WorldWideScience

Sample records for two-tissue compartmental models

  1. PET kinetic analysis. Compartmental model

    International Nuclear Information System (INIS)

    Watabe, Hiroshi; Ikoma, Yoko; Shidahara, Miho; Kimura, Yuichi; Naganawa, Mika

    2006-01-01

    Positron emission tomography (PET) enables not only visualization of the distribution of radiotracer, but also has ability to quantify several biomedical functions. Compartmental model is a basic idea to analyze dynamic PET data. This review describes the principle of the compartmental model and categorizes the techniques and approaches for the compartmental model according to various aspects: model design, experimental design, invasiveness, and mathematical solution. We also discussed advanced applications of the compartmental analysis with PET. (author)

  2. Compartmental modeling and tracer kinetics

    CERN Document Server

    Anderson, David H

    1983-01-01

    This monograph is concerned with mathematical aspects of compartmental an­ alysis. In particular, linear models are closely analyzed since they are fully justifiable as an investigative tool in tracer experiments. The objective of the monograph is to bring the reader up to date on some of the current mathematical prob­ lems of interest in compartmental analysis. This is accomplished by reviewing mathematical developments in the literature, especially over the last 10-15 years, and by presenting some new thoughts and directions for future mathematical research. These notes started as a series of lectures that I gave while visiting with the Division of Applied ~1athematics, Brown University, 1979, and have developed in­ to this collection of articles aimed at the reader with a beginning graduate level background in mathematics. The text can be used as a self-paced reading course. With this in mind, exercises have been appropriately placed throughout the notes. As an aid in reading the material, the e~d of a ...

  3. Approximations of kidney models and compartmental kidney models

    International Nuclear Information System (INIS)

    Nahorski, Z.

    1996-01-01

    Compartmental models were proposed in sixties to model the flow of isotopes through the kidney. These models were then criticized to not conform to the physiology of the kidney flow of isotopes. That is why they were abandoned, even thought their fits to the measured data were usually good. In this paper it is shown that some approximations of a physiological model proposed earlier by the present author can be interpreted as equations describing compartmental models. Their parameters have, however, different interpretation than the rates of intercompartmental flows. Diagrams of the time variations of the isotope content in the kidney are compared for the exact and approximate model using computer simulation technique

  4. Compartmental analysis of dynamic nuclear medicine data: models and identifiability

    Science.gov (United States)

    Delbary, Fabrice; Garbarino, Sara; Vivaldi, Valentina

    2016-12-01

    Compartmental models based on tracer mass balance are extensively used in clinical and pre-clinical nuclear medicine in order to obtain quantitative information on tracer metabolism in the biological tissue. This paper is the first of a series of two that deal with the problem of tracer coefficient estimation via compartmental modelling in an inverse problem framework. Specifically, here we discuss the identifiability problem for a general n-dimension compartmental system and provide uniqueness results in the case of two-compartment and three-compartment compartmental models. The second paper will utilize this framework in order to show how nonlinear regularization schemes can be applied to obtain numerical estimates of the tracer coefficients in the case of nuclear medicine data corresponding to brain, liver and kidney physiology.

  5. Animal-to-Human Extrapolation Using Compartmental Models

    Science.gov (United States)

    1991-01-01

    In this article, designates the excretory organ (for example, the kidney). The we will address the general methodology of extrapolation using symbol...must be true in any compartmental system because they are exposure (9). based on physical principles. In these equations the V1, Qj, k, In the setting...and diffusion approximation models to a simple perfusion-diffusion system governed by partial differential equations for v or, C,, which analytic

  6. Compartmentalization analysis using discrete fracture network models

    Energy Technology Data Exchange (ETDEWEB)

    La Pointe, P.R.; Eiben, T.; Dershowitz, W. [Golder Associates, Redmond, VA (United States); Wadleigh, E. [Marathon Oil Co., Midland, TX (United States)

    1997-08-01

    This paper illustrates how Discrete Fracture Network (DFN) technology can serve as a basis for the calculation of reservoir engineering parameters for the development of fractured reservoirs. It describes the development of quantitative techniques for defining the geometry and volume of structurally controlled compartments. These techniques are based on a combination of stochastic geometry, computational geometry, and graph the theory. The parameters addressed are compartment size, matrix block size and tributary drainage volume. The concept of DFN models is explained and methodologies to compute these parameters are demonstrated.

  7. Evaluation of a compartmental model for estimating tumor hypoxia via FMISO dynamic PET imaging

    International Nuclear Information System (INIS)

    Wang Wenli; Nehmeh, Sadek A; O'Donoghue, Joseph; Zanzonico, Pat B; Schmidtlein, C Ross; Lee, Nancy Y; Humm, John L; Georgi, Jens-Christoph; Paulus, Timo; Narayanan, Manoj; Bal, Matthieu

    2009-01-01

    This paper systematically evaluates a pharmacokinetic compartmental model for identifying tumor hypoxia using dynamic positron emission tomography (PET) imaging with 18 F-fluoromisonidazole (FMISO). A generic irreversible one-plasma two-tissue compartmental model was used. A dynamic PET image dataset was simulated with three tumor regions-normoxic, hypoxic and necrotic-embedded in a normal-tissue background, and with an image-based arterial input function. Each voxelized tissue's time activity curve (TAC) was simulated with typical values of kinetic parameters, as deduced from FMISO-PET data from nine head-and-neck cancer patients. The dynamic dataset was first produced without any statistical noise to ensure that correct kinetic parameters were reproducible. Next, to investigate the stability of kinetic parameter estimation in the presence of noise, 1000 noisy samples of the dynamic dataset were generated, from which 1000 noisy estimates of kinetic parameters were calculated and used to estimate the sample mean and covariance matrix. It is found that a more peaked input function gave less variation in various kinetic parameters, and the variation of kinetic parameters could also be reduced by two region-of-interest averaging techniques. To further investigate how bias in the arterial input function affected the kinetic parameter estimation, a shift error was introduced in the peak amplitude and peak location of the input TAC, and the bias of various kinetic parameters calculated. In summary, mathematical phantom studies have been used to determine the statistical accuracy and precision of model-based kinetic analysis, which helps to validate this analysis and provides guidance in planning clinical dynamic FMISO-PET studies.

  8. Efficient Vaccine Distribution Based on a Hybrid Compartmental Model.

    Directory of Open Access Journals (Sweden)

    Zhiwen Yu

    Full Text Available To effectively and efficiently reduce the morbidity and mortality that may be caused by outbreaks of emerging infectious diseases, it is very important for public health agencies to make informed decisions for controlling the spread of the disease. Such decisions must incorporate various kinds of intervention strategies, such as vaccinations, school closures and border restrictions. Recently, researchers have paid increased attention to searching for effective vaccine distribution strategies for reducing the effects of pandemic outbreaks when resources are limited. Most of the existing research work has been focused on how to design an effective age-structured epidemic model and to select a suitable vaccine distribution strategy to prevent the propagation of an infectious virus. Models that evaluate age structure effects are common, but models that additionally evaluate geographical effects are less common. In this paper, we propose a new SEIR (susceptible-exposed-infectious šC recovered model, named the hybrid SEIR-V model (HSEIR-V, which considers not only the dynamics of infection prevalence in several age-specific host populations, but also seeks to characterize the dynamics by which a virus spreads in various geographic districts. Several vaccination strategies such as different kinds of vaccine coverage, different vaccine releasing times and different vaccine deployment methods are incorporated into the HSEIR-V compartmental model. We also design four hybrid vaccination distribution strategies (based on population size, contact pattern matrix, infection rate and infectious risk for controlling the spread of viral infections. Based on data from the 2009-2010 H1N1 influenza epidemic, we evaluate the effectiveness of our proposed HSEIR-V model and study the effects of different types of human behaviour in responding to epidemics.

  9. Compartmental models for assessing the fishery production in the Indian Ocean

    Digital Repository Service at National Institute of Oceanography (India)

    Dalal, S.G.; Parulekar, A.H.

    Compartmental models for assessing the fishery production in the Indian Ocean is discussed. The article examines the theoretical basis on which modern fishery sciences is built. The model shows that, large changes in energy flux from one pathway...

  10. Spatial variability in compartmental fate modelling : Linking fugacity models and GIS.

    Science.gov (United States)

    Wania, F

    1996-03-01

    A new approach is presented which is designed to address the spatial heterogeneity of the environment in compartmental mass balance models of chemical fate in the environment. It rests on the assumption of chemical equilibration within one phase despite prevailing environmental heterogeneity. Composite D- and Z-values are derived from sub-unit specific environmental parameters and are used to solve mass balance equations which can be adopted essentially unchanged from existing compartmental fugacity models. With the resulting common fugacity value for each compartment, sub-unit specific concentrations and process rates can be calculated. The approach is illustrated using the QWASI lake model to calculate the fate of hexachlorobenzene in a hypothetical lake sub-divided in four distinct sub-units. The approach allows the subdivision of each compartment in a large number of sub-units with distinct environmental characteristics without substantially increasing model complexity. This is a necessary condition for linking fugacity models to geographical information systems.

  11. Global identifiability of linear compartmental models--a computer algebra algorithm.

    Science.gov (United States)

    Audoly, S; D'Angiò, L; Saccomani, M P; Cobelli, C

    1998-01-01

    A priori global identifiability deals with the uniqueness of the solution for the unknown parameters of a model and is, thus, a prerequisite for parameter estimation of biological dynamic models. Global identifiability is however difficult to test, since it requires solving a system of algebraic nonlinear equations which increases both in nonlinearity degree and number of terms and unknowns with increasing model order. In this paper, a computer algebra tool, GLOBI (GLOBal Identifiability) is presented, which combines the topological transfer function method with the Buchberger algorithm, to test global identifiability of linear compartmental models. GLOBI allows for the automatic testing of a priori global identifiability of general structure compartmental models from general multi input-multi output experiments. Examples of usage of GLOBI to analyze a priori global identifiability of some complex biological compartmental models are provided.

  12. Modeling influenza-like illnesses through composite compartmental models

    Science.gov (United States)

    Levy, Nir; , Michael, Iv; Yom-Tov, Elad

    2018-03-01

    Epidemiological models for the spread of pathogens in a population are usually only able to describe a single pathogen. This makes their application unrealistic in cases where multiple pathogens with similar symptoms are spreading concurrently within the same population. Here we describe a method which makes possible the application of multiple single-strain models under minimal conditions. As such, our method provides a bridge between theoretical models of epidemiology and data-driven approaches for modeling of influenza and other similar viruses. Our model extends the Susceptible-Infected-Recovered model to higher dimensions, allowing the modeling of a population infected by multiple viruses. We further provide a method, based on an overcomplete dictionary of feasible realizations of SIR solutions, to blindly partition the time series representing the number of infected people in a population into individual components, each representing the effect of a single pathogen. We demonstrate the applicability of our proposed method on five years of seasonal influenza-like illness (ILI) rates, estimated from Twitter data. We demonstrate that our method describes, on average, 44% of the variance in the ILI time series. The individual infectious components derived from our model are matched to known viral profiles in the populations, which we demonstrate matches that of independently collected epidemiological data. We further show that the basic reproductive numbers (R 0) of the matched components are in range known for these pathogens. Our results suggest that the proposed method can be applied to other pathogens and geographies, providing a simple method for estimating the parameters of epidemics in a population.

  13. Compartmental Model For Uptake Of 137cs By Pine In Forest Soil ...

    African Journals Online (AJOL)

    A compartmental model of soil to pine tree transfer of 137Cs following the Chernobyl nuclear accident is presented. The model was validated using data collected in 1996 at five sites in Northern Ukraine. The transfer constants of 137Cs between model compartments are estimated using a semi-empirical method.

  14. Statistical properties of compartmental model parameters extracted from dynamic positron emission tomography experiments

    International Nuclear Information System (INIS)

    Mazoyer, B.M.; Huesman, R.H.; Budinger, T.F.; Knittel, B.L.

    1986-01-01

    Over the past years a major focus of research in physiologic studies employing tracers has been the computer implementation of mathematical methods of kinetic modeling for extracting the desired physiological parameters from tomographically derived data. A study is reported of factors that affect the statistical properties of compartmental model parameters extracted from dynamic positron emission tomography (PET) experiments

  15. Reconstruction and modeling protein translocation and compartmentalization in Escherichia coli at the genome-scale

    DEFF Research Database (Denmark)

    Liu, Joanne K.; O’Brien, Edward J.; Lerman, Joshua A.

    2014-01-01

    cell morphology. Comparison of computations performed with this expanded ME-model, named iJL1678-ME, against available experimental data reveals that the model accurately describes translocation pathway expression and the functional proteome by compartmentalized mass. Conclusion: iJL1678-ME enables...

  16. A new method to estimate parameters of linear compartmental models using artificial neural networks

    International Nuclear Information System (INIS)

    Gambhir, Sanjiv S.; Keppenne, Christian L.; Phelps, Michael E.; Banerjee, Pranab K.

    1998-01-01

    At present, the preferred tool for parameter estimation in compartmental analysis is an iterative procedure; weighted nonlinear regression. For a large number of applications, observed data can be fitted to sums of exponentials whose parameters are directly related to the rate constants/coefficients of the compartmental models. Since weighted nonlinear regression often has to be repeated for many different data sets, the process of fitting data from compartmental systems can be very time consuming. Furthermore the minimization routine often converges to a local (as opposed to global) minimum. In this paper, we examine the possibility of using artificial neural networks instead of weighted nonlinear regression in order to estimate model parameters. We train simple feed-forward neural networks to produce as outputs the parameter values of a given model when kinetic data are fed to the networks' input layer. The artificial neural networks produce unbiased estimates and are orders of magnitude faster than regression algorithms. At noise levels typical of many real applications, the neural networks are found to produce lower variance estimates than weighted nonlinear regression in the estimation of parameters from mono- and biexponential models. These results are primarily due to the inability of weighted nonlinear regression to converge. These results establish that artificial neural networks are powerful tools for estimating parameters for simple compartmental models. (author)

  17. A Residual Approach for Balanced Truncation Model Reduction (BTMR of Compartmental Systems

    Directory of Open Access Journals (Sweden)

    William La Cruz

    2014-05-01

    Full Text Available This paper presents a residual approach of the square root balanced truncation algorithm for model order reduction of continuous, linear and time-invariante compartmental systems. Specifically, the new approach uses a residual method to approximate the controllability and observability gramians, whose resolution is an essential step of the square root balanced truncation algorithm, that requires a great computational cost. Numerical experiences are included to highlight the efficacy of the proposed approach.

  18. A compartmental model for computer virus propagation with kill signals

    Science.gov (United States)

    Ren, Jianguo; Xu, Yonghong

    2017-11-01

    Research in the area of kill signals for prevention of computer virus is of significant importance for computer users. The kill signals allow computer users to take precautions beforehand. In this paper, a computer virus propagation model based on the kill signals, called SEIR-KS model, is formulated and full dynamics of the proposed model are theoretically analyzed. An epidemic threshold is obtained and the existence and uniqueness of the virus equilibrium are investigated. It is proved that the virus-free equilibrium and virus equilibrium are locally and globally asymptotically stable by applying Routh-Hurwitz criterion and Lyapunov functional approach. The results of numerical simulations are provided that verifies the theoretical results. The availability of the proposed model has been validated with following observations: (1) the density of infected nodes in the proposed model drops to approximately 75% compared to the model in related literature; and (2) a higher density of KS is conductive to inhibition of virus diffusion.

  19. A three compartmental model for global distribution of tritium

    International Nuclear Information System (INIS)

    Sadarangani, S.H.

    1996-01-01

    Atmospheric testing of thermonuclear devices has introduced large quantities of residual tritium into the atmosphere and subsequently this tritium has found its way into the bio-sphere. Though the introduction of tritium into the atmosphere has ceased, migration of the earlier contribution through the different ecological compartments continues to be of interest. In order to assess its present distribution and future trends a mathematical model, based on production, decay and migration of tritium has been developed. The model identifies three distinct compartments i.e. atmosphere, land surface waters and ocean surface waters. Contribution from all the thermonuclear tests has been assessed and the tritium concentrations present in the different compartments are computed. The computed concentration values compare well with experimentally obtained concentration values. (author). 4 refs., 1 tab., 5 figs

  20. DISTING: A web application for fast algorithmic computation of alternative indistinguishable linear compartmental models.

    Science.gov (United States)

    Davidson, Natalie R; Godfrey, Keith R; Alquaddoomi, Faisal; Nola, David; DiStefano, Joseph J

    2017-05-01

    We describe and illustrate use of DISTING, a novel web application for computing alternative structurally identifiable linear compartmental models that are input-output indistinguishable from a postulated linear compartmental model. Several computer packages are available for analysing the structural identifiability of such models, but DISTING is the first to be made available for assessing indistinguishability. The computational algorithms embedded in DISTING are based on advanced versions of established geometric and algebraic properties of linear compartmental models, embedded in a user-friendly graphic model user interface. Novel computational tools greatly speed up the overall procedure. These include algorithms for Jacobian matrix reduction, submatrix rank reduction, and parallelization of candidate rank computations in symbolic matrix analysis. The application of DISTING to three postulated models with respectively two, three and four compartments is given. The 2-compartment example is used to illustrate the indistinguishability problem; the original (unidentifiable) model is found to have two structurally identifiable models that are indistinguishable from it. The 3-compartment example has three structurally identifiable indistinguishable models. It is found from DISTING that the four-compartment example has five structurally identifiable models indistinguishable from the original postulated model. This example shows that care is needed when dealing with models that have two or more compartments which are neither perturbed nor observed, because the numbering of these compartments may be arbitrary. DISTING is universally and freely available via the Internet. It is easy to use and circumvents tedious and complicated algebraic analysis previously done by hand. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Incorporating hydraulic/hydromorphologic properties and their stage dependency into hydrologic compartmental models

    Science.gov (United States)

    Gustafsson, A.; Wörman, A.

    2009-04-01

    According to recent studies, the volumetric error of the predicted size of the spring flood in Sweden can be as large as 20%. A significant part of this error originates from simplifications in the spatial and hydrodynamic description of watercourse networks, as well as statistical problems to give proper weight to extreme flows. Possible ways to improve current hydrological modelling practises is by making models more adapted to varying flow conditions as well as by increasing the coupling between model parameters and physical catchment characteristics. This study formulates a methodology based in hydrodynamical/hydraulic theory to investigate how river network characteristics vary with flow stage and how to transfer this information to compartmental hydrologic models such as the HBV/HYPE models. This is particularly important during extreme flows when a significant portion of the water flows outside the normal stream channels. The aim is to combine knowledge about the hydrodynamics and hydro-morphology of watercourse networks to improve the predictions of peak flows. HYPE is a semi-distributed conceptual compartmental hydrological model which is currently being developed at the SMHI as a successor to the HBV model. The model (HYPE) is thought to be better adapted to varying flow conditions by using the dynamical response functions derived by the methodology described here. The distribution of residence times within the watercourse network - and how these depend on flow stage is analysed. This information is then incorporated into the response functions of the HYPE model, i.e. the compartmental model receives a dynamic transformation function relating river discharge to storativity within the sub-catchment. This response function hence reflects the topologic and hydromorphologic characteristics of the watercourse network as well as flow stage. Seven subcatchments in Rönne River basin (1900 km2) are studied to show how this approach can improve the prediction of

  2. Reconstruction of Arabidopsis metabolic network models accounting for subcellular compartmentalization and tissue-specificity.

    Science.gov (United States)

    Mintz-Oron, Shira; Meir, Sagit; Malitsky, Sergey; Ruppin, Eytan; Aharoni, Asaph; Shlomi, Tomer

    2012-01-03

    Plant metabolic engineering is commonly used in the production of functional foods and quality trait improvement. However, to date, computational model-based approaches have only been scarcely used in this important endeavor, in marked contrast to their prominent success in microbial metabolic engineering. In this study we present a computational pipeline for the reconstruction of fully compartmentalized tissue-specific models of Arabidopsis thaliana on a genome scale. This reconstruction involves automatic extraction of known biochemical reactions in Arabidopsis for both primary and secondary metabolism, automatic gap-filling, and the implementation of methods for determining subcellular localization and tissue assignment of enzymes. The reconstructed tissue models are amenable for constraint-based modeling analysis, and significantly extend upon previous model reconstructions. A set of computational validations (i.e., cross-validation tests, simulations of known metabolic functionalities) and experimental validations (comparison with experimental metabolomics datasets under various compartments and tissues) strongly testify to the predictive ability of the models. The utility of the derived models was demonstrated in the prediction of measured fluxes in metabolically engineered seed strains and the design of genetic manipulations that are expected to increase vitamin E content, a significant nutrient for human health. Overall, the reconstructed tissue models are expected to lay down the foundations for computational-based rational design of plant metabolic engineering. The reconstructed compartmentalized Arabidopsis tissue models are MIRIAM-compliant and are available upon request.

  3. A compartmental model of the cAMP/PKA/MAPK pathway in Bio-PEPA

    Directory of Open Access Journals (Sweden)

    Federica Ciocchetta

    2009-11-01

    Full Text Available The vast majority of biochemical systems involve the exchange of information between different compartments, either in the form of transportation or via the intervention of membrane proteins which are able to transmit stimuli between bordering compartments. The correct quantitative handling of compartments is, therefore, extremely important when modelling real biochemical systems. The Bio-PEPA process algebra is equipped with the capability of explicitly defining quantitative information such as compartment volumes and membrane surface areas. Furthermore, the recent development of the Bio-PEPA Eclipse Plug-in allows us to perform a correct stochastic simulation of multi-compartmental models. Here we present a Bio-PEPA compartmental model of the cAMP/PKA/MAPK pathway. We analyse the system using the Bio-PEPA Eclipse Plug-in and we show the correctness of our model by comparison with an existing ODE model. Furthermore, we perform computational experiments in order to investigate certain properties of the pathway. Specifically, we focus on the system response to the inhibition and strengthening of feedback loops and to the variation in the activity of key pathway reactions and we observe how these modifications affect the behaviour of the pathway. These experiments are useful to understand the control and regulatory mechanisms of the system.

  4. A comprehensive compartmental model of blood glucose regulation for healthy and type 2 diabetic subjects

    DEFF Research Database (Denmark)

    Vahidi, O; Kwok, K E; Gopaluni, R B

    2016-01-01

    We have expanded a former compartmental model of blood glucose regulation for healthy and type 2 diabetic subjects. The former model was a detailed physiological model which considered the interactions of three substances, glucose, insulin and glucagon on regulating the blood sugar. The main...... variations of blood glucose concentrations following an oral glucose intake. Another model representing the incretins production in the gastrointestinal tract along with their hormonal effects on boosting pancreatic insulin production is also added to the former model. We have used two sets of clinical data...... obtained during oral glucose tolerance test and isoglycemic intravenous glucose infusion test from both type 2 diabetic and healthy subjects to estimate the model parameters and to validate the model results. The estimation of model parameters is accomplished through solving a nonlinear optimization...

  5. Assessment of spatial heterogeneity in continuous twin screw wet granulation process using three-compartmental population balance model.

    Science.gov (United States)

    Liu, Huolong; Galbraith, Shaun C; Park, Seo-Young; Cha, Bumjoon; Huang, Zhuangrong; Meyer, Robert Frederick; Flamm, Matthew H; O'Connor, Thomas; Lee, Sau; Yoon, Seongkyu

    2018-01-25

    In this study, a novel three-compartmental population balance model (PBM) for a continuous twin screw wet granulation process is developed, combining the techniques of PBM and regression process modeling. The developed model links screw configuration, screw speed, and blend throughput with granule properties to predict the granule size distribution (GSD) and volume-average granule diameter. The granulator screw barrel was divided into three compartments along barrel length: wetting compartment, mixing compartment, and steady growth compartment. Different granulation mechanisms are assumed in each compartment. The proposed model therefore considers spatial heterogeneity, improving model prediction accuracy. An industrial data set containing 14 experiments is applied for model development. Three validation experiments show that the three-compartmental PBM can accurately predict granule diameter and size distribution at randomly selected operating conditions. Sixteen combinations of aggregation and breakage kernels are investigated in predicting the experimental GSD to best judge the granulation mechanism. The three-compartmental model is compared with a one-compartmental model in predicting granule diameter at different experimental conditions to demonstrate its advantage. The influence of the screw configuration, screw speed and blend throughput on the volume-average granule diameter is analyzed based on the developed model.

  6. Compartmentalization today

    Science.gov (United States)

    Kevin T. Smith

    2006-01-01

    For more than 30 years, the compartmentdization concept has helped tree care practitioners and land managers interpret patterns of decay in living trees. Understanding these patterns can help guide the selection of treatments that meet the needs of people and communities while respecting the underlying tree biology. At its simplest, compartmentalization resists the...

  7. Savannah River Laboratory DOSTOMAN code: a compartmental pathways computer model of contaminant transport

    International Nuclear Information System (INIS)

    King, C.M.; Wilhite, E.L.; Root, R.W. Jr.

    1985-01-01

    The Savannah River Laboratory DOSTOMAN code has been used since 1978 for environmental pathway analysis of potential migration of radionuclides and hazardous chemicals. The DOSTOMAN work is reviewed including a summary of historical use of compartmental models, the mathematical basis for the DOSTOMAN code, examples of exact analytical solutions for simple matrices, methods for numerical solution of complex matrices, and mathematical validation/calibration of the SRL code. The review includes the methodology for application to nuclear and hazardous chemical waste disposal, examples of use of the model in contaminant transport and pathway analysis, a user's guide for computer implementation, peer review of the code, and use of DOSTOMAN at other Department of Energy sites. 22 refs., 3 figs

  8. The construction of next-generation matrices for compartmental epidemic models.

    Science.gov (United States)

    Diekmann, O; Heesterbeek, J A P; Roberts, M G

    2010-06-06

    The basic reproduction number (0) is arguably the most important quantity in infectious disease epidemiology. The next-generation matrix (NGM) is the natural basis for the definition and calculation of (0) where finitely many different categories of individuals are recognized. We clear up confusion that has been around in the literature concerning the construction of this matrix, specifically for the most frequently used so-called compartmental models. We present a detailed easy recipe for the construction of the NGM from basic ingredients derived directly from the specifications of the model. We show that two related matrices exist which we define to be the NGM with large domain and the NGM with small domain. The three matrices together reflect the range of possibilities encountered in the literature for the characterization of (0). We show how they are connected and how their construction follows from the basic model ingredients, and establish that they have the same non-zero eigenvalues, the largest of which is the basic reproduction number (0). Although we present formal recipes based on linear algebra, we encourage the construction of the NGM by way of direct epidemiological reasoning, using the clear interpretation of the elements of the NGM and of the model ingredients. We present a selection of examples as a practical guide to our methods. In the appendix we present an elementary but complete proof that (0) defined as the dominant eigenvalue of the NGM for compartmental systems and the Malthusian parameter r, the real-time exponential growth rate in the early phase of an outbreak, are connected by the properties that (0) > 1 if and only if r > 0, and (0) = 1 if and only if r = 0.

  9. A comprehensive compartmental model of blood glucose regulation for healthy and type 2 diabetic subjects.

    Science.gov (United States)

    Vahidi, O; Kwok, K E; Gopaluni, R B; Knop, F K

    2016-09-01

    We have expanded a former compartmental model of blood glucose regulation for healthy and type 2 diabetic subjects. The former model was a detailed physiological model which considered the interactions of three substances, glucose, insulin and glucagon on regulating the blood sugar. The main drawback of the former model was its restriction on the route of glucose entrance to the body which was limited to the intravenous glucose injection. To handle the oral glucose intake, we have added a model of glucose absorption in the gastrointestinal tract to the former model to address the resultant variations of blood glucose concentrations following an oral glucose intake. Another model representing the incretins production in the gastrointestinal tract along with their hormonal effects on boosting pancreatic insulin production is also added to the former model. We have used two sets of clinical data obtained during oral glucose tolerance test and isoglycemic intravenous glucose infusion test from both type 2 diabetic and healthy subjects to estimate the model parameters and to validate the model results. The estimation of model parameters is accomplished through solving a nonlinear optimization problem. The results show acceptable precision of the estimated model parameters and demonstrate the capability of the model in accurate prediction of the body response during the clinical studies.

  10. Dynamic PET scanning and compartmental model analysis to determine cellular level radiotracer distribution in vivo

    International Nuclear Information System (INIS)

    Smith, G.T.; Hubner, K.F.; Goodman, M.M.; Stubbs, J.B.

    1992-01-01

    Positron emission tomography (PET) has been used to measure tissue radiotracer concentration in vivo. Radiochemical distribution can be determined with compartmental model analysis. A two compartment model describes the kinetics of N-13 ammonia ( 13 NH 3 ) in the myocardium. The model consists of a vascular space, Q 1 and a space for 13 NH 3 bound within the tissue, Q 2 . Differential equations for the model can be written: X(t) = AX(t) + BU( t), Y(t)= CX(t)+ DU(t) (1) where X(t) is a column vector [Q 1 (t); Q 2 (t)], U(t) is the arterial input activity measured from the left ventricular blood pool, and Y(t) is the measured tissue activity using PET. Matrices A, B, C, and D are dependent on physiological parameters describing the kinetics of 13 NH 3 in the myocardium. Estimated parameter matrices in Equation 1 have been validated in dog experiments by measuring myocardial perfusion with dynamic PET scanning and intravenous injection of 13 NH 3 . Tracer concentrations for each compartment can be calculated by direct integration of Equation 1. If the cellular level distribution of each compartment is known, the concentration of tracer within the intracellular and extracellular space can be determined. Applications of this type of modeling include parameter estimation for measurement of physiological processes, organ level dosimetry, and determination of cellular radiotracer distribution

  11. Integrated compartmental model for describing the transport of solute in a fractured porous medium. [FRACPORT

    Energy Technology Data Exchange (ETDEWEB)

    DeAngelis, D.L.; Yeh, G.T.; Huff, D.D.

    1984-10-01

    This report documents a model, FRACPORT, that simulates the transport of a solute through a fractured porous matrix. The model should be useful in analyzing the possible transport of radionuclides from shallow-land burial sites in humid environments. The use of the model is restricted to transport through saturated zones. The report first discusses the general modeling approach used, which is based on the Integrated Compartmental Method. The basic equations of solute transport are then presented. The model, which assumes a known water velocity field, solves these equations on two different time scales; one related to rapid transport of solute along fractures and the other related to slower transport through the porous matrix. FRACPORT is validated by application to a simple example of fractured porous medium transport that has previously been analyzed by other methods. Then its utility is demonstrated in analyzing more complex cases of pulses of solute into a fractured matrix. The report serves as a user's guide to FRACPORT. A detailed description of data input, along with a listing of input for a sample problem, is provided. 16 references, 18 figures, 3 tables.

  12. Linear least squares compartmental-model-independent parameter identification in PET

    International Nuclear Information System (INIS)

    Thie, J.A.; Smith, G.T.; Hubner, K.F.

    1997-01-01

    A simplified approach involving linear-regression straight-line parameter fitting of dynamic scan data is developed for both specific and nonspecific models. Where compartmental-model topologies apply, the measured activity may be expressed in terms of: its integrals, plasma activity and plasma integrals -- all in a linear expression with macroparameters as coefficients. Multiple linear regression, as in spreadsheet software, determines parameters for best data fits. Positron emission tomography (PET)-acquired gray-matter images in a dynamic scan are analyzed: both by this method and by traditional iterative nonlinear least squares. Both patient and simulated data were used. Regression and traditional methods are in expected agreement. Monte-Carlo simulations evaluate parameter standard deviations, due to data noise, and much smaller noise-induced biases. Unique straight-line graphical displays permit visualizing data influences on various macroparameters as changes in slopes. Advantages of regression fitting are: simplicity, speed, ease of implementation in spreadsheet software, avoiding risks of convergence failures or false solutions in iterative least squares, and providing various visualizations of the uptake process by straight line graphical displays. Multiparameter model-independent analyses on lesser understood systems is also made possible

  13. Retinol metabolism in rats with low vitamin A status: A compartmental model

    International Nuclear Information System (INIS)

    Lewis, K.C.; Green, M.H.; Green, J.B.; Zech, L.A.

    1990-01-01

    A compartmental model was developed to describe the metabolism of vitamin A in rats with low vitamin A status maintained by a low dietary intake of vitamin A (approximately 2 micrograms retinol equivalents/day). After the IV bolus injection of [3H]retinol in its physiological transport complex, tracer and trace data were obtained from plasma, organs (liver, kidneys, small intestine, eyes, adrenals, testes, lungs, carcass), and tracer data were obtained from urine and feces. The dietary protocol developed for this study resulted in animals having plasma vitamin A levels less than 10 micrograms retinol/dl and total liver vitamin A levels of approximately 1 microgram retinol equivalent. Four compartments were used to model the plasma: one to describe retinol, one to describe the nonphysiological portion of the dose, and two to simulate polar metabolites derived from retinol. The liver required two compartments and a delay, the carcass (small intestine, eyes, adrenals, testes, and lungs, plus remaining carcass) required three compartments, and the kidneys required two. The model predicted a vitamin A utilization rate of 1.65 micrograms retinol equivalents/day with the urine and feces accounting for most of the output. The plasma retinol turnover rate was approximately 20 micrograms retinol equivalents/day; this was 12 times greater than the utilization rate. This indicated that, of the large amount of retinol moving through the plasma each day, less than 10% of this was actually being irreversibly utilized. Similarly, as compared to the whole-body utilization rate, there was a relatively high turnover rate of retinol in the kidneys, carcass, and liver, coupled with a high degree of recycling of vitamin A through these tissues. Of the total vitamin A that entered the liver from all sources including the diet, approximately 86% was mobilized into the plasma

  14. Computer Modeling of Sand Transport on Mars Using a Compart-Mentalized Fluids Algorithm (CFA)

    Science.gov (United States)

    Marshall, J.; Stratton, D.

    1999-01-01

    of sand comminution on Mars. A multiple-grain transport model using just the equations of grain motion describing lift and drag is impossible to develop owing to stochastic effects --the very effects we wish to model. Also, unless we were to employ supercomputing techniques and extremely complex computer codes that could deal with millions of grains simultaneously, it would also be difficult to model grain transport if we attempted to consider every grain in motion. No existing computer models were found that satisfactorily used the equations of motion to arrive at transport flux numbers for the different populations of saltation and reptation. Modeling all the grains in a transport system was an intractable problem within our resources, and thus we developed what we believe to be a new modeling approach to simulating grain transport. The CFA deals with grain populations, but considers them to belong to various compartmentalized fluid units in the boundary layer. In this way, the model circumvents the multigrain problem by dealing primarily with the consequences of grain transport --momentum transfer between air and grains, which is the physical essence of a dynamic grain-fluid mixture. We thus chose to model the aeolian transport process as a superposition of fluids. These fluids include the air as well as particle populations of various properties. The prime property distinguishing these fluids is upward and downward grain motion. In a normal saltation trajectory, a grain's downwind velocity increases with time, so a rising grain will have a smaller downwind velocity than a failing grain. Because of this disparity in rising and falling grain proper-ties, it seemed appropriate to track these as two separate grain populations within the same physical space. The air itself can be considered a separate fluid superimposed within and interacting with the various grain-cloud "fluids". Additional informaiton is contained in the original.

  15. Stratigraphic and structural compartmentalization observed within a model turbidite reservoir, Pennsylvanian Upper Jackfork Formation, Hollywood Quarry, Arkansas

    Energy Technology Data Exchange (ETDEWEB)

    Slatt, R. [Colorado School of Mines, Golden, CO (United States); Jordan, D. [Arco International Oil and Gas Co., Plano, TX (United States); Stone, C. [Arkansas Geological Commission, Little Rock, AR (United States)] [and others

    1995-08-01

    Hollywood Quarry is a 600 x 375 x 150 ft. (200 x 125 x 50m) excavation which provides a window into lower Pennsylvanian Jackfork Formation turbidite stratal architecture along the crest of a faulted anticlinal fold. A variety of turbidite facies are present, including: (a) lenticular, channelized sandstones, pebbly sandstones, and conglomerates within shale, (b) laterally continuous, interbedded thin sandstones and shales, and (c) thicker, laterally continuous shales. The sandstone and shale layers we broken by several strike-slip and reverse faults, with vertical displacements of up to several feet. This combination of facies and structural elements has resulted in a highly compartmentalized stratigraphic interval, both horizontally and vertically, along the anticlinal flexure. The quarry can be considered analogous to a scaled-down turbidite reservoir. Outcrop gamma-ray logs, measured sections, a fault map, and cross sections provide a database which is analogous to what would be available for a subsurface reservoir. Thus, the quarry provides an ideal outdoor geologic and engineering {open_quote}workshop{close_quote} venue for visualizing the potential complexities of a combination structural-stratigraphic (turbidite) reservoir. Since all forms of compartmentalization are readily visible in the quarry, problems related to management of compartmentalized reservoirs can be discussed and analyzed first-hand while standing in the quarry, within this {open_quote}model reservoir{close_quotes}. These problems include: (a) the high degree of stratigraphic and structural complexity that may be encountered, even at close well spacings, (b) uncertainty in well log correlations and log-shape interpretations, (c) variations in volumetric calculations as a function of amount of data available, and (d) potential production problems associated with specific {open_quote}field{close_quote} development plans.

  16. Use of a Distributed, Finite-Volume, Hydrologic Model to Assess the Sensitivity of the Everglades to De-compartmentalization

    Science.gov (United States)

    Senarath, S. U.

    2002-12-01

    The Everglades, the only remaining subtropical wilderness in the continental USA, is the home to a number of threatened and endangered species. Although the pre-drainage Everglades covered an area of approximately 11,048 km2, urbanization and farming have reduced its area by approximately 50%. The remaining Everglades has also changed as a result of drainage and compartmentalization by over 2,200 km of levees and canals. This area is also adversely affected by exotic species, nutrient enrichment, contaminants and altered freshwater flows. The \\8 billion Comprehensive Everglades Restoration Plan provides a ``framework and guide to restore, protect, and preserve the water resources of central and southern Florida, including the Everglades.'' The success of this project, one of the largest eco-system restoration projects in the world, depends heavily on our understanding of the quantity, quality, timing and distribution of South Florida's pre-drainage freshwater flow. Consequently, accurate hydrologic modeling is crucial for the restoration of the greater Everglades ecosystem. The Regional Simulation Model (RSM) developed by the South Florida Water Management District is currently being used to investigate the effect of de-compartmentalization on freshwater flow dynamics in parts of the remaining Everglades which includes the Everglades National Park and the Big Cypress National Preserve. The RSM is an implicit, finite-volume, continuous, distributed, integrated surface/ground-water model, capable of simulating one-dimensional canal flow and two-dimensional overland flow in arbitrarily shaped areas using a variable triangular mesh. It has physically-based formulations for the simulation of overland and groundwater flow, evapo-transpiration, infiltration, levee seepage, and canal and structure flows. It is capable of simulating features that are unique to South Florida such as low-relief topography, high water tables, saturation-excess runoff, depth

  17. Modulation of cytokine release by differentiated CACO-2 cells in a compartmentalized coculture model with mononuclear leucocytes and nonpathogenic bacteria

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Haller, D.; Brinz, S.

    2004-01-01

    To further investigate the interaction between human mononuclear leucocytes [peripheral blood mononuclear cells (PBMC)] and enterocytes, the effect of a confluent layer of differentiated CACO-2 cells on cytokine kinetics during challenge with bacteria in a compartmentalized coculture model...... was investigated. Nonpathogenic Escherichia coli were added either to the apical or the basolateral compartment of this transwell cell culture system, the latter of which contained human leucocytes. The synthesis of tumour necrosis factor (TNF-alpha) and interleukin (IL)-12 was significantly suppressed by CACO-2...... cells when leucocytes were stimulated directly with bacteria. This suppression was not paralleled by changes in the production of IL-10, IL-6 and transforming growth factor (TGF)-beta. When the bacteria were applied apically to the CACO-2 cell layer, the production of TNF-alpha, IL-12, IL-1beta, IL-8...

  18. Compartmental and noncompartmental modeling of 13C-lycopene absorption, isomerization, and distribution kinetics in healthy adults123

    Science.gov (United States)

    Moran, Nancy E; Cichon, Morgan J; Riedl, Kenneth M; Grainger, Elizabeth M; Schwartz, Steven J; Novotny, Janet A; Erdman, John W; Clinton, Steven K

    2015-01-01

    Background: Lycopene, which is a red carotenoid in tomatoes, has been hypothesized to mediate disease-preventive effects associated with tomato consumption. Lycopene is consumed primarily as the all-trans geometric isomer in foods, whereas human plasma and tissues show greater proportions of cis isomers. Objective: With the use of compartmental modeling and stable isotope technology, we determined whether endogenous all-trans-to-cis-lycopene isomerization or isomeric-bioavailability differences underlie the greater proportion of lycopene cis isomers in human tissues than in tomato foods. Design: Healthy men (n = 4) and women (n = 4) consumed 13C-lycopene (10.2 mg; 82% all-trans and 18% cis), and plasma was collected over 28 d. Unlabeled and 13C-labeled total lycopene and lycopene-isomer plasma concentrations, which were measured with the use of high-performance liquid chromatography–mass spectrometry, were fit to a 7-compartment model. Results: Subjects absorbed a mean ± SEM of 23% ± 6% of the lycopene. The proportion of plasma cis-13C-lycopene isomers increased over time, and all-trans had a shorter half-life than that of cis isomers (5.3 ± 0.3 and 8.8 ± 0.6 d, respectively; P isomerization was predictive of plasma 13C and unlabeled cis- and all-trans-lycopene concentrations. Although the bioavailability of cis (24.5% ± 6%) and all-trans (23.2% ± 8%) isomers did not differ, endogenous isomerization (0.97 ± 0.25 μmol/d in the fast-turnover tissue lycopene pool) drove tissue and plasma isomeric profiles. Conclusion: 13C-Lycopene combined with physiologic compartmental modeling provides a strategy for following complex in vivo metabolic processes in humans and reveals that postabsorptive trans-to-cis-lycopene isomerization, and not the differential bioavailability of isomers, drives tissue and plasma enrichment of cis-lycopene. This trial was registered at clinicaltrials.gov as NCT01692340. PMID:26561629

  19. Compartmental and noncompartmental modeling of ¹³C-lycopene absorption, isomerization, and distribution kinetics in healthy adults.

    Science.gov (United States)

    Moran, Nancy E; Cichon, Morgan J; Riedl, Kenneth M; Grainger, Elizabeth M; Schwartz, Steven J; Novotny, Janet A; Erdman, John W; Clinton, Steven K

    2015-12-01

    Lycopene, which is a red carotenoid in tomatoes, has been hypothesized to mediate disease-preventive effects associated with tomato consumption. Lycopene is consumed primarily as the all-trans geometric isomer in foods, whereas human plasma and tissues show greater proportions of cis isomers. With the use of compartmental modeling and stable isotope technology, we determined whether endogenous all-trans-to-cis-lycopene isomerization or isomeric-bioavailability differences underlie the greater proportion of lycopene cis isomers in human tissues than in tomato foods. Healthy men (n = 4) and women (n = 4) consumed (13)C-lycopene (10.2 mg; 82% all-trans and 18% cis), and plasma was collected over 28 d. Unlabeled and (13)C-labeled total lycopene and lycopene-isomer plasma concentrations, which were measured with the use of high-performance liquid chromatography-mass spectrometry, were fit to a 7-compartment model. Subjects absorbed a mean ± SEM of 23% ± 6% of the lycopene. The proportion of plasma cis-(13)C-lycopene isomers increased over time, and all-trans had a shorter half-life than that of cis isomers (5.3 ± 0.3 and 8.8 ± 0.6 d, respectively; P isomerization was predictive of plasma (13)C and unlabeled cis- and all-trans-lycopene concentrations. Although the bioavailability of cis (24.5% ± 6%) and all-trans (23.2% ± 8%) isomers did not differ, endogenous isomerization (0.97 ± 0.25 μmol/d in the fast-turnover tissue lycopene pool) drove tissue and plasma isomeric profiles. (13)C-Lycopene combined with physiologic compartmental modeling provides a strategy for following complex in vivo metabolic processes in humans and reveals that postabsorptive trans-to-cis-lycopene isomerization, and not the differential bioavailability of isomers, drives tissue and plasma enrichment of cis-lycopene. This trial was registered at clinicaltrials.gov as NCT01692340. © 2015 American Society for Nutrition.

  20. Two-compartmental population balance modeling of a pulsed spray fluidized bed granulation based on computational fluid dynamics (CFD) analysis.

    Science.gov (United States)

    Liu, Huolong; Li, Mingzhong

    2014-11-20

    In this work a two-compartmental population balance model (TCPBM) was proposed to model a pulsed top-spray fluidized bed granulation. The proposed TCPBM considered the spatially heterogeneous granulation mechanisms of the granule growth by dividing the granulator into two perfectly mixed zones of the wetting compartment and drying compartment, in which the aggregation mechanism was assumed in the wetting compartment and the breakage mechanism was considered in the drying compartment. The sizes of the wetting and drying compartments were constant in the TCPBM, in which 30% of the bed was the wetting compartment and 70% of the bed was the drying compartment. The exchange rate of particles between the wetting and drying compartments was determined by the details of the flow properties and distribution of particles predicted by the computational fluid dynamics (CFD) simulation. The experimental validation has shown that the proposed TCPBM can predict evolution of the granule size and distribution within the granulator under different binder spray operating conditions accurately. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Comparison of linear and nonlinear implementation of the compartmental tissue uptake model for dynamic contrast-enhanced MRI.

    Science.gov (United States)

    Kallehauge, Jesper F; Sourbron, Steven; Irving, Benjamin; Tanderup, Kari; Schnabel, Julia A; Chappell, Michael A

    2017-06-01

    Fitting tracer kinetic models using linear methods is much faster than using their nonlinear counterparts, although this comes often at the expense of reduced accuracy and precision. The aim of this study was to derive and compare the performance of the linear compartmental tissue uptake (CTU) model with its nonlinear version with respect to their percentage error and precision. The linear and nonlinear CTU models were initially compared using simulations with varying noise and temporal sampling. Subsequently, the clinical applicability of the linear model was demonstrated on 14 patients with locally advanced cervical cancer examined with dynamic contrast-enhanced magnetic resonance imaging. Simulations revealed equal percentage error and precision when noise was within clinical achievable ranges (contrast-to-noise ratio >10). The linear method was significantly faster than the nonlinear method, with a minimum speedup of around 230 across all tested sampling rates. Clinical analysis revealed that parameters estimated using the linear and nonlinear CTU model were highly correlated (ρ ≥ 0.95). The linear CTU model is computationally more efficient and more stable against temporal downsampling, whereas the nonlinear method is more robust to variations in noise. The two methods may be used interchangeably within clinical achievable ranges of temporal sampling and noise. Magn Reson Med 77:2414-2423, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

  2. A framework for 2-stage global sensitivity analysis of GastroPlus™ compartmental models.

    Science.gov (United States)

    Scherholz, Megerle L; Forder, James; Androulakis, Ioannis P

    2018-04-01

    Parameter sensitivity and uncertainty analysis for physiologically based pharmacokinetic (PBPK) models are becoming an important consideration for regulatory submissions, requiring further evaluation to establish the need for global sensitivity analysis. To demonstrate the benefits of an extensive analysis, global sensitivity was implemented for the GastroPlus™ model, a well-known commercially available platform, using four example drugs: acetaminophen, risperidone, atenolol, and furosemide. The capabilities of GastroPlus were expanded by developing an integrated framework to automate the GastroPlus graphical user interface with AutoIt and for execution of the sensitivity analysis in MATLAB ® . Global sensitivity analysis was performed in two stages using the Morris method to screen over 50 parameters for significant factors followed by quantitative assessment of variability using Sobol's sensitivity analysis. The 2-staged approach significantly reduced computational cost for the larger model without sacrificing interpretation of model behavior, showing that the sensitivity results were well aligned with the biopharmaceutical classification system. Both methods detected nonlinearities and parameter interactions that would have otherwise been missed by local approaches. Future work includes further exploration of how the input domain influences the calculated global sensitivity measures as well as extending the framework to consider a whole-body PBPK model.

  3. Application of compartmental metabolic models for determination of retention and excretion functions

    International Nuclear Information System (INIS)

    Rodrigues Junior, O.

    1994-01-01

    After an intake of radioactive material, its behaviour in the human body can be described by mathematical models, where organs, tissues or regions of the body are treated as a chain of linked compartments. The mathematical approach for such metabolic models is usually done through a system of differential equations of first order with constant coefficients. The solutions of this system of equations associates the radionuclide intake, with the fraction excreted or retained in the organ of interest. A computer program - called INCORP and for running in PC compatible microcomputers - was developed in order to find the solutions of such system of equations, using an analytical method based on expansion of series of exponential matrices. The metabolic model presented in the ICRP-30 publication was simulated using the INCORP program, in order to find the respective retention and excretion curves for selected radionuclides. (author)

  4. Compartmental model for tritium persistence in the soil-plant system

    International Nuclear Information System (INIS)

    Iyengar, T.S.; Sadarangani, S.H.; Vaze, P.K.; Soman, S.D.

    1977-01-01

    A three-component computer model for tritium persistence in the soil-plant system, on the basis of an exponential polynomial is attempted. A series of field experiments with four species of trees, viz. Cardia sebastina, Terminalia catappa, Aracaria bidwilli and Mangifera indica, were carried out to generate data for testing the model. It is observed that there are two short-term components and one long-term component for tritium mean residence time, corresponding to the three phases of tritium in the system, viz. Tissue-Free-Water-Tritium, labile component of Tissue-Bound-Tritium and non-labile component of Tissue-Bound-Tritium. (author)

  5. A multi-task learning approach for compartmental model parameter estimation in DCE-CT sequences.

    Science.gov (United States)

    Romain, Blandine; Letort, Véronique; Lucidarme, Olivier; Rouet, Laurence; Dalché-Buc, Florence

    2013-01-01

    Today's follow-up of patients presenting abdominal tumors is generally performed through acquisition of dynamic sequences of contrast-enhanced CT. Estimating parameters of appropriate models of contrast intake diffusion through tissues should help characterizing the tumor physiology, but is impeded by the high level of noise inherent to the acquisition conditions. To improve the quality of estimation, we consider parameter estimation in voxels as a multi-task learning problem (one task per voxel) that takes advantage from the similarity between two tasks. We introduce a temporal similarity between tasks based on a robust distance between observed contrast-intake profiles of intensity. Using synthetic images, we compare multi-task learning using this temporal similarity, a spatial similarity and a single-task learning. The similarities based on temporal profiles are shown to bring significant improvements compared to the spatial one. Results on real CT sequences also confirm the relevance of the approach.

  6. Classical algorithms for automated parameter-search methods in compartmental neural models - A critical survey based on simulations using neuron

    International Nuclear Information System (INIS)

    Mutihac, R.; Mutihac, R.C.; Cicuttin, A.

    2001-09-01

    gradient-descent techniques are adequate if the parameter space is low-dimensional, relatively smooth, and has a few local minima (e.g., parameterizing single-neuron compartmental models). Only the fast algorithms and/or a decent (low) number of model parameters are candidates for automated parameter search because of practical reasons. Eventually, the size of the parameter space may be reduced and/or parallel supercomputers may be used. Data overfitting may negatively affect the generalization ability of the model. Bayesian methods include Occam's factor, which set the preference for simpler models. Proliferation of (neural) models raises the question of rigorous criteria for comparing the overall performance of various models designed to match the same type of data. Bayesian methods provide the best framework to assess the neural models quantitatively. Paradoxically, parameter-search methods may sometimes be more useful when they fail by discarding unrealistic mechanisms used in the model design, rather than fitting experimental data to an alleged model

  7. Investigations of a compartmental model for leucine kinetics using non-linear mixed effects models with ordinary and stochastic differential equations.

    Science.gov (United States)

    Berglund, Martin; Sunnåker, Mikael; Adiels, Martin; Jirstrand, Mats; Wennberg, Bernt

    2012-12-01

    Non-linear mixed effects (NLME) models represent a powerful tool to simultaneously analyse data from several individuals. In this study, a compartmental model of leucine kinetics is examined and extended with a stochastic differential equation to model non-steady-state concentrations of free leucine in the plasma. Data obtained from tracer/tracee experiments for a group of healthy control individuals and a group of individuals suffering from diabetes mellitus type 2 are analysed. We find that the interindividual variation of the model parameters is much smaller for the NLME models, compared to traditional estimates obtained from each individual separately. Using the mixed effects approach, the population parameters are estimated well also when only half of the data are used for each individual. For a typical individual, the amount of free leucine is predicted to vary with a standard deviation of 8.9% around a mean value during the experiment. Moreover, leucine degradation and protein uptake of leucine is smaller, proteolysis larger and the amount of free leucine in the body is much larger for the diabetic individuals than the control individuals. In conclusion, NLME models offers improved estimates for model parameters in complex models based on tracer/tracee data and may be a suitable tool to reduce data sampling in clinical studies.

  8. Gadoxetate-enhanced MR imaging and compartmental modelling to assess hepatocyte bidirectional transport function in rats with advanced liver fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Giraudeau, Celine; Leporq, Benjamin; Doblas, Sabrina [University Paris Diderot, Sorbonne Paris Cite, Hopital Beaujon, Laboratory of Imaging Biomarkers, UMR1149 Inserm, Clichy (France); Lagadec, Matthieu; Daire, Jean-Luc; Van Beers, Bernard E. [University Paris Diderot, Sorbonne Paris Cite, Hopital Beaujon, Laboratory of Imaging Biomarkers, UMR1149 Inserm, Clichy (France); Beaujon University Hospital Paris Nord, Department of Radiology, Clichy (France); Pastor, Catherine M. [University Paris Diderot, Sorbonne Paris Cite, Hopital Beaujon, Laboratory of Imaging Biomarkers, UMR1149 Inserm, Clichy (France); Hopitaux Universitaires de Geneve, Departement d' Imagerie et des Sciences de l' Information Medicale, Geneva (Switzerland)

    2017-05-15

    Changes in the expression of hepatocyte membrane transporters in advanced fibrosis decrease the hepatic transport function of organic anions. The aim of our study was to assess if these changes can be evaluated with pharmacokinetic analysis of the hepatobiliary transport of the MR contrast agent gadoxetate. Dynamic gadoxetate-enhanced MRI was performed in 17 rats with advanced fibrosis and 8 normal rats. After deconvolution, hepatocyte three-compartmental analysis was performed to calculate the hepatocyte influx, biliary efflux and sinusoidal backflux rates. The expression of Oatp1a1, Mrp2 and Mrp3 organic anion membrane transporters was assessed with reverse transcription polymerase chain reaction. In the rats with advanced fibrosis, the influx and efflux rates of gadoxetate decreased and the backflux rate increased significantly (p = 0.003, 0.041 and 0.010, respectively). Significant correlations were found between influx and Oatp1a1 expression (r = 0.78, p < 0.001), biliary efflux and Mrp2 (r = 0.50, p = 0.016) and sinusoidal backflux and Mrp3 (r = 0.61, p = 0.002). These results show that changes in the bidirectional organic anion hepatocyte transport function in rats with advanced liver fibrosis can be assessed with compartmental analysis of gadoxetate-enhanced MRI. (orig.)

  9. epiModel: a system to build automatically systems of differential equations of compartmental type-epidemiological models.

    Science.gov (United States)

    Cortés, Juan-C; Sánchez-Sánchez, Almudena; Santonja, Francisco-J; Villanueva, Rafael-J

    2011-11-01

    In this paper we describe epiModel, a code developed in Mathematica that facilitates the building of systems of differential equations corresponding to type-epidemiological linear or quadratic models whose characteristics are defined in text files following an easy syntax. It includes the possibility of obtaining the equations of models involving age and/or sex groups. Copyright © 2011. Published by Elsevier Ltd.

  10. PET-based compartmental modeling of {sup 124}I-A33 antibody: quantitative characterization of patient-specific tumor targeting in colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zanzonico, Pat; O' Donoghue, Joseph A.; Humm, John L. [Memorial Sloan Kettering Cancer Center, Department of Medical Physics, New York, NY (United States); Carrasquillo, Jorge A.; Pandit-Taskar, Neeta; Ruan, Shutian; Larson, Steven M. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Smith-Jones, Peter [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Stony Brook School of Medicine, Departments of Psychiatry and Radiology, Stony Brook, NY (United States); Divgi, Chaitanya [Columbia University Medical Center, New York, NY (United States); Scott, Andrew M. [La Trobe University, Olivia Newton-John Cancer Research Institute, Melbourne (Australia); Kemeny, Nancy E.; Wong, Douglas; Scheinberg, David [Memorial Sloan Kettering Cancer Center, Department of Medicine, New York, NY (United States); Fong, Yuman [Memorial Sloan Kettering Cancer Center, Department of Surgery, New York, NY (United States); City of Hope, Department of Surgery, Duarte, CA (United States); Ritter, Gerd; Jungbluth, Achem; Old, Lloyd J. [Memorial Sloan Kettering Cancer Center, Ludwig Institute for Cancer Research, New York, NY (United States)

    2015-10-15

    The molecular specificity of monoclonal antibodies (mAbs) directed against tumor antigens has proven effective for targeted therapy of human cancers, as shown by a growing list of successful antibody-based drug products. We describe a novel, nonlinear compartmental model using PET-derived data to determine the ''best-fit'' parameters and model-derived quantities for optimizing biodistribution of intravenously injected {sup 124}I-labeled antitumor antibodies. As an example of this paradigm, quantitative image and kinetic analyses of anti-A33 humanized mAb (also known as ''A33'') were performed in 11 colorectal cancer patients. Serial whole-body PET scans of {sup 124}I-labeled A33 and blood samples were acquired and the resulting tissue time-activity data for each patient were fit to a nonlinear compartmental model using the SAAM II computer code. Excellent agreement was observed between fitted and measured parameters of tumor uptake, ''off-target'' uptake in bowel mucosa, blood clearance, tumor antigen levels, and percent antigen occupancy. This approach should be generally applicable to antibody-antigen systems in human tumors for which the masses of antigen-expressing tumor and of normal tissues can be estimated and for which antibody kinetics can be measured with PET. Ultimately, based on each patient's resulting ''best-fit'' nonlinear model, a patient-specific optimum mAb dose (in micromoles, for example) may be derived. (orig.)

  11. Current Ideas about Prebiological Compartmentalization

    Science.gov (United States)

    Monnard, Pierre-Alain; Walde, Peter

    2015-01-01

    Contemporary biological cells are highly sophisticated dynamic compartment systems which separate an internal volume from the external medium through a boundary, which controls, in complex ways, the exchange of matter and energy between the cell’s interior and the environment. Since such compartmentalization is a fundamental principle of all forms of life, scenarios have been elaborated about the emergence of prebiological compartments on early Earth, in particular about their likely structural characteristics and dynamic features. Chemical systems that consist of potentially prebiological compartments and chemical reaction networks have been designed to model pre-cellular systems. These systems are often referred to as “protocells”. Past and current protocell model systems are presented and compared. Since the prebiotic formation of cell-like compartments is directly linked to the prebiotic availability of compartment building blocks, a few aspects on the likely chemical inventory on the early Earth are also summarized. PMID:25867709

  12. Compartmentalization of decayed wood associated with Armillaria mellea in several tree species

    Science.gov (United States)

    Alex L. Shigo; Joanna T. Tippett

    1981-01-01

    Decayed wood associated with Armillaria mellea was compartmentalized according to the CODIT (Compartmentalization Of Decay In Trees) model. Compartmentalization in the sapwood began after the tree walled off the area of dead cambium associated with the inflection of the fungus. The fungus spread into dying sapwood beneath and beyond the area of...

  13. A Simple Plasma Retinol Isotope Ratio Method for Estimating β-Carotene Relative Bioefficacy in Humans: Validation with the Use of Model-Based Compartmental Analysis.

