter in heat treatable alloys as a function of heat treatment time can provide quantitative information about the kinetics of precipitate nucleation and growth in such alloys. Generally, information on the kinetics of phase transformations is obtained from time-sequenced electron microscopical examination and differential scanning microcalorimetry. The present nonlinear acoustical assessment of precipitation kinetics is based on the development of a multiparameter analytical model of the effects on the nonlinearity parameter of precipitate nucleation and growth in the alloy system. A nonlinear curve fit of the model equation to the experimental data is then used to extract the kinetic parameters related to the nucleation and growth of the targeted precipitate. The analytical model and curve fit is applied to the assessment of S' precipitation in aluminum alloy 2024 during artificial aging from the T4 to the T6 temper.

Simulating Chemical Kinetics Without Differential Equations: A Quantitative Theory Based on Chemical Pathways.

PubMed

Bai, Shirong; Skodje, Rex T

2017-08-17

A new approach is presented for simulating the time-evolution of chemically reactive systems. This method provides an alternative to conventional modeling of mass-action kinetics that involves solving differential equations for the species concentrations. The method presented here avoids the need to solve the rate equations by switching to a representation based on chemical pathways. In the Sum Over Histories Representation (or SOHR) method, any time-dependent kinetic observable, such as concentration, is written as a linear combination of probabilities for chemical pathways leading to a desired outcome. In this work, an iterative method is introduced that allows the time-dependent pathway probabilities to be generated from a knowledge of the elementary rate coefficients, thus avoiding the pitfalls involved in solving the differential equations of kinetics. The method is successfully applied to the model Lotka-Volterra system and to a realistic H 2 combustion model.

Detection of kinetic change points in piece-wise linear single molecule motion

NASA Astrophysics Data System (ADS)

Hill, Flynn R.; van Oijen, Antoine M.; Duderstadt, Karl E.

2018-03-01

Single-molecule approaches present a powerful way to obtain detailed kinetic information at the molecular level. However, the identification of small rate changes is often hindered by the considerable noise present in such single-molecule kinetic data. We present a general method to detect such kinetic change points in trajectories of motion of processive single molecules having Gaussian noise, with a minimum number of parameters and without the need of an assumed kinetic model beyond piece-wise linearity of motion. Kinetic change points are detected using a likelihood ratio test in which the probability of no change is compared to the probability of a change occurring, given the experimental noise. A predetermined confidence interval minimizes the occurrence of false detections. Applying the method recursively to all sub-regions of a single molecule trajectory ensures that all kinetic change points are located. The algorithm presented allows rigorous and quantitative determination of kinetic change points in noisy single molecule observations without the need for filtering or binning, which reduce temporal resolution and obscure dynamics. The statistical framework for the approach and implementation details are discussed. The detection power of the algorithm is assessed using simulations with both single kinetic changes and multiple kinetic changes that typically arise in observations of single-molecule DNA-replication reactions. Implementations of the algorithm are provided in ImageJ plugin format written in Java and in the Julia language for numeric computing, with accompanying Jupyter Notebooks to allow reproduction of the analysis presented here.

Antibacterial effect of silver nanoparticles and the modeling of bacterial growth kinetics using a modified Gompertz model.

PubMed

Chatterjee, Tanaya; Chatterjee, Barun K; Majumdar, Dipanwita; Chakrabarti, Pinak

2015-02-01

An alternative to conventional antibiotics is needed to fight against emerging multiple drug resistant pathogenic bacteria. In this endeavor, the effect of silver nanoparticle (Ag-NP) has been studied quantitatively on two common pathogenic bacteria Escherichia coli and Staphylococcus aureus, and the growth curves were modeled. The effect of Ag-NP on bacterial growth kinetics was studied by measuring the optical density, and was fitted by non-linear regression using the Logistic and modified Gompertz models. Scanning Electron Microscopy and fluorescence microscopy were used to study the morphological changes of the bacterial cells. Generation of reactive oxygen species for Ag-NP treated cells were measured by fluorescence emission spectra. The modified Gompertz model, incorporating cell death, fits the observed data better than the Logistic model. With increasing concentration of Ag-NP, the growth kinetics of both bacteria shows a decline in growth rate with simultaneous enhancement of death rate constants. The duration of the lag phase was found to increase with Ag-NP concentration. SEM showed morphological changes, while fluorescence microscopy using DAPI showed compaction of DNA for Ag-NP-treated bacterial cells. E. coli was found to be more susceptible to Ag-NP as compared to S. aureus. The modified Gompertz model, using a death term, was found to be useful in explaining the non-monotonic nature of the growth curve. The modified Gompertz model derived here is of general nature and can be used to study any microbial growth kinetics under the influence of antimicrobial agents. Copyright © 2014 Elsevier B.V. All rights reserved.

WE-FG-202-10: Assessing Hepatocellular Carcinoma (HCC) Response to SBRT Using DCE-MRI

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yuan, Y; Buckstein, M; Chao, M

2016-06-15

Purpose: To investigate the feasibility of using DCE-MRI to assess treatment response of HCC to SBRT. Methods: For seven liver HCC patients treated by photon SBRT with radiation dose ranging from 35 to 50 Gy in 5 fractions, T1-weighted DCE-MRI was performed before and at 1–3 months after the treatment. Each study included one pre-contrast and five post Gd-EOB-DTPA-enhanced imaging series. The target tumor and the liver were manually outlined on the arterial phase images. Then, a regional deformable image registration was applied to align liver volumes at different phases in order to compensate respiratory and cardiac motions. An unsupervisedmore » fuzzy c-means clustering technique was carried out to partition the tumor voxels into a number of groups based on their enhancement patterns over time. The representative kinetic curve of the tumor was selected as the one with the maximum enhancement. Six semi-quantitative features were extracted to depict the maximum contrast enhancement, uptake rate, washout rate, time to peak, the area under the kinetic curve (AUKC), as well as the ratio of the most enhanced area in each tumor. The change of these feature values after SBRT was compared using Wann-Whiteney test to characterize the tumor response to RT. Results: Eight HCCs from these seven patients were included in this retrospective study, in which four were identified to respond well to SBRT. The responding tumors showed reduced enhancement after SBRT while the non-responding tumors had steady or even enhanced kinetic dynamics. The median AUKC change after SBRT was −0.65 for responding tumors and 1.0165 for non-responding tumors (p=0.029) Conclusion: The preliminary results demonstrate that DCE-MRI has the potential to monitor the effects of SBRT in patients with HCC. We are expanding our database and developing more quantitative imaging biomarkers in the future study.« less

Chemical kinetic studies of atmospheric reactions using tunable diode laser spectroscopy

NASA Technical Reports Server (NTRS)

Worsnop, Douglas R.; Nelson, David D.; Zahniser, Mark S.

1993-01-01

IR absorption using tunable diode laser spectroscopy provides a sensitive and quantitative detection method for laboratory kinetic studies of atmospheric trace gases. Improvements in multipass cell design, real time signal processing, and computer controlled data acquisition and analysis have extended the applicability of the technique. We have developed several optical systems using off-axis resonator mirror designs which maximize path length while minimizing both the sample volume and the interference fringes inherent in conventional 'White' cells. Computerized signal processing using rapid scan (300 kHz), sweep integration with 100 percent duty cycle allows substantial noise reduction while retaining the advantages of using direct absorption for absolute absorbance measurements and simultaneous detection of multiple species. Peak heights and areas are determined by curve fitting using nonlinear least square methods. We have applied these techniques to measurements of: (1) heterogeneous uptake chemistry of atmospheric trace gases (HCl, H2O2, and N2O5) on aqueous and sulfuric acid droplets; (2) vapor pressure measurements of nitric acid and water over prototypical stratospheric aerosol (nitric acid trihydrate) surfaces; and (3) discharge flow tube kinetic studies of the HO2 radical using isotopic labeling for product channel and mechanistic analysis. Results from each of these areas demonstrate the versatility of TDL absorption spectroscopy for atmospheric chemistry applications.

A comparison of region-based and pixel-based CEUS kinetics parameters in the assessment of arthritis

NASA Astrophysics Data System (ADS)

Grisan, E.; Raffeiner, B.; Coran, A.; Rizzo, G.; Ciprian, L.; Stramare, R.

2014-03-01

Inflammatory rheumatic diseases are leading causes of disability and constitute a frequent medical disorder, leading to inability to work, high comorbidity and increased mortality. The gold-standard for diagnosing and differentiating arthritis is based on patient conditions and radiographic findings, as joint erosions or decalcification. However, early signs of arthritis are joint effusion, hypervascularization and synovial hypertrophy. In particular, vascularization has been shown to correlate with arthritis' destructive behavior, more than clinical assessment. Contrast Enhanced Ultrasound (CEUS) examination of the small joints is emerging as a sensitive tool for assessing vascularization and disease activity. The evaluation of perfusion pattern rely on subjective semi-quantitative scales, that are able to capture the macroscopic degree of vascularization, but are unable to detect the subtler differences in kinetics perfusion parameters that might lead to a deeper understanding of disease progression and a better management of patients. Quantitative assessment is mostly performed by means of the Qontrast software package, that requires the user to define a region of interest, whose mean intensity curve is fitted with an exponential function. We show that using a more physiologically motivated perfusion curve, and by estimating the kinetics parameters separately pixel per pixel, the quantitative information gathered is able to differentiate more effectively different perfusion patterns. In particular, we will show that a pixel-based analysis is able to provide significant markers differentiating rheumatoid arthritis from simil-rheumatoid psoriatic arthritis, that have non-significant differences in clinical evaluation (DAS28), serological markers, or region-based parameters.

Dynamic Recrystallization Kinetics of 690 Alloy During Hot Compression of Double-Cone Samples

NASA Astrophysics Data System (ADS)

Wang, Jue; Zhai, Shun-Chao

2017-03-01

Hot compression tests of double-cone samples were conducted for 690 alloy to study the kinetic behavior of the complete dynamic recrystallization (DRX) process under low deformation temperatures from 960 to 1080 °C. The microstructure of 82 points in the vertical section of every deformed sample was quantitatively analyzed to determine the DRX fraction. Corresponding strain of these points was calculated by finite element simulations. Kinetic curves of the specimens with different preheating temperatures were then constructed. The features of various boundaries with different misorientation angles were investigated by electron backscatter diffraction technology and transmission electron microscope. The results showed that the strain is continuously and symmetrically distributed along the centerline of the vertical section. Large strain of 1.84 was obtained when the compression amount is 12 mm for double-cone samples. All the fitted kinetic curves display an "S" type, which possess a low growth rate of DRX at the beginning and the end of compression. The critical strain of recrystallization decreases with the increase in preheating temperature, while the completion strain remains around 1.5 for all the samples. The initial and maximum growth rates of DRX fraction have the opposite trend with the change in temperature, which is considered to be attributed to the behaviors of different misorientation boundaries.

Microsecond Unfolding Kinetics of Sheep Prion Protein Reveals an Intermediate that Correlates with Susceptibility to Classical Scrapie

PubMed Central

Chen, Kai-Chun; Xu, Ming; Wedemeyer, William J.; Roder, Heinrich

2011-01-01

The microsecond folding and unfolding kinetics of ovine prion proteins (ovPrP) were measured under various solution conditions. A fragment comprising residues 94–233 of the full-length ovPrP was studied for four variants with differing susceptibilities to classical scrapie in sheep. The observed biexponential unfolding kinetics of ovPrP provides evidence for an intermediate species. However, in contrast to previous results for human PrP, there is no evidence for an intermediate under refolding conditions. Global analysis of the kinetic data, based on a sequential three-state mechanism, quantitatively accounts for all folding and unfolding data as a function of denaturant concentration. The simulations predict that an intermediate accumulates under both folding and unfolding conditions, but is observable only in unfolding experiments because the intermediate is optically indistinguishable from the native state. The relative population of intermediates in two ovPrP variants, both transiently and under destabilizing equilibrium conditions, correlates with their propensities for classical scrapie. The variant susceptible to classical scrapie has a larger population of the intermediate state than the resistant variant. Thus, the susceptible variant should be favored to undergo the PrPC to PrPSc conversion and oligomerization. PMID:21889460

Electro-dewatering of wastewater sludge: An investigation of the relationship between filtrate flow rate and electric current.

PubMed

Olivier, Jérémy; Conrardy, Jean-Baptiste; Mahmoud, Akrama; Vaxelaire, Jean

2015-10-01

Compared to conventional dewatering techniques, electrical assisted mechanical dewatering, also called electro-dewatering (EDW) is an alternative and an effective technology for the dewatering of sewage sludge with low energy consumption. The objectives of this study were to evaluate the dewatering performance and to determine the influence of the process parameters (e.g. applied electric current, applied voltage, and the initial amount of dry solids) on the kinetics of EDW-process for activated urban sludge. Also significant efforts have been devoted herein to provide comprehensive information about the EDW mechanisms and to understand the relationship between these operating conditions with regards to develop a qualitative and quantitative understanding model of the electro-dewatering process and then produce a robust design methodology. The results showed a very strong correlation between the applied electric current and the filtrate flow rate and consequently the electro-dewatering kinetics. A higher applied electric current leads to faster EDW kinetics and a higher final dry solids content. In contrast, the results of this work showed a significant enhancement of the dewatering kinetics by decreasing the mass of the dry solids introduced into the cell (commonly known as the sludge loading). Copyright © 2015 Elsevier Ltd. All rights reserved.

Phase-field Model for Interstitial Loop Growth Kinetics and Thermodynamic and Kinetic Models of Irradiated Fe-Cr Alloys

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Yulan; Hu, Shenyang Y.; Sun, Xin

2011-06-15

Microstructure evolution kinetics in irradiated materials has strongly spatial correlation. For example, void and second phases prefer to nucleate and grow at pre-existing defects such as dislocations, grain boundaries, and cracks. Inhomogeneous microstructure evolution results in inhomogeneity of microstructure and thermo-mechanical properties. Therefore, the simulation capability for predicting three dimensional (3-D) microstructure evolution kinetics and its subsequent impact on material properties and performance is crucial for scientific design of advanced nuclear materials and optimal operation conditions in order to reduce uncertainty in operational and safety margins. Very recently the meso-scale phase-field (PF) method has been used to predict gas bubblemore » evolution, void swelling, void lattice formation and void migration in irradiated materials,. Although most results of phase-field simulations are qualitative due to the lake of accurate thermodynamic and kinetic properties of defects, possible missing of important kinetic properties and processes, and the capability of current codes and computers for large time and length scale modeling, the simulations demonstrate that PF method is a promising simulation tool for predicting 3-D heterogeneous microstructure and property evolution, and providing microstructure evolution kinetics for higher scale level simulations of microstructure and property evolution such as mean field methods. This report consists of two parts. In part I, we will present a new phase-field model for predicting interstitial loop growth kinetics in irradiated materials. The effect of defect (vacancy/interstitial) generation, diffusion and recombination, sink strength, long-range elastic interaction, inhomogeneous and anisotropic mobility on microstructure evolution kinetics is taken into account in the model. The model is used to study the effect of elastic interaction on interstitial loop growth kinetics, the interstitial flux, and sink strength of interstitial loop for interstitials. In part II, we present a generic phase field model and discuss the thermodynamic and kinetic properties in phase-field models including the reaction kinetics of radiation defects and local free energy of irradiated materials. In particular, a two-sublattice thermodynamic model is suggested to describe the local free energy of alloys with irradiated defects. Fe-Cr alloy is taken as an example to explain the required thermodynamic and kinetic properties for quantitative phase-field modeling. Finally the great challenges in phase-field modeling will be discussed.« less

A mathematical model for foreign body reactions in 2D.

PubMed

Su, Jianzhong; Gonzales, Humberto Perez; Todorov, Michail; Kojouharov, Hristo; Tang, Liping

2011-02-01

The foreign body reactions are commonly referred to the network of immune and inflammatory reactions of human or animals to foreign objects placed in tissues. They are basic biological processes, and are also highly relevant to bioengineering applications in implants, as fibrotic tissue formations surrounding medical implants have been found to substantially reduce the effectiveness of devices. Despite of intensive research on determining the mechanisms governing such complex responses, few mechanistic mathematical models have been developed to study such foreign body reactions. This study focuses on a kinetics-based predictive tool in order to analyze outcomes of multiple interactive complex reactions of various cells/proteins and biochemical processes and to understand transient behavior during the entire period (up to several months). A computational model in two spatial dimensions is constructed to investigate the time dynamics as well as spatial variation of foreign body reaction kinetics. The simulation results have been consistent with experimental data and the model can facilitate quantitative insights for study of foreign body reaction process in general.

Correlations among void shape distributions, dynamic damage mode, and loading kinetics [Correlations among spall void shape distributions, damage mode and shock loading kinetics

DOE PAGES

Brown, A. D.; Pham, Q.; Fortin, E. V.; ...

2016-11-10

Here, three-dimensional x-ray tomography (XRT) provides a nondestructive technique to characterize the size, shape, and location of damage in dynamically loaded metals. A shape-fitting method comprising the inertia tensors of individual damage sites was applied to study differences of spall damage development in face-centered-cubic (FCC) and hexagonal-closed-packed (HCP) multicrystals and for a suite of experiments on high-purity copper to examine the influence of loading kinetics on the spall damage process. Applying a volume-weighted average to the best-fit ellipsoidal aspect-ratios allows a quantitative assessment for determining the extent of damage coalescence present in a shocked metal. It was found that incipientmore » transgranular HCP spall damage nucleates in a lenticular shape and is heavily oriented along particular crystallographic slip directions. In polycrystalline materials, shape distributions indicate that a decrease in the tensile loading rate leads to a transition to coalesced damage dominance and that the plastic processes driving void growth are time dependent.« less

Multi-technique approach for qualitative and quantitative characterization of furazidin degradation kinetics under alkaline conditions.

PubMed

Bērziņš, Kārlis; Kons, Artis; Grante, Ilze; Dzabijeva, Diana; Nakurte, Ilva; Actiņš, Andris

2016-09-10

Degradation of drug furazidin was studied under different conditions of environmental pH (11-13) and temperature (30-60°C). The novel approach of hybrid hard- and soft-multivariate curve resolution-alternating least squares (HS-MCR-ALS) method was applied to UV-vis spectral data to determine a valid kinetic model and kinetic parameters of the degradation process. The system was found to be comprised of three main species and best characterized by two consecutive first-order reactions. Furazidin degradation rate was found to be highly dependent on the applied environmental conditions, showing more prominent differences between both degradation steps towards higher pH and temperature. Complimentary qualitative analysis of the degradation process was carried out using HPLC-DAD-TOF-MS. Based on the obtained chromatographic and mass spectrometric results, as well as additional computational analysis of the species (theoretical UV-vis spectra calculations utilizing TD-DFT methodology), the operating degradation mechanism was proposed to include formation of a 5-hydroxyfuran derivative, followed by complete hydrolysis of furazidin hydantoin ring. Copyright © 2016 Elsevier B.V. All rights reserved.

Signatures of a macroscopic switching transition for a dynamic microtubule

NASA Astrophysics Data System (ADS)

Aparna, J. S.; Padinhateeri, Ranjith; Das, Dibyendu

2017-04-01

Characterising complex kinetics of non-equilibrium self-assembly of bio-filaments is of general interest. Dynamic instability in microtubules, consisting of successive catastrophes and rescues, is observed to occur as a result of the non-equilibrium conversion of GTP-tubulin to GDP-tubulin. We study this phenomenon using a model for microtubule kinetics with GTP/GDP state-dependent polymerisation, depolymerisation and hydrolysis of subunits. Our results reveal a sharp switch-like transition in the mean velocity of the filaments, from a growth phase to a shrinkage phase, with an associated co-existence of the two phases. This transition is reminiscent of the discontinuous phase transition across the liquid-gas boundary. We probe the extent of discontinuity in the transition quantitatively using characteristic signatures such as bimodality in velocity distribution, variance and Binder cumulant, and also hysteresis behaviour of the system. We further investigate ageing behaviour in catastrophes of the filament, and find that the multi-step nature of catastrophes is intensified in the vicinity of the switching transition. This assumes importance in the context of Microtubule Associated Proteins which have the potential of altering kinetic parameter values.

Growth kinetics and mass transport mechanisms of GaN columns by selective area metal organic vapor phase epitaxy

NASA Astrophysics Data System (ADS)

Wang, Xue; Hartmann, Jana; Mandl, Martin; Sadat Mohajerani, Matin; Wehmann, Hergo-H.; Strassburg, Martin; Waag, Andreas

2014-04-01

Three-dimensional GaN columns recently have attracted a lot of attention as the potential basis for core-shell light emitting diodes for future solid state lighting. In this study, the fundamental insights into growth kinetics and mass transport mechanisms of N-polar GaN columns during selective area metal organic vapor phase epitaxy on patterned SiOx/sapphire templates are systematically investigated using various pitch of apertures, growth time, and silane flow. Species impingement fluxes on the top surface of columns Jtop and on their sidewall Jsw, as well as, the diffusion flux from the substrate Jsub contribute to the growth of the GaN columns. The vertical and lateral growth rates devoted by Jtop, Jsw and Jsub are estimated quantitatively. The diffusion length of species on the SiOx mask surface λsub as well as on the sidewall surfaces of the 3D columns λsw are determined. The influences of silane on the growth kinetics are discussed. A growth model is developed for this selective area metal organic vapor phase epitaxy processing.

Overview of EPA Research on Drinking Water Distribution System Nitrification

EPA Science Inventory

Results from USEPA research investigating drinking water distribution system nitrification will be presented. The two research areas include: (1) monochloramine disinfection kinetics of Nitrosomonas europaea using Propidium Monoazide Quantitative Real-time PCR (PMA-qPCR) and (2...

SEDIMENT-ASSOCIATED REACTIONS OF AROMATIC AMINES: QSAR DEVELOPMENT

EPA Science Inventory

Despite the common occurrence of the aromatic amine functional group in environmental contaminants, few quantitative structure-activity relationships (QSARs) have been developed to predict sorption kinetics for aromatic amines in natural soils and sediments. Towards the goal of d...

Quantitative measurements of regional glucose utilization and rate of valine incorporation into proteins by double-tracer autoradiography in the rat brain tumor model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kirikae, M.; Diksic, M.; Yamamoto, Y.L.

1989-02-01

We examined the rate of glucose utilization and the rate of valine incorporation into proteins using 2-(/sup 18/F)fluoro-2-deoxyglucose and L-(1-14C)-valine in a rat brain tumor model by quantitative double-tracer autoradiography. We found that in the implanted tumor the rate of valine incorporation into proteins was about 22 times and the rate of glucose utilization was about 1.5 times that in the contralateral cortex. (In the ipsilateral cortex, the tumor had a profound effect on glucose utilization but no effect on the rate of valine incorporation into proteins.) Our findings suggest that it is more useful to measure protein synthesis thanmore » glucose utilization to assess the effectiveness of antitumor agents and their toxicity to normal brain tissue. We compared two methods to estimate the rate of valine incorporation: kinetic (quantitation done using an operational equation and the average brain rate coefficients) and washed slices (unbound labeled valine removed by washing brain slices in 10% trichloroacetic acid). The results were the same using either method. It would seem that the kinetic method can thus be used for quantitative measurement of protein synthesis in brain tumors and normal brain tissue using (/sup 11/C)-valine with positron emission tomography.« less

Assays for the determination of the activity of DNA nucleases based on the fluorometric properties of the YOYO dye.

PubMed

Fernández-Sierra, Mónica; Quiñones, Edwin

2015-03-15

Here we characterize the fluorescence of the YOYO dye as a tool for studying DNA-protein interactions in real time and present two continuous YOYO-based assays for sensitively monitoring the kinetics of DNA digestion by λ-exonuclease and the endonuclease EcoRV. The described assays rely on the different fluorescence intensities between single- and double-stranded DNA-YOYO complexes, allowing straightforward determination of nuclease activity and quantitative determination of reaction products. The assays were also employed to assess the effect of single-stranded DNA-binding proteins on the λ-exonuclease reaction kinetics, showing that the extreme thermostable single-stranded DNA-binding protein (ET-SSB) significantly reduced the reaction rate, while the recombination protein A (RecA) displayed no effect. Copyright © 2015 Elsevier Inc. All rights reserved.

Verification of continuum drift kinetic equation solvers in NIMROD

DOE Office of Scientific and Technical Information (OSTI.GOV)

Held, E. D.; Ji, J.-Y.; Kruger, S. E.

Verification of continuum solutions to the electron and ion drift kinetic equations (DKEs) in NIMROD [C. R. Sovinec et al., J. Comp. Phys. 195, 355 (2004)] is demonstrated through comparison with several neoclassical transport codes, most notably NEO [E. A. Belli and J. Candy, Plasma Phys. Controlled Fusion 54, 015015 (2012)]. The DKE solutions use NIMROD's spatial representation, 2D finite-elements in the poloidal plane and a 1D Fourier expansion in toroidal angle. For 2D velocity space, a novel 1D expansion in finite elements is applied for the pitch angle dependence and a collocation grid is used for the normalized speedmore » coordinate. The full, linearized Coulomb collision operator is kept and shown to be important for obtaining quantitative results. Bootstrap currents, parallel ion flows, and radial particle and heat fluxes show quantitative agreement between NIMROD and NEO for a variety of tokamak equilibria. In addition, velocity space distribution function contours for ions and electrons show nearly identical detailed structure and agree quantitatively. A Θ-centered, implicit time discretization and a block-preconditioned, iterative linear algebra solver provide efficient electron and ion DKE solutions that ultimately will be used to obtain closures for NIMROD's evolving fluid model.« less

Parameter Balancing in Kinetic Models of Cell Metabolism†

PubMed Central

2010-01-01

Kinetic modeling of metabolic pathways has become a major field of systems biology. It combines structural information about metabolic pathways with quantitative enzymatic rate laws. Some of the kinetic constants needed for a model could be collected from ever-growing literature and public web resources, but they are often incomplete, incompatible, or simply not available. We address this lack of information by parameter balancing, a method to complete given sets of kinetic constants. Based on Bayesian parameter estimation, it exploits the thermodynamic dependencies among different biochemical quantities to guess realistic model parameters from available kinetic data. Our algorithm accounts for varying measurement conditions in the input data (pH value and temperature). It can process kinetic constants and state-dependent quantities such as metabolite concentrations or chemical potentials, and uses prior distributions and data augmentation to keep the estimated quantities within plausible ranges. An online service and free software for parameter balancing with models provided in SBML format (Systems Biology Markup Language) is accessible at www.semanticsbml.org. We demonstrate its practical use with a small model of the phosphofructokinase reaction and discuss its possible applications and limitations. In the future, parameter balancing could become an important routine step in the kinetic modeling of large metabolic networks. PMID:21038890

Improved accuracy and precision of tracer kinetic parameters by joint fitting to variable flip angle and dynamic contrast enhanced MRI data.

PubMed

Dickie, Ben R; Banerji, Anita; Kershaw, Lucy E; McPartlin, Andrew; Choudhury, Ananya; West, Catharine M; Rose, Chris J

2016-10-01

To improve the accuracy and precision of tracer kinetic model parameter estimates for use in dynamic contrast enhanced (DCE) MRI studies of solid tumors. Quantitative DCE-MRI requires an estimate of precontrast T1 , which is obtained prior to fitting a tracer kinetic model. As T1 mapping and tracer kinetic signal models are both a function of precontrast T1 it was hypothesized that its joint estimation would improve the accuracy and precision of both precontrast T1 and tracer kinetic model parameters. Accuracy and/or precision of two-compartment exchange model (2CXM) parameters were evaluated for standard and joint fitting methods in well-controlled synthetic data and for 36 bladder cancer patients. Methods were compared under a number of experimental conditions. In synthetic data, joint estimation led to statistically significant improvements in the accuracy of estimated parameters in 30 of 42 conditions (improvements between 1.8% and 49%). Reduced accuracy was observed in 7 of the remaining 12 conditions. Significant improvements in precision were observed in 35 of 42 conditions (between 4.7% and 50%). In clinical data, significant improvements in precision were observed in 18 of 21 conditions (between 4.6% and 38%). Accuracy and precision of DCE-MRI parameter estimates are improved when signal models are fit jointly rather than sequentially. Magn Reson Med 76:1270-1281, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Mutation-induced protein interaction kinetics changes affect apoptotic network dynamic properties and facilitate oncogenesis

PubMed Central

Zhao, Linjie; Sun, Tanlin; Pei, Jianfeng; Ouyang, Qi

2015-01-01

It has been a consensus in cancer research that cancer is a disease caused primarily by genomic alterations, especially somatic mutations. However, the mechanism of mutation-induced oncogenesis is not fully understood. Here, we used the mitochondrial apoptotic pathway as a case study and performed a systematic analysis of integrating pathway dynamics with protein interaction kinetics to quantitatively investigate the causal molecular mechanism of mutation-induced oncogenesis. A mathematical model of the regulatory network was constructed to establish the functional role of dynamic bifurcation in the apoptotic process. The oncogenic mutation enrichment of each of the protein functional domains involved was found strongly correlated with the parameter sensitivity of the bifurcation point. We further dissected the causal mechanism underlying this correlation by evaluating the mutational influence on protein interaction kinetics using molecular dynamics simulation. We analyzed 29 matched mutant–wild-type and 16 matched SNP—wild-type protein systems. We found that the binding kinetics changes reflected by the changes of free energy changes induced by protein interaction mutations, which induce variations in the sensitive parameters of the bifurcation point, were a major cause of apoptosis pathway dysfunction, and mutations involved in sensitive interaction domains show high oncogenic potential. Our analysis provided a molecular basis for connecting protein mutations, protein interaction kinetics, network dynamics properties, and physiological function of a regulatory network. These insights provide a framework for coupling mutation genotype to tumorigenesis phenotype and help elucidate the logic of cancer initiation. PMID:26170328

Quantitative description of realistic wealth distributions by kinetic trading models

NASA Astrophysics Data System (ADS)

Lammoglia, Nelson; Muñoz, Víctor; Rogan, José; Toledo, Benjamín; Zarama, Roberto; Valdivia, Juan Alejandro

2008-10-01

Data on wealth distributions in trading markets show a power law behavior x-(1+α) at the high end, where, in general, α is greater than 1 (Pareto’s law). Models based on kinetic theory, where a set of interacting agents trade money, yield power law tails if agents are assigned a saving propensity. In this paper we are solving the inverse problem, that is, in finding the saving propensity distribution which yields a given wealth distribution for all wealth ranges. This is done explicitly for two recently published and comprehensive wealth datasets.

Antibody escape kinetics of equine infectious anemia virus infection of horses.

PubMed

Schwartz, Elissa J; Nanda, Seema; Mealey, Robert H

2015-07-01

Lentivirus escape from neutralizing antibodies (NAbs) is not well understood. In this work, we quantified antibody escape of a lentivirus, using antibody escape data from horses infected with equine infectious anemia virus. We calculated antibody blocking rates of wild-type virus, fitness costs of mutant virus, and growth rates of both viruses. These quantitative kinetic estimates of antibody escape are important for understanding lentiviral control by antibody neutralization and in developing NAb-eliciting vaccine strategies. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Quantitative Evaluation of Dichloroacetic Acid Kinetics in Human -- A Physiologically-Based Pharmacokinetic Modeling Investigation

DTIC Science & Technology

2008-01-01

weight) Plasma VPLAC 4.4 (Merrill et al., 2005) Liver VLC 2.6 (Brown et al., 1997) Kidney VKC 0.44 (Brown et al., 1997) Rapidly perfused VRC 9.86...entire data set with the exception of individual subject optimized kinetic data reported by Schultz and Shangraw (2006). Perhaps the most challenging ...GSTzeta as well as the 0.02 mg/kg DCA administered daily in drinking water between the 2 challenges . If a person is administered 50 mg/kg/day by IV

Simulation of Decomposition Kinetics of Supercooled Austenite in Powder Steel

NASA Astrophysics Data System (ADS)

Tsyganova, M. S.; Ivashko, A. G.; Polyshuk, I. N.; Nabatov, R. I.; Tsyganova, A. I.

2017-10-01

To approve heat treatment of steel modes, quantitative data on austenite decomposition are required. Gaining these data experimentally appears to be extremely complicated. In present work, few approaches to simulate the phase transformation process are proposed considering structure characteristics of powder steels. Results of comparative analysis of these approaches are also given. Predicting the transformation kinetics by simulation is verified for PK40N2M (0.38% C, 2.10% Ni, 0.40% Mo) steel with 3% porosity and PK80 (0.80% C) steel with different porosity using published experimental data.

Growth Kinetics and Size Distribution Dynamics of Viscous Secondary Organic Aerosol

DOE PAGES

Zaveri, Rahul A.; Shilling, John E.; Zelenyuk, Alla; ...

2017-12-15

Low bulk diffusivity inside viscous semisolid atmospheric secondary organic aerosol (SOA) can prolong equilibration time scale, but its broader impacts on aerosol growth and size distribution dynamics are poorly understood. In this article, we present quantitative insights into the effects of bulk diffusivity on the growth and evaporation kinetics of SOA formed under dry conditions from photooxidation of isoprene in the presence of a bimodal aerosol consisting of Aitken (ammonium sulfate) and accumulation (isoprene or α-pinene SOA) mode particles. Aerosol composition measurements and evaporation kinetics indicate that isoprene SOA is composed of several semivolatile organic compounds (SVOCs), with some reversiblymore » reacting to form oligomers. Model analysis shows that liquid-like bulk diffusivities can be used to fit the observed evaporation kinetics of accumulation mode particles but fail to explain the growth kinetics of bimodal aerosol by significantly under-predicting the evolution of the Aitken mode. In contrast, the semisolid scenario successfully reproduces both evaporation and growth kinetics, with the interpretation that hindered partitioning of SVOCs into large viscous particles effectively promotes the growth of smaller particles that have shorter diffusion time scales. This effect has important implications for the growth of atmospheric ultrafine particles to climatically active sizes.« less

Growth Kinetics and Size Distribution Dynamics of Viscous Secondary Organic Aerosol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zaveri, Rahul A.; Shilling, John E.; Zelenyuk, Alla

Low bulk diffusivity inside viscous semisolid atmospheric secondary organic aerosol (SOA) can prolong equilibration time scale, but its broader impacts on aerosol growth and size distribution dynamics are poorly understood. In this article, we present quantitative insights into the effects of bulk diffusivity on the growth and evaporation kinetics of SOA formed under dry conditions from photooxidation of isoprene in the presence of a bimodal aerosol consisting of Aitken (ammonium sulfate) and accumulation (isoprene or α-pinene SOA) mode particles. Aerosol composition measurements and evaporation kinetics indicate that isoprene SOA is composed of several semivolatile organic compounds (SVOCs), with some reversiblymore » reacting to form oligomers. Model analysis shows that liquid-like bulk diffusivities can be used to fit the observed evaporation kinetics of accumulation mode particles but fail to explain the growth kinetics of bimodal aerosol by significantly under-predicting the evolution of the Aitken mode. In contrast, the semisolid scenario successfully reproduces both evaporation and growth kinetics, with the interpretation that hindered partitioning of SVOCs into large viscous particles effectively promotes the growth of smaller particles that have shorter diffusion time scales. This effect has important implications for the growth of atmospheric ultrafine particles to climatically active sizes.« less

Quantitative estimation of Nipah virus replication kinetics in vitro

PubMed Central

Chang, Li-Yen; Ali, AR Mohd; Hassan, Sharifah Syed; AbuBakar, Sazaly

2006-01-01

Background Nipah virus is a zoonotic virus isolated from an outbreak in Malaysia in 1998. The virus causes infections in humans, pigs, and several other domestic animals. It has also been isolated from fruit bats. The pathogenesis of Nipah virus infection is still not well described. In the present study, Nipah virus replication kinetics were estimated from infection of African green monkey kidney cells (Vero) using the one-step SYBR® Green I-based quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) assay. Results The qRT-PCR had a dynamic range of at least seven orders of magnitude and can detect Nipah virus from as low as one PFU/μL. Following initiation of infection, it was estimated that Nipah virus RNA doubles at every ~40 minutes and attained peak intracellular virus RNA level of ~8.4 log PFU/μL at about 32 hours post-infection (PI). Significant extracellular Nipah virus RNA release occurred only after 8 hours PI and the level peaked at ~7.9 log PFU/μL at 64 hours PI. The estimated rate of Nipah virus RNA released into the cell culture medium was ~0.07 log PFU/μL per hour and less than 10% of the released Nipah virus RNA was infectious. Conclusion The SYBR® Green I-based qRT-PCR assay enabled quantitative assessment of Nipah virus RNA synthesis in Vero cells. A low rate of Nipah virus extracellular RNA release and low infectious virus yield together with extensive syncytial formation during the infection support a cell-to-cell spread mechanism for Nipah virus infection. PMID:16784519

Direct observation of pitting corrosion evolutions on carbon steel surfaces at the nano-to-micro- scales.

PubMed

Guo, Peng; La Plante, Erika Callagon; Wang, Bu; Chen, Xin; Balonis, Magdalena; Bauchy, Mathieu; Sant, Gaurav

2018-05-22

The Cl - -induced corrosion of metals and alloys is of relevance to a wide range of engineered materials, structures, and systems. Because of the challenges in studying pitting corrosion in a quantitative and statistically significant manner, its kinetics remain poorly understood. Herein, by direct, nano- to micro-scale observations using vertical scanning interferometry (VSI), we examine the temporal evolution of pitting corrosion on AISI 1045 carbon steel over large surface areas in Cl - -free, and Cl - -enriched solutions. Special focus is paid to examine the nucleation and growth of pits, and the associated formation of roughened regions on steel surfaces. By statistical analysis of hundreds of individual pits, three stages of pitting corrosion, namely, induction, propagation, and saturation, are quantitatively distinguished. By quantifying the kinetics of these processes, we contextualize our current understanding of electrochemical corrosion within a framework that considers spatial dynamics and morphology evolutions. In the presence of Cl - ions, corrosion is highly accelerated due to multiple autocatalytic factors including destabilization of protective surface oxide films and preservation of aggressive microenvironments within the pits, both of which promote continued pit nucleation and growth. These findings offer new insights into predicting and modeling steel corrosion processes in mid-pH aqueous environments.