    Science.gov (United States)

    Ford, Jennifer Lynn; Green, Joanne Balmer; Lietz, Georg; Oxley, Anthony; Green, Michael H

    2017-09-01

    Background: Provitamin A carotenoids are an important source of dietary vitamin A for many populations. Thus, accurate and simple methods for estimating carotenoid bioefficacy are needed to evaluate the vitamin A value of test solutions and plant sources. β-Carotene bioefficacy is often estimated from the ratio of the areas under plasma isotope response curves after subjects ingest labeled β-carotene and a labeled retinyl acetate reference dose [isotope reference method (IRM)], but to our knowledge, the method has not yet been evaluated for accuracy. Objectives: Our objectives were to develop and test a physiologically based compartmental model that includes both absorptive and postabsorptive β-carotene bioconversion and to use the model to evaluate the accuracy of the IRM and a simple plasma retinol isotope ratio [(RIR), labeled β-carotene-derived retinol/labeled reference-dose-derived retinol in one plasma sample] for estimating relative bioefficacy. Methods: We used model-based compartmental analysis (Simulation, Analysis and Modeling software) to develop and apply a model that provided known values for β-carotene bioefficacy. Theoretical data for 10 subjects were generated by the model and used to determine bioefficacy by RIR and IRM; predictions were compared with known values. We also applied RIR and IRM to previously published data. Results: Plasma RIR accurately predicted β-carotene relative bioefficacy at 14 d or later. IRM also accurately predicted bioefficacy by 14 d, except that, when there was substantial postabsorptive bioconversion, IRM underestimated bioefficacy. Based on our model, 1-d predictions of relative bioefficacy include absorptive plus a portion of early postabsorptive conversion. Conclusion: The plasma RIR is a simple tracer method that accurately predicts β-carotene relative bioefficacy based on analysis of one blood sample obtained at ≥14 d after co-ingestion of labeled β-carotene and retinyl acetate. The method also provides

  14. Drivers of compartmentalization in a Mediterranean pollination network

    DEFF Research Database (Denmark)

    Gonzalez, Ana M. Martin; Allesina, Stefano; Rodrigo, Anselm

    2012-01-01

    We study compartmentalization in a Mediterranean pollination network using three different analytical approaches: unipartite modularity (UM), bipartite modularity (BM) and the group model (GM). Our objectives are to compare compartments obtained with these three approaches and to explore the role...

  15. Lyophilized kits of diamino dithiol compounds for labelling with 99m-technetium. Pharmacokinetics studies and distribution compartmental models of the related complexes

    International Nuclear Information System (INIS)

    Araujo, Elaine Bortoleti de

    1995-01-01

    The present work reflects the clinical interest for labelling diamino dithiol compounds with technetium-99m. Both chosen compounds, L,L-Ethylene dicysteine (L,L-EC) and L,L-Ethylene dicysteine diethyl esther (L,L-ECD) were obtained with relative good yield and characterized by IR and NMR. The study of labelling conditions with technetium-99m showed the influence of the type and mass of reducing agent as well as the pH on the formation of complexes with desired biological characteristics. Radiochemical purity was determined by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). Lyophilised kits of L,L-EC and L,L-ECD for labelling with 99m Tc were obtained, with stability superior to 120 days, when stored under refrigeration, enabling the kits marketing. The ideal formulation of the kits as well as the use of liquid nitrogen in the freezing process, determined the lyophilization success. Distribution biological studies of the 99m Tc complexes were performed on mice by invasive method and on bigger animals by scintigraphic evaluation. Biological distribution studies of the complex 99m Tc-L,L-EC showed fast blood clearance, with the elimination of about 90% of the administered dose after 60 minutes, almost exclusively by the urinary system. The biological distribution results were adjusted to a three compartmental distribution model, as expected for a radiopharmaceutical designed to renal dynamic studies, with tubular elimination. The complex interaction with renal tubular receptors is related with structural characteristics of the compound, more specifically with the presence and location of polar groups. In comparison with 99m Tc-L,L-EC, biological studies of the complex 99m Tc -L,L-ECD showed different distribution aspects, despite some structural similarities. The presence of ethyl groups confers to the complex neutrality and lipophilicity. It cross the intact blood brain barrier and is retained in the brain for enough period

  16. Phase analysis of circadian-related genes in two tissues

    Directory of Open Access Journals (Sweden)

    Li Leping

    2006-02-01

    Full Text Available Abstract Background Recent circadian clock studies using gene expression microarray in two different tissues of mouse have revealed not all circadian-related genes are synchronized in phase or peak expression times across tissues in vivo. Instead, some circadian-related genes may be delayed by 4–8 hrs in peak expression in one tissue relative to the other. These interesting biological observations prompt a statistical question regarding how to distinguish the synchronized genes from genes that are systematically lagged in phase/peak expression time across two tissues. Results We propose a set of techniques from circular statistics to analyze phase angles of circadian-related genes in two tissues. We first estimate the phases of a cycling gene separately in each tissue, which are then used to estimate the paired angular difference of the phase angles of the gene in the two tissues. These differences are modeled as a mixture of two von Mises distributions which enables us to cluster genes into two groups; one group having synchronized transcripts with the same phase in the two tissues, the other containing transcripts with a discrepancy in phase between the two tissues. For each cluster of genes we assess the association of phases across the tissue types using circular-circular regression. We also develop a bootstrap methodology based on a circular-circular regression model to evaluate the improvement in fit provided by allowing two components versus a one-component von-Mises model. Conclusion We applied our proposed methodologies to the circadian-related genes common to heart and liver tissues in Storch et al. 2, and found that an estimated 80% of circadian-related transcripts common to heart and liver tissues were synchronized in phase, and the other 20% of transcripts were lagged about 8 hours in liver relative to heart. The bootstrap p-value for being one cluster is 0.063, which suggests the possibility of two clusters. Our methodologies can

  17. Biodistribution and biological characteristics of p-[(bis-carboxymethyl) aminomethyl carboxyamino] hippuric acid (Pahida) labelled with technetium-99m. Establishment of pharmacokinetics parameters through compartmental model

    International Nuclear Information System (INIS)

    Araujo, E.B. de.

    1990-01-01

    Biologic distribution of p- [(bis-carboxymethylaminomethyl carboxyamino)] hippuric acid (PAHIDA) labeled with sup(99m)Tc in Wistar rats, showed a selective renal uptake among the other organs and tissues. The compound is predominantly eliminated by urinary tract, with small enterohepatic percent of excretion Chromatographic analysis of urine showed the product and possible metabolites. PAHIDA- sup(99m)Tc blood clearance is relatively rapid and a good percent is transported by plasmatic proteins. The percent binding to the erythrocytes is significant after one hour, this is due probably to hydrolysed technetium. The extrapolation of the plasmatic curve denoted the existence of three exponentials, suggesting a model with three compartments: central or intravascular and two peripherics or extravasculars - rapid and slow exchange (retention). Exponential's half life and the transfer constant (k) among the compartments were determined. The compound retention was reaffirmed by whole body determination. The decomposition of the curve in two exponentials allowed to assess the component's half-life. The compartmental model proposed in agreement with the experimental results, showed the complex retention that may be related the binding with the blood components, the possibility of renal metabolization or a structural impediment in the interaction with the tubular cells receptors. (author)

  18. A Generic Multi-Compartmental CNS Distribution Model Structure for 9 Drugs Allows Prediction of Human Brain Target Site Concentrations

    NARCIS (Netherlands)

    Yamamoto, Yumi; Valitalo, Pyry A.; van den Berg, Dirk-Jan; Hartman, Robin; van den Brink, Willem; Wong, Yin Cheong; Huntjens, Dymphy R.; Proost, Johannes H.; Vermeulen, An; Krauwinkel, Walter; Bakshi, Suruchi; Aranzana-Climent, Vincent; Marchand, Sandrine; Dahyot-Fizelier, Claire; Couet, William; Danhof, Meindert; van Hasselt, Johan G. C.; de lange, Elizabeth C. M.

    Purpose Predicting target site drug concentration in the brain is of key importance for the successful development of drugs acting on the central nervous system. We propose a generic mathematical model to describe the pharmacokinetics in brain compartments, and apply this model to predict human

  19. Cellular compartmentalization of secondary metabolism

    Directory of Open Access Journals (Sweden)

    H. Corby eKistler

    2015-02-01

    Full Text Available Fungal secondary metabolism is often considered apart from the essential housekeeping functions of the cell. However, there are clear links between fundamental cellular metabolism and the biochemical pathways leading to secondary metabolite synthesis. Besides utilizing key biochemical precursors shared with the most essential processes of the cell (e.g. amino acids, acetyl CoA, NADPH, enzymes for secondary metabolite synthesis are compartmentalized at conserved subcellular sites that position pathway enzymes to use these common biochemical precursors. Co-compartmentalization of secondary metabolism pathway enzymes also may function to channel precursors, promote pathway efficiency and sequester pathway intermediates and products from the rest of the cell. In this review we discuss the compartmentalization of three well-studied fungal secondary metabolite biosynthetic pathways for penicillin G, aflatoxin and deoxynivalenol, and summarize evidence used to infer subcellular localization. We also discuss how these metabolites potentially are trafficked within the cell and may be exported.

  20. Nonnegative and Compartmental Dynamical Systems

    CERN Document Server

    Haddad, Wassim M; Hui, Qing

    2010-01-01

    This comprehensive book provides the first unified framework for stability and dissipativity analysis and control design for nonnegative and compartmental dynamical systems, which play a key role in a wide range of fields, including engineering, thermal sciences, biology, ecology, economics, genetics, chemistry, medicine, and sociology. Using the highest standards of exposition and rigor, the authors explain these systems and advance the state of the art in their analysis and active control design. Nonnegative and Compartmental Dynamical Systems presents the most complete treatment available o

  1. CELLULAR COMPARTMENTALIZATION AND HEAVY METAL ...

    African Journals Online (AJOL)

    CELLULAR COMPARTMENTALIZATION AND HEAVY METAL LOAD IN THE MOSS. Barbula lambarenensis AROUND A MEGA CEMENT FACTORY IN SOUTHWEST NIGERIA. *. Ogunkunle, C. O. and Fatoba, P. O.. Department of Plant Biology, University of Ilorin .... the free transport of Zn across the cell wall as it.

  2. Modelagem por compartimentos para integrar e comunicar conhecimento em nutrição Compartmental modeling to integrate and communicate nutritional knowledge

    Directory of Open Access Journals (Sweden)

    Edgar O. Oviedo-Rondón

    2007-07-01

    Full Text Available Esta palestra tem o objetivo de apresentar e discutir metodologias utilizadas para modelar e integrar o conhecimento clássico em nutrição animal, e o produzido por novas ciências moleculares como nutrigenoma, proteoma e metaboloma. Estas ciências e a bioinformática estão ajudando a expandir rapidamente o conhecimento dos sistemas biológicos de interesse em nutrição animal. Na palestra discutirei como é importante dedicar parte de nosso tempo a integrar o conhecimento existente para esclarecer os problemas em pesquisa, utilizando as ferramentas mais adequadas para evitar duplicação de pesquisas, que causam desperdício de recursos humanos, econômicos, e de tempo. A modelagem matemática por compartimentos utilizando programas de computador pode ser a melhor maneira de acumular estas informações, integrar diferentes descobertas, e comunicar o conhecimento atual dos sistemas, e do metabolismo de nutrientes às novas gerações, e avançar na determinação mais adequada das exigências nutricionais.This presentation aims to present and discuss methodologies used to model and integrate classical knowledge in animal nutrition, and new discoveries produced by new molecular sciences like nutrigenomics, proteomics and metabolomics. These sciences and bioinformatics are helping to expand >very quickly the knowledge of the biological systems of interest in animal nutrition. I will discuss the importance of dedicating part of our efforts to integrate current knowledge to prioritize research problems using the most adequate tools. This will help to avoid research duplication that causes waste of valuable resources. Compartmental mathematical modeling using computer software could be one of the best ways to accumulate this information. It can help to integrate new discoveries, communicate the knowledge about animal systems and nutrient metabolism to a new generation of scientists, and advance to more accurate determination of nutrient

  3. Advanced compositional gradient and compartmentalization analysis

    Energy Technology Data Exchange (ETDEWEB)

    Canas, Jesus A.; Petti, Daniela; Mullins, Oliver [Schlumberger Servicos de Petroleo Ltda., Rio de Janeiro, RJ (Brazil)

    2008-07-01

    acting as compartmentalization elements. Using this method we present field DFA and pressure gradient data acquisitions and integrate into numerical simulation modeling to conceptually evaluate the impact of fluid composition / properties gradation and compartmentalization in the productivity of some reservoirs. (author)

  4. Compartmentalized Signaling in Neurons: From Cell Biology to Neuroscience.

    Science.gov (United States)

    Terenzio, Marco; Schiavo, Giampietro; Fainzilber, Mike

    2017-11-01

    Neurons are the largest known cells, with complex and highly polarized morphologies. As such, neuronal signaling is highly compartmentalized, requiring sophisticated transfer mechanisms to convey and integrate information within and between sub-neuronal compartments. Here, we survey different modes of compartmentalized signaling in neurons, highlighting examples wherein the fundamental cell biological processes of protein synthesis and degradation, membrane trafficking, and organelle transport are employed to enable the encoding and integration of information, locally and globally within a neuron. Comparisons to other cell types indicate that neurons accentuate widely shared mechanisms, providing invaluable models for the compartmentalization and transfer mechanisms required and used by most eukaryotic cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. A new approach to the compartmental analysis in pharmacokinetics: fractional time evolution of diclofenac.

    Science.gov (United States)

    Popović, Jovan K; Atanacković, Milica T; Pilipović, Ana S; Rapaić, Milan R; Pilipović, Stevan; Atanacković, Teodor M

    2010-04-01

    This study presents a new two compartmental model and its application to the evaluation of diclofenac pharmacokinetics in a small number of healthy adults, during a bioequivalence trial. In the model the integer order derivatives are replaced by derivatives of real order often called fractional order derivatives. Physically that means that a history (memory) of a biological process, realized as a transfer from one compartment to another one with the mass balance conservation, is taken into account. This kind of investigations in pharmacokinetics is founded by Dokoumetzidis and Macheras through the one compartmental models while our contribution is the analysis of multi-dimensional compartmental models with the applications of the two compartmental model in evaluation of diclofenac pharmacokinetics. Two experiments were preformed with 12 healthy volunteers with two slow release 100 mg diclofenac tablet formulations. The agreement of the values predicted by the proposed model with the values obtained through experiments is shown to be good. Thus, pharmacokinetics of slow release diclofenac can be described well by a specific two compartmental model with fractional derivatives of the same order. Parameters in the model are determined by the least-squares method and the Particle Swarm Optimization (PSO) numerical procedure is used. The results show that the fractional order two compartmental model for diclofenac is superior in comparison to the classical two compartmental model. Actually this is true in general case since the classical one is a special case of the fractional one.

  6. A Novel Method for Performance Analysis of Compartmentalized Reservoirs

    Directory of Open Access Journals (Sweden)

    Shahamat Mohammad Sadeq

    2016-05-01

    Full Text Available This paper presents a simple analytical model for performance analysis of compartmentalized reservoirs producing under Constant Terminal Rate (CTR and Constant Terminal Pressure (CTP. The model is based on the well-known material balance and boundary dominated flow equations and is written in terms of capacitance and resistance of a production and a support compartment. These capacitance and resistance terms account for a combination of reservoir parameters which enable the developed model to be used for characterizing such systems. In addition to considering the properties contrast between the two reservoir compartments, the model takes into account existence of transmissibility barriers with the use of resistance terms. The model is used to analyze production performance of unconventional reservoirs, where the multistage fracturing of horizontal wells effectively creates a Stimulated Reservoir Volume (SRV with an enhanced permeability surrounded by a non-stimulated region. It can also be used for analysis of compartmentalized conventional reservoirs. The analytical solutions provide type curves through which the controlling reservoirs parameters of a compartmentalized system can be estimated. The contribution of the supporting compartment is modeled based on a boundary dominated flow assumption. The transient behaviour of the support compartment is captured by application of “distance of investigation” concept. The model shows that depletion of the production and support compartments exhibit two unit slopes on a log-log plot of pressure versus time for CTR. For CTP, however, the depletions display two exponential declines. The depletion signatures are separated by transition periods, which depend on the contribution of the support compartment (i.e. transient or boundary dominated flow. The developed equations can be implemented easily in a spreadsheet application, and are corroborated with the use of a numerical simulation. The study

  7. TNF and IL-10 are major factors in modulation of the phagocytic cell environment in lung and lymph node in tuberculosis: a next-generation two-compartmental model.

    Science.gov (United States)

    Marino, Simeone; Myers, Amy; Flynn, JoAnne L; Kirschner, Denise E

    2010-08-21

    Tuberculosis (TB) is one of the earliest recorded human diseases and still one of the deadliest worldwide. Its causative agent is the bacteria Mycobacterium tuberculosis (Mtb). Cytokine-mediated macrophage activation is a necessary step in control of bacterial growth, and early immunologic events in lymph node and lung are crucial to the outcome of infection, although the factors that influence these environments and the immune response are poorly understood. Our goal is to build the next-generation two-compartmental model of the immune response to provide a gateway to more spatial and mechanistic investigations of M. tuberculosis infection in the LN and lung. Crucial immune factors emerge that affect macrophage populations and inflammation, namely TNF-dependent recruitment and apoptosis, and IL-10 levels. Surprisingly, bacterial load plays a less important role than TNF in increasing the population of infected macrophages and inflammation. Using a mathematical model, it is possible to distinguish the effects of pro-inflammatory (TNF) and anti-inflammatory (IL-10) cytokines on the spectrum of phagocyte populations (macrophages and dendritic cells) in the lung and lymph node. Our results suggest that TNF is a major mediator of recruitment of phagocytes to the lungs. In contrast, IL-10 plays a role in balancing the dominant macrophage phenotype in LN and lung. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  8. Use of a "Super-child" Approach to Assess the Vitamin A Equivalence of Moringa oleifera Leaves, Develop a Compartmental Model for Vitamin A Kinetics, and Estimate Vitamin A Total Body Stores in Young Mexican Children.

    Science.gov (United States)

    Lopez-Teros, Veronica; Ford, Jennifer Lynn; Green, Michael H; Tang, Guangwen; Grusak, Michael A; Quihui-Cota, Luis; Muzhingi, Tawanda; Paz-Cassini, Mariela; Astiazaran-Garcia, Humberto

    2017-12-01

    Background: Worldwide, an estimated 250 million children children. Methods: β-Carotene was intrinsically labeled by growing MO plants in a 2 H 2 O nutrient solution. Fifteen well-nourished children (17-35 mo old) consumed puréed MO leaves (1 mg β-carotene) and a reference dose of [ 13 C 10 ]retinyl acetate (1 mg) in oil. Blood (2 samples/child) was collected 10 times (2 or 3 children each time) over 35 d. The bioefficacy of MO leaves was calculated from areas under the composite "super-child" plasma isotope response curves, and MO VA equivalence was estimated through the use of these values; a compartmental model was developed to predict VA TBS and retinol kinetics through the use of composite plasma [ 13 C 10 ]retinol data. TBS were also estimated with isotope dilution. Results: The relative bioefficacy of β-carotene retinol activity equivalents from MO was 28%; VA equivalence was 3.3:1 by weight (0.56 μmol retinol:1 μmol β-carotene). Kinetics of plasma retinol indicate more rapid plasma appearance and turnover and more extensive recycling in these children than are observed in adults. Model-predicted mean TBS (823 μmol) was similar to values predicted using a retinol isotope dilution equation applied to data from 3 to 6 d after dosing (mean ± SD: 832 ± 176 μmol; n = 7). Conclusions: The super-child approach can be used to estimate population carotenoid bioefficacy and VA equivalence, VA status, and parameters of retinol metabolism from a composite data set. Our results provide initial estimates of retinol kinetics in well-nourished young children with adequate VA stores and demonstrate that MO leaves may be an important source of VA. © 2017 American Society for Nutrition.

  9. Application of compartmental metabolic models for determination of retention and excretion functions; Aplicacao de modelos metabolicos para a determinacao de funcoes de excrecao e retencao

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues Junior, O

    1994-07-01

    After an intake of radioactive material, its behaviour in the human body can be described by mathematical models, where organs, tissues or regions of the body are treated as a chain of linked compartments. The mathematical approach for such metabolic models is usually done through a system of differential equations of first order with constant coefficients. The solutions of this system of equations associates the radionuclide intake, with the fraction excreted or retained in the organ of interest. A computer program - called INCORP and for running in PC compatible microcomputers - was developed in order to find the solutions of such system of equations, using an analytical method based on expansion of series of exponential matrices. The metabolic model presented in the ICRP-30 publication was simulated using the INCORP program, in order to find the respective retention and excretion curves for selected radionuclides. (author)

  10. The architecture of antagonistic networks: Node degree distribution, compartmentalization and nestedness

    Directory of Open Access Journals (Sweden)

    Savannah Nuwagaba

    2015-12-01

    Full Text Available Describing complex ecosystems as networks of interacting components has proved fruitful - revealing many distinctive patterns and dynamics of ecological systems. Of these patterns, three have often been brought up in literature, including species degree distribution, compartmentalization and nestedness, due largely to their implications for the functionality and stability of communities. Here, using 61 empirical antagonistic networks, we aim to settle the inconsistency in literature by (i fitting their node degree distributions to five different parametric models and identifying the one fits the best, (ii measuring the levels of nestedness and compartmentalization of these 61 networks and testing their significance using different null models, and (iii exploring how network connectance affects these three network architecture metrics. This research showed that most antagonistic networks do not display power law degree distributions and that resource species are generally uniformly distributed. We also clearly showed that the conclusion of whether a network is significantly compartmentalized or nested depends largely on the null model used.

  11. The Prediction of the Relative Importance of CYP3A/P-glycoprotein to the Nonlinear Intestinal Absorption of Drugs by Advanced Compartmental Absorption and Transit Model.

    Science.gov (United States)

    Takano, Junichi; Maeda, Kazuya; Bolger, Michael B; Sugiyama, Yuichi

    2016-11-01

    Intestinal CYP3A and P-glycoprotein (P-gp) decrease the intestinal absorption of substrate drugs. Since substrate specificity of CYP3A often overlaps that of P-gp, and estimation of their saturability in the intestine is difficult, dose-dependent F a F g (fraction of the administered drugs that reach the portal blood) of substrate drugs and the relative importance of CYP3A and P-gp have not been clarified in many cases. Thus, we tried to establish the universal methodology for predicting the in vivo absorption of several CYP3A and/or P-gp substrates from in vitro assays. One of the key points is to set up the scaling factor (SF), correcting the difference between the observed in vivo clearance and the predicted clearance from in vitro data. The SFs of V max for CYP3A (SF CYP3A ) and P-gp (SF P-gp ) were simultaneously optimized to explain the F a F g of CYP3A and/or P-gp substrate drugs. The best predictability of F a F g was achieved when considering both SF CYP3A and SF P-gp The simulation also clarified the relative importance of CYP3A and P-gp in determining F a F g In particular, the nonlinear intestinal absorption of verapamil was caused by the saturation of intestinal CYP3A, whereas that of quinidine was governed by the saturation of both CYP3A and P-gp. In addition, the dose-dependent F a F g of selective and dual CYP3A and/or P-gp substrates was well predicted. We therefore propose a methodology for predicting the F a F g of drugs using a mathematical model with optimized SF CYP3A and SF P-gp Our methodology is applicable to in vitro-in vivo extrapolation of intestinal absorption, even if absolute in vivo functions of enzymes/transporters are unclear. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  12. Co-Compartmentation of Terpene Biosynthesis and Storage via Synthetic Droplet

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Cheng [Texas; amp,M Agrilife Synthetic and Systems Biology Innovation Hub, Texas A& amp,M University, College Station, Texas 77843, United States; Department; amp,M University, College Station, Texas 77843, United States; Institute; amp,M University, College Station, Texas 77843, United States; Kim, YongKyoung [Texas; amp,M Agrilife Synthetic and Systems Biology Innovation Hub, Texas A& amp,M University, College Station, Texas 77843, United States; Department; amp,M University, College Station, Texas 77843, United States; Institute; amp,M University, College Station, Texas 77843, United States; Zeng, Yining [Biosciences; Li, Man [Texas; amp,M Agrilife Synthetic and Systems Biology Innovation Hub, Texas A& amp,M University, College Station, Texas 77843, United States; Department; amp,M University, College Station, Texas 77843, United States; Institute; amp,M University, College Station, Texas 77843, United States; Wang, Xin [Texas; amp,M Agrilife Synthetic and Systems Biology Innovation Hub, Texas A& amp,M University, College Station, Texas 77843, United States; Department; amp,M University, College Station, Texas 77843, United States; Institute; amp,M University, College Station, Texas 77843, United States; Hu, Cheng [Texas; amp,M Agrilife Synthetic and Systems Biology Innovation Hub, Texas A& amp,M University, College Station, Texas 77843, United States; Department; amp,M University, College Station, Texas 77843, United States; Institute; amp,M University, College Station, Texas 77843, United States; Gorman, Connor [Texas; amp,M Agrilife Synthetic and Systems Biology Innovation Hub, Texas A& amp,M University, College Station, Texas 77843, United States; Department; amp,M University, College Station, Texas 77843, United States; Institute; amp,M University, College Station, Texas 77843, United States; Dai, Susie Y. [State; Ding, Shi-You [Department; Yuan, Joshua S. [Texas; amp,M Agrilife Synthetic and Systems Biology Innovation Hub, Texas A& amp,M University, College Station, Texas 77843, United States; Department; amp,M University, College Station, Texas 77843, United States; Institute; amp,M University, College Station, Texas 77843, United States

    2018-02-16

    Traditional bioproduct engineering focuses on pathway optimization, yet is often complicated by product inhibition, downstream consumption, and the toxicity of certain products. Here, we present the co-compartmentation of biosynthesis and storage via a synthetic droplet as an effective new strategy to improve the bioproduct yield, with squalene as a model compound. A hydrophobic protein was designed and introduced into the tobacco chloroplast to generate a synthetic droplet for terpene storage. Simultaneously, squalene biosynthesis enzymes were introduced to chloroplasts together with the droplet-forming protein to co-compartmentalize the biosynthesis and storage of squalene. The strategy has enabled a record yield of squalene at 2.6 mg/g fresh weight without compromising plant growth. Confocal fluorescent microscopy imaging, stimulated Raman scattering microscopy, and droplet composition analysis confirmed the formation of synthetic storage droplet in chloroplast. The co-compartmentation of synthetic storage droplet with a targeted metabolic pathway engineering represents a new strategy for enhancing bioproduct yield.

  13. Compartmentation prevents a lethal turbo-explosion of glycolysis in trypanosomes

    NARCIS (Netherlands)

    J.R. Haanstra (Jurgen); A. van Tuijl (Arjen); P. Kessler (Peter); W. Reijnders (Willem); P.A.M. Michels (Paul); H.V. Westerhoff (Hans); M. Parsons (Marilyn); B.M. Bakker (Barbara)

    2008-01-01

    textabstractATP generation by both glycolysis and glycerol catabolism is autocatalytic, because the first kinases of these pathways are fuelled by ATP produced downstream. Previous modeling studies predicted that either feedback inhibition or compartmentation of glycolysis can protect cells from

  14. [Compartmentalized organization of human corpus striatum].

    Science.gov (United States)

    Prensa, L; Parent, A; Giménez-Amaya, J M

    The compartmentalization of the human striatum was first established thanks to the pioneer work of Graybiel and Ragsdale in 1978. These authors described in the human striatum, as well as in the cats and primates, zones poorly stained for the enzyme acetylcholinesterase, which they termed striosomes, that lie in more intensely stained matrix. The striosome/matrix subdivision of the striatum is supported by the distribution of a wide variety of transmitter-related substances and by the organization of striatal afferent and efferent connections. The results of many studies performed in different species in the last twenty years have indicated that the chemical heterogeneity of striatum is more complex than the simple subdivision into striosomes and matrix compartments. Thus, a further subdivisions of the dual striosome/matrix system has been proposed on the basis of the results of a huge amount of works combining tract tracing methods with histochemical techniques. The matrix has been demonstrated to be heterogeneous by containing numerous functional modules that were termed matrisomes. Furthermore, the most recent study of the distribution of a wide variety of neurochemical markers in the striosomal compartment of the human striatum, has revealed that the striosomes are themselves heterogeneous, being composed of a central core and a peripheral region. Since it is now twenty years from the first description of the striosome/matrix organization of the striatum, in this review we intend to summarize the major finding regarding the compartmental organization of this subcortical structure that have been obtained during this period of time.

  15. Compartmentation of redox metabolism in malaria parasites.

    Directory of Open Access Journals (Sweden)

    Sebastian Kehr

    Full Text Available Malaria, caused by the apicomplexan parasite Plasmodium, still represents a major threat to human health and welfare and leads to about one million human deaths annually. Plasmodium is a rapidly multiplying unicellular organism undergoing a complex developmental cycle in man and mosquito - a life style that requires rapid adaptation to various environments. In order to deal with high fluxes of reactive oxygen species and maintain redox regulatory processes and pathogenicity, Plasmodium depends upon an adequate redox balance. By systematically studying the subcellular localization of the major antioxidant and redox regulatory proteins, we obtained the first complete map of redox compartmentation in Plasmodium falciparum. We demonstrate the targeting of two plasmodial peroxiredoxins and a putative glyoxalase system to the apicoplast, a non-photosynthetic plastid. We furthermore obtained a complete picture of the compartmentation of thioredoxin- and glutaredoxin-like proteins. Notably, for the two major antioxidant redox-enzymes--glutathione reductase and thioredoxin reductase--Plasmodium makes use of alternative-translation-initiation (ATI to achieve differential targeting. Dual localization of proteins effected by ATI is likely to occur also in other Apicomplexa and might open new avenues for therapeutic intervention.

  16. Clade-specific differences in active viral replication and compartmentalization

    NARCIS (Netherlands)

    Sala, Monica; Centlivre, Mireille; Wain-Hobson, Simon

    2006-01-01

    This review focuses on the impact of HIV-1 clade-specific polymorphisms on the dynamics of viral replication and compartmentalization in vivo. HIV-1 transcription and compartmentalization are essentially modulated by interconnected parameters: cellular activation by T-cell receptor engagement or

  17. Passive Noise Filtering by Cellular Compartmentalization.

    Science.gov (United States)

    Stoeger, Thomas; Battich, Nico; Pelkmans, Lucas

    2016-03-10

    Chemical reactions contain an inherent element of randomness, which presents itself as noise that interferes with cellular processes and communication. Here we discuss the ability of the spatial partitioning of molecular systems to filter and, thus, remove noise, while preserving regulated and predictable differences between single living cells. In contrast to active noise filtering by network motifs, cellular compartmentalization is highly effective and easily scales to numerous systems without requiring a substantial usage of cellular energy. We will use passive noise filtering by the eukaryotic cell nucleus as an example of how this increases predictability of transcriptional output, with possible implications for the evolution of complex multicellularity. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Sustainability of a Compartmentalized Host-Parasite Replicator System under Periodic Washout-Mixing Cycles

    Directory of Open Access Journals (Sweden)

    Taro Furubayashi

    2018-01-01

    Full Text Available The emergence and dominance of parasitic replicators are among the major hurdles for the proliferation of primitive replicators. Compartmentalization of replicators is proposed to relieve the parasite dominance; however, it remains unclear under what conditions simple compartmentalization uncoupled with internal reaction secures the long-term survival of a population of primitive replicators against incessant parasite emergence. Here, we investigate the sustainability of a compartmentalized host-parasite replicator (CHPR system undergoing periodic washout-mixing cycles, by constructing a mathematical model and performing extensive simulations. We describe sustainable landscapes of the CHPR system in the parameter space and elucidate the mechanism of phase transitions between sustainable and extinct regions. Our findings revealed that a large population size of compartments, a high mixing intensity, and a modest amount of nutrients are important factors for the robust survival of replicators. We also found two distinctive sustainable phases with different mixing intensities. These results suggest that a population of simple host–parasite replicators assumed before the origin of life can be sustained by a simple compartmentalization with periodic washout-mixing processes.

  19. Diffusion and light-dependent compartmentalization of transducin.

    Science.gov (United States)

    Kerov, Vasily; Artemyev, Nikolai O

    2011-01-01

    Diffusion and light-dependent compartmentalization of transducin are essential for phototransduction and light adaptation of rod photoreceptors. Here, transgenic Xenopus laevis models were designed to probe the roles of transducin/rhodopsin interactions and lipid modifications in transducin compartmentalization, membrane mobility, and light-induced translocation. Localization and diffusion of EGFP-fused rod transducin-α subunit (Gα(t1)), mutant Gα(t1) that is predicted to be N-acylated and S-palmitoylated (Gα(t1)A3C), and mutant Gα(t1) uncoupled from light-activated rhodopsin (Gα(t1)-Ctα(s)), were examined by EGFP-fluorescence imaging and fluorescence recovery after photobleaching (FRAP). Similar to Gα(t1), Gα(t1)A3C and Gα(t1)-Ctα(s) were correctly targeted to the rod outer segments in the dark, however the light-dependent translocation of both mutants was markedly impaired. Our analysis revealed a moderate acceleration of the lateral diffusion for the activated Gα(t1) consistent with the diffusion of the separated Gα(t1)GTP and Gβ(1)γ(1) on the membrane surface. Unexpectedly, the kinetics of longitudinal diffusion were comparable for Gα(t1)GTP with a single lipid anchor and heterotrimeric Gα(t1)β(1)γ(1) or Gα(t1)-Ctα(s)β(1)γ(1) with two lipid modifications. This contrasted the lack of the longitudinal diffusion of the Gα(t1)A3C mutant apparently caused by its stable two lipid attachment to the membrane and suggests the existence of a mechanism that facilitates axial diffusion of Gα(t1)β(1)γ(1). Copyright © 2010 Elsevier Inc. All rights reserved.

  20. Field Testing of Compartmentalization Methods for Multifamily Construction

    Energy Technology Data Exchange (ETDEWEB)

    Ueno, K. [Building Science Corporation, Westford, MA (United States); Lstiburek, J. W. [Building Science Corporation, Westford, MA (United States)

    2015-03-01

    The 2012 International Energy Conservation Code (IECC) has an airtightness requirement of 3 air changes per hour at 50 Pascals test pressure (3 ACH50) for single-family and multifamily construction (in climate zones 3–8). The Leadership in Energy & Environmental Design certification program and ASHRAE Standard 189 have comparable compartmentalization requirements. ASHRAE Standard 62.2 will soon be responsible for all multifamily ventilation requirements (low rise and high rise); it has an exceptionally stringent compartmentalization requirement. These code and program requirements are driving the need for easier and more effective methods of compartmentalization in multifamily buildings.

  1. Compartmentalization of prostaglandins in the canine kidney

    International Nuclear Information System (INIS)

    Morgan-Boyd, R.L.

    1986-01-01

    The kidney has been shown to synthesize all of the naturally occurring major prostaglandins which may be restricted to a discrete part of the kidney where their actions are physiologically important, such as the vascular compartment and the tubular compartment. In order to examine this concept of compartmentalization, the authors conducted a series of experiments to determine whether PGl 2 , measured as 6-keto-pGF/sub 1α/, produced in the kidney is restricted to the renal vascular compartment or whether it also has access to the tubular compartment. Experiments were performed in the pentobarbital-anesthetized dog. Increasing pre-glomerular levels of 6-keto-PFG/sub 1α/ caused marked increases in both the urinary excretion and the renal venous outflow to 6-keto-PGF/sub 1α/. When 3 H-6-keto-PGF/sub 1α/ was co-infused with inulin into the renal artery, 33% of the radioactivity and 23% of the inulin was recovered on first pass. With infusion of 3 H-PGl 2 and inulin, 20% of the radioactivity and 28% of the inulin reached the urine on first pass. Radioactive PGl 2 appeared to be less filterable at the glomeruli than either 3 H-6-keto-PGF/sub 1α/ or inulin. In the final set of experiments, in which dogs were prepared for a ureteral stopped-flow study, the PGE 2 /U/P/sub In/ ratio a peak was observed proximal to the Na + plateau but distal to the Na+ nadir. In light of the results from the stopped-flow study and the intrarenal infusion studies, they conclude that PGE 2 synthesized in the kidney enters both the renal and tubular compartments. In contrast, they find that 6-keto-PGF/sub 1α/ of renal origin enters only the renal origin enters only the renal vascular compartment and not the tubular compartment

  2. Adaptive and neuroadaptive control for nonnegative and compartmental dynamical systems

    Science.gov (United States)

    Volyanskyy, Kostyantyn Y.

    Neural networks have been extensively used for adaptive system identification as well as adaptive and neuroadaptive control of highly uncertain systems. The goal of adaptive and neuroadaptive control is to achieve system performance without excessive reliance on system models. To improve robustness and the speed of adaptation of adaptive and neuroadaptive controllers several controller architectures have been proposed in the literature. In this dissertation, we develop a new neuroadaptive control architecture for nonlinear uncertain dynamical systems. The proposed framework involves a novel controller architecture with additional terms in the update laws that are constructed using a moving window of the integrated system uncertainty. These terms can be used to identify the ideal system weights of the neural network as well as effectively suppress system uncertainty. Linear and nonlinear parameterizations of the system uncertainty are considered and state and output feedback neuroadaptive controllers are developed. Furthermore, we extend the developed framework to discrete-time dynamical systems. To illustrate the efficacy of the proposed approach we apply our results to an aircraft model with wing rock dynamics, a spacecraft model with unknown moment of inertia, and an unmanned combat aerial vehicle undergoing actuator failures, and compare our results with standard neuroadaptive control methods. Nonnegative systems are essential in capturing the behavior of a wide range of dynamical systems involving dynamic states whose values are nonnegative. A sub-class of nonnegative dynamical systems are compartmental systems. These systems are derived from mass and energy balance considerations and are comprised of homogeneous interconnected microscopic subsystems or compartments which exchange variable quantities of material via intercompartmental flow laws. In this dissertation, we develop direct adaptive and neuroadaptive control framework for stabilization, disturbance

  3. The kinetics of multi-compartmentalized systems, studied by radioactive tracers

    International Nuclear Information System (INIS)

    Gouveia, A.S. de.

    1978-01-01

    The use of compartmental models to investigate kinetic problems is presented. This use is restricted, however, to linear models. As an application of different methods, the kinetic behaviour of haemaccel labelled with iodine 131 is studied, the interval of the physically viable solutions being established. The existence of a class of solutions is explained as a result of lack of knowledge of a complete data set. The possibility of obtaining a single solution is also discussed. The formalism of the program SAAM (Simulation, Analysis and modelling) now judged very important for the study of multi-compartimental analysis is presented. (I.C.R) [pt

  4. Compartmental analysis to predict biodistribution in radiopharmaceutical design studies

    Energy Technology Data Exchange (ETDEWEB)

    Lima, Marina F.; Pujatti, Priscilla B.; Araujo, Elaine B.; Mesquita, Carlos H. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)], e-mail: mflima@ipen.br

    2009-07-01

    The use of compartmental analysis allows the mathematical separation of tissues and organs to determinate the concentration of activity in each fraction of interest. Although the radiochemical purity must observe Pharmacopoeia specification (values upper 95%), very lower contains of free radionuclides could contribute significantly as dose in the neighborhood organs and make tumor up take studies not viable in case of radiopharmaceutical on the basis of labeled peptides. Animal studies with a product of Lutetium-177 labeled Bombesin derivative ({sup 177}Lu-BBNP) developed in IPEN-CNEN/SP and free Lutetium-177 developed in CNEA/EZEIZA was used to show how subtract free {sup 177}Lu contribution over {sup 177}Lu-BBNP to estimate the radiopharmaceutical potential as diagnosis or therapy agent. The first approach of the studies included the knowledge of chemical kinetics and mimetism of the Lutetium and the possible targets of the diagnosis/therapy to choose the possible models to apply over the sampling standard methods used in experimental works. A model with only one physical compartment (whole body) and one chemical compartment ({sup 177}Lu-BBNP) generated with the compartmental analysis protocol ANACOMP showed high differences between experimental and theoretical values over 2.5 hours, in spite of the concentration of activity had been in a good statistics rang of measurement. The values used in this work were residence time from three different kinds of study with free {sup 177}Lu: whole body, average excretion and maximum excretion as a chemical compartment. Activity concentration values as time function in measurements of total whole body and activity measurement in samples of blood with projection to total circulating blood volume with {sup 177}Lu-BBNP. Considering the two sources of data in the same modeling a better consistence was obtained. The next step was the statistic treatment of biodistribution and dosimetry in mice (Balb C) considering three chemical

  5. Macroanatomy of compartmentalization in fire scars of three western conifers

    Science.gov (United States)

    Kevin T. Smith; Elaine Sutherland; Estelle Arbellay; Markus Stoffel; Donald. Falk

    2013-01-01

    Fire scars are visible evidence of compartmentalization and closure processes that contribute to tree survival after fire injury. Preliminary observations of dissected fire scars from trees injured within the last decade showed centripetal development of wound-initiated discoloration (WID) through 2-3 decades of former sapwood in Larix occidentalis and Pseudotsuga...

  6. Synthesis of copper and nickel complexes using compartmental ...

    Indian Academy of Sciences (India)

    Administrator

    Synthesis of copper and nickel complexes using compartmental ligands: X-ray, electrochemical and magnetic studies. J MANONMANI, V NARAYANAN and M KANDASWAMY. Department of Inorganic Chemistry, University of Madras, Guindy Campus,. Chennai 600 025, India. The search for several synthetic routes leading ...

  7. Integration through compartmentalization? Pitfalls of 'poldering' in Bangladesh

    NARCIS (Netherlands)

    Warner, J.F.

    2010-01-01

    The article sketches the history of the Flood Action Plan 20 (FAP-20), an experiment with polder compartmentalization, seeking to integrate flood management, drainage, and irrigation, and make it more democratic in response to the destructive 1987 and 1988 floods in Bangladesh. As a transferred

  8. Integration through Compartmentalization? Pitfalls of “Poldering” in Bangladesh

    NARCIS (Netherlands)

    Warner, J.F.

    2010-01-01

    The article sketches the history of the Flood Action Plan 20 (FAP-20), an experiment with polder compartmentalization, seeking to integrate flood management, drainage, and irrigation, and make it more democratic in response to the destructive 1987 and 1988 floods in Bangladesh. As a transferred

  9. Lyophilized kits of diamino dithiol compounds for labelling with {sup 99m}-technetium. Pharmacokinetics studies and distribution compartmental models of the related complexes; Conjuntos de reativos liofilizados de compostos diaminoditiolicos para marcacao com tecnecio-99m. Estudo farmacocinetico e elaboracao de modelos compartimentalizados dos respectivos complexos

    Energy Technology Data Exchange (ETDEWEB)

    Araujo, Elaine Bortoleti de

    1995-07-01

    The present work reflects the clinical interest for labelling diamino dithiol compounds with technetium-99m. Both chosen compounds, L,L-Ethylene dicysteine (L,L-EC) and L,L-Ethylene dicysteine diethyl esther (L,L-ECD) were obtained with relative good yield and characterized by IR and NMR. The study of labelling conditions with technetium-99m showed the influence of the type and mass of reducing agent as well as the pH on the formation of complexes with desired biological characteristics. Radiochemical purity was determined by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). Lyophilised kits of L,L-EC and L,L-ECD for labelling with {sup 99m}Tc were obtained, with stability superior to 120 days, when stored under refrigeration, enabling the kits marketing. The ideal formulation of the kits as well as the use of liquid nitrogen in the freezing process, determined the lyophilization success. Distribution biological studies of the {sup 99m}Tc complexes were performed on mice by invasive method and on bigger animals by scintigraphic evaluation. Biological distribution studies of the complex {sup 99m}Tc-L,L-EC showed fast blood clearance, with the elimination of about 90% of the administered dose after 60 minutes, almost exclusively by the urinary system. The biological distribution results were adjusted to a three compartmental distribution model, as expected for a radiopharmaceutical designed to renal dynamic studies, with tubular elimination. The complex interaction with renal tubular receptors is related with structural characteristics of the compound, more specifically with the presence and location of polar groups. In comparison with {sup 99m}Tc-L,L-EC, biological studies of the complex {sup 99m}Tc -L,L-ECD showed different distribution aspects, despite some structural similarities. The presence of ethyl groups confers to the complex neutrality and lipophilicity. It cross the intact blood brain barrier and is retained in the brain

  10. Review of compartmental analysis in ecosystem science

    International Nuclear Information System (INIS)

    O'Neill, R.V.

    1978-01-01

    The compartment model has a large number of applications in ecosystem science. An attempt is made to outline the problem areas and objectives for which this type of model has particular advantages. The areas identified are an adequate model of tracer movement through an undisturbed but non-equilibrium ecosystem; an adequate model of the movement of material in greater than tracer quantity through an ecosystem near steady state; a minimal model based on limited data; a tool for extrapolating past trends; a framework for the summarization of large data sets; and a theoretical tool for exploring and comparing limited aspects of ecosystem dynamics. The review is set in an historical perspective which helps explain why these models were adopted in ecology. References are also provided to literature which documents available mathematical techniques in an ecological context

  11. Rifte Guaritas basin compartmentation in Camaqua

    International Nuclear Information System (INIS)

    Preissler, A; Rolim, S; Philipp, R.

    2010-01-01

    The study contributes to the knowledge of the tectonic evolution of the Guaritas rift basin in Camaqua. Were used aero magnetic geophysical data for modeling the geometry and the depth of the structures and geological units. The research was supported in processing and interpretation of Aster images (EOS-Terra), which were extracted from geophysical models and digital image

  12. Functional Compartmentalization within Starburst Amacrine Cell Dendrites in the Retina.

    Science.gov (United States)

    Poleg-Polsky, Alon; Ding, Huayu; Diamond, Jeffrey S

    2018-03-13

    Dendrites in many neurons actively compute information. In retinal starburst amacrine cells, transformations from synaptic input to output occur within individual dendrites and mediate direction selectivity, but directional signal fidelity at individual synaptic outputs and correlated activity among neighboring outputs on starburst dendrites have not been examined systematically. Here, we record visually evoked calcium signals simultaneously at many individual synaptic outputs within single starburst amacrine cells in mouse retina. We measure visual receptive fields of individual output synapses and show that small groups of outputs are functionally compartmentalized within starburst dendrites, creating distinct computational units. Inhibition enhances compartmentalization and directional tuning of individual outputs but also decreases the signal-to-noise ratio. Simulations suggest, however, that the noise underlying output signal variability is well tolerated by postsynaptic direction-selective ganglion cells, which integrate convergent inputs to acquire reliable directional information. Published by Elsevier Inc.

  13. Gas confinement in compartmentalized coordination polymers for highly selective sorption.

    Science.gov (United States)

    Giménez-Marqués, Mónica; Calvo Galve, Néstor; Palomino, Miguel; Valencia, Susana; Rey, Fernando; Sastre, Germán; Vitórica-Yrezábal, Iñigo J; Jiménez-Ruiz, Mónica; Rodríguez-Velamazán, J Alberto; González, Miguel A; Jordá, José L; Coronado, Eugenio; Espallargas, Guillermo Mínguez

    2017-04-01

    Discrimination between different gases is an essential aspect for industrial and environmental applications involving sensing and separation. Several classes of porous materials have been used in this context, including zeolites and more recently MOFs. However, to reach high selectivities for the separation of gas mixtures is a challenging task that often requires the understanding of the specific interactions established between the porous framework and the gases. Here we propose an approach to obtain an enhanced selectivity based on the use of compartmentalized coordination polymers, named CCP-1 and CCP-2 , which are crystalline materials comprising isolated discrete cavities. These compartmentalized materials are excellent candidates for the selective separation of CO 2 from methane and nitrogen. A complete understanding of the sorption process is accomplished with the use of complementary experimental techniques including X-ray diffraction, adsorption studies, inelastic- and quasi-elastic neutron scattering, magnetic measurements and molecular dynamics calculations.

  14. The nigrostriatal pathway: axonal collateralization and compartmental specificity.

    Science.gov (United States)

    Prensa, L; Giménez-Amaya, J M; Parent, A; Bernácer, J; Cebrián, C

    2009-01-01

    This paper reviews two of the major features of the nigrostriatal pathway, its axonal collateralization, and compartmental specificity, as revealed by single-axon labeling experiments in rodents and immunocytological analysis of human postmortem tissue. The dorsal and ventral tiers of the substantia nigra pars compacta harbor various types of neurons the axons of which branch not only within the striatum but also in other major components of the basal ganglia. Furthermore, some nigrostriatal axons send collaterals both to thalamus and to brainstem pedunculopontine tegmental nucleus. In humans, the compartmental specificity of the nigrostriatal pathway is revealed by the fact that the matrix compartment is densely innervated by dopaminergic fibers, whereas the striosomes display different densities of dopaminergic terminals depending on their location within the striatum. The nigral neurons most severely affected in Parkinson's disease are the ventral tier cells that project to the matrix and form deep clusters in the substantia nigra pars reticulata.

  15. A Numerical Simulation for a Deterministic Compartmental ...

    African Journals Online (AJOL)

    In this work, an earlier deterministic mathematical model of HIV/AIDS is revisited and numerical solutions obtained using Eulers numerical method. Using hypothetical values for the parameters, a program was written in VISUAL BASIC programming language to generate series for the system of difference equations from the ...

  16. Field Testing of Compartmentalization Methods for Multifamily Construction

    Energy Technology Data Exchange (ETDEWEB)

    Ueno, K. [Building Science Corporation, Westford, MA (United States); Lstiburek, J. [Building Science Corporation, Westford, MA (United States)

    2015-03-01

    The 2012 IECC has an airtightness requirement of 3 air changes per hour at 50 Pascals test pressure for both single-family and multifamily construction in Climate Zones 3-8. Other programs (LEED, ASHRAE 189, ASHRAE 62.2) have similar or tighter compartmentalization requirements, driving the need for easier and more effective methods of compartmentalization in multifamily buildings. Builders and practitioners have found that fire-resistance rated wall assemblies are a major source of difficulty in air sealing/compartmentalization, particularly in townhouse construction. This problem is exacerbated when garages are “tucked in” to the units and living space is located over the garages. In this project, Building Science Corporation examined the taping of exterior sheathing details to improve air sealing results in townhouse and multifamily construction, when coupled with a better understanding of air leakage pathways. Current approaches are cumbersome, expensive, time consuming, and ineffective; these details were proposed as a more effective and efficient method. The effectiveness of these air sealing methods was tested with blower door testing, including “nulled” or “guarded” testing (adjacent units run at equal test pressure to null out inter-unit air leakage, or “pressure neutralization”). Pressure diagnostics were used to evaluate unit-to-unit connections and series leakage pathways (i.e., air leakage from exterior, into the fire-resistance rated wall assembly, and to the interior).

  17. Compartmental architecture and dynamics of hematopoiesis.

    Directory of Open Access Journals (Sweden)

    David Dingli

    Full Text Available BACKGROUND: Blood cell formation is maintained by the replication of hematopoietic stem cells (HSC that continuously feed downstream "compartments" where amplification and differentiation of cells occurs, giving rise to all blood lineages. Whereas HSC replicate slowly, committed cells replicate faster as they become more differentiated. METHODOLOGY/SIGNIFICANT FINDING: We propose a multi-compartment model of hematopoiesis, designed on the principle of cell flow conservation under stationary conditions. Cells lost from one compartment due to differentiation are replaced by cells from the upstream compartment. We assume that there is a constant relationship between cell input and output in each compartment and fix the single parameter of the model using data available for granulocyte maturation. We predict that approximately 31 mitotic events separate the HSC from the mature cells observed in the circulation. Besides estimating the number of compartments, our model allows us to estimate the size of each compartment, the rate of cell replication within each compartment, the mean time a given cell type contributes to hematopoiesis, the amplification rate in each compartment, as well as the mean time separating stem-cell replication and mature blood-cell formation. CONCLUSIONS: Despite its simplicity, the model agrees with the limited in vivo data available and can make testable predictions. In particular, our prediction of the average lifetime of a PIG-A mutated clone agrees closely with the experimental results available for the PIG-A gene mutation in healthy adults. The present elucidation of the compartment structure and dynamics of hematopoiesis may prove insightful in further understanding a variety of hematopoietic disorders.

  18. Compartmentalized metabolic network reconstruction of microbial communities to determine the effect of agricultural intervention on soils.

    Science.gov (United States)

    Alvarez-Silva, María Camila; Álvarez-Yela, Astrid Catalina; Gómez-Cano, Fabio; Zambrano, María Mercedes; Husserl, Johana; Danies, Giovanna; Restrepo, Silvia; González-Barrios, Andrés Fernando

    2017-01-01

    Soil microbial communities are responsible for a wide range of ecological processes and have an important economic impact in agriculture. Determining the metabolic processes performed by microbial communities is crucial for understanding and managing ecosystem properties. Metagenomic approaches allow the elucidation of the main metabolic processes that determine the performance of microbial communities under different environmental conditions and perturbations. Here we present the first compartmentalized metabolic reconstruction at a metagenomics scale of a microbial ecosystem. This systematic approach conceives a meta-organism without boundaries between individual organisms and allows the in silico evaluation of the effect of agricultural intervention on soils at a metagenomics level. To characterize the microbial ecosystems, topological properties, taxonomic and metabolic profiles, as well as a Flux Balance Analysis (FBA) were considered. Furthermore, topological and optimization algorithms were implemented to carry out the curation of the models, to ensure the continuity of the fluxes between the metabolic pathways, and to confirm the metabolite exchange between subcellular compartments. The proposed models provide specific information about ecosystems that are generally overlooked in non-compartmentalized or non-curated networks, like the influence of transport reactions in the metabolic processes, especially the important effect on mitochondrial processes, as well as provide more accurate results of the fluxes used to optimize the metabolic processes within the microbial community.

  19. Compartmentalized metabolic network reconstruction of microbial communities to determine the effect of agricultural intervention on soils.

    Directory of Open Access Journals (Sweden)

    María Camila Alvarez-Silva

    Full Text Available Soil microbial communities are responsible for a wide range of ecological processes and have an important economic impact in agriculture. Determining the metabolic processes performed by microbial communities is crucial for understanding and managing ecosystem properties. Metagenomic approaches allow the elucidation of the main metabolic processes that determine the performance of microbial communities under different environmental conditions and perturbations. Here we present the first compartmentalized metabolic reconstruction at a metagenomics scale of a microbial ecosystem. This systematic approach conceives a meta-organism without boundaries between individual organisms and allows the in silico evaluation of the effect of agricultural intervention on soils at a metagenomics level. To characterize the microbial ecosystems, topological properties, taxonomic and metabolic profiles, as well as a Flux Balance Analysis (FBA were considered. Furthermore, topological and optimization algorithms were implemented to carry out the curation of the models, to ensure the continuity of the fluxes between the metabolic pathways, and to confirm the metabolite exchange between subcellular compartments. The proposed models provide specific information about ecosystems that are generally overlooked in non-compartmentalized or non-curated networks, like the influence of transport reactions in the metabolic processes, especially the important effect on mitochondrial processes, as well as provide more accurate results of the fluxes used to optimize the metabolic processes within the microbial community.

  20. Mathematical basis for the measurement of absolute and fractional cardiac output with diffusible tracers by compartmental analysis methods

    International Nuclear Information System (INIS)

    Charkes, N.D.

    1984-01-01

    Using compartmental analysis methods, a mathematical basis is given for the measurement of absolute and fractional cardiac output with diffusible tracers. Cardiac output is shown to be the product of the blood volume and the sum of the rate constants of tracer egress from blood, modified by a factor reflecting transcapillary diffusibility, the transfer fraction. The return of tracer to the blood and distant (intracellular) events are shown to play no role in the solution. Fractional cardiac output is the ratio of the rate constant of tracer egress from blood to an organ, divided by the sum of the egress constants from blood. Predominantly extracellular ions such as sodium or bromide are best suited for this technique, although theoretically any diffusible tracer whose compartmental model can be solved may be used. It is shown that fractional cardiac output is independent of the transfer fraction, and therefore can be measured accurately by tracers which are not freely diffusible

  1. The iDuo Bi-compartmental Knee Replacement: Our Early Experience.

    Directory of Open Access Journals (Sweden)

    Peter Jemmett

    2016-12-01

    Our early results suggest that the iDuo knee is a good option for those with isolated bi-compartmental disease and outcome scores are comparable with those reported for the BKA. This bi-compartmental design may bridge the gap between the uni-compartmental and total knee replacement. The choice between monolithic or modular designs remains in debate. We will continue to use this prosthesis for a carefully selected group of patients.

  2. Compartmentalization in PVC super-phylum: evolution and impact.

    Science.gov (United States)

    Pinos, Sandrine; Pontarotti, Pierre; Raoult, Didier; Baudoin, Jean Pierre; Pagnier, Isabelle

    2016-08-09

    The PVC super-phylum gathers bacteria from seven phyla (Planctomycetes, Verrucomicrobiae, Chlamydiae, Lentisphaera, Poribacteria, OP3, WWE2) presenting different lifestyles, cell plans and environments. Planctomyces and several Verrucomicrobiae exhibit a complex cell plan, with an intracytoplasmic membrane inducing the compartmentalization of the cytoplasm into two regions (pirellulosome and paryphoplasm). The evolution and function of this cell plan is still subject to debate. In this work, we hypothesized that it could play a role in protection of the bacterial DNA, especially against Horizontal Genes Transfers (HGT). Therefore, 64 bacterial genomes belonging to seven different phyla (whose four PVC phyla) were studied. We reconstructed the evolution of the cell plan as precisely as possible, thanks to information obtained by bibliographic study and electronic microscopy. We used a strategy based on comparative phylogenomic in order to determine the part occupied by the horizontal transfers for each studied genomes. Our results show that the bacteria Simkania negevensis (Chlamydiae) and Coraliomargarita akajimensis (Verrucomicrobiae), whose cell plan were unknown before, are compartmentalized, as we can see on the micrographies. This is one of the first indication of the presence of an intracytoplasmic membrane in a Chlamydiae. The proportion of HGT does not seems to be related to the cell plan of bacteria, suggesting that compartmentalization does not induce a protection of bacterial DNA against HGT. Conversely, lifestyle of bacteria seems to impact the ability of bacteria to exchange genes. Our study allows a best reconstruction of the evolution of intracytoplasmic membrane, but this structure seems to have no impact on HGT occurrences. This article was reviewed by Mircea Podar and Olivier Tenaillon.

  3. Intracellular compartmentalization of skeletal muscle glycogen metabolism and insulin signalling

    DEFF Research Database (Denmark)

    Prats Gavalda, Clara; Gomez-Cabello, Alba; Vigelsø Hansen, Andreas

    2011-01-01

    The interest in skeletal muscle metabolism and insulin signalling has increased exponentially in recent years as a consequence of their role in the development of type 2 diabetes mellitus. Despite this, the exact mechanisms involved in the regulation of skeletal muscle glycogen metabolism...... compartmentalization in the regulation of skeletal muscle glycogen metabolism and insulin signalling. As a result, a hypothetical regulatory mechanism is proposed by which cells could direct glycogen resynthesis towards different pools of glycogen particles depending on the metabolic needs. Furthermore, we discuss...

  4. Lower extremity compartmental anatomy: clinical relevance to radiologists

    Energy Technology Data Exchange (ETDEWEB)

    Toomayan, Glen A.; Robertson, Fabienne; Major, Nancy M. [Duke University Medical Center, Department of Radiology, Durham (United States)

    2005-06-01

    A thorough understanding of compartmental anatomy is necessary for the radiologist participating in the care of a patient with a lower extremity musculoskeletal malignancy. Localization of tumor to compartment of origin and identification of extracompartmental spread preoperatively are needed to correctly stage a tumor and determine the appropriate surgical management. An understanding of the locations of fascial boundaries, extracompartmental tissues, and neurovascular structures of the thigh and lower leg facilitates this diagnostic process. For the radiologist planning to biopsy a suspicious musculoskeletal lesion, consultation with the referring orthopaedic surgeon is recommended in order to jointly select an appropriate percutaneous biopsy approach. Adequate preprocedural planning ensures selection of an approach which prevents iatrogenic tumor spread beyond the compartment of origin, protects neurovascular structures, and allows complete resection of the biopsy tract and scar at the time of surgical resection without jeopardizing a potential limb-sparing procedure. Cross-sectional anatomic review and case examples demonstrate the importance of a detailed understanding of compartmental anatomy when approaching the patient with a lower extremity musculoskeletal tumor. (orig.)

  5. Compartmentation and equilibration of abscisic acid in isolated Xanthium cells

    International Nuclear Information System (INIS)

    Bray, E.A.; Zeevaart, J.A.D.

    1986-01-01

    The compartmentation of endogenous abscisic acid (ABA), applied (+/-)-[ 3 H]ABA, and (+/-)-trans-ABA was measured in isolated mesophyll cells of the Chicago strain of Xanthium strumarium L. The release of ABA to the medium in the presence or absence of DMSO was used to determine the equilibration of ABA in the cells. It was found that a greater percentage of the (+/-)-[ 3 H]ABA and the (+/-)-trans-ABA was released into the medium than of the endogenous ABA, indicating that applied ABA did not equilibrate with the endogenous material. Therefore, in further investigations only the compartmentation of endogenous ABA was studied. Endogenous ABA was released from Xanthium cells according to the pH gradients among the various cellular compartments. Thus, darkness, high external pH, KNO 2 , and drought-stress all increased the efflux of ABA from the cells. Efflux of ABA from the cells in the presence of 0.6 M mannitol occurred within 30 seconds, but only 8% of the endogenous material was released during the 20 minute treatment

  6. Functional Compartmentalization within Starburst Amacrine Cell Dendrites in the Retina

    Directory of Open Access Journals (Sweden)

    Alon Poleg-Polsky

    2018-03-01

    Full Text Available Summary: Dendrites in many neurons actively compute information. In retinal starburst amacrine cells, transformations from synaptic input to output occur within individual dendrites and mediate direction selectivity, but directional signal fidelity at individual synaptic outputs and correlated activity among neighboring outputs on starburst dendrites have not been examined systematically. Here, we record visually evoked calcium signals simultaneously at many individual synaptic outputs within single starburst amacrine cells in mouse retina. We measure visual receptive fields of individual output synapses and show that small groups of outputs are functionally compartmentalized within starburst dendrites, creating distinct computational units. Inhibition enhances compartmentalization and directional tuning of individual outputs but also decreases the signal-to-noise ratio. Simulations suggest, however, that the noise underlying output signal variability is well tolerated by postsynaptic direction-selective ganglion cells, which integrate convergent inputs to acquire reliable directional information. : Poleg-Polsky et al. examine the directional signaling fidelity of individual synapses on starburst amacrine cell dendrites. They identify functionally and morphologically distinct signaling compartments within SAC dendrites and show that inhibition enhances reliable decoding by postsynaptic direction-selective ganglion cells. Keywords: retina, synaptic transmission, amacrine cell, correlation, visual processing, inhibition, direction selectivity

  7. Transit-time and age distributions for nonlinear time-dependent compartmental systems.

    Science.gov (United States)

    Metzler, Holger; Müller, Markus; Sierra, Carlos A

    2018-02-06

    Many processes in nature are modeled using compartmental systems (reservoir/pool/box systems). Usually, they are expressed as a set of first-order differential equations describing the transfer of matter across a network of compartments. The concepts of age of matter in compartments and the time required for particles to transit the system are important diagnostics of these models with applications to a wide range of scientific questions. Until now, explicit formulas for transit-time and age distributions of nonlinear time-dependent compartmental systems were not available. We compute densities for these types of systems under the assumption of well-mixed compartments. Assuming that a solution of the nonlinear system is available at least numerically, we show how to construct a linear time-dependent system with the same solution trajectory. We demonstrate how to exploit this solution to compute transit-time and age distributions in dependence on given start values and initial age distributions. Furthermore, we derive equations for the time evolution of quantiles and moments of the age distributions. Our results generalize available density formulas for the linear time-independent case and mean-age formulas for the linear time-dependent case. As an example, we apply our formulas to a nonlinear and a linear version of a simple global carbon cycle model driven by a time-dependent input signal which represents fossil fuel additions. We derive time-dependent age distributions for all compartments and calculate the time it takes to remove fossil carbon in a business-as-usual scenario.

  8. A functional compartmental model of the Synechocystis PCC 6803 phycobilisome

    NARCIS (Netherlands)

    van Stokkum, Ivo H. M.; Gwizdala, Michal; Tian, Lijin; Snellenburg, Joris J.; van Grondelle, Rienk; van Amerongen, Herbert; Berera, Rudi

    In the light-harvesting antenna of the Synechocystis PCC 6803 phycobilisome (PB), the core consists of three cylinders, each composed of four disks, whereas each of the six rods consists of up to three hexamers (Arteni et al., Biochim Biophys Acta 1787(4):272–279, 2009). The rods and core contain

  9. A functional compartmental model of the Synechocystis PCC 6803 phycobilisome

    NARCIS (Netherlands)

    Stokkum, van Ivo H.M.; Gwizdala, Michal; Tian, Tian; Snellenburg, Joris J.; Grondelle, van Rienk; Amerongen, van Herbert; Berera, Rudi

    2018-01-01

    In the light-harvesting antenna of the Synechocystis PCC 6803 phycobilisome (PB), the core consists of three cylinders, each composed of four disks, whereas each of the six rods consists of up to three hexamers (Arteni et al., Biochim Biophys Acta 1787(4):272–279, 2009). The rods and core contain

  10. Measurement of renal glomerular filtration rate using labelled substances with compartmental analysis

    International Nuclear Information System (INIS)

    Eberstadt, P.L.

    1981-10-01

    Using a model for the two-compartmental open system and experiments on animals (rabbits and dogs) as well as on human healthy volunteers, an attempt was made to study the advantages and limitations of different radionuclide methods for glomerular filtration rate determination. Labelled compounds used in different combinations were: 3 H-inulin, sup(113m)In-EDTA, 131 I-iothalamate, sup(99m)Tc-DTPA and 14 C-creatinine. The results of the study lead to some working hypotheses concerning the value of creatinine and other labelled substances in the measurement of glomerular filtration rate in clinical practice. The advantages and disadvantages of individual methods summarized in the final report are generally in agreement with the present views of many research workers. Also the hypothesis can be justified that the different labelled compounds which have been studied might be handled independently by the membranes involved but at the long run produce similar homeostatic balance

  11. A quasi-3D compartmental multi-scale approach to detect and quantify diseased regional lung constriction using spirometry data.

    Science.gov (United States)

    Kannan, Ravishekar Ravi; Singh, Narender; Przekwas, Andrzej

    2018-02-27

    Spirometry is a widely used pulmonary function test to detect the airflow limitations associated with various obstructive lung diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and even obesity-related complications. These conditions arise due to the change in the airway resistance, alveolar compliance, and inductance values. Currently, zero-dimensional (0D) compartmental models are commonly used for calibrating these resistance, compliance, and inductance values, i.e., solving the inverse spirometry problem. However, 0D compartments cannot capture the flow physics or the spatial geometry effects, thereby generating a low fidelity prediction of the diseased lung. Computational fluid dynamics (CFD) models offer higher fidelity solutions but may be impractical for certain applications due to the duration of these simulations. Recently, a novel, fast-running and robust Quasi-3D (Q3D) wire model for simulating the airflow in the human lung airway was developed by CFD Research Corporation (CFDRC). This Q3D method preserved the 3D spatial nature of the airways and was favorably validated against CFD solutions. In the present study, the Q3D compartmental multi-scale combination is further improved to predict regional lung constriction of diseased lungs using spirometry data. The Q3D mesh is resolved up to the eighth lung airway generation. The remainder of the airways and the alveoli sections are modeled using a compartmental approach. The Q3D geometry is then split into different spatial sections and the resistance values in these regions are obtained using parameter inversion. Finally, the airway diameter values are then reduced to create the actual diseased lung model, corresponding to these resistance values. This diseased lung model can be used for patient-specific drug deposition predictions and the subsequent optimization of the orally inhaled drug products. This article is protected by copyright. All rights reserved.

  12. PKA catalytic subunit compartmentation regulates contractile and hypertrophic responses to β-adrenergic signaling

    Science.gov (United States)

    Yang, Jason H.; Polanowska-Grabowska, Renata K.; Smith, Jeffrey S.; Shields, Charles W.; Saucerman, Jeffrey J.

    2014-01-01

    β-adrenergic signaling is spatiotemporally heterogeneous in the cardiac myocyte, conferring exquisite control to sympathetic stimulation. Such heterogeneity drives the formation of protein kinase A (PKA) signaling microdomains, which regulate Ca2+ handling and contractility. Here, we test the hypothesis that the nucleus independently comprises a PKA signaling microdomain regulating myocyte hypertrophy. Spatially-targeted FRET reporters for PKA activity identified slower PKA activation and lower isoproterenol sensitivity in the nucleus (t50 = 10.60±0.68 min; EC50 = 89.00 nmol/L) than in the cytosol (t50 = 3.71±0.25 min; EC50 = 1.22 nmol/L). These differences were not explained by cAMP or AKAP-based compartmentation. A computational model of cytosolic and nuclear PKA activity was developed and predicted that differences in nuclear PKA dynamics and magnitude are regulated by slow PKA catalytic subunit diffusion, while differences in isoproterenol sensitivity are regulated by nuclear expression of protein kinase inhibitor (PKI). These were validated by FRET and immunofluorescence. The model also predicted differential phosphorylation of PKA substrates regulating cell contractility and hypertrophy. Ca2+ and cell hypertrophy measurements validated these predictions and identified higher isoproterenol sensitivity for contractile enhancements (EC50 = 1.84 nmol/L) over cell hypertrophy (EC50 = 85.88 nmol/L). Over-expression of spatially targeted PKA catalytic subunit to the cytosol or nucleus enhanced contractile and hypertrophic responses, respectively. We conclude that restricted PKA catalytic subunit diffusion is an important PKA compartmentation mechanism and the nucleus comprises a novel PKA signaling microdomain, insulating hypertrophic from contractile β-adrenergic signaling responses. PMID:24225179

  13. Compartmentalization of GPCR signalling controls unique cellular responses.

    Science.gov (United States)

    Ellisdon, Andrew M; Halls, Michelle L

    2016-04-15

    With >800 members, G protein-coupled receptors (GPCRs) are the largest class of cell-surface signalling proteins, and their activation mediates diverse physiological processes. GPCRs are ubiquitously distributed across all cell types, involved in many diseases and are major drug targets. However, GPCR drug discovery is still characterized by very high attrition rates. New avenues for GPCR drug discovery may be provided by a recent shift away from the traditional view of signal transduction as a simple chain of events initiated from the plasma membrane. It is now apparent that GPCR signalling is restricted to highly organized compartments within the cell, and that GPCRs activate distinct signalling pathways once internalized. A high-resolution understanding of how compartmentalized signalling is controlled will probably provide unique opportunities to selectively and therapeutically target GPCRs. © 2016 Authors; published by Portland Press Limited.

  14. Synapse-specific and compartmentalized expression of presynaptic homeostatic potentiation.

    Science.gov (United States)

    Li, Xiling; Goel, Pragya; Chen, Catherine; Angajala, Varun; Chen, Xun; Dickman, Dion K

    2018-04-05

    Postsynaptic compartments can be specifically modulated during various forms of synaptic plasticity, but it is unclear whether this precision is shared at presynaptic terminals. Presynaptic Homeostatic Plasticity (PHP) stabilizes neurotransmission at the Drosophila neuromuscular junction, where a retrograde enhancement of presynaptic neurotransmitter release compensates for diminished postsynaptic receptor functionality. To test the specificity of PHP induction and expression, we have developed a genetic manipulation to reduce postsynaptic receptor expression at one of the two muscles innervated by a single motor neuron. We find that PHP can be induced and expressed at a subset of synapses, over both acute and chronic time scales, without influencing transmission at adjacent release sites. Further, homeostatic modulations to CaMKII, vesicle pools, and functional release sites are compartmentalized and do not spread to neighboring pre- or post-synaptic structures. Thus, both PHP induction and expression mechanisms are locally transmitted and restricted to specific synaptic compartments. © 2018, Li et al.

  15. Intracellular transport and compartmentation of phosphate in plants.

    Science.gov (United States)

    Versaw, Wayne K; Garcia, L Rene

    2017-10-01

    Phosphate (Pi) is an essential macronutrient with structural and metabolic roles within every compartment of the plant cell. Intracellular Pi transporters direct Pi to each organelle and also control its exchange between subcellular compartments thereby providing the means to coordinate compartmented metabolic processes, including glycolysis, photosynthesis, and respiration. In this review we summarize recent advances in the identification and functional analysis of Pi transporters that localize to vacuoles, chloroplasts, non-photosynthetic plastids, mitochondria, and the Golgi apparatus. Electrical potentials across intracellular membranes and the pH of subcellular environments will also be highlighted as key factors influencing the energetics of Pi transport, and therefore pose limits for Pi compartmentation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Compartmentalization of NO signaling cascade in skeletal muscles

    International Nuclear Information System (INIS)

    Buchwalow, Igor B.; Minin, Evgeny A.; Samoilova, Vera E.; Boecker, Werner; Wellner, Maren; Schmitz, Wilhelm; Neumann, Joachim; Punkt, Karla

    2005-01-01

    Skeletal muscle functions regulated by NO are now firmly established. However, the literature on the compartmentalization of NO signaling in myocytes is highly controversial. To address this issue, we examined localization of enzymes engaged in L-arginine-NO-cGMP signaling in the rat quadriceps muscle. Employing immunocytochemical labeling complemented with tyramide signal amplification and electron microscopy, we found NO synthase expressed not only in the sarcolemma, but also along contractile fibers, in the sarcoplasmic reticulum and mitochondria. The expression pattern of NO synthase in myocytes showed striking parallels with the enzymes engaged in L-arginine-NO-cGMP signaling (arginase, phosphodiesterase, and soluble guanylyl cyclase). Our findings are indicative of an autocrine fashion of NO signaling in skeletal muscles at both cellular and subcellular levels, and challenge the notion that the NO generation is restricted to the sarcolemma

  17. Apartment Compartmentalization With an Aerosol-Based Sealing Process

    Energy Technology Data Exchange (ETDEWEB)

    Maxwell, S. [Consortium for Advanced Residential Buildings, Norwalk, CT (United States); Berger, D. [Consortium for Advanced Residential Buildings, Norwalk, CT (United States); Harrington, C. [Consortium for Advanced Residential Buildings, Norwalk, CT (United States)

    2015-03-01

    Air sealing of building enclosures is a difficult and time-consuming process. Current methods in new construction require laborers to physically locate small and sometimes large holes in multiple assemblies and then manually seal each of them. The innovation demonstrated under this research study was the automated air sealing and compartmentalization of buildings through the use of an aerosolized sealant, developed by the Western Cooling Efficiency Center at University of California Davis. CARB sought to demonstrate this new technology application in a multifamily building in Queens, NY. The effectiveness of the sealing process was evaluated by three methods: air leakage testing of overall apartment before and after sealing, point-source testing of individual leaks, and pressure measurements in the walls of the target apartment during sealing.

  18. Compartmental endoscopic surgical anatomy of the medial intraconal orbital space.

    Science.gov (United States)

    Bleier, Benjamin S; Healy, David Y; Chhabra, Nipun; Freitag, Suzanne

    2014-07-01

    Surgical management of intraconal pathology represents the next frontier in endoscopic endonasal surgery. Despite this, the medial intraconal space remains a relatively unexplored region, secondary to its variable and technically demanding anatomy. The purpose of this study is to define the neurovascular structures in this region and introduce a compartmentalized approach to enhance surgical planning. This study was an institutional review board (IRB)-exempt endoscopic anatomic study in 10 cadaveric orbits. After dissection of the medial intraconal space, the pattern and trajectory of the oculomotor nerve and ophthalmic arterial arborizations were analyzed. The position of all vessels as well as the length of the oculomotor trunk and branches relative to the sphenoid face were calculated. A mean of 1.5 arterial branches were identified (n = 15; range, 1-4) at a mean of 8.8 mm from the sphenoid face (range, 4-15 mm). The majority of the arteries (n = 7) inserted adjacent to the midline of medial rectus. The oculomotor nerve inserted at the level of the sphenoid face and arborized with a large proximal trunk 5.5 ± 1.1 mm in length and multiple branches extending 13.2 ± 2.7 mm from the sphenoid face. The most anterior nerve and vascular pedicle were identified at 17.0 and 15.0 mm from the sphenoid face, respectively. The neurovascular supply to the medial rectus muscle describes a varied but predictable pattern. This data allows the compartmentalization of the medial intraconal space into 3 zones relative to the neurovascular supply. These zones inform the complexity of the dissection and provide a guideline for safe medial rectus retraction relative to the fixed landmark of the sphenoid face. © 2014 ARS-AAOA, LLC.

  19. Cs-137 accumulation and elimination by Gracilaria caudata alga and Abudefduf saxatilis fish. Compartmental analysis

    International Nuclear Information System (INIS)

    Mattiolo-Marchese, Sandra Regina

    1998-01-01

    From the ecological point of view, 137 Cs is a critical radionuclide because its physical half-life is long (30 years), and it has a high fission yield. Besides, it presents similar characteristics to sodium and potassium, fundamental elements for the living organisms, in great concentration in all cells. This work has as aim to study the 137 Cs accumulation and elimination by the alga Gracilaria caudata and by the fish Abudefduf saxatilis as well as to obtain the transfer constants of the 137 Cs from the water into the organisms. The concentration factor found for the fish was 5.6 +- 0.2 and for the alga, 13.0 +- 0,6. With 7 and 22 days, the fish and alga respectively had already eliminated half of the accumulated radionuclide. The 137 Cs ingestion efficiency by the fish was also studied and it was verified that the fish assimilated only 47.6 % of the cesium content in the food; and within of 4 days it had eliminated more than half of ingested cesium. A compartmental model was proposed to explain the distribution of cesium in the compartments (water - alga and water - fish). Data obtained from the experiments of 137 Cs accumulation and elimination were applied in the Ana Comp Program. This program permits the compartmental analysis, and quantifies the cesium distribution from the sea-water to the organisms, and vice versa, through the transfer constants (k). The Ana Comp Program also allowed to calculate the dose that one would receive by the consumption of fish contaminated by cesium. Levels of 137 Cs from the global fallout in environmental samples, from Sao Sebastiao, northern coast of Sao Paulo, (where the 'Centro de Biologia Marinha da Universidade de Sao Paulo - CEBIMar - USP' is located), were verified. (author)

  20. Compartmentation of sucrose during radial transfer in mature sorghum culm

    Directory of Open Access Journals (Sweden)

    Vietor Donald M

    2007-06-01

    Full Text Available Abstract Background The sucrose that accumulates in the culm of sorghum (Sorghum bicolor (L. Moench and other large tropical andropogonoid grasses can be of commercial value, and can buffer assimilate supply during development. Previous study conducted with intact plants showed that sucrose can be radially transferred to the intracellular compartment of mature ripening sorghum internode without being hydrolysed. In this study, culm-infused radiolabelled sucrose was traced between cellular compartments and among related metabolites to determine if the compartmental path of sucrose during radial transfer in culm tissue was symplasmic or included an apoplasmic step. This transfer path was evaluated for elongating and ripening culm tissue of intact plants of two semidwarf grain sorghums. The metabolic path in elongating internode tissue was also evaluated. Results On the day after culm infusion of the tracer sucrose, the specific radioactivity of sucrose recovered from the intracellular compartment of growing axillary-branch tissue was greater (nearly twice than that in the free space, indicating that sucrose was preferentially transferred through symplasmic routes. In contrast, the sucrose specific radioactivity in the intracellular compartment of the mature (ripening culm tissue was probably less (about 3/4's than that in free space indicating that sucrose was preferentially transferred through routes that included an apoplasmic step. In growing internodes of the axillary branch of sorghum, the tritium label initially provided in the fructose moiety of sucrose molecules was largely (81% recovered in the fructose moiety, indicating that a large portion of sucrose molecules is not hydrolysed and resynthesized during radial transfer. Conclusion During radial transfer of sucrose in ripening internodes of intact sorghum plants, much of the sucrose is transferred intact (without hydrolysis and resynthesis and primarily through a path that includes an

  1. Compartmental analysis and dosimetric aspects applied to cholesterol with 3H labeled

    International Nuclear Information System (INIS)

    Oliveira, Adriano dos Santos

    2015-01-01

    Cardiovascular diseases (CVDs) are one of the major reasons of death around the world according to the World Health Organization (WHO). It is well known that changes in levels of plasma lipoproteins, which are responsible for the transport of cholesterol into the bloodstream, are associated with cardiovascular diseases. For this reason to know the biokinetic parameters of plasma lipoproteins and quantifies them is important to correct and deep understanding about the diseases associated with these disorders. The main aim of this study is to provide a biokinetic model and estimate the radiometric doses for 3 H-Cholesterol, a radioactive tracer widely used in physiological and metabolic studies. The model was based on [Schwartz et al. 2004] about the distribution of cholesterol by the lipoprotein and gastrointestinal model [ICRP 30, 1979]. The doses distribution in compartments of the model and other organs and tissues of a standard adult described in [ICRP 106, 2008] was calculated using MIRD method (Medical Internal Radiation Dose) and compartmental analysis using the computer program Matlab®. The dose coefficients were estimated for a standard phantom man (73 kg) described in [ICRP 60, 1991]. The estimated doses for both model and for other organs were low and did not exceed the highest dose obtained that was in the upper large intestine, as 44,8 μGy these parameters will assist in ethics committee's opinions on the use of works that use the 3 H-cholesterol which radioactive tracer. (author)

  2. Inositol lipid turnover and compartmentation in canine trachealis smooth muscle

    International Nuclear Information System (INIS)

    Baron, C.B.; Pring, M.; Coburn, R.F.

    1989-01-01

    We established conditions for the study of metabolism and compartmentation of inositol phospholipids in canine trachealis muscle. Unstimulated muscle was incubated with myo-[3H]inositol for 30 min at 37 degrees C which resulted in labeling of the tissue free myo-inositol pool, whereas only a small amount of radioactivity was incorporated into inositol phospholipids or inositol phosphates. After addition of 5.5 microM carbachol, phosphatidylinositol (PI), phosphatidylinositol-4-phosphate (PIP), and phosphatidylinositol-4,5-bisphosphate (PIP2), specific radioactivities increased exponentially, reaching apparent constant values in 180-240 min. Initial rates of increases in PI, PIP, and PIP2 specific radioactivities were 39, 32, and 66 times that measured in unstimulated muscle. Metabolic flux rates (nmol.100 nmol total lipid Pi-1.min-1) during development of force averaged 0.42 +/- 0.09 and during force maintenance averaged 0.14 +/- 0.01. Fractions of total PI, PIP, and PIP2 pools that were linked to muscarinic cholinergic activation were estimated to be 0.97, 0.85, and 0.65, respectively. Initial rates of increase in specific radioactivities and specific radioactivities during carbachol activation were similar in PI, PIP, and PIP2 fast active compartments, suggesting metabolic flux from PI to PIP to PIP2 was in near chemical equilibrium. Turnover times for PI, PIP, and PIP2 fast active compartments were estimated to be 21, 1.6, and 4.0 min, respectively

  3. In or out? On the tightness of glycosomal compartmentalization of metabolites and enzymes in Trypanosoma brucei

    NARCIS (Netherlands)

    Haanstra, Jurgen R.; Bakker, Barbara M.; Michels, Paul A. M.

    2014-01-01

    Trypanosomatids sequester large parts of glucose metabolism inside specialised peroxisomes, called glycosomes. Many studies have shown that correct glycosomal compartmentalization of glycolytic enzymes is essential for bloodstream-form Trypanosoma brucel. The recent finding of pore-forming

  4. Inter-compartmental transport of organophosphate and pyrethroid pesticides in South China: Implications for a regional risk assessment

    International Nuclear Information System (INIS)

    Li, Huizhen; Wei, Yanli; Lydy, Michael J.; You, Jing

    2014-01-01

    The dynamic flux of an organophosphate and four pyrethroid pesticides was determined in an air-(soil)-water-sediment system based on monitoring data from Guangzhou, China. The total air–water flux, including air–water gaseous exchange and atmospheric deposition, showed deposition from air to water for chlorpyrifos, bifenthrin and cypermethrin, but volatilization for lambda-cyhalothrin and permethrin. The transport of the pesticides from overlying water to sediment suggested that sediment acted as a sink for the pesticides. Additionally, distinct annual atmospheric depositional fluxes between legacy and current-use pesticides suggested the role of consumer usage in their transport throughout the system. Finally, pesticide toxicity was estimated from annual air–water-sediment flux within an urban stream in Guangzhou. A dynamic flux-based risk assessment indicated that inter-compartmental transport of chlorpyrifos decreased its atmospheric exposure, but had little influence on its aquatic toxicity. Instead, water-to-sediment transport of pyrethroids increased their sediment toxicity, which was supported by previously reported toxicity data. - Highlights: • Transport fluxes of chlorpyrifos and pyrethroids were assessed in Guangzhou, China. • Sediment acted as a sink for chlorpyrifos and pyrethroids. • Air-to-water transport decreased the exposure risk of atmospheric chlorpyrifos. • Dynamic transport might increase the risk of pyrethroids in air and sediment. • Flux-based pesticide concentrations provide a way to estimate sediment toxicity. - Regional risk assessment could be improved by integrating dynamic flux information derived from inter-compartmental models

  5. The Use of Metaphors in Poetry and Organization Theory: Toward De-Compartmentalization of Organizational Knowledge

    Directory of Open Access Journals (Sweden)

    Naveed Yazdani

    2011-09-01

    Full Text Available Since the time of Western modernity, knowledge is compartmentalized into differentiated fields. This has however not mitigated the influence of natural science model of theorizing on social sciences. As a result, the discipline of organization theory has grown without the influence of abstract, ephemeral and metaphysical fields such as religion, history, mystic philosophy, arts and literature. With the rise of organizational cultural studies and the emergence of symbolic-interpretive view of organizing during the last three or four decades, the trend is however gradually shifting. Corporate aesthetics is a field within organization theory which places value on the aesthetical aspects of managing and organizing. Taking the lead from corporate aesthetics, this paper highlights the link between Organization theory and literature (poetry, both English and Urdu. The linguistic and conceptual instrument of metaphors is isolated as the underpinning tool of this link. The role of metaphors in organization theory seems to have further importance because of the emergence of „social construction‟ and „sense making‟ views of organizations. The paper reinforces the views of contemporary writers of organization theory that the field draws from multiple and diverse disciplines by highlighting the link between organization theory and poetry through employing metaphoricity.

  6. Identification of HIV-1 genitourinary tract compartmentalization by analyzing the env gene sequences in urine.

    Science.gov (United States)

    Blasi, Maria; Carpenter, J Harris; Balakumaran, Bala; Cara, Andrea; Gao, Feng; Klotman, Mary E

    2015-08-24

    HIV-1 persists indefinitely in memory CD4 T cells and other long-lived cellular reservoirs despite antiretroviral therapy. Our group had previously demonstrated that HIV-1 can establish a productive infection in renal epithelial cells and that the kidney represents a separate compartment for HIV-1 replication. Here, to better understand the viruses in this unique site, we genetically characterized and compared the viruses in blood and urine specimens from 24 HIV-1 infected patients with detectable viremia. Blood and urine samples were obtained from 35 HIV-1 positive patients. Single-genome amplification was performed on HIV-1 env RNA and DNA isolated from urine supernatants and urine-derived cell pellets, respectively, as well as from plasma and peripheral blood mononuclear cell from the same individuals. Neighbor-joining trees were constructed under the Kimura 2-parameter model. We amplified and sequenced the full-length HIV-1 envelope (env) gene from 12 of the 24 individuals, indicating that 50% of the viremic HIV-1-positive patients had viral RNA in their urine. Phylogenetic analysis of the env sequences from four individuals with more than 15 urine-derived env sequences showed that the majority of the sequences from urine formed distinct cluster(s) independent of those peripheral blood mononuclear cell and plasma-derived sequences, consistent with viral compartmentalization in the urine. Our results suggest the presence of a distinct HIV compartment in the genitourinary tract.

  7. Compartmentalized system with membrane-bound glycerol kinase. Activity and product distribution versus asymmetrical substrate supply.

    Science.gov (United States)

    Girard, A; Merchie, B; Maïsterrena, B

    1991-03-15

    An artificial-membrane-bound glycerokinase chosen as a membrane-bound two-substrate-enzyme model has been used to separate two unequal compartments of a specially designed diffusion cell. An interesting feature is the asymmetry of compartments and the existence of a diffusion layer adjacent to only one face of the enzymic membrane. In such a situation the apparent enzyme activity and the product distribution in the system have been studied versus all the possibilities of combination of ATP and glycerol supply. Our approach has lead us to differentiate two different roles played by a diffusion layer adjacent to a permeable enzymic membrane. Depending on the spatial origin of the enzymic substrates (i.e. from which compartment they derive), the diffusion layer can play either the role of a passive additional resistance to that of the membrane or the role of a third compartment in which the reaction product can partially accumulate before splitting on both parts of the membrane. Our results mainly demonstrate that a membrane-bound enzyme activity and the resulting product distribution occurring in a compartmentalized system may be regulated by the cumulative effect due to the asymmetry in volumes of the compartments, the presence of a diffusion layer and the different possibilities of substrate supply. With the topography studied, which is close to that reported for many 'in vivo' situations, the product may be diffused lead to vectorial metabolism processes.

  8. Three-compartmental analysis of effects of D-propranolol on thyroid hormone kinetics

    International Nuclear Information System (INIS)

    Van Der Heijden, J.T.M.; Krenning, E.P.; Van Toor, H.; Hennemann, G.; Docter, R.

    1988-01-01

    Tracer thyroxine (T 4 ), 3,3',5-triiodothyronine (T 3 ), and 3,3',5'-triiodothyronine (rT 3 ) kinetic studies were performed in normal T 4 substituted subjects before and during oral D-propranolol treatment to determine whether changes in thyroid hormone metabolism in a propranolol-induced low-T 3 syndrome result from inhibition of 5'-deiodination or inhibition of transport of iodothyronines into tissues. Data were analyzed according to a three-compartmental model of distribution and metabolism. No changes were observed in size of the three T 4 compartments or in fractional and mass transfer rates of T 4 from plasma to the rapidly (REP) and slowly (SEP) equilibrating pools. Serum T 3 , free T 3 , T 3 plasma pool, T 3 mass transfer rate to REP and SEP, and the T 3 pool masses were all significantly decreased during propranolol to a similar extent as the T 3 plasma production rate (PR). It is concluded that the D-propranolol-induced changes in thyroid hormone metabolism, resulting in a low-T 3 syndrome, are due to inhibition of thyroid hormone deiodination. This is in contrast to the low-T 3 syndrome during caloric deprivation, which results from inhibition of transport of iodothyronines into the liver

  9. Differential compartmentalization of Streptococcus pyogenes virulence factors and host protein binding properties as a mechanism for host adaptation.

    Science.gov (United States)

    Kilsgård, Ola; Karlsson, Christofer; Malmström, Erik; Malmström, Johan

    2016-11-01

    Streptococcus pyogenes is an important human pathogen responsible for substantial morbidity and mortality worldwide. Although S. pyogenes is a strictly human pathogen with no other known animal reservoir, several murine infection models exist to explore different aspects of the bacterial pathogenesis. Inoculating mice with wild-type S. pyogenes strains can result in the generation of new bacterial phenotypes that are hypervirulent compared to the original inoculum. In this study, we used a serial mass spectrometry based proteomics strategy to investigate if these hypervirulent strains have an altered distribution of virulence proteins across the intracellular, surface associated and secreted bacterial compartments and if any change in compartmentalization can alter the protein-protein interaction network between bacteria and host proteins. Quantitative analysis of the S. pyogenes surface and secreted proteomes revealed that animal passaged strains are associated with significantly higher amount of virulence factors on the bacterial surface and in the media. This altered virulence factor compartmentalization results in increased binding of several mouse plasma proteins to the bacterial surface, a trend that was consistent for mouse plasma from several different mouse strains. In general, both the wild-type strain and animal passaged strain were capable of binding high amounts of human plasma proteins. However, compared to the non-passaged strains, the animal passaged strains displayed an increased ability to bind mouse plasma proteins, in particular for M protein binders, indicating that the increased affinity for mouse blood plasma proteins is a consequence of host adaptation of this pathogen to a new host. In conclusion, plotting the total amount of virulence factors against the total amount of plasma proteins associated to the bacterial surface could clearly separate out animal passaged strains from wild type strains indicating a virulence model that could

  10. An actomyosin-based barrier inhibits cell mixing at compartmental boundaries in Drosophila embryos.

    Science.gov (United States)

    Monier, Bruno; Pélissier-Monier, Anne; Brand, Andrea H; Sanson, Bénédicte

    2010-01-01

    Partitioning tissues into compartments that do not intermix is essential for the correct morphogenesis of animal embryos and organs. Several hypotheses have been proposed to explain compartmental cell sorting, mainly differential adhesion, but also regulation of the cytoskeleton or of cell proliferation. Nevertheless, the molecular and cellular mechanisms that keep cells apart at boundaries remain unclear. Here we demonstrate, in early Drosophila melanogaster embryos, that actomyosin-based barriers stop cells from invading neighbouring compartments. Our analysis shows that cells can transiently invade neighbouring compartments, especially when they divide, but are then pushed back into their compartment of origin. Actomyosin cytoskeletal components are enriched at compartmental boundaries, forming cable-like structures when the epidermis is mitotically active. When MyoII (non-muscle myosin II) function is inhibited, including locally at the cable by chromophore-assisted laser inactivation (CALI), in live embryos, dividing cells are no longer pushed back, leading to compartmental cell mixing. We propose that local regulation of actomyosin contractibility, rather than differential adhesion, is the primary mechanism sorting cells at compartmental boundaries.

  11. Krebs cycle metabolon formation: metabolite concentration gradient enhanced compartmentation of sequential enzymes.

    Science.gov (United States)

    Wu, Fei; Pelster, Lindsey N; Minteer, Shelley D

    2015-01-25

    Dynamics of metabolon formation in mitochondria was probed by studying diffusional motion of two sequential Krebs cycle enzymes in a microfluidic channel. Enhanced directional co-diffusion of both enzymes against a substrate concentration gradient was observed in the presence of intermediate generation. This reveals a metabolite directed compartmentation of metabolic pathways.

  12. The Contradictions and Compartmentalizing the Interactions between Integrated Business Structures: Aspect of Branding

    Directory of Open Access Journals (Sweden)

    Nifatova Olena M.

    2017-04-01

    Full Text Available The article is aimed at identifying contradictions and developing a compartmentalizing as to the interaction between integrated business structures, taking into consideration the branding approach to management. The main specific features and contradictions that arise in the process of integration in the domestic market of mergers and acquisitions have been allocated. The contradictions identified were systematized and substantiated at three economic levels: macro-, meso-, and microeconomic. A compartmentalizing of the business units interaction in a merge or an acquisition process has been proposed. This compartmentalizing takes account of the branding aspect through the introduction of «brands interaction» – cluster interaction, circular interaction, holding interaction, linear interaction, which enhances the scientific view of exploring the problem of business units interaction in the process of the formations becoming integrated. The development of a compartmentalizing as to the interaction between integrated business structures, taking into consideration the branding approach to management, would provide a more effective use of the fundamental nature of branding as synergistic force in terms of the system of integration of business structures at the current stage of development of the national economy. Further development of branding issues in this sphere will have a significant impact on the functioning of the integrated business structures with the participation of Ukrainian companies.

  13. Heterogeneity and compartmentalization of Pneumocystis carinii f. sp. hominis genotypes in autopsy lungs

    DEFF Research Database (Denmark)

    Helweg-Larsen, J; Lundgren, Bettina; Lundgren, Jens Dilling

    2001-01-01

    . Not all genotypes present in the lungs at autopsy were detected in the diagnostic respiratory samples. Compartmentalization of specific ITS and mtLSU rRNA sequence types was observed in different lung segments. In conclusion, the interpretation of genotype data and in particular ITS sequence types...

  14. Meningoencephalitis and Compartmentalization of the Cerebral Ventricles Caused by Enterobacter sakazakii

    Science.gov (United States)

    Kleiman, Martin B.; Allen, Stephen D.; Neal, Patricia; Reynolds, Janet

    1981-01-01

    A necrotizing meningoencephalitis complicated by ventricular compartmentalization and abscess formation caused by Enterobacter sakazakii in a previously healthy 5-week-old female is described. A detailed description of the isolate is presented. This communication firmly establishes the pathogenicity of E. sakazakii. PMID:7287892

  15. SYNCHROTRON X-RAY ABSORPTION-EDGE COMPUTED MICROTOMOGRAPHY IMAGING OF THALLIUM COMPARTMENTALIZATION IN IBERIS INTERMEDIA

    Science.gov (United States)

    Thallium (TI) is an extremely toxic metal which, due to its similarities to K, is readily taken up by plants. Thallium is efficiently hyperaccumulated in Iberis intermedia as TI(I). Distribution and compartmentalization of TI in I. intermedia is highes...

  16. Compartmentalization: a conceptual framework for understanding how trees grow and defend themselves

    Science.gov (United States)

    Alex L. Shigo

    1984-01-01

    The purpose of this chapter is to describe a conceptual framework for understanding how trees grow and how they and other perennial plants defend themselves. The concept of compartmentalization has developed over many years, a synthesis of ideas from a number of investigators. It is derived from detailed studies of the gross morphology and cellular anatomy of the wood...

  17. Compartmentalization and transport in β-lactam antibiotic biosynthesis by filamentous fungi

    NARCIS (Netherlands)

    Kamp, Mart van de; Driessen, Arnold J.M.; Konings, Wil N.

    1999-01-01

    A proper description of the biosynthesis of fungal β-lactam antibiotics requires detailed knowledge of the cell biology of the producing organisms. This involves a delineation of the compartmentalization of the biosynthetic pathways, and of the consequential transport steps across the cell-boundary

  18. Xylem Vessel Diameter Affects the Compartmentalization of the Vascular Pathogen Phaeomoniella chlamydospora in Grapevine

    Directory of Open Access Journals (Sweden)

    Jérôme Pouzoulet

    2017-08-01

    Full Text Available Fungal wilt diseases are a threat to global food safety. Previous studies in perennial crops showed that xylem vessel diameter affects disease susceptibility. We tested the hypothesis that xylem vessel diameter impacts occlusion processes and pathogen compartmentalization in Vitis vinifera L. We studied the interaction between four grape commercial cultivars with the vascular wilt pathogen Phaeomoniella chlamydospora. We used qPCR and wood necrotic lesion length to measure fungal colonization coupled with histological studies to assess differences in xylem morphology, pathogen compartmentalization, and fungal colonization strategy. We provided evidence that grape cultivar with wide xylem vessel diameter showed increased susceptibility to P. chlamydospora. The host response to pathogen included vessel occlusion with tyloses and gels, deposition of non-structural phenolic compounds and suberin in vessel walls and depletion of starch in parenchyma cells. Pathogen compartmentalization was less efficient in wide xylem vessels than in narrow diameter vessels. Large vessels displayed higher number of tyloses and gel pockets, which provided substrate for P. chlamydospora growth and routes to escape occluded vessels. We discuss in which capacity xylem vessel diameter is a key determinant of the compartmentalization process and in turn grape cultivar resistance to disease caused by P. chlamydospora.

  19. Compartmental and dosimetric studies of anti-CD20 labelled with 188Re

    International Nuclear Information System (INIS)

    Kuramoto, Graciela Barrio

    2016-01-01

    The radioimmunotherapy (RIT) uses MAbs conjugated to radionuclides α or β - emitters, both for therapy. Your treatment is based on the irradiation and tumor destruction, preserving the normal organs as the excess radiation. Radionuclides β - emitters as 131 I, 90 Y, 188 Re 177 Lu and are useful for the development of therapeutic radiopharmaceuticals and, when coupled with MAb and Anti-CD20 it is important mainly for the treatment of non-Hodgkin's lymphomas (NHL). 188 Re (E β = 2.12 MeV; E γ = 155 keV; t1/2 = 16.9 h) is an attractive radionuclide for RIT. However, 188 Re can be obtained from a radionuclide generator of 188 W/ 188 Re, commercially available, making it convenient for use in research and for clinical routine. The CR of IPEN has a project aimed at the production of radiopharmaceutical 188 Re-Anti-CD20, where the radionuclide can be obtained from a generator system 188 W/ 188 Re. With this proposed a study to assess the efficiency of this labeling technique for treatment in accordance compartmental and dosimetry. The objective of this study was to compare the marking of anti-CD20 MAb with 188 Re with the marking of the antibody with 90 Y, 131 I, 177 Lu and 99m Tc (for their similar chemical characteristics) and 211 At, 213 Bi, 223 Ra and 225 Ac); through the study of labeling techniques reported in literature, the proposal of a compartmental model to evaluate its pharmacokinetic and dosimetric studies, high interest for therapy. The result of the study shows a favorable kinetics for 188 Re, by their physical and chemical characteristics compared to the other evaluated radionuclides. The compartment proposed study describes the metabolism of 188 Reanti- CD20 through a compartment mammillary model, which by their pharmacokinetic analysis, performed compared to products emitters β -131 I-labeled anti CD20, 177 Luanti- CD20, the γ emitter 99m Tc-Anti-CD20 and α emitter 211 At-Anti-CD20 presented a elimination constant of approximately 0.05 hours

  20. Relationships between metal compartmentalization and biomarkers in earthworms exposed to field-contaminated soils.

    Science.gov (United States)

    Beaumelle, Léa; Hedde, Mickaël; Vandenbulcke, Franck; Lamy, Isabelle

    2017-05-01

    Partitioning tissue metal concentration into subcellular compartments reflecting toxicologically available pools may provide good descriptors of the toxicological effects of metals on organisms. Here we investigated the relationships between internal compartmentalization of Cd, Pb and Zn and biomarker responses in a model soil organism: the earthworm. The aim of this study was to identify metal fractions reflecting the toxic pressure in an endogeic, naturally occurring earthworm species (Aporrectodea caliginosa) exposed to realistic field-contaminated soils. After a 21 days exposure experiment to 31 field-contaminated soils, Cd, Pb and Zn concentrations in earthworms and in three subcellular fractions (cytosol, debris and granules) were quantified. Different biomarkers were measured: the expression of a metallothionein gene (mt), the activity of catalase (CAT) and of glutathione-s-transferase (GST), and the protein, lipid and glycogen reserves. Biomarkers were further combined into an integrated biomarker index (IBR). The subcellular fractionation provided better predictors of biomarkers than the total internal contents hence supporting its use when assessing toxicological bioavailability of metals to earthworms. The most soluble internal pools of metals were not always the best predictors of biomarker responses. metallothionein expression responded to increasing concentrations of Cd in the insoluble fraction (debris + granules). Protein and glycogen contents were also mainly related to Cd and Pb in the insoluble fraction. On the other hand, GST activity was better explained by Pb in the cytosolic fraction. CAT activity and lipid contents variations were not related to metal subcellular distribution. The IBR was best explained by both soluble and insoluble fractions of Pb and Cd. This study further extends the scope of mt expression as a robust and specific biomarker in an ecologically representative earthworm species exposed to field-contaminated soils. The

  1. Diversity in the dynamical behaviour of a compartmentalized programmable biochemical oscillator.

    Science.gov (United States)

    Weitz, Maximilian; Kim, Jongmin; Kapsner, Korbinian; Winfree, Erik; Franco, Elisa; Simmel, Friedrich C

    2014-04-01

    In vitro compartmentalization of biochemical reaction networks is a crucial step towards engineering artificial cell-scale devices and systems. At this scale the dynamics of molecular systems becomes stochastic, which introduces several engineering challenges and opportunities. Here we study a programmable transcriptional oscillator system that is compartmentalized into microemulsion droplets with volumes between 33 fl and 16 pl. Simultaneous measurement of large populations of droplets reveals major variations in the amplitude, frequency and damping of the oscillations. Variability increases for smaller droplets and depends on the operating point of the oscillator. Rather than reflecting the stochastic kinetics of the chemical reaction network itself, the variability can be attributed to the statistical variation of reactant concentrations created during their partitioning into droplets. We anticipate that robustness to partitioning variability will be a critical challenge for engineering cell-scale systems, and that highly parallel time-series acquisition from microemulsion droplets will become a key tool for characterization of stochastic circuit function.

  2. Compartmentalization of metabolic pathways in yeast mitochondria improves the production of branched-chain alcohols.

    Science.gov (United States)

    Avalos, José L; Fink, Gerald R; Stephanopoulos, Gregory

    2013-04-01

    Efforts to improve the production of a compound of interest in Saccharomyces cerevisiae have mainly involved engineering or overexpression of cytoplasmic enzymes. We show that targeting metabolic pathways to mitochondria can increase production compared with overexpression of the enzymes involved in the same pathways in the cytoplasm. Compartmentalization of the Ehrlich pathway into mitochondria increased isobutanol production by 260%, whereas overexpression of the same pathway in the cytoplasm only improved yields by 10%, compared with a strain overproducing enzymes involved in only the first three steps of the biosynthetic pathway. Subcellular fractionation of engineered strains revealed that targeting the enzymes of the Ehrlich pathway to the mitochondria achieves greater local enzyme concentrations. Other benefits of compartmentalization may include increased availability of intermediates, removing the need to transport intermediates out of the mitochondrion and reducing the loss of intermediates to competing pathways.

  3. Organization of parent knowledge: compartmentalization and integration in adult child-parent relationships.

    Science.gov (United States)

    Limke, Alicia; Showers, Carolin J

    2010-09-01

    Previous research has demonstrated an association between structure of beliefs about romantic partners and feelings for that partner. Here, the structure of college students' beliefs about their parents was linked to distinct types of ongoing parent-child relationships identified by cluster analysis. An integrative structure of mother knowledge was associated with an evaluatively complex type of relationship ("dealing"), characterized by greater liking and closeness and less cooperation and contact. Positive compartmentalization of mother knowledge was associated with mother relationships that were consistently positive ("denying") across different dimensions. In contrast, the most positive father relationships were reported by daughters with evaluatively integrative father structures. Possible reasons for daughters' tendency to integrate father structures and to compartmentalize mother structures are discussed.

  4. Etiopathogenical criteria in the early diagnosis of Compartmental Syndrome (CS of the shank

    Directory of Open Access Journals (Sweden)

    Șerban Al. O.

    2014-11-01

    Full Text Available Through the evaluation of some etiopathogenic risk factors one can anticipate the evaluation of some fractures towards Compartmental Syndrome (CS and then their diagnosis in early stage, when the symptomatology is still unconvincing and the treatment reduces the risk of ischemia lesions. Based both on some prospective observations, using a group of shank fractures, and also on the clinical facts of constituted CS, there were made correlations, statistically reported in the case of some etiopathogenic risk factors represented by the fracture localization and its characteristics, traumatic mechanisms, soft tissue quality and polytraumatism, having an objective common denominator, the compartmental pressure level measured directly. The authors propose an etiopathogenic risk score of CS for the fractures reaching the pressure level of 20-30mmHg, recommending the pressional and clinical monitoring for a score of minimum 10 points. These fractures have a certain risk of CS.

  5. The architecture of antagonistic networks: Node degree distribution, compartmentalization and nestedness

    OpenAIRE

    Savannah Nuwagaba; Cang Hui

    2015-01-01

    Describing complex ecosystems as networks of interacting components has proved fruitful - revealing many distinctive patterns and dynamics of ecological systems. Of these patterns, three have often been brought up in literature, including species degree distribution, compartmentalization and nestedness, due largely to their implications for the functionality and stability of communities. Here, using 61 empirical antagonistic networks, we aim to settle the inconsistency in literature by (i) fi...

  6. Aspects of astrocyte energy metabolism, amino acid neurotransmitter homoeostasis and metabolic compartmentation

    DEFF Research Database (Denmark)

    Kreft, Marko; Bak, Lasse Kristoffer; Waagepetersen, Helle S

    2012-01-01

    Astrocytes are key players in brain function; they are intimately involved in neuronal signalling processes and their metabolism is tightly coupled to that of neurons. In the present review, we will be concerned with a discussion of aspects of astrocyte metabolism, including energy-generating pat......-generating pathways and amino acid homoeostasis. A discussion of the impact that uptake of neurotransmitter glutamate may have on these pathways is included along with a section on metabolic compartmentation....

  7. Mapping intracellular diffusion distribution using single quantum dot tracking: compartmentalized diffusion defined by endoplasmic reticulum.

    Science.gov (United States)

    Li, Hui; Dou, Shuo-Xing; Liu, Yu-Ru; Li, Wei; Xie, Ping; Wang, Wei-Chi; Wang, Peng-Ye

    2015-01-14

    The crowded intracellular environment influences the diffusion-mediated cellular processes, such as metabolism, signaling, and transport. The hindered diffusion of macromolecules in heterogeneous cytoplasm has been studied over years, but the detailed diffusion distribution and its origin still remain unclear. Here, we introduce a novel method to map rapidly the diffusion distribution in single cells based on single-particle tracking (SPT) of quantum dots (QDs). The diffusion map reveals the heterogeneous intracellular environment and, more importantly, an unreported compartmentalization of QD diffusions in cytoplasm. Simultaneous observations of QD motion and green fluorescent protein-tagged endoplasmic reticulum (ER) dynamics provide direct evidence that the compartmentalization results from micron-scale domains defined by ER tubules, and ER cisternae form perinuclear areas that restrict QDs to enter. The same phenomenon was observed using fluorescein isothiocyanate-dextrans, further confirming the compartmentalized diffusion. These results shed new light on the diffusive movements of macromolecules in the cell, and the mapping of intracellular diffusion distribution may be used to develop strategies for nanoparticle-based drug deliveries and therapeutics.

  8. Repurposing the Saccharomyces cerevisiae peroxisome for compartmentalizing multi-enzyme pathways

    Energy Technology Data Exchange (ETDEWEB)

    DeLoache, William [Univ. of California, Berkeley, CA (United States); Russ, Zachary [Univ. of California, Berkeley, CA (United States); Samson, Jennifer [Univ. of California, Berkeley, CA (United States); Dueber, John [Univ. of California, Berkeley, CA (United States)

    2017-09-25

    The peroxisome of Saccharomyces cerevisiae was targeted for repurposing in order to create a synthetic organelle that provides a generalizable compartment for engineered metabolic pathways. Compartmentalization of enzymes into organelles is a promising strategy for limiting metabolic crosstalk, improving pathway efficiency, and ultimately modifying the chemical environment to be distinct from that of the cytoplasm. We focused on the Saccharomyces cerevisiae peroxisome, as this organelle is not required for viability when grown on conventional media. We identified an enhanced peroxisomal targeting signal type 1 (PTS1) for rapidly importing non-native cargo proteins. Additionally, we performed the first systematic in vivo measurements of nonspecific metabolite permeability across the peroxisomal membrane using a polymer exclusion assay and characterized the size dependency of metabolite trafficking. Finally, we applied these new insights to compartmentalize a two-enzyme pathway in the peroxisome and characterize the expression regimes where compartmentalization leads to improved product titer. This work builds a foundation for using the peroxisome as a synthetic organelle, highlighting both promise and future challenges on the way to realizing this goal.

  9. Self-concept structure and borderline personality disorder: evidence for negative compartmentalization.

    Science.gov (United States)

    Vater, Aline; Schröder-Abé, Michela; Weißgerber, Susan; Roepke, Stefan; Schütz, Astrid

    2015-03-01

    Borderline personality disorder (BPD) is characterized by an unstable and incongruent self-concept. However, there is a dearth of empirical studies investigating self-concept in BPD. In order to bridge this research gap, the purpose of this study was to apply an in-depth analysis of structural aspects of the self-concept in BPD. We examined the degree of compartmentalization, i.e., a tendency to organize knowledge about the self into discrete, extremely valenced (i.e., either positive or negative) categories (Showers, 1992). We hypothesized and found that BPD patients had the most compartmentalized self-concept structure and a higher proportion of negative self-attributes relative to both a non-clinical and a depressed control group. Moreover, BPD patients rated negative self-aspects as more important than positive ones relative to non-clinical controls. We cannot determine whether causal relationships exist between psychological symptoms and self-concept structure. Moreover, further comparisons to patients with other psychiatric disorders are necessary in order to further confirm the clinical specificity of our results. Our findings indicate that a negative compartmentalized self-concept is a specific feature of BPD. Implications for future research, psychological assessment, and psychotherapeutic treatment are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Compartmentalization of SIV Replication Within Secondary Lymphoid Tissues of Rhesus Macaques is Linked to Disease Stage and Inversely Related to Localization of Virus-Specific CTL1 2

    Science.gov (United States)

    Connick, Elizabeth; Folkvord, Joy M.; Lind, Katherine T.; Rakasz, Eva G.; Miles, Brodie; Wilson, Nancy A.; Santiago, Mario L.; Schmitt, Kimberly; Stephens, Edward B.; Kim, Hyeon O.; Wagstaff, Reece; Li, Shengbin; Abdelaal, Hadia M.; Kemp, Nathan; Watkins, David I.; MaWhinney, Samantha; Skinner, Pamela J.

    2014-01-01

    We previously demonstrated that HIV replication is concentrated in lymph node B cell follicles during chronic infection and that HIV-specific CTL fail to accumulate in large numbers at those sites. It is unknown whether these observations can be generalized to other secondary lymphoid tissues, or whether virus compartmentalization occurs in the absence of CTL. We evaluated these questions in SIVmac239-infected rhesus macaques by quantifying SIV RNA+ cells and SIV-specific CTL in situ in spleen, lymph nodes and intestinal tissues obtained at several stages of infection. During chronic asymptomatic infection prior to simian AIDS (SAIDS), SIV-producing cells were more concentrated in follicular compared to extrafollicular regions of secondary lymphoid tissues. At day 14 of infection, when CTL have minimal impact on virus replication, there was no compartmentalization of SIV-producing cells. Virus compartmentalization was diminished in animals with SAIDS, which often have low frequency CTL responses. SIV-specific CTL were consistently more concentrated within extrafollicular regions of lymph node and spleen in chronically infected animals regardless of epitope specificity. Frequencies of SIV-specific CTL within follicular and extrafollicular compartments predicted SIV RNA+ cells within these compartments in a mixed model. Few SIV-specific CTL expressed the follicular homing molecule CXCR5 in the absence of the extrafollicular retention molecule CCR7, possibly accounting for the paucity of follicular CTL. These findings bolster the hypothesis that B cell follicles are immune privileged sites and suggest that strategies to augment CTL in B cell follicles could lead to improved viral control and possibly a functional cure for HIV infection. PMID:25362178

  11. Modeling of the Renal Kinetics of the AT1 Receptor Specific PET Radioligand [11C]KR31173

    Directory of Open Access Journals (Sweden)

    Nedim C. M. Gulaldi

    2013-01-01

    Full Text Available Purpose. The radioligand [11C]KR31173 has been introduced for PET imaging of the angiotensin II subtype 1 receptor (AT1R. The purpose of the present project was to employ and validate a compartmental model for quantification of the kinetics of this radioligand in a porcine model of renal ischemia followed by reperfusion (IR. Procedures. Ten domestic pigs were included in the study: five controls and five experimental animals with IR of the left kidney. To achieve IR, acute ischemia was created with a balloon inserted into the left renal artery and inflated for 60 minutes. Reperfusion was achieved by deflation and removal of the balloon. Blood chemistries, urine specific gravity and PH values, and circulating hormones of the renin angiotensin system were measured and PET imaging was performed one week after IR. Cortical time-activity curves obtained from a 90 min [11C]KR31173 dynamic PET study were processed with a compartmental model that included two tissue compartments connected in parallel. Radioligand binding quantified by radioligand retention (80 min value to maximum value ratio was compared to the binding parameters derived from the compartmental model. A binding ratio was calculated as DVR=DVS/DVNS, where DVS and DVNS represented the distribution volumes of specific binding and nonspecific binding. Receptor binding was also determined by autoradiography in vitro. Results. Correlations between rate constants and binding parameters derived by the convolution and deconvolution curve fittings were significant (r>0.9. Also significant was the correlation between the retention parameter derived from the tissue activity curve (Yret and the retention parameter derived from the impulse response function (fret. Furthermore, significant correlations were found between these two retention parameters and DVR. Measurements with PET showed no significant changes in the radioligand binding parameters caused by IR, and these in vivo findings were

  12. Directed clustering in driven compartmentalized granular gas systems in zero gravity

    International Nuclear Information System (INIS)

    Li, Y; Hou, M; Evesque, P

    2011-01-01

    Clustering of shaken fluidized granular matter in connected compartments has been observed and studied in the laboratory. This clustering behavior in granular gas systems is related to the dissipative nature of granular system, and therefore shall not depend on gravity. This clustering phenomenon in compartmental configuration may provide a means for particle depletion and transportation in microgravity environment. In this work we propose different configurations for possible directed clustering in zero gravity. The related experiment has been planned for the Chinese satellite SJ-10.

  13. Folded genome as a platform for the functional compartmentalization of the eukaryotic cell nucleus

    Directory of Open Access Journals (Sweden)

    Ioudinkova E. S.

    2014-03-01

    Full Text Available In a number of recent studies a tight interconnection between the spatial organization of the eukaryotic genome and its functioning has been demonstrated. Moreover, it is becoming evident that the folded DNA by itself consti- tutes an important, if not the key, factor supporting the internal nuclear organization. In this review, we will discuss the current state of chromatin research with the special attention focused on chromosome territories, chromatin folding and dynamics, chromatin domains, transcription and replication factories. Based on this analysis we will show how interphase chromosomes define the assembly of different nuclear compartments and underlie the spatial compartmentalization of the cell nucleus.

  14. Intracellular Redox Compartmentation and ROS-Related Communication in Regulation and Signaling.

    Science.gov (United States)

    Noctor, Graham; Foyer, Christine H

    2016-07-01

    Recent years have witnessed enormous progress in understanding redox signaling related to reactive oxygen species (ROS) in plants. The consensus view is that such signaling is intrinsic to many developmental processes and responses to the environment. ROS-related redox signaling is tightly wedded to compartmentation. Because membranes function as barriers, highly redox-active powerhouses such as chloroplasts, peroxisomes, and mitochondria may elicit specific signaling responses. However, transporter functions allow membranes also to act as bridges between compartments, and so regulated capacity to transmit redox changes across membranes influences the outcome of triggers produced at different locations. As well as ROS and other oxidizing species, antioxidants are key players that determine the extent of ROS accumulation at different sites and that may themselves act as signal transmitters. Like ROS, antioxidants can be transported across membranes. In addition, the intracellular distribution of antioxidative enzymes may be modulated to regulate or facilitate redox signaling appropriate to the conditions. Finally, there is substantial plasticity in organellar shape, with extensions such as stromules, peroxules, and matrixules playing potentially crucial roles in organelle-organelle communication. We provide an overview of the advances in subcellular compartmentation, identifying the gaps in our knowledge and discussing future developments in the area. © 2016 American Society of Plant Biologists. All Rights Reserved.

  15. Compartmentalization of the gut viral reservoir in HIV-1 infected patients

    Directory of Open Access Journals (Sweden)

    Grant Tannika

    2007-12-01

    Full Text Available Abstract Background Recently there has been an increasing interest and appreciation for the gut as both a viral reservoir as well as an important host-pathogen interface in human immunodefiency virus type 1 (HIV-1 infection. The gut associated lymphoid tissue (GALT is the largest lymphoid organ infected by HIV-1. In this study we examined if different HIV-1 quasispecies are found in different parts of the gut of HIV-1 infected individuals. Results Gut biopsies (esophagus, stomach, duodenum and colorectum were obtained from eight HIV-1 infected preHAART (highly active antiretroviral therapy patients. HIV-1 Nef and Reverse transcriptase (RT encoding sequences were obtained through nested PCR amplification from DNA isolated from the gut biopsy tissues. The PCR fragments were cloned and sequenced. The resulting sequences were subjected to various phylogenetic analyses. Expression of the nef gene and viral RNA in the different gut tissues was determined using real-time RT-PCR. Phylogenetic analysis of the Nef protein-encoding region revealed compartmentalization of viral replication in the gut within patients. Viral diversity in both the Nef and RT encoding region varied in different parts of the gut. Moreover, increased nef gene expression (p Conclusion Our results indicated that different HIV-1 quasispecies populate different parts of the gut, and that viral replication in the gut is compartmentalized. These observations underscore the importance of the gut as a host-pathogen interface in HIV-1 infection.