Quantitative In Vivo Fluorescence Cross-Correlation Analyses Highlight the Importance of Competitive Effects in the Regulation of Protein-Protein Interactions

PubMed Central

Sadaie, Wakako; Harada, Yoshie; Matsuda, Michiyuki

2014-01-01

Computer-assisted simulation is a promising approach for clarifying complicated signaling networks. However, this approach is currently limited by a deficiency of kinetic parameters determined in living cells. To overcome this problem, we applied fluorescence cross-correlation spectrometry (FCCS) to measure dissociation constant (Kd) values of signaling molecule complexes in living cells (in vivo Kd). Among the pairs of fluorescent molecules tested, that of monomerized enhanced green fluorescent protein (mEGFP) and HaloTag-tetramethylrhodamine was most suitable for the measurement of in vivo Kd by FCCS. Using this pair, we determined 22 in vivo Kd values of signaling molecule complexes comprising the epidermal growth factor receptor (EGFR)–Ras–extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP) kinase pathway. With these parameters, we developed a kinetic simulation model of the EGFR-Ras-ERK MAP kinase pathway and uncovered a potential role played by stoichiometry in Shc binding to EGFR during the peak activations of Ras, MEK, and ERK. Intriguingly, most of the in vivo Kd values determined in this study were higher than the in vitro Kd values reported previously, suggesting the significance of competitive bindings inside cells. These in vivo Kd values will provide a sound basis for the quantitative understanding of signal transduction. PMID:24958104

Kinetics of enzymatic high-solid hydrolysis of lignocellulosic biomass studied by calorimetry.

PubMed

Olsen, Søren N; Lumby, Erik; McFarland, Kc; Borch, Kim; Westh, Peter

2011-03-01

Enzymatic hydrolysis of high-solid biomass (>10% w/w dry mass) has become increasingly important as a key step in the production of second-generation bioethanol. To this end, development of quantitative real-time assays is desirable both for empirical optimization and for detailed kinetic analysis. In the current work, we have investigated the application of isothermal calorimetry to study the kinetics of enzymatic hydrolysis of two substrates (pretreated corn stover and Avicel) at high-solid contents (up to 29% w/w). It was found that the calorimetric heat flow provided a true measure of the hydrolysis rate with a detection limit of about 500 pmol glucose s(-1). Hence, calorimetry is shown to be a highly sensitive real-time method, applicable for high solids, and independent on the complexity of the substrate. Dose-response experiments with a typical cellulase cocktail enabled a multidimensional analysis of the interrelationships of enzyme load and the rate, time, and extent of the reaction. The results suggest that the hydrolysis rate of pretreated corn stover is limited initially by available attack points on the substrate surface (<10% conversion) but becomes proportional to enzyme dosage (excess of attack points) at later stages (>10% conversion). This kinetic profile is interpreted as an increase in polymer end concentration (substrate for CBH) as the hydrolysis progresses, probably due to EG activity in the enzyme cocktail. Finally, irreversible enzyme inactivation did not appear to be the source of reduced hydrolysis rate over time.

Fundamental studies on kinetic isotope effect (KIE) of hydrogen isotope fractionation in natural gas systems

USGS Publications Warehouse

Ni, Y.; Ma, Q.; Ellis, G.S.; Dai, J.; Katz, B.; Zhang, S.; Tang, Y.

2011-01-01

Based on quantum chemistry calculations for normal octane homolytic cracking, a kinetic hydrogen isotope fractionation model for methane, ethane, and propane formation is proposed. The activation energy differences between D-substitute and non-substituted methane, ethane, and propane are 318.6, 281.7, and 280.2cal/mol, respectively. In order to determine the effect of the entropy contribution for hydrogen isotopic substitution, a transition state for ethane bond rupture was determined based on density function theory (DFT) calculations. The kinetic isotope effect (KIE) associated with bond rupture in D and H substituted ethane results in a frequency factor ratio of 1.07. Based on the proposed mathematical model of hydrogen isotope fractionation, one can potentially quantify natural gas thermal maturity from measured hydrogen isotope values. Calculated gas maturity values determined by the proposed mathematical model using ??D values in ethane from several basins in the world are in close agreement with similar predictions based on the ??13C composition of ethane. However, gas maturity values calculated from field data of methane and propane using both hydrogen and carbon kinetic isotopic models do not agree as closely. It is possible that ??D values in methane may be affected by microbial mixing and that propane values might be more susceptible to hydrogen exchange with water or to analytical errors. Although the model used in this study is quite preliminary, the results demonstrate that kinetic isotope fractionation effects in hydrogen may be useful in quantitative models of natural gas generation, and that ??D values in ethane might be more suitable for modeling than comparable values in methane and propane. ?? 2011 Elsevier Ltd.

Comprehensive report of the work done under contract AT(40-1)-3329 during the years 1970--1973

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bernheim, F.; Ottolenghi, A.

1973-11-01

During the past three years of the project the principal aims of the effort have been: (1) to establish the quantitative relationship between eosinophilic leukocytes and phospholipase B in all major areas of distribution of these cells; and (2) to develop procedures and approaches for studying the kinetics and regulatory mechanisms of the peripheral eosinophilic population. Both objectives have been accomplished and a number of related and new aspects of the problem have been brought to light. (auth)

Computer-aided global breast MR image feature analysis for prediction of tumor response to chemotherapy: performance assessment

NASA Astrophysics Data System (ADS)

Aghaei, Faranak; Tan, Maxine; Hollingsworth, Alan B.; Zheng, Bin; Cheng, Samuel

2016-03-01

Dynamic contrast-enhanced breast magnetic resonance imaging (DCE-MRI) has been used increasingly in breast cancer diagnosis and assessment of cancer treatment efficacy. In this study, we applied a computer-aided detection (CAD) scheme to automatically segment breast regions depicting on MR images and used the kinetic image features computed from the global breast MR images acquired before neoadjuvant chemotherapy to build a new quantitative model to predict response of the breast cancer patients to the chemotherapy. To assess performance and robustness of this new prediction model, an image dataset involving breast MR images acquired from 151 cancer patients before undergoing neoadjuvant chemotherapy was retrospectively assembled and used. Among them, 63 patients had "complete response" (CR) to chemotherapy in which the enhanced contrast levels inside the tumor volume (pre-treatment) was reduced to the level as the normal enhanced background parenchymal tissues (post-treatment), while 88 patients had "partially response" (PR) in which the high contrast enhancement remain in the tumor regions after treatment. We performed the studies to analyze the correlation among the 22 global kinetic image features and then select a set of 4 optimal features. Applying an artificial neural network trained with the fusion of these 4 kinetic image features, the prediction model yielded an area under ROC curve (AUC) of 0.83+/-0.04. This study demonstrated that by avoiding tumor segmentation, which is often difficult and unreliable, fusion of kinetic image features computed from global breast MR images without tumor segmentation can also generate a useful clinical marker in predicting efficacy of chemotherapy.

Wine yeast phenomics: A standardized fermentation method for assessing quantitative traits of Saccharomyces cerevisiae strains in enological conditions.

PubMed

Peltier, Emilien; Bernard, Margaux; Trujillo, Marine; Prodhomme, Duyên; Barbe, Jean-Christophe; Gibon, Yves; Marullo, Philippe

2018-01-01

This work describes the set up of a small scale fermentation methodology for measuring quantitative traits of hundreds of samples in an enological context. By using standardized screw cap vessels, the alcoholic fermentation kinetics of Saccharomyces cerevisiae strains were measured by following their weight loss over the time. This dispositive was coupled with robotized enzymatic assays for measuring metabolites of enological interest in natural grape juices. Despite the small volume used, kinetic parameters and fermentation end products measured are similar with those observed in larger scale vats. The vessel used also offers the possibility to assay 32 volatiles compounds using a headspace solid-phase micro-extraction coupled to gas chromatography and mass spectrometry. The vessel shaking applied strongly impacted most of the phenotypes investigated due to oxygen transfer occuring in the first hours of the alcoholic fermentation. The impact of grape must and micro-oxygenation was investigated illustrating some relevant genetic x environmental interactions. By phenotyping a wide panel of commercial wine starters in five grape juices, broad phenotypic correlations between kinetics and metabolic end products were evidentiated. Moreover, a multivariate analysis illustrates that some grape musts are more able than others to discriminate commercial strains since some are less robust to environmental changes.

Wine yeast phenomics: A standardized fermentation method for assessing quantitative traits of Saccharomyces cerevisiae strains in enological conditions

PubMed Central

Bernard, Margaux; Trujillo, Marine; Prodhomme, Duyên; Barbe, Jean-Christophe; Gibon, Yves; Marullo, Philippe

2018-01-01

This work describes the set up of a small scale fermentation methodology for measuring quantitative traits of hundreds of samples in an enological context. By using standardized screw cap vessels, the alcoholic fermentation kinetics of Saccharomyces cerevisiae strains were measured by following their weight loss over the time. This dispositive was coupled with robotized enzymatic assays for measuring metabolites of enological interest in natural grape juices. Despite the small volume used, kinetic parameters and fermentation end products measured are similar with those observed in larger scale vats. The vessel used also offers the possibility to assay 32 volatiles compounds using a headspace solid-phase micro-extraction coupled to gas chromatography and mass spectrometry. The vessel shaking applied strongly impacted most of the phenotypes investigated due to oxygen transfer occuring in the first hours of the alcoholic fermentation. The impact of grape must and micro-oxygenation was investigated illustrating some relevant genetic x environmental interactions. By phenotyping a wide panel of commercial wine starters in five grape juices, broad phenotypic correlations between kinetics and metabolic end products were evidentiated. Moreover, a multivariate analysis illustrates that some grape musts are more able than others to discriminate commercial strains since some are less robust to environmental changes. PMID:29351285

(18)F-FDG dynamic PET/CT in patients with multiple myeloma: patterns of tracer uptake and correlation with bone marrow plasma cell infiltration rate.

PubMed

Sachpekidis, Christos; Mai, Elias K; Goldschmidt, Hartmut; Hillengass, Jens; Hose, Dirk; Pan, Leyun; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

2015-06-01

The value of F-FDG PET in the diagnostic approach of multiple myeloma (MM) remains incompletely elicited. Little is known about the kinetics of F-FDG in the bone marrow and extramedullary sites in MM. This study aimed to evaluate quantitative data on kinetics and distribution patterns of F-FDG in MM patients with regard to pelvic bone marrow plasma cell infiltration. The study included 40 patients with primary MM. Dynamic PET/CT scanning of the lower lumbar spine and pelvis was performed after the administration of F-FDG. Whole-body PET/CT studies were performed. Sites of focal increased tracer uptake were considered as highly suggestive of myelomatous involvement after taking into account the patient history and CT findings. Bone marrow of the os ilium without pathologic tracer accumulation served as reference. The evaluation of dynamic PET/CT studies was based in addition to the conventional visual (qualitative) assessment, on semiquantitative (SUV) calculations, as well as on absolute quantitative estimations after application of a 2-tissue compartment model and a noncompartmental approach. F-FDG quantitative information and corresponding distribution patterns were correlated with pelvic bone marrow plasma cell infiltration. Fifty-two myelomatous lesions were detected in the pelvis. All parameters in suspected MM lesions ranged in significantly higher levels than in reference tissue (P < 0.01). Correlative analyses revealed that bone marrow plasma cell infiltration rate correlated significantly with SUVaverage, SUVmax, and the parameters K1, influx, and fractal dimension of F-FDG in reference bone marrow (P < 0.01). In addition, whole-body static PET/CT imaging demonstrated 4 patterns of tracer uptake; these are as follows: negative, focal, diffuse, and mixed (focal/diffuse) tracer uptake. Patients with a mixed pattern of radiotracer uptake had the highest mean plasma cell infiltration rate in their bone marrow, whereas those with negative PET/CT scans demonstrated the lowest bone marrow plasma cell infiltration. In total, 265 focal myeloma-indicative F-FDG-avid lesions were detected, 129 of which correlated with low-dose CT osteolytic findings. No significant correlation between the number of focal lesions detected in PET/CT and bone marrow infiltration was detected. The F-FDG kinetic parameters K1, influx, and fractal dimension as well as SUVaverage from reference tissue correlated significantly with bone marrow malignant plasma cell infiltration rate. Patients with negative PET/CT demonstrated the lowest bone marrow infiltration by malignant plasma cells, whereas those with a mixed pattern of tracer uptake had the highest infiltration.

Options and uncertainties in planetary defense: Mission planning and vehicle design for flexible response

NASA Astrophysics Data System (ADS)

Barbee, Brent W.; Syal, Megan Bruck; Dearborn, David; Gisler, Galen; Greenaugh, Kevin; Howley, Kirsten M.; Leung, Ron; Lyzhoft, Josh; Miller, Paul L.; Nuth, Joseph A.; Plesko, Catherine; Seery, Bernard D.; Wasem, Joseph; Weaver, Robert P.; Zebenay, Melak

2018-02-01

This paper is part of an integrated study by NASA and the NNSA to quantitatively understand the response timeframe should a threatening Earth-impacting near-Earth object (NEO) be identified. The two realistic responses considered are the use of a spacecraft functioning as either a kinetic impactor or a nuclear explosive carrier to deflect the approaching NEO. The choice depends on the NEO size and mass, the available response time prior to Earth impact, and the various uncertainties. Whenever practical, the kinetic impactor is the preferred approach, but various factors, such as large uncertainties or short available response time, reduce the kinetic impactor's suitability and, ultimately, eliminate its sufficiency. Herein we examine response time and the activities that occur between the time when an NEO is recognized as being a sufficient threat to require a deflection and the time when the deflection impulse is applied to the NEO. To use a kinetic impactor for successful deflection of an NEO, it is essential to minimize the reaction time and maximize the time available for the impulse delivered to the NEO by the kinetic impactor to integrate forward in time to the eventual deflection of the NEO away from Earth impact. To shorten the response time, we develop tools to survey the profile of needed spacecraft launches and the possible mission payloads. We further present a vehicle design capable of either serving as a kinetic impactor, or, if the need arises, serving as a system to transport a nuclear explosive to the NEO. These results are generated by analyzing a specific case study in which the simulated Earth-impacting NEO is modeled very closely after the real NEO known as 101955 Bennu (1999 RQ36). Bennu was selected for our case study in part because it is the best-studied of the known NEOs. It is also the destination of NASA's OSIRIS-REx sample return mission, which is, at the time of this writing, enroute to Bennu following a September 2016 launch.

Reaction of diazepam and related benzodiazepines with chlorine. Kinetics, transformation products and in-silico toxicological assessment.

PubMed

Carpinteiro, Inmaculada; Rodil, Rosario; Quintana, José Benito; Cela, Rafael

2017-09-01

In this work, the reaction of four benzodiazepines (diazepam, oxazepam, nordazepam and temazepam) during water chlorination was studied by means of liquid chromatography-quadrupole-time of flight-mass spectrometry (LC-QTOF-MS). For those compounds that showed a significant degradation, i.e. diazepam, oxazepam and nordazepam, parameters affecting to the reaction kinetics (pH, chlorine and bromide level) were studied in detail and transformation products were tentatively identified. The oxidation reactions followed pseudofirst-order kinetics with rate constants in the range of 1.8-42.5 M -1  s -1 , 0.13-1.16 M -1  s -1 and 0.04-20.4 M -1  s -1 corresponding to half-life values in the range of 1.9-146 min, 1.8-87 h and 2.5-637 h for oxazepam, nordazepam and diazepam, respectively, depending of the levels of studied parameters. Chlorine and pH affected significantly the reaction kinetics, where an increase of the pH resulted into a decrease of the reaction rate, whereas higher chlorine dosages led to faster kinetics, as expected in this case. The transformation of the studied benzodiazepines occurs mainly at the 1,4-diazepine 7-membered-ring, resulting in ring opening to form benzophenone derivatives or the formation of a 6-membered pyrimidine ring, leading to quinazoline derivatives. The formation of these by-products was also tested in real surface water samples observing kinetics of oxazepam degradation slower in river than in creek water, while the degradation of the two other benzodiazepines occurred only in the simpler sample (creek water). Finally, the acute and chronical toxicity and mutagenicity of precursors and transformation products were estimated using quantitative structure-activity relationship (QSAR) software tools: Ecological Structure Activity Relationships (ECOSAR) and Toxicity Estimation Software Tool (TEST), finding that some transformation products could be more toxic/mutagenic than the precursor drug, but additional test would be needed to confirm this fact. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Incomplete Glutathione Puzzle: Just Guessing at Numbers and Figures?

PubMed Central

2017-01-01

Abstract Significance: Glutathione metabolism is comparable to a jigsaw puzzle with too many pieces. It is supposed to comprise (i) the reduction of disulfides, hydroperoxides, sulfenic acids, and nitrosothiols, (ii) the detoxification of aldehydes, xenobiotics, and heavy metals, and (iii) the synthesis of eicosanoids, steroids, and iron–sulfur clusters. In addition, glutathione affects oxidative protein folding and redox signaling. Here, I try to provide an overview on the relevance of glutathione-dependent pathways with an emphasis on quantitative data. Recent Advances: Intracellular redox measurements reveal that the cytosol, the nucleus, and mitochondria contain very little glutathione disulfide and that oxidative challenges are rapidly counterbalanced. Genetic approaches suggest that iron metabolism is the centerpiece of the glutathione puzzle in yeast. Furthermore, recent biochemical studies provide novel insights on glutathione transport processes and uncoupling mechanisms. Critical Issues: Which parts of the glutathione puzzle are most relevant? Does this explain the high intracellular concentrations of reduced glutathione? How can iron–sulfur cluster biogenesis, oxidative protein folding, or redox signaling occur at high glutathione concentrations? Answers to these questions not only seem to depend on the organism, cell type, and subcellular compartment but also on different ideologies among researchers. Future Directions: A rational approach to compare the relevance of glutathione-dependent pathways is to combine genetic and quantitative kinetic data. However, there are still many missing pieces and too little is known about the compartment-specific repertoire and concentration of numerous metabolites, substrates, enzymes, and transporters as well as rate constants and enzyme kinetic patterns. Gathering this information might require the development of novel tools but is crucial to address potential kinetic competitions and to decipher uncoupling mechanisms to solve the glutathione puzzle. Antioxid. Redox Signal. 27, 1130–1161. PMID:28540740

The Incomplete Glutathione Puzzle: Just Guessing at Numbers and Figures?

PubMed

Deponte, Marcel

2017-11-20

Glutathione metabolism is comparable to a jigsaw puzzle with too many pieces. It is supposed to comprise (i) the reduction of disulfides, hydroperoxides, sulfenic acids, and nitrosothiols, (ii) the detoxification of aldehydes, xenobiotics, and heavy metals, and (iii) the synthesis of eicosanoids, steroids, and iron-sulfur clusters. In addition, glutathione affects oxidative protein folding and redox signaling. Here, I try to provide an overview on the relevance of glutathione-dependent pathways with an emphasis on quantitative data. Recent Advances: Intracellular redox measurements reveal that the cytosol, the nucleus, and mitochondria contain very little glutathione disulfide and that oxidative challenges are rapidly counterbalanced. Genetic approaches suggest that iron metabolism is the centerpiece of the glutathione puzzle in yeast. Furthermore, recent biochemical studies provide novel insights on glutathione transport processes and uncoupling mechanisms. Which parts of the glutathione puzzle are most relevant? Does this explain the high intracellular concentrations of reduced glutathione? How can iron-sulfur cluster biogenesis, oxidative protein folding, or redox signaling occur at high glutathione concentrations? Answers to these questions not only seem to depend on the organism, cell type, and subcellular compartment but also on different ideologies among researchers. A rational approach to compare the relevance of glutathione-dependent pathways is to combine genetic and quantitative kinetic data. However, there are still many missing pieces and too little is known about the compartment-specific repertoire and concentration of numerous metabolites, substrates, enzymes, and transporters as well as rate constants and enzyme kinetic patterns. Gathering this information might require the development of novel tools but is crucial to address potential kinetic competitions and to decipher uncoupling mechanisms to solve the glutathione puzzle. Antioxid. Redox Signal. 27, 1130-1161.

Integrated computational model of the bioenergetics of isolated lung mitochondria

PubMed Central

Zhang, Xiao; Jacobs, Elizabeth R.; Camara, Amadou K. S.; Clough, Anne V.

2018-01-01

Integrated computational modeling provides a mechanistic and quantitative framework for describing lung mitochondrial bioenergetics. Thus, the objective of this study was to develop and validate a thermodynamically-constrained integrated computational model of the bioenergetics of isolated lung mitochondria. The model incorporates the major biochemical reactions and transport processes in lung mitochondria. A general framework was developed to model those biochemical reactions and transport processes. Intrinsic model parameters such as binding constants were estimated using previously published isolated enzymes and transporters kinetic data. Extrinsic model parameters such as maximal reaction and transport velocities were estimated by fitting the integrated bioenergetics model to published and new tricarboxylic acid cycle and respirometry data measured in isolated rat lung mitochondria. The integrated model was then validated by assessing its ability to predict experimental data not used for the estimation of the extrinsic model parameters. For example, the model was able to predict reasonably well the substrate and temperature dependency of mitochondrial oxygen consumption, kinetics of NADH redox status, and the kinetics of mitochondrial accumulation of the cationic dye rhodamine 123, driven by mitochondrial membrane potential, under different respiratory states. The latter required the coupling of the integrated bioenergetics model to a pharmacokinetic model for the mitochondrial uptake of rhodamine 123 from buffer. The integrated bioenergetics model provides a mechanistic and quantitative framework for 1) integrating experimental data from isolated lung mitochondria under diverse experimental conditions, and 2) assessing the impact of a change in one or more mitochondrial processes on overall lung mitochondrial bioenergetics. In addition, the model provides important insights into the bioenergetics and respiration of lung mitochondria and how they differ from those of mitochondria from other organs. To the best of our knowledge, this model is the first for the bioenergetics of isolated lung mitochondria. PMID:29889855

Integrated computational model of the bioenergetics of isolated lung mitochondria.

PubMed

Zhang, Xiao; Dash, Ranjan K; Jacobs, Elizabeth R; Camara, Amadou K S; Clough, Anne V; Audi, Said H

2018-01-01

Integrated computational modeling provides a mechanistic and quantitative framework for describing lung mitochondrial bioenergetics. Thus, the objective of this study was to develop and validate a thermodynamically-constrained integrated computational model of the bioenergetics of isolated lung mitochondria. The model incorporates the major biochemical reactions and transport processes in lung mitochondria. A general framework was developed to model those biochemical reactions and transport processes. Intrinsic model parameters such as binding constants were estimated using previously published isolated enzymes and transporters kinetic data. Extrinsic model parameters such as maximal reaction and transport velocities were estimated by fitting the integrated bioenergetics model to published and new tricarboxylic acid cycle and respirometry data measured in isolated rat lung mitochondria. The integrated model was then validated by assessing its ability to predict experimental data not used for the estimation of the extrinsic model parameters. For example, the model was able to predict reasonably well the substrate and temperature dependency of mitochondrial oxygen consumption, kinetics of NADH redox status, and the kinetics of mitochondrial accumulation of the cationic dye rhodamine 123, driven by mitochondrial membrane potential, under different respiratory states. The latter required the coupling of the integrated bioenergetics model to a pharmacokinetic model for the mitochondrial uptake of rhodamine 123 from buffer. The integrated bioenergetics model provides a mechanistic and quantitative framework for 1) integrating experimental data from isolated lung mitochondria under diverse experimental conditions, and 2) assessing the impact of a change in one or more mitochondrial processes on overall lung mitochondrial bioenergetics. In addition, the model provides important insights into the bioenergetics and respiration of lung mitochondria and how they differ from those of mitochondria from other organs. To the best of our knowledge, this model is the first for the bioenergetics of isolated lung mitochondria.

Interpreting equilibrium-conductivity and conductivity-relaxation measurements to establish thermodynamic and transport properties for multiple charged defect conducting ceramics.

PubMed

Zhu, Huayang; Ricote, Sandrine; Coors, W Grover; Kee, Robert J

2015-01-01

A model-based interpretation of measured equilibrium conductivity and conductivity relaxation is developed to establish thermodynamic, transport, and kinetics parameters for multiple charged defect conducting (MCDC) ceramic materials. The present study focuses on 10% yttrium-doped barium zirconate (BZY10). In principle, using the Nernst-Einstein relationship, equilibrium conductivity measurements are sufficient to establish thermodynamic and transport properties. However, in practice it is difficult to establish unique sets of properties using equilibrium conductivity alone. Combining equilibrium and conductivity-relaxation measurements serves to significantly improve the quantitative fidelity of the derived material properties. The models are developed using a Nernst-Planck-Poisson (NPP) formulation, which enables the quantitative representation of conductivity relaxations caused by very large changes in oxygen partial pressure.

Colored Petri net modeling and simulation of signal transduction pathways.

PubMed

Lee, Dong-Yup; Zimmer, Ralf; Lee, Sang Yup; Park, Sunwon

2006-03-01

Presented herein is a methodology for quantitatively analyzing the complex signaling network by resorting to colored Petri nets (CPN). The mathematical as well as Petri net models for two basic reaction types were established, followed by the extension to a large signal transduction system stimulated by epidermal growth factor (EGF) in an application study. The CPN models based on the Petri net representation and the conservation and kinetic equations were used to examine the dynamic behavior of the EGF signaling pathway. The usefulness of Petri nets is demonstrated for the quantitative analysis of the signal transduction pathway. Moreover, the trade-offs between modeling capability and simulation efficiency of this pathway are explored, suggesting that the Petri net model can be invaluable in the initial stage of building a dynamic model.

Convergence optimization of parametric MLEM reconstruction for estimation of Patlak plot parameters.

PubMed

Angelis, Georgios I; Thielemans, Kris; Tziortzi, Andri C; Turkheimer, Federico E; Tsoumpas, Charalampos

2011-07-01

In dynamic positron emission tomography data many researchers have attempted to exploit kinetic models within reconstruction such that parametric images are estimated directly from measurements. This work studies a direct parametric maximum likelihood expectation maximization algorithm applied to [(18)F]DOPA data using reference-tissue input function. We use a modified version for direct reconstruction with a gradually descending scheme of subsets (i.e. 18-6-1) initialized with the FBP parametric image for faster convergence and higher accuracy. The results compared with analytic reconstructions show quantitative robustness (i.e. minimal bias) and clinical reproducibility within six human acquisitions in the region of clinical interest. Bland-Altman plots for all the studies showed sufficient quantitative agreement between the direct reconstructed parametric maps and the indirect FBP (--0.035x+0.48E--5). Copyright © 2011 Elsevier Ltd. All rights reserved.

SYMPOSIUM SESSION PROPOSAL: INCORPORATION OF MODE OF ACTION INTO MECHANISTICALLY-BASED QUANTITATIVE MODELS

EPA Science Inventory

The biological processes by which environmental pollutants induce adverse health effects is most likely regulated by complex interactions dependent upon the route of exposure, dose, kinetics of distribution, and multiple cellular responses. To further complicate deciphering thes...

Thermal history of sedimentary basins, maturation indices, and kinetics of oil and gas generation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tissot, B.P.; Pelet, R.; Ungerer, P.

1987-12-01

Temperature is the most sensitive parameter in hydrocarbon generation. Thus, reconstruction of temperature history is essential when evaluating petroleum prospects. No measurable parameter can be directly converted to paleotemperature. Maturation indices such as vitrinite reflectance, T/sub max/ from Rock-Eval pyrolysis, spore coloration, Thermal Alteration Index (TAI), or concentration of biological markers offer an indirect approach. All these indices are a function of the thermal history through rather complex kinetics, frequently influenced by the type of organic matter. Their significance and validity are reviewed. Besides the problems of identification (e.g. vitrinite) and interlaboratory calibration, it is important to simultaneously interpret kerogenmore » type and maturation and to avoid difficult conversions from one index to another. Geodynamic models, where structural and thermal histories are connected, are another approach to temperature reconstruction which could be calibrated against the present distribution of temperature and the present value of maturation indices. Kinetics of kerogen decomposition controls the amount and composition of hydrocarbons generated. An empirical time-temperature index (TTI), originally introduced by Lopatin, does not allow such a quantitative evaluation. Due to several limitations (no provision for different types of kerogen and different rates of reactions, poor calibration on vitrinite reflectance), it is of limited interest unless one has no access to a desk-top computer. Kinetic models, based on a specific calibration made on actual source rock samples, can simulate the evolution of all types of organic matter and can provide a quantitative evaluation of oil and gas generated. 29 figures.« less

Indocyanine green kinetics to assess liver function: Ready for a clinical dynamic assessment in major liver surgery?

PubMed Central

De Gasperi, Andrea; Mazza, Ernestina; Prosperi, Manlio

2016-01-01

Indocyanine green (ICG) kinetics (PDR/R15) used to quantitatively assess hepatic function in the perioperative period of major resective surgery and liver transplantation have been the object of an extensive, updated and critical review. New, non invasive bedside monitors (pulse dye densitometry technology) make this opportunity widely available in clinical practice. After having reviewed basic concepts of hepatic clearance, we analysed the most common indications ICG kinetic parameters have nowadays in clinical practice, focusing in particular on the diagnostic and prognostic role of PDR and R15 in the perioperative period of major liver surgery and liver transplantation. As recently pointed out, even if of extreme interest, ICG clearance parameters have still some limitations, to be considered when using these tests. PMID:26981173

Influence of film structure on the dewetting kinetics of thin polymer films in the solvent annealing process.

PubMed

Zhang, Huanhuan; Xu, Lin; Lai, Yuqing; Shi, Tongfei

2016-06-28

On a non-wetting solid substrate, the solvent annealing process of a thin polymer film includes the swelling process and the dewetting process. Owing to difficulties in the in situ analysis of the two processes simultaneously, a quantitative study on the solvent annealing process of thin polymer films on the non-wetting solid substrate is extremely rare. In this paper, we design an experimental method by combining spectroscopic ellipsometry with optical microscopy to achieve the simultaneous in situ study. Using this method, we investigate the influence of the structure of swollen film on its dewetting kinetics during the solvent annealing process. The results show that for a thin PS film with low Mw (Mw = 4.1 kg mol(-1)), acetone molecules can form an ultrathin enriched layer between the PS film and the solid substrate during the swelling process. The presence of the acetone enriched layer accounts for the exponential kinetic behavior in the case of a thin PS film with low Mw. However, the acetone enriched layer is not observed in the case of a thin PS film with high Mw (Mw = 400 kg mol(-1)) and the slippage effect of polymer chains is valid during the dewetting process.

Formation and dissolution processes of the 6-thioguanine (6TG) self-assembled monolayer. A kinetic study.

PubMed

Madueño, Rafael; Pineda, Teresa; Sevilla, José Manuel; Blázquez, Manuel

2005-02-03

This is a report on the kinetics of the destruction and formation processes of the 6-thioguanine self-assembled monolayer (6TG SAM) on a mercury electrode from acid solutions by chronoamperometry. The destruction of the 6TG SAM that has been previously formed under open circuit potential conditions is carried out by stepping the potential from an initial value where the chemisorbed layer is stable up to potentials where the molecules are no longer chemisorbed. The destruction of the SAM has been described by a model that involves three types of contributions: (i) a Langmuir-type adsorption process, (ii) a 2D nucleation mechanism followed by a growth controlled by surface diffusion, and (iii) a 2D nucleation mechanism followed by a growth at a constant rate. The nonlinear fit of the experimental transients by using this procedure allows the quantitative determination of the individual contributions to the overall process. The kinetics of the formation process is studied under electrochemical conditions. The chronoamperometric experiment allows us to monitor the early stages of 6TG SAM formation. The implications of the physisorbed state at low potentials in the type of monolayer formation and destruction processes as well as the influence of temperature are also discussed.

Kinetic analysis of inhibition of glucoamylase and active site mutants via chemoselective oxime immobilization of acarbose on SPR chip surfaces.

PubMed

Sauer, Jørgen; Abou Hachem, Maher; Svensson, Birte; Jensen, Knud J; Thygesen, Mikkel B

2013-06-28

We here report a quantitative study on the binding kinetics of inhibition of the enzyme glucoamylase and how individual active site amino acid mutations influence kinetics. To address this challenge, we have developed a fast and efficient method for anchoring native acarbose to gold chip surfaces for surface plasmon resonance studies employing wild type glucoamylase and active site mutants, Y175F, E180Q, and R54L, as analytes. The key method was the chemoselective and protecting group-free oxime functionalization of the pseudo-tetrasaccharide-based inhibitor acarbose. By using this technique we have shown that at pH 7.0 the association and dissociation rate constants for the acarbose-glucoamylase interaction are 10(4)M(-1)s(-1) and 10(3)s(-1), respectively, and that the conformational change to a tight enzyme-inhibitor complex affects the dissociation rate constant by a factor of 10(2)s(-1). Additionally, the acarbose-presenting SPR surfaces could be used as a glucoamylase sensor that allowed rapid, label-free affinity screening of small carbohydrate-based inhibitors in solution, which is otherwise difficult with immobilized enzymes or other proteins. Copyright © 2013 Elsevier Ltd. All rights reserved.

Reconnection in the Martian Magnetotail: Hall-MHD With Embedded Particle-in-Cell Simulations

NASA Astrophysics Data System (ADS)

Ma, Yingjuan; Russell, Christopher T.; Toth, Gabor; Chen, Yuxi; Nagy, Andrew F.; Harada, Yuki; McFadden, James; Halekas, Jasper S.; Lillis, Rob; Connerney, John E. P.; Espley, Jared; DiBraccio, Gina A.; Markidis, Stefano; Peng, Ivy Bo; Fang, Xiaohua; Jakosky, Bruce M.

2018-05-01

Mars Atmosphere and Volatile EvolutioN (MAVEN) mission observations show clear evidence of the occurrence of the magnetic reconnection process in the Martian plasma tail. In this study, we use sophisticated numerical models to help us understand the effects of magnetic reconnection in the plasma tail. The numerical models used in this study are (a) a multispecies global Hall-magnetohydrodynamic (HMHD) model and (b) a global HMHD model two-way coupled to an embedded fully kinetic particle-in-cell code. Comparison with MAVEN observations clearly shows that the general interaction pattern is well reproduced by the global HMHD model. The coupled model takes advantage of both the efficiency of the MHD model and the ability to incorporate kinetic processes of the particle-in-cell model, making it feasible to conduct kinetic simulations for Mars under realistic solar wind conditions for the first time. Results from the coupled model show that the Martian magnetotail is highly dynamic due to magnetic reconnection, and the resulting Mars-ward plasma flow velocities are significantly higher for the lighter ion fluid, which are quantitatively consistent with MAVEN observations. The HMHD with Embedded Particle-in-Cell model predicts that the ion loss rates are more variable but with similar mean values as compared with HMHD model results.

Application of Real-Time Fluorescent PCR for Quantitative Assessment of Neospora caninum Infections in Organotypic Slice Cultures of Rat Central Nervous System Tissue

PubMed Central

Müller, Norbert; Vonlaufen, Nathalie; Gianinazzi, Christian; Leib, Stephen L.; Hemphill, Andrew

2002-01-01

The previously described Nc5-specific PCR test for the diagnosis of Neospora caninum infections was used to develop a quantitative PCR assay which allows the determination of infection intensities within different experimental and diagnostic sample groups. The quantitative PCR was performed by using a dual fluorescent hybridization probe system and the LightCycler Instrument for online detection of amplified DNA. This assay was successfully applied for demonstrating the parasite proliferation kinetics in organotypic slice cultures of rat brain which were infected in vitro with N. caninum tachyzoites. This PCR-based method of parasite quantitation with organotypic brain tissue samples can be regarded as a novel ex vivo approach for exploring different aspects of cerebral N. caninum infection. PMID:11773124

HOW CAN BIOLOGICALLY-BASED MODELING OF ARSENIC KINETICS AND DYNAMICS INFORM THE RISK ASSESSMENT PROCESS?

EPA Science Inventory

Quantitative biologically-based models describing key events in the continuum from arsenic exposure to the development of adverse health effects provide a framework to integrate information obtained across diverse research areas. For example, genetic polymorphisms in arsenic met...

Kinetic modeling predicts a stimulatory role for ribosome collisions at elongation stall sites in bacteria

PubMed Central

Ferrin, Michael A; Subramaniam, Arvind R

2017-01-01

Ribosome stalling on mRNAs can decrease protein expression. To decipher ribosome kinetics at stall sites, we induced ribosome stalling at specific codons by starving the bacterium Escherichia coli for the cognate amino acid. We measured protein synthesis rates from a reporter library of over 100 variants that encoded systematic perturbations of translation initiation rate, the number of stall sites, and the distance between stall sites. Our measurements are quantitatively inconsistent with two widely-used kinetic models for stalled ribosomes: ribosome traffic jams that block initiation, and abortive (premature) termination of stalled ribosomes. Rather, our measurements support a model in which collision with a trailing ribosome causes abortive termination of the stalled ribosome. In our computational analysis, ribosome collisions selectively stimulate abortive termination without fine-tuning of kinetic rate parameters at ribosome stall sites. We propose that ribosome collisions serve as a robust timer for translational quality control pathways to recognize stalled ribosomes. DOI: http://dx.doi.org/10.7554/eLife.23629.001 PMID:28498106

Structural kinetic modeling of metabolic networks.

PubMed

Steuer, Ralf; Gross, Thilo; Selbig, Joachim; Blasius, Bernd

2006-08-08

To develop and investigate detailed mathematical models of metabolic processes is one of the primary challenges in systems biology. However, despite considerable advance in the topological analysis of metabolic networks, kinetic modeling is still often severely hampered by inadequate knowledge of the enzyme-kinetic rate laws and their associated parameter values. Here we propose a method that aims to give a quantitative account of the dynamical capabilities of a metabolic system, without requiring any explicit information about the functional form of the rate equations. Our approach is based on constructing a local linear model at each point in parameter space, such that each element of the model is either directly experimentally accessible or amenable to a straightforward biochemical interpretation. This ensemble of local linear models, encompassing all possible explicit kinetic models, then allows for a statistical exploration of the comprehensive parameter space. The method is exemplified on two paradigmatic metabolic systems: the glycolytic pathway of yeast and a realistic-scale representation of the photosynthetic Calvin cycle.