  16. Proline accumulation, ions dynamics and sodium root-shoot partition and compartmentation

    Directory of Open Access Journals (Sweden)

    Jesus Emanuel eBojorquez Quintal

    2014-11-01

    Full Text Available Despite its economic relevance, little is known about salt tolerance mechanisms in pepper plants. To address this question, we compared differences in responses to NaCl in two Capsicum chinense varieties: Rex (tolerant and Chichen-Itza (sensitive. Under salt stress (150 mM NaCl over 7 days roots of Rex variety accumulated 50 times more compatible solutes such as proline compared to Chichen-Itza. Mineral analysis indicated that Na+ is restricted to roots by preventing its transport to leaves. Fluorescence analysis suggested an efficient Na+ compartmentalization in vacuole-like structures and in small intracellular compartments in roots of Rex variety. At the same time, Na+ in Chichen-Itza plants was compartmentalized in the apoplast, suggesting substantial Na+ extrusion. Rex variety was found to retain more K+ in its roots under salt stress according to a mineral analysis and microelectrode ion flux estimation (MIFE. Vanadate-sensitive H+ efflux was higher in Chichen-Itza variety plants, suggesting a higher activity of the plasma membrane H+-ATPase, which fuels the extrusion of Na+, and, possibly, also the re-uptake of K+. Our results suggest a combination of stress tolerance mechanisms, in order to alleviate the salt-induced injury. Furthermore, Na+ extrusion to apoplast does not appear to be an efficient strategy for salt tolerance in pepper plants.

  17. Posttranslational protein S-palmitoylation and the compartmentalization of signaling molecules in neurons

    Directory of Open Access Journals (Sweden)

    SEAN I PATTERSON

    2002-01-01

    Full Text Available Protein domains play a fundamental role in the spatial and temporal organization of intracellular signaling systems. While protein phosphorylation has long been known to modify the interactions that underlie this organization, the dynamic cycling of lipids should now be included amongst the posttranslational processes determining specificity in signal transduction. The characteristics of this process are reminiscent of the properties of protein and lipid phosphorylation in determining compartmentalization through SH2 or PH domains. Recent studies have confirmed the functional importance of protein S-palmitoylation in the compartmentalization of signaling molecules that support normal physiological function in cell division and apoptosis, and synaptic transmission and neurite outgrowth. In neurons, S-palmitoylation and targeting of proteins to rafts are regulated differentially in development by a number of processes, including some related to synaptogenesis and synaptic plasticity. Alterations in the S-palmitoylation state of proteins substantially affect their cellular function, raising the possibility of new therapeutic targets in cancer and nervous system injury and disease.

  18. Modulation in Wistar Rats of Blood Corticosterone Compartmentation by Sex and a Cafeteria Diet

    Science.gov (United States)

    Romero, María del Mar; Holmgren-Holm, Fredrik; Grasa, Maria del Mar; Esteve, Montserrat; Remesar, Xavier; Fernández-López, José Antonio; Alemany, Marià

    2013-01-01

    In the metabolic syndrome, glucocorticoid activity is increased, but circulating levels show little change. Most of blood glucocorticoids are bound to corticosteroid-binding globulin (CBG), which liver expression and circulating levels are higher in females than in males. Since blood hormones are also bound to blood cells, and the size of this compartment is considerable for androgens and estrogens, we analyzed whether sex or eating a cafeteria diet altered the compartmentation of corticosterone in rat blood. The main corticosterone compartment in rat blood is that specifically bound to plasma proteins, with smaller compartments bound to blood cells or free. Cafeteria diet increased the expression of liver CBG gene, binding plasma capacity and the proportion of blood cell-bound corticosterone. There were marked sex differences in blood corticosterone compartmentation in rats, which were unrelated to testosterone. The use of a monoclonal antibody ELISA and a polyclonal Western blot for plasma CBG compared with both specific plasma binding of corticosterone and CBG gene expression suggested the existence of different forms of CBG, with varying affinities for corticosterone in males and females, since ELISA data showed higher plasma CBG for males, but binding and Western blot analyses (plus liver gene expression) and higher physiological effectiveness for females. Good cross- reactivity to the antigen for polyclonal CBG antibody suggests that in all cases we were measuring CBG.The different immunoreactivity and binding affinity may help explain the marked sex-related differences in plasma hormone binding as sex-linked different proportions of CBG forms. PMID:23451210

  19. The cell cycle of the planctomycete Gemmata obscuriglobus with respect to cell compartmentalization

    Directory of Open Access Journals (Sweden)

    Fuerst John A

    2009-01-01

    Full Text Available Abstract Background Gemmata obscuriglobus is a distinctive member of the divergent phylum Planctomycetes, all known members of which are peptidoglycan-less bacteria with a shared compartmentalized cell structure and divide by a budding process. G. obscuriglobus in addition shares the unique feature that its nucleoid DNA is surrounded by an envelope consisting of two membranes forming an analogous structure to the membrane-bounded nucleoid of eukaryotes and therefore G. obscuriglobus forms a special model for cell biology. Draft genome data for G. obscuriglobus as well as complete genome sequences available so far for other planctomycetes indicate that the key bacterial cell division protein FtsZ is not present in these planctomycetes, so the cell division process in planctomycetes is of special comparative interest. The membrane-bounded nature of the nucleoid in G. obscuriglobus also suggests that special mechanisms for the distribution of this nuclear body to the bud and for distribution of chromosomal DNA might exist during division. It was therefore of interest to examine the cell division cycle in G. obscuriglobus and the process of nucleoid distribution and nuclear body formation during division in this planctomycete bacterium via light and electron microscopy. Results Using phase contrast and fluorescence light microscopy, and transmission electron microscopy, the cell division cycle of G. obscuriglobus was determined. During the budding process, the bud was formed and developed in size from one point of the mother cell perimeter until separation. The matured daughter cell acted as a new mother cell and started its own budding cycle while the mother cell can itself initiate budding repeatedly. Fluorescence microscopy of DAPI-stained cells of G. obscuriglobus suggested that translocation of the nucleoid and formation of the bud did not occur at the same time. Confocal laser scanning light microscopy applied to cells stained for membranes as

  20. Utilization of stable isotopes for the study of in vivo compartmental metabolism of poly-insaturate fatty acids

    International Nuclear Information System (INIS)

    Brossard, N.; Croset, M.; Lecerf, J.; Lagarde, M.; Pachiaudi, C.; Normand, S.; Riou, J.P.; Chirouze, V.; Tayot, J.L.

    1994-01-01

    In order to study the compartmental metabolism of the 22:6n-3 fatty acid, and particularly the role of the transport plasmatic forms for the tissue uptake (especially brain), a technique is developed using carbon 13 stable isotope and an isotopic mass spectrometry coupled to gaseous chromatography technique. This method has been validated in rat with docosahexaenoic acid enriched in 13 C and esterified in triglycerides. The compartmental metabolism is monitored by measuring the variation of 22:6n-3 isotopic enrichment in the various lipoprotein lipidic fractions, in blood globules and in the brain. 1 fig., 1 tab., 12 refs

  1. Multi-compartmental transdermal patch for simultaneous delivery of multiple drugs: formulation and evaluation of newly developed novel dosage form

    Directory of Open Access Journals (Sweden)

    Vijayan Venugopal

    2015-07-01

    Full Text Available Objective: To evaluate the formulation of multi-compartmental transdermal patches for simultaneous delivery of multiple drugs: aceclofenac and serratiopeptidase. Methods: The patch was prepared by simple solvent casting method using hydroxy propyl methyl cellulose K100M as matrix forming agent and dimethyl sulphoxide as permeation enhancer. The prepared transdermal patch was evaluated by physiochemical parameters and in- vitro diffusion studies. Results: The multi-compartmental transdermal patch showed sustained drug release over the period of 12 h. Conclusions: Multicompartmental transdermal patches shows better bioavailability, therapeutic efficacy and very economic as compared with other dosage forms.

  2. Mdm4 loss in the intestinal epithelium leads to compartmentalized cell death but no tissue abnormalities

    Science.gov (United States)

    Valentin-Vega, Yasmine A.; Box, Neil; Terzian, Tamara; Lozano, Guillermina

    2014-01-01

    Mdm4 is a critical inhibitor of the p53 tumor suppressor. Mdm4 null mice die early during embryogenesis due to increased p53 activity. In this study, we explore the role that Mdm4 plays in the intestinal epithelium by crossing mice carrying the Mdm4 floxed allele to mice with the Villin Cre transgene. Our data show that loss of Mdm4 (Mdm4intΔ) in this tissue resulted in viable animals with no obvious morphological abnormalities. However, these mutants displayed increased p53 levels and apoptosis exclusively in the proliferative compartment of the intestinal epithelium. This phenotype was completely rescued in a p53 null background. Notably, the observed compartmentalized apoptosis in proliferative intestinal epithelial cells was not due to restricted Mdm4 expression in this region. Thus, in this specific cellular context, p53 is negatively regulated by Mdm4 exclusively in highly proliferative cells. PMID:19371999

  3. Compartmentalized liquid crystal alignment induced by sparse polymer ribbons with surface relief gratings.

    Science.gov (United States)

    Ji, Zhichao; Zhang, Xinzheng; Shi, Bin; Li, Wei; Luo, Weiwei; Drevensek-Olenik, Irena; Wu, Qiang; Xu, Jingjun

    2016-01-15

    We report on the liquid crystal (LC) alignment induced by sparse polymer ribbons fabricated by the two-photon polymerization-based direct laser writing method. Each ribbon is fabricated by a single scan of the laser through the photoresist and possesses surface relief gratings on both sides. The relief gratings are caused by the optical interference between the incident and reflected laser beams. With the aid of these relief gratings, LC molecules can be well aligned along the selected direction of the ribbons. LC cells with the Z-shaped and checkerboard-type microstructures are constructed based on the sparse out-of-plane polymeric ribbons. Our results show that with such polymer ribbons a compartmentalized LC alignment in the arbitrary microstructures can be realized.

  4. [Effect of NaCl stress on ion compartmentation, photosynthesis and growth of Salicornia bigelovii Torr].

    Science.gov (United States)

    Wang, Li-Yan; Zhao, Ke-Fu

    2004-02-01

    Seedlings of Salicornia bigelovii Torr. were treated with different concentrations of NaCl (0, 100, 300, 600 mmol/L). Ion contents, Na(+) subcelluar localization, photosynthetic rate, ultrastructure of chloroplast and other parameters were measured. The data showed both fresh and dry weight of whole plant of Salicornia bigelovii Torr. under salinity were higher than the control. When NaCl concentration is about 300 mmol/L Salicornia bigelovii Torr. grow strongest. The contents of Na(+) and Cl(-) and c(Na)/c(K) in shoots increased with the salinity. Both Na(+) and Cl(-) were mainly transported to shoots. Ion X-ray microanalysis indicated Na(+) was mainly compartmentalized into vacuoles. Photosynthetic rate increased with the salinity under NaCl 100-300 mmol/L, but declined under NaCl 600 mmol/L. Ultrastructure of chloroplast was destroyed by NaCl 600 mmol/L.

  5. Compartmentalization of metabolic pathways in yeast mitochondria improves production of branched chain alcohols

    Science.gov (United States)

    Avalos, José L.; Fink, Gerald R.; Stephanopoulos, Gregory

    2013-01-01

    Efforts to improve the production of a compound of interest in Saccharomyces cerevisiae have mainly involved engineering or overexpression of cytoplasmic enzymes. We show that targeted expression of metabolic pathways to mitochondria can increase production levels compared with expression of the same pathways in the cytoplasm. Compartmentalisation of the Ehrlich pathway into mitochondria increased isobutanol production by 260%, whereas overexpression of the same pathway in the cytoplasm only improved yields by 10%, compared with a strain overexpressing only the first three steps of the biosynthetic pathway. Subcellular fractionation of engineered strains reveals that targeting the enzymes of the Ehrlich pathway to the mitochondria achieves higher local enzyme concentrations. Other benefits of compartmentalization may include increased availability of intermediates, removing the need to transport intermediates out of the mitochondrion, and reducing the loss of intermediates to competing pathways. PMID:23417095

  6. Dual regulation of muscle glycogen synthase during exercise by activation and compartmentalization

    DEFF Research Database (Denmark)

    Prats, Clara; Helge, Jørn W; Nordby, Pernille

    2009-01-01

    Glycogen synthase (GS) is considered the rate-limiting enzyme in glycogenesis but still today there is a lack of understanding on its regulation. We have previously shown phosphorylation-dependent GS intracellular redistribution at the start of glycogen re-synthesis in rabbit skeletal muscle (Prats......, C., Cadefau, J. A., Cussó, R., Qvortrup, K., Nielsen, J. N., Wojtaszewki, J. F., Wojtaszewki, J. F., Hardie, D. G., Stewart, G., Hansen, B. F., and Ploug, T. (2005) J. Biol. Chem. 280, 23165-23172). In the present study we investigate the regulation of human muscle GS activity by glycogen, exercise......, and insulin. Using immunocytochemistry we investigate the existence and relevance of GS intracellular compartmentalization during exercise and during glycogen re-synthesis. The results show that GS intrinsic activity is strongly dependent on glycogen levels and that such regulation involves associated...

  7. Compartmentation of membrane processes and nucleotide dynamics in diffusion-restricted cardiac cell microenvironment

    Science.gov (United States)

    Alekseev, Alexey E.; Reyes, Santiago; Selivanov, Vitaly A.; Dzeja, Petras P.; Terzic, Andre

    2011-01-01

    Orchestrated excitation–contraction coupling in heart muscle requires adequate spatial arrangement of systems responsible for ion movement and metabolite turnover. Co-localization of regulatory and transporting proteins into macromolecular complexes within an environment of microanatomical cell components raises intracellular diffusion barriers that hamper the mobility of metabolites and signaling molecules. Compared to substrate diffusion in the cytosol, diffusional restrictions underneath the sarcolemma are much larger and could impede ion and nucleotide movement by a factor of 103–105. Diffusion barriers thus seclude metabolites within the submembrane space enabling rapid and vectorial effector targeting, yet hinder energy supply from the bulk cytosolic space implicating the necessity for a shunting transfer mechanism. Here, we address principles of membrane protein compartmentation, phosphotransfer enzyme-facilitated interdomain energy transfer, and nucleotide signal dynamics at the subsarcolemma–cytosol interface. This article is part of a Special Issue entitled ‘Local Signaling in Myocytes’. PMID:21704043

  8. Geo-environmental zoning using physiographic compartmentalization: a proposal for supporting sustainable decision-making

    Directory of Open Access Journals (Sweden)

    CLAUDIA V.S. CORRÊA

    Full Text Available ABSTRACT The geo-environmental zoning represents an important strategy in the territorial management. However, it requires a logical and structured procedure. Therefore, an approach using physiographic compartmentalization is proposed and applied as case study in a region covered by the topographic maps of São José dos Campos and Jacareí, Brazil. This region has great geological and geomorphological peculiarities, beyond being a place with large human interventions because of its quickly economic growth. The methodology is based on photointerpretation techniques and remote sensing in GIS environment. As a result, seven geo-environmental zones were obtained from a weighted integration by multicriteria analysis of physiographic units with land-use classes. In conclusion, taking into account potentialities and limitations, the proposed approach can be considered able to support sustainable decision-making, being applicable in other regions.

  9. Subcellular Compartmentalization and Trafficking of the Biosynthetic Machinery for Fungal Melanin

    Directory of Open Access Journals (Sweden)

    Srijana Upadhyay

    2016-03-01

    Full Text Available Protection by melanin depends on its subcellular location. Although most filamentous fungi synthesize melanin via a polyketide synthase pathway, where and how melanin biosynthesis occurs and how it is deposited as extracellular granules remain elusive. Using a forward genetic screen in the pathogen Aspergillus fumigatus, we find that mutations in an endosomal sorting nexin abolish melanin cell-wall deposition. We find that all enzymes involved in the early steps of melanin biosynthesis are recruited to endosomes through a non-conventional secretory pathway. In contrast, late melanin enzymes accumulate in the cell wall. Such subcellular compartmentalization of the melanin biosynthetic machinery occurs in both A. fumigatus and A. nidulans. Thus, fungal melanin biosynthesis appears to be initiated in endosomes with exocytosis leading to melanin extracellular deposition, much like the synthesis and trafficking of mammalian melanin in endosomally derived melanosomes.

  10. Cerebrospinal fluid analysis in the HIV infection and compartmentalization of HIV in the central nervous system

    Directory of Open Access Journals (Sweden)

    Sérgio Monteiro de Almeida

    2015-07-01

    Full Text Available The nervous system plays an important role in HIV infection. The purpose of this review is to discuss the indications for cerebrospinal fluid (CSF analysis in HIV infection in clinical practice. CSF analysis in HIV infection is indicated for the diagnosis of opportunistic infections and co-infections, diagnosis of meningitis caused by HIV, quantification of HIV viral load, and analysis of CNS HIV compartmentalization. Although several CSF biomarkers have been investigated, none are clinically applicable. The capacity of HIV to generate genetic diversity, in association with the constitutional characteristics of the CNS, facilitates the generation of HIV quasispecies in the CNS that are distinct from HIV in the systemic circulation. CSF analysis has a well-defined and valuable role in the diagnosis of CNS infections in HIV/AIDS patients. Further research is necessary to establish a clinically applicable biomarker for the diagnosis of HIV-associated neurocognitive disorders.

  11. Sequence Stratigraphy of the Dakota Sandstone, Eastern San Juan Basin, New Mexico, and its Relationship to Reservoir Compartmentalization

    Energy Technology Data Exchange (ETDEWEB)

    Varney, Peter J.

    2002-04-23

    This research established the Dakota-outcrop sequence stratigraphy in part of the eastern San Juan Basin, New Mexico, and relates reservoir quality lithologies in depositional sequences to structure and reservoir compartmentalization in the South Lindrith Field area. The result was a predictive tool that will help guide further exploration and development.

  12. Lipid droplet-associated proteins (LDAPs) are required for the dynamic regulation of neutral lipid compartmentation in plant cells

    Science.gov (United States)

    Eukaryotic cells compartmentalize neutral lipids into organelles called lipid droplets (LDs), and while much is known about the role of LDs in storing triacylglycerols (TAGs) in seeds, their biogenesis and function in non-seed tissues is poorly understood. Recently, we identified a class of plant-sp...

  13. 21 CFR 888.3535 - Knee joint femorotibial (uni-compartmental) metal/polymer porous-coated uncemented prosthesis.

    Science.gov (United States)

    2010-04-01

    .../polymer porous-coated uncemented prosthesis. 888.3535 Section 888.3535 Food and Drugs FOOD AND DRUG... prosthesis. (a) Identification. A knee joint femorotibial (uni-compartmental) metal/polymer porous-coated uncemented prosthesis is a device intended to be implanted to replace part of a knee joint. The device limits...

  14. Proteolytic compartmentalization and activity in the midgut of Andrallus spinidens Fabricius (Hemiptera: Pentatomidae

    Directory of Open Access Journals (Sweden)

    S. Sorkhabi-Abdolmaleki

    2013-04-01

    Full Text Available Digestive proteolytic activity in the alimentary canal of Andrallus spinidens, a potential biocontrol agent of lepidopteran larvae, was studied by considering enzyme compartmentalization and diversity. The alimentary canal of adults consists of a foregut, a four- sectioned midgut, namely V1 to V4 (ventriculus, and a hindgut. The optimal pH for general proteolytic activity was found to be at pH 8 with a small peak at pH 6. Results revealed that there are several specific proteases in the midgut of A. spinidens, including trypsin-like, chymotrypsin-like, and elastase as serine proteases, and cathepsins B, L and D as cysteine proteases, in addition to two exopeptidases of carboxy- and aminopetidases. Compartmentalization of digestive proteolytic activity showed that V3 is the main area of proteolytic secretion for both general and specific proteases and that V4 has the lowest enzymatic role, so that four out of the eight specific proteases found showed no activity in this section. The lowest and the highest proteolytic activity was found to be in the 1st and 4th nymphal instars, respectively. Using the specific inhibitors phenylmethylsulfonyl fluoride, Na-p-tosyl-L-lysine chloromethyl ketone, Ntosyl- L-phenylalanine chloromethyl ketone, L-trans-epoxysuccinyl-leucylamido-( 4-guanidino-butane, cystatin, phenanthroline and ethylendiamidetetraacetic acid, we verified the presence of all specific proteases noted using both biochemical assays and sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Our findings demonstrated that A. spinidens could utilize several caterpillars because of the presence of various of proteases in its midgut.

  15. Pathway Compartmentalization in Peroxisome of Saccharomyces cerevisiae to Produce Versatile Medium Chain Fatty Alcohols.

    Science.gov (United States)

    Sheng, Jiayuan; Stevens, Joseph; Feng, Xueyang

    2016-05-27

    Fatty alcohols are value-added chemicals and important components of a variety of industries, which have a >3 billion-dollar global market annually. Long chain fatty alcohols (>C12) are mainly used in surfactants, lubricants, detergents, pharmaceuticals and cosmetics while medium chain fatty alcohols (C6-C12) could be used as diesel-like biofuels. Microbial production of fatty alcohols from renewable feedstock stands as a promising strategy to enable sustainable supply of fatty alcohols. In this study, we report, for the first time, that medium chain fatty alcohols could be produced in yeast via targeted expression of a fatty acyl-CoA reductase (TaFAR) in the peroxisome of Saccharomyces cerevisiae. By tagging TaFAR enzyme with peroxisomal targeting signal peptides, the TaFAR could be compartmentalized into the matrix of the peroxisome to hijack the medium chain fatty acyl-CoA generated from the beta-oxidation pathway and convert them to versatile medium chain fatty alcohols (C10 &C12). The overexpression of genes encoding PEX7 and acetyl-CoA carboxylase further improved fatty alcohol production by 1.4-fold. After medium optimization in fed-batch fermentation using glucose as the sole carbon source, fatty alcohols were produced at 1.3 g/L, including 6.9% 1-decanol, 27.5% 1-dodecanol, 2.9% 1-tetradecanol and 62.7% 1-hexadecanol. This work revealed that peroxisome could be engineered as a compartmentalized organelle for producing fatty acid-derived chemicals in S. cerevisiae.

  16. Effects of Air Stacking Maneuver on Cough Peak Flow and Chest Wall Compartmental Volumes of Subjects With Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Sarmento, Antonio; Resqueti, Vanessa; Dourado-Júnior, Mario; Saturnino, Lailane; Aliverti, Andrea; Fregonezi, Guilherme; de Andrade, Armele Dornelas

    2017-11-01

    To assess the acute effects of air stacking on cough peak flow (CPF) and chest wall compartmental volumes of persons with amyotrophic lateral sclerosis (ALS) versus healthy subjects positioned at 45° body inclination. Cross-sectional study with a matched-pair design. University hospital. Persons (N=24) with ALS (n=12) and age-matched healthy subjects (n=12). CPF, chest wall compartmental inspiratory capacity, chest wall vital capacity, chest wall tidal volume and operational volumes, breathing pattern, and percentage of contribution of the compartments to the inspired volume were measured by optoelectronic plethysmography. Compared with healthy subjects, significantly lower CPF (P=.007), chest wall compartmental inspiratory capacity (P<.001), chest wall vital capacity (P<.001), and chest wall tidal volume (P<.001) were found in subjects with ALS. Immediately after air stacking, CPF (P<.001) and chest wall compartmental inspiratory capacity (P<.001) significantly increased in both groups, with values returning to basal only in healthy subjects. After air stacking, the abdominal compartment (P=.004) was determined to be responsible for the inspired volume in subjects with ALS. Significantly higher chest wall vital capacity (P=.05) was observed in subjects with ALS 5 minutes after air stacking, with the rib cage compartment (P=.049) being responsible for volume change. No differences were found in chest wall vital capacity and compartmental volumes of healthy subjects. Chest wall tidal volume (P<.001) significantly increased during the protocol in the healthy subjects, mainly because of end-inspiratory (P<.001) and abdominal volumes (P=.008). No significant differences were observed in percentage of contribution of the compartments to the inspired volume and end-expiratory volume of both groups. No significant differences were found in chest wall tidal volume, operational volume, and breathing pattern in persons with ALS. Air stacking is effective in increasing CPF

  17. Effect of scatter correction on the compartmental measurement of striatal and extrastriatal dopamine D{sub 2} receptors using [{sup 123}I]epidepride SPET

    Energy Technology Data Exchange (ETDEWEB)

    Fujita, Masahiro; Seneca, Nicholas; Innis, Robert B. [Department of Psychiatry, Yale University School of Medicine and VA Connecticut Healthcare System, West Haven, CT (United States); Molecular Imaging Branch, National Institute of Mental Health, Bethesda, MD (United States); Varrone, Andrea [Department of Psychiatry, Yale University School of Medicine and VA Connecticut Healthcare System, West Haven, CT (United States); Biostructure and Bioimaging Institute, National Research Council, Napoli (Italy); Kim, Kyeong Min; Watabe, Hiroshi; Iida, Hidehiro [Department of Investigative Radiology, National Cardiovascular Center Research Institute, Osaka (Japan); Zoghbi, Sami S. [Department of Psychiatry, Yale University School of Medicine and VA Connecticut Healthcare System, West Haven, CT (United States); Molecular Imaging Branch, National Institute of Mental Health, Bethesda, MD (United States); Department of Radiology, Yale University School of Medicine and VA Connecticut Healthcare System, West Haven, CT (United States); Tipre, Dnyanesh [Molecular Imaging Branch, National Institute of Mental Health, Bethesda, MD (United States); Seibyl, John P. [Institute for Neurodegenerative Disorders, New Haven, CT (United States)

    2004-05-01

    Prior studies with anthropomorphic phantoms and single, static in vivo brain images have demonstrated that scatter correction significantly improves the accuracy of regional quantitation of single-photon emission tomography (SPET) brain images. Since the regional distribution of activity changes following a bolus injection of a typical neuroreceptor ligand, we examined the effect of scatter correction on the compartmental modeling of serial dynamic images of striatal and extrastriatal dopamine D{sub 2} receptors using [{sup 123}I]epidepride. Eight healthy human subjects [age 30{+-}8 (range 22-46) years] participated in a study with a bolus injection of 373{+-}12 (354-389) MBq [{sup 123}I]epidepride and data acquisition over a period of 14 h. A transmission scan was obtained in each study for attenuation and scatter correction. Distribution volumes were calculated by means of compartmental nonlinear least-squares analysis using metabolite-corrected arterial input function and brain data processed with scatter correction using narrow-beam geometry {mu} (SC) and without scatter correction using broad-beam {mu} (NoSC). Effects of SC were markedly different among brain regions. SC increased activities in the putamen and thalamus after 1-1.5 h while it decreased activity during the entire experiment in the temporal cortex and cerebellum. Compared with NoSC, SC significantly increased specific distribution volume in the putamen (58%, P=0.0001) and thalamus (23%, P=0.0297). Compared with NoSC, SC made regional distribution of the specific distribution volume closer to that of [{sup 18}F]fallypride. It is concluded that SC is required for accurate quantification of distribution volumes of receptor ligands in SPET studies. (orig.)

  18. Measurement of microparticle tissue factor activity in clinical samples: A summary of two tissue factor-dependent FXa generation assays.

    Science.gov (United States)

    Hisada, Yohei; Alexander, Wyeth; Kasthuri, Raj; Voorhees, Peter; Mobarrez, Fariborz; Taylor, Angela; McNamara, Coleen; Wallen, Hakan; Witkowski, Marco; Key, Nigel S; Rauch, Ursula; Mackman, Nigel

    2016-03-01

    Thrombosis is a leading cause of morbidity and mortality. Detection of a prothrombotic state using biomarkers would be of great benefit to identify patients at risk of thrombosis that would benefit from thromboprophylaxis. Tissue factor (TF) is a highly procoagulant protein that under normal conditions is not present in the blood. However, increased levels of TF in the blood in the form of microparticles (MPs) (also called extracellular vesicles) are observed under various pathological conditions. In this review, we will discuss studies that have measured MP-TF activity in a variety of diseases using two similar FXa generation assay. One of the most robust signals for MP-TF activity (16-26 fold higher than healthy controls) is observed in pancreatic cancer patients with venous thromboembolism. In this case, the TF+ MPs appear to be derived from the cancer cells. Surprisingly, cirrhosis and acute liver injury are associated with 17-fold and 38-fold increases in MP-TF activity, respectively. Based on mouse models, we speculate that the TF+ MPs are derived from hepatocytes. More modest increases are observed in patients with urinary tract infections (6-fold) and in a human endotoxemia model (9-fold) where monocytes are the likely source of the TF+ MPs. Finally, there is no increase in MP-TF activity in the majority of cardiovascular disease patients. These studies indicate that MP-TF activity may be a useful biomarker to identify patients with particular diseases that have an increased risk of thrombosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. The construction of next-generation matrices for compartmental epidemic models

    NARCIS (Netherlands)

    Diekmann, O.|info:eu-repo/dai/nl/071896856; Heesterbeek, J.A.P.|info:eu-repo/dai/nl/073321427; Roberts, M.G.

    2010-01-01

    The basic reproduction number R0 is arguably the most important quantity in infectious disease epidemiology. The next-generation matrix (NGM) is the natural basis for the definition and calculation of R0 where finitely many different categories of individuals are recognized. We clear up confusion

  20. Micro-compartmentalized cultivation of cyanobacteria for mutant screening using glass slides with highly water-repellent mark

    Directory of Open Access Journals (Sweden)

    Sayuri Arai

    2014-12-01

    Full Text Available Photosynthetic microorganisms such as cyanobacteria have attracted attention for their potential to produce biofuels and biochemicals directly from CO2. Cell isolation by colony has conventionally been used for selecting target cells. Colony isolation methods require a significant amount of time for cultivation, and the colony-forming ratio is potentially low for cyanobacteria. Here, we overcome such limitations by encapsulating and culturing cells in droplets with an overlay of dodecane using glass slides printed with highly water-repellent mark. In the compartmentalized culture, the oil phase protects the small volume of culture medium from drying and increases the CO2 supply. Since a difference in cell growth was observed with and without the addition of antibiotics, this compartmentalized culture method could be a powerful tool for mutant selection.

  1. Compartmental analysis and dosimetric aspects applied to cholesterol with {sup 3}H labeled; Analise compartimental e aspectos dosimetricos aplicados ao colesterol marcado com {sup 3}H

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Adriano dos Santos

    2015-07-01

    Cardiovascular diseases (CVDs) are one of the major reasons of death around the world according to the World Health Organization (WHO). It is well known that changes in levels of plasma lipoproteins, which are responsible for the transport of cholesterol into the bloodstream, are associated with cardiovascular diseases. For this reason to know the biokinetic parameters of plasma lipoproteins and quantifies them is important to correct and deep understanding about the diseases associated with these disorders. The main aim of this study is to provide a biokinetic model and estimate the radiometric doses for {sup 3}H-Cholesterol, a radioactive tracer widely used in physiological and metabolic studies. The model was based on [Schwartz et al. 2004] about the distribution of cholesterol by the lipoprotein and gastrointestinal model [ICRP 30, 1979]. The doses distribution in compartments of the model and other organs and tissues of a standard adult described in [ICRP 106, 2008] was calculated using MIRD method (Medical Internal Radiation Dose) and compartmental analysis using the computer program Matlab®. The dose coefficients were estimated for a standard phantom man (73 kg) described in [ICRP 60, 1991]. The estimated doses for both model and for other organs were low and did not exceed the highest dose obtained that was in the upper large intestine, as 44,8 μGy these parameters will assist in ethics committee's opinions on the use of works that use the {sup 3}H-cholesterol which radioactive tracer. (author)

  2. Selective compartmental dominance: an explanation for a noninfectious, multifactorial etiology for acquired immune deficiency syndrome (AIDS), and a rationale for ozone therapy and other immune modulating therapies.

    Science.gov (United States)

    Shallenberger, F

    1998-01-01

    The most widely accepted etiological explanation for acquired immune deficiency syndrome (AIDS) currently invokes an infectious model involving the human immunodeficiency virus (HIV). Because this infectious model has failed to meet any conventional criteria for establishing microbial causation, this theory still relies on the high, though not perfect, statistical correlation linking presence of HIV antibodies with patients diagnosed with, and at risk for the syndrome. Many scientists and clinicians now doubt the HIV theory, though, and propose instead a multifactorial causation similar to that seen in cancer and heart disease. In order to discard the HIV model, however, it is necessary to explain the high statistical correlation mentioned above. Recent studies involving cellular mediated immunity and cytokine modulation may explain this statistical relationship without the need to invoke infectious causation, by suggesting certain functional characteristics and feedback loops in the immune system which the author calls selective compartmental dominance (SCD). SCD provides a model in which chronic dominance of the humoral immune compartment secondary to chronic high-dose antigenic challenge results in chronic suppression of the cellular immune compartment. This model predicts that even HIV-negative members of the risk groups are susceptible to AIDS, assigns no special causal role for HIV in AIDS, and suggests a rational course of nontoxic therapy that can potentially reverse cases in the earlier stages.

  3. Subcellular Optogenetic Stimulation for Activity-Dependent Myelination of Axons in a Novel Microfluidic Compartmentalized Platform.

    Science.gov (United States)

    Lee, Hae Ung; Nag, Sudip; Blasiak, Agata; Jin, Yan; Thakor, Nitish; Yang, In Hong

    2016-10-19

    Myelination is governed by neuron-glia communication, which in turn is modulated by neural activity. The exact mechanisms remain elusive. We developed a novel in vitro optogenetic stimulation platform that facilitates subcellular activity induction in hundreds of neurons simultaneously. The light isolation was achieved by creating a biocompatible, light-absorbent, black microfluidic device integrated with a programmable, high-power LED array. The system was applied to a compartmentalized culture of primary neurons whose distal axons were interacting with oligodendrocyte precursor cells. Neural activity was induced along whole neurons or was constrained to cell bodies with proximal axons or distal axons only. All three modes of stimulation promoted oligodendrocyte differentiation and the myelination of axons as evidenced by a decrease in the number of oligodendrocyte precursor cells followed by increases in the number of mature oligodendrocytes and myelin sheath fragments. These results demonstrated the potential of our novel optogenetic stimulation system for the global and focal induction of neural activity in vitro for studying axon myelination.

  4. Hypothalamic metabolic compartmentation during appetite regulation as revealed by magnetic resonance imaging and spectroscopy methods

    Science.gov (United States)

    Lizarbe, Blanca; Benitez, Ania; Peláez Brioso, Gerardo A.; Sánchez-Montañés, Manuel; López-Larrubia, Pilar; Ballesteros, Paloma; Cerdán, Sebastián

    2013-01-01

    We review the role of neuroglial compartmentation and transcellular neurotransmitter cycling during hypothalamic appetite regulation as detected by Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) methods. We address first the neurochemical basis of neuroendocrine regulation in the hypothalamus and the orexigenic and anorexigenic feed-back loops that control appetite. Then we examine the main MRI and MRS strategies that have been used to investigate appetite regulation. Manganese-enhanced magnetic resonance imaging (MEMRI), Blood oxygenation level-dependent contrast (BOLD), and Diffusion-weighted magnetic resonance imaging (DWI) have revealed Mn2+ accumulations, augmented oxygen consumptions, and astrocytic swelling in the hypothalamus under fasting conditions, respectively. High field 1H magnetic resonance in vivo, showed increased hypothalamic myo-inositol concentrations as compared to other cerebral structures. 1H and 13C high resolution magic angle spinning (HRMAS) revealed increased neuroglial oxidative and glycolytic metabolism, as well as increased hypothalamic glutamatergic and GABAergic neurotransmissions under orexigenic stimulation. We propose here an integrative interpretation of all these findings suggesting that the neuroendocrine regulation of appetite is supported by important ionic and metabolic transcellular fluxes which begin at the tripartite orexigenic clefts and become extended spatially in the hypothalamus through astrocytic networks becoming eventually MRI and MRS detectable. PMID:23781199

  5. Cadherins in cerebellar development: translation of embryonic patterning into mature functional compartmentalization.

    Science.gov (United States)

    Redies, Christoph; Neudert, Franziska; Lin, Juntang

    2011-09-01

    Cadherins are cell adhesion molecules with multiple morphogenic functions in brain development, for example, in neuroblast migration and aggregation, axon navigation, neural circuit formation, and synaptogenesis. More than 100 members of the cadherin superfamily are expressed in the developing and mature brain. Most of the cadherins investigated, in particular classic cadherins and δ-protocadherins, are expressed in the cerebellum. For several cadherin subtypes, expression begins at early embryonic stages and persists until mature stages of cerebellar development. At intermediate stages, distinct Purkinje cell clusters exhibit unique rostrocaudal and mediolateral expression profiles for each cadherin. In the chicken, mouse, and other species, the Purkinje cell clusters are separated by intervening raphes of migrating granule cells. This pattern of Purkinje cell clusters/raphes is, at least in part, continuous with the parasagittal striping pattern that is apparent in the mature cerebellar cortex, for example, for zebrin II/aldolase C. Moreover, subregions of the deep cerebellar nuclei, vestibular nuclei and the olivary complex also express cadherins differentially. Neuroanatomical evidence suggests that the nuclear subregions and cortical domains that express the same cadherin subtype are connected to each other, to form neural subcircuits of the cerebellar system. Cadherins thus provide a molecular code that specifies not only embryonic structures but also functional cerebellar compartmentalization. By following the implementation of this code, it can be revealed how mature functional architecture emerges from embryonic patterning during cerebellar development. Dysfunction of some cadherins is associated with psychiatric diseases and developmental impairments and may also affect cerebellar function.

  6. Fault assessment for basement reservoir compartmentalization: Case study at Northeast Betara gas field, South Sumatra Basin

    Science.gov (United States)

    Risyad, M.; Suta, I. N.; Haris, A.

    2017-07-01

    Northeast Betara field is situated on the northern part of prolific South Sumatra Basin. It has produced gas from Lower Talang Akar Formation sandstone and over 90 wells have been drilled. A 3D seismic data was acquired in 2000 and reprocessed in 2012 to enhance the subsurface image. In 2013 an exploratory well NEB Base-1 was drilled and made gas and condensate discovery from the subsequent pre-tertiary basement which is confirmed as granite. The well proved fractured basement reservoir play on paleo high of the structure. The absence of full-diameter conventional core prompts well logs and seismic data analysis by using a workstation. Main methods for fracture prediction have been seismic attributes extraction and structural geology studies of basement provided by image logs on a few exploration wells. Ant tracking attribute is widely employed to image seismic event discontinuities due to extensive faults which generated the natural fractures. Delineations well NEB Base-2 was drilled on second paleo high and unfortunately, it did not find any gas indication from pre-tertiary basement target. Seismic structural interpretation and seismic attributes are conducted to image distribution of event discontinuities related to faults or fracture. We found that compartmentalization on basement involved old faults and both paleo high have undergone different structural history and stress character which resulted in separated fractures distribution.

  7. Synthesis, characterization and biological activity of symmetric dinuclear complexes derived from a novel macrocyclic compartmental ligand

    International Nuclear Information System (INIS)

    Mruthyunjayaswamy, B.H.M.; Ijare, Omkar B.; Jadegoud, Y.

    2005-01-01

    A phenol based novel macrocyclic binucleating compartmental ligand N,N-bis(2,6-diiminomethyl-4-methyl-1-hydroxyphenyl)malonoyldicarboxamide was prepared. The complexes were prepared by template method by reacting 2,6-diformyl-4-methylphenol, malonoyl dihydrazide and the metal chlorides of Cu(II), Ni(II), Co(II), Cd(II), Zn(II) and Hg(II) in methanol to get a series of dinuclear complexes. The complexes were characterized by elemental analyses, conductivity measurements, magnetic susceptibility data, IR, UV-Vis, ESR, NMR and FAB mass spectral data. The dinuclear nature of the complexes was confirmed on the basis of elemental analyses, magnetic susceptibility, ESR and FAB mass spectral data. The ligand as well as Cu(II), Ni(II), Co(II) and Zn(II) complexes were tested for their antibacterial and antifungal properties against Escherichia coli, Staphyloccocus aureus, Aspergillus niger and Fusarium oxysporum. Magnetic susceptibility measurements of Cu(II), Ni(II) and Co(II) complexes reveal that these complexes exhibit antiferromagnetic coupling behavior due to the presence of two metal ions in close proximity. FAB mass spectrum of the Cu(II) complex gave a clear evidence for the dinuclear nature. The ligand and the complexes were found to be less active against the tested bacteria, but the ligand alone was found active against the fungus Fusarium oxysporum. (author)

  8. PGI2 synthesis and excretion in dog kidney: evidence for renal PG compartmentalization

    International Nuclear Information System (INIS)

    Boyd, R.M.; Nasjletti, A.; Heerdt, P.M.; Baer, P.G.

    1986-01-01

    To assess the concept of compartmentalization of renal prostaglandins (PG), we compared entry of PGE2 and the PGI2 metabolite 6-keto-PGF1 alpha into the renal vascular and tubular compartments, in sodium pentobarbital-anesthetized dogs. Renal arterial 6-keto-PGF1 alpha infusion increased both renal venous and urinary 6-keto-PGF1 alpha outflow. In contrast, renal arterial infusion of arachidonic acid (AA) or bradykinin (BK) increased renal venous 6-keto-PGF1 alpha outflow but had no effect on its urinary outflow. Both urinary and renal venous PGE2 outflows increased during AA or BK infusion. Ureteral stopped-flow studies revealed no postglomerular 6-keto-PGF1 alpha entry into tubular fluid. During renal arterial infusion of [3H]PGI2 and inulin, first-pass 3H clearance was 40% of inulin clearance; 35% of urinary 3H was 6-keto-PGF1 alpha, and two other urinary metabolites were found. During renal arterial infusion of [3H]6-keto-PGF1 alpha and inulin, first-pass 3H clearance was 150% of inulin clearance; 75% of urinary 3H was 6-keto-PGF1 alpha, and only one other metabolite was found. We conclude that in the dog PGE2 synthesized in the kidney enters directly into both the renal vascular and tubular compartments, but 6-keto-PGF1 alpha of renal origin enters directly into only the renal vascular compartment

  9. Technology Solutions Case Study: Apartment Compartmentalization with an Aerosol-Based Sealing Process

    Energy Technology Data Exchange (ETDEWEB)

    None

    2015-07-01

    Air sealing of building enclosures is a difficult and time-consuming process. Current methods in new construction require laborers to physically locate small and sometimes large holes in multiple assemblies and then manually seal each of them. This research study by Building America team Consortium for Advanced Residential Buildings demonstrated the automated air sealing and compartmentalization of buildings through the use of an aerosolized sealant developed by the Western Cooling Efficiency Center at University of California Davis. CARB demonstrated this new technology application in a multifamily building in Queens, NY. The effectiveness of the sealing process was evaluated by three methods: air leakage testing of overall apartment before and after sealing, point-source testing of individual leaks, and pressure measurements in the walls of the target apartment during sealing. Aerosolized sealing was successful by several measures in this study. Many individual leaks that are labor-intensive to address separately were well sealed by the aerosol particles. In addition, many diffuse leaks that are difficult to identify and treat were also sealed. The aerosol-based sealing process resulted in an average reduction of 71% in air leakage across three apartments and an average apartment airtightness of 0.08 CFM50/SF of enclosure area.

  10. Hydraulic characteristics and their effects on working performance of compartmentalized anaerobic reactor.

    Science.gov (United States)

    Ji, Jun-yuan; Zheng, Kai; Xing, Ya-juan; Zheng, Ping

    2012-07-01

    The compartmentalized anaerobic reactor (CAR) is a patent novel high-rate reactor and shows a great potential for its application. The hydraulic characteristics and their effects on the working performance of CAR were investigated. The flow pattern tended to plug flow at normal organic loading rate (OLR) and completely mixed flow at high OLRs. The relation of hydraulic dead space (HDS or V(h)) with hydraulic loading rate (HLR or L) and biogas production rate (BPR or G) was V(h) = 3.75 L + 0.19 G-9.47. The hydraulic efficiency of CAR was good or near to good. Both HLR and BPR had significant effects on the hydraulic efficiency, but their effect became less at super-high OLR. They also had a slight influence on the effective volume ratios of CAR, but the influence of BPR almost disappeared at super-high OLR. The good working performance of CAR was ascribed to the improved reactor configuration. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Dynamic compartmentalization of DNA repair proteins within spiral ganglion neurons in response to noise stress.

    Science.gov (United States)

    Guthrie, O'neil W

    2012-12-01

    ABSTRACT In response to stress, spiral ganglion neurons may remodel intracellular pools of DNA repair proteins. This hypothesis was addressed by determining the intracellular location of three classic DNA excision repair proteins (XPA, CSA, and XPC) within the neurons under normal conditions, one day after noise stress (105 dB/4 hr) and following DNA repair adjuvant therapy with carboxy alkyl esters (CAEs; 160 mg/kg/28 days). Under normal conditions, three intracellular compartments were enriched with at least one repair protein. These intracellular compartments were designated nuclear, cytoplasmic, and perinuclear. After the noise stress each repair protein aggregated in the cytoplasm. After CAE therapy each intracellular compartment was enriched with the three DNA repair proteins. Combining noise stress with CAE therapy resulted in the enrichment of at least two repair proteins in each intracellular compartment. The combined results suggest that in response to noise stress and/or otoprotective therapy, spiral ganglion neurons may selectively remodel compartmentalized DNA repair proteins.

  12. Reservoir compartmentalization and management strategies: Lessons learned in the Illinois basin

    Energy Technology Data Exchange (ETDEWEB)

    Grube, J.P.; Crockett, J.E.; Huff, B.G. [and others

    1997-08-01

    A research project jointly sponsored by the US Department of Energy and the Illinois State Geological Survey focused on the Cypress and Aux Vases Formations (Mississippian), major clastic reservoirs in the Illinois Basin. Results from the research showed that understanding the nature and distribution of reservoir compartments, and using effective reservoir management strategies, can significantly improve recovery efficiencies from oil fields in this mature basin. Compartments can be most effectively drained where they are geologically well defined and reservoir management practices are coordinated through unified, compartment-wide, development programs. Our studies showed that the Cypress and Aux Vases reservoirs contain lateral and vertical permeability barriers forming compartments that range in size from isolated, interlaminated sandstone and shale beds to sandstone bodies tens of feet in thickness and more than a mile in length. Stacked or shingled, genetically similar sandstone bodies are commonly separated by thin impermeable intervals that can be difficult to distinguish on logs and can, therefore, cause correlation problems, even between wells drilled on spacing of less than ten acres. Lateral separation of sandstone bodies causes similar problems. Reservoir compartmentalization reduces primary and particularly secondary recovery by trapping pockets of by-passed or banked oil. Compartments can be detected by comparing recovery factors of genetically similar sandstone bodies within a field; using packers to separate commingled intervals and analyzing fluid recoveries and pressures; making detailed core-to-log calibrations that identify compartment boundaries; and analyzing pressure data from waterflood programs.

  13. Compartmentalization of Total and Virus-Specific Tissue-Resident Memory CD8+ T Cells in Human Lymphoid Organs.

    OpenAIRE

    Heng Giap Woon; Asolina Braun; Jane Li; Corey Smith; Jarem Edwards; Frederic Sierro; Carl G Feng; Rajiv Khanna; Michael Elliot; Andrew Bell; Andrew D Hislop; Stuart G Tangye; Alan B Rickinson; Thomas Gebhardt; Warwick J Britton

    2016-01-01

    Disruption of T cell memory during severe immune suppression results in reactivation of chronic viral infections, such as Epstein Barr virus (EBV) and Cytomegalovirus (CMV). How different subsets of memory T cells contribute to the protective immunity against these viruses remains poorly defined. In this study we examined the compartmentalization of virus-specific, tissue resident memory CD8+ T cells in human lymphoid organs. This revealed two distinct populations of memory CD8+ T cells, that...

  14. Compartmental Schiff-base ligands--a rich library of tectons in designing magnetic and luminescent materials.

    Science.gov (United States)

    Andruh, Marius

    2011-03-21

    The binuclear complexes (3d-3d, 3d-3d', 3d-4f) with compartmental ligands can efficiently act as tectons in crystal engineering. Various high nuclearity clusters and coordination polymers can be easily obtained by choosing the appropriate spacers. The main interest in such systems arises from their magnetic and photophysical properties. Moreover, 3d-3d' and 3d-4f complexes are useful precursors in designing heterotrimetallic systems with relevance in molecular magnetism.

  15. cGMP Signaling in the Cardiovascular System—The Role of Compartmentation and Its Live Cell Imaging

    Science.gov (United States)

    Bork, Nadja I.; Nikolaev, Viacheslav O.

    2018-01-01

    The ubiquitous second messenger 3′,5′-cyclic guanosine monophosphate (cGMP) regulates multiple physiologic processes in the cardiovascular system. Its intracellular effects are mediated by stringently controlled subcellular microdomains. In this review, we will illustrate the current techniques available for real-time cGMP measurements with a specific focus on live cell imaging methods. We will also discuss currently accepted and emerging mechanisms of cGMP compartmentation in the cardiovascular system. PMID:29534460

  16. The Importance of Bank Storage in Supplying Baseflow to Rivers Flowing Through Compartmentalized, Alluvial Aquifers

    Science.gov (United States)

    Rhodes, Kimberly A.; Proffitt, Tiffany; Rowley, Taylor; Knappett, Peter S. K.; Montiel, Daniel; Dimova, Natasha; Tebo, Daniel; Miller, Gretchen R.

    2017-12-01

    As water grows scarcer in semiarid and arid regions around the world, new tools are needed to quantify fluxes of water and chemicals between aquifers and rivers. In this study, we quantify the volumetric flux of subsurface water to a 24 km reach of the Brazos River, a lowland river that meanders through the Brazos River Alluvium Aquifer (BRAA), with 8 months of high-frequency differential gaging measurements using fixed gaging stations. Subsurface discharge sources were determined using natural tracers and End-Member Mixing Analysis (EMMA). During a 4 month river stage recession following a high stage event, subsurface discharge decreased from 50 m3/s to 0, releasing a total of 1.0 × 108 m3 of water. Subsurface discharge dried up even as the groundwater table at two locations in the BRAA located 300-500 m from the river remained ˜4 m higher than the river stage. Less than 4% of the water discharged from the subsurface during the prolonged recession period resembled the chemical fingerprint of the alluvial aquifer. Instead, the chemistry of this discharged water closely resembled high stage "event" river water. Together, these findings suggest that the river is well connected to rechargeable bank storage reservoirs but disconnected from the broader alluvial aquifer. The average width of discrete bank storage zones on each side of the river, identified with Electrical Resistivity Tomography (ERT), was approximately 1.5 km. In such highly compartmentalized aquifers, groundwater pumping is unlikely to impact the exchange between the river and the alluvium.

  17. Ocular pharmacokinetics of a novel tetrahydroquinoline analog in rabbit: absorption, disposition, and non-compartmental analysis.

    Science.gov (United States)

    Pamulapati, Chandrasena R; Schoenwald, Ronald D

    2011-12-01

    The pharmacologically active compound (33% reduction in rabbit intraocular pressure recovery rate assay) 1-ethyl-6-fluoro-1,2,3,4-tetrahydroquinoline (MC4), which showed ocular hypotensive action and had optimum physicochemical properties, was characterized for its ocular absorption and distribution properties to better understand its in vivo potency in comparison with an inactive compound, N-ethyl-1,4-benzoxazine (MC1). Tissue distribution to various ocular tissues was determined after absorption by both corneal and conjunctival-scleral routes, following administration by the "topical infusion" technique. The rank order of penetration for both the compounds was cornea > iris-ciliary body > aqueous humor > lens > conjunctiva-sclera. Overall, MC4 had significantly higher concentrations than MC1 in various ocular tissues, but particularly in the iris-ciliary body, which is the site of action (biophase). Ocular disposition studies of the active compound MC4 were then conducted to characterize its elimination kinetics, and the pharmacokinetic parameters were determined by non-compartmental and moment analysis using equations specific to "topical infusion" technique: first-order absorption rate constant, 4.1 × 10(-4) min(-1) ; elimination rate constant, 0.012 min(-1) ; mean residence time, 39.6 min; steady-state volume of distribution, 0.721 mL; and aqueous humor ocular clearance, 8.44 µL/min. The results were consistent with the conclusion that MC4 is well absorbed and distributed to the active site. Copyright © 2011 Wiley-Liss, Inc.

  18. Comparison of total and compartmental gastric emptying and antral motility between healthy men and women

    Energy Technology Data Exchange (ETDEWEB)

    Bennink, R.; Van den Maegdenbergh, V.; Roo, M. de; Mortelmans, L. [Department of Nuclear Medicine, UZ KU Leuven (Belgium); Peeters, M.; Geypens, B.; Rutgeerts, P. [Department of Gastroenterology, UZ KU Leuven (Belgium)

    1998-09-01

    There is increasing evidence of gender-related differences in gastric emptying. The purpose of this study was first, to confirm the difference in gastric emptying for both solid and liquid test meals between healthy men and women, and secondly, to investigate the origin of this difference by studying regional gastric emptying and antral motility. A standard gastric emptying test with additional compartmental (proximal and distal) evaluation and dynamic imaging of the antrum was performed in 20 healthy women studied during the first 10 days of the menstrual cycle, and in 31 healthy age-matched men. In concordance with previous reports, women had a longer half-emptying time for solids as compared to men (86.2{+-}5.1 vs 52.2{+-}2.9 min, P<0.05). In our observations this seemed to be related to a significantly prolonged lag phase and a significant decrease in terminal slope. Dynamical antral scintigraphy did not show a significant difference. The distribution of the test meal within the stomach (proximal vs distal) showed more early proximal retention in women as compared to men. The terminal slope of the distal somach was significantly lower in women. We did not observe a significant difference in gastric emptying of the liquid test meal between men and women. Gastric emptying of solids is significantly slower in healthy women as compared to men. These findings emphasise the importance of using different normal values for clinical and research purposes in gastric emptying scintigraphy in men and women. The difference could not be explained by antral motility alone. Increased proximal retention and a lower terminal emptying rate in women are observations to be further investigated. (orig.) With 5 figs., 2 tabs., 36 refs.

  19. Distribution and compartmental organization of GABAergic medium-sized spiny neurons in the mouse Nucleus Accumbens

    Directory of Open Access Journals (Sweden)

    Giuseppe eGangarossa

    2013-02-01

    Full Text Available The nucleus accumbens (NAc is a critical brain region involved in many reward-related behaviors. The NAc comprises major compartments the core and the shell, which encompass several subterritories. GABAergic medium-sized spiny neurons (MSNs constitute the output neurons of the NAc core and shell. While the functional organization of the NAc core outputs resembles the one described for the dorsal striatum, a simple classification of the NAc shell neurons has been difficult to define due to the complexity of the compartmental segregation of cells. We used a variety of BAC transgenic mice expressing enhanced green fluorescence (EGFP or the Cre-recombinase (Cre under the control of the promoter of dopamine D1, D2, and D3 receptors and of adenosine A2a receptor to dissect the microanatomy of the NAc. Moreover, using various immunological markers we characterized in detail the distribution of MSNs in the mouse NAc. In addition, cell-type specific ERK phosphorylation in the NAc subterritories was analyzed following acute administration of SKF81297 (a D1R-like agonist, quinpirole (a D2R-like agonist, apomorphine (a non-selective DA receptor agonist, raclopride (a D2R-like antagonist, and psychostimulant drugs, including cocaine and d-amphetamine. Each drug generated a unique topography and cell-type specific activation of ERK in the NAc. Our results show the existence of marked differences in the receptor expression pattern and functional activation of MSNs within the shell subterritories. This study emphasizes the anatomical and functional heterogeneity of the NAc, which will have to be considered in its further study.

  20. Application of oil gas-chromatography in reservoir compartmentalization in a mature Venezuelan oil field

    Energy Technology Data Exchange (ETDEWEB)

    Munoz, N.G.; Mompart, L. [Maraven, Caracas (Venezuela); Talukdar, S.C.

    1996-08-01

    Gas chromatographic oil {open_quotes}fingerprinting{close_quotes} was successfully applied in a multidisciplinary production geology project by Maraven, S.A. to define the extent of vertical and lateral continuity of Eocene and Miocene sandstone reservoirs in the highly faulted Bloque I field, Maracaibo Basin, Venezuela. Seventy-five non-biodegraded oils (20{degrees}-37.4{degrees} API) were analyzed with gas chromatography. Fifty were produced from the Eocene Misoa C-4, C-5, C-6 or C-7 horizons, fifteen from the Miocene basal La Rosa and ten from multizone completions. Gas chromatographic and terpane and sterane biomarker data show that all of the oils are genetically related. They were expelled from a type II, Upper Cretaceous marine La Luna source rock at about 0.80-0.90% R{sub o} maturity. Alteration in the reservoir by gas stripping with or without subsequent light hydrocarbons mixing was observed in some oils. Detailed chromatographic comparisons among the oils shown by star plots and cluster analysis utilizing several naphthenic and aromatic peak height ratios, resulted in oil pool groupings. This led to finding previously unknown lateral and vertical reservoir communication and also helped in checking and updating the scaling character of faults. In the commingled oils, percentages of each contributing zone in the mixture were also determined giving Maraven engineers a proven, rapid and inexpensive tool for production allocation and reservoir management The oil pool compartmentalization defined by the geochemical fingerprinting is in very good agreement with the sequence stratigraphic interpretation of the reservoirs and helped evaluate the influence of structure in oil migration and trapping.

  1. Dendritic compartmentalization of chloride cotransporters underlies directional responses of starburst amacrine cells in retina.

    Science.gov (United States)

    Gavrikov, Konstantin E; Nilson, James E; Dmitriev, Andrey V; Zucker, Charles L; Mangel, Stuart C

    2006-12-05

    The mechanisms in the retina that generate light responses selective for the direction of image motion remain unresolved. Recent evidence indicates that directionally selective light responses occur first in the retina in the dendrites of an interneuron, i.e., the starburst amacrine cell, and that these responses are highly sensitive to the activity of Na-K-2Cl (NKCC) and K-Cl (KCC), two types of chloride cotransporter that determine whether the neurotransmitter GABA depolarizes or hyperpolarizes neurons, respectively. We show here that selective blockade of the NKCC2 and KCC2 cotransporters located on starburst dendrites consistently hyperpolarized and depolarized the starburst cells, respectively, and greatly reduced or eliminated their directionally selective light responses. By mapping NKCC2 and KCC2 antibody staining on these dendrites, we further show that NKCC2 and KCC2 are preferentially located in the proximal and distal dendritic compartments, respectively. Finally, measurements of the GABA reversal potential in different starburst dendritic compartments indicate that the GABA reversal potential at the distal dendrite is more hyperpolarized than at the proximal dendrite due to KCC2 activity. These results thus demonstrate that the differential distribution of NKCC2 on the proximal dendrites and KCC2 on the distal dendrites of starburst cells results in a GABA-evoked depolarization and hyperpolarization at the NKCC2 and KCC2 compartments, respectively, and underlies the directionally selective light responses of the dendrites. The functional compartmentalization of interneuron dendrites may be an important means by which the nervous system encodes complex information at the subcellular level.

  2. DNA precursor compartmentation in mammalian cells: distribution and rates of equilibration between nucleus and cytoplasm

    International Nuclear Information System (INIS)

    Leeds, J.M.