Quantitative remineralization evolution kinetics of artificially demineralized human enamel using photothermal radiometry and modulated luminescence.

PubMed

Hellen, Adam; Mandelis, Andreas; Finer, Yoav; Amaechi, Bennett T

2011-11-01

Human molars were subjected to demineralization in acid gel followed by incubation in remineralization solutions without or with fluoride (1 or 1000 ppm). Photothermal radiometry (PTR) and modulated luminescence (LUM) frequency scans were performed prior to and during de/remineralization treatments. Transverse Micro-Radiography (TMR) analysis followed at treatment conclusion to determine mineral loss and lesion depth. The remineralization process illustrated a complex interplay between surface and subsurface mineral deposition, confining the thermal-wave centroid toward the dominating layer. Experimental amplitudes and phases were fitted to a coupled diffuse-photon-density-wave and thermal-wave theoretical model used to quantitatively evaluate evolving changes in thermal and optical properties of de/remineralized enamel lesions. Additional information obtained from the LUM data corroborated the remineralization kinetics affecting the PTR signals. The results pointed to enhanced effectiveness of subsurface lesion remineralization in the presence of fluoride. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Electrostatic Effects in Filamentous Protein Aggregation

PubMed Central

Buell, Alexander K.; Hung, Peter; Salvatella, Xavier; Welland, Mark E.; Dobson, Christopher M.; Knowles, Tuomas P.J.

2013-01-01

Electrostatic forces play a key role in mediating interactions between proteins. However, gaining quantitative insights into the complex effects of electrostatics on protein behavior has proved challenging, due to the wide palette of scenarios through which both cations and anions can interact with polypeptide molecules in a specific manner or can result in screening in solution. In this article, we have used a variety of biophysical methods to probe the steady-state kinetics of fibrillar protein self-assembly in a highly quantitative manner to detect how it is modulated by changes in solution ionic strength. Due to the exponential modulation of the reaction rate by electrostatic forces, this reaction represents an exquisitely sensitive probe of these effects in protein-protein interactions. Our approach, which involves a combination of experimental kinetic measurements and theoretical analysis, reveals a hierarchy of electrostatic effects that control protein aggregation. Furthermore, our results provide a highly sensitive method for the estimation of the magnitude of binding of a variety of ions to protein molecules. PMID:23473495

Brain glucose transport and phosphorylation under acute insulin-induced hypoglycemia in mice: an 18F-FDG PET study.

PubMed

Alf, Malte F; Duarte, João M N; Schibli, Roger; Gruetter, Rolf; Krämer, Stefanie D

2013-12-01

We addressed the questions of how cerebral glucose transport and phosphorylation change under acute hypoglycemia and what the underlying mechanisms of adaptation are. Quantitative (18)F-FDG PET combined with the acquisition of real-time arterial input function was performed on mice. Hypoglycemia was induced and maintained by insulin infusion. PET data were analyzed with the 2-tissue-compartment model for (18)F-FDG, and the results were evaluated with Michaelis-Menten saturation kinetics. Glucose clearance from plasma to brain (K1,glc) and the phosphorylation rate constant increased with decreasing plasma glucose (Gp), in particular at a Gp of less than 2.5 mmol/L. Estimated cerebral glucose extraction ratios taking into account an increased cerebral blood flow (CBF) at a Gp of less than 2 mmol/L were between 0.14 and 0.79. CBF-normalized K1,glc values were in agreement with saturation kinetics. Phosphorylation rate constants indicated intracellular glucose depletion at a Gp of less than 2-3 mmol/L. When brain regions were compared, glucose transport under hypoglycemia was lowest in the hypothalamus. Alterations in glucose transport and phosphorylation, as well as intracellular glucose depletion, under acute hypoglycemia can be modeled by saturation kinetics taking into account an increase in CBF. Distinct transport kinetics in the hypothalamus may be involved in its glucose-sensing function.

Quantitative in vivo receptor binding. III. Tracer kinetic modeling of muscarinic cholinergic receptor binding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frey, K.A.; Hichwa, R.D.; Ehrenkaufer, R.L.

1985-10-01

A tracer kinetic method is developed for the in vivo estimation of high-affinity radioligand binding to central nervous system receptors. Ligand is considered to exist in three brain pools corresponding to free, nonspecifically bound, and specifically bound tracer. These environments, in addition to that of intravascular tracer, are interrelated by a compartmental model of in vivo ligand distribution. A mathematical description of the model is derived, which allows determination of regional blood-brain barrier permeability, nonspecific binding, the rate of receptor-ligand association, and the rate of dissociation of bound ligand, from the time courses of arterial blood and tissue tracer concentrations.more » The term ''free receptor density'' is introduced to describe the receptor population measured by this method. The technique is applied to the in vivo determination of regional muscarinic acetylcholine receptors in the rat, with the use of (TH)scopolamine. Kinetic estimates of free muscarinic receptor density are in general agreement with binding capacities obtained from previous in vivo and in vitro equilibrium binding studies. In the striatum, however, kinetic estimates of free receptor density are less than those in the neocortex--a reversal of the rank ordering of these regions derived from equilibrium determinations. A simplified model is presented that is applicable to tracers that do not readily dissociate from specific binding sites during the experimental period.« less

Thermodynamics and kinetics of DNA nanotube polymerization from single-filament measurements† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c3sc53331j Click here for additional data file. Click here for additional data file. Click here for additional data file. Click here for additional data file. Click here for additional data file.

PubMed Central

Hariadi, Rizal F.; Yurke, Bernard

2015-01-01

DNA nanotubes provide a programmable architecture for molecular self-assembly and can serve as model systems for one-dimensional biomolecular assemblies. While a variety of DNA nanotubes have been synthesized and employed as models for natural biopolymers, an extensive investigation of DNA nanotube kinetics and thermodynamics has been lacking. Using total internal reflection microscopy, DNA nanotube polymerization was monitored in real time at the single filament level over a wide range of free monomer concentrations and temperatures. The measured polymerization rates were subjected to a global nonlinear fit based on polymerization theory in order to simultaneously extract kinetic and thermodynamic parameters. For the DNA nanotubes used in this study, the association rate constant is (5.99 ± 0.15) × 105 M–1 s–1, the enthalpy is 87.9 ± 2.0 kcal mol–1, and the entropy is 0.252 ± 0.006 kcal mol–1 K–1. The qualitative and quantitative similarities between the kinetics of DNA nanotubes, actin filaments, and microtubules polymerization highlight the prospect of building complex dynamic systems from DNA molecules inspired by biological architecture. PMID:29308139

Cell Population Kinetics of Collagen Scaffolds in Ex Vivo Oral Wound Repair

PubMed Central

Agis, Hermann; Collins, Amy; Taut, Andrei D.; Jin, Qiming; Kruger, Laura; Görlach, Christoph; Giannobile, William V.

2014-01-01

Biodegradable collagen scaffolds are used clinically for oral soft tissue augmentation to support wound healing. This study sought to provide a novel ex vivo model for analyzing healing kinetics and gene expression of primary human gingival fibroblasts (hGF) within collagen scaffolds. Sponge type and gel type scaffolds with and without platelet-derived growth factor-BB (PDGF) were assessed in an hGF containing matrix. Morphology was evaluated with scanning electron microscopy, and hGF metabolic activity using MTT. We quantitated the population kinetics within the scaffolds based on cell density and distance from the scaffold border of DiI-labled hGFs over a two-week observation period. Gene expression was evaluated with gene array and qPCR. The sponge type scaffolds showed a porous morphology. Absolute cell number and distance was higher in sponge type scaffolds when compared to gel type scaffolds, in particular during the first week of observation. PDGF incorporated scaffolds increased cell numbers, distance, and formazan formation in the MTT assay. Gene expression dynamics revealed the induction of key genes associated with the generation of oral tissue. DKK1, CYR61, CTGF, TGFBR1 levels were increased and integrin ITGA2 levels were decreased in the sponge type scaffolds compared to the gel type scaffold. The results suggest that this novel model of oral wound healing provides insights into population kinetics and gene expression dynamics of biodegradable scaffolds. PMID:25397671

Thermal inactivation kinetics of β-galactosidase during bread baking.

PubMed

Zhang, Lu; Chen, Xiao Dong; Boom, Remko M; Schutyser, Maarten A I

2017-06-15

In this study, β-galactosidase was utilized as a model enzyme to investigate the mechanism of enzyme inactivation during bread baking. Thermal inactivation of β-galactosidase was investigated in a wheat flour/water system at varying temperature-moisture content combinations, and in bread during baking at 175 or 205°C. In the wheat flour/water system, the thermostability of β-galactosidase increased with decreased moisture content, and a kinetic model was accurately fitted to the corresponding inactivation data (R 2 =0.99). Interestingly, the residual enzyme activity in the bread crust (about 30%) was hundredfold higher than that in the crumb (about 0.3%) after baking, despite the higher temperature in the crust throughout baking. This result suggested that the reduced moisture content in the crust increased the thermostability of the enzyme. Subsequently, the kinetic model reasonably predicted the enzyme inactivation in the crumb using the same parameters derived from the wheat flour/water system. However, the model predicted a lower residual enzyme activity in the crust compared with the experimental result, which indicated that the structure of the crust may influence the enzyme inactivation mechanism during baking. The results reported can provide a quantitative understanding of the thermal inactivation kinetics of enzyme during baking, which is essential to better retain enzymatic activity in bakery products supplemented with heat-sensitive enzymes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Unchanged mitochondrial organization and compartmentation of high-energy phosphates in creatine-deficient GAMT−/− mouse hearts

PubMed Central

Branovets, Jelena; Sepp, Mervi; Kotlyarova, Svetlana; Jepihhina, Natalja; Sokolova, Niina; Aksentijevic, Dunja; Lygate, Craig A.; Neubauer, Stefan; Birkedal, Rikke

2013-01-01

Disruption of the creatine kinase (CK) system in hearts of CK-deficient mice leads to changes in the ultrastructure and regulation of mitochondrial respiration. We expected to see similar changes in creatine-deficient mice, which lack the enzyme guanidinoacetate methyltransferase (GAMT) to produce creatine. The aim of this study was to characterize the changes in cardiomyocyte mitochondrial organization, regulation of respiration, and intracellular compartmentation associated with GAMT deficiency. Three-dimensional mitochondrial organization was assessed by confocal microscopy. On populations of permeabilized cardiomyocytes, we recorded ADP and ATP kinetics of respiration, competition between mitochondria and pyruvate kinase for ADP produced by ATPases, ADP kinetics of endogenous pyruvate kinase, and ATP kinetics of ATPases. These data were analyzed by mathematical models to estimate intracellular compartmentation. Quantitative analysis of morphological and kinetic data as well as derived model fits showed no difference between GAMT-deficient and wild-type mice. We conclude that inactivation of the CK system by GAMT deficiency does not alter mitochondrial organization and intracellular compartmentation in relaxed cardiomyocytes. Thus, our results suggest that the healthy heart is able to preserve cardiac function at a basal level in the absence of CK-facilitated energy transfer without compromising intracellular organization and the regulation of mitochondrial energy homeostasis. This raises questions on the importance of the CK system as a spatial energy buffer in unstressed cardiomyocytes. PMID:23792673

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

The objective of Task 1 is to prepare and evaluate catalysts and to develop efficient reactor systems for the selective conversion of hydrogen-lean synthesis gas to alcohol fuel extender and octane enhancers. Task 1 is subdivided into three separate subtasks: laboratory and equipment setup; catalysis research; and reaction engineering and modeling. Research at West Virginia University (WVU) is focused on molybdenum-based catalysts for higher alcohol synthesis. Parallel research carried out at Union Carbide Corporation (UCC) is focused on transition-metal-oxide catalysts. During this time period, at WVU, we tried several methods to eliminate problems related to condensation of heavier products whenmore » reduced Mo-Ni-K/C materials were used as catalysts. We then resumed our kinetic study on the reduced Mo-Ni-K/C materials were used as catalysts. We then resumed our kinetic study on the reduced Mo-Ni-K/C catalysts. We have also obtained same preliminary results in our attempts to analyze quantitatively the temperature-programmed reduction spectra for C- supported Mo-based catalysts. We have completed the kinetic study for the sulfided Co-K-MoS{sub 2}/C catalyst. We have compared the results of methanol synthesis using the membrane reactor with those using a simple plug-flow reactor. At UCC, the complete characterization of selected catalysts has been completed. The results suggest that catalyst pretreatment under different reducing conditions yield different surface compositions and thus different catalytic reactivities.« less

Cancer imaging phenomics toolkit: quantitative imaging analytics for precision diagnostics and predictive modeling of clinical outcome.

PubMed

Davatzikos, Christos; Rathore, Saima; Bakas, Spyridon; Pati, Sarthak; Bergman, Mark; Kalarot, Ratheesh; Sridharan, Patmaa; Gastounioti, Aimilia; Jahani, Nariman; Cohen, Eric; Akbari, Hamed; Tunc, Birkan; Doshi, Jimit; Parker, Drew; Hsieh, Michael; Sotiras, Aristeidis; Li, Hongming; Ou, Yangming; Doot, Robert K; Bilello, Michel; Fan, Yong; Shinohara, Russell T; Yushkevich, Paul; Verma, Ragini; Kontos, Despina

2018-01-01

The growth of multiparametric imaging protocols has paved the way for quantitative imaging phenotypes that predict treatment response and clinical outcome, reflect underlying cancer molecular characteristics and spatiotemporal heterogeneity, and can guide personalized treatment planning. This growth has underlined the need for efficient quantitative analytics to derive high-dimensional imaging signatures of diagnostic and predictive value in this emerging era of integrated precision diagnostics. This paper presents cancer imaging phenomics toolkit (CaPTk), a new and dynamically growing software platform for analysis of radiographic images of cancer, currently focusing on brain, breast, and lung cancer. CaPTk leverages the value of quantitative imaging analytics along with machine learning to derive phenotypic imaging signatures, based on two-level functionality. First, image analysis algorithms are used to extract comprehensive panels of diverse and complementary features, such as multiparametric intensity histogram distributions, texture, shape, kinetics, connectomics, and spatial patterns. At the second level, these quantitative imaging signatures are fed into multivariate machine learning models to produce diagnostic, prognostic, and predictive biomarkers. Results from clinical studies in three areas are shown: (i) computational neuro-oncology of brain gliomas for precision diagnostics, prediction of outcome, and treatment planning; (ii) prediction of treatment response for breast and lung cancer, and (iii) risk assessment for breast cancer.

iSCHRUNK--In Silico Approach to Characterization and Reduction of Uncertainty in the Kinetic Models of Genome-scale Metabolic Networks.

PubMed

Andreozzi, Stefano; Miskovic, Ljubisa; Hatzimanikatis, Vassily

2016-01-01

Accurate determination of physiological states of cellular metabolism requires detailed information about metabolic fluxes, metabolite concentrations and distribution of enzyme states. Integration of fluxomics and metabolomics data, and thermodynamics-based metabolic flux analysis contribute to improved understanding of steady-state properties of metabolism. However, knowledge about kinetics and enzyme activities though essential for quantitative understanding of metabolic dynamics remains scarce and involves uncertainty. Here, we present a computational methodology that allow us to determine and quantify the kinetic parameters that correspond to a certain physiology as it is described by a given metabolic flux profile and a given metabolite concentration vector. Though we initially determine kinetic parameters that involve a high degree of uncertainty, through the use of kinetic modeling and machine learning principles we are able to obtain more accurate ranges of kinetic parameters, and hence we are able to reduce the uncertainty in the model analysis. We computed the distribution of kinetic parameters for glucose-fed E. coli producing 1,4-butanediol and we discovered that the observed physiological state corresponds to a narrow range of kinetic parameters of only a few enzymes, whereas the kinetic parameters of other enzymes can vary widely. Furthermore, this analysis suggests which are the enzymes that should be manipulated in order to engineer the reference state of the cell in a desired way. The proposed approach also sets up the foundations of a novel type of approaches for efficient, non-asymptotic, uniform sampling of solution spaces. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Permeabilization Activated Reduction in Fluorescence (PARF): a novel method to measure kinetics of protein interactions with intracellular structures

PubMed Central

Singh, Pali P.; Hawthorne, Jenci L.; Davis, Christie A.; Quintero, Omar A.

2016-01-01

Understanding kinetic information is fundamental in understanding biological function. Advanced imaging technologies have fostered the development of kinetic analyses in cells. We have developed Permeabilization Activated Reduction in Fluorescence (PARF) analysis for determination of apparent t1/2 and immobile fraction, describing the dissociation of a protein of interest from intracellular structures. To create conditions where dissociation events are observable, cells expressing a fluorescently-tagged protein are permeabilized with digitonin, diluting the unbound protein into the extracellular media. As the media volume is much larger than the cytosolic volume, the concentration of the unbound pool decreases drastically, shifting the system out of equilibrium--favoring dissociation events. Loss of bound protein is observed as loss of fluorescence from intracellular structures and can be fit to an exponential decay. We compared PARF dissociation kinetics with previously published equilibrium kinetics as determined by FRAP. PARF dissociation rates agreed with the equilibrium-based FRAP analysis predictions of the magnitude of those rates. When used to investigate binding kinetics of a panel of cytoskeletal proteins, PARF analysis revealed that filament stabilization resulted in slower fluorescence loss. Additionally, commonly used “general” F-actin labels display differences in kinetic properties, suggesting that not all fluorescently-tagged actin labels interact with the actin network in the same way. We also observed differential dissociation kinetics for GFP-VASP depending on which cellular structure was being labeled. These results demonstrate that PARF analysis of non-equilibrium systems reveals kinetic information without the infrastructure investment required for other quantitative approaches such as FRAP, photoactivation, or in vitro reconstitution assays. PMID:27126922

The size effects upon shock plastic compression of nanocrystals

NASA Astrophysics Data System (ADS)

Malygin, G. A.; Klyavin, O. V.

2017-10-01

For the first time a theoretical analysis of scale effects upon the shock plastic compression of nanocrystals is implemented in the context of a dislocation kinetic approach based on the equations and relationships of dislocation kinetics. The yield point of crystals τy is established as a quantitative function of their cross-section size D and the rate of shock deformation as τy ɛ2/3 D. This dependence is valid in the case of elastic stress relaxation on account of emission of dislocations from single-pole Frank-Read sources near the crystal surface.

Chemical kinetics of homogeneous atmospheric oxidation of sulfur dioxide

NASA Technical Reports Server (NTRS)

Sander, S. P.; Seinfeld, J. H.

1976-01-01

A systematic evaluation of known homogeneous SO2 reactions which might be important in air pollution chemistry is carried out. A mechanism is developed to represent the chemistry of NOx/hydrocarbon/SO2 systems, and the mechanism is used to analyze available experimental data appropriate for quantitative analysis of SO2 oxidation kinetics. Detailed comparisons of observed and predicted concentration behavior are presented. In all cases, observed SO2 oxidation rates cannot be explained solely on the basis of those SO2 reactions for which rate constants have been measured. The role of ozone-olefin reactions in SO2 oxidation is elucidated.

Structural and silver/vanadium ratio effects on silver vanadium phosphorous oxide solution formation kinetics: impact on battery electrochemistry.

PubMed

Bock, David C; Takeuchi, Kenneth J; Marschilok, Amy C; Takeuchi, Esther S

2015-01-21

The detailed understanding of non-faradaic parasitic reactions which diminish battery calendar life is essential to the development of effective batteries for use in long life applications. The dissolution of cathode materials including manganese, cobalt and vanadium oxides in battery systems has been identified as a battery failure mechanism, yet detailed dissolution studies including kinetic analysis are absent from the literature. The results presented here provide a framework for the quantitative and kinetic analyses of the dissolution of cathode materials which will aid the broader community in more fully understanding this battery failure mechanism. In this study, the dissolution of silver vanadium oxide, representing the primary battery powering implantable cardioverter defibrillators (ICD), is compared with the dissolution of silver vanadium phosphorous oxide (Ag(w)VxPyOz) materials which were targeted as alternatives to minimize solubility. This study contains the first kinetic analyses of silver and vanadium solution formation from Ag0.48VOPO4·1.9H2O and Ag2VP2O8, in a non-aqueous battery electrolyte. The kinetic results are compared with those of Ag2VO2PO4 and Ag2V4O11 to probe the relationships among crystal structure, stoichiometry, and solubility. For vanadium, significant dissolution was observed for Ag2V4O11 as well as for the phosphate oxide Ag0.49VOPO4·1.9H2O, which may involve structural water or the existence of multiple vanadium oxidation states. Notably, the materials from the SVPO family with the lowest vanadium solubility are Ag2VO2PO4 and Ag2VP2O8. The low concentrations and solution rates coupled with their electrochemical performance make these materials interesting alternatives to Ag2V4O11 for the ICD application.

Compactness and robustness: Applications in the solution of integral equations for chemical kinetics and electromagnetic scattering

NASA Astrophysics Data System (ADS)

Zhou, Yajun

This thesis employs the topological concept of compactness to deduce robust solutions to two integral equations arising from chemistry and physics: the inverse Laplace problem in chemical kinetics and the vector wave scattering problem in dielectric optics. The inverse Laplace problem occurs in the quantitative understanding of biological processes that exhibit complex kinetic behavior: different subpopulations of transition events from the "reactant" state to the "product" state follow distinct reaction rate constants, which results in a weighted superposition of exponential decay modes. Reconstruction of the rate constant distribution from kinetic data is often critical for mechanistic understandings of chemical reactions related to biological macromolecules. We devise a "phase function approach" to recover the probability distribution of rate constants from decay data in the time domain. The robustness (numerical stability) of this reconstruction algorithm builds upon the continuity of the transformations connecting the relevant function spaces that are compact metric spaces. The robust "phase function approach" not only is useful for the analysis of heterogeneous subpopulations of exponential decays within a single transition step, but also is generalizable to the kinetic analysis of complex chemical reactions that involve multiple intermediate steps. A quantitative characterization of the light scattering is central to many meteoro-logical, optical, and medical applications. We give a rigorous treatment to electromagnetic scattering on arbitrarily shaped dielectric media via the Born equation: an integral equation with a strongly singular convolution kernel that corresponds to a non-compact Green operator. By constructing a quadratic polynomial of the Green operator that cancels out the kernel singularity and satisfies the compactness criterion, we reveal the universality of a real resonance mode in dielectric optics. Meanwhile, exploiting the properties of compact operators, we outline the geometric and physical conditions that guarantee a robust solution to the light scattering problem, and devise an asymptotic solution to the Born equation of electromagnetic scattering for arbitrarily shaped dielectric in a non-perturbative manner.

Kinetics and Mechanisms of Phosphorus Adsorption in Soils from Diverse Ecological Zones in the Source Area of a Drinking-Water Reservoir

PubMed Central

Zhang, Liang; Loáiciga, Hugo A.; Xu, Meng; Du, Chao; Du, Yun

2015-01-01

On-site soils are increasingly used in the treatment and restoration of ecosystems to harmonize with the local landscape and minimize costs. Eight natural soils from diverse ecological zones in the source area of a drinking-water reservoir in central China are used as adsorbents for the uptake of phosphorus from aqueous solutions. The X-ray fluorescence (XRF) spectrometric and BET (Brunauer-Emmett-Teller) tests and the Scanning Electron Microscopy (SEM) and Fourier Transform Infrared (FTIR) spectral analyses are carried out to investigate the soils’ chemical properties and their potential changes with adsorbed phosphorous from aqueous solutions. The intra-particle diffusion, pseudo-first-order, and pseudo-second-order kinetic models describe the adsorption kinetic processes. Our results indicate that the adsorption processes of phosphorus in soils occurred in three stages and that the rate-controlling steps are not solely dependent on intra-particle diffusion. A quantitative comparison of two kinetics models based on their linear and non-linear representations, and using the chi-square (χ2) test and the coefficient of determination (r2), indicates that the adsorptive properties of the soils are best described by the non-linear pseudo-second-order kinetic model. The adsorption characteristics of aqueous phosphorous are determined along with the essential kinetic parameters. PMID:26569278

Neurotomy of the rectus femoris nerve: Short-term effectiveness for spastic stiff knee gait: Clinical assessment and quantitative gait analysis.

PubMed

Gross, R; Robertson, J; Leboeuf, F; Hamel, O; Brochard, S; Perrouin-Verbe, B

2017-02-01

Stiff knee gait is a troublesome gait disturbance related to spastic paresis, frequently associated with overactivity of the rectus femoris muscle in the swing phase of gait. The aim of this study was to assess the short-term effects of rectus femoris neurotomy for the treatment of spastic stiff-knee gait in patients with hemiparesis. An Intervention study (before-after trial) with an observational design was carried out in a university hospital. Seven ambulatory patients with hemiparesis of spinal or cerebral origin and spastic stiff-knee gait, which had previously been improved by botulinum toxin injections, were proposed a selective neurotomy of the rectus femoris muscle. A functional evaluation (Functional Ambulation Classification and maximal walking distance), clinical evaluation (spasticity - Ashworth scale and Duncan-Ely test, muscle strength - Medical Research Council scale), and quantitative gait analysis (spatiotemporal parameters, stiff knee gait-related kinematic and kinetic parameters, and dynamic electromyography of rectus femoris) were performed as outcome measures, before and 3 months after rectus femoris neurotomy. Compared with preoperative values, there was a significant increase in maximal walking distance, gait speed, and stride length at 3 months. All kinematic parameters improved, and the average early swing phase knee extension moment decreased. The duration of the rectus femoris burst decreased post-op. This study is the first to show that rectus femoris neurotomy helps to normalise muscle activity during gait, and results in improvements in kinetic, kinematic, and functional parameters in patients with spastic stiff knee gait. Copyright © 2016 Elsevier B.V. All rights reserved.

PET Imaging Stability Measurements During Simultaneous Pulsing of Aggressive MR Sequences on the SIGNA PET/MR System.

PubMed

Deller, Timothy W; Khalighi, Mohammad Mehdi; Jansen, Floris P; Glover, Gary H

2018-01-01

The recent introduction of simultaneous whole-body PET/MR scanners has enabled new research taking advantage of the complementary information obtainable with PET and MRI. One such application is kinetic modeling, which requires high levels of PET quantitative stability. To accomplish the required PET stability levels, the PET subsystem must be sufficiently isolated from the effects of MR activity. Performance measurements have previously been published, demonstrating sufficient PET stability in the presence of MR pulsing for typical clinical use; however, PET stability during radiofrequency (RF)-intensive and gradient-intensive sequences has not previously been evaluated for a clinical whole-body scanner. In this work, PET stability of the GE SIGNA PET/MR was examined during simultaneous scanning of aggressive MR pulse sequences. Methods: PET performance tests were acquired with MR idle and during simultaneous MR pulsing. Recent system improvements mitigating RF interference and gain variation were used. A fast recovery fast spin echo MR sequence was selected for high RF power, and an echo planar imaging sequence was selected for its high heat-inducing gradients. Measurements were performed to determine PET stability under varying MR conditions using the following metrics: sensitivity, scatter fraction, contrast recovery, uniformity, count rate performance, and image quantitation. A final PET quantitative stability assessment for simultaneous PET scanning during functional MRI studies was performed with a spiral in-and-out gradient echo sequence. Results: Quantitation stability of a 68 Ge flood phantom was demonstrated within 0.34%. Normalized sensitivity was stable during simultaneous scanning within 0.3%. Scatter fraction measured with a 68 Ge line source in the scatter phantom was stable within the range of 40.4%-40.6%. Contrast recovery and uniformity were comparable for PET images acquired simultaneously with multiple MR conditions. Peak noise equivalent count rate was 224 kcps at an effective activity concentration of 18.6 kBq/mL, and the count rate curves and scatter fraction curve were consistent for the alternating MR pulsing states. A final test demonstrated quantitative stability during a spiral functional MRI sequence. Conclusion: PET stability metrics demonstrated that PET quantitation was not affected during simultaneous aggressive MRI. This stability enables demanding applications such as kinetic modeling. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Effects of finite spatial resolution on quantitative CBF images from dynamic PET

DOE Office of Scientific and Technical Information (OSTI.GOV)

Phelps, M.E.; Huang, S.C.; Mahoney, D.K.

1985-05-01

The finite spatial resolution of PET causes the time-activity responses on pixels around the boundaries between gray and white matter regions to contain kinetic components from tissues of different CBF's. CBF values estimated from kinetics of such mixtures are underestimated because of the nonlinear relationship between the time-activity response and the estimated CBF. Computer simulation is used to investigate these effects on phantoms of circular structures and realistic brain slice in terms of object size and quantitative CBF values. The CBF image calculated is compared to the case of having resolution loss alone. Results show that the size of amore » high flow region in the CBF image is decreased while that of a low flow region is increased. For brain phantoms, the qualitative appearance of CBF images is not seriously affected, but the estimated CBF's are underestimated by 11 to 16 percent in local gray matter regions (of size 1 cm/sup 2/) with about 14 percent reduction in global CBF over the whole slice. It is concluded that the combined effect of finite spatial resolution and the nonlinearity in estimating CBF from dynamic PET is quite significant and must be considered in processing and interpreting quantitative CBF images.« less

The effect of respiratory induced density variations on non-TOF PET quantitation in the lung.

PubMed

Holman, Beverley F; Cuplov, Vesna; Hutton, Brian F; Groves, Ashley M; Thielemans, Kris

2016-04-21

Accurate PET quantitation requires a matched attenuation map. Obtaining matched CT attenuation maps in the thorax is difficult due to the respiratory cycle which causes both motion and density changes. Unlike with motion, little attention has been given to the effects of density changes in the lung on PET quantitation. This work aims to explore the extent of the errors caused by pulmonary density attenuation map mismatch on dynamic and static parameter estimates. Dynamic XCAT phantoms were utilised using clinically relevant (18)F-FDG and (18)F-FMISO time activity curves for all organs within the thorax to estimate the expected parameter errors. The simulations were then validated with PET data from 5 patients suffering from idiopathic pulmonary fibrosis who underwent PET/Cine-CT. The PET data were reconstructed with three gates obtained from the Cine-CT and the average Cine-CT. The lung TACs clearly displayed differences between true and measured curves with error depending on global activity distribution at the time of measurement. The density errors from using a mismatched attenuation map were found to have a considerable impact on PET quantitative accuracy. Maximum errors due to density mismatch were found to be as high as 25% in the XCAT simulation. Differences in patient derived kinetic parameter estimates and static concentration between the extreme gates were found to be as high as 31% and 14%, respectively. Overall our results show that respiratory associated density errors in the attenuation map affect quantitation throughout the lung, not just regions near boundaries. The extent of this error is dependent on the activity distribution in the thorax and hence on the tracer and time of acquisition. Consequently there may be a significant impact on estimated kinetic parameters throughout the lung.

The effect of respiratory induced density variations on non-TOF PET quantitation in the lung

NASA Astrophysics Data System (ADS)

Holman, Beverley F.; Cuplov, Vesna; Hutton, Brian F.; Groves, Ashley M.; Thielemans, Kris

2016-04-01

Accurate PET quantitation requires a matched attenuation map. Obtaining matched CT attenuation maps in the thorax is difficult due to the respiratory cycle which causes both motion and density changes. Unlike with motion, little attention has been given to the effects of density changes in the lung on PET quantitation. This work aims to explore the extent of the errors caused by pulmonary density attenuation map mismatch on dynamic and static parameter estimates. Dynamic XCAT phantoms were utilised using clinically relevant 18F-FDG and 18F-FMISO time activity curves for all organs within the thorax to estimate the expected parameter errors. The simulations were then validated with PET data from 5 patients suffering from idiopathic pulmonary fibrosis who underwent PET/Cine-CT. The PET data were reconstructed with three gates obtained from the Cine-CT and the average Cine-CT. The lung TACs clearly displayed differences between true and measured curves with error depending on global activity distribution at the time of measurement. The density errors from using a mismatched attenuation map were found to have a considerable impact on PET quantitative accuracy. Maximum errors due to density mismatch were found to be as high as 25% in the XCAT simulation. Differences in patient derived kinetic parameter estimates and static concentration between the extreme gates were found to be as high as 31% and 14%, respectively. Overall our results show that respiratory associated density errors in the attenuation map affect quantitation throughout the lung, not just regions near boundaries. The extent of this error is dependent on the activity distribution in the thorax and hence on the tracer and time of acquisition. Consequently there may be a significant impact on estimated kinetic parameters throughout the lung.

Kinetic limitation of chemical ordering in Bi2Te3-x Se x layers grown by molecular beam epitaxy

NASA Astrophysics Data System (ADS)

Schreyeck, S.; Brunner, K.; Kirchner, A.; Bass, U.; Grauer, S.; Schumacher, C.; Gould, C.; Karczewski, G.; Geurts, J.; Molenkamp, L. W.

2016-04-01

We study the chemical ordering in Bi2Te3-x Se x grown by molecular beam epitaxy on Si substrates. We produce films in the full composition range from x  =  0 to 3, and determine their material properties using energy dispersive x-ray spectroscopy, x-ray diffraction and Raman spectroscopy. By fitting the parameters of a kinetic growth model to these results, we obtain a consistent description of growth at a microscopic level. Our main finding is that despite the incorporation of Se in the central layer being much more probable than that of Te, the formation of a fully ordered Te-Bi-Se-Bi-Te layer is prevented by kinetic of the growth process. Indeed, the Se concentration in the central layer of Bi2Te2Se1 reaches a maximum of only  ≈75% even under ideal growth conditions. A second finding of our work is that the intensity ratio of the 0 0 12 and 0 0 6 x-ray reflections serves as an experimentally accessible quantitative measure of the degree of ordering in these films.

Monitoring of interaction of low-frequency electric field with biological tissues upon optical clearing with optical coherence tomography.

PubMed

Peña, Adrián F; Doronin, Alexander; Tuchin, Valery V; Meglinski, Igor

2014-08-01

The influence of a low-frequency electric field applied to soft biological tissues ex vivo at normal conditions and upon the topical application of optical clearing agents has been studied by optical coherence tomography (OCT). The electro-kinetic response of tissues has been observed and quantitatively evaluated by the double correlation OCT approach, utilizing consistent application of an adaptive Wiener filtering and Fourier domain correlation algorithm. The results show that fluctuations, induced by the electric field within the biological tissues are exponentially increased in time. We demonstrate that in comparison to impedance measurements and the mapping of the temperature profile at the surface of the tissue samples, the double correlation OCT approach is much more sensitive to the changes associated with the tissues' electro-kinetic response. We also found that topical application of the optical clearing agent reduces the tissues' electro-kinetic response and is cooling the tissue, thus reducing the temperature induced by the electric current by a few degrees. We anticipate that dcOCT approach can find a new application in bioelectrical impedance analysis and monitoring of the electric properties of biological tissues, including the resistivity of high water content tissues and its variations.

Kinetics modeling of precipitation with characteristic shape during post-implantation annealing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Kun-Dar, E-mail: kundar@mail.nutn.edu.tw; Chen, Kwanyu

2015-11-15

In this study, we investigated the precipitation with characteristic shape in the microstructure during post-implantation annealing via a theoretical modeling approach. The processes of precipitates formation and evolution during phase separation were based on a nucleation and growth mechanism of atomic diffusion. Different stages of the precipitation, including the nucleation, growth and coalescence, were distinctly revealed in the numerical simulations. In addition, the influences of ion dose, temperature and crystallographic symmetry on the processes of faceted precipitation were also demonstrated. To comprehend the kinetic mechanism, the simulation results were further analyzed quantitatively by the Kolmogorov-Johnson-Mehl-Avrami (KJMA) equation. The Avrami exponentsmore » obtained from the regression curves varied from 1.47 to 0.52 for different conditions. With the increase of ion dose and temperature, the nucleation and growth of precipitations were expedited in accordance with the shortened incubation time and the raised coefficient of growth rate. A miscellaneous shape of precipitates in various crystallographic symmetry systems could be simulated through this anisotropic model. From the analyses of the kinetics, more fundamental information about the nucleation and growth mechanism of faceted precipitation during post-implantation annealing was acquired for future application.« less

Quantitative Kinetics Evaluation of Blocks Versus Granules of Biphasic Calcium Phosphate Scaffolds (HA/β-TCP 30/70) by Synchrotron Radiation X-ray Microtomography: A Human Study.

PubMed

Giuliani, Alessandra; Manescu, Adrian; Mohammadi, Sara; Mazzoni, Serena; Piattelli, Adriano; Mangano, Francesco; Iezzi, Giovanna; Mangano, Carlo

2016-02-01

Successful bone regeneration using both granules and blocks of biphasic calcium phosphate materials has been reported in the recent literature, in some clinical applications for maxillary sinus elevation, but the long-term kinetics of bone regeneration has still not been fully investigated. Twenty-four bilateral sinus augmentation procedures were performed and grafted with hydroxyapatite/β-tricalcium phosphate 30/70, 12 with granules and 12 with blocks. The samples were retrieved at different time points and were evaluated for bone regeneration, graft resorption, neovascularization, and morphometric parameters by computed microtomography and histology. A large amount of newly formed bone was detected in the retrieved specimens, together with a good rate of biomaterial resorption and the formation of a homogeneous and rich net of new vessels. The morphometric values were comparable at 5/6 months from grafting but, 9 months after grafting, revealed that the block-based specimens mimicked slightly better than granule-based samples the healthy native bone of the maxillary site. The scaffold morphology was confirmed to influence the long-term kinetics of bone regeneration.

Kinetics of the cooperative binding of glucose to dimeric yeast hexokinase P-I.

PubMed

Hoggett, J G; Kellett, G L

1995-01-15

Kinetic studies of the cooperative binding of glucose to yeast hexokinase P-I at pH 6.5 have been carried out using the fluorescence temperature-jump technique. Three relaxation effects were observed: a fast low-amplitude effect which could only be resolved at low glucose concentrations (tau 1(-1) = 500-800 s-1), an intermediate effect (tau 2) which showed a linear dependence of reciprocal relaxation time on concentration, and a slow effect (tau 3) which showed a curved dependence on glucose concentration, increasing from approximately 28 s-1 at low concentrations to 250 s-1 at high levels. The findings are interpreted in terms of the concerted Monod-Wyman-Changeux mechanism, the two faster relaxations being assigned to binding to the R and T states, and the slow relaxation to isomerization between the states. Quantitative fitting of the kinetic data to the mechanism has been carried out using independent estimates of the equilibrium parameters of the model; these have been derived from equilibrium dialysis data and by determining the enhancement of the intrinsic ATPase activity of the enzyme by the non-phosphorylatable sugar lyxose, which switches the conformation of the enzyme to the active R state.

Purified reconstituted lac carrier protein from Escherichia coli is fully functional.

PubMed

Viitanen, P; Garcia, M L; Kaback, H R

1984-03-01

Proteoliposomes reconstituted with lac carrier protein purified from the plasma membrane of Escherichia coli catalyze each of the translocation reactions typical of the beta-galactoside transport system (i.e., active transport, counterflow, facilitated influx and efflux) with turnover numbers and apparent Km values comparable to those observed in right-side-out membrane vesicles. Furthermore, detailed kinetic studies show that the reconstituted system exhibits properties analogous to those observed in membrane vesicles. Imposition of a membrane potential (delta psi, interior negative) causes a marked decrease in apparent Km (by a factor of 7 to 10) with a smaller increase in Vmax (approximately equal to 3-fold). At submaximal values of delta psi, the reconstituted carrier exhibits biphasic kinetics, with one component manifesting the kinetic parameters of active transport and the other exhibiting the characteristics of facilitated diffusion. Finally, at low lactose concentrations, the initial velocity of influx varies linearly with the square of the proton electro-chemical gradient. The results provide quantitative support for the contention that a single polypeptide species, the product of the lac y gene, is responsible for each of the transport reactions typical of the beta-galactoside transport system.

Kinetics of Forming Aldehydes in Frying Oils and Their Distribution in French Fries Revealed by LC-MS-Based Chemometrics.

PubMed

Wang, Lei; Csallany, A Saari; Kerr, Brian J; Shurson, Gerald C; Chen, Chi

2016-05-18

In this study, the kinetics of aldehyde formation in heated frying oils was characterized by 2-hydrazinoquinoline derivatization, liquid chromatography-mass spectrometry (LC-MS) analysis, principal component analysis (PCA), and hierarchical cluster analysis (HCA). The aldehydes contributing to time-dependent separation of heated soybean oil (HSO) in a PCA model were grouped by the HCA into three clusters (A1, A2, and B) on the basis of their kinetics and fatty acid precursors. The increases of 4-hydroxynonenal (4-HNE) and the A2-to-B ratio in HSO were well-correlated with the duration of thermal stress. Chemometric and quantitative analysis of three frying oils (soybean, corn, and canola oils) and French fry extracts further supported the associations between aldehyde profiles and fatty acid precursors and also revealed that the concentrations of pentanal, hexanal, acrolein, and the A2-to-B ratio in French fry extracts were more comparable to their values in the frying oils than other unsaturated aldehydes. All of these results suggest the roles of specific aldehydes or aldehyde clusters as novel markers of the lipid oxidation status for frying oils or fried foods.

Dynamic quantitative photothermal monitoring of cell death of individual human red blood cells upon glucose depletion

NASA Astrophysics Data System (ADS)

Vasudevan, Srivathsan; Chen, George Chung Kit; Andika, Marta; Agarwal, Shuchi; Chen, Peng; Olivo, Malini

2010-09-01

Red blood cells (RBCs) have been found to undergo ``programmed cell death,'' or eryptosis, and understanding this process can provide more information about apoptosis of nucleated cells. Photothermal (PT) response, a label-free photothermal noninvasive technique, is proposed as a tool to monitor the cell death process of living human RBCs upon glucose depletion. Since the physiological status of the dying cells is highly sensitive to photothermal parameters (e.g., thermal diffusivity, absorption, etc.), we applied linear PT response to continuously monitor the death mechanism of RBC when depleted of glucose. The kinetics of the assay where the cell's PT response transforms from linear to nonlinear regime is reported. In addition, quantitative monitoring was performed by extracting the relevant photothermal parameters from the PT response. Twofold increases in thermal diffusivity and size reduction were found in the linear PT response during cell death. Our results reveal that photothermal parameters change earlier than phosphatidylserine externalization (used for fluorescent studies), allowing us to detect the initial stage of eryptosis in a quantitative manner. Hence, the proposed tool, in addition to detection of eryptosis earlier than fluorescence, could also reveal physiological status of the cells through quantitative photothermal parameter extraction.

How Can Biologically-Based Modeling of Arsenic Kinetics and Dynamics Inform the Risk Assessment Process? -- ETD

EPA Science Inventory

Quantitative biologically-based models describing key events in the continuum from arsenic exposure to the development of adverse health effects provide a framework to integrate information obtained across diverse research areas. For example, genetic polymorphisms in arsenic me...

Electrochemical Removal of Metal Cations from Wastewater Monitored by Differential Pulse Polarography

ERIC Educational Resources Information Center

Bruce, Delphine; Kuhn, Alexander; Sojic, Neso

2004-01-01

Electrodeposition eliminates wastewater pollutants such as electrochemically active metal cations, with different pulse polarography (DPP) scrutinizing the kinetics of the treatment process. These mechanisms produce qualitative and quantitative data about the removal process, while students appreciate the use of electrochemistry in resolving…

LIF measurements and chemical kinetic analysis of methylidyne formation in high-pressure counter-flow partially premixed and non-premixed flames

NASA Astrophysics Data System (ADS)

Naik, S. V.; Laurendeau, N. M.

2004-11-01

We report quantitative, spatially resolved, linear laser-induced fluorescence (LIF) measurements of methylidyne concentration ([CH]) in laminar, methane air, counter-flow partially premixed and non-premixed flames using excitation near 431.5 nm in the A X (0,0) band. For partially premixed flames, fuel-side equivalence ratios (ϕB) of 1.45, 1.6 and 2.0 are studied at pressures of 1, 3, 6, 9 and 12 atm. For non-premixed flames, the fuel-side mixture consists of 25% CH4 and 75% N2; measurements are obtained at pressures of 1, 2, 3, 4, 5, 6, 9 and 12 atm. The quantitative CH measurements are compared with predictions from an opposed-flow flame code utilizing two GRI chemical kinetic mechanisms (versions 2.11 and 3.0). LIF measurements of [CH] are corrected for variations in the quenching rate coefficient by using major species concentrations and temperatures generated by the code along with suitable quenching cross sections for CH available from the literature. A pathway analysis provides relative contributions from important elementary reactions to the total amount of CH produced at various pressures. Key reactions controlling peak CH concentrations are also identified by using a sensitivity analysis. For the partially premixed flames, measured CH profiles are reproduced reasonably well by GRI 3.0, although some quantitative disagreement exists at all pressures. Two CH radical peaks are observed for ϕB=1.45 and ϕB=1.6 at pressures above 3 atm. Peak CH concentrations for the non-premixed flames are significantly underpredicted by GRI 3.0. The latter agrees with previously reported NO concentrations, which are also underpredicted in these same high-pressure counter-flow diffusion flames.

Repair of x-ray-induced DNA double-strand breaks in specific Not I restriction fragments in human fibroblasts: joining of correct and incorrect ends

NASA Technical Reports Server (NTRS)

Lobrich, M.; Rydberg, B.; Cooper, P. K.; Chatterjee, A. (Principal Investigator)

1995-01-01

An assay that allows measurement of absolute induction frequencies for DNA double-strand breaks (dsbs) in defined regions of the genome and that quantitates rejoining of correct DNA ends has been used to study repair of dsbs in normal human fibroblasts after x-irradiation. The approach involves hybridization of single-copy DNA probes to Not I restriction fragments separated according to size by pulsed-field gel electrophoresis. Induction of dsbs is quantitated from the decrease in the intensity of the hybridizing restriction fragment and an accumulation of a smear below the band. Rejoining of dsbs results in reconstitution of the intact restriction fragment only if correct DNA ends are joined. By comparing results from this technique with results from a conventional electrophoresis assay that detects all rejoining events, it is possible to quantitate the misrejoining frequency. Three Not I fragments on the long arm of chromosome 21 were investigated with regard to dsb induction, yielding an identical induction rate of 5.8 X 10(-3) break per megabase pair per Gy. Correct dsb rejoining was measured for two of these Not I fragments after initial doses of 80 and 160 Gy. The misrejoining frequency was about 25% for both fragments and was independent of dose. This result appears to be representative for the whole genome as shown by analysis of the entire Not I fragment distribution. The correct rejoining events primarily occurred within the first 2 h, while the misrejoining kinetics included a much slower component, with about half of the events occurring between 2 and 24 h. These misrejoining kinetics are similar to those previously reported for production of exchange aberrations in interphase chromosomes.

Evaluating reporter genes of different luciferases for optimized in vivo bioluminescence imaging of transplanted neural stem cells in the brain.

PubMed

Mezzanotte, Laura; Aswendt, Markus; Tennstaedt, Annette; Hoeben, Rob; Hoehn, Mathias; Löwik, Clemens

2013-01-01

Bioluminescence imaging (BLI) has become the method of choice for optical tracking of cells in small laboratory animals. However, the use of luciferases from different species, depending on different substrates and emitting at distinct wavelengths, has not been optimized for sensitive neuroimaging. In order to identify the most suitable luciferase, this quantitative study compared the luciferases Luc2, CBG99, PpyRE9 and hRluc. Human embryonic kidney (HEK-293) cells and mouse neural stem cells were transduced by lentiviral vector-mediated transfer to express one of the four luciferases, together with copGFP. A T2A peptide linker promoted stoichiometric expression between both imaging reporters and the comparison of cell populations upon flow cytometry. Cell dilution series were used to determine highest BLI sensitivity in vitro for Luc2. However, Coelenterazine h-dependent hRluc signals clearly exceeded d-luciferin-dependent BLI in vitro. For the quantitative in vivo analysis, cells were transplanted into mouse brain and BLI was performed including the recording of emission kinetics and spectral characteristics. Differences in light kinetics were observed for d-luciferin vs Coelenterazine h. The emission spectra of Luc2 and PpyRE9 remained almost unchanged, while the emission spectrum of CBG99 became biphasic. Most importantly, photon emission decreased in the order of Luc2, CBG99, PpyRE9 to hRluc. The feasibility of combining different luciferases for dual color and dual substrate neuroimaging was tested and discussed. This investigation provides the first complete quantitative comparison of different luciferases expressed by neural stem cells. It results in a clear recommendation of Luc2 as the best luciferase selection for in vivo neuroimaging. Copyright © 2013 John Wiley & Sons, Ltd.

Reproducibility of Quantitative Brain Imaging Using a PET-Only and a Combined PET/MR System

PubMed Central

Lassen, Martin L.; Muzik, Otto; Beyer, Thomas; Hacker, Marcus; Ladefoged, Claes Nøhr; Cal-González, Jacobo; Wadsak, Wolfgang; Rausch, Ivo; Langer, Oliver; Bauer, Martin

2017-01-01

The purpose of this study was to test the feasibility of migrating a quantitative brain imaging protocol from a positron emission tomography (PET)-only system to an integrated PET/MR system. Potential differences in both absolute radiotracer concentration as well as in the derived kinetic parameters as a function of PET system choice have been investigated. Five healthy volunteers underwent dynamic (R)-[11C]verapamil imaging on the same day using a GE-Advance (PET-only) and a Siemens Biograph mMR system (PET/MR). PET-emission data were reconstructed using a transmission-based attenuation correction (AC) map (PET-only), whereas a standard MR-DIXON as well as a low-dose CT AC map was applied to PET/MR emission data. Kinetic modeling based on arterial blood sampling was performed using a 1-tissue-2-rate constant compartment model, yielding kinetic parameters (K1 and k2) and distribution volume (VT). Differences for parametric values obtained in the PET-only and the PET/MR systems were analyzed using a 2-way Analysis of Variance (ANOVA). Comparison of DIXON-based AC (PET/MR) with emission data derived from the PET-only system revealed average inter-system differences of −33 ± 14% (p < 0.05) for the K1 parameter and −19 ± 9% (p < 0.05) for k2. Using a CT-based AC for PET/MR resulted in slightly lower systematic differences of −16 ± 18% for K1 and −9 ± 10% for k2. The average differences in VT were −18 ± 10% (p < 0.05) for DIXON- and −8 ± 13% for CT-based AC. Significant systematic differences were observed for kinetic parameters derived from emission data obtained from PET/MR and PET-only imaging due to different standard AC methods employed. Therefore, a transfer of imaging protocols from PET-only to PET/MR systems is not straightforward without application of proper correction methods. Clinical Trial Registration: www.clinicaltrialsregister.eu, identifier 2013-001724-19 PMID:28769742

Very Tiny Rocks: Site-Specific, Size-Dependent Reaction Kinetics at Nanoparticle-Water Interfaces

NASA Astrophysics Data System (ADS)

Rustad, J. R.

2008-12-01

One of the most fundamental challenges in geochemistry is to be able to understand the rates and mechanisms of elementary reactions that describe chemical processes occurring at mineral-water interfaces. One of the reasons for the primitive conceptual state of reaction kinetics in solid earth geochemistry is that it is very difficult to identify defensible elementary reactions where theoretical predictions can be made and the results can tested experimentally at the same length and time scale of the prediction. For example, the most fundamental predictor of complexation kinetics in aqueous solution is the characteristic water exchange rate, which are well known for the aquo ions and vary by 20 orders of magnitude even for simple trivalent ions. In contrast, for interfacial reactions, it was not even known whether water exchange rates were faster or slower than equivalent metal sites in solution, prohibiting any quantitive understanding of mineral reaction kinetics at the molecular level. Recent advances in synthesis and characterization of materials at nanometer length scales has been able to bridge the gap in scale, and nanometer-sized minerals have given us our first quantitative understanding of elementary reaction rates for fundamental processes involving water and hydroxide exchange reactions. I describe the results of molecular dynamics calculation and experimental measurement of the rates of water, hydroxide, and proton exchange reactions on nanoparticle surfaces. The calculations already show that transition state theory is completely inadequate to understand the rates of even the simplest elementary reactions. Furthermore, the mechanistic implications of rate parameters such as activation volume and activation enthalpy may be different in moving from aquo ions to interfaces. Is a molecular understanding of geochemical processes really needed? One might have asked a biologist at the turn of the century whether studying the structure of proteins would ever be useful for curing disease. True molecular level understanding of interfacial interactions has the potential to revolutionize geology, allowing unprecedented detail and accuracy in such important contexts as climate reconstruction and tectonic history. Geology has an inevitable molecular future.

The role of fluid compression in energy conversion and particle energization during magnetic reconnection

NASA Astrophysics Data System (ADS)

Li, X.; Guo, F.; Li, G.; Li, H.

2016-12-01

Theories of particle transport and acceleration have shown that fluid compression is the leading mechanism for particle acceleration and plasma energization. However, the role of compression in particle acceleration during magnetic reconnection is unclear. We use two approaches to study this issue. First, using fully kinetic simulations, we quantitatively calculate the effect of compression in energy conversion and particle energization during magnetic reconnection for a range of plasma beta and guide field. We show that compression has an important contribution for the energy conversion between the bulk kinetic energy and the internal energy when the guide field is smaller than the reconnecting component. Based on this result, we then study the large-scale reconnection acceleration by solving the Parker's transport equation in a background reconnecting flow provided by MHD simulations. Due to the compression effect, the simulations suggest fast particle acceleration to high energies in the reconnection layer. This study clarifies the nature of particle acceleration in reconnection layer, and may be important to understand particle acceleration and plasma energization during solar flares.

A simple and inexpensive image analysis technique to study the effect of disintegrants concentration and diluents type on disintegration.

PubMed

Berardi, Alberto; Bisharat, Lorina; Blaibleh, Anaheed; Pavoni, Lucia; Cespi, Marco

2018-06-20

Tablets disintegration is often the result of a size expansion of the tablets. In this study, we quantified the extent and direction of size expansion of tablets during disintegration, using readily available techniques, i.e. a digital camera and a public domain image analysis software. After validating the method, the influence of disintegrants concentration and diluents type on kinetics and mechanisms of disintegration were studied. Tablets containing diluent, disintegrant (sodium starch glycolate-SSG, crospovidone-PVPP or croscarmellose sodium-CCS) and lubricant were prepared by direct compression. Projected area and aspect ratio of the tablets were monitored using image analysis techniques. The developed method could describe the kinetics and mechanisms of disintegration qualitatively and quantitatively. SSG and PVPP acted purely by swelling and shape recovery mechanisms. Instead, CCS worked by a combination of both mechanisms, the extent of which changed depending on its concentration and the diluent type. We anticipate that the method described here could provide a framework for the routine screening of tablets disintegration using readily available equipment. Copyright © 2018. Published by Elsevier Inc.

Tuning the free-energy landscape of a WW domain by temperature, mutation, and truncation

PubMed Central

Nguyen, Houbi; Jäger, Marcus; Moretto, Alessandro; Gruebele, Martin; Kelly, Jeffery W.

2003-01-01

The equilibrium unfolding of the Formin binding protein 28 (FBP) WW domain, a stable three-stranded β-sheet protein, can be described as reversible apparent two-state folding. Kinetics studied by laser temperature jump reveal a third state at temperatures below the midpoint of unfolding. The FBP free-energy surface can be tuned between three-state and two-state kinetics by changing the temperature, by truncation of the C terminus, or by selected point mutations. FBP WW domain is the smallest three-state folder studied to date and the only one that can be freely tuned between three-state and apparent two-state folding by several methods (temperature, truncation, and mutation). Its small size (28–37 residues), the availability of a quantitative reaction coordinate (φT), the fast folding time scale (10s of μs), and the tunability of the folding routes by small temperature or sequence changes make this system the ideal prototype for studying more subtle features of the folding free-energy landscape by simulations or analytical theory. PMID:12651955

Tuning the free-energy landscape of a WW domain by temperature, mutation, and truncation.

PubMed

Nguyen, Houbi; Jager, Marcus; Moretto, Alessandro; Gruebele, Martin; Kelly, Jeffery W

2003-04-01

The equilibrium unfolding of the Formin binding protein 28 (FBP) WW domain, a stable three-stranded beta-sheet protein, can be described as reversible apparent two-state folding. Kinetics studied by laser temperature jump reveal a third state at temperatures below the midpoint of unfolding. The FBP free-energy surface can be tuned between three-state and two-state kinetics by changing the temperature, by truncation of the C terminus, or by selected point mutations. FBP WW domain is the smallest three-state folder studied to date and the only one that can be freely tuned between three-state and apparent two-state folding by several methods (temperature, truncation, and mutation). Its small size (28-37 residues), the availability of a quantitative reaction coordinate (phi(T)), the fast folding time scale (10s of micros), and the tunability of the folding routes by small temperature or sequence changes make this system the ideal prototype for studying more subtle features of the folding free-energy landscape by simulations or analytical theory.

Kinetics of Surface-Mediated Fibrillization of Amyloid-β (12-28) Peptides.

PubMed

Lin, Yi-Chih; Li, Chen; Fakhraai, Zahra

2018-04-17

Surfaces or interfaces are considered to be key factors in facilitating the formation of amyloid fibrils under physiological conditions. In this report, we study the kinetics of the surface-mediated fibrillization (SMF) of an amyloid-β fragment (Aβ 12-28 ) on mica. We employ a spin-coating-based drying procedure to control the exposure time of the substrate to a low-concentration peptide solution and then monitor the fibril growth as a function of time via atomic force microscopy (AFM). The evolution of surface-mediated fibril growth is quantitatively characterized in terms of the length histogram of imaged fibrils and their surface concentration. A two-dimensional (2D) kinetic model is proposed to numerically simulate the length evolution of surface-mediated fibrils by assuming a diffusion-limited aggregation (DLA) process along with size-dependent rate constants. We find that both monomer and fibril diffusion on the surface are required to obtain length histograms as a function of time that resemble those observed in experiments. The best-fit simulated data can accurately describe the key features of experimental length histograms and suggests that the mobility of loosely bound amyloid species is crucial in regulating the kinetics of SMF. We determine that the mobility exponent for the size dependence of the DLA rate constants is α = 0.55 ± 0.05, which suggests that the diffusion of loosely bound surface fibrils roughly depends on the inverse of the square root of their size. These studies elucidate the influence of deposition rate and surface diffusion on the formation of amyloid fibrils through SMF. The method used here can be broadly adopted to study the diffusion and aggregation of peptides or proteins on various surfaces to investigate the role of chemical interactions in two-dimensional fibril formation and diffusion.

Exact kinetic energy enables accurate evaluation of weak interactions by the FDE-vdW method.

PubMed

Sinha, Debalina; Pavanello, Michele

2015-08-28

The correlation energy of interaction is an elusive and sought-after interaction between molecular systems. By partitioning the response function of the system into subsystem contributions, the Frozen Density Embedding (FDE)-vdW method provides a computationally amenable nonlocal correlation functional based on the adiabatic connection fluctuation dissipation theorem applied to subsystem density functional theory. In reproducing potential energy surfaces of weakly interacting dimers, we show that FDE-vdW, either employing semilocal or exact nonadditive kinetic energy functionals, is in quantitative agreement with high-accuracy coupled cluster calculations (overall mean unsigned error of 0.5 kcal/mol). When employing the exact kinetic energy (which we term the Kohn-Sham (KS)-vdW method), the binding energies are generally closer to the benchmark, and the energy surfaces are also smoother.

Multivariate curve resolution applied to kinetic-spectroscopic data matrices: Dye determination in foods by means of enzymatic oxidation.

PubMed

Boeris, Valeria; Arancibia, Juan A; Olivieri, Alejandro C

2017-07-01

In this work, the combination of chemometric techniques with kinetic-spectroscopic data allowed quantifying two dyes (tartrazine and carminic acid) in complex matrices as mustard, ketchup, asparagus soup powder, pumpkin soup powder, plum jam and orange-strawberry juice. Quantitative analysis was performed without the use of tedious sample pretreatment, due to the achievement of the second-order advantage. The results obtained showed an improvement in simplicity, speed and cost with respect to usual separation techniques, allowing to properly quantifying these dyes obtaining limits of detection below 0.6mgL -1 . In addition, to the best of our knowledge, is the first time that kinetic-spectroscopic data are obtained from the action of laccase for analytical purposes. Copyright © 2017 Elsevier B.V. All rights reserved.

Exact kinetic energy enables accurate evaluation of weak interactions by the FDE-vdW method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sinha, Debalina; Pavanello, Michele, E-mail: m.pavanello@rutgers.edu

2015-08-28

The correlation energy of interaction is an elusive and sought-after interaction between molecular systems. By partitioning the response function of the system into subsystem contributions, the Frozen Density Embedding (FDE)-vdW method provides a computationally amenable nonlocal correlation functional based on the adiabatic connection fluctuation dissipation theorem applied to subsystem density functional theory. In reproducing potential energy surfaces of weakly interacting dimers, we show that FDE-vdW, either employing semilocal or exact nonadditive kinetic energy functionals, is in quantitative agreement with high-accuracy coupled cluster calculations (overall mean unsigned error of 0.5 kcal/mol). When employing the exact kinetic energy (which we term themore » Kohn-Sham (KS)-vdW method), the binding energies are generally closer to the benchmark, and the energy surfaces are also smoother.« less

Development and Application of Quantitative Detection Method for Viral Hemorrhagic Septicemia Virus (VHSV) Genogroup IVa

PubMed Central

Kim, Jong-Oh; Kim, Wi-Sik; Kim, Si-Woo; Han, Hyun-Ja; Kim, Jin Woo; Park, Myoung Ae; Oh, Myung-Joo

2014-01-01

Viral hemorrhagic septicemia virus (VHSV) is a problematic pathogen in olive flounder (Paralichthys olivaceus) aquaculture farms in Korea. Thus, it is necessary to develop a rapid and accurate diagnostic method to detect this virus. We developed a quantitative RT-PCR (qRT-PCR) method based on the nucleocapsid (N) gene sequence of Korean VHSV isolate (Genogroup IVa). The slope and R2 values of the primer set developed in this study were −0.2928 (96% efficiency) and 0.9979, respectively. Its comparison with viral infectivity calculated by traditional quantifying method (TCID50) showed a similar pattern of kinetic changes in vitro and in vivo. The qRT-PCR method reduced detection time compared to that of TCID50, making it a very useful tool for VHSV diagnosis. PMID:24859343

Kinetic evidence for folding and unfolding intermediates in staphylococcal nuclease.

PubMed

Walkenhorst, W F; Green, S M; Roder, H

1997-05-13

The complex kinetic behavior commonly observed in protein folding studies suggests that a heterogeneous population of molecules exists in solution and that a number of discrete steps are involved in the conversion of unfolded molecules to the fully native form. A central issue in protein folding is whether any of these kinetic events represent conformational steps important for efficient folding rather than side reactions caused by slow steps such as proline isomerization or misfolding of the polypeptide chain. In order to address this question, we used stopped-flow fluorescence techniques to characterize the kinetic mechanism of folding and unfolding for a Pro- variant of SNase in which all six proline residues were replaced by glycines or alanines. Compared to the wild-type protein, which exhibits a series of proline-dependent slow folding phases, the folding kinetics of Pro- SNase were much simpler, which made quantitative kinetic analysis possible. Despite the absence of prolines or other complicating factors, the folding kinetics still contain several phases and exhibit a complex denaturant dependence. The GuHCl dependence of the major observable folding phase and a distinct lag in the appearance of the native state provide clear evidence for an early folding intermediate. The fluorescence of Trp140 in the alpha-helical domain is insensitive to the formation of this early intermediate, which is consistent with a partially folded state with a stable beta-domain and a largely disordered alpha-helical region. A second intermediate is required to model the kinetics of unfolding for the Pro- variant, which shows evidence for a denaturant-induced change in the rate-limiting unfolding step. With the inclusion of these two intermediates, we are able to completely model the major phase(s) in both folding and unfolding across a wide range of denaturant concentrations using a sequential four-state folding mechanism. In order to model the minor slow phase observed for the Pro- mutant, a six-state scheme containing a parallel pathway originating from a distinct unfolded state was required. The properties of this alternate unfolded conformation are consistent with those expected due to the presence of a non-prolyl cis peptide bond. To test the kinetic model, we used simulations based on the six-state scheme and were able to completely reproduce the folding kinetics for Pro- SNase across a range of denaturant concentrations.

Direct and Quantitative Characterization of Dynamic Ligand Exchange between Coordination-Driven Self-Assembled Supramolecular Polygons

PubMed Central

Zheng, Yao-Rong; Stang, Peter J.

2009-01-01

The direct observation of dynamic ligand exchange beween Pt-N coordination-driven self-assembled supramolecular polygons (triangles and rectangles) has been achieved using stable isotope labeling (1H/2D) of the pyridyl donors and electrospray ionization mass spectrometry (ESI-MS) together with NMR spectroscopy. Both the thermodynamic and kinetic aspects of such exchange processes have been established based on quantitative mass spectral results. Further investigation showed that the exchange is highly dependent on experimental conditions such as temperature, solvent, and the counter anions. PMID:19243144

Direct and quantitative characterization of dynamic ligand exchange between coordination-driven self-assembled supramolecular polygons.

PubMed

Zheng, Yao-Rong; Stang, Peter J

2009-03-18

The direct observation of dynamic ligand exchange between Pt-N coordination-driven self-assembled supramolecular polygons (triangles and rectangles) has been achieved using stable (1)H/(2)D isotope labeling of the pyridyl donors and electrospray ionization mass spectrometry combined with NMR spectroscopy. Both the thermodynamic and kinetic aspects of such exchange processes have been established on the basis of quantitative mass spectral results. Further investigation has shown that the exchange is highly dependent on experimental conditions such as temperature, solvent, and the counteranions.

Epigenetics meets mathematics: towards a quantitative understanding of chromatin biology.

PubMed

Steffen, Philipp A; Fonseca, João P; Ringrose, Leonie

2012-10-01

How fast? How strong? How many? So what? Why do numbers matter in biology? Chromatin binding proteins are forever in motion, exchanging rapidly between bound and free pools. How do regulatory systems whose components are in constant flux ensure stability and flexibility? This review explores the application of quantitative and mathematical approaches to mechanisms of epigenetic regulation. We discuss methods for measuring kinetic parameters and protein quantities in living cells, and explore the insights that have been gained by quantifying and modelling dynamics of chromatin binding proteins. Copyright © 2012 WILEY Periodicals, Inc.

Aggregation and Disaggregation of Senile Plaques in Alzheimer Disease

NASA Astrophysics Data System (ADS)

Cruz, L.; Urbanc, B.; Buldyrev, S. V.; Christie, R.; Gomez-Isla, T.; Havlin, S.; McNamara, M.; Stanley, H. E.; Hyman, B. T.

1997-07-01

We quantitatively analyzed, using laser scanning confocal microscopy, the three-dimensional structure of individual senile plaques in Alzheimer disease. We carried out the quantitative analysis using statistical methods to gain insights about the processes that govern Aβ peptide deposition. Our results show that plaques are complex porous structures with characteristic pore sizes. We interpret plaque morphology in the context of a new dynamical model based on competing aggregation and disaggregation processes in kinetic steady-state equilibrium with an additional diffusion process allowing Aβ deposits to diffuse over the surface of plaques.

Light-Mediated Kinetic Control Reveals the Temporal Effect of the Raf/MEK/ERK Pathway in PC12 Cell Neurite Outgrowth

PubMed Central

Zhang, Kai; Duan, Liting; Ong, Qunxiang; Lin, Ziliang; Varman, Pooja Mahendra; Sung, Kijung; Cui, Bianxiao

2014-01-01

It has been proposed that differential activation kinetics allows cells to use a common set of signaling pathways to specify distinct cellular outcomes. For example, nerve growth factor (NGF) and epidermal growth factor (EGF) induce different activation kinetics of the Raf/MEK/ERK signaling pathway and result in differentiation and proliferation, respectively. However, a direct and quantitative linkage between the temporal profile of Raf/MEK/ERK activation and the cellular outputs has not been established due to a lack of means to precisely perturb its signaling kinetics. Here, we construct a light-gated protein-protein interaction system to regulate the activation pattern of the Raf/MEK/ERK signaling pathway. Light-induced activation of the Raf/MEK/ERK cascade leads to significant neurite outgrowth in rat PC12 pheochromocytoma cell lines in the absence of growth factors. Compared with NGF stimulation, light stimulation induces longer but fewer neurites. Intermittent on/off illumination reveals that cells achieve maximum neurite outgrowth if the off-time duration per cycle is shorter than 45 min. Overall, light-mediated kinetic control enables precise dissection of the temporal dimension within the intracellular signal transduction network. PMID:24667437

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zaveri, Rahul A.; Shilling, John E.; Zelenyuk, Alla

Low bulk diffusivity inside viscous semisolid atmospheric secondary organic aerosol (SOA) can prolong equilibration time scale, but its broader impacts on aerosol growth and size distribution dynamics are poorly understood. In this article, we present quantitative insights into the effects of bulk diffusivity on the growth and evaporation kinetics of SOA formed under dry conditions from photooxidation of isoprene in the presence of a bimodal aerosol consisting of Aitken (ammonium sulfate) and accumulation (isoprene or α-pinene SOA) mode particles. Aerosol composition measurements and evaporation kinetics indicate that isoprene SOA is composed of several semivolatile organic compounds (SVOCs), with some reversiblymore » reacting to form oligomers. Model analysis shows that liquid-like bulk diffusivities can be used to fit the observed evaporation kinetics of accumulation mode particles but fail to explain the growth kinetics of bimodal aerosol by significantly under-predicting the evolution of the Aitken mode. In contrast, the semisolid scenario successfully reproduces both evaporation and growth kinetics, with the interpretation that hindered partitioning of SVOCs into large viscous particles effectively promotes the growth of smaller particles that have shorter diffusion time scales. This effect has important implications for the growth of atmospheric ultrafine particles to climatically active sizes.« less

Phytochemicals content and antioxidant properties of sea buckthorn (Hippophae rhamnoides L.) as affected by heat treatment - Quantitative spectroscopic and kinetic approaches.

PubMed

Ursache, Florentina-Mihaela; Ghinea, Ioana Otilia; Turturică, Mihaela; Aprodu, Iuliana; Râpeanu, Gabriela; Stănciuc, Nicoleta

2017-10-15

The effect of thermal processing (50-100°C) on the degradation of the phytochemicals in sea buckthorn extract was investigated using chromatographic, fluorescence and FT-IR spectroscopy techniques and degradation kinetics. Heating the sea buckthorn extract resulted in structural changes that led to red- or blue-shifts in maximum emission, depending on temperature and excitation wavelengths. The attenuated total reflectance analysis of the sea buckthorn extract revealed a satisfactory thermostability of compounds at high temperatures. A fractional conversion kinetic model was used to describe the mechanism of degradation in terms of rate and activation energy. Activation energies for total carotenoids, polyphenolic, flavonoids, and antioxidant activity were 8.45±0.93kJ/mol, 2.50±0.66kJ/mol, 22.50±7.26kJ/mol and 15.22±2.75kJ/mol, respectively. The kinetic parameters evidence a higher thermal stability of carotenoids and polyphenols, suggesting higher degradation rates for flavonoids and antioxidant activity. Our results demonstrate that industrial process optimization in terms of time-temperature combinations demands product specific kinetic data. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reactions driving conformational movements (molecular motors) in gels: conformational and structural chemical kinetics.

PubMed

Otero, Toribio F

2017-01-18

In this perspective the empirical kinetics of conducting polymers exchanging anions and solvent during electrochemical reactions to get dense reactive gels is reviewed. The reaction drives conformational movements of the chains (molecular motors), exchange of ions and solvent with the electrolyte and structural (relaxation, swelling, shrinking and compaction) gel changes. Reaction-driven structural changes are identified and quantified from electrochemical responses. The empirical reaction activation energy (E a ), the reaction coefficient (k) and the reaction orders (α and β) change as a function of the conformational energy variation during the reaction. This conformational energy becomes an empirical magnitude. E a , k, α and β include and provide quantitative conformational and structural information. The chemical kinetics becomes structural chemical kinetics (SCK) for reactions driving conformational movements of the reactants. The electrochemically stimulated conformational relaxation model describes empirical results and some results from the literature for biochemical reactions. In parallel the development of an emerging technological world of soft, wet, multifunctional and biomimetic tools and anthropomorphic robots driven by reactions of the constitutive material, as in biological organs, can be now envisaged being theoretically supported by the kinetic model.

A systematic investigation of aluminium ion speciation at high temperature. Part 1. Solution studies.

PubMed

Shafran, Kirill L; Perry, Carole C

2005-06-21

Speciation diagrams of aluminium ions in aqueous solution (0.2 M) at high temperature (90 degrees C) have been obtained from 48 h time-resolved multi-batch titration experiments monitored by 27Al NMR spectroscopy, potentiometry and dynamic light scattering. The quantitative speciation patterns and kinetic data obtained offer a dynamic picture of the distribution of soluble and insoluble Al species as a function of hydrolysis ratio h(h=[OH-]/[Al3+]) over a very broad range of conditions (-1.0 < or =h < or = 4.0). Monomeric, small oligomeric, tridecameric (the 'Al13-mer') and the recently characterised 30-meric aluminium species (the 'Al30-mer') as well as aluminium hydroxide have been identified and quantified. The Al13-mer species dominates over a relatively broad range of hydrolysis ratios (1.5 < or =h< or = 2.7) during the first 6 h of experiment, but are gradually replaced by Al30-mers at longer reaction times. Kinetic profiles indicate that the formation of the Al30-mer is limited by the disappearance of the Al13 species at mildly acidic conditions. The estimated rate constants of both hydrolytic processes show good internal correlation at h> or = 1.5. The effect of local perturbations leading to the formation of aluminium hydroxide below the electroneutrality point (h= 3.0) has been estimated quantitatively.

Quantitative in vivo fluorescence cross-correlation analyses highlight the importance of competitive effects in the regulation of protein-protein interactions.

PubMed

Sadaie, Wakako; Harada, Yoshie; Matsuda, Michiyuki; Aoki, Kazuhiro

2014-09-01

Computer-assisted simulation is a promising approach for clarifying complicated signaling networks. However, this approach is currently limited by a deficiency of kinetic parameters determined in living cells. To overcome this problem, we applied fluorescence cross-correlation spectrometry (FCCS) to measure dissociation constant (Kd) values of signaling molecule complexes in living cells (in vivo Kd). Among the pairs of fluorescent molecules tested, that of monomerized enhanced green fluorescent protein (mEGFP) and HaloTag-tetramethylrhodamine was most suitable for the measurement of in vivo Kd by FCCS. Using this pair, we determined 22 in vivo Kd values of signaling molecule complexes comprising the epidermal growth factor receptor (EGFR)-Ras-extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP) kinase pathway. With these parameters, we developed a kinetic simulation model of the EGFR-Ras-ERK MAP kinase pathway and uncovered a potential role played by stoichiometry in Shc binding to EGFR during the peak activations of Ras, MEK, and ERK. Intriguingly, most of the in vivo Kd values determined in this study were higher than the in vitro Kd values reported previously, suggesting the significance of competitive bindings inside cells. These in vivo Kd values will provide a sound basis for the quantitative understanding of signal transduction. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Dual fluorescence of excited state intra-molecular proton transfer of HBFO: mechanistic understanding, substituent and solvent effects.