    1986-01-01

    A rapid nuclear isolation technique was adapted in order to examine the question of DNA precursor compartmentation in mammalian cells. By using this method a reproducible proportion of the cellular nucleotides remained associated with the isolated nuclei. Examination, at several different cell densities, of exponentially growing HeLa cells showed that the nuclei contained a constant but distinct proportion of each dNTP. The nuclear dATP and dTTP concentrations were equal at all densities examined even though the dTTP pool was 150% of the dATP whole-cell pool. The nuclear portion of the whole-cell pools was roughly equal to the volume occupied by the nucleus. The nuclear-cytoplasmic dNTP pool distribution did not change throughout the cell cycle of synchronized Chinese hamster ovary (CHO) cells. The rates at which either radiolabeled cytidine or deoxycytidine equilibrated with the nuclear and whole-cell dCTP pools of G1 and S phase CHO cells were compared. Experiments comparing the labeling kinetics of 3 H-thymidine in G1, S phase, and exponentially growing cells revealed that the S phase dTTP pool equilibrated with exogenously added thymidine faster than the G1 phase pool. The rate of equilibration in exponentially growing cells appeared to be a combination of that seen in G1 and S phases. A linear rate of 3 H-thymidine incorporation into DNA occurred at the same rate in S phase and exponentially growing cells

  3. Barcoding of GPCR trafficking and signaling through the various trafficking roadmaps by compartmentalized signaling networks.

    Science.gov (United States)

    Bahouth, Suleiman W; Nooh, Mohammed M

    2017-08-01

    Proper signaling by G protein coupled receptors (GPCR) is dependent on the specific repertoire of transducing, enzymatic and regulatory kinases and phosphatases that shape its signaling output. Activation and signaling of the GPCR through its cognate G protein is impacted by G protein-coupled receptor kinase (GRK)-imprinted "barcodes" that recruit β-arrestins to regulate subsequent desensitization, biased signaling and endocytosis of the GPCR. The outcome of agonist-internalized GPCR in endosomes is also regulated by sequence motifs or "barcodes" within the GPCR that mediate its recycling to the plasma membrane or retention and eventual degradation as well as its subsequent signaling in endosomes. Given the vast number of diverse sequences in GPCR, several trafficking mechanisms for endosomal GPCR have been described. The majority of recycling GPCR, are sorted out of endosomes in a "sequence-dependent pathway" anchored around a type-1 PDZ-binding module found in their C-tails. For a subset of these GPCR, a second "barcode" imprinted onto specific GPCR serine/threonine residues by compartmentalized kinase networks was required for their efficient recycling through the "sequence-dependent pathway". Mutating the serine/threonine residues involved, produced dramatic effects on GPCR trafficking, indicating that they played a major role in setting the trafficking itinerary of these GPCR. While endosomal SNX27, retromer/WASH complexes and actin were required for efficient sorting and budding of all these GPCR, additional proteins were required for GPCR sorting via the second "barcode". Here we will review recent developments in GPCR trafficking in general and the human β 1 -adrenergic receptor in particular across the various trafficking roadmaps. In addition, we will discuss the role of GPCR trafficking in regulating endosomal GPCR signaling, which promote biochemical and physiological effects that are distinct from those generated by the GPCR signal transduction

  4. cAMP Signaling Compartmentation: Adenylyl Cyclases as Anchors of Dynamic Signaling Complexes.

    Science.gov (United States)

    Johnstone, Timothy B; Agarwal, Shailesh R; Harvey, Robert D; Ostrom, Rennolds S

    2018-04-01

    It is widely accepted that cAMP signaling is compartmentalized within cells. However, our knowledge of how receptors, cAMP signaling enzymes, effectors, and other key proteins form specific signaling complexes to regulate specific cell responses is limited. The multicomponent nature of these systems and the spatiotemporal dynamics involved as proteins interact and move within a cell make cAMP responses highly complex. Adenylyl cyclases, the enzymatic source of cAMP production, are key starting points for understanding cAMP compartments and defining the functional signaling complexes. Three basic elements are required to form a signaling compartment. First, a localized signal is generated by a G protein-coupled receptor paired to one or more of the nine different transmembrane adenylyl cyclase isoforms that generate the cAMP signal in the cytosol. The diffusion of cAMP is subsequently limited by several factors, including expression of any number of phosphodiesterases (of which there are 24 genes plus spice variants). Finally, signal response elements are differentially localized to respond to cAMP produced within each locale. A-kinase-anchoring proteins, of which there are 43 different isoforms, facilitate this by targeting protein kinase A to specific substrates. Thousands of potential combinations of these three elements are possible in any given cell type, making the characterization of cAMP signaling compartments daunting. This review will focus on what is known about how cells organize cAMP signaling components as well as identify the unknowns. We make an argument for adenylyl cyclases being central to the formation and maintenance of these signaling complexes. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

  5. In vitro digestion of short-dough biscuits enriched in proteins and/or fibres, using a multi-compartmental and dynamic system (1): viscosity measurement and prediction.

    Science.gov (United States)

    Villemejane, C; Wahl, R; Aymard, P; Denis, S; Michon, C

    2015-09-01

    The effects of biscuit composition on the viscosity generated during digestion were investigated. A control biscuit, one with proteins, one with fibres, and one with both proteins and fibres were digested under the same conditions, using the TNO intestinal model (TIM-1). The TIM-1 is a multi-compartmental and dynamic in vitro system, simulating digestion in the upper tract (stomach and small intestine) of healthy adult humans. Digesta were collected at different times, in the different compartments of the TIM-1 (stomach, duodenum, jejunum and ileum) and viscosity was measured with a dynamic rheometer. Results showed a marked effect of biscuit composition on chyme viscosity. Highest viscosity was obtained with biscuits containing viscous soluble fibres, followed by those enriched in both proteins and fibres, then by protein-enriched and control biscuits. The viscosity was maintained throughout the gut up to the ileal compartment. A prediction of the evolution of the chyme viscosity in each compartment of the TIM-1 was built, based on model curves describing the evolution of the viscosity as a function of biscuit concentration, and on dilution factors measured by spectrophotometry on a blank digestion. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. [CLINICAL APPLICATION OF OXFORD MOBILE-BEARING BIPOLAR PROSTHESIS UNICOMPARTMENTAL KNEE ARTHROPLASTY FOR SINGLE COMPARTMENTAL KNEE OSTEOARTHRITIS].

    Science.gov (United States)

    Wang, Shangzeng; Cheng, Shao; Wang, Yisheng

    2016-01-01

    To evaluate the effectiveness of Oxford mobile-bearing bipolar prosthesis unicompartmental knee arthroplasty (UKA) in the treatment of single compartmental knee osteoarthritis. Between June 2011 and July 2013, 22 cases of single compartmental knee osteoarthritis were treated by Oxford mobile-bearing bipolar prosthesis UKA. Of 22 cases, 8 were male and 14 were female with an average age of 65 years (range, 45-80 years); the left knee was involved in 12 cases, and the right knee in 10 cases, with a mean disease duration of 32.5 months (range, 8-90 months). The mean weight was 55.2 kg (range, 50-65 kg), and the mean body mass index was 20.8 kg/m2 (range, 17-25 kg/m2). Osteoarthritis involved in the single knee medial compartment in all patients. Knee society score (KSS) and range of motion (ROM) were measured to evaluate the knee joint function. Primary healing of incision was obtained in all patients, and there was no complication of infection, bedsore, or deep venous thrombosis. Postoperative follow-up was 2-4 years (mean, 3.2 years). The X-ray films showed good position of prosthesis, no prosthesis dislocation, or periprosthetic infection during follow-up. Knee ROM, KSS function score, and KSS clinical score were significantly improved at 1 week after operation and at last follow-up when compared with preoperative ones (P 0.05). Oxford mobile-bearing bipolar prosthesis UKA is an effective method to treat single compartmental knee osteoarthritis, with the advantages of less trauma, earlier rehabilitation exercise, near physiological state in joint function, and less risk of complications.

  7. Compartmentalization of innate immune responses in the central nervous system during cryptococcal meningitis/HIV coinfection.

    Science.gov (United States)

    Naranbhai, Vivek; Chang, Christina C; Durgiah, Raveshni; Omarjee, Saleha; Lim, Andrew; Moosa, Mahomed-Yunus S; Elliot, Julian H; Ndung'u, Thumbi; Lewin, Sharon R; French, Martyn A; Carr, William H

    2014-03-13

    The role of innate immunity in the pathogenesis of cryptococcal meningitis is unclear. We hypothesized that natural killer (NK) cell and monocyte responses show central nervous system (CNS) compartment-specific profiles, and are altered by antifungal therapy and combination antiretroviral therapy (cART) during cryptococcal meningitis/HIV coinfection. Substudy of a prospective cohort study of adults with cryptococcal meningitis/HIV coinfection in Durban, South Africa. We used multiparametric flow cytometry to study compartmentalization of subsets, CD69 (a marker of activation), CXCR3 and CX3CR1 expression, and cytokine secretion of NK cells and monocytes in freshly collected blood and cerebrospinal fluid (CSF) at diagnosis (n = 23), completion of antifungal therapy induction (n = 19), and after a further 4 weeks of cART (n = 9). Relative to blood, CSF was enriched with CD56(bright) (immunoregulatory) NK cells (P = 0.0004). At enrolment, CXCR3 expression was more frequent among blood CD56(bright) than either blood CD56(dim) (P pos) NK-cell proportions nor CX3CR1(pos) NK-cell proportions. CD56(bright) and CD56(dim) NK cells were more activated in CSF than blood (P < 0.0001). Antifungal therapy induction reduced CD56(dim) NK-cell activation in CSF (P = 0.02). Activation of blood CD56(bright) and CD56(dim) NK cells was diminished following cART commencement (P < 0.0001, P = 0.03). Immunoregulatory NK cells in CSF tended to secrete higher levels of CXCL10 (P = 0.06) and lower levels of tumor necrosis factor α (P = 0.06) than blood immunoregulatory NK cells. CSF was enriched with nonclassical monocytes (P = 0.001), but antifungal therapy restored proportions of classical monocytes (P = 0.007). These results highlight CNS activation, trafficking, and function of NK cells and monocytes in cryptococcal meningitis/HIV and implicate immunoregulatory NK cells and proinflammatory monocytes as potential modulators of cryptococcal meningitis pathogenesis during HIV coinfection.

  8. Cytoplasmic compartmentalization of the fetal piRNA pathway in mice.

    Directory of Open Access Journals (Sweden)

    Alexei A Aravin

    2009-12-01

    Full Text Available Derepression of transposable elements (TEs in the course of epigenetic reprogramming of the mouse embryonic germline necessitates the existence of a robust defense that is comprised of PIWI/piRNA pathway and de novo DNA methylation machinery. To gain further insight into biogenesis and function of piRNAs, we studied the intracellular localization of piRNA pathway components and used the combination of genetic, molecular, and cell biological approaches to examine the performance of the piRNA pathway in germ cells of mice lacking Maelstrom (MAEL, an evolutionarily conserved protein implicated in transposon silencing in fruit flies and mice. Here we show that principal components of the fetal piRNA pathway, MILI and MIWI2 proteins, localize to two distinct types of germinal cytoplasmic granules and exhibit differential association with components of the mRNA degradation/translational repression machinery. The first type of granules, pi-bodies, contains the MILI-TDRD1 module of the piRNA pathway and is likely equivalent to the enigmatic "cementing material" first described in electron micrographs of rat gonocytes over 35 years ago. The second type of granules, piP-bodies, harbors the MIWI2-TDRD9-MAEL module of the piRNA pathway and signature components of P-bodies, GW182, DCP1a, DDX6/p54, and XRN1 proteins. piP-bodies are found predominantly in the proximity of pi-bodies and the two frequently share mouse VASA homolog (MVH protein, an RNA helicase. In Mael-mutant gonocytes, MIWI2, TDRD9, and MVH are lost from piP-bodies, whereas no effects on pi-body composition are observed. Further analysis revealed that MAEL appears to specifically facilitate MIWI2-dependent aspects of the piRNA pathway including biogenesis of secondary piRNAs, de novo DNA methylation, and efficient downregulation of TEs. Cumulatively, our data reveal elaborate cytoplasmic compartmentalization of the fetal piRNA pathway that relies on MAEL function.

  9. Foliar or root exposures to smelter particles: Consequences for lead compartmentalization and speciation in plant leaves

    Energy Technology Data Exchange (ETDEWEB)

    Schreck, Eva [Université de Toulouse, INP, UPS, EcoLab (Laboratoire Ecologie Fonctionnelle et Environnement), ENSAT, Avenue de l' Agrobiopole, 31326 Castanet-Tolosan (France); CNRS, EcoLab, 31326 Castanet-Tolosan (France); Géosciences Environnement Toulouse (GET), Observatoire Midi Pyrénées, Université de Toulouse, CNRS, IRD, 14 Avenue E. Belin, F-31400 Toulouse (France); Dappe, Vincent [LASIR (UMR CNRS 8516), Université de Lille 1, Bât. C5, 59655 Villeneuve d' Ascq Cedex (France); Sarret, Géraldine [ISTerre, UMR 5275, Université Grenoble I, CNRS, F-38041 Grenoble (France); Sobanska, Sophie [LASIR (UMR CNRS 8516), Université de Lille 1, Bât. C5, 59655 Villeneuve d' Ascq Cedex (France); Nowak, Dorota; Nowak, Jakub; Stefaniak, Elżbieta Anna [Department of Chemistry, John Paul II Catholic University of Lublin, Al. Kraśnicka 102, 20-718 Lublin (Poland); Magnin, Valérie [ISTerre, UMR 5275, Université Grenoble I, CNRS, F-38041 Grenoble (France); Ranieri, Vincent [CEA-INAC, 17 rue des Martyrs, 38054 Grenoble Cedex 9 (France); Dumat, Camille, E-mail: camille.dumat@ensat.fr [Université de Toulouse, INP, UPS, EcoLab (Laboratoire Ecologie Fonctionnelle et Environnement), ENSAT, Avenue de l' Agrobiopole, 31326 Castanet-Tolosan (France); CNRS, EcoLab, 31326 Castanet-Tolosan (France)

    2014-04-01

    better assess the health risks involved. - Highlights: • Plants were exposed to factory process particles via atmosphere or soil transfer. • Pathways of Pb uptake were investigated using microscopy and spectroscopy. • Contrary to lettuces, Pb speciation has changed in the leaf surfaces of rye-grass. • In the case of root exposure, pyromorphite was formed in the leaves of rye-grass. • Pb compartmentalization and speciation depend on transfer way and plant species.

  10. High resolution sequencing of hepatitis C virus reveals limited intra-hepatic compartmentalization in end-stage liver disease.

    Science.gov (United States)

    Hedegaard, Ditte L; Tully, Damien C; Rowe, Ian A; Reynolds, Gary M; Bean, David J; Hu, Ke; Davis, Christopher; Wilhelm, Annika; Ogilvie, Colin B; Power, Karen A; Tarr, Alexander W; Kelly, Deirdre; Allen, Todd M; Balfe, Peter; McKeating, Jane A

    2017-01-01

    The high replication and mutation rate of hepatitis C virus (HCV) results in a heterogeneous population of viral sequences in vivo. HCV replicates in the liver and infected hepatocytes occur as foci surrounded by uninfected cells that may promote compartmentalization of viral variants. Given recent reports showing interferon stimulated gene (ISG) expression in chronic hepatitis C, we hypothesized that local interferon responses may limit HCV replication and evolution. To investigate the spatial influence of liver architecture on viral replication we measured HCV RNA and ISG mRNA from each of the 8 Couinaud segments of the liver from 21 patients undergoing liver transplant. HCV RNA and ISG mRNA levels were comparable across all sites from an individual liver but showed up to 500-fold difference between patients. Importantly, there was no association between ISG and HCV RNA expression across all sites in the liver or plasma. Deep sequencing of HCV RNA isolated from the 8 hepatic sites from two subjects showed a similar distribution of viral quasispecies across the liver and uniform sequence diversity. Single genome amplification of HCV E1E2-envelope clones from 6 selected patients at 2 hepatic sites supported these data and showed no evidence for HCV compartmentalization. We found no differences between the hepatic and plasma viral quasispecies in all patients sampled. We conclude that in end-stage liver disease HCV RNA levels and the genetic pool of HCV envelope sequences are indistinguishable between distant sites in the liver and plasma, arguing against viral compartmentalization. HCV is an RNA virus that exists as a quasispecies of closely related genomes that are under continuous selection by host innate and adaptive immune responses and antiviral drug therapy. The primary site of HCV replication is the liver and yet our understanding of the spatial distribution of viral variants within the liver is limited. High resolution sequencing of HCV and monitoring of

  11. A physiologically required G protein-coupled receptor (GPCR)-regulator of G protein signaling (RGS) interaction that compartmentalizes RGS activity.

    Science.gov (United States)

    Croft, Wayne; Hill, Claire; McCann, Eilish; Bond, Michael; Esparza-Franco, Manuel; Bennett, Jeannette; Rand, David; Davey, John; Ladds, Graham

    2013-09-20

    G protein-coupled receptors (GPCRs) can interact with regulator of G protein signaling (RGS) proteins. However, the effects of such interactions on signal transduction and their physiological relevance have been largely undetermined. Ligand-bound GPCRs initiate by promoting exchange of GDP for GTP on the Gα subunit of heterotrimeric G proteins. Signaling is terminated by hydrolysis of GTP to GDP through intrinsic GTPase activity of the Gα subunit, a reaction catalyzed by RGS proteins. Using yeast as a tool to study GPCR signaling in isolation, we define an interaction between the cognate GPCR (Mam2) and RGS (Rgs1), mapping the interaction domains. This reaction tethers Rgs1 at the plasma membrane and is essential for physiological signaling response. In vivo quantitative data inform the development of a kinetic model of the GTPase cycle, which extends previous attempts by including GPCR-RGS interactions. In vivo and in silico data confirm that GPCR-RGS interactions can impose an additional layer of regulation through mediating RGS subcellular localization to compartmentalize RGS activity within a cell, thus highlighting their importance as potential targets to modulate GPCR signaling pathways.

  12. Activation of PKA in cell requires higher concentration of cAMP than in vitro: implications for compartmentalization of cAMP signalling.

    Science.gov (United States)

    Koschinski, Andreas; Zaccolo, Manuela

    2017-10-26

    cAMP is a ubiquitous second messenger responsible for the cellular effects of multiple hormones and neurotransmitters via activation of its main effector, protein kinase A (PKA). Multiple studies have shown that the basal concentration of cAMP in several cell types is about 1 μM. This value is well above the reported concentration of cAMP required to half-maximally activate PKA, which measures in the 100-300 nM range. Several hypotheses have been suggested to explain this apparent discrepancy including inaccurate measurements of intracellular free cAMP, inaccurate measurement of the apparent activation constant of PKA or shielding of PKA from bulk cytosolic cAMP via localization of the enzyme to microdomains with lower basal cAMP concentration. However, direct experimental evidence in support of any of these models is limited and a firm conclusion is missing. In this study we use multiple FRET-based reporters for the detection of cAMP and PKA activity in intact cells and we establish that the sensitivity of PKA to cAMP is almost twenty times lower when measured in cell than when measured in vitro. Our findings have important implications for the understanding of compartmentalized cAMP signalling.

  13. Model description and evaluation of model performance: DOSDIM model

    International Nuclear Information System (INIS)

    Lewyckyj, N.; Zeevaert, T.

    1996-01-01

    DOSDIM was developed to assess the impact to man from routine and accidental atmospheric releases. It is a compartmental, deterministic, radiological model. For an accidental release, dynamic transfer are used in opposition to a routine release for which equilibrium transfer factors are used. Parameters values were chosen to be conservative. Transfer between compartments are described by first-order differential equations. 2 figs

  14. Controlled synthesis of 3D multi-compartmental particles with centrifuge-based microdroplet formation from a multi-barrelled capillary.

    Science.gov (United States)

    Maeda, Kazuki; Onoe, Hiroaki; Takinoue, Masahiro; Takeuchi, Shoji

    2012-03-08

    Controlled synthesis of micro multi-compartmental particles using a centrifuge droplet shooting device (CDSD) is reported. Sodium alginate solutions introduced in a multi-barreled capillary form droplets at the capillary orifice under ultrahigh gravity and gelify in a CaCl(2) solution. The size, shape, and compartmentalization of the particles are controlled. Co-encapsulation of Jurkat cells and magnetic colloids into Janus particles is demonstrated. The Janus particles present sensitive reaction toward magnetic fields, while the viability of the encapsulated cells is 91%. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Full-length cellular β-secretase has a trimeric subunit stoichiometry, and its sulfur-rich transmembrane interaction site modulates cytosolic copper compartmentalization.

    Science.gov (United States)

    Liebsch, Filip; Aurousseau, Mark R P; Bethge, Tobias; McGuire, Hugo; Scolari, Silvia; Herrmann, Andreas; Blunck, Rikard; Bowie, Derek; Multhaup, Gerd

    2017-08-11

    The β-secretase (BACE1) initiates processing of the amyloid precursor protein (APP) into Aβ peptides, which have been implicated as central players in the pathology of Alzheimer disease. BACE1 has been described as a copper-binding protein and its oligomeric state as being monomeric, dimeric, and/or multimeric, but the native cellular stoichiometry has remained elusive. Here, by using single-molecule fluorescence and in vitro cross-linking experiments with photo-activatable unnatural amino acids, we show that full-length BACE1, independently of its subcellular localization, exists as trimers in human cells. We found that trimerization requires the BACE1 transmembrane sequences (TMSs) and cytoplasmic domains, with residues Ala 463 and Cys 466 buried within the trimer interface of the sulfur-rich core of the TMSs. Our 3D model predicts that the sulfur-rich core of the trimeric BACE1 TMS is accessible to metal ions, but copper ions did not trigger trimerization. The results of functional assays of endogenous BACE1 suggest that it has a role in intracellular copper compartmentalization by transferring cytosolic copper to intracellular compartments, while leaving the overall cellular copper concentration unaltered. Adding to existing physiological models, our results provide novel insight into the atypical interactions between copper and BACE1 and into its non-enzymatic activities. In conclusion, therapeutic Alzheimer disease prevention strategies aimed at decreasing BACE1 protein levels should be regarded with caution, because adverse effects in copper homeostasis may occur. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Levels, spatial variation and compartmentalization of trace elements in brown algae Cystoseira from marine protected areas of Crimea (Black Sea).

    Science.gov (United States)

    Kravtsova, Alexandra V; Milchakova, Nataliya A; Frontasyeva, Marina V

    2015-08-15

    Levels of Al, Sc, V, Co, Ni, As, Br, Rb, Sr, Ag, Sb, I, Cs, Ba, Th and U that were rarely or never studied, as well as the concentrations of classically investigated Mn, Fe and Zn in brown algae Cystoseira barbata C. Ag. and Cystoseira crinita (Desf.) Bory from the coastal waters of marine protected areas (Crimea, Black Sea), were determined using neutron activation analysis. Spatial variation and compartmentalization were studied for all 19 trace elements (TE). Concentrations of most TE were higher in "branches" than in "stems". Spatial variations of V, Co, Ni and Zn can be related to anthropogenic activities while Al, Sc, Fe, Rb, Cs, Th and U varied depending on chemical peculiarities of the coastal zone rocks. TE concentrations in C. crinita from marine protected areas near Tarkhankut peninsula and Cape Fiolent, identified as the most clean water areas, are submitted as the background concentrations. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Use of flux analysis to study the compartmentation of copper in copper tolerant and non-tolerant Mimulus guttatus

    International Nuclear Information System (INIS)

    Shaw, P.; Collins, J.C.; Thurman, D.A.

    1987-01-01

    Compartmental flux analysis using 64 Cu and a stereological study have been used to estimate the amount and concentrations of copper in the cell wall, cytoplasm and vacuole of roots of non-tolerant and copper tolerant clones of Mimulus guttatus. The cell wall was not found to be a major site of copper accumulation in either clone compared with the cytoplasmic and vacuolar phases. The cytoplasmic concentrations of copper in the non-tolerant clone were significantly grater than those of the tolerant clone when grown in 2.0 and 10.0 μM external copper. At all external copper concentrations and for both clones vacuolar levels of copper were lower than the cytoplasmic ones. At 10.0 μM external copper the vacuolar concentrations of the non-tolerant clone were significantly higher than those of the tolerant clone

  18. The cellular and compartmental profile of mouse retinal glycolysis, tricarboxylic acid cycle, oxidative phosphorylation, and ~P transferring kinases.

    Science.gov (United States)

    Rueda, Elda M; Johnson, Jerry E; Giddabasappa, Anand; Swaroop, Anand; Brooks, Matthew J; Sigel, Irena; Chaney, Shawnta Y; Fox, Donald A

    2016-01-01

    The homeostatic regulation of cellular ATP is achieved by the coordinated activity of ATP utilization, synthesis, and buffering. Glucose is the major substrate for ATP synthesis through glycolysis and oxidative phosphorylation (OXPHOS), whereas intermediary metabolism through the tricarboxylic acid (TCA) cycle utilizes non-glucose-derived monocarboxylates, amino acids, and alpha ketoacids to support mitochondrial ATP and GTP synthesis. Cellular ATP is buffered by specialized equilibrium-driven high-energy phosphate (~P) transferring kinases. Our goals were twofold: 1) to characterize the gene expression, protein expression, and activity of key synthesizing and regulating enzymes of energy metabolism in the whole mouse retina, retinal compartments, and/or cells and 2) to provide an integrative analysis of the results related to function. mRNA expression data of energy-related genes were extracted from our whole retinal Affymetrix microarray data. Fixed-frozen retinas from adult C57BL/6N mice were used for immunohistochemistry, laser scanning confocal microscopy, and enzymatic histochemistry. The immunoreactivity levels of well-characterized antibodies, for all major retinal cells and their compartments, were obtained using our established semiquantitative confocal and imaging techniques. Quantitative cytochrome oxidase (COX) and lactate dehydrogenase (LDH) activity was determined histochemically. The Affymetrix data revealed varied gene expression patterns of the ATP synthesizing and regulating enzymes found in the muscle, liver, and brain. Confocal studies showed differential cellular and compartmental distribution of isozymes involved in glucose, glutamate, glutamine, lactate, and creatine metabolism. The pattern and intensity of the antibodies and of the COX and LDH activity showed the high capacity of photoreceptors for aerobic glycolysis and OXPHOS. Competition assays with pyruvate revealed that LDH-5 was localized in the photoreceptor inner segments. The

  19. Add-in macros for rapid and versatile calculation of non-compartmental pharmacokinetic parameters on Microsoft Excel spreadsheets.

    Science.gov (United States)

    Sato, H; Sato, S; Wang, Y M; Horikoshi, I

    1996-06-01

    We developed a package of macro programs (named PK_MOMENT) to automatically calculate non-compartmental pharmacokinetic parameters on Microsoft Excel spreadsheets. These macros include rigorous algorithms to execute moment calculations in a comprehensive manner. An optimum number of terminal data points for infinite-time extrapolation can be calculated with one of these macros so that automatic calculation of infinite moment parameters is possible. The moment calculation with PK_MOMENT provided satisfactory results using the hybrid (mixed linear-logarithmic) trapezoidal method rather than the conventional linear trapezoidal method. The macro-aided pharmacokinetic analyses turned out to be useful in that the macro-containing cells can be easily copied and pasted to analyze other data sets and that powerful tools of Excel can be utilized. The use of our macros will be significantly time-saving for routine pharmacokinetic analyses, considering that pharmacokinetic data are usually stored in a spreadsheet format, typically with Excel.

  20. On the contributions of photorespiration and compartmentation to the contrasting intramolecular 2H profiles of C3 and C4 plant sugars

    Science.gov (United States)

    Youping Zhou; Benli Zhang; Hilary Stuart-Williams; Kliti Grice; Charles H. Hocart; Arthur Gessler; Zachary E. Kayler; Graham D. Farquhar

    2018-01-01

    Compartmentation of C4 photosynthetic biochemistry into bundle sheath (BS) and mesophyll (M) cells, and photorespiration in C3 plants is predicted to have hydrogen isotopic consequences for metabolites at both molecular and site-specific levels. Molecular-level evidence was recently reported (Zhou et al., 2016), but...

  1. Subcellular compartmentation of sugar signalling: Links among carbon cellular status, route of sucrolysis, sink-source allocation, and metabolic partitioning

    Directory of Open Access Journals (Sweden)

    Axel eTiessen

    2013-01-01

    Full Text Available Recent findings suggest that both subcellular compartmentation and route of sucrolysis are important for plant development, growth, and yield. Signalling effects are dependent on the tissue, cell type and stage of development. Downstream effects also depend on the amount and localisation of hexoses and disaccharides. All enzymes of sucrose metabolism (e.g. invertase, hexokinase, fructokinase, sucrose synthase, and sucrose 6-phosphate synthase are not produced from single genes, but from paralogue families in plant genomes. Each paralogue has unique expression across plant organs and developmental stages. Multiple isoforms can be targeted to different cellular compartments (e.g. plastids, mitochondria, nuclei, and cytosol. Many of the key enzymes are regulated by post-transcriptional modifications and associate in multimeric protein complexes. Some isoforms have regulatory functions, either in addition to or in replacement of their catalytic activity. This explains why some isozymes are not redundant, but also complicates elucidation of their specific involvement in sugar signalling. The subcellular compartmentation of sucrose metabolism forces refinement of some of the paradigms of sugar signalling during physiological processes. For example, the catalytic and signalling functions of diverse paralogues needs to be more carefully analysed in the context of post-genomic biology. It is important to note that it is the differential localization of both the sugars themselves as well as the sugar-metabolizing enzymes that ultimately led to sugar signalling. We conclude that a combination of subcellular complexity and gene duplication/subfunctionalization gave rise to sugar signalling as a regulatory mechanism in plant cells.

  2. Lipid Droplet-Associated Proteins (LDAPs) Are Required for the Dynamic Regulation of Neutral Lipid Compartmentation in Plant Cells1

    Science.gov (United States)

    Park, Sunjung; Wu, Peng

    2016-01-01

    Eukaryotic cells compartmentalize neutral lipids into organelles called lipid droplets (LDs), and while much is known about the role of LDs in storing triacylglycerols in seeds, their biogenesis and function in nonseed tissues are poorly understood. Recently, we identified a class of plant-specific, lipid droplet-associated proteins (LDAPs) that are abundant components of LDs in nonseed cell types. Here, we characterized the three LDAPs in Arabidopsis (Arabidopsis thaliana) to gain insight to their targeting, assembly, and influence on LD function and dynamics. While all three LDAPs targeted specifically to the LD surface, truncation analysis of LDAP3 revealed that essentially the entire protein was required for LD localization. The association of LDAP3 with LDs was detergent sensitive, but the protein bound with similar affinity to synthetic liposomes of various phospholipid compositions, suggesting that other factors contributed to targeting specificity. Investigation of LD dynamics in leaves revealed that LD abundance was modulated during the diurnal cycle, and characterization of LDAP misexpression mutants indicated that all three LDAPs were important for this process. LD abundance was increased significantly during abiotic stress, and characterization of mutant lines revealed that LDAP1 and LDAP3 were required for the proper induction of LDs during heat and cold temperature stress, respectively. Furthermore, LDAP1 was required for proper neutral lipid compartmentalization and triacylglycerol degradation during postgerminative growth. Taken together, these studies reveal that LDAPs are required for the maintenance and regulation of LDs in plant cells and perform nonredundant functions in various physiological contexts, including stress response and postgerminative growth. PMID:26896396

  3. Lipid Droplet-Associated Proteins (LDAPs) Are Required for the Dynamic Regulation of Neutral Lipid Compartmentation in Plant Cells.

    Science.gov (United States)

    Gidda, Satinder K; Park, Sunjung; Pyc, Michal; Yurchenko, Olga; Cai, Yingqi; Wu, Peng; Andrews, David W; Chapman, Kent D; Dyer, John M; Mullen, Robert T

    2016-04-01

    Eukaryotic cells compartmentalize neutral lipids into organelles called lipid droplets (LDs), and while much is known about the role of LDs in storing triacylglycerols in seeds, their biogenesis and function in nonseed tissues are poorly understood. Recently, we identified a class of plant-specific, lipid droplet-associated proteins (LDAPs) that are abundant components of LDs in nonseed cell types. Here, we characterized the three LDAPs in Arabidopsis (Arabidopsis thaliana) to gain insight to their targeting, assembly, and influence on LD function and dynamics. While all three LDAPs targeted specifically to the LD surface, truncation analysis of LDAP3 revealed that essentially the entire protein was required for LD localization. The association of LDAP3 with LDs was detergent sensitive, but the protein bound with similar affinity to synthetic liposomes of various phospholipid compositions, suggesting that other factors contributed to targeting specificity. Investigation of LD dynamics in leaves revealed that LD abundance was modulated during the diurnal cycle, and characterization of LDAP misexpression mutants indicated that all three LDAPs were important for this process. LD abundance was increased significantly during abiotic stress, and characterization of mutant lines revealed that LDAP1 and LDAP3 were required for the proper induction of LDs during heat and cold temperature stress, respectively. Furthermore, LDAP1 was required for proper neutral lipid compartmentalization and triacylglycerol degradation during postgerminative growth. Taken together, these studies reveal that LDAPs are required for the maintenance and regulation of LDs in plant cells and perform nonredundant functions in various physiological contexts, including stress response and postgerminative growth. © 2016 American Society of Plant Biologists. All Rights Reserved.

  4. Molecular analysis reveals high compartmentalization in aphid-primary parasitoid networks and low parasitoid sharing between crop and noncrop habitats.

    Science.gov (United States)

    Derocles, Stephane A P; Le Ralec, Anne; Besson, Mathilde M; Maret, Marion; Walton, Alan; Evans, Darren M; Plantegenest, Manuel

    2014-08-01

    The ecosystem service of insect pest regulation by natural enemies, such as primary parasitoids, may be enhanced by the presence of uncultivated, semi-natural habitats within agro-ecosystems, although quantifying such host-parasitoid interactions is difficult. Here, we use rRNA 16S gene sequencing to assess both the level of parasitism by Aphidiinae primary parasitoids and parasitoid identity on a large sample of aphids collected in cultivated and uncultivated agricultural habitats in Western France. We used these data to construct ecological networks to assess the level of compartmentalization between aphid and parasitoid food webs of cultivated and uncultivated habitats. We evaluated the extent to which uncultivated margins provided a resource for parasitoids shared between pest and nonpest aphids. We compared the observed quantitative ecological network described by our molecular approach to an empirical qualitative network based on aphid-parasitoid interactions from traditional rearing data found in the literature. We found that the molecular network was highly compartmentalized and that parasitoid sharing is relatively rare between aphids, especially between crop and noncrop compartments. Moreover, the few cases of putative shared generalist parasitoids were questionable and could be due to the lack of discrimination of cryptic species or from intraspecific host specialization. Our results suggest that apparent competition mediated by Aphidiinae parasitoids is probably rare in agricultural areas and that the contribution of field margins as a source of these biocontrol agents is much more limited than expected. Further large-scale (spatial and temporal) studies on other crops and noncrop habitats are needed to confirm this. © 2014 John Wiley & Sons Ltd.

  5. Compartmentalization of Total and Virus-Specific Tissue-Resident Memory CD8+ T Cells in Human Lymphoid Organs.

    Directory of Open Access Journals (Sweden)

    Heng Giap Woon

    2016-08-01

    Full Text Available Disruption of T cell memory during severe immune suppression results in reactivation of chronic viral infections, such as Epstein Barr virus (EBV and Cytomegalovirus (CMV. How different subsets of memory T cells contribute to the protective immunity against these viruses remains poorly defined. In this study we examined the compartmentalization of virus-specific, tissue resident memory CD8+ T cells in human lymphoid organs. This revealed two distinct populations of memory CD8+ T cells, that were CD69+CD103+ and CD69+CD103-, and were retained within the spleen and tonsils in the absence of recent T cell stimulation. These two types of memory cells were distinct not only in their phenotype and transcriptional profile, but also in their anatomical localization within tonsils and spleen. The EBV-specific, but not CMV-specific, CD8+ memory T cells preferentially accumulated in the tonsils and acquired a phenotype that ensured their retention at the epithelial sites where EBV replicates. In vitro studies revealed that the cytokine IL-15 can potentiate the retention of circulating effector memory CD8+ T cells by down-regulating the expression of sphingosine-1-phosphate receptor, required for T cell exit from tissues, and its transcriptional activator, Kruppel-like factor 2 (KLF2. Within the tonsils the expression of IL-15 was detected in regions where CD8+ T cells localized, further supporting a role for this cytokine in T cell retention. Together this study provides evidence for the compartmentalization of distinct types of resident memory T cells that could contribute to the long-term protection against persisting viral infections.

  6. Compartmental and dosimetric studies of anti-CD20 labelled with {sup 188}Re; Estudo compartimental e dosimetrico do Anti-CD20 marcado com {sup 188}Re

    Energy Technology Data Exchange (ETDEWEB)

    Kuramoto, Graciela Barrio

    2016-10-01

    The radioimmunotherapy (RIT) uses MAbs conjugated to radionuclides α or β{sup -} emitters, both for therapy. Your treatment is based on the irradiation and tumor destruction, preserving the normal organs as the excess radiation. Radionuclides β{sup -} emitters as {sup 131}I, {sup 90}Y, {sup 188}Re {sup 177}Lu and are useful for the development of therapeutic radiopharmaceuticals and, when coupled with MAb and Anti-CD20 it is important mainly for the treatment of non-Hodgkin's lymphomas (NHL). {sup 188}Re (E{sub β} = 2.12 MeV; E{sub γ} = 155 keV; t1/2 = 16.9 h) is an attractive radionuclide for RIT. However, {sup 188}Re can be obtained from a radionuclide generator of {sup 188}W/{sup 188}Re, commercially available, making it convenient for use in research and for clinical routine. The CR of IPEN has a project aimed at the production of radiopharmaceutical {sup 188}Re-Anti-CD20, where the radionuclide can be obtained from a generator system {sup 188}W/{sup 188}Re. With this proposed a study to assess the efficiency of this labeling technique for treatment in accordance compartmental and dosimetry. The objective of this study was to compare the marking of anti-CD20 MAb with {sup 188}Re with the marking of the antibody with {sup 90}Y, {sup 131}I, {sup 177}Lu and {sup 99m}Tc (for their similar chemical characteristics) and {sup 211}At, {sup 213}Bi, {sup 223}Ra and {sup 225}Ac); through the study of labeling techniques reported in literature, the proposal of a compartmental model to evaluate its pharmacokinetic and dosimetric studies, high interest for therapy. The result of the study shows a favorable kinetics for {sup 188}Re, by their physical and chemical characteristics compared to the other evaluated radionuclides. The compartment proposed study describes the metabolism of {sup 188}Reanti- CD20 through a compartment mammillary model, which by their pharmacokinetic analysis, performed compared to products emitters β{sup -131}I-labeled anti CD20, {sup 177

  7. Transmission Models of Historical Ebola Outbreaks

    OpenAIRE

    Drake, John M.; Bakach, Iurii; Just, Matthew R.; O?Regan, Suzanne M.; Gambhir, Manoj; Fung, Isaac Chun-Hai

    2015-01-01

    To guide the collection of data under emergent epidemic conditions, we reviewed compartmental models of historical Ebola outbreaks to determine their implications and limitations. We identified future modeling directions and propose that the minimal epidemiologic dataset for Ebola model construction comprises duration of incubation period and symptomatic period, distribution of secondary cases by infection setting, and compliance with intervention recommendations.

  8. Metabolic hormones, apolipoproteins, adipokines, and cytokines in the alveolar lining fluid of healthy adults: compartmentalization and physiological correlates.

    Directory of Open Access Journals (Sweden)

    Carlos O Mendivil

    Full Text Available Our current understanding of hormone regulation in lung parenchyma is quite limited. We aimed to quantify a diverse array of biologically relevant protein mediators in alveolar lining fluid (ALF, compared to serum concentrations, and explore factors associated with protein compartmentalization on either side of the air-blood barrier.Participants were 24 healthy adult non-smoker volunteers without respiratory symptoms or significant medical conditions, with normal lung exams and office spirometry. Cell-free bronchoalveolar lavage fluid and serum were analyzed for 24 proteins (including enteric and metabolic hormones, apolipoproteins, adipokines, and cytokines using a highly sensitive multiplex ELISA. Measurements were normalized to ALF concentrations. The ALF:serum concentration ratios were examined in relation to measures of protein size, hydrophobicity, charge, and to participant clinical and spirometric values.ALF measurements from 24 individuals detected 19 proteins, including adiponectin, adipsin, apoA-I, apoA-II, apoB, apoC-II, apoC-III, apoE, C-reactive protein, ghrelin, glucose-dependent insulinotropic peptide (GIP, glucagon-like peptide-1 (GLP-1, glucagon, insulin, leptin, monocyte chemoattractant protein-1, plasminogen activator inhibitor-1, resistin, and visfatin. C-peptide and serpin E1 were not detected in ALF for any individual, and IL-6, IL-10, and TNF-alpha were not detected in either ALF or serum for any individual. In general, ALF levels were similar or lower in concentration for most proteins compared to serum. However, ghrelin, resistin, insulin, visfatin and GLP-1 had ALF concentrations significantly higher compared to serum. Importantly, elevated ALF:serum ratios of ghrelin, visfatin and resistin correlated with protein net charge and isoelectric point, but not with molecular weight or hydrophobicity.Biologically relevant enteric and metabolic hormones, apolipoproteins, adipokines, and cytokines can be detected in the ALF of

  9. Anti-tuberculosis drug combination for controlled oral delivery using 3D printed compartmental dosage forms: From drug product design to in vivo testing

    DEFF Research Database (Denmark)

    Genina, Natalja; Boetker, Johan Peter; Colombo, Stefano

    2017-01-01

    The design and production of an oral dual-compartmental dosage unit (dcDU) was examined in vitro and in vivo with the purpose of physically isolating and modulating the release profile of an anti-tuberculosis drug combination. Rifampicin (RIF) and isoniazid (ISO) are first line combination drugs...... for treatment of tuberculosis (TB) that negatively interact with each other upon simultaneous release in acidic environment. The dcDUs were designed in silico by computer aided design (CAD) and fabricated in two steps; first three-dimensional (3D) printing of the outer structure, followed by hot-melt extrusion...... (HME) of the drug-containing filaments. The structure of the fabricated dcDUs was visualized by scanning electron microscopy (SEM). The 3D printed compartmentalized shells were loaded with filaments containing active pharmaceutical ingredient (API) and selectively sealed to modulate drug dissolution...

  10. Fault seal analysis to predict the compartmentalization of gas reservoir: Case study of Steenkool formation Bintuni Basin

    Science.gov (United States)

    Ginanjar, W. C. B.; Haris, A.; Riyanto, A.

    2017-07-01

    This study is aimed to analyze the mechanism of hydrocarbons trapping in the field on a relatively new play in the Bintuni basin particularly Steenkool formation. The first well in this field has been drilled with a shallow target in the Steenkool formation and the drilling is managed to find new gas reserves in the shale-sandstone layer. In the structure of this gas discovery, there is the potential barrier for compartmentalization that draws attention to analyze how the patterns of structural of fault become a part of reservoir compartment. In order to measure the risk associated with prospects on a field bounded by faults, it is important to understand the processes that contribute to fault seal. The method of Fault Seal Analysis (FSA) is one of the methods used for the analysis of the nature of a fault whether the fault is sealing or leaking the fluid flow in the reservoir. Trapping systems that are limited by faults play an important role in creating a trap of hydrocarbon. The ability of a fault to seal fluid is quantitatively reflected by the value of Shale Gouge Ratio (SGR). SGR is the calculation of the amount of fine-grained material that fills fault plane (fault gouge) as a result of the movement mechanism of fault. The result of this study is a valuable resource for the systematic evaluation of the analysis of hydrocarbon prospects in the field.

  11. Drug compartmentalization as strategy to improve the physico-chemical properties of diclofenac sodium loaded niosomes for topical applications.

    Science.gov (United States)

    Tavano, Lorena; de Cindio, Bruno; Picci, Nevio; Ioele, Giuseppina; Muzzalupo, Rita

    2014-12-01

    The objective of this research was to study the effect of diclofenac sodium compartmentalization on the physico-chemical properties (such as size, drug entrapment efficiency and percutaneous permeation across rabbit skin) of niosomal vesicles used as carriers. Niosomes were prepared starting from nonionic commercial surfactants belonging to the class of Polysorbates and Pluronics: mixtures of Span 60/F127 and Tween 60/F127 at different ratios were used to obtain vesicles and all formulations were compared in terms of dimensions, morphology, polydispersity index and entrapment efficiency. Moreover, the enhancing effect of niosomes on the ex vivo percutaneous penetration of diclofenac sodium was investigated using Franz-type diffusion chambers and compared to that obtained by using the corresponding drug solution. Results demonstrated that niosomes were spherical and homogeneous in shape. Their size was found to be dependent on the hydrophile-lipophile balance of the surfactant mixture: increasing hydrophobicity resulted in smaller vesicles. Drug incorporation led to a significant variation in vesicle size dependently from the compartment in which the drug was located. The permeation of diclofenac from free solution used as control was found to be lower respect to that obtained for all niosomal formulations, that can be considered as percutaneous permeation enhancers. In particular, the results indicated that the highest cumulative amounts of diclofenac permeated across rabbit skin after 24 h were obtained by formulations in which the drug was located in the aqueous core.

  12. Role of cellular compartmentalization in the trophic transfer of mercury species in a freshwater plant-crustacean food chain.

    Science.gov (United States)

    Beauvais-Flück, Rebecca; Chaumot, Arnaud; Gimbert, Frédéric; Quéau, Hervé; Geffard, Olivier; Slaveykova, Vera I; Cosio, Claudia

    2016-12-15

    Mercury (Hg) represents an important risk for human health through the food webs contamination. Macrophytes bioaccumulate Hg and play a role in Hg transfer to food webs in shallow aquatic ecosystems. Nevertheless, the compartmentalization of Hg within macrophytes, notably major accumulation in the cell wall and its impact on trophic transfer to primary consumers are overlooked. The present work focusses on the trophic transfer of inorganic Hg (IHg) and monomethyl-Hg (MMHg) from the intracellular and cell wall compartments of the macrophyte Elodea nuttallii - considered a good candidate for phytoremediation - to the crustacean Gammarus fossarum. The results demonstrated that Hg accumulated in both compartments was trophically bioavailable to gammarids. Besides IHg from both compartments were similarly transferred to G. fossarum, while for MMHg, uptake rates were ∼2.5-fold higher in G. fossarum fed with the cell wall vs the intracellular compartment. During the depuration phase, Hg concentrations in G. fossarum varied insignificantly suggesting that both IHg and MMHg were strongly bound to biological ligands in the crustacean. Our data imply that cell walls have to be considered as an important source of Hg to consumers in freshwater food webs when developing procedures for enhancing aquatic environment protection during phytoremediation programs. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Levels, spatial variation and compartmentalization of trace elements in brown algae Cystoseira from marine protected areas of Crimea (Black Sea)

    International Nuclear Information System (INIS)

    Kravtsova, Alexandra V.; Milchakova, Nataliya A.; Frontasyeva, Marina V.

    2015-01-01

    Highlights: • 19 trace elements were determined in Cystoseira spp. from marine protected areas. • Levels of 10 elements were lower than reported data for Black Sea Cystoseira spp. • Concentrations of most trace elements were higher in “branches” than in “stems”. • Spatial variations of V, Co, Ni and Zn can be related to anthropogenic activities. • Al, Sc, Fe, Rb, Cs, Th, U varied depending on geological composition of the coast. - Abstract: Levels of Al, Sc, V, Co, Ni, As, Br, Rb, Sr, Ag, Sb, I, Cs, Ba, Th and U that were rarely or never studied, as well as the concentrations of classically investigated Mn, Fe and Zn in brown algae Cystoseira barbata C. Ag. and Cystoseira crinita (Desf.) Bory from the coastal waters of marine protected areas (Crimea, Black Sea), were determined using neutron activation analysis. Spatial variation and compartmentalization were studied for all 19 trace elements (TE). Concentrations of most TE were higher in “branches” than in “stems”. Spatial variations of V, Co, Ni and Zn can be related to anthropogenic activities while Al, Sc, Fe, Rb, Cs, Th and U varied depending on chemical peculiarities of the coastal zone rocks. TE concentrations in C. crinita from marine protected areas near Tarkhankut peninsula and Cape Fiolent, identified as the most clean water areas, are submitted as the background concentrations

  14. Estimate of FDG Excretion by means of Compartmental Analysis and Ant Colony Optimization of Nuclear Medicine Data

    Science.gov (United States)

    Garbarino, Sara; Caviglia, Giacomo; Brignone, Massimo; Massollo, Michela; Sambuceti, Gianmario; Piana, Michele

    2013-01-01

    [18F]fluoro-2-deoxy-D-glucose (FDG) is one of the most utilized tracers for positron emission tomography (PET) applications in oncology. FDG-PET relies on higher glycolytic activity in tumors compared to normal structures as the basis of image contrast. As a glucose analog, FDG is transported into malignant cells which typically exhibit an increased radioactivity. However, different from glucose, FDG is not reabsorbed by the renal system and is excreted to the bladder. The present paper describes a novel computational method for the quantitative assessment of this excretion process. The method is based on a compartmental analysis of FDG-PET data in which the excretion process is explicitly accounted for by the bladder compartment and on the application of an ant colony optimization (ACO) algorithm for the determination of the tracer coefficients describing the FDG transport effectiveness. The validation of this approach is performed by means of both synthetic data and real measurements acquired by a PET device for small animals (micro-PET). Possible oncological applications of the results are discussed in the final section. PMID:24191175

  15. Lipid droplet-associated proteins (LDAPs) are involved in the compartmentalization of lipophilic compounds in plant cells.

    Science.gov (United States)

    Gidda, Satinder K; Watt, Samantha; Collins-Silva, Jillian; Kilaru, Aruna; Arondel, Vincent; Yurchenko, Olga; Horn, Patrick J; James, Christopher N; Shintani, David; Ohlrogge, John B; Chapman, Kent D; Mullen, Robert T; Dyer, John M

    2013-11-01

    While lipid droplets have traditionally been considered as inert sites for the storage of triacylglycerols and sterol esters, they are now recognized as dynamic and functionally diverse organelles involved in energy homeostasis, lipid signaling, and stress responses. Unlike most other organelles, lipid droplets are delineated by a half-unit membrane whose protein constituents are poorly understood, except in the specialized case of oleosins, which are associated with seed lipid droplets. Recently, we identified a new class of lipid-droplet associated proteins called LDAPs that localize specifically to the lipid droplet surface within plant cells and share extensive sequence similarity with the small rubber particle proteins (SRPPs) found in rubber-accumulating plants. Here, we provide additional evidence for a role of LDAPs in lipid accumulation in oil-rich fruit tissues, and further explore the functional relationships between LDAPs and SRPPs. In addition, we propose that the larger LDAP/SRPP protein family plays important roles in the compartmentalization of lipophilic compounds, including triacylglycerols and polyisoprenoids, into lipid droplets within plant cells. Potential roles in lipid droplet biogenesis and function of these proteins also are discussed.

  16. Surface interactions with compartmentalized cellular phosphates explain rare earth oxide nanoparticle hazard and provide opportunities for safer design.

    Science.gov (United States)

    Li, Ruibin; Ji, Zhaoxia; Chang, Chong Hyun; Dunphy, Darren R; Cai, Xiaoming; Meng, Huan; Zhang, Haiyuan; Sun, Bingbing; Wang, Xiang; Dong, Juyao; Lin, Sijie; Wang, Meiying; Liao, Yu-Pei; Brinker, C Jeffrey; Nel, Andre; Xia, Tian

    2014-02-25

    Growing international exploitation of rare earth oxides (REOs) for commercial and biological use has increased the possibility of human exposure and adverse health effects. Occupational exposure to rare earth materials in miners and polishers leads to a severe form of pneumoconiosis, while gadolinium-containing MRI contrast agents cause nephrogenic systemic fibrosis in patients with renal impairment. The mechanisms for inducing these adverse pro-fibrogenic effects are of considerable importance for the safety assessment of REO particles as well as presenting opportunities for safer design. In this study, using a well-prepared REO library, we obtained a mechanistic understanding of how REOs induce cellular and pulmonary damage by a compartmentalized intracellular biotransformation process in lysosomes that results in pro-fibrogenic growth factor production and lung fibrosis. We demonstrate that rare earth oxide ion shedding in acidifying macrophage lysosomes leads to biotic phosphate complexation that results in organelle damage due to stripping of phosphates from the surrounding lipid bilayer. This results in nanoparticle biotransformation into urchin shaped structures and setting in motion a series of events that trigger NLRP3 inflammasome activation, IL-1β release, TGF-β1 and PDGF-AA production. However, pretreatment of REO nanoparticles with phosphate in a neutral pH environment prevents biological transformation and pro-fibrogenic effects. This can be used as a safer design principle for producing rare earth nanoparticles for biological use.

  17. Acute effects of incremental inspiratory loads on compartmental chest wall volume and predominant activity frequency of inspiratory muscle.

    Science.gov (United States)

    Da Gama, Alana Elza Fontes; de Andrade Carvalho, Larissa; Feitosa, Larissa Andrade; do Nascimento Junior, Jasiel Frutuoso; da Silva, Marilú Gomes Netto Monte; Amorim, César F; Aliverti, Andréa; Lambertz, Daniel; Rodrigues, Marco Aurélio Benedetti; de Andrade, Armèle Dornelas

    2013-12-01

    This research aims to analyze the acute effect of incremental inspiratory loads on respiratory pattern and on the predominant activity frequency of inspiratory muscle, taking into account differences in gender responses. Optoelectronic Plethysmography was performed during loads in 39 healthy subjects (20 women), placing 89 markers on the thoracic-abdominal wall to obtain total and regional volumes. Surface electromyography (SEMG) was taken simultaneously on the Sternocleidomastoid and Diaphragm muscles, to calculate the predominant muscle activity frequency through wavelet analysis. Inspiratory loads were performed using Threshold(®)with 2 min of breathing at different levels, ranging from a load of 10 cmH(2)O plus 5 cmH(2)O to 40 cmH(2)O or fatigue. Inspiratory Time increased during loads. Total and compartmental volumes increased with different regions, changing at different loads. These changes in volume occur earlier in women (20 cmH(2)O) than in men (30 cmH(2)O). The predominant activity frequency of Sternocleidmastoid muscle decreased at 30 cmH(2)O, while Diaphragm activity decreased at 40 cmH(2)O. The acute effects of incremental inspiratory loads are increases of total and regional volumes and inspiratory time. As for muscle activity, the predominant activity frequency declined in Sternocleidomastoid and Diaphragm muscles, but at different loads. Such respiratory and SEMG patterns and gender differences should be considered when clinical interventions are performed. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Inter-compartmental transport of organophosphate and pyrethroid pesticides in South China: implications for a regional risk assessment.

    Science.gov (United States)

    Li, Huizhen; Wei, Yanli; Lydy, Michael J; You, Jing

    2014-07-01

    The dynamic flux of an organophosphate and four pyrethroid pesticides was determined in an air-(soil)-water-sediment system based on monitoring data from Guangzhou, China. The total air-water flux, including air-water gaseous exchange and atmospheric deposition, showed deposition from air to water for chlorpyrifos, bifenthrin and cypermethrin, but volatilization for lambda-cyhalothrin and permethrin. The transport of the pesticides from overlying water to sediment suggested that sediment acted as a sink for the pesticides. Additionally, distinct annual atmospheric depositional fluxes between legacy and current-use pesticides suggested the role of consumer usage in their transport throughout the system. Finally, pesticide toxicity was estimated from annual air-water-sediment flux within an urban stream in Guangzhou. A dynamic flux-based risk assessment indicated that inter-compartmental transport of chlorpyrifos decreased its atmospheric exposure, but had little influence on its aquatic toxicity. Instead, water-to-sediment transport of pyrethroids increased their sediment toxicity, which was supported by previously reported toxicity data. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. The effect of boron deficiency on gene expression and boron compartmentalization in sugarbeet

    Science.gov (United States)

    NIP5, BOR1, NIP6, and WRKY6 genes were investigated for their role in boron deficiency in sugar beet, each with a proposed role in boron use in model plant species. All genes showed evidence of polymorphism in fragment size and gene expression in the target genomic DNA and cDNA libraries, with no co...

  20. Compartmentalized Microfluidic Platforms: The Unrivaled Breakthrough of In Vitro Tools for Neurobiological Research.

    Science.gov (United States)

    Neto, Estrela; Leitão, Luís; Sousa, Daniela M; Alves, Cecília J; Alencastre, Inês S; Aguiar, Paulo; Lamghari, Meriem

    2016-11-16

    Microfluidic technology has become a valuable tool to the scientific community, allowing researchers to study fine cellular mechanisms with higher variable control compared with conventional systems. It has evolved tremendously, and its applicability and flexibility made its usage grow exponentially and transversely to several research fields. This has been particularly noticeable in neuroscience research, where microfluidic platforms made it possible to address specific questions extending from axonal guidance, synapse formation, or axonal transport to the development of 3D models of the CNS to allow pharmacological testing and drug screening. Furthermore, the continuous upgrade of microfluidic platforms has allowed a deeper study of the communication occurring between different neuronal and glial cells or between neurons and other peripheral tissues, both in physiological and pathological conditions. Importantly, the evolution of microfluidic technology has always been accompanied by the development of new computational tools addressing data acquisition, analysis, and modeling. Copyright © 2016 the authors 0270-6474/16/3611573-12$15.00/0.

  1. The TNO gastro-intestinal model (TIM)

    NARCIS (Netherlands)

    Minekus, M.

    2015-01-01

    The TNO Gastro–Intestinal Model (TIM) is a multi–compartmental model, designed to realistically simulate conditions in the lumen of the gastro–intestinal tract. TIM is successfully used to study the gastro–intestinal behavior of a wide variety of feed, food and pharmaceutical products. Experiments

  2. The Effect of Compartmental Asymmetry on the Monitoring of Pulmonary Mechanics and Lung Volumes.

    Science.gov (United States)

    Keenan, Joseph C; Cortes-Puentes, Gustavo A; Adams, Alexander B; Dries, David J; Marini, John J

    2016-11-01

    Esophageal pressure measurement for computation of transpulmonary pressure (P tp ) has begun to be incorporated into clinical use for evaluating forces across the lungs. Gaps exist in our understanding of how esophageal pressure (and therefore P tp ), a value measured at a single site, responds when respiratory system compartments are asymmetrically affected by whole-lung atelectasis or unilateral injury as well as changes in chest wall compliance. We reasoned that P tp would track with aerated volume changes as estimated by functional residual capacity (FRC) and tidal volume. We examined this hypothesis in the setting of asymmetric lungs and changes in intra-abdominal pressure. This study was conducted in the animal laboratory of a university-affiliated hospital. Models of unilateral atelectasis and unilateral and bilateral lung injury exposed to intra-abdominal hypertension (IAH) in 10 deeply sedated mechanically ventilated swine. Atelectasis was created by balloon occlusion of the left main bronchus. Unilateral lung injury was induced by saline lavage of isolated right lung. Diffuse lung injury was induced by saline lavage of both lungs. The peritoneum was insufflated with air to create a model of pressure-regulated IAH. We measured esophageal pressures, airway pressures, FRC by gas dilution, and oxygenation. FRC was reduced by IAH in normal lungs (P lung pathologies (P lung injury (P = .003) as well as unilateral atelectasis (P = .019). In the setting of both lung injury models, end-expiratory P tp showed a moderate correlation in tracking with FRC. P tp tracks with aerated lung volume in the setting of thoracic asymmetry and changes in intra-abdominal pressure. However, used alone, it cannot distinguish the relative contributions of air-space distention and recruitment of lung units. Copyright © 2016 by Daedalus Enterprises.