PubMed

Yang, Wenjing; Chen, Xuebo

2014-03-07

A combined approach of the multiconfigurational perturbation theory with the Rice-Ramsperger-Kassel-Marcus methodology has been employed to calculate the minimum potential energy profiles and the rates of excited state intra-molecular proton transfer (ESIPT) for the WOLED material molecule of HBFO and its four meta- or para-substituted compounds in gas phase, acetonitrile and cyclohexane solvents. The kinetic control for these reactions is quantitatively determined and extensively studied on the basis of the accurate potential energy surfaces when the thermodynamic factor associated with the free energy change becomes negligible in the case of the existence of a significant barrier in the ESIPT process. These computational efforts contribute to a deep understanding of the ESIPT mechanism, dual emission characteristics, kinetic controlling factor, substituent and solvent effects for these material molecules. The white light emission is generated by the establishment of dynamic equilibrium between enol and keto forms in the charge transfer excited SCT((1)ππ*) state. The performance of white light emission is quantitatively demonstrated to be mainly sensitive to the molecular tailoring approach of the electronic properties of meta- or para- substituents by the modulation of the forward/backward ESIPT rate ratio. The quality of white light emission is slightly tunable through its surrounding solvent environment. These computational results will provide a useful strategy for the molecular design of OLED and WOLED materials.

Lipid-associated Oral Delivery: Mechanisms and Analysis of Oral Absorption Enhancement

PubMed Central

Rezhdo, Oljora; Speciner, Lauren; Carrier, Rebecca L.

2016-01-01

The majority of newly discovered oral drugs are poorly water soluble, and co-administration with lipids has proven effective in significantly enhancing bioavailability of some compounds with low aqueous solubility. Yet, lipid-based delivery technologies have not been widely employed in commercial oral products. Lipids can impact drug transport and fate in the gastrointestinal (GI) tract through multiple mechanisms including enhancement of solubility and dissolution kinetics, enhancement of permeation through the intestinal mucosa, and triggering drug precipitation upon lipid emulsion depletion (e.g., by digestion). The effect of lipids on drug absorption is currently not quantitatively predictable, in part due to the multiple complex dynamic processes that can be impacted by lipids. Quantitative mechanistic analysis of the processes significant to lipid system function and overall impact on drug absorption can aid understanding of drug-lipid interactions in the GI tract and exploitation of such interactions to achieve optimal lipid-based drug delivery. In this review, we discuss the impact of co-delivered lipids and lipid digestion on drug dissolution, partitioning, and absorption in the context of the experimental tools and associated kinetic expressions used to study and model these processes. The potential benefit of a systems-based consideration of the concurrent multiple dynamic processes occurring upon co-dosing lipids and drugs to predict the impact of lipids on drug absorption and enable rational design of lipid-based delivery systems is presented. PMID:27520734

TROSY-based z-exchange spectroscopy: application to the determination of the activation energy for intermolecular protein translocation between specific sites on different DNA molecules.

PubMed

Sahu, Debashish; Clore, G Marius; Iwahara, Junji

2007-10-31

A two-dimensional TROSY-based z-exchange 1H-15N correlation experiment for the quantitative analysis of kinetic processes in the slow exchange regime is presented. The pulse scheme converts the product operator terms Nz into 2NzHz and 2NzHz into -Nz in the middle of the z-mixing period, thereby suppressing the buildup of spurious semi-TROSY peaks arising from the different relaxation rates for the Nz and 2NzHz terms and simplifying the behavior of longitudinal magnetization for an exchanging system during the mixing period. Theoretical considerations and experimental data demonstrate that the TROSY-based z-exchange experiment permits quantitative determination of rate constants using the same procedure as that for the conventional non-TROSY 15Nz-exchange experiment. Line narrowing as a consequence of the use of the TROSY principle makes the method particularly suitable for kinetic studies at low temperature, thereby permitting activation energies to be extracted from data acquired over a wider temperature range. We applied this method to the investigation of the process whereby the HoxD9 homeodomain translocates between specific target sites on different DNA molecules via a direct transfer mechanism without going through the intermediary of free protein. The activation enthalpy for intermolecular translocation was determined to be 17 kcal/mol.

Disproportionation of a crystalline citrate salt of a developmental pharmaceutical compound: characterization of the kinetics using pH monitoring and online Raman spectroscopy plus quantitation of the crystalline free base form in binary physical mixtures using FT-Raman, XRPD and DSC.

PubMed

Skrdla, Peter J; Zhang, Dan

2014-03-01

The crystalline citrate salt (CS) of a developmental pharmaceutical compound, MK-Q, was investigated in this work from two different, but related, perspectives. In the first part of the paper, the apparent disproportionation kinetics were surveyed using two different slurry systems, one containing water and the other a pH 6.9 phosphate buffer, using time-dependent measurements of the solution pH or by acquiring online Raman spectra of the solids. While the CS is generally stable when stored as a solid under ambient conditions of temperature and humidity, its low pHmax (<3) facilitates rapid disproportionation in aqueous solution, particularly at higher pH values. The rate of disappearance of the CS was found to obey first-order (Noyes-Whitney/dissolution rate-limited) kinetics, however, the formation of the crystalline product form in the slurry system was observed to exhibit kinetics consistent with a heterogeneous nucleation-and-growth mechanism. In the second part of this paper, more sensitive offline measurements made using XRPD, DSC and FT-Raman spectroscopy were applied to the characterization of binary physical mixtures of the CS and free base (FB) crystalline forms of MK-Q to obtain a calibration curve for each technique. It was found that all calibration plots exhibited good linearity of response, with the limit of detection (LOD) for each technique estimated to be ≤7 wt% FB. While additional calibration curves would need to be constructed to allow for accurate quantitation in various slurry systems, the general feasibility of these techniques is demonstrated for detecting low levels of CS disproportionation. Copyright © 2013 Elsevier B.V. All rights reserved.

Quantitative interpretation of molecular dynamics simulations for X-ray photoelectron spectroscopy of aqueous solutions

NASA Astrophysics Data System (ADS)

Olivieri, Giorgia; Parry, Krista M.; Powell, Cedric J.; Tobias, Douglas J.; Brown, Matthew A.

2016-04-01

Over the past decade, energy-dependent ambient pressure X-ray photoelectron spectroscopy (XPS) has emerged as a powerful analytical probe of the ion spatial distributions at the vapor (vacuum)-aqueous electrolyte interface. These experiments are often paired with complementary molecular dynamics (MD) simulations in an attempt to provide a complete description of the liquid interface. There is, however, no systematic protocol that permits a straightforward comparison of the two sets of results. XPS is an integrated technique that averages signals from multiple layers in a solution even at the lowest photoelectron kinetic energies routinely employed, whereas MD simulations provide a microscopic layer-by-layer description of the solution composition near the interface. Here, we use the National Institute of Standards and Technology database for the Simulation of Electron Spectra for Surface Analysis (SESSA) to quantitatively interpret atom-density profiles from MD simulations for XPS signal intensities using sodium and potassium iodide solutions as examples. We show that electron inelastic mean free paths calculated from a semi-empirical formula depend strongly on solution composition, varying by up to 30% between pure water and concentrated NaI. The XPS signal thus arises from different information depths in different solutions for a fixed photoelectron kinetic energy. XPS signal intensities are calculated using SESSA as a function of photoelectron kinetic energy (probe depth) and compared with a widely employed ad hoc method. SESSA simulations illustrate the importance of accounting for elastic-scattering events at low photoelectron kinetic energies (<300 eV) where the ad hoc method systematically underestimates the preferential enhancement of anions over cations. Finally, some technical aspects of applying SESSA to liquid interfaces are discussed.

International Symposium on Gas Kinetics (8th) Held in Nottingham, England on 15-20 July 1984. Abstracts

DTIC Science & Technology

1984-07-20

Hall 16.00 -17.30 Tea, Hugh Stewart Hall 19.00 Buffet/Reception, Hugh Stewart Hall 19.00- 24.00 Cash bar in Hugh Stewart Hall Accesion For STATEMENT ...transfer involving highly vibrationally excited molecules J. R. Barker (SRI), T. C. Brown and K. D. King (Adelaide) 10.45-11.15 Coffee SESSION IV...D. King (Adelaide) and R. G. Gilbert (Sydney) 15.15-15.35 J4 Quantitative intermolecular energy transfer efficiencies from thermal studies C. D. Eley

Communication: Dominance of extreme statistics in a prototype many-body Brownian ratchet.

PubMed

Hohlfeld, Evan; Geissler, Phillip L

2014-10-28

Many forms of cell motility rely on Brownian ratchet mechanisms that involve multiple stochastic processes. We present a computational and theoretical study of the nonequilibrium statistical dynamics of such a many-body ratchet, in the specific form of a growing polymer gel that pushes a diffusing obstacle. We find that oft-neglected correlations among constituent filaments impact steady-state kinetics and significantly deplete the gel's density within molecular distances of its leading edge. These behaviors are captured quantitatively by a self-consistent theory for extreme fluctuations in filaments' spatial distribution.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leitner, Peter; Heyn, Martin F.; Kernbichler, Winfried

In this paper, the impact of momentum and energy conservation of the collision operator in the kinetic description for Resonant Magnetic Perturbations (RMPs) in a tokamak is studied. The particle conserving differential collision operator of Ornstein-Uhlenbeck type is supplemented with integral parts such that energy and momentum are conserved. The application to RMP penetration in a tokamak shows that energy conservation in the electron collision operator is important for the quantitative description of plasma shielding effects at the resonant surface. On the other hand, momentum conservation in the ion collision operator does not significantly change the results.

Continuous time Boolean modeling for biological signaling: application of Gillespie algorithm.

PubMed

Stoll, Gautier; Viara, Eric; Barillot, Emmanuel; Calzone, Laurence

2012-08-29

Mathematical modeling is used as a Systems Biology tool to answer biological questions, and more precisely, to validate a network that describes biological observations and predict the effect of perturbations. This article presents an algorithm for modeling biological networks in a discrete framework with continuous time. There exist two major types of mathematical modeling approaches: (1) quantitative modeling, representing various chemical species concentrations by real numbers, mainly based on differential equations and chemical kinetics formalism; (2) and qualitative modeling, representing chemical species concentrations or activities by a finite set of discrete values. Both approaches answer particular (and often different) biological questions. Qualitative modeling approach permits a simple and less detailed description of the biological systems, efficiently describes stable state identification but remains inconvenient in describing the transient kinetics leading to these states. In this context, time is represented by discrete steps. Quantitative modeling, on the other hand, can describe more accurately the dynamical behavior of biological processes as it follows the evolution of concentration or activities of chemical species as a function of time, but requires an important amount of information on the parameters difficult to find in the literature. Here, we propose a modeling framework based on a qualitative approach that is intrinsically continuous in time. The algorithm presented in this article fills the gap between qualitative and quantitative modeling. It is based on continuous time Markov process applied on a Boolean state space. In order to describe the temporal evolution of the biological process we wish to model, we explicitly specify the transition rates for each node. For that purpose, we built a language that can be seen as a generalization of Boolean equations. Mathematically, this approach can be translated in a set of ordinary differential equations on probability distributions. We developed a C++ software, MaBoSS, that is able to simulate such a system by applying Kinetic Monte-Carlo (or Gillespie algorithm) on the Boolean state space. This software, parallelized and optimized, computes the temporal evolution of probability distributions and estimates stationary distributions. Applications of the Boolean Kinetic Monte-Carlo are demonstrated for three qualitative models: a toy model, a published model of p53/Mdm2 interaction and a published model of the mammalian cell cycle. Our approach allows to describe kinetic phenomena which were difficult to handle in the original models. In particular, transient effects are represented by time dependent probability distributions, interpretable in terms of cell populations.

MODELING HEXAVALENT CHROMIUM REDUCTION IN GROUND- WATER IN FIELD-SCALE TRANSPORT AND LABORATORY BATCH EXPERIMENTS

EPA Science Inventory

A plausible and consistent model is developed to obtain a quantitative description of the gradual disappearance of hexavalent chromium (Cr(VI)) from groundwater in a small-scale field tracer test and in batch kinetic experiments using aquifer sediments under similar chemical cond...

Towards a Quantitative Analysis of the Temperature Dependence of Electron Attachment Processes

DTIC Science & Technology

2016-06-24

from an Arrhenius law should become pronounced when the temperature range would be extended considerably. Such experiments then were done as reported...in Ref. 13. Indeed marked deviations from the Arrhenius law became visible and, in addition, very good agreement with predictions from our “kinetic

QUANTITATIVE MODELING APPROACHES TO PREDICTING THE ACUTE NEUROTOXICITY OF VOLATILE ORGANIC COMPOUNDS (VOCS).

EPA Science Inventory

Lack of complete and appropriate human data requires prediction of the hazards for exposed human populations by extrapolation from available animal and in vitro data. Predictive models for the toxicity of chemicals can be constructed by linking kinetic and mode of action data uti...

Silver nanoparticles coated with natural polysaccharides as models to study AgNP aggregation kinetics using UV-Visible spectrophotometry upon discharge in complex environments.

PubMed

Lodeiro, Pablo; Achterberg, Eric P; Pampín, Joaquín; Affatati, Alice; El-Shahawi, Mohammed S

2016-01-01

This study provides quantitative information on the aggregation and dissolution behaviour of silver nanoparticles (AgNPs) upon discharge in fresh and sea waters, represented here as NaCl solutions of increasing ionic strength (up to 1M) and natural fjord waters. Natural polysaccharides, sodium alginate (ALG) and gum Arabic (GA), were used as coatings to stabilize the AgNPs and the compounds acted as models to study AgNP aggregation kinetics. The DLVO theory was used to quantitatively describe the interactions between the AgNPs. The stability of AgNPs was established using UV-Visible spectrophotometry, including unique information collected during the first seconds of the aggregaton process. Alginate coating resulted in a moderate stabilization of AgNPs in terms of critical coagulation concentration (~82mM NaCl) and a low dissolution of <10% total Ag in NaCl solutions up to 1M. Gum Arabic coated AgNPs were more strongly stabilized, with ~7-30% size increase up to 77mM NaCl, but only when the silver ion content initially present in solution was low (<10% total Ag). The ALG and GA coated AgNPs showed a strongly enhanced stability in natural fjord waters (ca. 5h required to reduce the area of the surface plasmon resonance band (SPRB) by two fold) compared with NaCl at an equivalent ionic strength (1-2min period for a two fold SPRB reduction). This is ascribed to a stabilizing effect from dissolved organic matter present in natural fjord waters. Interestingly, for AgNP-GA solutions with 40% of total silver present as unreacted silver ions in the NP stock solution, fast aggregation kinetics were observed in NaCl solutions (SPRB area was reduced by ca. 50% within 40-150min), with even more rapid removal in fjord waters, attributed to the high amount of silver-chloride charged species, that interact with the NP coating and/or organic matter and reduce the NPs stabilization. Copyright © 2015 Elsevier B.V. All rights reserved.

Quantitative confirmation of diffusion-limited oxidation theories

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gillen, K.T.; Clough, R.L.

1990-01-01

Diffusion-limited (heterogeneous) oxidation effects are often important for studies of polymer degradation. Such effects are common in polymers subjected to ionizing radiation at relatively high dose rate. To better understand the underlying oxidation processes and to aid in the planning of accelerated aging studies, it would be desirable to be able to monitor and quantitatively understand these effects. In this paper, we briefly review a theoretical diffusion approach which derives model profiles for oxygen surrounded sheets of material by combining oxygen permeation rates with kinetically based oxygen consumption expressions. The theory leads to a simple governing expression involving the oxygenmore » consumption and permeation rates together with two model parameters {alpha} and {beta}. To test the theory, gamma-initiated oxidation of a sheet of commercially formulated EPDM rubber was performed under conditions which led to diffusion-limited oxidation. Profile shapes from the theoretical treatments are shown to accurately fit experimentally derived oxidation profiles. In addition, direct measurements on the same EPDM material of the oxygen consumption and permeation rates, together with values of {alpha} and {beta} derived from the fitting procedure, allow us to quantitatively confirm for the first time the governing theoretical relationship. 17 refs., 3 figs.« less

Validation of Bayesian analysis of compartmental kinetic models in medical imaging.

PubMed

Sitek, Arkadiusz; Li, Quanzheng; El Fakhri, Georges; Alpert, Nathaniel M

2016-10-01

Kinetic compartmental analysis is frequently used to compute physiologically relevant quantitative values from time series of images. In this paper, a new approach based on Bayesian analysis to obtain information about these parameters is presented and validated. The closed-form of the posterior distribution of kinetic parameters is derived with a hierarchical prior to model the standard deviation of normally distributed noise. Markov chain Monte Carlo methods are used for numerical estimation of the posterior distribution. Computer simulations of the kinetics of F18-fluorodeoxyglucose (FDG) are used to demonstrate drawing statistical inferences about kinetic parameters and to validate the theory and implementation. Additionally, point estimates of kinetic parameters and covariance of those estimates are determined using the classical non-linear least squares approach. Posteriors obtained using methods proposed in this work are accurate as no significant deviation from the expected shape of the posterior was found (one-sided P>0.08). It is demonstrated that the results obtained by the standard non-linear least-square methods fail to provide accurate estimation of uncertainty for the same data set (P<0.0001). The results of this work validate new methods for a computer simulations of FDG kinetics. Results show that in situations where the classical approach fails in accurate estimation of uncertainty, Bayesian estimation provides an accurate information about the uncertainties in the parameters. Although a particular example of FDG kinetics was used in the paper, the methods can be extended for different pharmaceuticals and imaging modalities. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Dynamics and Kinetics Study of "In-Water" Chemical Reactions by Enhanced Sampling of Reactive Trajectories.

PubMed

Zhang, Jun; Yang, Y Isaac; Yang, Lijiang; Gao, Yi Qin

2015-11-12

High potential energy barriers and engagement of solvent coordinates set challenges for in silico studies of chemical reactions, and one is quite commonly limited to study reactions along predefined reaction coordinate(s). A systematic protocol, QM/MM MD simulations using enhanced sampling of reactive trajectories (ESoRT), is established to quantitatively study chemical transitions in complex systems. A number of trajectories for Claisen rearrangement in water and toluene were collected and analyzed, respectively. Evidence was found that the bond making and breaking during this reaction are concerted processes in solutions, preferentially through a chairlike configuration. Water plays an important dynamic role that helps stabilize the transition sate, and the dipole-dipole interaction between water and the solute also lowers the transition barrier. The calculated rate coefficient is consistent with the experimental measurement. Compared with water, the reaction pathway in toluene is "narrower" and the reaction rate is slower by almost three orders of magnitude due to the absence of proper interactions to stabilize the transition state. This study suggests that the "in-water" nature of the Claisen rearrangement in aqueous solution influences its thermodynamics, kinetics, as well as dynamics.

Carbonate-mediated Fe(II) oxidation in the air-cathode fuel cell: a kinetic model in terms of Fe(II) speciation.

PubMed

Song, Wei; Zhai, Lin-Feng; Cui, Yu-Zhi; Sun, Min; Jiang, Yuan

2013-06-06

Due to the high redox activity of Fe(II) and its abundance in natural waters, the electro-oxidation of Fe(II) can be found in many air-cathode fuel cell systems, such as acid mine drainage fuel cells and sediment microbial fuel cells. To deeply understand these iron-related systems, it is essential to elucidate the kinetics and mechanisms involved in the electro-oxidation of Fe(II). This work aims to develop a kinetic model that adequately describes the electro-oxidation process of Fe(II) in air-cathode fuel cells. The speciation of Fe(II) is incorporated into the model, and contributions of individual Fe(II) species to the overall Fe(II) oxidation rate are quantitatively evaluated. The results show that the kinetic model can accurately predict the electro-oxidation rate of Fe(II) in air-cathode fuel cells. FeCO3, Fe(OH)2, and Fe(CO3)2(2-) are the most important species determining the electro-oxidation kinetics of Fe(II). The Fe(II) oxidation rate is primarily controlled by the oxidation of FeCO3 species at low pH, whereas at high pH Fe(OH)2 and Fe(CO3)2(2-) are the dominant species. Solution pH, carbonate concentration, and solution salinity are able to influence the electro-oxidation kinetics of Fe(II) through changing both distribution and kinetic activity of Fe(II) species.

Metabolic Mapping: Quantitative Enzyme Cytochemistry and Histochemistry to Determine the Activity of Dehydrogenases in Cells and Tissues.

PubMed

Molenaar, Remco J; Khurshed, Mohammed; Hira, Vashendriya V V; Van Noorden, Cornelis J F

2018-05-26

Altered cellular metabolism is a hallmark of many diseases, including cancer, cardiovascular diseases and infection. The metabolic motor units of cells are enzymes and their activity is heavily regulated at many levels, including the transcriptional, mRNA stability, translational, post-translational and functional level. This complex regulation means that conventional quantitative or imaging assays, such as quantitative mRNA experiments, Western Blots and immunohistochemistry, yield incomplete information regarding the ultimate activity of enzymes, their function and/or their subcellular localization. Quantitative enzyme cytochemistry and histochemistry (i.e., metabolic mapping) show in-depth information on in situ enzymatic activity and its kinetics, function and subcellular localization in an almost true-to-nature situation. We describe a protocol to detect the activity of dehydrogenases, which are enzymes that perform redox reactions to reduce cofactors such as NAD(P) + and FAD. Cells and tissue sections are incubated in a medium that is specific for the enzymatic activity of one dehydrogenase. Subsequently, the dehydrogenase that is the subject of investigation performs its enzymatic activity in its subcellular site. In a chemical reaction with the reaction medium, this ultimately generates blue-colored formazan at the site of the dehydrogenase's activity. The formazan's absorbance is therefore a direct measure of the dehydrogenase's activity and can be quantified using monochromatic light microscopy and image analysis. The quantitative aspect of this protocol enables researchers to draw statistical conclusions from these assays. Besides observational studies, this technique can be used for inhibition studies of specific enzymes. In this context, studies benefit from the true-to-nature advantages of metabolic mapping, giving in situ results that may be physiologically more relevant than in vitro enzyme inhibition studies. In all, metabolic mapping is an indispensable technique to study metabolism at the cellular or tissue level. The technique is easy to adopt, provides in-depth, comprehensive and integrated metabolic information and enables rapid quantitative analysis.

Monitoring and quantitative assessment of tumor burden using in vivo bioluminescence imaging

NASA Astrophysics Data System (ADS)

Chen, Chia-Chi; Hwang, Jeng-Jong; Ting, Gann; Tseng, Yun-Long; Wang, Shyh-Jen; Whang-Peng, Jaqueline

2007-02-01

In vivo bioluminescence imaging (BLI) is a sensitive imaging modality that is rapid and accessible, and may comprise an ideal tool for evaluating tumor growth. In this study, the kinetic of tumor growth has been assessed in C26 colon carcinoma bearing BALB/c mouse model. The ability of BLI to noninvasively quantitate the growth of subcutaneous tumors transplanted with C26 cells genetically engineered to stably express firefly luciferase and herpes simplex virus type-1 thymidine kinase (C26/ tk-luc). A good correlation ( R2=0.998) of photon emission to the cell number was found in vitro. Tumor burden and tumor volume were monitored in vivo over time by quantitation of photon emission using Xenogen IVIS 50 and standard external caliper measurement, respectively. At various time intervals, tumor-bearing mice were imaged to determine the correlation of in vivo BLI to tumor volume. However, a correlation of BLI to tumor volume was observed when tumor volume was smaller than 1000 mm 3 ( R2=0.907). γ Scintigraphy combined with [ 131I]FIAU was another imaging modality used for verifying the previous results. In conclusion, this study showed that bioluminescence imaging is a powerful and quantitative tool for the direct assay to monitor tumor growth in vivo. The dual reporter genes transfected tumor-bearing animal model can be applied in the evaluation of the efficacy of new developed anti-cancer drugs.

The role of surface oxides on hydrogen sorption kinetics in titanium thin films

NASA Astrophysics Data System (ADS)

Hadjixenophontos, Efi; Michalek, Lukas; Roussel, Manuel; Hirscher, Michael; Schmitz, Guido

2018-05-01

Titanium is presently discussed as a catalyst to accelerate the hydrogenation kinetics of hydrogen storage materials. It is however known that H absorption in Ti decisively depends on the surface conditions (presence or absence of the natural surface oxide). In this work, we use Ti thin films of controlled thickness (50-800 nm) as a convenient tool for quantifying the atomic transport. XRD and TEM investigations allow us to follow the hydrogenation progress inside the film. Hydrogenation of TiO2/Ti bi-layers is studied at 300 °C, for different durations (10 s to 600 min) and at varying pressures of pure H2 atmosphere. Under these conditions, the hydrogenation is found to be linear in time. By comparing films with and without TiO2, as well as by studying the pressure dependence of hydrogenation, it is demonstrated that hydrogen transport across the oxide represents the decisive kinetic barrier rather than the splitting of H2 molecules at the surface. Hydrogenation appears by a layer-like reaction initiated by heterogeneous nucleation at the backside interface to the substrate. The linear growth constant and the H diffusion coefficient inside the oxide are quantified, as well as a reliable lower bound to the hydrogen diffusion coefficient in Ti is derived. The pressure dependence of hydrogen absorption is quantitatively modelled.

Thermodynamic and kinetic studies of biosorption of iron and manganese from aqueous medium using rice husk ash

NASA Astrophysics Data System (ADS)

Adekola, F. A.; Hodonou, D. S. S.; Adegoke, H. I.

2016-11-01

The adsorption behavior of rice husk ash with respect to manganese and iron has been studied by batch methods to consider its application for water and waste water treatment. The optimum conditions of adsorption were determined by investigating the effect of initial metal ion concentration, contact time, adsorbent dose, pH value of aqueous solution and temperature. Adsorption equilibrium time was observed at 120 min. The adsorption efficiencies were found to be pH dependent. The equilibrium adsorption experimental data were found to fit the Langmuir, Freundlich and Temkin isotherms for iron, but fitted only Langmuir isotherm for manganese. The pseudo-second order kinetic model was found to describe the manganese and iron kinetics more effectively. The thermodynamic experiment revealed that the adsorption processes involving both metals were exothermic. The adsorbent was finally applied to typical raw water with initial manganese and iron concentrations of 3.38 mg/l for Fe and 6.28 mg/l, respectively, and the removal efficiency was 100 % for Mn and 70 % for Fe. The metal ions were desorbed from the adsorbent using 0.01 M HCl, it was found to quantitatively remove 67 and 86 % of Mn and Fe, respectively, within 2 h. The results revealed that manganese and iron are considerably adsorbed on the adsorbent and could be an economic method for the removal of these metals from aqueous solutions.

Final Report: Mechanisms of sputter ripple formation: coupling among energetic ions, surface kinetics, stress and composition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chason, Eric; Shenoy, Vivek

Self-organized pattern formation enables the creation of nanoscale surface structures over large areas based on fundamental physical processes rather than an applied template. Low energy ion bombardment is one such method that induces the spontaneous formation of a wide variety of interesting morphological features (e.g., sputter ripples and/or quantum dots). This program focused on the processes controlling sputter ripple formation and the kinetics controlling the evolution of surfaces and nanostructures in high flux environments. This was done by using systematic, quantitative experiments to measure ripple formation under a variety of processing conditions coupled with modeling to interpret the results.

Label-Free, LC-MS-Based Assays to Quantitate Small-Molecule Antagonist Binding to the Mammalian BLT1 Receptor.

PubMed

Chen, Xun; Stout, Steven; Mueller, Uwe; Boykow, George; Visconti, Richard; Siliphaivanh, Phieng; Spencer, Kerrie; Presland, Jeremy; Kavana, Michael; Basso, Andrea D; McLaren, David G; Myers, Robert W

2017-08-01

We have developed and validated label-free, liquid chromatography-mass spectrometry (LC-MS)-based equilibrium direct and competition binding assays to quantitate small-molecule antagonist binding to recombinant human and mouse BLT1 receptors expressed in HEK 293 cell membranes. Procedurally, these binding assays involve (1) equilibration of the BLT1 receptor and probe ligand, with or without a competitor; (2) vacuum filtration through cationic glass fiber filters to separate receptor-bound from free probe ligand; and (3) LC-MS analysis in selected reaction monitoring mode for bound probe ligand quantitation. Two novel, optimized probe ligands, compounds 1 and 2, were identified by screening 20 unlabeled BLT1 antagonists for direct binding. Saturation direct binding studies confirmed the high affinity, and dissociation studies established the rapid binding kinetics of probe ligands 1 and 2. Competition binding assays were established using both probe ligands, and the affinities of structurally diverse BLT1 antagonists were measured. Both binding assay formats can be executed with high specificity and sensitivity and moderate throughput (96-well plate format) using these approaches. This highly versatile, label-free method for studying ligand binding to membrane-associated receptors should find broad application as an alternative to traditional methods using labeled ligands.

Quantitative fluorescence correlation spectroscopy on DNA in living cells

NASA Astrophysics Data System (ADS)

Hodges, Cameron; Kafle, Rudra P.; Meiners, Jens-Christian

2017-02-01

FCS is a fluorescence technique conventionally used to study the kinetics of fluorescent molecules in a dilute solution. Being a non-invasive technique, it is now drawing increasing interest for the study of more complex systems like the dynamics of DNA or proteins in living cells. Unlike an ordinary dye solution, the dynamics of macromolecules like proteins or entangled DNA in crowded environments is often slow and subdiffusive in nature. This in turn leads to longer residence times of the attached fluorophores in the excitation volume of the microscope and artifacts from photobleaching abound that can easily obscure the signature of the molecular dynamics of interest and make quantitative analysis challenging.We discuss methods and procedures to make FCS applicable to quantitative studies of the dynamics of DNA in live prokaryotic and eukaryotic cells. The intensity autocorrelation is computed function from weighted arrival times of the photons on the detector that maximizes the information content while simultaneously correcting for the effect of photobleaching to yield an autocorrelation function that reflects only the underlying dynamics of the sample. This autocorrelation function in turn is used to calculate the mean square displacement of the fluorophores attached to DNA. The displacement data is more amenable to further quantitative analysis than the raw correlation functions. By using a suitable integral transform of the mean square displacement, we can then determine the viscoelastic moduli of the DNA in its cellular environment. The entire analysis procedure is extensively calibrated and validated using model systems and computational simulations.

Nonequilibrium phase coexistence and criticality near the second explosion limit of hydrogen combustion

NASA Astrophysics Data System (ADS)

Newcomb, Lucas B.; Alaghemandi, Mohammad; Green, Jason R.

2017-07-01

While hydrogen is a promising source of clean energy, the safety and optimization of hydrogen technologies rely on controlling ignition through explosion limits: pressure-temperature boundaries separating explosive behavior from comparatively slow burning. Here, we show that the emergent nonequilibrium chemistry of combustible mixtures can exhibit the quantitative features of a phase transition. With stochastic simulations of the chemical kinetics for a model mechanism of hydrogen combustion, we show that the boundaries marking explosive domains of kinetic behavior are nonequilibrium critical points. Near the pressure of the second explosion limit, these critical points terminate the transient coexistence of dynamical phases—one that autoignites and another that progresses slowly. Below the critical point temperature, the chemistry of these phases is indistinguishable. In the large system limit, the pseudo-critical temperature converges to the temperature of the second explosion limit derived from mass-action kinetics.

ER-PM Contacts Define Actomyosin Kinetics for Proper Contractile Ring Assembly.

PubMed

Zhang, Dan; Bidone, Tamara C; Vavylonis, Dimitrios

2016-03-07

The cortical endoplasmic reticulum (ER), an elaborate network of tubules and cisternae [1], establishes contact sites with the plasma membrane (PM) through tethering machinery involving a set of conserved integral ER proteins [2]. The physiological consequences of forming ER-PM contacts are not fully understood. Here, we reveal a kinetic restriction role of ER-PM contacts over ring compaction process for proper actomyosin ring assembly in Schizosaccharomyces pombe. We show that fission yeast cells deficient in ER-PM contacts exhibit aberrant equatorial clustering of actin cables during ring assembly and are particularly susceptible to compromised actin filament crosslinking activity. Using quantitative image analyses and computer simulation, we demonstrate that ER-PM contacts function to modulate the distribution of ring components and to constrain their compaction kinetics. We propose that ER-PM contacts have evolved as important physical modulators to ensure robust ring assembly. Copyright © 2016 Elsevier Ltd. All rights reserved.

Kinetics of ATP hydrolysis catalyzed by isolated TF1 and reconstituted TF0F1 ATPase.

PubMed

Rögner, M; Gräber, P

1986-09-01

The rate of ATP hydrolysis catalyzed by isolated TF1 and reconstituted TF0F1 was measured as a function of the ATP concentration in the presence of inhibitors [ADP, Pi and 3'-O-(1-naphthoyl)ATP]. ATP hydrolysis can be described by Michaelis-Menten kinetics with Km(TF1) = 390 microM and Km (TF0F1) = 180 microM. The inhibition constants are for ADP Ki(TF1) = 20 microM and Ki(TF0F1) = 100 microM, for 3'-O-(1-naphthoyl)ATP Ki(TF1) = 150 microM and Ki(TF0F1) = 3 microM, and for Pi Ki(TF1) = 60 mM. From these results it is concluded that upon binding of TF0 to TF1 the mechanism of ATP hydrolysis catalyzed by TF1 is not changed qualitatively; however, the kinetic constants differ quantitatively.

Nonlinear machine learning and design of reconfigurable digital colloids.

PubMed

Long, Andrew W; Phillips, Carolyn L; Jankowksi, Eric; Ferguson, Andrew L

2016-09-14

Digital colloids, a cluster of freely rotating "halo" particles tethered to the surface of a central particle, were recently proposed as ultra-high density memory elements for information storage. Rational design of these digital colloids for memory storage applications requires a quantitative understanding of the thermodynamic and kinetic stability of the configurational states within which information is stored. We apply nonlinear machine learning to Brownian dynamics simulations of these digital colloids to extract the low-dimensional intrinsic manifold governing digital colloid morphology, thermodynamics, and kinetics. By modulating the relative size ratio between halo particles and central particles, we investigate the size-dependent configurational stability and transition kinetics for the 2-state tetrahedral (N = 4) and 30-state octahedral (N = 6) digital colloids. We demonstrate the use of this framework to guide the rational design of a memory storage element to hold a block of text that trades off the competing design criteria of memory addressability and volatility.

Crystallization of hard spheres revisited. I. Extracting kinetics and free energy landscape from forward flux sampling.

PubMed

Richard, David; Speck, Thomas

2018-03-28

We investigate the kinetics and the free energy landscape of the crystallization of hard spheres from a supersaturated metastable liquid though direct simulations and forward flux sampling. In this first paper, we describe and test two different ways to reconstruct the free energy barriers from the sampled steady state probability distribution of cluster sizes without sampling the equilibrium distribution. The first method is based on mean first passage times, and the second method is based on splitting probabilities. We verify both methods for a single particle moving in a double-well potential. For the nucleation of hard spheres, these methods allow us to probe a wide range of supersaturations and to reconstruct the kinetics and the free energy landscape from the same simulation. Results are consistent with the scaling predicted by classical nucleation theory although a quantitative fit requires a rather large effective interfacial tension.

Role of small oligomers on the amyloidogenic aggregation free-energy landscape.

PubMed

He, Xianglan; Giurleo, Jason T; Talaga, David S

2010-01-08

We combine atomic-force-microscopy particle-size-distribution measurements with earlier measurements on 1-anilino-8-naphthalene sulfonate, thioflavin T, and dynamic light scattering to develop a quantitative kinetic model for the aggregation of beta-lactoglobulin into amyloid. We directly compare our simulations to the population distributions provided by dynamic light scattering and atomic force microscopy. We combine species in the simulation according to structural type for comparison with fluorescence fingerprint results. The kinetic model of amyloidogenesis leads to an aggregation free-energy landscape. We define the roles of and propose a classification scheme for different oligomeric species based on their location in the aggregation free-energy landscape. We relate the different types of oligomers to the amyloid cascade hypothesis and the toxic oligomer hypothesis for amyloid-related diseases. We discuss existing kinetic mechanisms in terms of the different types of oligomers. We provide a possible resolution to the toxic oligomer-amyloid coincidence.

Ultrasonic evidence of hydrophobic interactions. Effect of ultrasound on benzoin condensation and some other reactions in aqueous ethanol.

PubMed

Tuulmets, Ants; Hagu, Hannes; Salmar, Siim; Cravotto, Giancarlo; Järv, Jaak

2007-03-29

The kinetics of KCN-catalyzed benzoin condensation of benzaldehyde in water and ethanol-water binary mixtures was investigated both under ultrasound at 22 kHz and without sonication. Thermodynamic activation parameters were calculated from kinetic data obtained at 35, 50, and 65 degrees C. Evidence that ultrasound can retard reactions is reported and hence a direct proof that sonochemical processes occur in the bulk solution. Former results and literature data for ester hydrolyses and tert-butyl chloride solvolysis are involved in the discussion. A quantitative relationship between sonication effects and the hydrophobicity of reagents is presented for the first time. Ultrasound affects hydrophobic interactions with the solvent, which are not manifested in conventional kinetics. When it suppresses the stabilization of the encounter complexes between reagents, sonication hinders the reaction but accelerates it when it perturbs the hydrophobic stabilization of the ground state of a reagent.

Crystallization of hard spheres revisited. I. Extracting kinetics and free energy landscape from forward flux sampling

NASA Astrophysics Data System (ADS)

Richard, David; Speck, Thomas

2018-03-01

We investigate the kinetics and the free energy landscape of the crystallization of hard spheres from a supersaturated metastable liquid though direct simulations and forward flux sampling. In this first paper, we describe and test two different ways to reconstruct the free energy barriers from the sampled steady state probability distribution of cluster sizes without sampling the equilibrium distribution. The first method is based on mean first passage times, and the second method is based on splitting probabilities. We verify both methods for a single particle moving in a double-well potential. For the nucleation of hard spheres, these methods allow us to probe a wide range of supersaturations and to reconstruct the kinetics and the free energy landscape from the same simulation. Results are consistent with the scaling predicted by classical nucleation theory although a quantitative fit requires a rather large effective interfacial tension.