  3. A Compartmental Analysis for Morphine and Its Metabolites in Young Children After a Single Oral Dose.

    Science.gov (United States)

    Velez de Mendizabal, Nieves; Jimenez-Mendez, Ricardo; Cooke, Erin; Montgomery, Carolyne J; Dawes, Joy; Rieder, Michael J; Aleksa, Katarina; Koren, Gideon; Jacobo-Cabral, Carlos O; Gonzalez-Ramirez, Rodrigo; Castañeda-Hernandez, Gilberto; Carleton, Bruce C

    2015-10-01

    Currently, the majority of the surgical procedures performed in paediatric hospitals are done on a day care basis, with post-operative pain being managed by caregivers at home. Pain after discharge of these post-operative children has historically been managed with oral codeine in combination with paracetamol (acetaminophen). Codeine is an opioid, which elicits its analgesic effects via metabolism to morphine and codeine-6-glucuronide. Oral morphine is a feasible alternative for outpatient analgesia; however, the pharmacokinetics of morphine after oral administration have been previously described only sparsely, and there is little information in healthy children. The clinical trial included 40 children from 2 to 6 years of age, with an American Society of Anaesthesiologists physical status classification of 1 or 2, who were undergoing surgical procedures requiring opioid analgesia. Morphine was orally administered prior to surgery in one of three doses: 0.1 mg/kg, 0.2 mg/kg and 0.3 mg/kg. Blood samples were collected for plasma morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) concentrations at 30, 60, 90, 120, 180 and 240 min after administration. All analyses were performed with the non-linear mixed-effect modelling software NONMEM version 7.2, using the first-order conditional estimation (FOCE) method. A pharmacokinetic model was developed to simultaneously describe the plasma profiles of morphine and its metabolites M3G and M6G after a single dose of oral morphine in young children (2-6 years of age). The disposition of morphine, M3G and M6G in plasma was best described by a one-compartment model. M3G and M6G metabolite formation was best described by a delay transit compartment, indicating a delay in the appearance of these two major metabolites. This model provides a foundation on which to further evaluate the use of oral morphine and its safety in young children. Longer follow-up time for morphine oral doses and incorporation of

  4. Compartmental and noncompartmental modeling of 13C-lycopene absorption, isomerization, and distribution kinetics in healthy adults

    Science.gov (United States)

    Lycopene is a red carotenoid found in tomatoes hypothesized to mediate disease preventive effects associated with tomato consumption. Lycopene is consumed primarily as the all-trans geometric isomer in foods, while human plasma and tissues demonstrate greater proportions of cis isomers. The objecti...

  5. Adaptive learning in a compartmental model of visual cortex - how feedback enables stable category learning and refinement

    Directory of Open Access Journals (Sweden)

    Georg eLayher

    2014-12-01

    Full Text Available The categorization of real world objects is often reflected in the similarity of their visual appearances. Such categories of objects do not necessarily form disjunct sets of objects, neither semantically nor visually. The relationship between categories can often be described in terms of a hierarchical structure. For instance, tigers and leopards build two separate mammalian categories, but both belong to the category of felines. In other words, tigers and leopards are subcategories of the category Felidae. In the last decades, the unsupervised learning of categories of visual input stimuli has been addressed by numerous approaches in machine learning as well as in the computational neurosciences. However, the question of what kind of mechanisms might be involved in the process of subcategory learning, or category refinement, remains a topic of active investigation. We propose a recurrent computational network architecture for the unsupervised learning of categorial and subcategorial visual input representations. During learning, the connection strengths of bottom-up weights from input to higher-level category representations are adapted according to the input activity distribution. In a similar manner, top-down weights learn to encode the characteristics of a specific stimulus category. Feedforward and feedback learning in combination realize an associative memory mechanism, enabling the selective top-down propagation of a category's feedback weight distribution. We suggest that the difference between the expected input encoded in the projective field of a category node and the current input pattern controls the amplification of feedforward-driven representations. Large enough differences trigger the recruitment of new representational resources and the establishment of (sub- category representations. We demonstrate the temporal evolution of such learning and show how the approach successully establishes category and subcategory representations.

  6. Compartmentalized activities of the pyruvate dehydrogenase complex sustain lipogenesis in prostate cancer.

    Science.gov (United States)

    Chen, Jingjing; Guccini, Ilaria; Mitri, Diletta Di; Brina, Daniela; Revandkar, Ajinkya; Sarti, Manuela; Pasquini, Emiliano; Alajati, Abdullah; Pinton, Sandra; Losa, Marco; Civenni, Gianluca; Catapano, Carlo V; Sgrignani, Jacopo; Cavalli, Andrea; D'Antuono, Rocco; Asara, John M; Morandi, Andrea; Chiarugi, Paola; Crotti, Sara; Agostini, Marco; Montopoli, Monica; Masgras, Ionica; Rasola, Andrea; Garcia-Escudero, Ramon; Delaleu, Nicolas; Rinaldi, Andrea; Bertoni, Francesco; Bono, Johann de; Carracedo, Arkaitz; Alimonti, Andrea

    2018-02-01

    The mechanisms by which mitochondrial metabolism supports cancer anabolism remain unclear. Here, we found that genetic and pharmacological inactivation of pyruvate dehydrogenase A1 (PDHA1), a subunit of the pyruvate dehydrogenase complex (PDC), inhibits prostate cancer development in mouse and human xenograft tumor models by affecting lipid biosynthesis. Mechanistically, we show that in prostate cancer, PDC localizes in both the mitochondria and the nucleus. Whereas nuclear PDC controls the expression of sterol regulatory element-binding transcription factor (SREBF)-target genes by mediating histone acetylation, mitochondrial PDC provides cytosolic citrate for lipid synthesis in a coordinated manner, thereby sustaining anabolism. Additionally, we found that PDHA1 and the PDC activator pyruvate dehydrogenase phosphatase 1 (PDP1) are frequently amplified and overexpressed at both the gene and protein levels in prostate tumors. Together, these findings demonstrate that both mitochondrial and nuclear PDC sustain prostate tumorigenesis by controlling lipid biosynthesis, thus suggesting this complex as a potential target for cancer therapy.

  7. Zika Virus Tissue and Blood Compartmentalization in Acute Infection of Rhesus Macaques.

    Science.gov (United States)

    Coffey, Lark L; Pesavento, Patricia A; Keesler, Rebekah I; Singapuri, Anil; Watanabe, Jennifer; Watanabe, Rie; Yee, JoAnn; Bliss-Moreau, Eliza; Cruzen, Christina; Christe, Kari L; Reader, J Rachel; von Morgenland, Wilhelm; Gibbons, Anne M; Allen, A Mark; Linnen, Jeff; Gao, Kui; Delwart, Eric; Simmons, Graham; Stone, Mars; Lanteri, Marion; Bakkour, Sonia; Busch, Michael; Morrison, John; Van Rompay, Koen K A

    2017-01-01

    Animal models of Zika virus (ZIKV) are needed to better understand tropism and pathogenesis and to test candidate vaccines and therapies to curtail the pandemic. Humans and rhesus macaques possess similar fetal development and placental biology that is not shared between humans and rodents. We inoculated 2 non-pregnant rhesus macaques with a 2015 Brazilian ZIKV strain. Consistent with most human infections, the animals experienced no clinical disease but developed short-lived plasma viremias that cleared as neutralizing antibody developed. In 1 animal, viral RNA (vRNA) could be detected longer in whole blood than in plasma. Despite no major histopathologic changes, many adult tissues contained vRNA 14 days post-infection with highest levels in hemolymphatic tissues. These observations warrant further studies to investigate ZIKV persistence and its potential clinical implications for transmission via blood products or tissue and organ transplants.

  8. Zika Virus Tissue and Blood Compartmentalization in Acute Infection of Rhesus Macaques.

    Directory of Open Access Journals (Sweden)

    Lark L Coffey

    Full Text Available Animal models of Zika virus (ZIKV are needed to better understand tropism and pathogenesis and to test candidate vaccines and therapies to curtail the pandemic. Humans and rhesus macaques possess similar fetal development and placental biology that is not shared between humans and rodents. We inoculated 2 non-pregnant rhesus macaques with a 2015 Brazilian ZIKV strain. Consistent with most human infections, the animals experienced no clinical disease but developed short-lived plasma viremias that cleared as neutralizing antibody developed. In 1 animal, viral RNA (vRNA could be detected longer in whole blood than in plasma. Despite no major histopathologic changes, many adult tissues contained vRNA 14 days post-infection with highest levels in hemolymphatic tissues. These observations warrant further studies to investigate ZIKV persistence and its potential clinical implications for transmission via blood products or tissue and organ transplants.

  9. Peptidases Compartmentalized to the Ascaris suum Intestinal Lumen and Apical Intestinal Membrane

    Science.gov (United States)

    Rosa, Bruce A.

    2015-01-01

    The nematode intestine is a tissue of interest for developing new methods of therapy and control of parasitic nematodes. However, biological details of intestinal cell functions remain obscure, as do the proteins and molecular functions located on the apical intestinal membrane (AIM), and within the intestinal lumen (IL) of nematodes. Accordingly, methods were developed to gain a comprehensive identification of peptidases that function in the intestinal tract of adult female Ascaris suum. Peptidase activity was detected in multiple fractions of the A. suum intestine under pH conditions ranging from 5.0 to 8.0. Peptidase class inhibitors were used to characterize these activities. The fractions included whole lysates, membrane enriched fractions, and physiological- and 4 molar urea-perfusates of the intestinal lumen. Concanavalin A (ConA) was confirmed to bind to the AIM, and intestinal proteins affinity isolated on ConA-beads were compared to proteins from membrane and perfusate fractions by mass spectrometry. Twenty-nine predicted peptidases were identified including aspartic, cysteine, and serine peptidases, and an unexpectedly high number (16) of metallopeptidases. Many of these proteins co-localized to multiple fractions, providing independent support for localization to specific intestinal compartments, including the IL and AIM. This unique perfusion model produced the most comprehensive view of likely digestive peptidases that function in these intestinal compartments of A. suum, or any nematode. This model offers a means to directly determine functions of these proteins in the A. suum intestine and, more generally, deduce the wide array functions that exist in these cellular compartments of the nematode intestine. PMID:25569475

  10. Further analysis of open-respirometry systems: an a-compartmental mechanistic approach

    Directory of Open Access Journals (Sweden)

    Chaui-Berlinck J.G.

    2000-01-01

    Full Text Available A system is said to be "instantaneous" when for a given constant input an equilibrium output is obtained after a while. In the meantime, the output is changing from its initial value towards the equilibrium one. This is the transient period of the system and transients are important features of open-respirometry systems. During transients, one cannot compute the input amplitude directly from the output. The existing models (e.g., first or second order dynamics cannot account for many of the features observed in real open-respirometry systems, such as time lag. Also, these models do not explain what should be expected when a system is speeded up or slowed down. The purpose of the present study was to develop a mechanistic approach to the dynamics of open-respirometry systems, employing basic thermodynamic concepts. It is demonstrated that all the main relevant features of the output dynamics are due to and can be adequately explained by a distribution of apparent velocities within the set of molecules travelling along the system. The importance of the rate at which the molecules leave the sensor is explored for the first time. The study approaches the difference in calibrating a system with a continuous input and with a "unit impulse": the former truly reveals the dynamics of the system while the latter represents the first derivative (in time of the former and, thus, cannot adequately be employed in the apparent time-constant determination. Also, we demonstrate why the apparent order of the output changes with volume or flow.

  11. Elevated compartmentalization of Na+ into vacuoles improves salt and cold stress tolerance in sweet potato (Ipomoea batatas).

    Science.gov (United States)

    Fan, Weijuan; Deng, Gaifang; Wang, Hongxia; Zhang, Hongxia; Zhang, Peng

    2015-08-01

    Salinity and low temperature are the main limiting factors for sweet potato (Ipomoea batatas) growth and agricultural productivity. Various studies have shown that plant NHX-type antiporter plays a crucial role in regulating plant tolerance to salt stress by intracellular Na(+) compartmentalization. The Arabidopsis thaliana AtNHX1 gene that encodes a vacuolar Na(+) /H(+) antiporter was introduced into the sweet potato cultivar Xushu-22 by Agrobacterium-mediated transformation to confer abiotic stress tolerance. Stable insertion of AtNHX1 into the sweet potato genome and its expression was confirmed by Southern blot and reverse transcription-polymerase chain reaction (RT-PCR). A remarkably higher Na(+) /H(+) exchange activity of tonoplast membrane from transgenic sweet potato lines (NOE) in comparison with wild-type (WT) plants confirmed the vacuolar antiporter function in mediating Na(+) /H(+) exchange. Under salt stress, NOE plants accumulated higher Na(+) and K(+) levels in their tissues compared with WT plants, maintaining high K(+) /Na(+) ratios. Consequently, NOE plants showed enhanced protection against cell damage due to the increased proline accumulation, preserved cell membrane integrity, enhanced reactive oxygen species (ROS) scavenging (e.g. increased superoxide dismutase activity), and reduced H2 O2 and malondialdehyde (MDA) production. Moreover, the transgenic plants showed improved cold tolerance through multiple mechanisms of action, revealing the first molecular evidence for NHX1 function in cold response. The transgenic plants showed better biomass production and root yield under stressful conditions. These findings demonstrate that overexpressing AtNHX1 in sweet potato renders the crop tolerant to both salt and cold stresses, providing a greater capacity for the use of AtNHX1 in improving crop performance under combined abiotic stress conditions. © 2014 Scandinavian Plant Physiology Society.

  12. Compartmentalized self-replication (CSR) selection of Thermococcus litoralis Sh1B DNA polymerase for diminished uracil binding.

    Science.gov (United States)

    Tubeleviciute, Agne; Skirgaila, Remigijus

    2010-08-01

    The thermostable archaeal DNA polymerase Sh1B from Thermococcus litoralis has a typical uracil-binding pocket, which in nature plays an essential role in preventing the accumulation of mutations caused by cytosine deamination to uracil and subsequent G-C base pair transition to A-T during the genomic DNA replication. The uracil-binding pocket recognizes and binds uracil base in a template strand trapping the polymerase. Since DNA replication stops, the repair systems have a chance to correct the promutagenic event. Archaeal family B DNA polymerases are employed in various PCR applications. Contrary to nature, in PCR the uracil-binding property of archaeal polymerases is disadvantageous and results in decreased DNA amplification yields and lowered sensitivity. Furthermore, in diagnostics qPCR, RT-qPCR and end-point PCR are performed using dNTP mixtures, where dTTP is partially or fully replaced by dUTP. Uracil-DNA glycosylase treatment and subsequent heating of the samples is used to degrade the DNA containing uracil and prevent carryover contamination, which is the main concern in diagnostic laboratories. A thermostable archaeal DNA polymerase with the abolished uracil binding would be a highly desirable and commercially interesting product. An attempt to disable uracil binding in DNA polymerase Sh1B from T. litoralis by generating site-specific mutants did not yield satisfactory results. However, a combination of random mutagenesis of the whole polymerase gene and compartmentalized self-replication was successfully used to select variants of thermostable Sh1B polymerase capable of performing PCR with dUTP instead of dTTP.

  13. Morphological features, distribution and compartmental organization of the nicotinamide adenine dinucleotide phosphate reduced-diaphorase interneurons in the human striatum.

    Science.gov (United States)

    Bernácer, Javier; Prensa, Lucía; Giménez-Amaya, José Manuel

    2005-08-29

    Striatal nicotinamide adenine dinucleotide phosphate reduced-diaphorase (NADPH-d)-positive (+) cells are one of the major classes of striatal interneurons. The present study analyzes their somatodendritic morphology, distribution pattern, and compartmental organization in the caudate nucleus (CN) and putamen (Put) of nine normal human brains. The following striatal territories are examined: 1) the precommissural head of the CN; 2) the postcommissural head of the CN; 3) the body of the CN; 4) the gyrus of the CN; 5) the tail of the CN; 6) the precommissural Put; and 7) the postcommissural Put. Three morphologically distinct types of NADPH-d+ neurons were found in each of these territories. The two most common NADPH-d+ neurons displayed an ovoid or triangular perikaryon from which several thick primary dendrites emerged, although much less numerous, bipolar-shaped NADPH-d+ cells were also observed. The highest density of NADPH-d+ neurons was found in the gyrus of the CN, followed by the body of the CN, tail of the CN, postcommissural head of the CN, postcommissural Put, precommissural head of the CN, and precommissural Put. The matrix was the striatal compartment with the densest NADPH-d+ neuronal population. Some of these cells also occurred in the center and peripheral regions of the striosomes located in the head of the CN and in the Put. In the body and gyrus of the CN, the striosomes were largely devoid of these striatal interneurons. Knowledge of the density and distribution of these interneurons should advance our understanding of the organization of the normal human striatum and help to evaluate the effects of neurodegenerative processes on cell density. (c) 2005 Wiley-Liss, Inc.

  14. Gait analysis of patients with an off-the-shelf total knee replacement versus customized bi-compartmental knee replacement.

    Science.gov (United States)

    Wang, Henry; Foster, Jonathan; Franksen, Natasha; Estes, Jill; Rolston, Lindsey

    2017-09-04

    Newer TKR designs have been introduced to the market with the aim of overcoming common sizing problems with older TKR designs. Furthermore, since a sizable percentage of patients with OA present with disease limited to the medial/lateral knee compartment in addition to the patellofemoral joint, for whom, a customized bi-compartmental knee replacement (BKR) is available as a treatment option. To date, there is very little information regarding knee strength and mechanics during gait for patients implanted with these modern TKR and BKR designs. The purpose of the study was to evaluate knee strength and mechanics during walking for patients with either a modern off the shelf TKR or a customized BKR and compare these findings to a cohort of healthy controls. Twelve healthy controls, eight BKR, and nine TKR patients participated in the study. Maximal isometric knee strength was evaluated. 3D kinematic and kinetic analyses were conducted for level walking. The TKR knee exhibited less peak extensor torque when compared to, both the BKR and control limbs (p < 0.05). The TKR knee had less extensor moment at stance than both the BKR and control knees (p < 0.05). Both the BKR and control knees displayed larger internal rotation at stance than that of the TKR knee (p < 0.05). This study suggests that, for patients that exhibit isolated OA of the tibiofemoral joint, using a customized BKR implant is a viable treatment option and may contribute to superior mechanical advantages.

  15. Compartmental analysis of asialoglycoprotein receptor scintigraphy for quantitative measurement of liver function: a multicentre study

    Energy Technology Data Exchange (ETDEWEB)

    Ha-Kawa, Sang Kil [Department of Radiology, Kansai Medical University (Japan); Tanaka, Yoshimasa [Department of Radiology, Kansai Medical University (Japan); Hasebe, Shin [Department of Radiology, Fujigaoka Hospital, Showa University (Japan); Kuniyasu, Yoshio [Department of Radiology, Fujigaoka Hospital, Showa University (Japan); Koizumi, Kiyoshi [Department of Radiology, Yamanashi Medical University (Japan); Ishii, Yasushi [Department of Radiology, Fukui Medical School (Japan); Yamamoto, Kazutaka [Department of Radiology, Fukui Medical School (Japan); Kashiwagi, Toru [Department of Internal Medicine, Osaka Koseinennkin Hospital (Japan); Ito, Akihiko [Department of Internal Medicine, Osaka Koseinennkin Hospital (Japan); Kudo, Masatoshi [Division of Gastroenterology, Kobe City General Hospital (Japan); Ikekubo, Katsuji [Department of Nuclear Medicine, Kobe City General Hospital (Japan); Tsuda, Takaharu [Department of Radiology, Ehime University School of Medicine (Japan); Murase, Kenya [Department of Radiology, Ehime University School of Medicine (Japan)

    1997-02-01

    A multicentre study on multicompartmental analysis of hepatic scintigraphy using technetium-99m labelled galactosyl serum albumin (GSA), which binds to the asialoglycoprotein receptor, was carried out at seven institutions in Japan. Seventy-four patients with liver disease received 3 mg (185 MBq) of {sup 99m}Tc-GSA by intravenous injection. Sequential scanning was performed 30 min after injection to obtain anterior images of the heart and liver, followed by single-photon emission tomography (SPET). The indices included in this analysis were hepatic blood flow (Q) and maximal receptor binding rate (R{sub max}), which showed a good correlation with semiquantitative ratio indices for {sup 99m}Tc-GSA, namely the retention rate in blood (HH15) and the hepatic uptake rate (LHL15). Q and R{sub max}also showed a significant correlation with other measures of hepatic function. When patients were grouped according to the severity of chronic liver damage (hepatocellular functional damage), Q was reduced in the moderate and severe groups, while R {sub max}was reduced in proportion to the functional stage. Both parameters showed no inter-institution difference using analysis of co-variance with the functional stage as a co-variant. With regard to the hepatic uptake rate, anterior planar images and SPET images gave similar results for Q and R {sub max}. Acquisition times of 15 or 30 min provided the same results. The multicompartmental model analysis permitted comparable results to be obtained at institutions using different gamma cameras, and is therefore considered a universally applicable method. These results indicate that Q and R {sub max}are useful general indices for evaluating the functional reserve capacity of the liver. (orig.). With 8 figs., 2 tabs.

  16. Analysis of a Mathematical Model to Investigate the Dynamics of ...

    African Journals Online (AJOL)

    In this paper, we formulated a compartmental model to investigate the dynamics of dengue fever in a population with some measure of disease control. We qualitatively and quantitatively analyzed the model and found that the model has a disease free equilibrium (DFE), an endemic equilibrium point and undergoes the ...

  17. Analysis of a Mathematical Model to Investigate the Dynamics of ...

    African Journals Online (AJOL)

    ADOWIE PERE

    ABSTRACT: In this paper, we formulated a compartmental model to investigate the dynamics of dengue fever in a population with some measure of disease control. We qualitatively and quantitatively analyzed the model and found that the model has a disease free equilibrium. (DFE), an endemic equilibrium point and ...

  18. A compartmental approach to the mechanism of calcification in hermatypic corals

    Science.gov (United States)

    TambuttÉ; Allemand; Mueller; Jaubert

    1996-01-01

    Ca2+ compartments, Ca2+ transport and the calcification process were studied by using 45Ca as a tracer. The biological model used was clones of Stylophora pistillata developed into microcolonies whose skeleton is entirely covered by tissues, thus avoiding direct radioisotope exchange between the sea water and the skeleton. The study of Ca2+ compartments was performed by measuring two complementary parameters: Ca2+ influx and Ca2+ efflux kinetics. Kinetic analysis of 45Ca uptake revealed three exchangeable and one non-exchangeable Ca2+ compartments in these microcolonies. The first compartment was saturable with a short half-time (4 min), correlated to external Ca2+ concentration and insensitive to metabolic or ion transport inhibitors. This compartment (72.88 nmol Ca2+ mg-1 protein) has been previously attributed to sea water present in the coelenteron. The second Ca2+ compartment (7.12 nmol Ca2+ mg-1 protein) was soluble in NaOH, saturable with a half-time of 20 min and displayed a combination of Michaelis-Menten kinetics and diffusional entry. It was insensitive to a variety of inhibitors but its loading was stimulated by Ca2+ channel inhibitors. On the basis of uptake experiments, the existence of a third compartment with a rapid turnover rate (about 2 min) and a very small size is predicted. It is suggested that this compartment corresponds to the calicoblastic epithelium. Ca2+ flux through this compartment was facilitated by voltage-dependent Ca2+ channels (with L-type characteristics) and Ca2+-ATPase and was coupled to an anion carrier. Transcellular Ca2+ movement was dependent on the cytoskeleton. The rate of Ca2+ flux across this epithelium was about 975 pmol mg-1 protein min-1. The fourth calcium compartment, corresponding to the skeleton, was soluble in HCl and non-exchangeable. After a short lag phase (about 2 min), the rate of Ca2+ deposition was linear over a period of at least 5 h. The calcification rate was 975 pmol mg-1 protein h-1 at an irradiance

  19. Going Multi-viral: Synthedemic Modelling of Internet-based Spreading Phenomena

    Directory of Open Access Journals (Sweden)

    Marily Nika

    2015-02-01

    Full Text Available Epidemics of a biological and technological nature pervade modern life. For centuries, scientific research focused on biological epidemics, with simple compartmental epidemiological models emerging as the dominant explanatory paradigm. Yet there has been limited translation of this effort to explain internet-based spreading phenomena. Indeed, single-epidemic models are inadequate to explain the multimodal nature of complex phenomena. In this paper we propose a novel paradigm for modelling internet-based spreading phenomena based on the composition of multiple compartmental epidemiological models. Our approach is inspired by Fourier analysis, but rather than trigonometric wave forms, our components are compartmental epidemiological models. We show results on simulated multiple epidemic data, swine flu data and BitTorrent downloads of a popular music artist. Our technique can characterise these multimodal data sets utilising a parsimonous number of subepidemic models.

  20. Subcellular compartmentalization of Cd and Zn in two bivalves. I. Significance of metal-sensitive fractions (MSF) and biologically detoxified metal (BDM)

    Science.gov (United States)

    Wallace, W.G.; Lee, B.-G.; Luoma, S.N.

    2003-01-01

    Many aspects of metal accumulation in aquatic invertebrates (i.e. toxicity, tolerance and trophic transfer) can be understood by examining the subcellular partitioning of accumulated metal. In this paper, we use a compartmentalization approach to interpret the significance of metal, species and size dependence in the subcellular partitioning of Cd and Zn in the bivalves Macoma balthica and Potamocorbula amurensis. Of special interest is the compartmentalization of metal as metal-sensitive fractions (MSF) (i.e. organelles and heat-sensitive proteins, termed 'enzymes' hereafter) and biologically detoxified metal (BDM) (i.e. metallothioneins [MT] and metal-rich granules [MRG]). Clams from San Francisco Bay, CA, were exposed for 14 d to seawater (20??? salinity) containing 3.5 ??g l-1 Cd and 20.5 ??g l-1 Zn, including 109Cd and 65Zn as radiotracers. Uptake was followed by 21 d of depuration. The subcellular partitioning of metal within clams was examined following exposure and loss. P. amurensis accumulated ???22x more Cd and ???2x more Zn than M. balthica. MT played an important role in the storage of Cd in P. amurensis, while organelles were the major site of Zn accumulation. In M. balthica, Cd and Zn partitioned similarly, although the pathway of detoxification was metal-specific (MRG for Cd; MRG and MT for Zn). Upon loss, M. balthica depurated ???40% of Cd with Zn being retained; P. amurensis retained Cd and depurated Zn (???40%). During efflux, Cd and Zn concentrations in the MSF compartment of both clams declined with metal either being lost from the animal or being transferred to the BDM compartment. Subcellular compartmentalization was also size-dependent, with the importance of BDM increasing with clam size; MSF decreased accordingly. We hypothesized that progressive retention of metal as BDM (i.e. MRG) with age may lead to size dependency of metal concentrations often observed in some populations of M. balthica.

  1. The assembly of metals chelation by thiols and vacuolar compartmentalization conferred increased tolerance to and accumulation of cadmium and arsenic in transgenic Arabidopsis thaliana

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Jiangbo [Key Laboratory of Plant Resources, Institute of Botany, The Chinese Academy of Sciences, Beijing 100093 (China); Inner Mongolia Key Laboratory of Biomass-Energy Conversion, The Institute of Bioengineering and Technology, Inner Mongolia University of Science and Technology, Baotou 040100 (China); Xu, Wenzhong [Key Laboratory of Plant Resources, Institute of Botany, The Chinese Academy of Sciences, Beijing 100093 (China); Ma, Mi, E-mail: mami@ibcas.ac.cn [Key Laboratory of Plant Resources, Institute of Botany, The Chinese Academy of Sciences, Beijing 100093 (China)

    2012-01-15

    Highlights: Black-Right-Pointing-Pointer Simultaneous transformation of AsPCS1 and ScYCF1 into Arabidopsis thaliana which is sensitive to heavy metals, leads to transgenic plants tolerant to Arsenic and cadmium. Black-Right-Pointing-Pointer Dual-gene transgenic Arabidopsis showed higher accumulation of Arsenic and cadmium than single and non-transgenic plants. Black-Right-Pointing-Pointer Our results proved that improved thiol peptides synthesis and vacuolar compartmentation in plant dramatically boosted the survival rates of plants when exposed to heavy metals. Black-Right-Pointing-Pointer A new strategy for efficient phytoremediation of heavy metals by stacking genes transformation in plants was developed in this article. - Abstract: Transgenic Arabidopsis thaliana were developed to increase tolerance for and accumulation of heavy metals and metalloids by simultaneous overexpression of AsPCS1 and YCF1 (derived from garlic and baker's yeast) based on the fact that chelation of metals and vacuolar compartmentalization are the main strategies for heavy metals/metalloids detoxification and tolerance in plants. Dual-gene transgenic lines had the longest roots and the highest accumulation of Cd and As than single-gene transgenic lines and wildtype. When grown on cadmium or arsenic (arsenite/arsenate), Dual-gene transgenic lines accumulated over 2-10 folds cadmium/arsenite and 2-3 folds arsenate than wild type or plants expressing AsPCS1 or YCF1 alone. Such stacking modified genes involved in chelation of toxic metals and vacuolar compartmentalization represents a highly promising new tool for use in phytoremediation efforts.

  2. The assembly of metals chelation by thiols and vacuolar compartmentalization conferred increased tolerance to and accumulation of cadmium and arsenic in transgenic Arabidopsis thaliana

    International Nuclear Information System (INIS)

    Guo, Jiangbo; Xu, Wenzhong; Ma, Mi

    2012-01-01

    Highlights: ► Simultaneous transformation of AsPCS1 and ScYCF1 into Arabidopsis thaliana which is sensitive to heavy metals, leads to transgenic plants tolerant to Arsenic and cadmium. ► Dual-gene transgenic Arabidopsis showed higher accumulation of Arsenic and cadmium than single and non-transgenic plants. ► Our results proved that improved thiol peptides synthesis and vacuolar compartmentation in plant dramatically boosted the survival rates of plants when exposed to heavy metals. ► A new strategy for efficient phytoremediation of heavy metals by stacking genes transformation in plants was developed in this article. - Abstract: Transgenic Arabidopsis thaliana were developed to increase tolerance for and accumulation of heavy metals and metalloids by simultaneous overexpression of AsPCS1 and YCF1 (derived from garlic and baker's yeast) based on the fact that chelation of metals and vacuolar compartmentalization are the main strategies for heavy metals/metalloids detoxification and tolerance in plants. Dual-gene transgenic lines had the longest roots and the highest accumulation of Cd and As than single-gene transgenic lines and wildtype. When grown on cadmium or arsenic (arsenite/arsenate), Dual-gene transgenic lines accumulated over 2–10 folds cadmium/arsenite and 2–3 folds arsenate than wild type or plants expressing AsPCS1 or YCF1 alone. Such stacking modified genes involved in chelation of toxic metals and vacuolar compartmentalization represents a highly promising new tool for use in phytoremediation efforts.

  3. Metabolic models for methyl and inorganic mercury

    Energy Technology Data Exchange (ETDEWEB)

    Bernard, S.R.; Purdue, P.

    1984-03-01

    Following the outbreak of mercury poisoning in Minimata, Japan (1953-60), much work has been done on the toxicology of mercury - in particular methyl mercury. In this paper, the authors derive two compartmental models for the metabolism of methyl mercury and inorganic mercury based upon the data which have been collected since 1960.

  4. Typing of MRI in medial meniscus degeneration in relation to radiological grade in medial compartmental osteoarthritis of the knee

    Energy Technology Data Exchange (ETDEWEB)

    Nagata, Nobuhito; Koshino, Tomihisa; Saito, Tomoyuki; Sakai, Naotaka; Takagi, Toshitaka; Takeuchi, Ryohei [Yokohama City Univ. (Japan). School of Medicine

    1998-10-01

    The advancement of degeneration of 50 medial menisci in patients with medial compartmental osteoarthritic knees (OA) were evaluated with magnetic resonance imaging (MRI). The average age of the patients was 66.6 years (range, 39 to 86). According to a radiographical grading system, 6 knees were classified as Grade 1, 24 as Grade 2, 16 as Grade 3, and 4 as Grade 4. The extent and the location of a high intensity region in MRI were observed in 3 parts of the meniscus, namely, the anterior, middle and posterior part. In Grade 1, no high intensity region was observed in 3 knees, and a high intensity region was observed only in the posterior part in 2 knees. A high intensity region was observed from the medial to the posterior part in 13 knees, and only in the posterior part in 10 knees of Grade 2; from the medial to the posterior part in 12 knees, and only in the posterior part in 3 knees of Grade 3, and from the anterior to the posterior part in 2 knees of Grade 4. The shape of the high intensity region in the medial meniscus was classified into 5 types, as follows: Type 1, there was no high intensity region; Type 2, the high intensity region was observed to be restricted within the meniscus; Type 3, the high intensity region resembled a horizontal tear; Type 4, the high intensity region was observed as all of the medial joint space without a marginal area; Type 5, the high intensity region was observed as all of the medial joint space. In Grade 1, 3 knees were classified as Type 1, and 2 knees as Type 2; in Grade 2, 7 knees as Type 2, and 13 knees as Type 3, and 4 knees into Type 4; in Grade 3, 6 knees as Type 3, and 7 knees as Type 4; and in Grade 4, 2 knees as Type 4, and 2 knees as Type 5. These findings might suggest that the degeneration of medial meniscus in the medial type of OA was accelerated by mechanical stress due to varus deformity. (author)

  5. HIV-1 tropism testing in subjects achieving undetectable HIV-1 RNA: diagnostic accuracy, viral evolution and compartmentalization.

    Directory of Open Access Journals (Sweden)

    Christian Pou

    Full Text Available BACKGROUND: Technically, HIV-1 tropism can be evaluated in plasma or peripheral blood mononuclear cells (PBMCs. However, only tropism testing of plasma HIV-1 has been validated as a tool to predict virological response to CCR5 antagonists in clinical trials. The preferable tropism testing strategy in subjects with undetectable HIV-1 viremia, in whom plasma tropism testing is not feasible, remains uncertain. METHODS & RESULTS: We designed a proof-of-concept study including 30 chronically HIV-1-infected individuals who achieved HIV-1 RNA <50 copies/mL during at least 2 years after first-line ART initiation. First, we determined the diagnostic accuracy of 454 and population sequencing of gp120 V3-loops in plasma and PBMCs, as well as of MT-2 assays before ART initiation. The Enhanced Sensitivity Trofile Assay (ESTA was used as the technical reference standard. 454 sequencing of plasma viruses provided the highest agreement with ESTA. The accuracy of 454 sequencing decreased in PBMCs due to reduced specificity. Population sequencing in plasma and PBMCs was slightly less accurate than plasma 454 sequencing, being less sensitive but more specific. MT-2 assays had low sensitivity but 100% specificity. Then, we used optimized 454 sequence data to investigate viral evolution in PBMCs during viremia suppression and only found evolution of R5 viruses in one subject. No de novo CXCR4-using HIV-1 production was observed over time. Finally, Slatkin-Maddison tests suggested that plasma and cell-associated V3 forms were sometimes compartmentalized. CONCLUSIONS: The absence of tropism shifts during viremia suppression suggests that, when available, testing of stored plasma samples is generally safe and informative, provided that HIV-1 suppression is maintained. Tropism testing in PBMCs may not necessarily produce equivalent biological results to plasma, because the structure of viral populations and the diagnostic performance of tropism assays may sometimes vary

  6. Typing of MRI in medial meniscus degeneration in relation to radiological grade in medial compartmental osteoarthritis of the knee

    International Nuclear Information System (INIS)

    Nagata, Nobuhito; Koshino, Tomihisa; Saito, Tomoyuki; Sakai, Naotaka; Takagi, Toshitaka; Takeuchi, Ryohei

    1998-01-01

    The advancement of degeneration of 50 medial menisci in patients with medial compartmental osteoarthritic knees (OA) were evaluated with magnetic resonance imaging (MRI). The average age of the patients was 66.6 years (range, 39 to 86). According to a radiographical grading system, 6 knees were classified as Grade 1, 24 as Grade 2, 16 as Grade 3, and 4 as Grade 4. The extent and the location of a high intensity region in MRI were observed in 3 parts of the meniscus, namely, the anterior, middle and posterior part. In Grade 1, no high intensity region was observed in 3 knees, and a high intensity region was observed only in the posterior part in 2 knees. A high intensity region was observed from the medial to the posterior part in 13 knees, and only in the posterior part in 10 knees of Grade 2; from the medial to the posterior part in 12 knees, and only in the posterior part in 3 knees of Grade 3, and from the anterior to the posterior part in 2 knees of Grade 4. The shape of the high intensity region in the medial meniscus was classified into 5 types, as follows: Type 1, there was no high intensity region; Type 2, the high intensity region was observed to be restricted within the meniscus; Type 3, the high intensity region resembled a horizontal tear; Type 4, the high intensity region was observed as all of the medial joint space without a marginal area; Type 5, the high intensity region was observed as all of the medial joint space. In Grade 1, 3 knees were classified as Type 1, and 2 knees as Type 2; in Grade 2, 7 knees as Type 2, and 13 knees as Type 3, and 4 knees into Type 4; in Grade 3, 6 knees as Type 3, and 7 knees as Type 4; and in Grade 4, 2 knees as Type 4, and 2 knees as Type 5. These findings might suggest that the degeneration of medial meniscus in the medial type of OA was accelerated by mechanical stress due to varus deformity. (author)

  7. Analysis of an asymmetric two-strain dengue model.

    NARCIS (Netherlands)

    Kooi, B.W.; Aguiar, M.; Stollenwerk, N.

    2014-01-01

    In this paper we analyse a two-strain compartmental dengue fever model that allows us to study the behaviour of a Dengue fever epidemic. Dengue fever is the most common mosquito-borne viral disease of humans that in recent years has become a major international public health concern. The model is an

  8. Anti-tuberculosis drug combination for controlled oral delivery using 3D printed compartmental dosage forms: From drug product design to in vivo testing.

    Science.gov (United States)

    Genina, Natalja; Boetker, Johan Peter; Colombo, Stefano; Harmankaya, Necati; Rantanen, Jukka; Bohr, Adam

    2017-12-28

    The design and production of an oral dual-compartmental dosage unit (dcDU) was examined in vitro and in vivo with the purpose of physically isolating and modulating the release profile of an anti-tuberculosis drug combination. Rifampicin (RIF) and isoniazid (ISO) are first line combination drugs for treatment of tuberculosis (TB) that negatively interact with each other upon simultaneous release in acidic environment. The dcDUs were designed in silico by computer aided design (CAD) and fabricated in two steps; first three-dimensional (3D) printing of the outer structure, followed by hot-melt extrusion (HME) of the drug-containing filaments. The structure of the fabricated dcDUs was visualized by scanning electron microscopy (SEM). The 3D printed compartmentalized shells were loaded with filaments containing active pharmaceutical ingredient (API) and selectively sealed to modulate drug dissolution. The drug release profile of the dcDUs was characterized by pH-transfer dissolution in vitro and pharmacokinetics studies in rats, and resulted in modified release of the APIs from the dcDUs as compared to the free filaments. Furthermore, the selective physical sealing of the compartments resulted in an effective retardation of the in vitro API release. The findings of this study support the development of controllable-by-design dcDU systems for combination therapies to enable efficient therapeutic translation of oral dosage forms. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. The candidate phylum Poribacteria by single-cell genomics: new insights into phylogeny, cell-compartmentation, eukaryote-like repeat proteins, and other genomic features.

    Directory of Open Access Journals (Sweden)

    Janine Kamke

    Full Text Available The candidate phylum Poribacteria is one of the most dominant and widespread members of the microbial communities residing within marine sponges. Cell compartmentalization had been postulated along with their discovery about a decade ago and their phylogenetic association to the Planctomycetes, Verrucomicrobia, Chlamydiae superphylum was proposed soon thereafter. In the present study we revised these features based on genomic data obtained from six poribacterial single cells. We propose that Poribacteria form a distinct monophyletic phylum contiguous to the PVC superphylum together with other candidate phyla. Our genomic analyses supported the possibility of cell compartmentalization in form of bacterial microcompartments. Further analyses of eukaryote-like protein domains stressed the importance of such proteins with features including tetratricopeptide repeats, leucin rich repeats as well as low density lipoproteins receptor repeats, the latter of which are reported here for the first time from a sponge symbiont. Finally, examining the most abundant protein domain family on poribacterial genomes revealed diverse phyH family proteins, some of which may be related to dissolved organic posphorus uptake.

  10. Are complex DCE-MRI models supported by clinical data?

    DEFF Research Database (Denmark)

    Duan, Chong; Kallehauge, Jesper F; Bretthorst, G Larry

    2016-01-01

    PURPOSE: To ascertain whether complex dynamic contrast enhanced (DCE) MRI tracer kinetic models are supported by data acquired in the clinic and to determine the consequences of limited contrast-to-noise. METHODS: Generically representative in silico and clinical (cervical cancer) DCE-MRI data were...... selection is particularly important when high-order, multiparametric models are under consideration. (Parameters obtained from kinetic modeling of cervical cancer clinical DCE-MRI data showed significant changes at an early stage of radiotherapy.)...... examined. Bayesian model selection evaluated support for four compartmental DCE-MRI models: the Tofts model (TM), Extended Tofts model, Compartmental Tissue Uptake model (CTUM), and Two-Compartment Exchange model. RESULTS: Complex DCE-MRI models were more sensitive to noise than simpler models with respect...

  11. Compartmentation of metals in foliage of Populus tremula grown on soils with mixed contamination. II. Zinc binding inside leaf cell organelles

    Energy Technology Data Exchange (ETDEWEB)

    Vollenweider, Pierre, E-mail: pierre.vollenweider@wsl.c [Swiss Federal Institute for Forest, Snow and Landscape Research (WSL), Zuercherstrasse 111, 8903 Birmensdorf (Switzerland); Bernasconi, Petra [Swiss Federal Institute for Forest, Snow and Landscape Research (WSL), Zuercherstrasse 111, 8903 Birmensdorf (Switzerland); Environmental Protection Office (AfU), Aabachstrasse 5, 6300 Zug (Switzerland); Gautschi, Hans-Peter [Centre for Microscopy and Image Analysis (CMI), University of Zurich, Gloriastrasse 30, 8006 Zuerich (Switzerland); Menard, Terry; Frey, Beat; Guenthardt-Goerg, Madeleine S. [Swiss Federal Institute for Forest, Snow and Landscape Research (WSL), Zuercherstrasse 111, 8903 Birmensdorf (Switzerland)

    2011-01-15

    The phytoextraction potential of plants for removing heavy metals from polluted soils is determined by their capacity to store contaminants in aboveground organs and complex them safely. In this study, the metal compartmentation, elemental composition of zinc deposits and zinc complexation within leaves from poplars grown on soil with mixed metal contamination was analysed combining several histochemical and microanalytical approaches. Zinc was the only heavy metal detected and was stored in several organelles in the form of globoid deposits showing {beta}-metachromasy. It was associated to oxygen anions and different cations, noteworthy phosphorous. The deposit structure, elemental composition and element ratios indicated that zinc was chelated by phytic acid ligands. Maturation processes in vacuolar vs. cytoplasmic deposits were suggested by differences in size and amounts of complexed zinc. Hence, zinc complexation by phytate contributed to metal detoxification and accumulation in foliage but could not prevent toxicity reactions therein. - Zinc contaminants translocated to symplast of aged leaves were detoxified by phytic acid ligands.

  12. Biodegradation of a mixture of the herbicides ametryn, and 2,4-dichlorophenoxyacetic acid (2,4-D) in a compartmentalized biofilm reactor.

    Science.gov (United States)

    Sandoval-Carrasco, Carlos A; Ahuatzi-Chacón, Deifilia; Galíndez-Mayer, Juvencio; Ruiz-Ordaz, Nora; Juárez-Ramírez, Cleotilde; Martínez-Jerónimo, Fernando

    2013-10-01

    In this work, an efficient degradation process for the removal of 2,4-D and ametryn, together with organic and inorganic adjuvants used in the commercial formulations of both herbicides, was developed. Although both compounds are toxic for microbial communities, ametryn is markedly more toxic than 2,4-D. In spite of this, the microbial consortium used could resist loading rates up to 31.5 mg L(-1) d(-1) of ametryn, with removal efficiencies up to 97% for both herbicides. Thus, an alternative use of this consortium could be bioaugmentation, as a tool to protect the structure and function of an activated-sludge biota against ametryn or 2,4-D shock loads. The process was carried out in a lab-scale prototype of aerobic biobarrier constructed as a compartmentalized fixed film reactor with airlift recirculation of oxygenated liquid. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Work-related pain in extrinsic finger extensor musculature of instrumentalists is associated with intracellular pH compartmentation during exercise.

    Directory of Open Access Journals (Sweden)

    Angel Moreno-Torres

    Full Text Available BACKGROUND: Although non-specific pain in the upper limb muscles of workers engaged in mild repetitive tasks is a common occupational health problem, much is unknown about the associated structural and biochemical changes. In this study, we compared the muscle energy metabolism of the extrinsic finger extensor musculature in instrumentalists suffering from work-related pain with that of healthy control instrumentalists using non-invasive phosphorus magnetic resonance spectroscopy ((31P-MRS. We hypothesize that the affected muscles will show alterations related with an impaired energy metabolism. METHODOLOGY/PRINCIPAL FINDINGS: We studied 19 volunteer instrumentalists (11 subjects with work-related pain affecting the extrinsic finger extensor musculature and 8 healthy controls. We used (31P-MRS to find deviations from the expected metabolic response to exercise in phosphocreatine (PCr, inorganic phosphate (Pi, Pi/PCr ratio and intracellular pH kinetics. We observed a reduced finger extensor exercise tolerance in instrumentalists with myalgia, an intracellular pH compartmentation in the form of neutral and acid compartments, as detected by Pi peak splitting in (31P-MRS spectra, predominantly in myalgic muscles, and a strong association of this pattern with the condition. CONCLUSIONS/SIGNIFICANCE: Work-related pain in the finger extrinsic extensor muscles is associated with intracellular pH compartmentation during exercise, non-invasively detectable by (31P-MRS and consistent with the simultaneous energy production by oxidative metabolism and glycolysis. We speculate that a deficit in energy production by oxidative pathways may exist in the affected muscles. Two possible explanations for this would be the partial and/or local reduction of blood supply and the reduction of the muscle oxidative capacity itself.

  14. Compartmentalized localization of 11β-HSD 1 and 2 at the feto-maternal interface in the first trimester of human pregnancy.

    Science.gov (United States)

    Yang, Qianlan; Wang, Wangsheng; Liu, Chao; Wang, Yu; Sun, Kang

    2016-10-01

    Glucocorticoids are engaged in a number of actions at the feto-maternal interface for the establishment of early pregnancy. However, excessive glucocorticoids can be deleterious to fetal development. Therefore, compartmentalized distribution of 11β-hydroxysteroid dehydrogenase 1 and 2 (11β-HSD1 and 2), which regenerates and inactivates cortisol respectively, would ensure an optimal cortisol concentration at the feto-maternal interface for the establishment of early gestation. However, the distribution pattern of 11β-HSD1 and 2 at the feto-maternal interface in early human pregnancy is not clearly defined. Here we showed that 11β-HSD1 distributed extensively on the maternal side including decidual stromal cells and epithelial cells but scarcely on the fetal side except for localization in the fetal blood vessels of the chorionic villi. In contrast, 11β-HSD2 was abundantly localized in syncytial layer of the chorionic villi and the decidual epithelium. In primary cultures, cortisol upregulated not only 11β-HSD1 expression in decidual stromal cells but also 11β-HSD2 expression in villous trophoblasts of early pregnancy. Further studies revealed that cortisol inhibited the expression of interleukin-1β and 6 in decidual stromal cells and villous trophoblasts, and stimulated expression of human chorionic gonadotropin in villous trophoblasts. Collectively, this study has revealed a compartmentalized distribution pattern of 11β-HSD 1 and 2 at the feto-maternal interface, both of which can be upregulated by glucocorticoids, suggesting that a coordinated interaction between 11β-HSD 1 and 2 may exist to ensure an optimal cortisol concentration at discrete locations at the feto-maternal interface for the establishment of early pregnancy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Tracer kinetic model selection for dynamic contrast-enhanced magnetic resonance imaging of locally advanced cervical cancer

    DEFF Research Database (Denmark)

    Kallehauge, Jesper Folsted; Tanderup, Kari; Duan, Chong

    2014-01-01

    conditions the Tofts (TM), extended Tofts (ETM), compartmental tissue uptake model (C-TU) and 2-compartment exchange model (2CXM) were the optimal tracer kinetic models (TKMs) for the analysis of DCE-MRI in patients with cervical cancer. Material and methods. Ten patients with locally advanced cervical...

  16. Sensitivity analysis of a simple linear model of a savanna ecosystem at Nyslvley

    CSIR Research Space (South Africa)

    Getz, WA

    1975-12-01

    Full Text Available The construction of a linear compartmental model of the savanna ecosystem at Nylsvley is discussed. Using crude estimates for the standing crop of the compartments and intercompartmental flow rates the sensitivity of the model to changes in its...

  17. Understanding post-operative temperature drop in cardiac surgery: a mathematical model

    NARCIS (Netherlands)

    Tindall, M. J.; Peletier, M. A.; Severens, N. M. W.; Veldman, D. J.; de Mol, B. A. J. M.

    2008-01-01

    A mathematical model is presented to understand heat transfer processes during the cooling and re-warming of patients during cardiac surgery. Our compartmental model is able to account for many of the qualitative features observed in the cooling of various regions of the body including the central

  18. Cytoplasmic localization of Hug1p, a negative regulator of the MEC1 pathway, coincides with the compartmentalization of Rnr2p–Rnr4p

    International Nuclear Information System (INIS)

    Ainsworth, William B.; Hughes, Bridget Todd; Au, Wei Chun; Sakelaris, Sally; Kerscher, Oliver; Benton, Michael G.; Basrai, Munira A.

    2013-01-01

    Highlights: •Hug1p overexpression sensitizes wild-type cells to DNA damage and hydroxyurea (HU). •Expression of Hug1p in response to HU treatment is delayed relative to Rnr3p. •MEC1 pathway genes are required for cytoplasmic localization of Hug1p. •Hug1p subcellular compartmentalization to the cytoplasm coincides with Rnr2p–Rnr4p. -- Abstract: The evolutionarily conserved MEC1 checkpoint pathway mediates cell cycle arrest and induction of genes including the RNR (Ribonucleotide reductase) genes and HUG1 (Hydroxyurea, ultraviolet, and gamma radiation) in response to DNA damage and replication arrest. Rnr complex activity is in part controlled by cytoplasmic localization of the Rnr2p–Rnr4p subunits and inactivation of negative regulators Sml1p and Dif1p upon DNA damage and hydroxyurea (HU) treatment. We previously showed that a deletion of HUG1 rescues lethality of mec1Δ and suppresses dun1Δ strains. In this study, multiple approaches demonstrate the regulatory response of Hug1p to DNA damage and HU treatment and support its role as a negative effector of the MEC1 pathway. Consistent with our hypothesis, wild-type cells are sensitive to DNA damage and HU when HUG1 is overexpressed. A Hug1 polyclonal antiserum reveals that HUG1 encodes a protein in budding yeast and its MEC1-dependent expression is delayed compared to the rapid induction of Rnr3p in response to HU treatment. Cell biology and subcellular fractionation experiments show localization of Hug1p-GFP to the cytoplasm upon HU treatment. The cytoplasmic localization of Hug1p-GFP is dependent on MEC1 pathway genes and coincides with the cytoplasmic localization of Rnr2p–Rnr4p. Taken together, the genetic interactions, gene expression, and localization studies support a novel role for Hug1p as a negative regulator of the MEC1 checkpoint response through its compartmentalization with Rnr2p–Rnr4p

  19. Cytoplasmic localization of Hug1p, a negative regulator of the MEC1 pathway, coincides with the compartmentalization of Rnr2p–Rnr4p

    Energy Technology Data Exchange (ETDEWEB)

    Ainsworth, William B. [Cain Department of Chemical Engineering, Louisiana State University, Baton Rouge, LA 70803 (United States); Hughes, Bridget Todd; Au, Wei Chun; Sakelaris, Sally [Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Kerscher, Oliver [Biology Department, The College of William and Mary, Williamsburg, VA 23185 (United States); Benton, Michael G., E-mail: benton@lsu.edu [Cain Department of Chemical Engineering, Louisiana State University, Baton Rouge, LA 70803 (United States); Basrai, Munira A., E-mail: basraim@mail.nih.gov [Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2013-10-04

    Highlights: •Hug1p overexpression sensitizes wild-type cells to DNA damage and hydroxyurea (HU). •Expression of Hug1p in response to HU treatment is delayed relative to Rnr3p. •MEC1 pathway genes are required for cytoplasmic localization of Hug1p. •Hug1p subcellular compartmentalization to the cytoplasm coincides with Rnr2p–Rnr4p. -- Abstract: The evolutionarily conserved MEC1 checkpoint pathway mediates cell cycle arrest and induction of genes including the RNR (Ribonucleotide reductase) genes and HUG1 (Hydroxyurea, ultraviolet, and gamma radiation) in response to DNA damage and replication arrest. Rnr complex activity is in part controlled by cytoplasmic localization of the Rnr2p–Rnr4p subunits and inactivation of negative regulators Sml1p and Dif1p upon DNA damage and hydroxyurea (HU) treatment. We previously showed that a deletion of HUG1 rescues lethality of mec1Δ and suppresses dun1Δ strains. In this study, multiple approaches demonstrate the regulatory response of Hug1p to DNA damage and HU treatment and support its role as a negative effector of the MEC1 pathway. Consistent with our hypothesis, wild-type cells are sensitive to DNA damage and HU when HUG1 is overexpressed. A Hug1 polyclonal antiserum reveals that HUG1 encodes a protein in budding yeast and its MEC1-dependent expression is delayed compared to the rapid induction of Rnr3p in response to HU treatment. Cell biology and subcellular fractionation experiments show localization of Hug1p-GFP to the cytoplasm upon HU treatment. The cytoplasmic localization of Hug1p-GFP is dependent on MEC1 pathway genes and coincides with the cytoplasmic localization of Rnr2p–Rnr4p. Taken together, the genetic interactions, gene expression, and localization studies support a novel role for Hug1p as a negative regulator of the MEC1 checkpoint response through its compartmentalization with Rnr2p–Rnr4p.

  20. Compartmentalization of the Coso East Flank geothermal field imaged by 3-D full-tensor MT inversion

    Science.gov (United States)

    Lindsey, Nathaniel J.; Kaven, Joern; Davatzes, Nicholas C.; Newman, Gregory A.

    2017-01-01

    Previous magnetotelluric (MT) studies of the high-temperature Coso geothermal system in California identified a subvertical feature of low resistivity (2–5 Ohm m) and appreciable lateral extent (>1 km) in the producing zone of the East Flank field. However, these models could not reproduce gross 3-D effects in the recorded data. We perform 3-D full-tensor inversion and retrieve a resistivity model that out-performs previous 2-D and 3-D off-diagonal models in terms of its fit to the complete 3-D MT data set as well as the degree of modelling bias. Inclusion of secondary Zxx and Zyy data components leads to a robust east-dip (60†) to the previously identified conductive East Flank reservoir feature, which correlates strongly with recently mapped surface faults, downhole well temperatures, 3-D seismic reflection data, and local microseismicity. We perform synthetic forward modelling to test the best-fit dip of this conductor using the response at a nearby MT station. We interpret the dipping conductor as a fractured and fluidized compartment, which is structurally controlled by an unmapped blind East Flank fault zone.

  1. Compartmentalization of the Coso East Flank geothermal field imaged by 3-D full-tensor MT inversion

    Science.gov (United States)

    Lindsey, Nathaniel J.; Kaven, Joern Ole; Davatzes, Nicholas; Newman, Gregory A.

    2017-02-01

    Previous magnetotelluric (MT) studies of the high-temperature Coso geothermal system in California identified a subvertical feature of low resistivity (2-5 Ohm m) and appreciable lateral extent (>1 km) in the producing zone of the East Flank field. However, these models could not reproduce gross 3-D effects in the recorded data. We perform 3-D full-tensor inversion and retrieve a resistivity model that out-performs previous 2-D and 3-D off-diagonal models in terms of its fit to the complete 3-D MT data set as well as the degree of modelling bias. Inclusion of secondary Zxx and Zyy data components leads to a robust east-dip (60†) to the previously identified conductive East Flank reservoir feature, which correlates strongly with recently mapped surface faults, downhole well temperatures, 3-D seismic reflection data, and local microseismicity. We perform synthetic forward modelling to test the best-fit dip of this conductor using the response at a nearby MT station. We interpret the dipping conductor as a fractured and fluidized compartment, which is structurally controlled by an unmapped blind East Flank fault zone.

  2. Boron compartmentation in roots of sunflower plants of different boron status: A study using the stable isotopes 10B and 11B adopting two independent approaches

    International Nuclear Information System (INIS)

    Pfeffer, H.; Dannel, F.; Roemheld, V.

    2001-01-01

    The intracellular compartmentation of boron (B) in roots of sunflower plants precultured with 100 μM B (high B) or 1 μM B (low B) was studied using two independent approaches. In the first approach, short-term efflux studies using the stable isotopes 11 B and 10 B were carried out. In roots of high B plants, the calculated concentrations of B (nmol g FW -1 ) were 52.6 in the cell wall, 7.5 in the vacuole, 27.1 in the cytosol and 48.0 in the free space. In roots of low B plants, the concentrations of B (nmol g FW -1 ) were 43.4 in the cell wall, 2.8 in the vacuole, 17.9 in the cytosol and almost zero in the free space. Although the B supply differed by a factor 100, the B concentrations in the cytosol and the vacuole of low B plants were 66 and 37% of the respective concentrations in high B plants. This suggests an additional role for B in plant metabolism, besides its function in the cell wall. In the second approach, root B pools (cell sap and water-insoluble residue) were determined for comparison, and found to be in good agreement with the results from the efflux study. (au)

  3. Building America Case Study: Apartment Compartmentalization with an Aerosol-Based Sealing Process - Queens, NY; Technology Solutions for New and Existing Homes, Energy Efficiency & Renewable Energy (EERE)

    Energy Technology Data Exchange (ETDEWEB)

    None

    2015-07-01

    Air sealing of building enclosures is a difficult and time-consuming process. Current methods in new construction require laborers to physically locate small and sometimes large holes in multiple assemblies and then manually seal each of them. The innovation demonstrated under this research study was the automated air sealing and compartmentalization of buildings through the use of an aerosolized sealant, developed by the Western Cooling Efficiency Center at University of California Davis.
    CARB sought to demonstrate this new technology application in a multifamily building in Queens, NY. The effectiveness of the sealing process was evaluated by three methods: air leakage testing of overall apartment before and after sealing, point-source testing of individual leaks, and pressure measurements in the walls of the target apartment during sealing. Aerosolized sealing was successful by several measures in this study. Many individual leaks that are labor-intensive to address separately were well sealed by the aerosol particles. In addition, many diffuse leaks that are difficult to identify and treat were also sealed. The aerosol-based sealing process resulted in an average reduction of 71% in air leakage across three apartments and an average apartment airtightness of 0.08 CFM50/SF of enclosure area.

  4. Nature of rate-limiting steps in a compartmentalized enzyme system. Quantitation of dopamine transport and hydroxylation rates in resealed chromaffin granule ghosts

    International Nuclear Information System (INIS)

    Ahn, N.G.; Klinman, J.P.