Acid Gas Stability of Zeolitic Imidazolate Frameworks: Generalized Kinetic and Thermodynamic Characteristics

DOE PAGES

Bhattacharyya, Souryadeep; Han, Rebecca; Kim, Wun -Gwi; ...

2018-05-29

Here, acid gases such as SO 2 and CO 2 are present in many environments in which the use of nanoporous metal-organic frameworks (MOFs) is envisaged. Among metal-organic frameworks, zeolitic imidazolate frameworks (ZIFs) have been extensively explored as membranes or adsorbents. However, there is little systematic knowledge of the effects of acid gas exposure on the structure of ZIFs, in particular the mechanistic aspects of ZIF degradation by acid gases as well as the effects of ZIF crystal topology and linker composition on their stability. Here we present a generalized and quantitative investigation of the kinetic and thermodynamic acid gasmore » stability of a diverse range of ZIF materials. The stability of 16 ZIFs (of SOD, RHO, ANA, and GME topologies) under different environments – humid air, liquid water, and acid gases CO 2 and SO 2 (dry, humid, and aqueous) – are investigated by a suite of experimental and computational methods. The kinetics of ZIF degradation under exposure to humid SO 2 is studied in detail, and effective rate constants for acid gas degradation of ZIFs are reported for the first time. Remarkably, the kinetics of degradation of the diverse ZIFs correlate strongly with the linker pKa and ZIF water adsorption in a manner contrary to that expected from previous predictions in the literature. Furthermore, we find that the material ZIF-71 (RHO topology) shows much higher stability relative to the other ZIFs in humid SO 2 and CO 2 environments.« less

Acid Gas Stability of Zeolitic Imidazolate Frameworks: Generalized Kinetic and Thermodynamic Characteristics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhattacharyya, Souryadeep; Han, Rebecca; Kim, Wun -Gwi

Here, acid gases such as SO 2 and CO 2 are present in many environments in which the use of nanoporous metal-organic frameworks (MOFs) is envisaged. Among metal-organic frameworks, zeolitic imidazolate frameworks (ZIFs) have been extensively explored as membranes or adsorbents. However, there is little systematic knowledge of the effects of acid gas exposure on the structure of ZIFs, in particular the mechanistic aspects of ZIF degradation by acid gases as well as the effects of ZIF crystal topology and linker composition on their stability. Here we present a generalized and quantitative investigation of the kinetic and thermodynamic acid gasmore » stability of a diverse range of ZIF materials. The stability of 16 ZIFs (of SOD, RHO, ANA, and GME topologies) under different environments – humid air, liquid water, and acid gases CO 2 and SO 2 (dry, humid, and aqueous) – are investigated by a suite of experimental and computational methods. The kinetics of ZIF degradation under exposure to humid SO 2 is studied in detail, and effective rate constants for acid gas degradation of ZIFs are reported for the first time. Remarkably, the kinetics of degradation of the diverse ZIFs correlate strongly with the linker pKa and ZIF water adsorption in a manner contrary to that expected from previous predictions in the literature. Furthermore, we find that the material ZIF-71 (RHO topology) shows much higher stability relative to the other ZIFs in humid SO 2 and CO 2 environments.« less

Subtle Differences in Virus Composition Affect Disinfection Kinetics and Mechanisms

PubMed Central

Sigstam, Thérèse; Gannon, Greg; Cascella, Michele; Pecson, Brian M.; Wigginton, Krista Rule

2013-01-01

Viral disinfection kinetics have been studied in depth, but the molecular-level inactivation mechanisms are not understood. Consequently, it is difficult to predict the disinfection behavior of nonculturable viruses, even when related, culturable viruses are available. The objective of this work was to determine how small differences in the composition of the viral genome and proteins impact disinfection. To this end, we investigated the inactivation of three related bacteriophages (MS2, fr, and GA) by UV254, singlet oxygen (1O2), free chlorine (FC), and chlorine dioxide (ClO2). Genome damage was quantified by PCR, and protein damage was assessed by quantitative matrix-assisted laser desorption ionization (MALDI) mass spectrometry. ClO2 caused great variability in the inactivation kinetics between viruses and was the only treatment that did not induce genome damage. The inactivation kinetics were similar for all viruses when treated with disinfectants possessing a genome-damaging component (FC, 1O2, and UV254). On the protein level, UV254 subtly damaged MS2 and fr capsid proteins, whereas GA's capsid remained intact. 1O2 oxidized a methionine residue in MS2 but did not affect the other two viruses. In contrast, FC and ClO2 rapidly degraded the capsid proteins of all three viruses. Protein composition alone could not explain the observed degradation trends; instead, molecular dynamics simulations indicated that degradation is dictated by the solvent-accessible surface area of individual amino acids. Finally, despite the similarities of the three viruses investigated, their mode of inactivation by a single disinfectant varied. This explains why closely related viruses can exhibit drastically different inactivation kinetics. PMID:23542618

KINETIC ENERGY AND MASS DISTRIBUTIONS FOR NUCLEAR FISSION AT MODERATE EXCITATION ENERGY (thesis)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burnett, D.S.

1963-10-01

Fission fragment kinetic energy measurements using semiconductor detectors were made for the alpha-induced fission of Au/sup 197/, Bi/sup 209/, Th/ sup 232/, and U/sup 238/ at alpha energi es of 21 to 65 Mev. The data were recorded as the number of events at fragment energies E/sub 1/ and E/sub 2/, N(E/ sub 1/,E/sub 2/). The data were then transformed into mass--total kinetic energy maps and analyzed by means of moments. The Bi and Au data are in good agreement with quantitative theoretical predictions from the liquid drop model available for the lighter elements. The U and Th data aremore » discussed in terms of qualitative ideas that have been proposed to explain the properties of the fission process for the heavier elements. The changes in the U and Th mass and total kinetic energy distributions with excitation energy are emphasized. Pulse- height energy relations for the detectors used were obtained by a detailed comparison of detector and time-offlight results for the spontaneous fission of Cf/sup 252/. 54 references. (auth)« less

Experimental and Computational Interrogation of Fast SCR Mechanism and Active Sites on H-Form SSZ-13

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Sichi; Zheng, Yang; Gao, Feng

Experiment and density functional theory (DFT) models are combined to develop a unified, quantitative model of the mechanism and kinetics of fast selective catalytic reduction (SCR) of NO/NO2 mixtures over H-SSZ-13 zeolite. Rates, rate orders, and apparent activation energies collected under differential conditions reveal two distinct kinetic regimes. First-principles thermodynamics simulations are used to determine the relative coverages of free Brønsted sites, chemisorbed NH4+ and physisorbed NH3 as a function of reaction conditions. First-principles metadynamics calculations show that all three sites can contribute to the rate-limiting N-N bond forming step in fast SCR. The results are used to parameterize amore » kinetic model that encompasses the full range of reaction conditions and recovers observed rate orders and apparent activation energies. Observed kinetic regimes are related to changes in most-abundant surface intermediates. Financial support was provided by the National Science Foundation GAOLI program under award number 1258690-CBET. We thank the Center for Research Computing at Notre« less

Curing kinetics of visible light curing dental resin composites investigated by dielectric analysis (DEA).

PubMed

Steinhaus, Johannes; Hausnerova, Berenika; Haenel, Thomas; Großgarten, Mandy; Möginger, Bernhard

2014-03-01

During the curing process of light curing dental composites the mobility of molecules and molecule segments is reduced leading to a significant increase of the viscosity as well as the ion viscosity. Thus, the kinetics of the curing behavior of 6 different composites was derived from dielectric analysis (DEA) using especially redesigned flat sensors with interdigit comb electrodes allowing for irradiation at the top side and measuring the ion viscosity at the bottom side. As the ion viscosities of dental composites change 1-3 orders of magnitude during the curing process, DEA provides a sensitive approach to evaluate their curing behavior, especially in the phase of undisturbed chain growth. In order to determine quantitative kinetic parameters a kinetic model is presented and examined for the evaluation of the ion viscosity curves. From the obtained results it is seen that DEA might be employed in the investigation of the primary curing process, the quality assurance of ingredients as well as the control of processing stability of the light curing dental composites. Copyright © 2014 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Kinetically limited weathering at low denudation rates in semi-arid climates

NASA Astrophysics Data System (ADS)

Vanacker, V.; Schoonejans, J.; Opfergelt, S.; Ameijeiras-Marino, Y.; Christl, M.

2016-12-01

On Earth, the Critical Zone supports terrestrial life, being the near-surface environment where interactions between the atmosphere, lithosphere, hydrosphere, and biosphere take place Quantitative understanding of the interaction between mechanical rock breakdown, chemical weathering, and physical erosion is essential for unraveling Earth's biogeochemical cycles. In this study, we explore the role of soil water balance on regulating soil chemical weathering under water deficit regimes. Weathering rates and intensities were evaluated for nine soil profiles located on convex ridge crests of three mountain ranges in the Spanish Betic Cordillera. We present and compare quantitative information on soil weathering, chemical depletion and total denudation that were derived based on geochemical mass balance, 10Be cosmogenic nuclides and U-series disequilibria. Soil production rates determined based on U-series isotopes (238U, 234U, 230Th and 226Ra) are of the same order of magnitude as 10Be-derived denudation rates, suggesting steady state soil thickness, in two out of three sampling sites. The chemical weathering intensities are relatively low (˜5 to 30% of the total denudation of the soil) and negatively correlated with the magnitude of the water deficit in soils. Soil weathering extents increase (nonlinearly) with soil thickness and decrease with increasing surface denudation rates, consistent with kinetically limited or controlled weathering. Our study suggests that soil residence time and water availability limit weathering processes in semi-arid climates, which has not been validated previously with field data. An important implication of this finding is that climatic regimes may strongly regulate soil weathering by modulating soil solute fluxes.

Bifurcation and extinction limit of stretched premixed flames with chain-branching intermediate kinetics and radiative loss

NASA Astrophysics Data System (ADS)

Zhang, Huangwei; Chen, Zheng

2018-05-01

Premixed counterflow flames with thermally sensitive intermediate kinetics and radiation heat loss are analysed within the framework of large activation energy. Unlike previous studies considering one-step global reaction, two-step chemistry consisting of a chain branching reaction and a recombination reaction is considered here. The correlation between the flame front location and stretch rate is derived. Based on this correlation, the extinction limit and bifurcation characteristics of the strained premixed flame are studied, and the effects of fuel and radical Lewis numbers as well as radiation heat loss are examined. Different flame regimes and their extinction characteristics can be predicted by the present theory. It is found that fuel Lewis number affects the flame bifurcation qualitatively and quantitatively, whereas radical Lewis number only has a quantitative influence. Stretch rates at the stretch and radiation extinction limits respectively decrease and increase with fuel Lewis number before the flammability limit is reached, while the radical Lewis number shows the opposite tendency. In addition, the relation between the standard flammability limit and the limit derived from the strained near stagnation flame is affected by the fuel Lewis number, but not by the radical Lewis number. Meanwhile, the flammability limit increases with decreased fuel Lewis number, but with increased radical Lewis number. Radical behaviours at flame front corresponding to flame bifurcation and extinction are also analysed in this work. It is shown that radical concentration at the flame front, under extinction stretch rate condition, increases with radical Lewis number but decreases with fuel Lewis number. It decreases with increased radiation loss.

Utilizing time-lapse micro-CT-correlated bisphosphonate binding kinetics and soft tissue-derived input functions to differentiate site-specific changes in bone metabolism in vivo.

PubMed

Tower, R J; Campbell, G M; Müller, M; Glüer, C C; Tiwari, S

2015-05-01

The turnover of bone is a tightly regulated process between bone formation and resorption to ensure skeletal homeostasis. This process differs between bone types, with trabecular bone often associated with higher turnover than cortical bone. Analyses of bone by micro-computed tomography (micro-CT) reveal changes in structure and mineral content, but are limited in the study of metabolic activity at a single time point, while analyses of serum markers can reveal changes in bone metabolism, but cannot delineate the origin of any aberrant findings. To obtain a site-specific assessment of bone metabolic status, bisphosphonate binding kinetics were utilized. Using a fluorescently-labeled bisphosphonate, we show that early binding kinetics monitored in vivo using fluorescent molecular tomography (FMT) can monitor changes in bone metabolism in response to bone loss, stimulated by ovariectomy (OVX), or bone gain, resulting from treatment with the anabolic bone agent parathyroid hormone (PTH), and is capable of distinguishing different, metabolically distinct skeletal sites. Using time-lapse micro-CT, longitudinal bone turnover was quantified. The spine showed a significantly greater percent resorbing volume and surface in response to OVX, while mice treated with PTH showed significantly greater resorbing volume per bone surface in the spine and significantly greater forming surfaces in the knee. Correlation studies between binding kinetics and micro-CT suggest that forming surfaces, as assessed by time-lapse micro-CT, are preferentially reflected in the rate constant values while forming and resorbing bone volumes primarily affect plateau values. Additionally, we developed a blood pool correction method which now allows for quantitative multi-compartment analyses to be conducted using FMT. These results further expand our understanding of bisphosphonate binding and the use of bisphosphonate binding kinetics as a tool to monitor site-specific changes in bone metabolism in vivo. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Factor analysis for delineation of organ structures, creation of in- and output functions, and standardization of multicenter kinetic modeling

NASA Astrophysics Data System (ADS)

Schiepers, Christiaan; Hoh, Carl K.; Dahlbom, Magnus; Wu, Hsiao-Ming; Phelps, Michael E.

1999-05-01

PET imaging can quantify metabolic processes in-vivo; this requires the measurement of an input function which is invasive and labor intensive. A non-invasive, semi-automated, image based method of input function generation would be efficient, patient friendly, and allow quantitative PET to be applied routinely. A fully automated procedure would be ideal for studies across institutions. Factor analysis (FA) was applied as processing tool for definition of temporally changing structures in the field of view. FA has been proposed earlier, but the perceived mathematical difficulty has prevented widespread use. FA was utilized to delineate structures and extract blood and tissue time-activity-curves (TACs). These TACs were used as input and output functions for tracer kinetic modeling, the results of which were compared with those from an input function obtained with serial blood sampling. Dynamic image data of myocardial perfusion studies with N-13 ammonia, O-15 water, or Rb-82, cancer studies with F-18 FDG, and skeletal studies with F-18 fluoride were evaluated. Correlation coefficients of kinetic parameters obtained with factor and plasma input functions were high. Linear regression usually furnished a slope near unity. Processing time was 7 min/patient on an UltraSPARC. Conclusion: FA can non-invasively generate input functions from image data eliminating the need for blood sampling. Output (tissue) functions can be simultaneously generated. The method is simple, requires no sophisticated operator interaction and has little inter-operator variability. FA is well suited for studies across institutions and standardized evaluations.

Longitudinal studies of the 18F-FDG kinetics after ipilimumab treatment in metastatic melanoma patients based on dynamic FDG PET/CT.

PubMed

Sachpekidis, Christos; Anwar, Hoda; Winkler, Julia K; Kopp-Schneider, Annette; Larribere, Lionel; Haberkorn, Uwe; Hassel, Jessica C; Dimitrakopoulou-Strauss, Antonia

2018-06-05

Immunotherapy has raised the issue of appropriate treatment response evaluation, due to the unique mechanism of action of the immunotherapeutic agents. Aim of this analysis is to evaluate the potential role of quantitative analysis of 2-deoxy-2-( 18 F)fluoro-D-glucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) data in monitoring of patients with metastatic melanoma undergoing ipilimumab therapy. 25 patients with unresectable metastatic melanoma underwent dynamic PET/CT (dPET/CT) of the thorax and upper abdomen as well as static, whole body PET/CT with 18 F-FDG before the start of ipilimumab treatment (baseline PET/CT), after two cycles of treatment (interim PET/CT) and at the end of treatment after four cycles (late PET/CT). The evaluation of dPET/CT studies was based on semi-quantitative (standardized uptake value, SUV) calculation as well as quantitative analysis, based on two-tissue compartment modeling and a fractal approach. Patients' best clinical response, assessed at a mean of 59 weeks, was used as reference. According to their best clinical response, patients were dichotomized in those demonstrating clinical benefit (CB, n = 16 patients) and those demonstrating no clinical benefit (no-CB, n = 9 patients). No statistically significant differences were observed between CB and no-CB regarding either semi-quantitative or quantitative parameters in all scans. On contrary, the application of the recently introduced PET response evaluation criteria for immunotherapy (PERCIMT) led to a correct classification rate of 84% (21/25 patients). Quantitative analysis of 18 F-FDG PET data does not provide additional information in treatment response evaluation of metastatic melanoma patients receiving ipilimumab. PERCIMT criteria correlated better with clinical response.

The oxidation/reduction kinetics of the plastoquinone pool controls the appearance of the I-peak in the O-J-I-P chlorophyll fluorescence rise: effects of various electron acceptors.

PubMed

Joly, David; Carpentier, Robert

2007-07-27

Quantitative analysis of the fluorescence induction (FI) rise was used in this study to elucidate the complex effects of N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) on thylakoids. Reduced TMPD molecules, responsible for the ADRY agent effect, caused an increase in the amplitude of the O-J rise. Also, only oxidized TMPD molecules were shown to have the ability to bind the Q(B) pocket of photosystem II (PSII). On the other hand, the I-P rise was slowed in proportion with the oxidized TMPD concentration, inducing the clear appearance of the I-peak. While this property was previously thought to be unique to TMPD, this study shows that some artificial electron acceptors of PSII, silicomolybdate, 2,5-dichloro-p-benzoquinone, and phenyl-p-benzoquinone, have a similar effect. These results demonstrated a major role of the oxido-reduction kinetics of the PQ-pool in the resolution of J-I and I-P phases in the FI of isolated thylakoids.

Ultrasound-assisted extraction and quantitation of oils from Syzygium aromaticum flower bud (clove) with supercritical carbon dioxide.

PubMed

Yang, Yu-Chiao; Wei, Ming-Chi; Hong, Show-Jen

2014-01-03

This study evaluated ultrasound-assisted supercritical carbon dioxide (USC-CO2) extraction for determining the extraction yields of oils and the contents of eugenol, β-caryophyllene, eugenyl acetate and α-humulene from clove buds. Compared to traditional SC-CO2 extraction, USC-CO2 extraction might provide a 13.5% increase in the extraction yield for the oil while utilizing less severe operating parameters, such as temperature, pressure, CO2 flow rate and the time consumed by the process. Our results were comparable to those obtained using the heat reflux extraction method, though the yield was improved by 20.8% using USC-CO2. In kinetic studies, the USC-CO2 extraction of clove oil followed second-order kinetics. The activation energy for the oil extraction was 76.56kJ/mol. The USC-CO2 procedure facilitated the use of mild extraction conditions, improved extraction efficiency and the quality of products and is a potential method for industry. Copyright © 2013 Elsevier B.V. All rights reserved.

Investigating rate-limiting barriers to nanoscale nonviral gene transfer with nanobiophotonics

NASA Astrophysics Data System (ADS)

Chen, Hunter H.

Nucleic acids are a novel class of therapeutics poised to address many unmet clinical needs. Safe and efficient delivery remains a significant challenge that has delayed the realization of the full therapeutic potential of nucleic acids. Nanoscale nonviral vectors offer an attractive alternative to viral vectors as natural and synthetic polymers or polypeptides may be rationally designed to meet the unique demands of individual applications. A mechanistic understanding of cellular barriers is necessary to develop guidelines for designing custom gene carriers which are expected to greatly impact this delivery challenge. The work herein focused on the relationships among nanocomplex stability, intracellular trafficking and unpacking kinetics, and DNA degradation. Ultrasensitive nanosensors based on QD-FRET were developed to characterize the biophysical properties of nanocomplexes and study these rate-limiting steps. Quantitative image analysis enabled the distributions of the subpopulation of condensed or released DNA to be determined within the major cellular compartments encountered during gene transfer. The steady state stability and unpacking kinetics within these compartments were found to impact transgene expression, elucidating multiple design strategies to achieve efficient gene transfer. To address enzymatic barriers, a novel two-step QD-FRET nanosensor was developed to analyze unpacking and DNA degradation simultaneously, which has not been accomplished previously. Bioresponsive strategies such as disulfide crosslinking and thermosensitivity were evaluated by QD-FRET and quantitative compartmental analysis as case studies to determine appropriate design specifications for thiolated polymers and thermoresponsive polypeptides. Relevant nanobiophotonic tools were developed as a platform to study major rate-limiting barriers to nanomedicine and demonstrated the feasibility of using mechanistic information gained from these tools to guide the rational design of gene carriers and achieve the desired properties that enable efficient gene transfer.

Media Effects on Nitrosomonas Europaea Monochloramine Disinfection Kinetics Using Propidium Monoazide Quantitative Real-time PCR

EPA Science Inventory

Monochloramine use as a secondary disinfectant in the United States is predicted to increase to 57% of all surface and 7% of all ground water systems. With monochloramine addition, there is a risk of nitrification in the distribution system by ammonia-oxidizing bacteria (AOB). Ba...

Media effects on Nitrosomonas Europaea Monochloramine Disinfection Kinetics using Propidium Monoazide Quantitative Real-time PCR

EPA Science Inventory

Monochloramine use as a secondary disinfectant in the United States is predicted to increase to 57% of all surface and 7% of all ground water systems. With monochloramine addition, there is a risk of nitrification in the distribution system by ammonia-oxidizing bacteria (AOB). Ba...

Media Effects on Nitrosomonas Europaea Monochloramine Disinfection Kinetics Using Propidium Monoazide Quantitative Real-time PCR

EPA Science Inventory

Monochloramine use as a secondary disinfectant in the United States is predicted to increase to 57% of all surface and 7% of all ground water systems. With monochloramine addition, there is a risk of nitrification in the distribution system by ammonia-oxidizing bacteria (AOB). Ni...

QUANTITATIVE STRUCTURE—PROPERTY RELATIONSHIPS FOR ENHANCING PREDICTIONS OF SYNTHETIC ORGANIC CHEMICAL REMOVAL FROM DRINKING WATER BY GRANULAR ACTIVATED CARBON

EPA Science Inventory

A number of mathematical models have been developed to predict activated carbon column performance using single-solute isotherm data as inputs. Many assumptions are built into these models to account for kinetics of adsorption and competition for adsorption sites. This work...

Which Reaches the Bottom First?

ERIC Educational Resources Information Center

Solbes, Jordi; Tarin, Francisco

2008-01-01

A well-known classroom demonstration involves the rolling of hollow and solid objects down an incline. The fact that the objects roll at different rates can be used as a starting point in introducing students to rotational dynamics and rotational kinetic energy. In this paper we describe a simple quantitative version of the demonstration that is…

Monochloramine disinfection kinetics of Nitrosomonas europaea using propidium monoazide quantitative real-time PCR (PMA-qPCR)

EPA Science Inventory

As a result of the implementation of the Stage 1 and Stage 2 Disinfectants and Disinfection Byproduct Rules, monochloramine use as a secondary disinfectant in the United States is predicted to increase to 57% of all surface and 7% of all ground water treatment systems. In additi...

Functional and quantitative alterations in T lymphocyte subpopulations in acute toxoplasmosis.

PubMed

Luft, B J; Kansas, G; Engleman, E G; Remington, J S

1984-11-01

The cellular immune response to Toxoplasma gondii has been studied in 23 patients with acute toxoplasma infection. Abnormalities of T cell subpopulations included a marked and significant elevation in suppressor (Leu 2) T cells in patients with prolonged symptoms due to acute infection and either a decrease in the number of T helper cells or an increase in the number of suppressor cells--or both--in patients with asymptomatic lymphadenopathy. There was no significant difference in lymphocyte proliferation to phytohemagglutinin or pokeweed mitogen among the various groups tested. The peak lymphocyte response to toxoplasma antigen, however, was significantly depressed in patients with acute infection compared with that in chronically infected control patients. The kinetics of the depression were consistent with the induction of a non-Leu 2 suppressor cell. These results demonstrate marked quantitative alterations in T lymphocyte subpopulations and functional alterations of T cells to toxoplasma antigen during infection with T. gondii.

Burnett-Cattaneo continuum theory for shock waves.

PubMed

Holian, Brad Lee; Mareschal, Michel; Ravelo, Ramon

2011-02-01

We model strong shock-wave propagation, both in the ideal gas and in the dense Lennard-Jones fluid, using a refinement of earlier work, which accounts for the cold compression in the early stages of the shock rise by a nonlinear, Burnett-like, strain-rate dependence of the thermal conductivity, and relaxation of kinetic-temperature components on the hot, compressed side of the shock front. The relaxation of the disequilibrium among the three components of the kinetic temperature, namely, the difference between the component in the direction of a planar shock wave and those in the transverse directions, particularly in the region near the shock front, is accomplished at a much more quantitative level by a rigorous application of the Cattaneo-Maxwell relaxation equation to a reference solution, namely, the steady shock-wave solution of linear Navier-Stokes-Fourier theory, along with the nonlinear Burnett heat-flux term. Our new continuum theory is in nearly quantitative agreement with nonequilibrium molecular-dynamics simulations under strong shock-wave conditions, using relaxation parameters obtained from the reference solution. ©2011 American Physical Society

Quantitative analysis of desorption and decomposition kinetics of formic acid on Cu(111): The importance of hydrogen bonding between adsorbed species

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shiozawa, Yuichiro; Koitaya, Takanori; Mukai, Kozo

2015-12-21

Quantitative analysis of desorption and decomposition kinetics of formic acid (HCOOH) on Cu(111) was performed by temperature programmed desorption (TPD), X-ray photoelectron spectroscopy, and time-resolved infrared reflection absorption spectroscopy. The activation energy for desorption is estimated to be 53–75 kJ/mol by the threshold TPD method as a function of coverage. Vibrational spectra of the first layer HCOOH at 155.3 K show that adsorbed molecules form a polymeric structure via the hydrogen bonding network. Adsorbed HCOOH molecules are dissociated gradually into monodentate formate species. The activation energy for the dissociation into monodentate formate species is estimated to be 65.0 kJ/mol atmore » a submonolayer coverage (0.26 molecules/surface Cu atom). The hydrogen bonding between adsorbed HCOOH species plays an important role in the stabilization of HCOOH on Cu(111). The monodentate formate species are stabilized at higher coverages, because of the lack of vacant sites for the bidentate formation.« less

Stereodirectional Origin of anti-Arrhenius Kinetics for a Tetraatomic Hydrogen Exchange Reaction: Born-Oppenheimer Molecular Dynamics for OH + HBr.

PubMed

Coutinho, Nayara D; Aquilanti, Vincenzo; Silva, Valter H C; Camargo, Ademir J; Mundim, Kleber C; de Oliveira, Heibbe C B

2016-07-14

Among four-atom processes, the reaction OH + HBr → H2O + Br is one of the most studied experimentally: its kinetics has manifested an unusual anti-Arrhenius behavior, namely, a marked decrease of the rate constant as the temperature increases, which has intrigued theoreticians for a long time. Recently, salient features of the potential energy surface have been characterized and most kinetic aspects can be considered as satisfactorily reproduced by classical trajectory simulations. Motivation of the work reported in this paper is the investigation of the stereodirectional dynamics of this reaction as the prominent reason for the peculiar kinetics: we started in a previous Letter ( J. Phys. Chem. Lett. 2015 , 6 , 1553 - 1558 ) a first-principles Born-Oppenheimer "canonical" molecular dynamics approach. Trajectories are step-by-step generated on a potential energy surface quantum mechanically calculated on-the-fly and are thermostatically equilibrated to correspond to a specific temperature. Here, refinements of the method permitted a major increase of the number of trajectories and the consideration of four temperatures -50, +200, +350, and +500 K, for which the sampling of initial conditions allowed us to characterize the stereodynamical effect. The role is documented of the adjustment of the reactants' mutual orientation to encounter the entrance into the "cone of acceptance" for reactivity. The aperture angle of this cone is dictated by a range of directions of approach compatible with the formation of the specific HOH angle of the product water molecule; and consistently the adjustment is progressively less effective the higher the kinetic energy. Qualitatively, this emerging picture corroborates experiments on this reaction, involving collisions of aligned and oriented molecular beams, and covering a range of energies higher than the thermal ones. The extraction of thermal rate constants from this molecular dynamics approach is discussed and the systematic sampling of the canonical ensemble is indicated as needed for quantitative comparison with the kinetic experiments.

Kinetic modeling of electron transfer reactions in photosystem I complexes of various structures with substituted quinone acceptors.

PubMed

Milanovsky, Georgy E; Petrova, Anastasia A; Cherepanov, Dmitry A; Semenov, Alexey Yu

2017-09-01

The reduction kinetics of the photo-oxidized primary electron donor P 700 in photosystem I (PS I) complexes from cyanobacteria Synechocystis sp. PCC 6803 were analyzed within the kinetic model, which considers electron transfer (ET) reactions between P 700 , secondary quinone acceptor A 1 , iron-sulfur clusters and external electron donor and acceptors - methylviologen (MV), 2,3-dichloro-naphthoquinone (Cl 2 NQ) and oxygen. PS I complexes containing various quinones in the A 1 -binding site (phylloquinone PhQ, plastoquinone-9 PQ and Cl 2 NQ) as well as F X -core complexes, depleted of terminal iron-sulfur F A /F B clusters, were studied. The acceleration of charge recombination in F X -core complexes by PhQ/PQ substitution indicates that backward ET from the iron-sulfur clusters involves quinone in the A 1 -binding site. The kinetic parameters of ET reactions were obtained by global fitting of the P 700 + reduction with the kinetic model. The free energy gap ΔG 0 between F X and F A /F B clusters was estimated as -130 meV. The driving force of ET from A 1 to F X was determined as -50 and -220 meV for PhQ in the A and B cofactor branches, respectively. For PQ in A 1A -site, this reaction was found to be endergonic (ΔG 0  = +75 meV). The interaction of PS I with external acceptors was quantitatively described in terms of Michaelis-Menten kinetics. The second-order rate constants of ET from F A /F B , F X and Cl 2 NQ in the A 1 -site of PS I to external acceptors were estimated. The side production of superoxide radical in the A 1 -site by oxygen reduction via the Mehler reaction might comprise ≥0.3% of the total electron flow in PS I.

Studies on silicon NMR characterization and kinetic modeling of the structural evolution of siloxane-based materials and their applications in drug delivery and adsorption

NASA Astrophysics Data System (ADS)

Ambati, Jyothirmai

This dissertation presents studies of the synthetic processes and applications of siloxane-based materials. Kinetic investigations of bridged organoalkoxysilanes that are precursors to organic-inorganic hybrid polysilsesquioxanes are a primary focus. Quick gelation despite extensive cyclization is found during the polymerization of bridged silane precursors except for silanes with certain short bridges. This work is an attempt to characterize and understand some of the distinct features of bridged silanes using experimental characterization, kinetic modeling and simulation. In addition to this, the dissertation shows how the properties of siloxane-materials can be engineered for drug delivery and adsorption. The phase behavior of polymerizing mixtures is first investigated to identify the solutions that favor kinetic characterization. Microphase separation is found to cause gradual loss of NMR signal for certain initial compositions. Distortionless Enhancement by Polarization Transfer 29Si NMR is employed to identify the products of polymerization of some short-bridged silanes under no signal loss conditions. This technique requires knowing indirect 29Si-1H scalar coupling constants which sometimes cannot be measured due to second-order effects. However, the B3LYP density functional method with 6-31G basis set is found to predict accurate 29Si- 1H coupling constants of organoalkoxysilanes and siloxanes. The scalar coupling constants thus estimated are employed to resolve non-trivial coupled NMR spectra and quantitative kinetic modeling is performed using the DEPT Si NMR transients. In order to investigate the role of the organic bridging group, the structural evolution of bridged and non-bridged silanes are compared using Monte Carlo simulations. Kinetic and simulation models suggest that cyclization plays a key role right from the onset of polymerization for bridged silanes even more than in non-bridged silanes. The simulations indicate that the carbosiloxane rings formed from short-bridged precursors slow down but do not prevent gelation. The tuning of siloxane-based materials for adsorption technologies are also discussed here. In the first example, antioxidant enzyme loading is investigated as a means to reduce oxidative stress generated by silica nanoparticle drug carriers. Materials are engineered for promising enzyme loading and protection from proteolysis. Second, the potential of copper sulfate impregnation to enhance adsorption of ammonia by silica is explored by molecular simulation. KEYWORDS: Sol-gel Polymerization, Kinetic Investigation, Si NMR, Bridged Silanes, DFT Calculations.

Quantitative gait analysis in parkin disease: Possible role of dystonia.

PubMed

Castagna, Anna; Frittoli, Serena; Ferrarin, Maurizio; Del Sorbo, Francesca; Romito, Luigi M; Elia, Antonio E; Albanese, Alberto

2016-11-01

Parkin disease (PARK2, OMIM 602544) is an autosomal-recessive early-onset parkinsonism characterized by an early occurrence of lower limb dystonia. The aim of this study was to analyze spatiotemporal, kinematic, and kinetic gait parameters in patients with parkin disease in the OFF and ON conditions compared to healthy age-matched controls. Fifteen patients with parkin disease and 15 healthy age-matched controls were studied in a gait analysis laboratory with an integrated optoelectronic system. Spatiotemporal, kinematic, and kinetic gait parameters at a self-selected speed were recorded in the OFF and ON conditions. A jerk index was computed to quantify the possible reduction of smoothness of joint movements. Compared to controls, parkin patients had, either in the OFF or in the ON conditions, significant reduction of walking velocity, increased step width, and decreased percentage of double support. Kinematic analysis in both conditions showed: increased ankle dorsiflexion and knee flexion at the initial contact; maximal flexion and increased range of motion in mid stance; increased hip flexion and max extension in stance at pelvis; and increased mean tilt antiversion. Kinetics showed increased hip and knee power generation in stance in either condition. The jerk index was increased at all joints both in OFF and ON. There were no correlations between individual gait parameters and clinical ratings. Parkin patients have an abnormal gait pattern that does not vary between the OFF and the ON conditions. Variations recorded with instrumented analysis are more evident for kinematic than kinetic parameters at lower limbs. Severity of dystonia does not correlate with any individual kinematic parameter. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Kinetic analysis using low-molecular mass xyloglucan oligosaccharides defines the catalytic mechanism of a Populus xyloglucan endotransglycosylase

PubMed Central

Saura-Valls, Marc; Fauré, Régis; Ragàs, Sergi; Piens, Kathleen; Brumer, Harry; Teeri, Tuula T.; Cottaz, Sylvain; Driguez, Hugues; Planas, Antoni

2005-01-01

Plant XETs [XG (xyloglucan) endotransglycosylases] catalyse the transglycosylation from a XG donor to a XG or low-molecular-mass XG fragment as the acceptor, and are thought to be important enzymes in the formation and remodelling of the cellulose-XG three-dimensional network in the primary plant cell wall. Current methods to assay XET activity use the XG polysaccharide as the donor substrate, and present limitations for kinetic and mechanistic studies of XET action due to the polymeric and polydisperse nature of the substrate. A novel activity assay based on HPCE (high performance capillary electrophoresis), in conjunction with a defined low-molecular-mass XGO {XG oligosaccharide; (XXXGXXXG, where G=Glcβ1,4- and X=[Xylα1,6]Glcβ1,4-)} as the glycosyl donor and a heptasaccharide derivatized with ANTS [8-aminonaphthalene-1,3,6-trisulphonic acid; (XXXG-ANTS)] as the acceptor substrate was developed and validated. The recombinant enzyme PttXET16A from Populus tremula x tremuloides (hybrid aspen) was characterized using the donor/acceptor pair indicated above, for which preparative scale syntheses have been optimized. The low-molecular-mass donor underwent a single transglycosylation reaction to the acceptor substrate under initial-rate conditions, with a pH optimum at 5.0 and maximal activity between 30 and 40 °C. Kinetic data are best explained by a ping-pong bi-bi mechanism with substrate inhibition by both donor and acceptor. This is the first assay for XETs using a donor substrate other than polymeric XG, enabling quantitative kinetic analysis of different XGO donors for specificity, and subsite mapping studies of XET enzymes. PMID:16356166

Kinetic analysis using low-molecular mass xyloglucan oligosaccharides defines the catalytic mechanism of a Populus xyloglucan endotransglycosylase.

PubMed

Saura-Valls, Marc; Fauré, Régis; Ragàs, Sergi; Piens, Kathleen; Brumer, Harry; Teeri, Tuula T; Cottaz, Sylvain; Driguez, Hugues; Planas, Antoni

2006-04-01

Plant XETs [XG (xyloglucan) endotransglycosylases] catalyse the transglycosylation from a XG donor to a XG or low-molecular-mass XG fragment as the acceptor, and are thought to be important enzymes in the formation and remodelling of the cellulose-XG three-dimensional network in the primary plant cell wall. Current methods to assay XET activity use the XG polysaccharide as the donor substrate, and present limitations for kinetic and mechanistic studies of XET action due to the polymeric and polydisperse nature of the substrate. A novel activity assay based on HPCE (high performance capillary electrophoresis), in conjunction with a defined low-molecular-mass XGO {XG oligosaccharide; (XXXGXXXG, where G=Glcbeta1,4- and X=[Xylalpha1,6]Glcbeta1,4-)} as the glycosyl donor and a heptasaccharide derivatized with ANTS [8-aminonaphthalene-1,3,6-trisulphonic acid; (XXXG-ANTS)] as the acceptor substrate was developed and validated. The recombinant enzyme PttXET16A from Populus tremula x tremuloides (hybrid aspen) was characterized using the donor/acceptor pair indicated above, for which preparative scale syntheses have been optimized. The low-molecular-mass donor underwent a single transglycosylation reaction to the acceptor substrate under initial-rate conditions, with a pH optimum at 5.0 and maximal activity between 30 and 40 degrees C. Kinetic data are best explained by a ping-pong bi-bi mechanism with substrate inhibition by both donor and acceptor. This is the first assay for XETs using a donor substrate other than polymeric XG, enabling quantitative kinetic analysis of different XGO donors for specificity, and subsite mapping studies of XET enzymes.