    1989-01-01

    Using isolated chromaffin granule ghosts from bovine adrenal medullae, we have studied the kinetics of dopamine beta-monooxygenase (D beta M) activity as it is linked to dopamine transport. Measurements of the initial rates of transport and of transport-linked norepinephrine formation suggested that enzyme activity may be partially rate-limiting in the coupled carrier/enzyme system. This was confirmed by (i) measurements of initial rates of norepinephrine formation using deuterated substrate, which gave isotope effects greater than 2.0, and (ii) kinetic measurements using ghosts pulsed with varying concentrations of labeled dopamine, which indicated substantial substrate accumulation in the vesicle interior as a function of time. Initial rates of product formation, when combined with approximations of internal substrate concentrations, allowed estimates of Kcat and Km for intravesicular D beta M. Activation by external reductant was apparent in both initial rate parameters and the measurements of transients. Under conditions of optimal D beta M activity, the enzyme rate parameters (kcat = 0.31 nmol/s.mg and Km = 2 mM) indicated partial rate limitation compared to dopamine transport (kcat = 0.38 nmol/s.mg and Km = 32 microM). Compartmental analysis of the time curves, performed using numerical nonlinear least squares methods, gave least squares estimates of rate constants for a simple carrier mechanism and kcat values for D beta M which were consistent with estimates from initial rates

  5. An inexpensive and innovative correction of medial compartmental osteoarthritis knee joint by high tibial lateral closed wedge osteotomy in a rural set up

    Directory of Open Access Journals (Sweden)

    Prasad DV, Arun AA, Tushar Chaudhari, Sagar Jawale, Shakthi Panda, Abhinav Jadhav, Deepak Dathrange

    2014-11-01

    Full Text Available Osteoarthritis of Knee joint with Varus deformity causes considerable disability. Operative treatment aims at shifting the mechanical load bearing axis to the less affected compartment of the knee to relieve the symptoms. Exclusion Criteria: Non-walkers due to generalized arthropathies / medical comorbidities, Flexion deformity > 10 degrees, Range of motion 1cm lateral subluxation in standing A-P X rays of both knees. Methodology: 32 (12 Males and 20 Females cases of Medial compartment osteoarthritis presenting in our OPD between 2008-2012 were treated by HTOand cortical screw and SS wire fixation (TBW Technique. Results: Evaluation of results was done based on knee rating scale by Japanese orthopaedic association. 22 cases were Excellent, 8 cases were good. One case of failure, an iatrogenic intracondylar fracture of Tibia, and another secondary haematoma under the suture line, aspirated and complete healing was achieved. Patients had good range of motion, were able to squat and sit cross legged comfortably. Conclusion: HTO by Closed Medial wedge osteotomy and fixation with cortical screw and SS wire provides a good alternative to unicompartmental knee Arthroplasty and even Total knee Arthroplasty (may be up to 10-15 years in patients with Medial compartmental osteoarthritis. It is a cost effective technique with the use of minimum hardware and early postoperative mobilization in patients who cannot afford Knee Arthroplasty in a Rural set up.

  6. A dynamic model of digestion and absorption in pigs

    DEFF Research Database (Denmark)

    Strathe, Anders Bjerring; Danfær, Allan Christian; Chwalibog, Andrzej

    2008-01-01

    The paper describes and evaluates the construction of a mathematical model to study the kinetics of digestion and absorption in growing pigs. The core of the model is based on a compartmental structure, which divides the gastro-intestinal tract into four anatomical segments: the stomach, two part......, starch, sugars and dietary fibre. Besides a chemical description of the feed, the model further requires information about daily dry matter intake and feeding frequency.......The paper describes and evaluates the construction of a mathematical model to study the kinetics of digestion and absorption in growing pigs. The core of the model is based on a compartmental structure, which divides the gastro-intestinal tract into four anatomical segments: the stomach, two parts...

  7. Frontal Plane Tibiofemoral Alignment is Strongly Related to Compartmental Knee Joint Contact Forces and Muscle Control Strategies during Stair Ascent.

    Science.gov (United States)

    Bennett, Hunter J; Weinhandl, Joshua T; Fleenor, Kristina; Zhang, Songning

    2018-03-12

    Static frontal plane tibiofemoral alignment is an important factor in dynamic knee alignment and knee adduction moments. However, little is known about the relationship between alignment and compartment contact forces or muscle control strategies. The purpose of this study was to estimate medial (MCF) and lateral (LCF) compartment knee joint contact forces and muscle forces during stair ascent using a musculoskeletal model implementing subject specific knee alignments. Kinematic and kinetic data from 20 healthy individuals with radiographically confirmed varus or valgus knee alignments were simulated using alignment specific models to predict MCFs and LCFs. Muscle forces were determined using static optimization. Independent samples t-tests compared contact and knee and frontal plane hip muscle forces between groups during weight acceptance and during pushoff. The varus group exhibited increased weight acceptance peak MCFs, while the valgus group exhibited increased pushoff peak LCFs. The varus group utilized increased vasti muscle forces during weight acceptance and hip adductor forces during pushoff. The valgus group utilized increased hip abductor forces during pushoff. The alignment dependent contact forces provide evidence of the significance of frontal plane knee alignment in healthy individuals, which may be important in considering future knee joint health. The differing muscle control strategies between alignments detail specific neuromuscular responses to control frontal plane knee loads.

  8. Modeling the Dynamics of Compromised Networks

    Energy Technology Data Exchange (ETDEWEB)

    Soper, B; Merl, D M

    2011-09-12

    Accurate predictive models of compromised networks would contribute greatly to improving the effectiveness and efficiency of the detection and control of network attacks. Compartmental epidemiological models have been applied to modeling attack vectors such as viruses and worms. We extend the application of these models to capture a wider class of dynamics applicable to cyber security. By making basic assumptions regarding network topology we use multi-group epidemiological models and reaction rate kinetics to model the stochastic evolution of a compromised network. The Gillespie Algorithm is used to run simulations under a worst case scenario in which the intruder follows the basic connection rates of network traffic as a method of obfuscation.

  9. Compartmentalized beta subunit distribution determines characteristics and ethanol sensitivity of somatic, dendritic, and terminal large-conductance calcium-activated potassium channels in the rat central nervous system.

    Science.gov (United States)

    Wynne, P M; Puig, S I; Martin, G E; Treistman, S N

    2009-06-01

    Neurons are highly differentiated and polarized cells, whose various functions depend upon the compartmentalization of ion channels. The rat hypothalamic-neurohypophysial system (HNS), in which cell bodies and dendrites reside in the hypothalamus, physically separated from their nerve terminals in the neurohypophysis, provides a particularly powerful preparation in which to study the distribution and regional properties of ion channel proteins. Using electrophysiological and immunohistochemical techniques, we characterized the large-conductance calcium-activated potassium (BK) channel in each of the three primary compartments (soma, dendrite, and terminal) of HNS neurons. We found that dendritic BK channels, in common with somatic channels but in contrast to nerve terminal channels, are insensitive to iberiotoxin. Furthermore, analysis of dendritic BK channel gating kinetics indicates that they, like somatic channels, have fast activation kinetics, in contrast to the slow gating of terminal channels. Dendritic and somatic channels are also more sensitive to calcium and have a greater conductance than terminal channels. Finally, although terminal BK channels are highly potentiated by ethanol, somatic and dendritic channels are insensitive to the drug. The biophysical and pharmacological properties of somatic and dendritic versus nerve terminal channels are consistent with the characteristics of exogenously expressed alphabeta1 versus alphabeta4 channels, respectively. Therefore, one possible explanation for our findings is a selective distribution of auxiliary beta1 subunits to the somatic and dendritic compartments and beta4 to the terminal compartment. This hypothesis is supported immunohistochemically by the appearance of distinct punctate beta1 or beta4 channel clusters in the membrane of somatic and dendritic or nerve terminal compartments, respectively.

  10. Studies of labelling conditions for gentamicin with sup(99m)Tc. Complexation with ruthexium. Establishment of pharmacokinetics parameters through compartmental analysis

    International Nuclear Information System (INIS)

    Carvalho, O.G. de.

    1988-01-01

    Gentamicin sulphate is an aminoglycoside antibiotic type specifically used for treatment of infections produced by Gram-negative bacterias but at the other hand it presents ototoxic reactions as a serious side effect. The main purpose of labelling gentamicin with sup(99m)Tc was to obtain a radioactive tracer to carry out biological studies and compartmental analysis of this antibiotic. The optimal labelling conditions of gentamicin sulphate with sup(99m)Tc, using sodium pertechnetate solution eluted from a sup(99)Mo- sup(99m)Tc generator, were stablished by testing different masses of antibiotic, and reduction agent (SnCl sub(2).2H sub(2)O), and also different reaction time and final labelling PH. The same labelling procedure was used with Re (amonium perrenate) in order to obtain some semi-quantitative approximations of the chemical structure of the complex formed, since Re and Tc present similar chemical characteristics. In this way it is possible to suggest the role that the groups NH2 and C-O bonding of the gentamicin play in the complexation process. From the studies of the biological uptake of sup(99m)Tc-gentamicin sulphate in rats, the kidneys showed the highest affinity for the antibiotic. The maximum uptake was observed in 180 to 240 minutes followed by a decrease of it afterwards. For the dose and time used, no significative uptake by the auricular region was detected. Curve of plasma decay of sup(99m)Tc-gentamicin was obtained, and from the exponentials of each beanch of this curve respective half-lives were calculated. Furthermore the apparent volume of distribution was determined, and with the residual radioactivity in the body, the biological half-life and total clearance were obtained. The distribution of sup(99m)Tc-gentamicin in rats was set in a bi-compartments in addition to a retention one for the 24 hours time interval studied. (author)

  11. Metabolic compartmentalization in the human cortex and hippocampus: evidence for a cell- and region-specific localization of lactate dehydrogenase 5 and pyruvate dehydrogenase

    Directory of Open Access Journals (Sweden)

    Kovari Enikö

    2007-05-01

    at the regional level, that support the notion of metabolic compartmentalization between astrocytes and neurons, whereby lactate produced by astrocytes could be oxidized by neurons.

  12. Compartmental HBV evolution and replication in liver and extrahepatic sites after nucleos/tide analogue therapy in chronic hepatitis B carriers.

    Science.gov (United States)

    Gao, Shan; Duan, Zhong-Ping; Chen, Yu; van der Meer, Frank; Lee, Samuel S; Osiowy, Carla; van Marle, Guido; Coffin, Carla S

    2017-09-01

    Hepatitis B virus (HBV) variants are associated with nucleos/tide analogue (NA) response and liver disease but it is unknown whether NA influences extrahepatic HBV persistence. To investigate HBV replication and genetic evolution in hepatic and extrahepatic sites of chronic hepatitis B (CHB) before and after NA therapy. A total of 13 paired plasma, peripheral blood mononuclear cells (PBMC), were collected from chronic HBV carriers at baseline and after a median 53 weeks NA therapy as well as liver biopsy (N=7 baseline, N=5 follow-up). HBV covalently closed circular DNA (cccDNA) and messenger (m) RNA in liver and PBMC were analyzed. HBV polymerase (P)/surface (S), basal core promoter (BCP)/pre-core (PC)/C gene clonal sequencing was done in plasma, peripheral blood mononuclear cells (PBMC), and liver. Compare to baseline, at ∼53 weeks follow-up, there was no significant change in HBV cccDNA levels in liver (0.2-0.08 copies/hepatocyte, p>0.05) or in PBMC 0.003-0.02 copies/PBMC, p>0.05), and HBV mRNA remained detectable in both sites. At baseline, BCP variants were higher in PBMC vs. liver and plasma. After therapy, drug resistant (DR) and immune escape (IE) variants increased in liver but IE and PC variants were more frequent in PBMC. HBV P/S diversity was significantly higher in PBMC compared to plasma. Continuous HBV replication occurs in liver and PBMC and shows compartmentalized evolution under selective pressure of potent NA therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Ultra–Short-Term Reproducibility of Speckle-Noise Freed Fluid and Tissue Compartmentalization of the Choroid Analyzed by Standard OCT

    Science.gov (United States)

    Maloca, Peter; Gyger, Cyrill; Schoetzau, Andreas; Hasler, Pascal W.

    2015-01-01

    Purpose We measured reproducibility of speckle-noise freed fluid and tissue compartmentalization of the choroid (choroidal angiography and tissue characterization). Methods This study included 26 eyes of 13 healthy females: 13 were used for repeated measurements and 13 were used for side comparison. A semiautomated algorithm removed speckle-noise with structure preservation. Results Intraclass correlation (ICC), with respect to reproducibility of the method, showed an ICC for choroidal fluid inner space analysis (FISA) of 95.15% (90.01–98.24). The ICC of tissue inner space analysis (TISA) was 99.75% (99.47–99.91). The total choroid ratio (TCR), calculated from volumes of tissue to vessels, showed an ICC of 88.84% (78.28–95.82). Comparison of eyes (left to right) showed a difference for FISA of 0.033 (95% confidence interval [CI] −0.0018–0.0680, P = 0.063), TISA −0.118 (CI −0.2373–0.0023, P = 0.055), and TCR −0.590 (CI −0.9047 to −0.2754, P = 0.004). The ICC for FISA and TISA showed a trend in the difference comparing left and right eyes; however, TCR showed a significant difference between the eyes in the measured area (P OCT). Findings from basic science about speckle noise were translated into a novel, medical image postprocessing application that can separate signal from speckle noise with structure preservation with high reproducibility and enhance medical imaging. PMID:26629399

  14. Micro-seismicity, fault structure, and hydrologic compartmentalization within the Coso Geothermal Field, California, from 1996 until present

    Science.gov (United States)

    Kaven, J. O.; Hickman, S.; Davatzes, N. C.

    2010-12-01

    which we interpret the faults to be located. The faults that are identified reveal a complicated image of the subsurface structure of the CGF and tend to fall within and between hydrologic compartments known to exist within the reservoir. This suggests that some of the faults in the CGF serve as conduits for fluids and heat, while others seal portions of the reservoir and function as hydrologic domain boundaries. We anticipate that our method can be applied in many conventional geothermal systems, either before plant design to guide well placement (if natural seismicity is present and recorded well) or as part of evaluating the hydraulic network stimulated by EGS. This type of information will also be useful in locating and designing EGS, either in seismically active areas lacking prior geothermal development or on the margins of existing geothermal fields. The improved knowledge of subsurface structure provided by this type of modeling can also aid in assessing seismic hazards associated with EGS stimulations or ongoing injection and production when used in concert with fault-stress transfer models.

  15. Structure and development of the subesophageal zone of the Drosophila brain. I. Segmental architecture, compartmentalization, and lineage anatomy.

    Science.gov (United States)

    Hartenstein, Volker; Omoto, Jaison J; Ngo, Kathy T; Wong, Darren; Kuert, Philipp A; Reichert, Heinrich; Lovick, Jennifer K; Younossi-Hartenstein, Amelia

    2018-01-01

    The subesophageal zone (SEZ) of the Drosophila brain houses the circuitry underlying feeding behavior and is involved in many other aspects of sensory processing and locomotor control. Formed by the merging of four neuromeres, the internal architecture of the SEZ can be best understood by identifying segmentally reiterated landmarks emerging in the embryo and larva, and following the gradual changes by which these landmarks become integrated into the mature SEZ during metamorphosis. In previous works, the system of longitudinal fibers (connectives) and transverse axons (commissures) has been used as a scaffold that provides internal landmarks for the neuromeres of the larval ventral nerve cord. We have extended the analysis of this scaffold to the SEZ and, in addition, reconstructed the tracts formed by lineages and nerves in relationship to the connectives and commissures. As a result, we establish reliable criteria that define boundaries between the four neuromeres (tritocerebrum, mandibular neuromere, maxillary neuromere, labial neuromere) of the SEZ at all stages of development. Fascicles and lineage tracts also demarcate seven columnar neuropil domains (ventromedial, ventro-lateral, centromedial, central, centrolateral, dorsomedial, dorsolateral) identifiable throughout development. These anatomical subdivisions, presented in the form of an atlas including confocal sections and 3D digital models for the larval, pupal and adult stage, allowed us to describe the morphogenetic changes shaping the adult SEZ. Finally, we mapped MARCM-labeled clones of all secondary lineages of the SEZ to the newly established neuropil subdivisions. Our work will facilitate future studies of function and comparative anatomy of the SEZ. © 2017 Wiley Periodicals, Inc.

  16. Identification of compartmentalization and Free Water Level using Borehole Images and high Resolution Formation Testing in the Panonian basin

    Science.gov (United States)

    Sőreg, Viktor; Amran, Ahmed; Balogh, József; Tóth, József; Vargáné Tóth, Ilona; Bize, Emmanuel; Bize-Forest, Nadege; Ngallemo, Edmond

    2010-05-01

    Of all the methods used for investigating petroleum reservoirs, Well Testing is of particular interest because it proves reservoir potential and confirms well performance. Well testing involves flowing the well at a control rate and measuring the reservoir response. Conventional well testing is performed in a completed well while high resolution well testing applies to uncompleted well, using wireline technology. This paper describes the use of high technology wireline formation testers to improve reservoir characterization. The Schlumberger formation testing tools (PressureXpress and Modular Reservoir Dynamic Tester) are presented, with applications in geological modeling, drilling, completion and testing optimization as well as formation evaluation. One of the main goal of the study was to identify the gas (oil) saturated layers, to avoid testing unproductive zones. In well K4 utilization of formation tester allowed to point only the potential layers in a sand shale reservoir and a thorough study of these zones has allow the determination of potential reserves. Second successful objective was also to determine eventual compartments in the reservoir, i.e. which reservoir where in the same hydrodynamic system. Last but no least it has allowed an estimation of the free water level. Combination of formation tester with FMI has also helped to visualize the Free Water Level (FWL) in the well, and to determine, in real time, the different points to be tested with XPT. FMI was also of huge benefits in these fractured reservoirs. The determination of free water level and the identification of hydrocarbon saturated layers reduce the cost of completion and conventional testing. Downhole fluid analysis provides a unique solution to the understanding of complex reservoirs. Based on the lessons learned, Improvements have been proposed for future operations.

  17. The potential impact of an HIV vaccine with limited protection on HIV incidence in Thailand: a modeling study.

    NARCIS (Netherlands)

    Nagelkerke, N.J.; Hontelez, J.A.; Vlas, S.J. de

    2011-01-01

    BACKGROUND: The RV144 trial on the ALVAC/AIDSVAX candidate HIV vaccine, carried out in Thailand, showed short-lived protection against infection. METHODS: Using a deterministic compartmental model we explored the potential impact of this vaccine on heterosexual HIV transmission in Thailand. Both

  18. Mathematical modelling with case studies using Maple and Matlab

    CERN Document Server

    Barnes, B

    2014-01-01

    Introduction to Mathematical ModelingMathematical models An overview of the book Some modeling approaches Modeling for decision makingCompartmental Models Introduction Exponential decay and radioactivity Case study: detecting art forgeries Case study: Pacific rats colonize New Zealand Lake pollution models Case study: Lake Burley Griffin Drug assimilation into the blood Case study: dull, dizzy, or dead? Cascades of compartments First-order linear DEs Equilibrium points and stability Case study: money, money, money makes the world go aroundModels of Single PopulationsExponential growth Density-

  19. Kinetics model for lutate dosimetry

    International Nuclear Information System (INIS)

    Lima, M.F.; Mesquita, C.H.

    2013-01-01

    The use of compartmental analysis to predict the behavior of drugs in the organism is considered the better option among numerous methods employed in pharmacodynamics. A six compartments model was developed to determinate the kinetic constants of 177Lu-DOTATATO biodistribution using data from one published study with 67 patients treated by PRRT (Peptide receptor radionuclide therapy) and followed by CT during 68,25 hours. The compartmental analysis was made using the software AnaComp®. The influence of the time pos-injection over the dose assessment was studied taking into account the renal excretion management by aminoacid coinfusion, whose direct effects persist in the first day. The biodistribution curve was split in five sectors: 0-0.25h; 0-3.25h; 3.25-24.25h; 24.25-68.25h and 3.25-68.25h. After the examination of that influence, the study was concentrated in separate the biodistribution curve in two phases. Phase 1: governed by uptake from the blood, considering the time pos-injection until 3.25h and phase 2: governed by renal excretion, considering the time pos-injection from 3.25h to 68.25h. The model considered the organs and tissues superposition in the CT image acquisition by sampling parameters as the contribution of the the activity concentration in blood and relation between the sizes of the whole body and measured organs. The kinetic constants obtained from each phase (1 and 2) were used in dose assessment to patients in 26 organs and tissues described by MIRD. Dosimetry results were in agreement with the available results from literature, restrict to whole body, kidneys, bone marrow, spleen and liver. The advantage of the proposed model is the compartmental method quickness and power to estimate dose in organs and tissues, including tumor that, in the most part, were not discriminate by voxels of phantoms built using CT images. (author)

  20. Evaluation of physiological parameters and their influence on doses calculated from two alternative dosimetric models for the gastrointestinal tract

    International Nuclear Information System (INIS)

    Lessard, E.T.; Skrable, K.W.

    1981-01-01

    Two dosimetric models, the catenary compartmental model and the slug flow model are examined using three sets of physiological parameters. The impact of physiological parameters on the dosimetry of the tract is illustrated by comparing calculated maximum permissible daily activity ingestion rates for single, unabsorbed, particle emitting radionuclides with an effective energy term of unity. The conclusions drawn from this intercomparison of six different cases are: (1) Current dosimetric models which use physiological parameters described in this article do not significantly disagree, and (2) For the determination of average dose equivalent rates to segments of the tract due to chronic, long term ingestion of any radionuclide, the catenary compartmental model is a mathematically simpler approach. The catenary model in addition has certain advantages for the calculation of the photon dose contribution to one segment from cumulated activity (disintegrations) in another segment

  1. Modeling hepatitis C virus transmission among people who inject drugs: Assumptions, limitations and future challenges.

    Science.gov (United States)

    Scott, Nick; Hellard, Margaret; McBryde, Emma Sue

    2016-01-01

    The discovery of highly effective hepatitis C virus (HCV) treatments has led to discussion of elimination and intensified interest in models of HCV transmission. In developed settings, HCV disproportionally affects people who inject drugs (PWID), and models are typically used to provide an evidence base for the effectiveness of interventions such as needle and syringe programs, opioid substitution therapy and more recently treating PWID with new generation therapies to achieve specified reductions in prevalence and / or incidence. This manuscript reviews deterministic compartmental S-I, deterministic compartmental S-I-S and network-based transmission models of HCV among PWID. We detail typical assumptions made when modeling injecting risk behavior, virus transmission, treatment and re-infection and how they correspond with available evidence and empirical data.

  2. Utility of a Bayesian Mathematical Model to Predict the Impact of Immunogenicity on Pharmacokinetics of Therapeutic Proteins.

    Science.gov (United States)

    Kathman, Steven; Thway, Theingi M; Zhou, Lei; Lee, Stephanie; Yu, Steven; Ma, Mark; Chirmule, Naren; Jawa, Vibha

    2016-03-01

    The impact of an anti-drug antibody (ADA) response on pharmacokinetic (PK) of a therapeutic protein (TP) requires an in-depth understanding of both PK parameters and ADA characteristics. The ADA and PK bioanalytical assays have technical limitations due to high circulating levels of TP and ADA, respectively, hence, significantly hindering the interpretation of this assessment. The goal of this study was to develop a population-based modeling and simulation approach that can identify a more relevant PK parameter associated with ADA-mediated clearance. The concentration-time data from a single dose PK study using five monoclonal antibodies were modeled using a non-compartmental analysis (NCA), one-compartmental, and two-compartmental Michaelis-Menten kinetic model (MMK). A novel PK parameter termed change in clearance time of the TP (α) derived from the MMK model could predict variations in α much earlier than the time points when ADA could be bioanalytically detectable. The model could also identify subjects that might have been potentially identified as false negative due to interference of TP with ADA detection. While NCA and one-compartment models can estimate loss of exposures, and changes in clearance, the two-compartment model provides this additional ability to predict that loss of exposure by means of α. Modeling data from this study showed that the two-compartment model along with the conventional modeling approaches can help predict the impact of ADA response in the absence of relevant ADA data.

  3. A computational code for resolution of general compartment models applied to internal dosimetry

    International Nuclear Information System (INIS)

    Claro, Thiago R.; Todo, Alberto S.

    2011-01-01

    The dose resulting from internal contamination can be estimated with the use of biokinetic models combined with experimental results obtained from bio analysis and the knowledge of the incorporation time. The biokinetics models can be represented by a set of compartments expressing the transportation, retention and elimination of radionuclides from the body. The ICRP publications, number 66, 78 and 100, present compartmental models for the respiratory tract, gastrointestinal tract and for systemic distribution for an array of radionuclides of interest for the radiological protection. The objective of this work is to develop a computational code for designing, visualization and resolution of compartmental models of any nature. There are available four different techniques for the resolution of system of differential equations, including semi-analytical and numerical methods. The software was developed in C≠ programming, using a Microsoft Access database and XML standards for file exchange with other applications. Compartmental models for uranium, thorium and iodine radionuclides were generated for the validation of the CBT software. The models were subsequently solved by SSID software and the results compared with the values published in the issue 78 of ICRP. In all cases the system is in accordance with the values published by ICRP. (author)

  4. A computational code for resolution of general compartment models applied to internal dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Claro, Thiago R.; Todo, Alberto S., E-mail: claro@usp.br, E-mail: astodo@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    The dose resulting from internal contamination can be estimated with the use of biokinetic models combined with experimental results obtained from bio analysis and the knowledge of the incorporation time. The biokinetics models can be represented by a set of compartments expressing the transportation, retention and elimination of radionuclides from the body. The ICRP publications, number 66, 78 and 100, present compartmental models for the respiratory tract, gastrointestinal tract and for systemic distribution for an array of radionuclides of interest for the radiological protection. The objective of this work is to develop a computational code for designing, visualization and resolution of compartmental models of any nature. There are available four different techniques for the resolution of system of differential equations, including semi-analytical and numerical methods. The software was developed in C{ne} programming, using a Microsoft Access database and XML standards for file exchange with other applications. Compartmental models for uranium, thorium and iodine radionuclides were generated for the validation of the CBT software. The models were subsequently solved by SSID software and the results compared with the values published in the issue 78 of ICRP. In all cases the system is in accordance with the values published by ICRP. (author)

  5. A Phase Separation Model for Transcriptional Control.

    Science.gov (United States)

    Hnisz, Denes; Shrinivas, Krishna; Young, Richard A; Chakraborty, Arup K; Sharp, Phillip A

    2017-03-23

    Phase-separated multi-molecular assemblies provide a general regulatory mechanism to compartmentalize biochemical reactions within cells. We propose that a phase separation model explains established and recently described features of transcriptional control. These features include the formation of super-enhancers, the sensitivity of super-enhancers to perturbation, the transcriptional bursting patterns of enhancers, and the ability of an enhancer to produce simultaneous activation at multiple genes. This model provides a conceptual framework to further explore principles of gene control in mammals. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Multicompartmental fate of persistent substances. Comparison of predictions from multi-media box models and a multicompartment chemistry-atmospheric transport model.

    Science.gov (United States)

    Lammel, Gerhard; Klöpffer, Walter; Semeena, V S; Schmidt, Elisabeth; Leip, Adrian

    2007-05-01

    Modelling of the fate of environmental chemicals can be done by relatively simple multi-media box models or using complex atmospheric transport models. It was the aim of this work to compare the results obtained for both types of models using a small set of non-ionic and non-polar or moderately polar organic chemicals, known to be distributed over long distances. Predictions of multimedia exposure models of different types, namely three multimedia mass-balance box models (MBMs), two in the steady state and one in the non-steady state mode, and one non-steady state multicompartment chemistry-atmospheric transport model (MCTM), are compared for the first time. The models used are SimpleBox, Chemrange, the MPI-MBM and the MPI-MCTM. The target parameters addressed are compartmental distributions (i.e. mass fractions in the compartments), overall environmental residence time (i.e. overall persistence and eventually including other final sinks, such as loss to the deep sea) and a measure for the long-range transport potential. These are derived for atrazine, benz-[a]-pyrene, DDT, alpha and gamma-hexachlorocyclohexane, methyl parathion and various modes of substance entry into the model world. Compartmental distributions in steady state were compared. Steady state needed 2-10 years to be established in the MCTM. The highest fraction of the substances in air is predicted by the MCTM. Accordingly, the other models predict longer substance persistence in most cases. The results suggest that temperature affects the compartmental distribution more in the box models, while it is only one among many climate factors acting in the transport model. The representation of final sinks in the models, e.g. burial in the sediment, is key for model-based compartmental distribution and persistence predictions. There is a tendency of MBMs to overestimate substance sinks in air and to underestimate atmospheric transport velocity as a consequence of the neglection of the temporal and spatial

  7. Research Methods in Healthcare Epidemiology and Antimicrobial Stewardship-Mathematical Modeling.

    Science.gov (United States)

    Barnes, Sean L; Kasaie, Parastu; Anderson, Deverick J; Rubin, Michael

    2016-11-01

    Mathematical modeling is a valuable methodology used to study healthcare epidemiology and antimicrobial stewardship, particularly when more traditional study approaches are infeasible, unethical, costly, or time consuming. We focus on 2 of the most common types of mathematical modeling, namely compartmental modeling and agent-based modeling, which provide important advantages-such as shorter developmental timelines and opportunities for extensive experimentation-over observational and experimental approaches. We summarize these advantages and disadvantages via specific examples and highlight recent advances in the methodology. A checklist is provided to serve as a guideline in the development of mathematical models in healthcare epidemiology and antimicrobial stewardship. Infect Control Hosp Epidemiol 2016;1-7.

  8. Software for biokinetic modeling of the radiopharmaceuticals used in PET

    International Nuclear Information System (INIS)

    Cordeiro, Leanderson P.; Vieira, Igor F.; Lima, Fernando R.A. de; Vieira, Jose W.

    2013-01-01

    In this work will be presented the current state of software in development to estimate the dose from PET images. Will be given the main biokinetic models used in PET, as well as the general features of a tool in development, whose current features allow quantitative analysis of compartmental models. Further, the tool allows display images 2D PET (in DICOM format) and quantify the intensity map of regions of interest in counts per second coincidence events. The next step is to insert in the same tool to estimate the activity concentration for ROI and estimate dose from PET images static and / or dynamic

  9. Mathematical models of human african trypanosomiasis epidemiology.

    Science.gov (United States)

    Rock, Kat S; Stone, Chris M; Hastings, Ian M; Keeling, Matt J; Torr, Steve J; Chitnis, Nakul

    2015-03-01

    Human African trypanosomiasis (HAT), commonly called sleeping sickness, is caused by Trypanosoma spp. and transmitted by tsetse flies (Glossina spp.). HAT is usually fatal if untreated and transmission occurs in foci across sub-Saharan Africa. Mathematical modelling of HAT began in the 1980s with extensions of the Ross-Macdonald malaria model and has since consisted, with a few exceptions, of similar deterministic compartmental models. These models have captured the main features of HAT epidemiology and provided insight on the effectiveness of the two main control interventions (treatment of humans and tsetse fly control) in eliminating transmission. However, most existing models have overestimated prevalence of infection and ignored transient dynamics. There is a need for properly validated models, evolving with improved data collection, that can provide quantitative predictions to help guide control and elimination strategies for HAT. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Parametric modeling of DSC-MRI data with stochastic filtration and optimal input design versus non-parametric modeling.

    Science.gov (United States)

    Kalicka, Renata; Pietrenko-Dabrowska, Anna

    2007-03-01

    In the paper MRI measurements are used for assessment of brain tissue perfusion and other features and functions of the brain (cerebral blood flow - CBF, cerebral blood volume - CBV, mean transit time - MTT). Perfusion is an important indicator of tissue viability and functioning as in pathological tissue blood flow, vascular and tissue structure are altered with respect to normal tissue. MRI enables diagnosing diseases at an early stage of their course. The parametric and non-parametric approaches to the identification of MRI models are presented and compared. The non-parametric modeling adopts gamma variate functions. The parametric three-compartmental catenary model, based on the general kinetic model, is also proposed. The parameters of the models are estimated on the basis of experimental data. The goodness of fit of the gamma variate and the three-compartmental models to the data and the accuracy of the parameter estimates are compared. Kalman filtering, smoothing the measurements, was adopted to improve the estimate accuracy of the parametric model. Parametric modeling gives a better fit and better parameter estimates than non-parametric and allows an insight into the functioning of the system. To improve the accuracy optimal experiment design related to the input signal was performed.

  11. One-step parameter estimation of the acid-base equilibria in the ground and excited states of 2-naphthol by global compartmental analysis of the fluorescence decay surface

    Science.gov (United States)

    Van den Bergh, Viviane; Boens, Noël; De Schryver, Frans C.; Ameloot, Marcel; Gallay, Jacques; Kowalczyk, Andrzej

    1992-10-01

    In this paper a new implementation of global bicompartmental analysis of the fluorescence decay surface is presented and applied to the acid-base equilibria in the ground and excited states of 2-naphthol. It is shown that, when the total concentration and absorbance in the ground state of a bicompartmental system are known, global bicompartmental analysis allows one to fit directly for the rate constants of the excited-state process, the normalized spectral emission weighting factors, the equilibrium constant of the ground-state process and the extinction coefficient of one of the species. This one-step global compartmental analysis yields the following values for the rate constants, the ground-state acidity constant and the extinction coefficient of 2-naphtholate at 320 nm: k01=(1.12±0.01)×10 8 s -1, k21=(5±1)×10 10 M -1 s -1, k02=(1.33±0.01)×10 8 s -1, k12=(7.1±0.6)×10 7 s -1, Ka=(2.7±0.4)×10 -10 M and ɛ=1600±300 M -1 cm -1. These values are in good agreement with those reported previously from separate analyses of fluorescence and absorbance. The species-associated emission and excitation spectra of the 2-naphthol and 2-naphtholate emission are calculated from the steady-state spectra and the obtained fluorescence decay parameters.

  12. Quantitative evaluation of small breast masses using a compartment model analysis on dynamic MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ikeda, Osamu; Morishita, Shoji; Kido, Taeko; Kitajima, Mika; Okamura, Kenji; Fukuda, Seiji [Kumamoto Rosai Hospital, Yatsushiro (Japan); Yamashita, Yasuyuki; Takahashi, Mutsumasa

    1998-07-01

    To differentiate between malignant and benign breast masses using a compartmental analysis, 55 patients with breast masses (fibroadenoma, n=22; invasive ductal carcinoma, n=29; noninvasive ductal carcinoma, n=8) underwent Gd-DTPA enhanced dynamic MR imaging. Dynamic MR images obtained using two-dimensional fat-saturated fast multiplanar corrupted gradient echo technique over 10 minutes following bolus injection of Gd-DTPA. The triexponential concentration curve of Gd-DTPA was fitted to a theoretical model based on compartmental analysis. Using this method, the transfer constant (or permeability surface product per unit volume of component k) and f{sub 3}/f{sub 1}=f were measured, where f{sub 1} represents tumor vessel volume and f{sub 3} represents extracellular volume. The k value was significantly greater (p<0.01) for malignant tumors, and the k value seen in cases of noninvasive ductal carcinoma was less than that for invasive ductal carcinoma. The f value was significantly smaller (p<0.01) for malignant tumors, whereas the f value for noninvasive ductal carcinoma was not significantly different from that for invasive ductal carcinoma. We believe that this type of compartmental analysis may be of value for the evaluation of breast masses. (author)

  13. Reduced Genetic Diversity in Lymphoid and Central Nervous System Tissues and Selection-Induced Tissue-Specific Compartmentalization of Neuropathogenic SIVsmmFGb during Acute Infection

    OpenAIRE

    Reeve, Aaron B.; Patel, Kalpana; Pearce, Nicholas C.; Augustus, Katherine V.; Domingues, Heber G.; O'Neil, Shawn P.; Novembre, Francis J.

    2009-01-01

    The simian lentivirus strain SIVsmmFGb is a viral swarm population inducing neuropathology in over 90% of infected pigtailed macaques and serves as a reliable model for HIV neuropathogenesis. However, little is understood about the genetic diversity of this virus, how said diversity influences the initial seeding of the central nervous system and lymph nodes, or whether the virus forms distinct genetic compartments between tissues during acute infection. In this study, we establish that our S...

  14. Models to capture the potential for disease transmission in domestic sheep flocks.

    Science.gov (United States)

    Schley, David; Whittle, Sophie; Taylor, Michael; Kiss, Istvan Zoltan

    2012-09-15

    Successful control of livestock diseases requires an understanding of how they spread amongst animals and between premises. Mathematical models can offer important insight into the dynamics of disease, especially when built upon experimental and/or field data. Here the dynamics of a range of epidemiological models are explored in order to determine which models perform best in capturing real-world heterogeneities at sufficient resolution. Individual based network models are considered together with one- and two-class compartmental models, for which the final epidemic size is calculated as a function of the probability of disease transmission occurring during a given physical contact between two individuals. For numerical results the special cases of a viral disease with a fast recovery rate (foot-and-mouth disease) and a bacterial disease with a slow recovery rate (brucellosis) amongst sheep are considered. Quantitative results from observational studies of physical contact amongst domestic sheep are applied and results from the differently structured flocks (ewes with newborn lambs, ewes with nearly weaned lambs and ewes only) compared. These indicate that the breeding cycle leads to significant changes in the expected basic reproduction ratio of diseases. The observed heterogeneity of contacts amongst animals is best captured by full network simulations, although simple compartmental models describe the key features of an outbreak but, as expected, often overestimate the speed of an outbreak. Here the weights of contacts are heterogeneous, with many low weight links. However, due to the well-connected nature of the networks, this has little effect and differences between models remain small. These results indicate that simple compartmental models can be a useful tool for modelling real-world flocks; their applicability will be greater still for more homogeneously mixed livestock, which could be promoted by higher intensity farming practices. Copyright © 2012

  15. Modeling malware propagation using a carrier compartment

    Science.gov (United States)

    Hernández Guillén, J. D.; Martín del Rey, A.

    2018-03-01

    The great majority of mathematical models proposed to simulate malware spreading are based on systems of ordinary differential equations. These are compartmental models where the devices are classified according to some types: susceptible, exposed, infectious, recovered, etc. As far as we know, there is not any model considering the special class of carrier devices. This type is constituted by the devices whose operative systems is not targeted by the malware (for example, iOS devices for Android malware). In this work a novel mathematical model considering this new compartment is considered. Its qualitative study is presented and a detailed analysis of the efficient control measures is shown by studying the basic reproductive number.

  16. Adiabatic equilibrium models for direct containment heating

    International Nuclear Information System (INIS)

    Pilch, M.; Allen, M.D.

    1991-01-01

    Probabilistic risk assessment (PRA) studies are being extended to include a wider spectrum of reactor plants than was considered in NUREG-1150. There is a need for simple direct containment heating (DCH) models that can be used for screening studies aimed at identifying potentially significant contributors to overall risk in individual nuclear power plants. This paper presents two adiabatic equilibrium models suitable for the task. The first, a single-cell model, places a true upper bound on DCH loads. This upper bound, however, often far exceeds reasonable expectations of containment loads based on CONTAIN calculations and experiment observations. In this paper, a two cell model is developed that captures the major mitigating feature of containment compartmentalization, thus providing more reasonable estimates of the containment load

  17. Population pharmacokinetic modeling of glibenclamide in poorly controlled South African type 2 diabetic subjects

    Directory of Open Access Journals (Sweden)

    Rambiritch V

    2016-07-01

    Full Text Available Virendra Rambiritch,1 Poobalan Naidoo,2 Breminand Maharaj,1 Goonaseelan Pillai3 1University of KwaZulu-Natal, Durban, 2Department of Internal Medicine, RK Khan Regional Hospital, Chatsworth, South Africa; 3Novartis Pharma AG, Basel, Switzerland Aim: The aim of this study was to describe the pharmacokinetics (PK of glibenclamide in poorly controlled South African type 2 diabetic subjects using noncompartmental and model-based methods. Methods: A total of 24 subjects with type 2 diabetes were administered increasing doses (0 mg/d, 2.5 mg/d, 5 mg/d, 10 mg/d, and 20 mg/d of glibenclamide daily at 2-week intervals. Plasma glibenclamide, glucose, and insulin determinations were performed. Blood sampling times were 0 minute, 30 minutes, 60 minutes, 90 minutes, and 120 minutes (post breakfast sampling and 240 minutes, 270 minutes, 300 minutes, 330 minutes, 360 minutes, and 420 minutes (post lunch sampling on days 14, 28, 42, 56, and 70 for doses of 0 mg, 2.5 mg, 5.0 mg, 10 mg, and 20 mg, respectively. Blood sampling was performed after the steady state was reached.  A total of 24 individuals in the data set contributed to a total of 841 observation records. The PK was analyzed using noncompartmental analysis methods, which were implemented in WinNonLin®, and population PK analysis using NONMEM®. Glibenclamide concentration data were log transformed prior to fitting. Results: A two-compartmental disposition model was selected after evaluating one-, two-, and three-compartmental models to describe the time course of glibenclamide plasma concentration data. The one-compartment model adequately described the data; however, the two-compartment model provided a better fit. The three-compartment model failed to achieve successful convergence. A more complex model, to account for enterohepatic recirculation that was observed in the data, was unsuccessful. Conclusion: In South African diabetic subjects, glibenclamide demonstrates linear PK and was best

  18. Ras acylation, compartmentalization and signaling nanoclusters (Review)

    OpenAIRE

    HENIS, YOAV I.; HANCOCK, JOHN F.; PRIOR, IAN A.

    2008-01-01

    Ras proteins have become paradigms for isoform- and compartment-specific signaling. Recent work has shown that Ras isoforms are differentially distributed within cell surface signaling nanoclusters and on endomembranous compartments. The critical feature regulating Ras protein localization and isoform-specific functions is the C-terminal hypervariable region (HVR). In this review we discuss the differential post-translational modifications and reversible targeting functions of Ras isoform HVR...

  19. Membrane compartmentalization of melanosomal gp75.

    Science.gov (United States)

    Giacomini, P; Fraioli, R; Cuomo, M; Natali, P G

    1992-03-01

    A melanosomal integral membrane glycoprotein of 75 kD (gp75) has been previously identified as the human homologue of the product specified by the murine brown locus. We presently report that this molecule may be susceptible to limited proteolysis and extrinsic radioiodination in intact, live cells. Consequently, it is suggested that its cellular location might include the plasma membrane and/or a cellular compartment easily accessible to proteases and to chemically catalyzed vectorial iodination. This is of interest in view of the potential applicative value of gp75 as a target for the radioimmunoscintography of melanoma lesions.

  20. Modeling in biopharmaceutics, pharmacokinetics and pharmacodynamics homogeneous and heterogeneous approaches

    CERN Document Server

    Macheras, Panos

    2016-01-01

    The state of the art in Biopharmaceutics, Pharmacokinetics, and Pharmacodynamics Modeling is presented in this new second edition book. It shows how advanced physical and mathematical methods can expand classical models in order to cover heterogeneous drug-biological processes and therapeutic effects in the body. The book is divided into four parts; the first deals with the fundamental principles of fractals, diffusion and nonlinear dynamics; the second with drug dissolution, release, and absorption; the third with epirical, compartmental, and stochastic pharmacokinetic models, with two new chapters, one on fractional pharmacokinetics and one on bioequivalence; and the fourth mainly with classical and nonclassical aspects of pharmacodynamics. The classical models that have relevance and application to these sciences are also considered throughout. This second edition has new information on reaction limited models of dissolution, non binary biopharmaceutic classification system, time varying models, and interf...

  1. A fugacity-based indoor residential pesticide fate model

    Energy Technology Data Exchange (ETDEWEB)

    Bennett, Deborah H.; Furtaw, Edward J.; McKone, Thomas E.

    2002-06-01

    Dermal and non-dietary pathways are potentially significant exposure pathways to pesticides used in residences. Exposure pathways include dermal contact with residues on surfaces, ingestion from hand- and object-to-mouth activities, and absorption of pesticides into food. A limited amount of data has been collected on pesticide concentrations in various residential compartments following an application. But models are needed to interpret this data and make predictions about other pesticides based on chemical properties. In this paper, we propose a mass-balance compartment model based on fugacity principles. We include air (both gas phase and aerosols), carpet, smooth flooring, and walls as model compartments. Pesticide concentrations on furniture and toys, and in food, are being added to the model as data becomes available. We determine the compartmental fugacity capacity and mass transfer-rate coefficient for wallboard as an example. We also present the framework and equations needed for a dynamic mass-balance model.

  2. Modeling in biopharmaceutics, pharmacokinetics, and pharmacodynamics homogeneous and heterogeneous approaches

    CERN Document Server

    Macheras, Panos

    2006-01-01

    The state of the art in Biopharmaceutics, Pharmacokinetics, and Pharmacodynamics Modeling is presented in this book. It shows how advanced physical and mathematical methods can expand classical models in order to cover heterogeneous drug-biological processes and therapeutic effects in the body. The book is divided into four parts; the first deals with the fundamental principles of fractals, diffusion and nonlinear dynamics; the second with drug dissolution, release, and absorption; the third with empirical, compartmental, and stochastic pharmacokinetic models, and the fourth mainly with nonclassical aspects of pharmacodynamics. The classical models that have relevance and application to these sciences are also considered throughout. Many examples are used to illustrate the intrinsic complexity of drug administration related phenomena in the human, justifying the use of advanced modeling methods. This timely and useful book will appeal to graduate students and researchers in pharmacology, pharmaceutical scienc...

  3. Model for cadmium transport and distribution in CHO cells

    Energy Technology Data Exchange (ETDEWEB)

    Hayden, T.L.; Turner, J.E.; Williams, M.W.; Cook, J.S.; Hsie, A.W.

    1982-01-01

    A compartmental model is developed to study the transport and distribution of cadmium in Chinese hamster ovary (CHO) cells. Of central importance to the model is the role played by sequestering components which bind free Cd/sup 2 +/ ions. The most important of these is a low-molecular-weight protein, metallothionein, which is produced by the cells in response to an increase in the cellular concentration of Cd/sup 2 +/. Monte Carlo techniques are used to generate a stochastic model based on existing experimental data describing the intracellular transport of cadmium between different compartments. This approach provides an alternative to the usual numerical solution of differential-delay equations that arise in deterministic models. Our model suggests subcellular structures which may be responsible for the accumulation of cadmium and, hence, could account for cadmium detoxification. 4 figures, 1 table.

  4. Patient Specific Modeling of Head-Up Tilt

    DEFF Research Database (Denmark)

    Williams, Nakeya; Wright, Andrew; Mehlsen, Jesper

    2014-01-01

    blood pressure. The model contains five compartments representing arteries and veins in the upper and lower body of the systemic circulation, as well as the left ventricle facilitating pumping of the heart. A physiologically based sub-model describes gravitational effects on pooling of blood during......Short term cardiovascular responses to head-up tilt (HUT) experiments involve complex cardiovascular regulation in order to maintain blood pressure at homeostatic levels. This manuscript presents a patient specific compartmental model developed to predict dynamic changes in heart rate and arterial...... that it is possible to estimate a subset of model parameters that allows prediction of observed changes in arterial blood pressure. Furthermore, the model adequately predicts arterial and venous blood pressures, as well as cardiac output in compartments for which data are not available....

  5. Modelling

    CERN Document Server

    Spädtke, P

    2013-01-01

    Modeling of technical machines became a standard technique since computer became powerful enough to handle the amount of data relevant to the specific system. Simulation of an existing physical device requires the knowledge of all relevant quantities. Electric fields given by the surrounding boundary as well as magnetic fields caused by coils or permanent magnets have to be known. Internal sources for both fields are sometimes taken into account, such as space charge forces or the internal magnetic field of a moving bunch of charged particles. Used solver routines are briefly described and some bench-marking is shown to estimate necessary computing times for different problems. Different types of charged particle sources will be shown together with a suitable model to describe the physical model. Electron guns are covered as well as different ion sources (volume ion sources, laser ion sources, Penning ion sources, electron resonance ion sources, and H$^-$-sources) together with some remarks on beam transport.

  6. Labelling, biodistribution and compartmental analysis of N-acetylcysteine labelled with Tc-99m. Comparative investigation with with sup 9 sup 9 sup m Tc-MIBI in an in vivo tumoral model

    CERN Document Server

    Faintuch, B L

    1997-01-01

    Labelling and biodistribution studies were done with two different ligands, respectively Methoxy isobutyl isonitrile (MIBI) and N-acetylcysteine (NAC), employing Tc-99m as a tracer. The main objective was to assess the pharmacokinetic properties of the second substance, aiming at its possible application in cancer diagnosis. To this purpose an in vivo investigation was done using healthy and tumor-bearing rats with experimental cancer. Images of tumor-bearing rats registered in a scintillation camera indicated that with sup 9 sup 9 sup m Tc-MIBI none of the two selected times was adequate for visualization of the cancer mass. In contrast, sup 9 sup 9 sup m Tc-NAC permitted clear identification of the humor, four hours after injection. The results have demonstrated that sup 9 sup 9 sup m Tc-NAC is a radiopharmaceutical with affinity for cancer tissue and promising for further investigation concerning imaging diagnosis of tumors.

  7. Labelling, biodistribution and compartmental analysis of N-acetylcysteine labelled with Tc-99m. Comparative investigation with with 99m Tc-MIBI in an in vivo tumoral model

    International Nuclear Information System (INIS)

    Faintuch, Bluma Linkowski

    1997-01-01

    Labelling and biodistribution studies were done with two different ligands, respectively Methoxy isobutyl isonitrile (MIBI) and N-acetylcysteine (NAC), employing Tc-99m as a tracer. The main objective was to assess the pharmacokinetic properties of the second substance, aiming at its possible application in cancer diagnosis. To this purpose an in vivo investigation was done using healthy and tumor-bearing rats with experimental cancer. Images of tumor-bearing rats registered in a scintillation camera indicated that with 99m Tc-MIBI none of the two selected times was adequate for visualization of the cancer mass. In contrast, 99m Tc-NAC permitted clear identification of the humor, four hours after injection. The results have demonstrated that 99m Tc-NAC is a radiopharmaceutical with affinity for cancer tissue and promising for further investigation concerning imaging diagnosis of tumors. (author)

  8. Mathematical models for the study of the dynamics of indium-111-labelled platelets in idiopathic thrombocytopenic purpura

    Energy Technology Data Exchange (ETDEWEB)

    Savolainen, S.

    1992-01-01

    Platelet kinetics in patients with idiopathic thrombocytopenic purpura (ITP) was investigated by applying various models (compartmental and open models, and functional and uptake analyses) to data on indium-111 labelled platelets monitored with a gamma camera following intravenous injection of labelled platelets. The usefulness of the selected models was tested by relating kinetic data to pathophysiological phenomena. A comparison of the results of platelet and colloid kinetics showed that the splenic platelet kinetics in ITP patients does not seem to be primarily dependent on the reticuloendothelial system. Although closed three-compartmental analysis seemed to be superior to the other models applied, none of the methods of analysis tested in this study appears to provide a complete description of short-lived platelet dynamics, as for every model certain assumptions that are not entirely relevant have to be made; this stresses the importance of combining various methods for a comprehensive analysis of a complex phenomenon. Conclusions concerning the function of biological systems should be based on more than one dynamic model or calculation method, since applying only one model (or calculation method) may give artifactual results due to poor statistics of observed data or to inexactness of the assumptions concerning the model.

  9. Dynamics of Zika virus outbreaks: an overview of mathematical modeling approaches.

    Science.gov (United States)

    Wiratsudakul, Anuwat; Suparit, Parinya; Modchang, Charin

    2018-01-01

    The Zika virus was first discovered in 1947. It was neglected until a major outbreak occurred on Yap Island, Micronesia, in 2007. Teratogenic effects resulting in microcephaly in newborn infants is the greatest public health threat. In 2016, the Zika virus epidemic was declared as a Public Health Emergency of International Concern (PHEIC). Consequently, mathematical models were constructed to explicitly elucidate related transmission dynamics. In this review article, two steps of journal article searching were performed. First, we attempted to identify mathematical models previously applied to the study of vector-borne diseases using the search terms "dynamics," "mathematical model," "modeling," and "vector-borne" together with the names of vector-borne diseases including chikungunya, dengue, malaria, West Nile, and Zika. Then the identified types of model were further investigated. Second, we narrowed down our survey to focus on only Zika virus research. The terms we searched for were "compartmental," "spatial," "metapopulation," "network," "individual-based," "agent-based" AND "Zika." All relevant studies were included regardless of the year of publication. We have collected research articles that were published before August 2017 based on our search criteria. In this publication survey, we explored the Google Scholar and PubMed databases. We found five basic model architectures previously applied to vector-borne virus studies, particularly in Zika virus simulations. These include compartmental, spatial, metapopulation, network, and individual-based models. We found that Zika models carried out for early epidemics were mostly fit into compartmental structures and were less complicated compared to the more recent ones. Simple models are still commonly used for the timely assessment of epidemics. Nevertheless, due to the availability of large-scale real-world data and computational power, recently there has been growing interest in more complex modeling frameworks

  10. Evaluation of physiological parameters and their influence on doses calculated from two alternative dosimetric models for the gastrointestinal tract

    International Nuclear Information System (INIS)

    Lessard, E.T.; Skrable, K.W.

    1981-01-01

    Two dosimetric models, the catenary compartmental model (Be70) and the slug flow model (Sk75), are examined using three sets of physiological parameters: those proposed by Eve, those proposed by ICRP, and those obtained from the Textbook of Physiology and Biochemistry by Bell et al. The impact of physiological parameters on the dosimetry of the tract is illustrated by comparing calculated maximum permissible daily activity ingestion rates for single, unabsorbed, particle emitting radionuclides with an effective energy term of unity. The conclusions drawn from this intercomparison of six different cases are: Current dosimetric models which use physiological parameters described in this article do not significantly disagree, and for the determination of average dose equivalent rates to segments of the tract due to chronic, long term ingestion of any radionuclide, the catenary compartmental model is a mathematically simpler approach. The catenary model in addition has certain advantages for the calculation of the photon dose contribution to one segment from cumulated activity (disintegrations) in another segment

  11. OFFl Models: Novel Schema for Dynamical Modeling of Biological Systems.

    Directory of Open Access Journals (Sweden)

    C Brandon Ogbunugafor

    Full Text Available Flow diagrams are a common tool used to help build and interpret models of dynamical systems, often in biological contexts such as consumer-resource models and similar compartmental models. Typically, their usage is intuitive and informal. Here, we present a formalized version of flow diagrams as a kind of weighted directed graph which follow a strict grammar, which translate into a system of ordinary differential equations (ODEs by a single unambiguous rule, and which have an equivalent representation as a relational database. (We abbreviate this schema of "ODEs and formalized flow diagrams" as OFFL. Drawing a diagram within this strict grammar encourages a mental discipline on the part of the modeler in which all dynamical processes of a system are thought of as interactions between dynamical species that draw parcels from one or more source species and deposit them into target species according to a set of transformation rules. From these rules, the net rate of change for each species can be derived. The modeling schema can therefore be understood as both an epistemic and practical heuristic for modeling, serving both as an organizational framework for the model building process and as a mechanism for deriving ODEs. All steps of the schema beyond the initial scientific (intuitive, creative abstraction of natural observations into model variables are algorithmic and easily carried out by a computer, thus enabling the future development of a dedicated software implementation. Such tools would empower the modeler to consider significantly more complex models than practical limitations might have otherwise proscribed, since the modeling framework itself manages that complexity on the modeler's behalf. In this report, we describe the chief motivations for OFFL, carefully outline its implementation, and utilize a range of classic examples from ecology and epidemiology to showcase its features.

  12. A New Coronary Model for MRI Perfusion Studies

    National Research Council Canada - National Science Library

    Nouri-Baranger, T

    2001-01-01

    .... A compartmental description of the blood flow is used. The compartments taken into account are the arteries, capillaries, lymphatic and venous systems, extravascular/extracellular and cellular domains...

  13. Human physiologically based pharmacokinetic model for propofol

    Directory of Open Access Journals (Sweden)

    Schnider Thomas W

    2005-04-01

    Full Text Available Abstract Background Propofol is widely used for both short-term anesthesia and long-term sedation. It has unusual pharmacokinetics because of its high lipid solubility. The standard approach to describing the pharmacokinetics is by a multi-compartmental model. This paper presents the first detailed human physiologically based pharmacokinetic (PBPK model for propofol. Methods PKQuest, a freely distributed software routine http://www.pkquest.com, was used for all the calculations. The "standard human" PBPK parameters developed in previous applications is used. It is assumed that the blood and tissue binding is determined by simple partition into the tissue lipid, which is characterized by two previously determined set of parameters: 1 the value of the propofol oil/water partition coefficient; 2 the lipid fraction in the blood and tissues. The model was fit to the individual experimental data of Schnider et. al., Anesthesiology, 1998; 88:1170 in which an initial bolus dose was followed 60 minutes later by a one hour constant infusion. Results The PBPK model provides a good description of the experimental data over a large range of input dosage, subject age and fat fraction. Only one adjustable parameter (the liver clearance is required to describe the constant infusion phase for each individual subject. In order to fit the bolus injection phase, for 10 or the 24 subjects it was necessary to assume that a fraction of the bolus dose was sequestered and then slowly released from the lungs (characterized by two additional parameters. The average weighted residual error (WRE of the PBPK model fit to the both the bolus and infusion phases was 15%; similar to the WRE for just the constant infusion phase obtained by Schnider et. al. using a 6-parameter NONMEM compartmental model. Conclusion A PBPK model using standard human parameters and a simple description of tissue binding provides a good description of human propofol kinetics. The major advantage of a

  14. Joint coevolutionary-epidemiological models dampen Red Queen cycles and alter conditions for epidemics.

    Science.gov (United States)

    MacPherson, Ailene; Otto, Sarah P

    2017-12-28

    Host-parasite interactions in the form of infectious diseases are a topic of interest in both evolutionary biology and public health. Both fields have relied on mathematical models to predict and understand the dynamics and consequences of these interactions. Yet few models explicitly incorporate both epidemiological and coevolutionary dynamics, allowing for genetic variation in both hosts and parasites. By comparing a matching-alleles model of coevolution, a susceptible-infected-recovered-susceptible compartmental model from epidemiology, and a combined coevolutionary-epidemiology model we assess the effect of the coevolutionary feedback on the epidemiological dynamics and vice versa. We find that Red-Queen cycles are not robust in an epidemiological framework and that coevolutionary interactions can alter the conditions under which epidemic cycles arise. Incorporating both explicit epidemiology and genetic diversity may have important implications for the maintenance of sexual reproduction as well as disease management. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Malaria transmission model for different levels of acquired immunity and temperature-dependent parameters (vector

    Directory of Open Access Journals (Sweden)

    Yang Hyun M

    2000-01-01

    Full Text Available OBJECTIVE: Describe the overall transmission of malaria through a compartmental model, considering the human host and mosquito vector. METHODS: A mathematical model was developed based on the following parameters: human host immunity, assuming the existence of acquired immunity and immunological memory, which boosts the protective response upon reinfection; mosquito vector, taking into account that the average period of development from egg to adult mosquito and the extrinsic incubation period of parasites (transformation of infected but non-infectious mosquitoes into infectious mosquitoes are dependent on the ambient temperature. RESULTS: The steady state equilibrium values obtained with the model allowed the calculation of the basic reproduction ratio in terms of the model's parameters. CONCLUSIONS: The model allowed the calculation of the basic reproduction ratio, one of the most important epidemiological variables.

  16. Predicting Oral Drug Absorption: Mini Review on Physiologically-Based Pharmacokinetic Models

    Directory of Open Access Journals (Sweden)

    Louis Lin

    2017-09-01

    Full Text Available Most marketed drugs are administered orally, despite the complex process of oral absorption that is difficult to predict. Oral bioavailability is dependent on the interplay between many processes that are dependent on both compound and physiological properties. Because of this complexity, computational oral physiologically-based pharmacokinetic (PBPK models have emerged as a tool to integrate these factors in an attempt to mechanistically capture the process of oral absorption. These models use inputs from in vitro assays to predict the pharmacokinetic behavior of drugs in the human body. The most common oral PBPK models are compartmental approaches, in which the gastrointestinal tract is characterized as a series of compartments through which the drug transits. The focus of this review is on the development of oral absorption PBPK models, followed by a brief discussion of the major applications of oral PBPK models in the pharmaceutical industry.