Degradation of organic pollutants by Vacuum-Ultraviolet (VUV): Kinetic model and efficiency.

PubMed

Xie, Pengchao; Yue, Siyang; Ding, Jiaqi; Wan, Ying; Li, Xuchun; Ma, Jun; Wang, Zongping

2018-04-15

Vacuum-Ultraviolet (VUV), an efficient and green method to produce hydroxyl radical (•OH), is effective in degrading numerous organic contaminants in aqueous solution. Here, we proposed an effective and simple kinetic model to describe the degradation of organic pollutants in VUV system, by taking the •OH scavenging effects of formed organic intermediates as co-existing organic matter in whole. Using benzoic acid (BA) as a •OH probe, •OH was regarded vital for pollutant degradation in VUV system, and the thus developed model successfully predicted its degradation kinetics under different conditions. Effects of typical influencing factors such as BA concentrations and UV intensity were investigated quantitatively by the model. Temperature was found to be an important influencing factor in the VUV system, and the quantum yield of •OH showed a positive linear dependence on temperature. Impacts of humic acid (HA), alkalinity, chloride, and water matrices (realistic waters) on the oxidation efficiency were also examined. BA degradation was significantly inhibited by HA due to its scavenging of •OH, but was influenced much less by the alkalinity and chloride; high oxidation efficiency was still obtained in the realistic water. The degradation kinetics of three other typical micropollutants including bisphenol A (BPA), nitrobenzene (NB) and dimethyl phthalate (DMP), and the mixture of co-existing BA, BPA and DMP were further studied, and the developed model predicted the experimental data well, especially in realistic water. It is expected that this study will provide an effective approach to predict the degradation of organic micropollutants by the promising VUV system, and broaden the application of VUV system in water treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

On-Line Analysis and Kinetic Behavior of Arsenic Release during Coal Combustion and Pyrolysis.

PubMed

Shen, Fenghua; Liu, Jing; Zhang, Zhen; Dai, Jinxin

2015-11-17

The kinetic behavior of arsenic (As) release during coal combustion and pyrolysis in a fluidized bed was investigated by applying an on-line analysis system of trace elements in flue gas. This system, based on inductively coupled plasma optical emission spectroscopy (ICP-OES), was developed to measure trace elements concentrations in flue gas quantitatively and continuously. Obvious variations of arsenic concentration in flue gas were observed during coal combustion and pyrolysis, indicating strong influences of atmosphere and temperature on arsenic release behavior. Kinetic laws governing the arsenic release during coal combustion and pyrolysis were determined based on the results of instantaneous arsenic concentration in flue gas. A second-order kinetic law was determined for arsenic release during coal combustion, and the arsenic release during coal pyrolysis followed a fourth-order kinetic law. The results showed that the arsenic release rate during coal pyrolysis was faster than that during coal combustion. Thermodynamic calculations were carried out to identify the forms of arsenic in vapor and solid phases during coal combustion and pyrolysis, respectively. Ca3(AsO4)2 and Ca(AsO2)2 are the possible species resulting from As-Ca interaction during coal combustion. Ca(AsO2)2 is the most probable species during coal pyrolysis.

Iterative Addition of Kinetic Effects to Cold Plasma RF Wave Solvers

NASA Astrophysics Data System (ADS)

Green, David; Berry, Lee; RF-SciDAC Collaboration

2017-10-01

The hot nature of fusion plasmas requires a wave vector dependent conductivity tensor for accurate calculation of wave heating and current drive. Traditional methods for calculating the linear, kinetic full-wave plasma response rely on a spectral method such that the wave vector dependent conductivity fits naturally within the numerical method. These methods have seen much success for application to the well-confined core plasma of tokamaks. However, quantitative prediction of high power RF antenna designs for fusion applications has meant a requirement of resolving the geometric details of the antenna and other plasma facing surfaces for which the Fourier spectral method is ill-suited. An approach to enabling the addition of kinetic effects to the more versatile finite-difference and finite-element cold-plasma full-wave solvers was presented by where an operator-split iterative method was outlined. Here we expand on this approach, examine convergence and present a simplified kinetic current estimator for rapidly updating the right-hand side of the wave equation with kinetic corrections. This research used resources of the Oak Ridge Leadership Computing Facility at the Oak Ridge National Laboratory, which is supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC05-00OR22725.

Theoretical Analysis of Drug Dissolution: I. Solubility and Intrinsic Dissolution Rate.

PubMed

Shekunov, Boris; Montgomery, Eda Ross

2016-09-01

The first-principles approach presented in this work combines surface kinetics and convective diffusion modeling applied to compounds with pH-dependent solubility and in different dissolution media. This analysis is based on experimental data available for approximately 100 compounds of pharmaceutical interest. Overall, there is a linear relationship between the drug solubility and intrinsic dissolution rate expressed through the total kinetic coefficient of dissolution and dimensionless numbers defining the mass transfer regime. The contribution of surface kinetics appears to be significant constituting on average ∼20% resistance to the dissolution flux in the compendial rotating disk apparatus at 100 rpm. The surface kinetics contribution becomes more dominant under conditions of fast laminar or turbulent flows or in cases when the surface kinetic coefficient may decrease as a function of solution composition or pH. Limitations of the well-known convective diffusion equation for rotating disk by Levich are examined using direct computational modeling with simultaneous dissociation and acid-base reactions in which intrinsic dissolution rate is strongly dependent on pH profile and solution ionic strength. It is shown that concept of diffusion boundary layer does not strictly apply for reacting/interacting species and that thin-film diffusion models cannot be used quantitatively in general case. Copyright © 2016. Published by Elsevier Inc.

Systems biology from micro-organisms to human metabolic diseases: the role of detailed kinetic models.

PubMed

Bakker, Barbara M; van Eunen, Karen; Jeneson, Jeroen A L; van Riel, Natal A W; Bruggeman, Frank J; Teusink, Bas

2010-10-01

Human metabolic diseases are typically network diseases. This holds not only for multifactorial diseases, such as metabolic syndrome or Type 2 diabetes, but even when a single gene defect is the primary cause, where the adaptive response of the entire network determines the severity of disease. The latter may differ between individuals carrying the same mutation. Understanding the adaptive responses of human metabolism naturally requires a systems biology approach. Modelling of metabolic pathways in micro-organisms and some mammalian tissues has yielded many insights, qualitative as well as quantitative, into their control and regulation. Yet, even for a well-known pathway such as glycolysis, precise predictions of metabolite dynamics from experimentally determined enzyme kinetics have been only moderately successful. In the present review, we compare kinetic models of glycolysis in three cell types (African trypanosomes, yeast and skeletal muscle), evaluate their predictive power and identify limitations in our understanding. Although each of these models has its own merits and shortcomings, they also share common features. For example, in each case independently measured enzyme kinetic parameters were used as input. Based on these 'lessons from glycolysis', we will discuss how to make best use of kinetic computer models to advance our understanding of human metabolic diseases.

Non-classical nuclei and growth kinetics of Cr precipitates in FeCr alloys during ageing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Yulan; Hu, Shenyang Y.; Zhang, Lei

2014-01-10

In this manuscript, we quantitatively calculated the thermodynamic properties of critical nuclei of Cr precipitates in FeCr alloys. The concentration profiles of the critical nuclei and nucleation energy barriers were predicted by the constrained shrinking dimer dynamics (CSDD) method. It is found that Cr concentration distribution in the critical nuclei strongly depend on the overall Cr concentration as well as temperature. The critical nuclei are non-classical because the concentration in the nuclei is smaller than the thermodynamic equilibrium value. These results are in agreement with atomic probe observation. The growth kinetics of both classical and non-classical nuclei was investigated bymore » the phase field approach. The simulations of critical nucleus evolution showed a number of interesting phenomena: 1) a critical classical nucleus first shrinks toward its non-classical nucleus and then grows; 2) a non-classical nucleus has much slower growth kinetics at its earlier growth stage compared to the diffusion-controlled growth kinetics. 3) a critical classical nucleus grows faster at the earlier growth stage than the non-classical nucleus. All of these results demonstrate that it is critical to introduce the correct critical nuclei in order to correctly capture the kinetics of precipitation.« less

Parabolic quantitative structure-activity relationships and photodynamic therapy: application of a three-compartment model with clearance to the in vivo quantitative structure-activity relationships of a congeneric series of pyropheophorbide derivatives used as photosensitizers for photodynamic therapy.

PubMed

Potter, W R; Henderson, B W; Bellnier, D A; Pandey, R K; Vaughan, L A; Weishaupt, K R; Dougherty, T J

1999-11-01

An open three-compartment pharmacokinetic model was applied to the in vivo quantitative structure-activity relationship (QSAR) data of a homologous series of pyropheophorbide photosensitizers for photodynamic therapy (PDT). The physical model was a lipid compartment sandwiched between two identical aqueous compartments. The first compartment was assumed to clear irreversibly at a rate K0. The measured octanol-water partition coefficients, P(i) (where i is the number of carbons in the alkyl chain) and the clearance rate K0 determined the clearance kinetics of the drugs. Solving the coupled differential equations of the three-compartment model produced clearance kinetics for each of the sensitizers in each of the compartments. The third compartment was found to contain the target of PDT. This series of compounds is quite lipophilic. Therefore these drugs are found mainly in the second compartment. The drug level in the third compartment represents a small fraction of the tissue level and is thus not accessible to direct measurement by extraction. The second compartment of the model accurately predicted the clearance from the serum of mice of the hexyl ether of pyropheophorbide a, one member of this series of compounds. The diffusion and clearance rate constants were those found by fitting the pharmacokinetics of the third compartment to the QSAR data. This result validated the magnitude and mechanistic significance of the rate constants used to model the QSAR data. The PDT response to dose theory was applied to the kinetic behavior of the target compartment drug concentration. This produced a pharmacokinetic-based function connecting PDT response to dose as a function of time postinjection. This mechanistic dose-response function was fitted to published, single time point QSAR data for the pheophorbides. As a result, the PDT target threshold dose together with the predicted QSAR as a function of time postinjection was found.

Crystal-melt interface mobility in bcc Fe: Linking molecular dynamics to phase-field and phase-field crystal modeling

NASA Astrophysics Data System (ADS)

Guerdane, M.; Berghoff, M.

2018-04-01

By combining molecular dynamics (MD) simulations with phase-field (PF) and phase-field crystal (PFC) modeling we study collision-controlled growth kinetics from the melt for pure Fe. The MD/PF comparison shows, on the one hand, that the PF model can be properly designed to reproduce quantitatively different aspects of the growth kinetics and anisotropy of planar and curved solid-liquid interfaces. On the other hand, this comparison demonstrates the ability of classical MD simulations to predict morphology and dynamics of moving curved interfaces up to a length scale of about 0.15 μ m . After mapping the MD model to the PF one, the latter permits to analyze the separate contribution of different anisotropies to the interface morphology. The MD/PFC agreement regarding the growth anisotropy and morphology extends the trend already observed for the here used PFC model in describing structural and elastic properties of bcc Fe.

Progress in Studying Scintillator Proportionality: Phenomenological Model

NASA Astrophysics Data System (ADS)

Bizarri, G.; Cherepy, N. J.; Choong, W. S.; Hull, G.; Moses, W. W.; Payne, S. A.; Singh, J.; Valentine, J. D.; Vasilev, A. N.; Williams, R. T.

2009-08-01

We present a model to describe the origin of non-proportional dependence of scintillator light yield on the energy of an ionizing particle. The non-proportionality is discussed in terms of energy relaxation channels and their linear and non-linear dependences on the deposited energy. In this approach, the scintillation response is described as a function of the deposited energy deposition and the kinetic rates of each relaxation channel. This mathematical framework allows both a qualitative interpretation and a quantitative fitting representation of scintillation non-proportionality response as function of kinetic rates. This method was successfully applied to thallium doped sodium iodide measured with SLYNCI, a new facility using the Compton coincidence technique. Finally, attention is given to the physical meaning of the dominant relaxation channels, and to the potential causes responsible for the scintillation non-proportionality. We find that thallium doped sodium iodide behaves as if non-proportionality is due to competition between radiative recombinations and non-radiative Auger processes.

A highly versatile automatized setup for quantitative measurements of PHIP enhancements

NASA Astrophysics Data System (ADS)

Kiryutin, Alexey S.; Sauer, Grit; Hadjiali, Sara; Yurkovskaya, Alexandra V.; Breitzke, Hergen; Buntkowsky, Gerd

2017-12-01

The design and application of a versatile and inexpensive experimental extension to NMR spectrometers is described that allows to carry out highly reproducible PHIP experiments directly in the NMR sample tube, i.e. under PASADENA condition, followed by the detection of the NMR spectra of hyperpolarized products with high spectral resolution. Employing this high resolution it is feasible to study kinetic processes in the solution with high accuracy. As a practical example the dissolution of hydrogen gas in the liquid and the PHIP kinetics during the hydrogenation reaction of Fmoc-O-propargyl-L-tyrosine in acetone-d6 are monitored. The timing of the setup is fully controlled by the pulse-programmer of the NMR spectrometer. By flushing with an inert gas it is possible to efficiently quench the hydrogenation reaction in a controlled fashion and to detect the relaxation of hyperpolarization without a background reaction. The proposed design makes it possible to carry out PHIP experiments in an automatic mode and reliably determine the enhancement of polarized signals.

Geochemical Reaction Mechanism Discovery from Molecular Simulation

DOE PAGES

Stack, Andrew G.; Kent, Paul R. C.

2014-11-10

Methods to explore reactions using computer simulation are becoming increasingly quantitative, versatile, and robust. In this review, a rationale for how molecular simulation can help build better geochemical kinetics models is first given. We summarize some common methods that geochemists use to simulate reaction mechanisms, specifically classical molecular dynamics and quantum chemical methods and discuss their strengths and weaknesses. Useful tools such as umbrella sampling and metadynamics that enable one to explore reactions are discussed. Several case studies wherein geochemists have used these tools to understand reaction mechanisms are presented, including water exchange and sorption on aqueous species and mineralmore » surfaces, surface charging, crystal growth and dissolution, and electron transfer. The impact that molecular simulation has had on our understanding of geochemical reactivity are highlighted in each case. In the future, it is anticipated that molecular simulation of geochemical reaction mechanisms will become more commonplace as a tool to validate and interpret experimental data, and provide a check on the plausibility of geochemical kinetic models.« less

A time to search: finding the meaning of variable activation energy.

PubMed

Vyazovkin, Sergey

2016-07-28

This review deals with the phenomenon of variable activation energy frequently observed when studying the kinetics in the liquid or solid phase. This phenomenon commonly manifests itself through nonlinear Arrhenius plots or dependencies of the activation energy on conversion computed by isoconversional methods. Variable activation energy signifies a multi-step process and has a meaning of a collective parameter linked to the activation energies of individual steps. It is demonstrated that by using appropriate models of the processes, the link can be established in algebraic form. This allows one to analyze experimentally observed dependencies of the activation energy in a quantitative fashion and, as a result, to obtain activation energies of individual steps, to evaluate and predict other important parameters of the process, and generally to gain deeper kinetic and mechanistic insights. This review provides multiple examples of such analysis as applied to the processes of crosslinking polymerization, crystallization and melting of polymers, gelation, and solid-solid morphological and glass transitions. The use of appropriate computational techniques is discussed as well.

Ligand-induced type II interleukin-4 receptor dimers are sustained by rapid re-association within plasma membrane microcompartments

NASA Astrophysics Data System (ADS)

Richter, David; Moraga, Ignacio; Winkelmann, Hauke; Birkholz, Oliver; Wilmes, Stephan; Schulte, Markos; Kraich, Michael; Kenneweg, Hella; Beutel, Oliver; Selenschik, Philipp; Paterok, Dirk; Gavutis, Martynas; Schmidt, Thomas; Garcia, K. Christopher; Müller, Thomas D.; Piehler, Jacob

2017-07-01

The spatiotemporal organization of cytokine receptors in the plasma membrane is still debated with models ranging from ligand-independent receptor pre-dimerization to ligand-induced receptor dimerization occurring only after receptor uptake into endosomes. Here, we explore the molecular and cellular determinants governing the assembly of the type II interleukin-4 receptor, taking advantage of various agonists binding the receptor subunits with different affinities and rate constants. Quantitative kinetic studies using artificial membranes confirm that receptor dimerization is governed by the two-dimensional ligand-receptor interactions and identify a critical role of the transmembrane domain in receptor dimerization. Single molecule localization microscopy at physiological cell surface expression levels, however, reveals efficient ligand-induced receptor dimerization by all ligands, largely independent of receptor binding affinities, in line with the similar STAT6 activation potencies observed for all IL-4 variants. Detailed spatiotemporal analyses suggest that kinetic trapping of receptor dimers in actin-dependent microcompartments sustains robust receptor dimerization and signalling.

Helicase Stepping Investigated with One-Nucleotide Resolution Fluorescence Resonance Energy Transfer

NASA Astrophysics Data System (ADS)

Lin, Wenxia; Ma, Jianbing; Nong, Daguan; Xu, Chunhua; Zhang, Bo; Li, Jinghua; Jia, Qi; Dou, Shuoxing; Ye, Fangfu; Xi, Xuguang; Lu, Ying; Li, Ming

2017-09-01

Single-molecule Förster resonance energy transfer is widely applied to study helicases by detecting distance changes between a pair of dyes anchored to overhangs of a forked DNA. However, it has been lacking single-base pair (1-bp) resolution required for revealing stepping kinetics of helicases. We designed a nanotensioner in which a short DNA is bent to exert force on the overhangs, just as in optical or magnetic tweezers. The strategy improved the resolution of Förster resonance energy transfer to 0.5 bp, high enough to uncover differences in DNA unwinding by yeast Pif1 and E. coli RecQ whose unwinding behaviors cannot be differentiated by currently practiced methods. We found that Pif1 exhibits 1-bp-stepping kinetics, while RecQ breaks 1 bp at a time but sequesters the nascent nucleotides and releases them randomly. The high-resolution data allowed us to propose a three-parameter model to quantitatively interpret the apparently different unwinding behaviors of the two helicases which belong to two superfamilies.

Prediction of La0.6Sr0.4Co0.2Fe0.8O3 cathode microstructures during sintering: Kinetic Monte Carlo (KMC) simulations calibrated by artificial neural networks

NASA Astrophysics Data System (ADS)

Yan, Zilin; Kim, Yongtae; Hara, Shotaro; Shikazono, Naoki

2017-04-01

The Potts Kinetic Monte Carlo (KMC) model, proven to be a robust tool to study all stages of sintering process, is an ideal tool to analyze the microstructure evolution of electrodes in solid oxide fuel cells (SOFCs). Due to the nature of this model, the input parameters of KMC simulations such as simulation temperatures and attempt frequencies are difficult to identify. We propose a rigorous and efficient approach to facilitate the input parameter calibration process using artificial neural networks (ANNs). The trained ANN reduces drastically the number of trial-and-error of KMC simulations. The KMC simulation using the calibrated input parameters predicts the microstructures of a La0.6Sr0.4Co0.2Fe0.8O3 cathode material during sintering, showing both qualitative and quantitative congruence with real 3D microstructures obtained by focused ion beam scanning electron microscopy (FIB-SEM) reconstruction.

Optimization of Fe2+ supplement in anaerobic digestion accounting for the Fe-bioavailability.

PubMed

Cai, Yafan; Zhao, Xiaoling; Zhao, Yubin; Wang, Hongliang; Yuan, Xufeng; Zhu, Wanbin; Cui, Zongjun; Wang, Xiaofen

2018-02-01

Fe is widely used as an additive in anaerobic digestion, but its bioavailability and the mechanism by which it enhances digestion are unclear. In this study, sequential extraction was used to measure Fe bioavailability, while biochemical parameters, kinetics model and Q-PCR (fluorescence quantitative PCR) were used to explore its mechanism of stimulation. The results showed that sequential extraction is a suitable method to assess the anaerobic system bioavailability of Fe, which is low and fluctuates to a limited extent (1.7 to -3.1wt%), indicating that it would be easy for Fe levels to be insufficient. Methane yield increased when the added Fe 2+ was 10-500mg/L. Appropriate amounts of Fe 2+ accelerated the decomposition of rice straw and facilitated methanogen metabolism, thereby improving reactor performance. The modified Gompertz model better fitted the results than the first-order kinetic model. Feasibility analysis showed that addition of Fe 2+ at ≤50mg/L was suitable. Copyright © 2017. Published by Elsevier Ltd.

Quantitative and Mechanistic Assessment of Model Lipophilic Drugs in Micellar Solutions in the Transport Kinetics Across MDR1-MDCK Cell Monolayers.

PubMed

Ho, Norman F H; Nielsen, James; Peterson, Michelle; Burton, Philip S

2016-02-01

An approach to characterizing P-glycoprotein (Pgp) interaction potential for sparingly water-soluble compounds was developed using bidirectional transport kinetics in MDR1-MDCK cell monolayers. Paclitaxel, solubilized in a dilute polysorbate 80 (PS80) micellar solution, was used as a practical example. Although the passage of paclitaxel across the cell monolayer was initially governed by the thermodynamic activity of the micelle-solubilized drug solution, Pgp inhibition was sustained by the thermodynamic activity (i.e., critical micelle concentration) of the PS80 micellar solution bathing the apical (ap) membrane. The mechanistic understanding of the experimental strategies and treatment of data was supported by a biophysical model expressed in the form of transport events occurring at the ap and basolateral (bl) membranes in series whereas the vectorial directions of the transcellular kinetics were accommodated. The derived equations permitted the stepwise quantitative delineation of the Pgp efflux activity (inhibited and uninhibited by PS80) and the passive permeability coefficient of the ap membrane, the passive permeability at the bl membrane and, finally, the distinct coupling of these with efflux pump activity to identify the rate-determining steps and mechanisms. The Jmax/KM(∗) for paclitaxel was in the order of 10(-4) cm/s and the ap- and bl-membrane passive permeability coefficients were asymmetric, with bl-membrane permeability significantly greater than ap. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Modulation of Crystal Surface and Lattice by Doping: Achieving Ultrafast Metal-Ion Insertion in Anatase TiO2.

PubMed

Wang, Hsin-Yi; Chen, Han-Yi; Hsu, Ying-Ya; Stimming, Ulrich; Chen, Hao Ming; Liu, Bin

2016-10-26

We report that an ultrafast kinetics of reversible metal-ion insertion can be realized in anatase titanium dioxide (TiO 2 ). Niobium ions (Nb 5+ ) were carefully chosen to dope and drive anatase TiO 2 into very thin nanosheets standing perpendicularly onto transparent conductive electrode (TCE) and simultaneously construct TiO 2 with an ion-conducting surface together with expanded ion diffusion channels, which enabled ultrafast metal ions to diffuse across the electrolyte/solid interface and into the bulk of TiO 2 . To demonstrate the superior metal-ion insertion rate, the electrochromic features induced by ion intercalation were examined, which exhibited the best color switching speed of 4.82 s for coloration and 0.91 s for bleaching among all reported nanosized TiO 2 devices. When performed as the anode for the secondary battery, the modified TiO 2 was capable to deliver a highly reversible capacity of 61.2 mAh/g at an ultrahigh specific current rate of 60 C (10.2 A/g). This fast metal-ion insertion behavior was systematically investigated by the well-controlled electrochemical approaches, which quantitatively revealed both the enhanced surface kinetics and bulk ion diffusion rate. Our study could provide a facile methodology to modulate the ion diffusion kinetics for metal oxides.

Photoplasma of optically excited metal vapors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bezuglov, N.N.; Llyucharev, A.N.; Stacewicz, T.

1994-09-01

A wide range of questions associated with various aspects of photoplasma physics is considered. A comprehensive analysis of processes of optical excitation and de-excitation depending on optical characteristics of an absorbing gas medium is given. Analytical methods used for determining the excitation degree of photoresonance plasma in conditions of resonance radiation transfer are described. The accuracy of the Biberman approximation for effective lifetimes in population kinetics of resonance plasma states is analyzed for many experimental conditions. A detailed discussion of primary ionization mechanisms in photoplasma is given; the kinetics of ionization processes is discussed; and systematization of various types ofmore » photoresonance plasma is presented. Basis aspects of the LIBORS model, which is widely used for studying ionization kinetics of laser photoresonance plasma, and its limitations are considered. An ingenious method used to analytically solve a class of decay-type nonlinear problems, which arise for the capture equation in the case of noticeable saturation of a resonance transition by a short laser pulse, is described. A reliable quantitative description of fluorescence decay curve peculiarities that are associated with the bleaching of gases at resonance line frequencies can be obtained by this method. Some possible applications of photoplasma in problems of optics and spectroscopy are considered. 75 refs., 24 figs., 1 tab.« less

Kinetics of the cooperative binding of glucose to dimeric yeast hexokinase P-I.

PubMed Central

Hoggett, J G; Kellett, G L

1995-01-01

Kinetic studies of the cooperative binding of glucose to yeast hexokinase P-I at pH 6.5 have been carried out using the fluorescence temperature-jump technique. Three relaxation effects were observed: a fast low-amplitude effect which could only be resolved at low glucose concentrations (tau 1(-1) = 500-800 s-1), an intermediate effect (tau 2) which showed a linear dependence of reciprocal relaxation time on concentration, and a slow effect (tau 3) which showed a curved dependence on glucose concentration, increasing from approximately 28 s-1 at low concentrations to 250 s-1 at high levels. The findings are interpreted in terms of the concerted Monod-Wyman-Changeux mechanism, the two faster relaxations being assigned to binding to the R and T states, and the slow relaxation to isomerization between the states. Quantitative fitting of the kinetic data to the mechanism has been carried out using independent estimates of the equilibrium parameters of the model; these have been derived from equilibrium dialysis data and by determining the enhancement of the intrinsic ATPase activity of the enzyme by the non-phosphorylatable sugar lyxose, which switches the conformation of the enzyme to the active R state. Images Figure 1 PMID:7832753

Mechanism of 1,4,5,8-naphthalene tetracarboxylic acid dianhydride hydrolysis and formation in aqueous solution.

PubMed

Barros, T C; Cuccovia, I M; Farah, J P S; Masini, J C; Chaimovich, H; Politi, M J

2006-01-07

The study of highly conjugated, carbonyl-containing molecules such as 1,4,5,8-naphthalene tetracarboxylic dianhydride, III, is of interest since reactivity differences and transmission of electronic effects through the conjugated framework can be evidenced. The kinetics of hydrolysis of III in aqueous solution were determined from 5 M acid to pH 10. In basic solution hydrolysis of III yields, sequentially, 1,4,5,8-naphthalene diacid monoanhydride, II, and 1,4,5,8-naphthalene tetracarboxylic acid, I. The second order rate constant for alkaline hydrolysis is 200 fold higher for the first ring opening. The water-catalyzed hydrolysis of III yields a pH-dependent mixture of ionic forms of I and II. The rate constant for water-catalyzed hydrolysis of III is 25 fold higher than that for II. In concentrated acid the rates for reaching equilibrium (I, II and III) increase and III is the major product. The pK(a)s of I (3.24, 5.13 and 6.25) and II (3.05, 5.90) were determined by potentiometric, fluorescence and UV spectroscopy titrations and by quantitative fit of the kinetic and equilibrium data. The apparent, pH-dependent, equilibrium constants, K(EqII), for anhydride formation between I and II were obtained from the UV spectra. The quantitative fit of kinetic and equilibrium data are consistent with the assumption that anhydride formation only proceeds with the fully protonated species for both I and II and permitted the estimation of the equilibrium constants for anhydride formation, K(EqII). The value of K(EqII) (I <==> II) between pH 1 and 6 was ca. 5. Geometry optimization calculations in the gas phase of the reactions of III in alkaline, neutral and acid conditions, at the DFT level of theory, gave electronic distributions that were qualitatively consistent with the experimental results.

Development of a core Clostridium thermocellum kinetic metabolic model consistent with multiple genetic perturbations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dash, Satyakam; Khodayari, Ali; Zhou, Jilai

Background. Clostridium thermocellum is a Gram-positive anaerobe with the ability to hydrolyze and metabolize cellulose into biofuels such as ethanol, making it an attractive candidate for consolidated bioprocessing (CBP). At present, metabolic engineering in C. thermocellum is hindered due to the incomplete description of its metabolic repertoire and regulation within a predictive metabolic model. Genome-scale metabolic (GSM) models augmented with kinetic models of metabolism have been shown to be effective at recapitulating perturbed metabolic phenotypes. Results. In this effort, we first update a second-generation genome-scale metabolic model (iCth446) for C. thermocellum by correcting cofactor dependencies, restoring elemental and charge balances,more » and updating GAM and NGAM values to improve phenotype predictions. The iCth446 model is next used as a scaffold to develop a core kinetic model (k-ctherm118) of the C. thermocellum central metabolism using the Ensemble Modeling (EM) paradigm. Model parameterization is carried out by simultaneously imposing fermentation yield data in lactate, malate, acetate, and hydrogen production pathways for 19 measured metabolites spanning a library of 19 distinct single and multiple gene knockout mutants along with 18 intracellular metabolite concentration data for a Δgldh mutant and ten experimentally measured Michaelis–Menten kinetic parameters. Conclusions. The k-ctherm118 model captures significant metabolic changes caused by (1) nitrogen limitation leading to increased yields for lactate, pyruvate, and amino acids, and (2) ethanol stress causing an increase in intracellular sugar phosphate concentrations (~1.5-fold) due to upregulation of cofactor pools. Robustness analysis of k-ctherm118 alludes to the presence of a secondary activity of ketol-acid reductoisomerase and possible regulation by valine and/or leucine pool levels. In addition, cross-validation and robustness analysis allude to missing elements in k-ctherm118 and suggest additional experiments to improve kinetic model prediction fidelity. Overall, the study quantitatively assesses the advantages of EM-based kinetic modeling towards improved prediction of C. thermocellum metabolism and develops a predictive kinetic model which can be used to design biofuel-overproducing strains.« less

Development of a core Clostridium thermocellum kinetic metabolic model consistent with multiple genetic perturbations

DOE PAGES

Dash, Satyakam; Khodayari, Ali; Zhou, Jilai; ...

2017-05-02

Background. Clostridium thermocellum is a Gram-positive anaerobe with the ability to hydrolyze and metabolize cellulose into biofuels such as ethanol, making it an attractive candidate for consolidated bioprocessing (CBP). At present, metabolic engineering in C. thermocellum is hindered due to the incomplete description of its metabolic repertoire and regulation within a predictive metabolic model. Genome-scale metabolic (GSM) models augmented with kinetic models of metabolism have been shown to be effective at recapitulating perturbed metabolic phenotypes. Results. In this effort, we first update a second-generation genome-scale metabolic model (iCth446) for C. thermocellum by correcting cofactor dependencies, restoring elemental and charge balances,more » and updating GAM and NGAM values to improve phenotype predictions. The iCth446 model is next used as a scaffold to develop a core kinetic model (k-ctherm118) of the C. thermocellum central metabolism using the Ensemble Modeling (EM) paradigm. Model parameterization is carried out by simultaneously imposing fermentation yield data in lactate, malate, acetate, and hydrogen production pathways for 19 measured metabolites spanning a library of 19 distinct single and multiple gene knockout mutants along with 18 intracellular metabolite concentration data for a Δgldh mutant and ten experimentally measured Michaelis–Menten kinetic parameters. Conclusions. The k-ctherm118 model captures significant metabolic changes caused by (1) nitrogen limitation leading to increased yields for lactate, pyruvate, and amino acids, and (2) ethanol stress causing an increase in intracellular sugar phosphate concentrations (~1.5-fold) due to upregulation of cofactor pools. Robustness analysis of k-ctherm118 alludes to the presence of a secondary activity of ketol-acid reductoisomerase and possible regulation by valine and/or leucine pool levels. In addition, cross-validation and robustness analysis allude to missing elements in k-ctherm118 and suggest additional experiments to improve kinetic model prediction fidelity. Overall, the study quantitatively assesses the advantages of EM-based kinetic modeling towards improved prediction of C. thermocellum metabolism and develops a predictive kinetic model which can be used to design biofuel-overproducing strains.« less

Quantitative studies of bone using (18)F-fluoride and (99m)Tc-methylene diphosphonate: evaluation of renal and whole-blood kinetics.

PubMed

Park-Holohan, S J; Blake, G M; Fogelman, I

2001-09-01

We report a study of the renal and whole-blood kinetics of (18)F-fluoride and (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) and their effect on the evaluation of the skeletal kinetics of the two bone tracers. Data were obtained during an investigation of postmenopausal women taking hormone replacement therapy who were compared with untreated, age-matched controls. After intravenous injection of 18F-fluoride (1 MBq), (99m)Tc-MDP (1 MBq), (51)Cr-ethylenediaminetetraacetic acid (51Cr-EDTA) (3 MBq) and (125)I-human serum albumin ((125)I-HSA) (0.25 MBq), multiple blood samples and urine collections were taken between 0 and 4 h after injection. (51)Cr-EDTA data were used to evaluate the glomerular filtration rate (GFR) and the completeness of each timed urine collection. (125)I-HSA data were used to evaluate the plasma volume and the red cell uptake of the other three tracers. At 4 h, the cumulative urine excretions (and standard deviations, SDs) were: (99m)Tc-MDP, 58.2% (4.8%); (18)F-fluoride, 36.1% (5.7%); (51)Cr-EDTA, 81.5% (4.5%). Plots of the renal clearance of (18)F-fluoride against urine volume showed that urine flow rates greater than 5 ml.min-1 were necessary to ensure a constant renal clearance of (18)F and hence stable conditions for the evaluation of bone tracer kinetics. In contrast, a low urine flow rate had no effect on the renal kinetics of (99m)Tc-MDP. For MDP, the evaluation of skeletal kinetics requires data on protein binding so that calculations can be performed for free MDP. In the present study, protein binding of MDP was evaluated from the ratio of total (99m)Tc-MDP renal clearance to GFR based on the principle that free (99m)Tc-MDP is a GFR tracer. Between 0 and 4 h after injection, the fractional protein binding of MDP increased linearly with time, changing from 21+/-5% immediately after injection to 58+/-5% at 4 h. Although red cell uptake of (99m)Tc-MDP was negligible, for (18)F-fluoride around 30% of circulating tracer was transported in red cells. In view of the data showing the rapid transport of (18)F-fluoride across the red cell membrane, bone kinetic data for (18)F are more accurately reported as whole-blood clearance rather than plasma clearance.

Measuring the Enzyme Activity of Arabidopsis Deubiquitylating Enzymes.

PubMed

Kalinowska, Kamila; Nagel, Marie-Kristin; Isono, Erika

2016-01-01

Deubiquitylating enzymes, or DUBs, are important regulators of ubiquitin homeostasis and substrate stability, though the molecular mechanisms of most of the DUBs in plants are not yet understood. As different ubiquitin chain types are implicated in different biological pathways, it is important to analyze the enzyme characteristic for studying a DUB. Quantitative analysis of DUB activity is also important to determine enzyme kinetics and the influence of DUB binding proteins on the enzyme activity. Here, we show methods to analyze DUB activity using immunodetection, Coomassie Brilliant Blue staining, and fluorescence measurement that can be useful for understanding the basic characteristic of DUBs.

Dynamic PET image reconstruction integrating temporal regularization associated with respiratory motion correction for applications in oncology

NASA Astrophysics Data System (ADS)

Merlin, Thibaut; Visvikis, Dimitris; Fernandez, Philippe; Lamare, Frédéric

2018-02-01

Respiratory motion reduces both the qualitative and quantitative accuracy of PET images in oncology. This impact is more significant for quantitative applications based on kinetic modeling, where dynamic acquisitions are associated with limited statistics due to the necessity of enhanced temporal resolution. The aim of this study is to address these drawbacks, by combining a respiratory motion correction approach with temporal regularization in a unique reconstruction algorithm for dynamic PET imaging. Elastic transformation parameters for the motion correction are estimated from the non-attenuation-corrected PET images. The derived displacement matrices are subsequently used in a list-mode based OSEM reconstruction algorithm integrating a temporal regularization between the 3D dynamic PET frames, based on temporal basis functions. These functions are simultaneously estimated at each iteration, along with their relative coefficients for each image voxel. Quantitative evaluation has been performed using dynamic FDG PET/CT acquisitions of lung cancer patients acquired on a GE DRX system. The performance of the proposed method is compared with that of a standard multi-frame OSEM reconstruction algorithm. The proposed method achieved substantial improvements in terms of noise reduction while accounting for loss of contrast due to respiratory motion. Results on simulated data showed that the proposed 4D algorithms led to bias reduction values up to 40% in both tumor and blood regions for similar standard deviation levels, in comparison with a standard 3D reconstruction. Patlak parameter estimations on reconstructed images with the proposed reconstruction methods resulted in 30% and 40% bias reduction in the tumor and lung region respectively for the Patlak slope, and a 30% bias reduction for the intercept in the tumor region (a similar Patlak intercept was achieved in the lung area). Incorporation of the respiratory motion correction using an elastic model along with a temporal regularization in the reconstruction process of the PET dynamic series led to substantial quantitative improvements and motion artifact reduction. Future work will include the integration of a linear FDG kinetic model, in order to directly reconstruct parametric images.

Dynamic PET image reconstruction integrating temporal regularization associated with respiratory motion correction for applications in oncology.

PubMed

Merlin, Thibaut; Visvikis, Dimitris; Fernandez, Philippe; Lamare, Frédéric

2018-02-13

Respiratory motion reduces both the qualitative and quantitative accuracy of PET images in oncology. This impact is more significant for quantitative applications based on kinetic modeling, where dynamic acquisitions are associated with limited statistics due to the necessity of enhanced temporal resolution. The aim of this study is to address these drawbacks, by combining a respiratory motion correction approach with temporal regularization in a unique reconstruction algorithm for dynamic PET imaging. Elastic transformation parameters for the motion correction are estimated from the non-attenuation-corrected PET images. The derived displacement matrices are subsequently used in a list-mode based OSEM reconstruction algorithm integrating a temporal regularization between the 3D dynamic PET frames, based on temporal basis functions. These functions are simultaneously estimated at each iteration, along with their relative coefficients for each image voxel. Quantitative evaluation has been performed using dynamic FDG PET/CT acquisitions of lung cancer patients acquired on a GE DRX system. The performance of the proposed method is compared with that of a standard multi-frame OSEM reconstruction algorithm. The proposed method achieved substantial improvements in terms of noise reduction while accounting for loss of contrast due to respiratory motion. Results on simulated data showed that the proposed 4D algorithms led to bias reduction values up to 40% in both tumor and blood regions for similar standard deviation levels, in comparison with a standard 3D reconstruction. Patlak parameter estimations on reconstructed images with the proposed reconstruction methods resulted in 30% and 40% bias reduction in the tumor and lung region respectively for the Patlak slope, and a 30% bias reduction for the intercept in the tumor region (a similar Patlak intercept was achieved in the lung area). Incorporation of the respiratory motion correction using an elastic model along with a temporal regularization in the reconstruction process of the PET dynamic series led to substantial quantitative improvements and motion artifact reduction. Future work will include the integration of a linear FDG kinetic model, in order to directly reconstruct parametric images.

Real-time monitoring of glucose-6-phosphate dehydrogenase activity using liquid droplet arrays and its application to human plasma samples.

PubMed

Jung, Se-Hui; Ji, Su-Hyun; Han, Eun-Taek; Park, Won Sun; Hong, Seok-Ho; Kim, Young-Myeong; Ha, Kwon-Soo

2016-05-15

Glucose-6-phosphate dehydrogenase (G6PD) regulates nicotinamide adenine dinucleotide phosphate (NADPH) levels and is related to the pathogenesis of various diseases, including G6PD deficiency, type 2 diabetes, aldosterone-induced endothelial dysfunction, and cancer. Therefore, a highly sensitive array-based assay for determining quantitative G6PD activity is required. Here, we developed an on-chip G6PD activity assay using liquid droplet fluorescence arrays. Quantitative G6PD activity was determined by calculating reduced resorufin concentrations in liquid droplets. The limit of detection (LOD) of this assay was 0.162 mU/ml (2.89 pM), which is much more sensitive than previous assays. We used our activity assay to determine kinetic parameters, including Michaelis-Menten constants (Km) and maximum rates of enzymatic reaction (Vmax) for NADP(+) and G6P, and half-maximal inhibitory concentrations (IC50). We successfully applied this new assay to determine G6PD activity in human plasma from normal healthy individuals (n=30) and patients with inflammation (n=30). The inflammatory group showed much higher G6PD activities than did the normal group (p<0.001), with a high area under the curve value of 0.939. Therefore, this new activity assay has the potential to be used for diagnosis of G6PD-associated diseases and utilizing kinetic studies. Copyright © 2016 Elsevier B.V. All rights reserved.

Dynamic PET and Optical Imaging and Compartment Modeling using a Dual-labeled Cyclic RGD Peptide Probe

PubMed Central

Zhu, Lei; Guo, Ning; Li, Quanzheng; Ma, Ying; Jacboson, Orit; Lee, Seulki; Choi, Hak Soo; Mansfield, James R.; Niu, Gang; Chen, Xiaoyuan

2012-01-01

Purpose: The aim of this study is to determine if dynamic optical imaging could provide comparable kinetic parameters to that of dynamic PET imaging by a near-infrared dye/64Cu dual-labeled cyclic RGD peptide. Methods: The integrin αvβ3 binding RGD peptide was conjugated with a macrocyclic chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) for copper labeling and PET imaging and a near-infrared dye ZW-1 for optical imaging. The in vitro biological activity of RGD-C(DOTA)-ZW-1 was characterized by cell staining and receptor binding assay. Sixty-min dynamic PET and optical imaging were acquired on a MDA-MB-435 tumor model. Singular value decomposition (SVD) method was applied to compute the dynamic optical signal from the two-dimensional optical projection images. Compartment models were used to quantitatively analyze and compare the dynamic optical and PET data. Results: The dual-labeled probe 64Cu-RGD-C(DOTA)-ZW-1 showed integrin specific binding in vitro and in vivo. The binding potential (Bp) derived from dynamic optical imaging (1.762 ± 0.020) is comparable to that from dynamic PET (1.752 ± 0.026). Conclusion: The signal un-mixing process using SVD improved the accuracy of kinetic modeling of 2D dynamic optical data. Our results demonstrate that 2D dynamic optical imaging with SVD analysis could achieve comparable quantitative results as dynamic PET imaging in preclinical xenograft models. PMID:22916074

A comparative kinetic RT/-PCR strategy for the quantitation of mRNAs in microdissected human renal biopsy specimens.

PubMed

Del Prete, D; Forino, M; Gambaro, G; D'Angelo, A; Baggio, B; Anglani, F

1998-01-01

Molecular biology techniques, to be applicable to a diagnostic renal biopsy specimen, should (1) be highly sensitive to be performed on a very small quantity of tissue; (2) be quantitative because they have to analyze genes normally expressed in the tissue and (3) allow the analysis of as large a number of genes as possible. Among different methods, only the reverse-transcriptase polymerase chain reaction (RT/-PCR) might comply with previous requisites, but the few RT/-PCR examples on renal biopsies in the literature do not allow starting RNA quantification and quality control; furthermore they have the drawback of analyzing only few genes. In an ongoing study to assess the expression of a number of genes in glomeruli and in tubulointerstitium of patients with different nephropathies, we developed a comparative RT/-PCR kinetic strategy based on the purification and quantification of total glomerular and tubulointerstitial RNA and on the use of an internal standard, the housekeeping gene G3PDH. We demonstrate that in microdissected diagnostic renal biopsies (1) glomerular and interstitial starting RNA can be quantified; (2) the G3PDH gene may be used both as an internal standard and as an indirect marker of RNA integrity; (3) as low as 28 ng of total RNA is sufficient to obtain PCR products of eight genes, and (4) it is worth to operate on microdissected biopsy specimens because of the different expression of genes in the two renal compartments.

Dynamic PET and Optical Imaging and Compartment Modeling using a Dual-labeled Cyclic RGD Peptide Probe.

PubMed

Zhu, Lei; Guo, Ning; Li, Quanzheng; Ma, Ying; Jacboson, Orit; Lee, Seulki; Choi, Hak Soo; Mansfield, James R; Niu, Gang; Chen, Xiaoyuan

2012-01-01

The aim of this study is to determine if dynamic optical imaging could provide comparable kinetic parameters to that of dynamic PET imaging by a near-infrared dye/(64)Cu dual-labeled cyclic RGD peptide. The integrin α(v)β(3) binding RGD peptide was conjugated with a macrocyclic chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) for copper labeling and PET imaging and a near-infrared dye ZW-1 for optical imaging. The in vitro biological activity of RGD-C(DOTA)-ZW-1 was characterized by cell staining and receptor binding assay. Sixty-min dynamic PET and optical imaging were acquired on a MDA-MB-435 tumor model. Singular value decomposition (SVD) method was applied to compute the dynamic optical signal from the two-dimensional optical projection images. Compartment models were used to quantitatively analyze and compare the dynamic optical and PET data. The dual-labeled probe (64)Cu-RGD-C(DOTA)-ZW-1 showed integrin specific binding in vitro and in vivo. The binding potential (Bp) derived from dynamic optical imaging (1.762 ± 0.020) is comparable to that from dynamic PET (1.752 ± 0.026). The signal un-mixing process using SVD improved the accuracy of kinetic modeling of 2D dynamic optical data. Our results demonstrate that 2D dynamic optical imaging with SVD analysis could achieve comparable quantitative results as dynamic PET imaging in preclinical xenograft models.

Differential substrate behaviour of phenol and aniline derivatives during oxidation by horseradish peroxidase: kinetic evidence for a two-step mechanism.

PubMed

Gilabert, María Angeles; Hiner, Alexander N P; García-Ruiz, Pedro Antonio; Tudela, José; García-Molina, Francisco; Acosta, Manuel; García-Cánovas, Francisco; Rodríguez-López, José Neptuno

2004-06-01

The catalytic constant (k(cat)) and the second-order association constant of compound II with reducing substrate (k(5)) of horseradish peroxidase C (HRPC) acting on phenols and anilines have been determined from studies of the steady-state reaction velocities (V(0) vs. [S(0)]). Since k(cat)=k(2)k(6)/k(2)+k(6), and k(2) (the first-order rate constant for heterolytic cleavage of the oxygen-oxygen bond of hydrogen peroxide during compound I formation) is known, it has been possible to calculate the first-order rate constant for the transformation of each phenol or aniline by HRPC compound II (k(6)). The values of k(6) are quantitatively correlated to the sigma values (Hammett equation) and can be rationalized by an aromatic substrate oxidation mechanism in which the substrate donates an electron to the oxyferryl group in HRPC compound II, accompanied by two proton additions to the ferryl oxygen atom, one from the substrate and the other the protein or solvent. k(6) is also quantitatively correlated to the experimentally determined (13)C-NMR chemical shifts (delta(1)) and the calculated ionization potentials, E (HOMO), of the substrates. Similar dependencies were observed for k(cat) and k(5). From the kinetic analysis, the absolute values of the Michaelis constants for hydrogen peroxide and the reducing substrates (K(M)(H(2)O(2)) and K(M)(S)), respectively, were obtained.

Specificity and Affinity Quantification of Flexible Recognition from Underlying Energy Landscape Topography

PubMed Central

Chu, Xiakun; Wang, Jin

2014-01-01

Flexibility in biomolecular recognition is essential and critical for many cellular activities. Flexible recognition often leads to moderate affinity but high specificity, in contradiction with the conventional wisdom that high affinity and high specificity are coupled. Furthermore, quantitative understanding of the role of flexibility in biomolecular recognition is still challenging. Here, we meet the challenge by quantifying the intrinsic biomolecular recognition energy landscapes with and without flexibility through the underlying density of states. We quantified the thermodynamic intrinsic specificity by the topography of the intrinsic binding energy landscape and the kinetic specificity by association rate. We found that the thermodynamic and kinetic specificity are strongly correlated. Furthermore, we found that flexibility decreases binding affinity on one hand, but increases binding specificity on the other hand, and the decreasing or increasing proportion of affinity and specificity are strongly correlated with the degree of flexibility. This shows more (less) flexibility leads to weaker (stronger) coupling between affinity and specificity. Our work provides a theoretical foundation and quantitative explanation of the previous qualitative studies on the relationship among flexibility, affinity and specificity. In addition, we found that the folding energy landscapes are more funneled with binding, indicating that binding helps folding during the recognition. Finally, we demonstrated that the whole binding-folding energy landscapes can be integrated by the rigid binding and isolated folding energy landscapes under weak flexibility. Our results provide a novel way to quantify the affinity and specificity in flexible biomolecular recognition. PMID:25144525

Lipid-associated oral delivery: Mechanisms and analysis of oral absorption enhancement.

PubMed

Rezhdo, Oljora; Speciner, Lauren; Carrier, Rebecca

2016-10-28

The majority of newly discovered oral drugs are poorly water soluble, and co-administration with lipids has proven effective in significantly enhancing bioavailability of some compounds with low aqueous solubility. Yet, lipid-based delivery technologies have not been widely employed in commercial oral products. Lipids can impact drug transport and fate in the gastrointestinal (GI) tract through multiple mechanisms including enhancement of solubility and dissolution kinetics, enhancement of permeation through the intestinal mucosa, and triggering drug precipitation upon lipid emulsion depletion (e.g., by digestion). The effect of lipids on drug absorption is currently not quantitatively predictable, in part due to the multiple complex dynamic processes that can be impacted by lipids. Quantitative mechanistic analysis of the processes significant to lipid system function and overall impact on drug absorption can aid in the understanding of drug-lipid interactions in the GI tract and exploitation of such interactions to achieve optimal lipid-based drug delivery. In this review, we discuss the impact of co-delivered lipids and lipid digestion on drug dissolution, partitioning, and absorption in the context of the experimental tools and associated kinetic expressions used to study and model these processes. The potential benefit of a systems-based consideration of the concurrent multiple dynamic processes occurring upon co-dosing lipids and drugs to predict the impact of lipids on drug absorption and enable rational design of lipid-based delivery systems is presented. Copyright © 2016 Elsevier B.V. All rights reserved.

Specificity and affinity quantification of flexible recognition from underlying energy landscape topography.

PubMed

Chu, Xiakun; Wang, Jin

2014-08-01

Flexibility in biomolecular recognition is essential and critical for many cellular activities. Flexible recognition often leads to moderate affinity but high specificity, in contradiction with the conventional wisdom that high affinity and high specificity are coupled. Furthermore, quantitative understanding of the role of flexibility in biomolecular recognition is still challenging. Here, we meet the challenge by quantifying the intrinsic biomolecular recognition energy landscapes with and without flexibility through the underlying density of states. We quantified the thermodynamic intrinsic specificity by the topography of the intrinsic binding energy landscape and the kinetic specificity by association rate. We found that the thermodynamic and kinetic specificity are strongly correlated. Furthermore, we found that flexibility decreases binding affinity on one hand, but increases binding specificity on the other hand, and the decreasing or increasing proportion of affinity and specificity are strongly correlated with the degree of flexibility. This shows more (less) flexibility leads to weaker (stronger) coupling between affinity and specificity. Our work provides a theoretical foundation and quantitative explanation of the previous qualitative studies on the relationship among flexibility, affinity and specificity. In addition, we found that the folding energy landscapes are more funneled with binding, indicating that binding helps folding during the recognition. Finally, we demonstrated that the whole binding-folding energy landscapes can be integrated by the rigid binding and isolated folding energy landscapes under weak flexibility. Our results provide a novel way to quantify the affinity and specificity in flexible biomolecular recognition.

Quantitative imaging of protein targets in the human brain with PET

NASA Astrophysics Data System (ADS)

Gunn, Roger N.; Slifstein, Mark; Searle, Graham E.; Price, Julie C.

2015-11-01

PET imaging of proteins in the human brain with high affinity radiolabelled molecules has a history stretching back over 30 years. During this period the portfolio of protein targets that can be imaged has increased significantly through successes in radioligand discovery and development. This portfolio now spans six major categories of proteins; G-protein coupled receptors, membrane transporters, ligand gated ion channels, enzymes, misfolded proteins and tryptophan-rich sensory proteins. In parallel to these achievements in radiochemical sciences there have also been significant advances in the quantitative analysis and interpretation of the imaging data including the development of methods for image registration, image segmentation, tracer compartmental modeling, reference tissue kinetic analysis and partial volume correction. In this review, we analyze the activity of the field around each of the protein targets in order to give a perspective on the historical focus and the possible future trajectory of the field. The important neurobiology and pharmacology is introduced for each of the six protein classes and we present established radioligands for each that have successfully transitioned to quantitative imaging in humans. We present a standard quantitative analysis workflow for these radioligands which takes the dynamic PET data, associated blood and anatomical MRI data as the inputs to a series of image processing and bio-mathematical modeling steps before outputting the outcome measure of interest on either a regional or parametric image basis. The quantitative outcome measures are then used in a range of different imaging studies including tracer discovery and development studies, cross sectional studies, classification studies, intervention studies and longitudinal studies. Finally we consider some of the confounds, challenges and subtleties that arise in practice when trying to quantify and interpret PET neuroimaging data including motion artifacts, partial volume effects, age effects, image registration and normalization, input functions and metabolites, parametric imaging, receptor internalization and genetic factors.

Kinetics of hairpin ribozyme cleavage in yeast.

PubMed Central

Donahue, C P; Fedor, M J

1997-01-01

Hairpin ribozymes catalyze a self-cleavage reaction that provides a simple model for quantitative analyses of intracellular mechanisms of RNA catalysis. Decay rates of chimeric mRNAs containing self-cleaving ribozymes give a direct measure of intracellular cleavage kinetics in yeast. Intracellular ribozyme-mediated cleavage occurs at similar rates and shows similar inhibition by ribozyme mutations as ribozyme-mediated reactions in vitro, but only when ribozymes are located in a favorable mRNA sequence context. The impact of cleavage on mRNA abundance is shown to depend directly on intrinsic mRNA stability. Surprisingly, cleavage products are no more labile than uncleaved mRNAs despite the loss of terminal cap structures or poly (A). PMID:9292496

Ion induced electron emission statistics under Agm- cluster bombardment of Ag

NASA Astrophysics Data System (ADS)

Breuers, A.; Penning, R.; Wucher, A.

2018-05-01

The electron emission from a polycrystalline silver surface under bombardment with Agm- cluster ions (m = 1, 2, 3) is investigated in terms of ion induced kinetic excitation. The electron yield γ is determined directly by a current measurement method on the one hand and implicitly by the analysis of the electron emission statistics on the other hand. Successful measurements of the electron emission spectra ensure a deeper understanding of the ion induced kinetic electron emission process, with particular emphasis on the effect of the projectile cluster size to the yield as well as to emission statistics. The results allow a quantitative comparison to computer simulations performed for silver atoms and clusters impinging onto a silver surface.

Microgravimetric Analysis Method for Activation-Energy Extraction from Trace-Amount Molecule Adsorption.

PubMed

Xu, Pengcheng; Yu, Haitao; Li, Xinxin

2016-05-03

Activation-energy (Ea) value for trace-amount adsorption of gas molecules on material is rapidly and inexpensively obtained, for the first time, from a microgravimetric analysis experiment. With the material loaded, a resonant microcantilever is used to record in real time the adsorption process at two temperatures. The kinetic parameter Ea is thereby extracted by solving the Arrhenius equation. As an example, two CO2 capture nanomaterials are examined by the Ea extracting method for evaluation/optimization and, thereby, demonstrating the applicability of the microgravimetric analysis method. The achievement helps to solve the absence in rapid quantitative characterization of sorption kinetics and opens a new route to investigate molecule adsorption processes and materials.

Non-thermal plasma destruction of allyl alcohol in waste gas: kinetics and modelling

NASA Astrophysics Data System (ADS)

DeVisscher, A.; Dewulf, J.; Van Durme, J.; Leys, C.; Morent, R.; Van Langenhove, H.

2008-02-01

Non-thermal plasma treatment is a promising technique for the destruction of volatile organic compounds in waste gas. A relatively unexplored technique is the atmospheric negative dc multi-pin-to-plate glow discharge. This paper reports experimental results of allyl alcohol degradation and ozone production in this type of plasma. A new model was developed to describe these processes quantitatively. The model contains a detailed chemical degradation scheme, and describes the physics of the plasma by assuming that the fraction of electrons that takes part in chemical reactions is an exponential function of the reduced field. The model captured the experimental kinetic data to less than 2 ppm standard deviation.

Self-similar structure and experimental signatures of suprathermal ion distribution in inertial confinement fusion implosions

DOE PAGES

Kagan, Grigory; Svyatskiy, D.; Rinderknecht, H. G.; ...

2015-09-03

The distribution function of suprathermal ions is found to be self-similar under conditions relevant to inertial confinement fusion hot spots. By utilizing this feature, interference between the hydrodynamic instabilities and kinetic effects is for the first time assessed quantitatively to find that the instabilities substantially aggravate the fusion reactivity reduction. Thus, the ion tail depletion is also shown to lower the experimentally inferred ion temperature, a novel kinetic effect that may explain the discrepancy between the exploding pusher experiments and rad-hydro simulations and contribute to the observation that temperature inferred from DD reaction products is lower than from DT atmore » the National Ignition Facility.« less

Self-Similar Structure and Experimental Signatures of Suprathermal Ion Distribution in Inertial Confinement Fusion Implosions

NASA Astrophysics Data System (ADS)

Kagan, Grigory; Svyatskiy, D.; Rinderknecht, H. G.; Rosenberg, M. J.; Zylstra, A. B.; Huang, C.-K.; McDevitt, C. J.

2015-09-01

The distribution function of suprathermal ions is found to be self-similar under conditions relevant to inertial confinement fusion hot spots. By utilizing this feature, interference between the hydrodynamic instabilities and kinetic effects is for the first time assessed quantitatively to find that the instabilities substantially aggravate the fusion reactivity reduction. The ion tail depletion is also shown to lower the experimentally inferred ion temperature, a novel kinetic effect that may explain the discrepancy between the exploding pusher experiments and rad-hydro simulations and contribute to the observation that temperature inferred from DD reaction products is lower than from DT at the National Ignition Facility.

Effect of nonlocal electron kinetics on the characteristics of a dielectric barrier discharge in xenon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Avtaeva, S. V.; Skornyakov, A. V.

2009-07-15

The established dynamics of a dielectric barrier discharge in xenon at a pressure of 400 Torr is simulated in the framework of a one-dimensional fluid model in the local and nonlocal field approximations. It is shown that taking into account the nonlocal character of the electric field does not qualitatively change physical processes in a dielectric barrier discharge, but significantly affects its quantitative characteristics. In particular, the sheath thickness decreases, plasma ionization intensifies, the spatiotemporal distribution of the mean electron energy changes, and the discharge radiation efficiency increases. Electron kinetics in a dielectric barrier discharge in xenon is analyzed usingmore » the nonlocal field approximation.« less

Ultrasonic wave propagation in powders

NASA Astrophysics Data System (ADS)

Al-Lashi, R. S.; Povey, M. J. W.; Watson, N. J.

2018-05-01

Powder clumps (cakes) has a significant effect on the flowability and stability of powders. Powder caking is mainly caused by moisture migration due to wetting and environmental (temperature and humidity) changes. The process of moisture migration caking involves creating liquid bridges between the particles during condensation which subsequently harden to form solid bridges. Therefore, an effective and reliable technique is required to quantitatively and non-invasively monitor caking kinetics and effective stiffness. This paper describes two ultrasonic instruments (ultrasonic velocity pulse and airborne ultrasound systems) that have been used to monitor the caking phenomenon. Also, it discusses the relationship between the ultrasonic velocity and attenuation measurements and tracking caking kinetics and the effective stiffness of powders.

The kinetics of dissolution of dolomite in CO2-H2O systems at 1.5 to 65oC and 0 to 1 atm PCO2.

USGS Publications Warehouse

Busenberg, E.; Plummer, Niel

1982-01-01

Weight loss measurements at different T and PCO2 during experimental investigations of the dissolution kinetics of eight samples of dolomite permitted recognition of a two-stage process. During the first stage, which is brief, the surface composition of the dolomite becomes enriched with the MgCO3 component and the CaCO3 component dissolves faster. In the second and more important stage both components of the solid are released stoichiometrically, described quantitatively by three parallel consecutive forward reactions and one significant backward reaction. Dissolution rates are apparently more dependent on crystallographic order than on compositional variations. -M.S.

Microstructure development in Kolmogorov, Johnson-Mehl, and Avrami nucleation and growth kinetics

NASA Astrophysics Data System (ADS)

Pineda, Eloi; Crespo, Daniel

1999-08-01

A statistical model with the ability to evaluate the microstructure developed in nucleation and growth kinetics is built in the framework of the Kolmogorov, Johnson-Mehl, and Avrami theory. A populational approach is used to compute the observed grain-size distribution. The impingement process which delays grain growth is analyzed, and the effective growth rate of each population is estimated considering the previous grain history. The proposed model is integrated for a wide range of nucleation and growth protocols, including constant nucleation, pre-existing nuclei, and intermittent nucleation with interface or diffusion-controlled grain growth. The results are compared with Monte Carlo simulations, giving quantitative agreement even in cases where previous models fail.

Molecular-level simulations of turbulence and its decay

DOE PAGES

Gallis, M. A.; Bitter, N. P.; Koehler, T. P.; ...

2017-02-08

Here, we provide the first demonstration that molecular-level methods based on gas kinetic theory and molecular chaos can simulate turbulence and its decay. The direct simulation Monte Carlo (DSMC) method, a molecular-level technique for simulating gas flows that resolves phenomena from molecular to hydrodynamic (continuum) length scales, is applied to simulate the Taylor-Green vortex flow. The DSMC simulations reproduce the Kolmogorov –5/3 law and agree well with the turbulent kinetic energy and energy dissipation rate obtained from direct numerical simulation of the Navier-Stokes equations using a spectral method. This agreement provides strong evidence that molecular-level methods for gases can bemore » used to investigate turbulent flows quantitatively.« less

Improved Protein Arrays for Quantitative Systems Analysis of the Dynamics of Signaling Pathway Interactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Chin-Rang

Astronauts and workers in nuclear plants who repeatedly exposed to low doses of ionizing radiation (IR, <10 cGy) are likely to incur specific changes in signal transduction and gene expression in various tissues of their body. Remarkable advances in high throughput genomics and proteomics technologies enable researchers to broaden their focus from examining single gene/protein kinetics to better understanding global gene/protein expression profiling and biological pathway analyses, namely Systems Biology. An ultimate goal of systems biology is to develop dynamic mathematical models of interacting biological systems capable of simulating living systems in a computer. This Glue Grant is to complementmore » Dr. Boothman’s existing DOE grant (No. DE-FG02-06ER64186) entitled “The IGF1/IGF-1R-MAPK-Secretory Clusterin (sCLU) Pathway: Mediator of a Low Dose IR-Inducible Bystander Effect” to develop sensitive and quantitative proteomic technology that suitable for low dose radiobiology researches. An improved version of quantitative protein array platform utilizing linear Quantum dot signaling for systematically measuring protein levels and phosphorylation states for systems biology modeling is presented. The signals are amplified by a confocal laser Quantum dot scanner resulting in ~1000-fold more sensitivity than traditional Western blots and show the good linearity that is impossible for the signals of HRP-amplification. Therefore this improved protein array technology is suitable to detect weak responses of low dose radiation. Software is developed to facilitate the quantitative readout of signaling network activities. Kinetics of EGFRvIII mutant signaling was analyzed to quantify cross-talks between EGFR and other signaling pathways.« less

Dissipation Rate of Turbulent Kinetic Energy in Diel Vertical Migrations: Comparison of ANSYS Fluent Model to Measurements

NASA Astrophysics Data System (ADS)

Dean, Cayla; Soloviev, Alexander; Hirons, Amy; Frank, Tamara; Wood, Jon

2015-04-01

Recent studies suggest that diel vertical migrations of zooplankton may have an impact on ocean mixing, though details are not completely clear. A strong sound scattering layer of zooplankton undergoing diel vertical migrations was observed in Saanich Inlet, British Colombia, Canada by Kunze et al. (2006). In this study, a shipboard 200-kHz echosounder was used to track vertical motion of the sound scattering layer, and microstructure profiles were collected to observe turbulence. An increase of dissipation rate of turbulent kinetic energy by four to five orders of magnitude was measured during diel vertical migrations of zooplankton in one case (but not observed during other cases). A strong sound scattering layer undergoing diel vertical migration was also observed in the Straits of Florida via a bottom mounted acoustic Doppler current profiler at 244 m isobath. A 3-D non-hydrostatic computational fluid dynamics model with Lagrangian particle injections (a proxy for migrating zooplankton) via a discrete phase model was used to simulate the effect of diel vertical migrations on the turbulence for both Saanich Inlet and the Straits of Florida. The model was initialized with idealized (but based on observation) density and velocity profiles. Particles, with buoyancy adjusted to serve as a proxy for vertically swimming zooplankton, were injected to simulate diel vertical migration cycles. Results of models run with extreme concentrations of particles showed an increase in dissipation rate of turbulent kinetic energy of approximately five orders of magnitude over background turbulence during migration of particles in both Saanich Inlet and the Straits of Florida cases (though direct relation of the turbulence produced by buoyant particles and swimming organisms isn't straightforward). This increase was quantitatively consistent, with turbulence measurements by Kunze et al. (2006). When 10 times fewer particles were injected into the model, the effect on dissipation rate of turbulent kinetic energy was an order of magnitude smaller than that from the extreme concentration. At a concentration of particles 100 times smaller than the extreme concentration, there was no longer an observable effect. In the Straits of Florida, direct turbulence measurements were not available to make a quantitative comparison. However, a small, but statistically significant decrease in northward current velocity profiles during migration times were observed after averaging these profiles over 11 months. A small decrease of current velocity connected to the vertical migrations of particles was reproduced in the Straits of Florida model case. The deviations in the velocity profiles can be explained by the increase in turbulent mixing during vertical migration periods.

Understanding longitudinal wood fiber ultra-structure for producing cellulose nanofibrils using disk milling with diluted acid prehydrolysis

Treesearch

Yanlin Qin; Xueqing Qiu; Junyong Zhu

2016-01-01

Here we used dilute oxalic acid to pretreat a kraft bleached Eucalyptus pulp (BEP) fibers to facilitate mechanical fibrillation in producing cellulose nanofibrils using disk milling with substantial mechanical energy savings. We successfully applied a reaction kinetics based combined hydrolysis factor (CHFx) as a severity factor to quantitatively...

Antioxidant pool in beer and kinetics of EPR spin-trapping.

PubMed

Kocherginsky, Nikolai M; Kostetski, Yuri Yu; Smirnov, Alex I

2005-08-24

The kinetics of spin-trap adduct formation in beer oxidation exhibits an induction period if the reaction is carried out at elevated temperatures and in the presence of air. This lag period lasts until the endogenous antioxidants are almost completely depleted, and its duration is used as an indicator of the flavor stability and shelf life of beer. This paper demonstrates that the total kinetics of the process can be characterized by three parameters-the lag period, the rate of spin-trap adduct formation, and, finally, the steady-state spin-adduct concentration. A steady-state chain reaction mechanism is described, and quantitative estimates of the main kinetic parameters such as the initiation rate, antioxidant pool, effective content of organic molecules participating in the chain reactions, and the rate constant of the 1-hydroxyethyl radical EtOH(*) spin-adduct disappearance are given. An additional new dimensionless parameter is suggested to characterize the antioxidant pool-the product of the lag time and the rate of spin-trap radical formation immediately after the lag time, normalized by the steady-state concentration of the adducts. The results of spin-tapping EPR experiments are compared with the nitroxide reduction kinetics measured in the same beer samples. It is shown that although the kinetics of nitroxide reduction in beer can be used to evaluate the reducing power of beer, the latter parameter does not correlate with the antioxidant pool. The relationship of free radical processes, antioxidant pool, reducing power, and beer staling is discussed.

Predicting kinetic nanocrystal shapes through multi-scale theory and simulation: Polyvinylpyrrolidone-mediated growth of Ag nanocrystals

NASA Astrophysics Data System (ADS)

Balankura, Tonnam; Qi, Xin; Zhou, Ya; Fichthorn, Kristen A.

2016-10-01

In the shape-controlled synthesis of colloidal Ag nanocrystals, structure-directing agents, particularly polyvinylpyrrolidone (PVP), are known to be a key additive in making nanostructures with well-defined shapes. Although many Ag nanocrystals have been successfully synthesized using PVP, the mechanism by which PVP actuates shape control remains elusive. Here, we present a multi-scale theoretical framework for kinetic Wulff shape predictions that accounts for the chemical environment, which we used to probe the kinetic influence of the adsorbed PVP film. Within this framework, we use umbrella-sampling molecular dynamics simulations to calculate the potential of mean force and diffusion coefficient profiles of Ag atom deposition onto Ag(100) and Ag(111) in ethylene glycol solution with surface-adsorbed PVP. We use these profiles to calculate the mean-first passage times and implement extensive Brownian dynamics simulations, which allows the kinetic effects to be quantitatively evaluated. Our results show that PVP films can regulate the flux of Ag atoms to be greater towards Ag(111) than Ag(100). PVP's preferential binding towards Ag(100) over Ag(111) gives PVP its flux-regulating capabilities through the lower free-energy barrier of Ag atoms to cross the lower-density PVP film on Ag(111) and enhanced Ag trapping by the extended PVP film on Ag(111). Under kinetic control, {100}-faceted nanocrystals will be formed when the Ag flux is greater towards Ag(111). The predicted kinetic Wulff shapes are in agreement with the analogous experimental system.

Studies on the relationship between epidermal cell turnover kinetics and permeability of hairless mouse skin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, S.R.

The primary aim of this study was to develop non-invasive, physical means to quantitatively assess the epidermal turnover kinetics and barrier properties of the skin and relate these to the cutaneous irritation which results from ultraviolet light irradiation and mold thermal burns. After systematically injecting radiolabeled glycine, the appearance of radioactivity at the skin's surface indicated the transit time of radiolabeled cells through the skin. By plotting the data as the cumulative specific activity against time and then fitting them with a third order polynomial equation, it is possible to estimate the turnover time of the stratum corneum. The skinmore » turnover was coordinated with non-invasive transepidermal water loss (TEWL) studies determined with an evaporimeter. In vitro diffusion studies of the permeability of hydrocortisone through UVB irradiated and thermally burned skin were also performed. The studies indicated that irritated skin offers a relatively low diffusional resistance to hydrocortisone. Depending on the severity of the trauma, the increases in hydrocortisone's permeability coefficient through irritated skin ranged from a low of about 2 times normal to a high of about 210 times normal. Trauma-induced changes in hydrocortisone permeability parallel changes in TEWL, proving that the barrier deficient state resulting from rapid epidermal turnover is a general phenomenon.« less

Kinetics model for the wavelength-dependence of excited-state dynamics of hetero-FRET sensors

NASA Astrophysics Data System (ADS)

Schwarz, Jacob; Leighton, Ryan; Leopold, Hannah J.; Currie, Megan; Boersma, Arnold J.; Sheets, Erin D.; Heikal, Ahmed A.

2017-08-01

Foerster (or fluorescence) resonance energy transfer (FRET) is a powerful tool for investigating protein-protein interactions, in both living cells and in controlled environments. A typical hetero-FRET pair consists of a donor and acceptor tethered together with a linker. The corresponding energy transfer efficiency of a hetero-FRET pair probe depends upon the donor-acceptor distance, relative dipole orientation, and spectral overlap. Because of the sensitivity of the energy transfer efficiency on the donor-acceptor distance, FRET is often referred to as a "molecular ruler". Time-resolved fluorescence approach for measuring the excited-state lifetime of the donor and acceptor emissions is one of the most reliable approaches for quantitative assessment of the energy transfer efficiency in hetero-FRET pairs. In this contribution, we provide an analytical kinetics model that describes the excited-state depopulation of a FRET probe as a means to predicts the time-resolved fluorescence profile as a function of excitation and detection wavelengths. In addition, we used this developed kinetics model to simulate the time-dependence of the excited-state population of both the donor and acceptor. These results should serve as a guide for our ongoing studies of newly developed hetero-FRET sensors (mCerulean3-linker-mCitrine) that are designed specifically for in vivo studies of macromolecular crowding. The same model is applicable to other FRET pairs with the careful consideration of their steady-state spectroscopy and the experimental design for wavelength- dependence of the fluorescence lifetime measurements.

Development of an LC-MS based enzyme activity assay for MurC: application to evaluation of inhibitors and kinetic analysis.

PubMed

Deng, Gejing; Gu, Rong-Fang; Marmor, Stephen; Fisher, Stewart L; Jahic, Haris; Sanyal, Gautam

2004-06-29

An enzyme activity assay, based on mass spectrometric (MS) detection of specific reaction product following HPLC separation, has been developed to evaluate pharmaceutical hits identified from primary high throughput screening (HTS) against target enzyme Escherichia coli UDP-N-acetyl-muramyl-L-alanine ligase (MurC), an essential enzyme in the bacterial peptidoglycan biosynthetic pathway, and to study the kinetics of the enzyme. A comparative analysis of this new liquid chromatographic-MS (LC-MS) based assay with a conventional spectrophotometric Malachite Green (MG) assay, which detects phosphate produced in the reaction, was performed. The results demonstrated that the LC-MS assay, which determines specific ligase activity of MurC, offers several advantages including a lower background (0.2% versus 26%), higher sensitivity (> or = 10 fold), lower limit of quantitation (LOQ) (0.02 microM versus 1 microM) and wider linear dynamic range (> or = 4 fold) than the MG assay. Good precision for the LC-MS assay was demonstrated by the low intraday and interday coefficient of variation (CV) values (3 and 6%, respectively). The LC-MS assay, free of the artifacts often seen in the Malachite Green assay, offers a valuable secondary assay for hit evaluation in which the false positives from the primary high throughput screening can be eliminated. In addition, the applicability of this assay to the study of enzyme kinetics has also been demonstrated. Copyright 2004 Elsevier B.V.

Time-course, negative-stain electron microscopy–based analysis for investigating protein–protein interactions at the single-molecule level

PubMed Central

Nogal, Bartek; Bowman, Charles A.; Ward, Andrew B.

2017-01-01

Several biophysical approaches are available to study protein–protein interactions. Most approaches are conducted in bulk solution, and are therefore limited to an average measurement of the ensemble of molecular interactions. Here, we show how single-particle EM can enrich our understanding of protein–protein interactions at the single-molecule level and potentially capture states that are unobservable with ensemble methods because they are below the limit of detection or not conducted on an appropriate time scale. Using the HIV-1 envelope glycoprotein (Env) and its interaction with receptor CD4-binding site neutralizing antibodies as a model system, we both corroborate ensemble kinetics-derived parameters and demonstrate how time-course EM can further dissect stoichiometric states of complexes that are not readily observable with other methods. Visualization of the kinetics and stoichiometry of Env–antibody complexes demonstrated the applicability of our approach to qualitatively and semi-quantitatively differentiate two highly similar neutralizing antibodies. Furthermore, implementation of machine-learning techniques for sorting class averages of these complexes into discrete subclasses of particles helped reduce human bias. Our data provide proof of concept that single-particle EM can be used to generate a “visual” kinetic profile that should be amenable to studying many other protein–protein interactions, is relatively simple and complementary to well-established biophysical approaches. Moreover, our method provides critical insights into broadly neutralizing antibody recognition of Env, which may inform vaccine immunogen design and immunotherapeutic development. PMID:28972148