  17. Translational mixed-effects PKPD modelling of recombinant human growth hormone - from hypophysectomized rat to patients

    DEFF Research Database (Denmark)

    Thorsted, Anders; Thygesen, Peter; Agersø, Henrik

    2016-01-01

    and validated through simulations relative to patient data. KEY RESULTS: The final model described rhGH PK as a two compartmental model with parallel linear and non-linear elimination terms, parallel first-order absorption with a total s.c. bioavailability of 87% in rats. Induction of IGF-1 was described...... by an indirect response model with stimulation of kin and related to rhGH exposure through an Emax relationship. Increase in bodyweight was directly linked to individual concentrations of IGF-1 by a linear relation. The scaled model provided robust predictions of human systemic PK of rhGH, but exposure following...... a clinically relevant biomarker, IGF-1, to a primary clinical end-point, growth/bodyweight gain. Scaling of the model parameters provided robust predictions of the human PKPD in growth hormone-deficient patients including variability....

  18. Study of the stability of a SEIRS model for computer worm propagation

    Science.gov (United States)

    Hernández Guillén, J. D.; Martín del Rey, A.; Hernández Encinas, L.

    2017-08-01

    Nowadays, malware is the most important threat to information security. In this sense, several mathematical models to simulate malware spreading have appeared. They are compartmental models where the population of devices is classified into different compartments: susceptible, exposed, infectious, recovered, etc. The main goal of this work is to propose an improved SEIRS (Susceptible-Exposed-Infectious-Recovered-Susceptible) mathematical model to simulate computer worm propagation. It is a continuous model whose dynamic is ruled by means of a system of ordinary differential equations. It considers more realistic parameters related to the propagation; in fact, a modified incidence rate has been used. Moreover, the equilibrium points are computed and their local and global stability analyses are studied. From the explicit expression of the basic reproductive number, efficient control measures are also obtained.

  19. Giant plasma membrane vesicles: models for understanding membrane organization.

    Science.gov (United States)

    Levental, Kandice R; Levental, Ilya

    2015-01-01

    The organization of eukaryotic membranes into functional domains continues to fascinate and puzzle cell biologists and biophysicists. The lipid raft hypothesis proposes that collective lipid interactions compartmentalize the membrane into coexisting liquid domains that are central to membrane physiology. This hypothesis has proven controversial because such structures cannot be directly visualized in live cells by light microscopy. The recent observations of liquid-liquid phase separation in biological membranes are an important validation of the raft hypothesis and enable application of the experimental toolbox of membrane physics to a biologically complex phase-separated membrane. This review addresses the role of giant plasma membrane vesicles (GPMVs) in refining the raft hypothesis and expands on the application of GPMVs as an experimental model to answer some of key outstanding problems in membrane biology. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Mathematical models used to inform study design or surveillance systems in infectious diseases: a systematic review.

    Science.gov (United States)

    Herzog, Sereina A; Blaizot, Stéphanie; Hens, Niel

    2017-12-18

    Mathematical models offer the possibility to investigate the infectious disease dynamics over time and may help in informing design of studies. A systematic review was performed in order to determine to what extent mathematical models have been incorporated into the process of planning studies and hence inform study design for infectious diseases transmitted between humans and/or animals. We searched Ovid Medline and two trial registry platforms (Cochrane, WHO) using search terms related to infection, mathematical model, and study design from the earliest dates to October 2016. Eligible publications and registered trials included mathematical models (compartmental, individual-based, or Markov) which were described and used to inform the design of infectious disease studies. We extracted information about the investigated infection, population, model characteristics, and study design. We identified 28 unique publications but no registered trials. Focusing on compartmental and individual-based models we found 12 observational/surveillance studies and 11 clinical trials. Infections studied were equally animal and human infectious diseases for the observational/surveillance studies, while all but one between humans for clinical trials. The mathematical models were used to inform, amongst other things, the required sample size (n = 16), the statistical power (n = 9), the frequency at which samples should be taken (n = 6), and from whom (n = 6). Despite the fact that mathematical models have been advocated to be used at the planning stage of studies or surveillance systems, they are used scarcely. With only one exception, the publications described theoretical studies, hence, not being utilised in real studies.

  1. A systems approach to college drinking: development of a deterministic model for testing alcohol control policies.

    Science.gov (United States)

    Scribner, Richard; Ackleh, Azmy S; Fitzpatrick, Ben G; Jacquez, Geoffrey; Thibodeaux, Jeremy J; Rommel, Robert; Simonsen, Neal

    2009-09-01

    The misuse and abuse of alcohol among college students remain persistent problems. Using a systems approach to understand the dynamics of student drinking behavior and thus forecasting the impact of campus policy to address the problem represents a novel approach. Toward this end, the successful development of a predictive mathematical model of college drinking would represent a significant advance for prevention efforts. A deterministic, compartmental model of college drinking was developed, incorporating three processes: (1) individual factors, (2) social interactions, and (3) social norms. The model quantifies these processes in terms of the movement of students between drinking compartments characterized by five styles of college drinking: abstainers, light drinkers, moderate drinkers, problem drinkers, and heavy episodic drinkers. Predictions from the model were first compared with actual campus-level data and then used to predict the effects of several simulated interventions to address heavy episodic drinking. First, the model provides a reasonable fit of actual drinking styles of students attending Social Norms Marketing Research Project campuses varying by "wetness" and by drinking styles of matriculating students. Second, the model predicts that a combination of simulated interventions targeting heavy episodic drinkers at a moderately "dry" campus would extinguish heavy episodic drinkers, replacing them with light and moderate drinkers. Instituting the same combination of simulated interventions at a moderately "wet" campus would result in only a moderate reduction in heavy episodic drinkers (i.e., 50% to 35%). A simple, five-state compartmental model adequately predicted the actual drinking patterns of students from a variety of campuses surveyed in the Social Norms Marketing Research Project study. The model predicted the impact on drinking patterns of several simulated interventions to address heavy episodic drinking on various types of campuses.

  2. Toxicokinetic modeling challenges for aquatic nanotoxicology

    Directory of Open Access Journals (Sweden)

    Wei-Yu eChen

    2016-01-01

    Full Text Available Nanotoxicity has become of increasing concern since the rapid development of metal nanoparticles (NPs. Aquatic nanotoxicity depends on crucial qualitative and quantitative properties of nanomaterials that induce adverse effects on subcellular, tissue, and organ level. The dose-response effects of size-dependent metal NPs, however, are not well investigated in aquatic organisms. In order to determine the uptake and elimination rate constants for metal NPs in the metabolically active/ detoxified pool of tissues, a one-compartmental toxicokinetic model can be applied when subcellular partitioning of metal NPs data would be available. The present review is an attempt to describe the nano-characteristics of toxicokinetics and subcellular partitioning on aquatic organisms with the help of the mechanistic modeling for NP size-dependent physiochemical properties and parameters. Physiologically-based pharmacokinetic (PBPK models can provide an effective tool to estimate the time course of NP accumulation in target organs and is useful in quantitative risk assessments. NP accumulation in fish should take into account different effects of different NP sizes to better understand tissue accumulative capacities and dynamics. The size-dependent NP partition coefficient is a crucial parameter that influences tissue accumulation levels in PBPK modeling. Further research is needed to construct the effective systems-level oriented toxicokinetic model that can provide a useful tool to develop quantitatively the robustly approximate relations that convey a better insight into the impacts of environmental metal NPs on subcellular and tissue/organ responses in aquatic organisms.

  3. Systemic Distribution and Tumor Localization of Adoptively Transferred Lymphocytes in Mice: Comparison with Physiologically Based Pharmacokinetic Model

    Directory of Open Access Journals (Sweden)

    Robert J. Melder

    2002-01-01

    Full Text Available The mechanisms by which tumors are able to evade cellular immune responses are still largely unknown. It is likely, however, that the initial recruitment of lymphocytes to tumor vessels is limited by cell retention in normal tissue, which results in a low flux of these cells into the tumor vasculature. We grew MCaIV. (20mouse mammary carcinoma tumors in the leg of SCID mice and injected 111In-oxine-labeled, primed T lymphocytes directed against the tumor intravenously. The systemic distribution of cells in normal organs was similar between mice injected with primed and control lymphocyte populations, except for a delayed clearance of primed lymphocytes from the lungs. Kinetics of lymphocyte localization to the tumor were identical between the primed and control lymphocyte populations. Splenectomy before the injection of primed lymphocytes increased delivery of cells to the lungs and liver after 1 hour with no significant improvement in tumor localization. Within 24 to 168 hours after injection, localization of cells in the liver of splenectomized mice was higher than in the control group. However, no significant difference in tumor localization was observed between groups. A physiologically based compartmental model of lymphocyte distribution predicted the compartmental sequestration and identified model parameters critical for experimental planning and therapeutic optimization.

  4. On Spatially Explicit Models of Cholera Epidemics: Hydrologic controls, environmental drivers, human-mediated transmissions (Invited)

    Science.gov (United States)

    Rinaldo, A.; Bertuzzo, E.; Mari, L.; Righetto, L.; Gatto, M.; Casagrandi, R.; Rodriguez-Iturbe, I.

    2010-12-01

    A recently proposed model for cholera epidemics is examined. The model accounts for local communities of susceptibles and infectives in a spatially explicit arrangement of nodes linked by networks having different topologies. The vehicle of infection (Vibrio cholerae) is transported through the network links which are thought of as hydrological connections among susceptible communities. The mathematical tools used are borrowed from general schemes of reactive transport on river networks acting as the environmental matrix for the circulation and mixing of water-borne pathogens. The results of a large-scale application to the Kwa Zulu (Natal) epidemics of 2001-2002 will be discussed. Useful theoretical results derived in the spatially-explicit context will also be reviewed (like e.g. the exact derivation of the speed of propagation for traveling fronts of epidemics on regular lattices endowed with uniform population density). Network effects will be discussed. The analysis of the limit case of uniformly distributed population density proves instrumental in establishing the overall conditions for the relevance of spatially explicit models. To that extent, it is shown that the ratio between spreading and disease outbreak timescales proves the crucial parameter. The relevance of our results lies in the major differences potentially arising between the predictions of spatially explicit models and traditional compartmental models of the SIR-like type. Our results suggest that in many cases of real-life epidemiological interest timescales of disease dynamics may trigger outbreaks that significantly depart from the predictions of compartmental models. Finally, a view on further developments includes: hydrologically improved aquatic reservoir models for pathogens; human mobility patterns affecting disease propagation; double-peak emergence and seasonality in the spatially explicit epidemic context.

  5. Modeling Cerebral Blood Flow Control During Posture Change from Sitting to Standing

    DEFF Research Database (Denmark)

    Olufsen, Mette; Tran, Hien; Ottesen, Johnny T.

    2004-01-01

    Hypertension, decreased cerebral blood flow, and diminished cerebral blood flow regulation, are among the first signs indicating the presence of cerebral vascular disease. In this paper, we will present a mathematical model that can predict blood flow and pressure during posture change from sitting...... to standing. The mathematical model uses a compartmental approach to describe pulsatile blood flow and pressure in a number of compartments representing the systemic circulation. Our model includes compartments representing the trunk and upper extremities, the lower extremities, the brain, the atria......, the heart, and venous valves. We use physiologically based control mechanisms to describe the regulation of cerebral blood velocity and arterial pressure in response to orthostatic hypotension resulting from postural change. Beyond active control mechanisms we also have to include certain passive non...

  6. Biosphere transport of radionuclides. First modelling by using a selected example

    International Nuclear Information System (INIS)

    Bundi, A.

    1984-12-01

    The dispersion of radionuclides in the biosphere and their uptake by man via various nutritional pathways is studied using a compartment model. The sample environment is the area of the lower Limmat and Aare valleys. General considerations of the compartmental description of the biosphere are made. The problem of the description of surface features, in particular soil, sediment and water, is studied in detail using the code BIOPATH. This study is intended to be an example of how a model of the biosphere could be constructed. It is shown that this is a reasonable model to calculate the spreading of radionuclides in the biosphere and that it indicates the relative significance of individual compartments, pathways and radionuclides. Calculated values of doses to man, however, should not be used as reference data for safety analyses. (author)

  7. Thermodynamic modeling, energy equipartition, and nonconservation of entropy for discrete-time dynamical systems

    Directory of Open Access Journals (Sweden)

    Chellaboina Vijaysekhar

    2005-01-01

    Full Text Available We develop thermodynamic models for discrete-time large-scale dynamical systems. Specifically, using compartmental dynamical system theory, we develop energy flow models possessing energy conservation, energy equipartition, temperature equipartition, and entropy nonconservation principles for discrete-time, large-scale dynamical systems. Furthermore, we introduce a new and dual notion to entropy; namely, ectropy, as a measure of the tendency of a dynamical system to do useful work and grow more organized, and show that conservation of energy in an isolated thermodynamic system necessarily leads to nonconservation of ectropy and entropy. In addition, using the system ectropy as a Lyapunov function candidate, we show that our discrete-time, large-scale thermodynamic energy flow model has convergent trajectories to Lyapunov stable equilibria determined by the system initial subsystem energies.

  8. Modelling and sensitivity analysis of urinary platinum excretion in anticancer chemotherapy for the recovery of platinum

    DEFF Research Database (Denmark)

    Folens, Karel; Mortier, Séverine Thérèse F C; Baeten, Janis

    2016-01-01

    University Hospital in combination with compartmental models for urinary Pt excretion was performed to simulate the average Pt excretion profile during common treatment schemes. These average profiles can be used to assess the technical, social and economic feasibility of Pt-recovery from urine or wastewater...... are toxic for aquatic organisms. Therefore, efforts should be made to recover the Pt. The urinary excretion of Pt from two antineoplastics are taken under consideration, i.e. cisplatin and carboplatin. Using these reference compounds, a scenario analysis based on administration statistics from Ghent....... A one-compartment model is used for cisplatin, which is calibrated using the experimental data of six patients. In contrast, a two-compartment model with parameters from literature is used for carboplatin. A Global Sensitivity Analysis revealed kel, the rate constant of elimination, is the most...

  9. Energy metabolism in neuronal/glial induction and in iPSC models of brain disorders.

    Science.gov (United States)

    Mlody, Barbara; Lorenz, Carmen; Inak, Gizem; Prigione, Alessandro

    2016-04-01

    The metabolic switch associated with the reprogramming of somatic cells to pluripotency has received increasing attention in recent years. However, the impact of mitochondrial and metabolic modulation on stem cell differentiation into neuronal/glial cells and related brain disease modeling still remains to be fully addressed. Here, we seek to focus on this aspect by first addressing brain energy metabolism and its inter-cellular metabolic compartmentalization. We then review the findings related to the mitochondrial and metabolic reconfiguration occurring upon neuronal/glial specification from pluripotent stem cells (PSCs). Finally, we provide an update of the PSC-based models of mitochondria-related brain disorders and discuss the challenges and opportunities that may exist on the road to develop a new era of brain disease modeling and therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Reproduction numbers of infectious disease models

    Directory of Open Access Journals (Sweden)

    Pauline van den Driessche

    2017-08-01

    Full Text Available This primer article focuses on the basic reproduction number, ℛ0, for infectious diseases, and other reproduction numbers related to ℛ0 that are useful in guiding control strategies. Beginning with a simple population model, the concept is developed for a threshold value of ℛ0 determining whether or not the disease dies out. The next generation matrix method of calculating ℛ0 in a compartmental model is described and illustrated. To address control strategies, type and target reproduction numbers are defined, as well as sensitivity and elasticity indices. These theoretical ideas are then applied to models that are formulated for West Nile virus in birds (a vector-borne disease, cholera in humans (a disease with two transmission pathways, anthrax in animals (a disease that can be spread by dead carcasses and spores, and Zika in humans (spread by mosquitoes and sexual contacts. Some parameter values from literature data are used to illustrate the results. Finally, references for other ways to calculate ℛ0 are given. These are useful for more complicated models that, for example, take account of variations in environmental fluctuation or stochasticity. Keywords: Basic reproduction number, Disease control, West Nile virus, Cholera, Anthrax, Zika virus

  11. Mechanistic formulation of a lineal-quadratic-linear (LQL) model: split-dose experiments and exponentially decaying sources.

    Science.gov (United States)

    Guerrero, Mariana; Carlone, Marco

    2010-08-01

    In recent years, several models were proposed that modify the standard linear-quadratic (LQ) model to make the predicted survival curve linear at high doses. Most of these models are purely phenomenological and can only be applied in the particular case of acute doses per fraction. The authors consider a mechanistic formulation of a linear-quadratic-linear (LQL) model in the case of split-dose experiments and exponentially decaying sources. This model provides a comprehensive description of radiation response for arbitrary dose rate and fractionation with only one additional parameter. The authors use a compartmental formulation of the LQL model from the literature. They analytically solve the model's differential equations for the case of a split-dose experiment and for an exponentially decaying source. They compare the solutions of the survival fraction with the standard LQ equations and with the lethal-potentially lethal (LPL) model. In the case of the split-dose experiment, the LQL model predicts a recovery ratio as a function of dose per fraction that deviates from the square law of the standard LQ. The survival fraction as a function of time between fractions follows a similar exponential law as the LQ but adds a multiplicative factor to the LQ parameter beta. The LQL solution for the split-dose experiment is very close to the LPL prediction. For the decaying source, the differences between the LQL and the LQ solutions are negligible when the half-life of the source is much larger than the characteristic repair time, which is the clinically relevant case. The compartmental formulation of the LQL model can be used for arbitrary dose rates and provides a comprehensive description of dose response. When the survival fraction for acute doses is linear for high dose, a deviation of the square law formula of the recovery ratio for split doses is also predicted.

  12. Mechanistic formulation of a lineal-quadratic-linear (LQL) model: Split-dose experiments and exponentially decaying sources

    Energy Technology Data Exchange (ETDEWEB)

    Guerrero, Mariana; Carlone, Marco [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland 21201 (United States) and Department of Radiation Therapy, Department of Veterans Affairs Medical Center, Washington, DC 20422 (United States); Princess Margaret Hospital and Peel Regional Cancer Center, Toronto, Ontario M5G 2M9 (Canada)

    2010-08-15

    Purpose: In recent years, several models were proposed that modify the standard linear-quadratic (LQ) model to make the predicted survival curve linear at high doses. Most of these models are purely phenomenological and can only be applied in the particular case of acute doses per fraction. The authors consider a mechanistic formulation of a linear-quadratic-linear (LQL) model in the case of split-dose experiments and exponentially decaying sources. This model provides a comprehensive description of radiation response for arbitrary dose rate and fractionation with only one additional parameter. Methods: The authors use a compartmental formulation of the LQL model from the literature. They analytically solve the model's differential equations for the case of a split-dose experiment and for an exponentially decaying source. They compare the solutions of the survival fraction with the standard LQ equations and with the lethal-potentially lethal (LPL) model. Results: In the case of the split-dose experiment, the LQL model predicts a recovery ratio as a function of dose per fraction that deviates from the square law of the standard LQ. The survival fraction as a function of time between fractions follows a similar exponential law as the LQ but adds a multiplicative factor to the LQ parameter {beta}. The LQL solution for the split-dose experiment is very close to the LPL prediction. For the decaying source, the differences between the LQL and the LQ solutions are negligible when the half-life of the source is much larger than the characteristic repair time, which is the clinically relevant case. Conclusions: The compartmental formulation of the LQL model can be used for arbitrary dose rates and provides a comprehensive description of dose response. When the survival fraction for acute doses is linear for high dose, a deviation of the square law formula of the recovery ratio for split doses is also predicted.

  13. Nonlinear Synapses for Large-Scale Models: An Efficient Representation Enables Complex Synapse Dynamics Modeling in Large-Scale Simulations

    Directory of Open Access Journals (Sweden)

    Eric eHu

    2015-09-01

    Full Text Available Chemical synapses are comprised of a wide collection of intricate signaling pathways involving complex dynamics. These mechanisms are often reduced to simple spikes or exponential representations in order to enable computer simulations at higher spatial levels of complexity. However, these representations cannot capture important nonlinear dynamics found in synaptic transmission. Here, we propose an input-output (IO synapse model capable of generating complex nonlinear dynamics while maintaining low computational complexity. This IO synapse model is an extension of a detailed mechanistic glutamatergic synapse model capable of capturing the input-output relationships of the mechanistic model using the Volterra functional power series. We demonstrate that the IO synapse model is able to successfully track the nonlinear dynamics of the synapse up to the third order with high accuracy. We also evaluate the accuracy of the IO synapse model at different input frequencies and compared its performance with that of kinetic models in compartmental neuron models. Our results demonstrate that the IO synapse model is capable of efficiently replicating complex nonlinear dynamics that were represented in the original mechanistic model and provide a method to replicate complex and diverse synaptic transmission within neuron network simulations.

  14. Environmental modelling as an interface between policy and science

    International Nuclear Information System (INIS)

    Blaauboer, R.O.

    1991-01-01

    In this paper some recent developments in environmental modelling in the Netherlands are reviewed from a radiological background. An example is the growing interest in the integration of risk-analysis for exposures to ionizing radiation with that for chemicals and other environmental pollutants. Also since the Chernobyl accident the need of interdisciplinary cooperation, in order to obtain on-line predictive models is more strongly felt. For example atmospheric transport models for chemical pollutants are used for the modelling of the dispersion of radioactive material and vice versa models that were primarily meant for radiation protection purposes are used for other environmental pollutants such as dioxins. At the same time this tendency to integrate and/or couple compartmental models requires harmonization and has its own specific problems. Examples are the difficulties in handling uncertainties, validation, handling of large data bases, correlations between processes in various models and the differing methods and applications of the constituent models (deterministic, probabilistic, for normal or emergency situations etc.). It is thought that the radiological expertise can play an important role in some if not most of these trends in environmental modelling. (9 refs., 1 fig.)

  15. Modeling and optimization of tissue 10B concentration and dosimetry for arbitrary BPA-F infusion schedules in humans

    International Nuclear Information System (INIS)

    Kiger, W.S. III; Newton, T.H.; Palmer, M.R.

    2000-01-01

    Separate compartmental models have been derived for the concentration of 10 B resulting from BPA-F infusion in the central vascular space (i.e., blood or, more appropriately, plasma) and in glioblastoma multiforme and normal brain. By coupling the model for the temporal variation of 10 B concentration in the central vascular space with that for tissue, the dynamic behavior of the 10 B concentration and the resulting dosimetry in the relevant tissues and blood may be predicted for arbitrary infusion schedules. This coupled model may be used as a tool for identifying the optimal time for BNCT irradiation and optimal BPA-F infusion schedule (i.e., temporal targeting) in humans without the need for expensive and time-consuming pharmacokinetic studies for every infusion schedule considered. This model was used to analyze the concentration profiles resulting from a wide range of infusion schedules and their implications for dosimetry. (author)

  16. A Population Pharmacokinetic Model for Disposition in Plasma, Saliva and Urine of Scopolamine after Intranasal Administration to Healthy Human Subjects

    Science.gov (United States)

    Wu, L.; Tam, V. H.; Chow, D. S. L.; Putcha, L.

    2014-01-01

    An intranasal gel formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness. The bioavailability and pharmacokinetics (PK) were evaluated under the Food and Drug Administration guidelines for clinical trials with an Investigative New Drug (IND) protocol. The aim of this project was to develop a PK model that can predict the relationship between plasma, saliva and urinary scopolamine concentrations using data collected from the IND clinical trials with INSCOP. Methods: Twelve healthy human subjects were administered three dose levels (0.1, 0.2 and 0.4 mg) of INSCOP. Serial blood, saliva and urine samples were collected between 5 min and 24 h after dosing and scopolamine concentrations were measured by using a validated LC-MS-MS assay. Pharmacokinetic Compartmental models, using actual dosing and sampling times, were built using Phoenix (version 1.2). Model selection was based on the likelihood ratio test on the difference of criteria (-2LL) and comparison of the quality of fit plots. Results: The best structural model for INSCOP (minimal -2LL= 502.8) was established. It consisted of one compartment each for plasma, saliva and urine, respectively, which were connected with linear transport processes except the nonlinear PK process from plasma to saliva compartment. The best-fit estimates of PK parameters from individual PK compartmental analysis and Population PK model analysis were shown in Tables 1 and 2, respectively. Conclusion: A population PK model that could predict population and individual PK of scopolamine in plasma, saliva and urine after dosing was developed and validated. Incorporating a non-linear transfer from plasma to saliva compartments resulted in a significantly improved model fitting. The model could be used to predict scopolamine plasma concentrations from salivary and urinary drug levels, allowing non-invasive therapeutic monitoring of scopolamine in space and other remote environments.

  17. Focuss algorithm application in kinetic compartment modeling for PET tracer

    International Nuclear Information System (INIS)

    Huang Xinrui; Bao Shanglian

    2004-01-01

    Molecular imaging is in the process of becoming. Its application mostly depends on the molecular discovery process of imaging probes and drugs, from the mouse to the patient, from research to clinical practice. Positron emission tomography (PET) can non-invasively monitor . pharmacokinetic and functional processes of drugs in intact organisms at tracer concentrations by kinetic modeling. It has been known that for all biological systems, linear or nonlinear, if the system is injected by a tracer in a steady state, the distribution of the tracer follows the kinetics of a linear compartmental system, which has sums of exponential solutions. Based on the general compartmental description of the tracer's fate in vivo, we presented a novel kinetic modeling approach for the quantification of in vivo tracer studies with dynamic positron emission tomography (PET), which can determine a parsimonious model consisting with the measured data. This kinetic modeling technique allows for estimation of parametric images from a voxel based analysis and requires no a priori decision about the tracer's fate in vivo, instead determining the most appropriate model from the information contained within the kinetic data. Choosing a set of exponential functions, convolved with the plasma input function, as basis functions, the time activity curve of a region or a pixel can be written as a linear combination of the basis functions with corresponding coefficients. The number of non-zero coefficients returned corresponds to the model order which is related to the number of tissue compartments. The system macro parameters are simply determined using the focal underdetermined system solver (FOCUSS) algorithm. The FOCUSS algorithm is a nonparametric algorithm for finding localized energy solutions from limited data and is a recursive linear estimation procedure. FOCUSS algorithm usually converges very fast, so demands a few iterations. The effectiveness is verified by simulation and clinical

  18. Denervation-induced homeostatic dendritic plasticity in morphological granule cell models

    Directory of Open Access Journals (Sweden)

    Hermann Cuntz

    2014-03-01

    Full Text Available Neuronal death and subsequent denervation of target areas are major consequences of several neurological conditions such asischemia or neurodegeneration (Alzheimer's disease. The denervation-induced axonal loss results in reorganization of the dendritic tree of denervated neurons. The dendritic reorganization has been previously studied using entorhinal cortex lesion (ECL. ECL leads to shortening and loss of dendritic segments in the denervated outer molecular layer of the dentate gyrus. However, the functional importance of these long-term dendritic alterations is not yet understood and their impact on neuronal electrical properties remains unclear. Here we analyzed what happens to the electrotonic structure and excitability of dentate granule cells after lesion-induced alterations of their dendritic morphology, assuming all other parameters remain equal. We performed comparative electrotonic analysis in anatomically and biophysically realistic compartmental models of 3D-reconstructed healthy and denervated granule cells. Using the method of morphological modeling based on optimization principles minimizing the amount of wiring and maximizing synaptic democracy, we built artificial granule cells which replicate morphological features of their real counterparts. Our results show that somatofugal and somatopetal voltage attenuation in the passive cable model are strongly reduced in denervated granule cells. In line with these predictions, the attenuation both of simulated backpropagating action potentials and forward propagating EPSPs was significantly reduced in dendrites of denervated neurons. Intriguingly, the enhancement of action potential backpropagation occurred specifically in the denervated dendritic layers. Furthermore, simulations of synaptic f-I curves revealed a homeostatic increase of excitability in denervated granule cells. In summary, our morphological and compartmental modeling indicates that unless modified by changes of

  19. Integrative approaches for modeling regulation and function of the respiratory system.

    Science.gov (United States)

    Ben-Tal, Alona; Tawhai, Merryn H

    2013-01-01

    Mathematical models have been central to understanding the interaction between neural control and breathing. Models of the entire respiratory system-which comprises the lungs and the neural circuitry that controls their ventilation-have been derived using simplifying assumptions to compartmentalize each component of the system and to define the interactions between components. These full system models often rely-through necessity-on empirically derived relationships or parameters, in addition to physiological values. In parallel with the development of whole respiratory system models are mathematical models that focus on furthering a detailed understanding of the neural control network, or of the several functions that contribute to gas exchange within the lung. These models are biophysically based, and rely on physiological parameters. They include single-unit models for a breathing lung or neural circuit, through to spatially distributed models of ventilation and perfusion, or multicircuit models for neural control. The challenge is to bring together these more recent advances in models of neural control with models of lung function, into a full simulation for the respiratory system that builds upon the more detailed models but remains computationally tractable. This requires first understanding the mathematical models that have been developed for the respiratory system at different levels, and which could be used to study how physiological levels of O2 and CO2 in the blood are maintained. Copyright © 2013 Wiley Periodicals, Inc.

  20. Mathematical modeling and simulation in animal health - Part II: principles, methods, applications, and value of physiologically based pharmacokinetic modeling in veterinary medicine and food safety assessment.

    Science.gov (United States)

    Lin, Z; Gehring, R; Mochel, J P; Lavé, T; Riviere, J E

    2016-10-01

    This review provides a tutorial for individuals interested in quantitative veterinary pharmacology and toxicology and offers a basis for establishing guidelines for physiologically based pharmacokinetic (PBPK) model development and application in veterinary medicine. This is important as the application of PBPK modeling in veterinary medicine has evolved over the past two decades. PBPK models can be used to predict drug tissue residues and withdrawal times in food-producing animals, to estimate chemical concentrations at the site of action and target organ toxicity to aid risk assessment of environmental contaminants and/or drugs in both domestic animals and wildlife, as well as to help design therapeutic regimens for veterinary drugs. This review provides a comprehensive summary of PBPK modeling principles, model development methodology, and the current applications in veterinary medicine, with a focus on predictions of drug tissue residues and withdrawal times in food-producing animals. The advantages and disadvantages of PBPK modeling compared to other pharmacokinetic modeling approaches (i.e., classical compartmental/noncompartmental modeling, nonlinear mixed-effects modeling, and interspecies allometric scaling) are further presented. The review finally discusses contemporary challenges and our perspectives on model documentation, evaluation criteria, quality improvement, and offers solutions to increase model acceptance and applications in veterinary pharmacology and toxicology. © 2016 John Wiley & Sons Ltd.

  1. A parametric model of radioisotopic tracer flow through the kidney

    International Nuclear Information System (INIS)

    Nahorski, Z.

    1996-01-01

    To assess the state of a kidney from radiological examination a dynamic model of flow of an isotopic tracer through the kidney, of a convolution type, is commonly used. It is a nonparametric model where the output is related to the input by an integral relation. In this paper a new parametric model of tracer flow through the kidney is presented. It takes to much bigger extent into account the physiology of the tracer flow in kidney than previously proposed compartmental models. It consists of the submodels of flow through nephrons which are in the form of ordinary differential equations with pure delays between input and the output flows. The delay is caused by the time of passage of the isotope through nephrons and depends on the nephron length. It is assumed that the distribution of nephrons of different length is exponential. The renal pelvis is described as the one-compartment model. The solutions of the equations are given for the assumed two-exponential decay of the isotope tracer in the blood following the bolus injection of the tracer. The formulae obtained are then used to simulate the influence of changes in the model parameters, representing the flow condition through the kidney, on the shape of the waveforms depicting time evolution of the amount of the isotope being in the kidney

  2. Towards a characterization of behavior-disease models.

    Directory of Open Access Journals (Sweden)

    Nicola Perra

    Full Text Available The last decade saw the advent of increasingly realistic epidemic models that leverage on the availability of highly detailed census and human mobility data. Data-driven models aim at a granularity down to the level of households or single individuals. However, relatively little systematic work has been done to provide coupled behavior-disease models able to close the feedback loop between behavioral changes triggered in the population by an individual's perception of the disease spread and the actual disease spread itself. While models lacking this coupling can be extremely successful in mild epidemics, they obviously will be of limited use in situations where social disruption or behavioral alterations are induced in the population by knowledge of the disease. Here we propose a characterization of a set of prototypical mechanisms for self-initiated social distancing induced by local and non-local prevalence-based information available to individuals in the population. We characterize the effects of these mechanisms in the framework of a compartmental scheme that enlarges the basic SIR model by considering separate behavioral classes within the population. The transition of individuals in/out of behavioral classes is coupled with the spreading of the disease and provides a rich phase space with multiple epidemic peaks and tipping points. The class of models presented here can be used in the case of data-driven computational approaches to analyze scenarios of social adaptation and behavioral change.

  3. Noise-induced divisive gain control in neuron models.

    Science.gov (United States)

    Longtin, André; Doiron, Brent; Bulsara, Adi R

    2002-01-01

    A recent computational study of gain control via shunting inhibition has shown that the slope of the frequency-versus-input (f-I) characteristic of a neuron can be decreased by increasing the noise associated with the inhibitory input (Neural Comput. 13, 227-248). This novel noise-induced divisive gain control relies on the concommittant increase of the noise variance with the mean of the total inhibitory conductance. Here we investigate this effect using different neuronal models. The effect is shown to occur in the standard leaky integrate-and-fire (LIF) model with additive Gaussian white noise, and in the LIF with multiplicative noise acting on the inhibitory conductance. The noisy scaling of input currents is also shown to occur in the one-dimensional theta-neuron model, which has firing dynamics, as well as a large scale compartmental model of a pyramidal cell in the electrosensory lateral line lobe of a weakly electric fish. In this latter case, both the inhibition and the excitatory input have Poisson statistics; noise-induced divisive inhibition is thus seen in f-I curves for which the noise increases along with the input I. We discuss how the variation of the noise intensity along with inputs is constrained by the physiological context and the class of model used, and further provide a comparison of the divisive effect across models.

  4. Functional scintiscanning using iodine 131-tagged BSP and compartmental analysis to predict disorders of the liver and biliary tract. /sup 131/J-BSP-Funktionsszintigraphie und Kompartmentanalyse bei der Abklaerung von Leber- und Gallenwegserkrankungen

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, K.

    1984-02-03

    164 individuals with normal liver findings or with overt disorders of the liver were subjected to functional scintiscanning using iodine 131-tagged bromosulfophthalein and subsequent quantitative analysis of liver function parameters. The curves of the cardiac and hepatic activity plotted against time showed a bi-exponential course. The number of compartments involved was in keeping with the number of exponential summands, which were determined solely from the values measured. Our considerations were based on a two-compartment model with plasma (P) and liver (L) as the two volumes of distribution; from this, the liver function was calculated in terms of the velocity constants k/sub 12/ (plasma-liver), k/sub 20/ (liver-gallbladder) and k/sub 21/ (liver-plasma). In the majority of hepatobiliary disorders the clearance rate (k/sub 12/) was seen to be decreased at a statistically significant level, the only exception here being fatty changes of the liver and choledocholithiasis. The excretion constant (k/sub 20/) was considerably increased in liver cirrhosis and non-obstructive disorders of the gallbladder and biliary tract, while it was decreased in biliary tract disorders associated with signs of impaired bile flow. In order to be able to make a clear distinction between intrahepatic and extrahepatic cholestasis, which is necessary in the differential diagnosis of icterus, sequential scintiscans are still required in addition to determinations of k/sub 12/ and k/sub 20/, as they offer the advantage of visual evaluation of the recorded excretion pattern of the tracer substance. The determination of the ratio between the velocity constants (k/sub 12/:k/sub 20/) provides useful information on the function of the liver cells. During follow-up observations any incipient changes in liver function can easily be predicted from the velocity constants mentioned above and evaluated on a quantitative basis. (TRV).

  5. Modelling of long-term and short-term mechanisms of arterial pressure control in the cardiovascular system: an object-oriented approach.

    Science.gov (United States)

    Fernandez de Canete, J; Luque, J; Barbancho, J; Munoz, V

    2014-04-01

    A mathematical model that provides an overall description of both the short- and long-term mechanisms of arterial pressure regulation is presented. Short-term control is exerted through the baroreceptor reflex while renal elimination plays a role in long-term control. Both mechanisms operate in an integrated way over the compartmental model of the cardiovascular system. The whole system was modelled in MODELICA, which uses a hierarchical object-oriented modelling strategy, under the DYMOLA simulation environment. The performance of the controlled system was analysed by simulation in light of the existing hypothesis and validation tests previously performed with physiological data, demonstrating the effectiveness of both regulation mechanisms under physiological and pathological conditions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Guidelines for visualizing and annotating rule-based models.

    Science.gov (United States)

    Chylek, Lily A; Hu, Bin; Blinov, Michael L; Emonet, Thierry; Faeder, James R; Goldstein, Byron; Gutenkunst, Ryan N; Haugh, Jason M; Lipniacki, Tomasz; Posner, Richard G; Yang, Jin; Hlavacek, William S

    2011-10-01

    Rule-based modeling provides a means to represent cell signaling systems in a way that captures site-specific details of molecular interactions. For rule-based models to be more widely understood and (re)used, conventions for model visualization and annotation are needed. We have developed the concepts of an extended contact map and a model guide for illustrating and annotating rule-based models. An extended contact map represents the scope of a model by providing an illustration of each molecule, molecular component, direct physical interaction, post-translational modification, and enzyme-substrate relationship considered in a model. A map can also illustrate allosteric effects, structural relationships among molecular components, and compartmental locations of molecules. A model guide associates elements of a contact map with annotation and elements of an underlying model, which may be fully or partially specified. A guide can also serve to document the biological knowledge upon which a model is based. We provide examples of a map and guide for a published rule-based model that characterizes early events in IgE receptor (FcεRI) signaling. We also provide examples of how to visualize a variety of processes that are common in cell signaling systems but not considered in the example model, such as ubiquitination. An extended contact map and an associated guide can document knowledge of a cell signaling system in a form that is visual as well as executable. As a tool for model annotation, a map and guide can communicate the content of a model clearly and with precision, even for large models.

  7. Laplace transform in tracer kinetic modeling

    International Nuclear Information System (INIS)

    Hauser, Eliete B.

    2013-01-01

    The main objective this paper is to quantify the pharmacokinetic processes: absorption, distribution and elimination of radiopharmaceutical(tracer), using Laplace transform method. When the drug is administered intravenously absorption is complete and is available in the bloodstream to be distributed throughout the whole body in all tissues and fluids, and to be eliminated. Mathematical modeling seeks to describe the processes of distribution and elimination through compartments, where distinct pools of tracer (spatial location or chemical state) are assigned to different compartments. A compartment model is described by a system of differential equations, where each equation represents the sum of all the transfer rates to and from a specific compartment. In this work a two-tissue irreversible compartment model is used for description of tracer, [ 18 F]2-fluor-2deoxy-D-glucose. In order to determine the parameters of the model, it is necessary to have information about the tracer delivery in the form of an input function representing the time-course of tracer concentration in arterial blood or plasma. We estimate the arterial input function in two stages and apply the Levenberg-Marquardt Method to solve nonlinear regressions. The transport of FDG across de arterial blood is very fast in the first ten minutes and then decreases slowly. We use de Heaviside function to represent this situation and this is the main contribution of this study. We apply the Laplace transform and the analytical solution for two-tissue irreversible compartment model is obtained. The only approach is to determinate de arterial input function. (author)

  8. Laplace transform in tracer kinetic modeling

    Energy Technology Data Exchange (ETDEWEB)

    Hauser, Eliete B., E-mail: eliete@pucrs.br [Instituto do Cerebro (InsCer/FAMAT/PUC-RS), Porto Alegre, RS, (Brazil). Faculdade de Matematica

    2013-07-01

    The main objective this paper is to quantify the pharmacokinetic processes: absorption, distribution and elimination of radiopharmaceutical(tracer), using Laplace transform method. When the drug is administered intravenously absorption is complete and is available in the bloodstream to be distributed throughout the whole body in all tissues and fluids, and to be eliminated. Mathematical modeling seeks to describe the processes of distribution and elimination through compartments, where distinct pools of tracer (spatial location or chemical state) are assigned to different compartments. A compartment model is described by a system of differential equations, where each equation represents the sum of all the transfer rates to and from a specific compartment. In this work a two-tissue irreversible compartment model is used for description of tracer, [{sup 18}F]2-fluor-2deoxy-D-glucose. In order to determine the parameters of the model, it is necessary to have information about the tracer delivery in the form of an input function representing the time-course of tracer concentration in arterial blood or plasma. We estimate the arterial input function in two stages and apply the Levenberg-Marquardt Method to solve nonlinear regressions. The transport of FDG across de arterial blood is very fast in the first ten minutes and then decreases slowly. We use de Heaviside function to represent this situation and this is the main contribution of this study. We apply the Laplace transform and the analytical solution for two-tissue irreversible compartment model is obtained. The only approach is to determinate de arterial input function. (author)

  9. Modeling elemental strontium in human bone based on in vivo x-ray fluorescence measurements in osteoporotic females self-supplementing with strontium citrate.

    Science.gov (United States)

    Moise, H; Chettle, D R; Pejović-Milić, A

    2016-03-01

    An in-house custom I-125 excited in vivo x-ray fluorescence (IVXRF) system was used to perform bone strontium (Sr) measurements in individuals suffering from osteoporosis and/or osteopenia. These individuals, who were self-administering with Sr supplements of their choice, were measured frequently, ranging from weekly to biweekly to monthly, over four years, as part of the Ryerson and McMaster Sr in Bone Research Study. Based on these data collected, data from eight subjects were used to perform kinetic modeling of Sr in human bone. Power and exponential models were used to model the data based on one and two compartmental systems. Model parameters included: mean normalized baseline bone Sr signal, half-life and bone Sr uptake. A one compartmental exponential model applied to finger and ankle bone measurements gave half-lives of (508  ±  331) d and (232  ±  183) d, respectively, but did not show statistically significant differences (p  =  0.087 96). However, the values fall within literature estimates. When a two compartmental model was applied to finger bone measurements, half-lives of (300  ±  163) d and (2201  ±  1662) d were observed. Ankle bone data gave half-lives of (156  ±  117) d and (1681  ±  744) d. A two sample t-test, assuming unequal variances, showed these half-lives to be statistically different in both the finger and ankle bone measurements (p  =  0.0147 and p  =  0.00711, respectively). Common kinetic parameters amongst the different subjects could not be unambiguously identified due to the wide scatter of data, leading to an inconclusive kinetic model. The wide distribution of data is suggested to be physiological since technical and positioning factors were eliminated as possible causes. This outcome indicates the need for a more controlled study and further understanding of the physiological mechanism of Sr absorption.

  10. Positron Emission Tomography in clinical research and clinical diagnosis: tracer modelling and radioreceptors

    International Nuclear Information System (INIS)

    Beckers, C.; Goffinet, A.; Bol, A.

    1989-01-01

    Positron emission tomography (PET) allows noninvasive studies of different metabolic pathways in man in a unique way. Human biochemistry can now be studied using physiological tracers like glucose or oxygen; promising investigations are now underway with various neurotransmitters. The aim of this workshop, sponsored by the European Community, has been to convene a group of experts to discuss more deeply the problems related to the study of receptors and energy metabolism, and this particularly in relationship with the compartmental analysis and the modelling of the data. Up to now, these have mostly been accumulated for the brain and heart. Oncology is now a growing field of interest and more applications are certain to arise in the near future. The papers included in this volume summarize the main points discussed during the workshop. (author). refs.; figs.; tabs

  11. Modeling the 3D functional architecture of the nucleus in animal and plant kingdoms.

    Science.gov (United States)

    Gaudin, Valérie; Andrey, Philippe; Devinoy, Eve; Kress, Clémence; Kieu, Kiên; Beaujean, Nathalie; Maurin, Yves; Debey, Pascale

    2009-11-01

    Compartmentalization is one of the fundamental principles which underly nuclear function. Numerous studies describe complex and sometimes conflicting relationships between nuclear gene positioning and transcription regulation. Therefore the question is whether topological landmarks and/or organization principles exist to describe the nuclear architecture and, if existing, whether these principles are identical in the animal and plant kingdoms. In the frame of an agroBI-INRA program on nuclear architecture, we set up a multidisciplinary approach combining biological studies, spatial statistics and 3D modeling to investigate spatial organization of a nuclear compartment in both plant and animal cells in their physiological contexts. In this article, we review the questions addressed in this program and the methodology of our work.

  12. Immunological tumor destruction in a murine melanoma model by targeted LTalpha independent of secondary lymphoid tissue

    DEFF Research Database (Denmark)

    Schrama, D.; Voigt, H.; Eggert, A.O.

    2008-01-01

    BACKGROUND: We previously demonstrated that targeting lymphotoxin alpha (LTalpha) to the tumor evokes its immunological destruction in a syngeneic B16 melanoma model. Since treatment was associated with the induction of peritumoral tertiary lymphoid tissue, we speculated that the induced immune...... of specific T-cell responses even in the absence of secondary lymphoid organs. In addition, this effect is accompanied by the initiation of tertiary lymphoid tissue at the tumor site in which B and T lymphocytes are compartmentalized in defined areas and which harbor expanded numbers of tumor specific T cells...... as demonstrated by in situ TRP-2/K(b) tetramer staining. Mechanistically, targeted LTalpha therapy seems to induce changes at the tumor site which allows a coordinated interaction of immune competent cells triggering the induction of tertiary lymphoid tissue. CONCLUSION: Thus, our data demonstrate that targeted...

  13. Modelling dynamics of plasmid-gene mediated antimicrobial resistance in enteric bacteria using stochastic differential equations.

    Science.gov (United States)

    Volkova, Victoriya V; Lu, Zhao; Lanzas, Cristina; Scott, H Morgan; Gröhn, Yrjö T

    2013-01-01

    The ubiquitous commensal bacteria harbour genes of antimicrobial resistance (AMR), often on conjugative plasmids. Antimicrobial use in food animals subjects their enteric commensals to antimicrobial pressure. A fraction of enteric Escherichia coli in cattle exhibit plasmid-gene mediated AMR to a third-generation cephalosporin ceftiofur. We adapted stochastic differential equations with diffusion approximation (a compartmental stochastic mathematical model) to research the sources and roles of stochasticity in the resistance dynamics, both during parenteral antimicrobial therapy and in its absence. The results demonstrated that demographic stochasticity among enteric E. coli in the occurrence of relevant events was important for the AMR dynamics only when bacterial numbers were depressed during therapy. However, stochasticity in the parameters of enteric E. coli ecology, whether externally or intrinsically driven, contributed to a wider distribution of the resistant E. coli fraction, both during therapy and in its absence, with stochasticities in individual parameters interacting in their contribution.

  14. Optimal control of vaccination rate in an epidemiological model of Clostridium difficile transmission.

    Science.gov (United States)

    Stephenson, Brittany; Lanzas, Cristina; Lenhart, Suzanne; Day, Judy

    2017-12-01

    The spore-forming, gram-negative bacteria Clostridium difficile can cause severe intestinal illness. A striking increase in the number of cases of C. difficile infection (CDI) among hospitals has highlighted the need to better understand how to prevent the spread of CDI. In our paper, we modify and update a compartmental model of nosocomial C. difficile transmission to include vaccination. We then apply optimal control theory to determine the time-varying optimal vaccination rate that minimizes a combination of disease prevalence and spread in the hospital population as well as cost, in terms of time and money, associated with vaccination. Various hospital scenarios are considered, such as times of increased antibiotic prescription rate and times of outbreak, to see how such scenarios modify the optimal vaccination rate. By comparing the values of the objective functional with constant vaccination rates to those with time-varying optimal vaccination rates, we illustrate the benefits of time-varying controls.

  15. Pharmacokinetic Modeling of Intranasal Scopolamine in Plasma Saliva and Urine

    Science.gov (United States)

    Wu, L.; Tam, V. H.; Chow, D. S. L.; Putcha, L.

    2015-01-01

    An intranasal gel dosage formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness (SMS). The bioavailability and pharmacokinetics (PK) were evaluated under IND (Investigational New Drug) guidelines. The aim of the project was to develop a PK model that can predict the relationships among plasma, saliva and urinary scopolamine concentrations using data collected from the IND clinical trial protocol with INSCOP. Twelve healthy human subjects were administered at three dose levels (0.1, 0.2 and 0.4 mg) of INSCOP. Serial blood, saliva and urine samples were collected between 5 min to 24 h after dosing and scopolamine concentrations were measured by using a validated LC-MS-MS assay. PK compartmental models, using actual dosing and sampling time, were established using Phoenix (version 1.2). Model selection was based on a likelihood ratio test on the difference of criteria (-2LL (i.e. log-likelihood ratio test)) and comparison of the quality of fit plots. The results: Predictable correlations among scopolamine concentrations in compartments of plasma, saliva and urine were established, and for the first time the model satisfactorily predicted the population and individual PK of INSCOP in plasma, saliva and urine. The model can be utilized to predict the INSCOP plasma concentration by saliva and urine data, and it will be useful for monitoring the PK of scopolamine in space and other remote environments using non-invasive sampling of saliva and/or urine.

  16. Modeling liver electrical conductivity during hypertonic injection.

    Science.gov (United States)

    Castellví, Quim; Sánchez-Velázquez, Patricia; Moll, Xavier; Berjano, Enrique; Andaluz, Anna; Burdío, Fernando; Bijnens, Bart; Ivorra, Antoni

    2018-01-01

    Metastases in the liver frequently grow as scattered tumor nodules that neither can be removed by surgical resection nor focally ablated. Previously, we have proposed a novel technique based on irreversible electroporation that may be able to simultaneously treat all nodules in the liver while sparing healthy tissue. The proposed technique requires increasing the electrical conductivity of healthy liver by injecting a hypersaline solution through the portal vein. Aiming to assess the capability of increasing the global conductivity of the liver by means of hypersaline fluids, here, it is presented a mathematical model that estimates the NaCl distribution within the liver and the resulting conductivity change. The model fuses well-established compartmental pharmacokinetic models of the organ with saline injection models used for resuscitation treatments, and it considers changes in sinusoidal blood viscosity because of the hypertonicity of the solution. Here, it is also described a pilot experimental study in pigs in which different volumes of NaCl 20% (from 100 to 200 mL) were injected through the portal vein at different flow rates (from 53 to 171 mL/minute). The in vivo conductivity results fit those obtained by the model, both quantitatively and qualitatively, being able to predict the maximum conductivity with a 14.6% average relative error. The maximum conductivity value was 0.44 second/m, which corresponds to increasing 4 times the mean basal conductivity (0.11 second/m). The results suggest that the presented model is well suited for predicting on liver conductivity changes during hypertonic saline injection. Copyright © 2017 John Wiley & Sons, Ltd.

  17. Discrete Fracture Network Models for Risk Assessment of Carbon Sequestration in Coal

    Energy Technology Data Exchange (ETDEWEB)

    Jack Pashin; Guohai Jin; Chunmiao Zheng; Song Chen; Marcella McIntyre

    2008-07-01

    A software package called DFNModeler has been developed to assess the potential risks associated with carbon sequestration in coal. Natural fractures provide the principal conduits for fluid flow in coal-bearing strata, and these fractures present the most tangible risks for the leakage of injected carbon dioxide. The objectives of this study were to develop discrete fracture network (DFN) modeling tools for risk assessment and to use these tools to assess risks in the Black Warrior Basin of Alabama, where coal-bearing strata have high potential for carbon sequestration and enhanced coalbed methane recovery. DFNModeler provides a user-friendly interface for the construction, visualization, and analysis of DFN models. DFNModeler employs an OpenGL graphics engine that enables real-time manipulation of DFN models. Analytical capabilities in DFNModeler include display of structural and hydrologic parameters, compartmentalization analysis, and fluid pathways analysis. DFN models can be exported to third-party software packages for flow modeling. DFN models were constructed to simulate fracturing in coal-bearing strata of the upper Pottsville Formation in the Black Warrior Basin. Outcrops and wireline cores were used to characterize fracture systems, which include joint systems, cleat systems, and fault-related shear fractures. DFN models were constructed to simulate jointing, cleating, faulting, and hydraulic fracturing. Analysis of DFN models indicates that strata-bound jointing compartmentalizes the Pottsville hydrologic system and helps protect shallow aquifers from injection operations at reservoir depth. Analysis of fault zones, however, suggests that faulting can facilitate cross-formational flow. For this reason, faults should be avoided when siting injection wells. DFN-based flow models constructed in TOUGH2 indicate that fracture aperture and connectivity are critical variables affecting the leakage of injected CO{sub 2} from coal. Highly transmissive joints

  18. A pharmacokinetic drug-drug interaction model of simvastatin and clarithromycin in humans.

    Science.gov (United States)

    Methaneethorn, Janthima; Chaiwong, Krissanapong; Pongpanich, Komwut; Sonsingh, Phakawat; Lohitnavy, Manupat

    2014-01-01

    Simvastatin is a HMG-CoA reductase Inhibitor and a substrate of CYP3A4. Clarithromycin is a commonly used macrolide antibiotics and a potent inhibitor of CYP3A4. When co-administered with simvastatin, clarithromycin can significantly increase simvastatin plasma concentration levels, thereby, increase the risk of rhabdomyolysis. At present, pharmacokinetic data of the interaction between both drugs are available. However, they are being used for semi-quantitative application only, not for quantitative prediction. We aimed to develop a mathematical model describing a drug-drug interaction between simvastatin and clarithromycin in humans. Selected pharmacokinetic interaction study was obtained from PubMed search. Concentration-time course data were subsequently extracted and used for model development. Compartmental pharmacokinetic interaction model was developed using Advanced Continuous Simulating Language Extreme (ACSLX), a FORTRAN language-based computer program. The drug-drug interaction between simvastatin and clarithromycin was modeled simultaneously with a parent-metabolite model for clarithromycin and a one-compartment model for simvastatin linked to its active form, simvastatin hydroxy acid. The simulated simvastatin concentrations obtained from the final model displayed satisfactory goodness of fit to the data from the literature. Our model could successfully describe concentration-time course of simvastatin-clarithromycin interaction. The resulting interaction model can be able to use for further development of a quantitative model predicting rhabdomyolysis occurrence in patients concurrently receiving simvastatin and clarithromycin.

  19. Volterra representation enables modeling of complex synaptic nonlinear dynamics in large-scale simulations.

    Science.gov (United States)

    Hu, Eric Y; Bouteiller, Jean-Marie C; Song, Dong; Baudry, Michel; Berger, Theodore W

    2015-01-01

    Chemical synapses are comprised of a wide collection of intricate signaling pathways involving complex dynamics. These mechanisms are often reduced to simple spikes or exponential representations in order to enable computer simulations at higher spatial levels of complexity. However, these representations cannot capture important nonlinear dynamics found in synaptic transmission. Here, we propose an input-output (IO) synapse model capable of generating complex nonlinear dynamics while maintaining low computational complexity. This IO synapse model is an extension of a detailed mechanistic glutamatergic synapse model capable of capturing the input-output relationships of the mechanistic model using the Volterra functional power series. We demonstrate that the IO synapse model is able to successfully track the nonlinear dynamics of the synapse up to the third order with high accuracy. We also evaluate the accuracy of the IO synapse model at different input frequencies and compared its performance with that of kinetic models in compartmental neuron models. Our results demonstrate that the IO synapse model is capable of efficiently replicating complex nonlinear dynamics that were represented in the original mechanistic model and provide a method to replicate complex and diverse synaptic transmission within neuron network simulations.

  20. Spatiotemporal compartmentalization of key physiological processes during muscle precursor differentiation

    OpenAIRE

    Özbudak, Ertuğrul M; Tassy, Olivier; Pourquié, Olivier

    2010-01-01

    The development of multicellular organisms is controlled by transcriptional networks. Understanding the role of these networks requires a full understanding of transcriptome regulation during embryogenesis. Several microarray studies have characterized the temporal evolution of the transcriptome during development in different organisms [Wang QT, et al. (2004) Dev Cell 6:133–144; Furlong EE, Andersen EC, Null B, White KP, Scott MP (2001) Science 293:1629–1633; Mitiku N, Baker JC (2007) Dev Ce...

  1. Synthesis of copper and nickel complexes using compartmental ...

    Indian Academy of Sciences (India)

    Administrator

    been analysed by X-ray crystallography. Complexes 1 and 3 have square pyramidal geometry. The co-ordination geometry around the metal ion in complex 7 is square planar and that in complex 10 is octahedral. The electrochemical property of the complexes was studied using cyclic voltammetry. A single quasi-reversible ...

  2. Cation-sensitive compartmentalization in metallacarborane containing polymer nanoparticles

    Czech Academy of Sciences Publication Activity Database

    Ďorďovič, V.; Uchman, M.; Reza, M.; Ruokolainen, J.; Zhigunov, Alexander; Ivankov, O. I.; Matějíček, P.

    2016-01-01

    Roč. 6, č. 12 (2016), s. 9884-9892 ISSN 2046-2069 R&D Projects: GA ČR(CZ) GA14-14608S Institutional support: RVO:61389013 Keywords : polymer nanoparticles * metallacarborane * double-hydrophilic block copolymer Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.108, year: 2016

  3. Glucose 6-phosphate compartmentation and the control of glycogen synthesis

    NARCIS (Netherlands)

    Meijer, Alfred

    2002-01-01

    Using adenovirus-mediated gene transfer into FTO-2B cells, a rat hepatoma cell line, we have overexpressed hexokinase I, (HK I), glucokinase (GK), liver glycogen synthase (LGS), muscle glycogen synthase (MGS), and combinations of each of the two glucose phosphorylating enzymes with each one of the

  4. Differential compartmentalization of mRNAs in squid giant axon.

    Science.gov (United States)

    Chun, J T; Gioio, A E; Crispino, M; Giuditta, A; Kaplan, B B

    1996-11-01

    Previously, we reported that the squid giant axon contains a heterogeneous population of mRNAs that includes beta-actin, beta-tubulin, kinesin, neurofilament proteins, and enolase. To define the absolute levels and relative distribution of these mRNAs, we have used competitive reverse transcription-PCR to quantify the levels of five mRNAs present in the giant axon and giant fiber lobe (GFL), the location of the parental cell soma. In the GFL, the number of transcripts for these mRNAs varied over a fourfold range, with beta-tubulin being the most abundant mRNA species (1.25 x 10(9) molecules per GFL). Based on transcript number, the rank order of mRNA levels in the GFL was beta-tubulin > beta-actin > kinesin > enolase > microtubule-associated protein (MAP) H1. In contrast, kinesin mRNA was most abundant in the axon (4.1 x 10(7) molecules per axon) with individual mRNA levels varying 15-fold. The rank order of mRNA levels in the axon was kinesin > beta-tubulin > MAP H1 > beta-actin > enolase. The relative abundance of the mRNA species in the axon did not correlate with the size of the transcript, nor was it directly related to their corresponding levels in the GFL. Taken together, these findings confirm that significant amounts of mRNA are present in the giant axon and suggest that specific mRNAs are differentially transported into the axonal domain.

  5. OSIRIS : Efficient and consistent recovery of compartmentalized operating systems

    NARCIS (Netherlands)

    Bhat, Koustubha; Vogt, Dirk; Kouwe, Erik Van Der; Gras, Ben; Sambuc, Lionel; Tanenbaum, Andrew S.; Bos, Herbert; Giuffrida, Cristiano

    2016-01-01

    Much research has gone into making operating systems more amenable to recovery and more resilient to crashes. Traditional solutions rely on partitioning the operating system (OS) to contain the effects of crashes within compartments and facilitate modular recovery. However, state dependencies among

  6. The effects of membrane compartmentalization of csk on TCR signaling

    Czech Academy of Sciences Publication Activity Database

    Otáhal, Pavel; Pata, Supansa; Angelisová, Pavla; Hořejší, Václav; Brdička, Tomáš

    2010-01-01

    Roč. 1813, č. 2 (2010), s. 367-376 ISSN 0006-3002 R&D Projects: GA ČR GEMEM/09/E011; GA MŠk 1M0506 Institutional research plan: CEZ:AV0Z50520514 Keywords : T-cell activation * lipid rafts * CBP Subject RIV: EB - Genetics ; Molecular Biology

  7. Barriers in the brain : resolving dendritic spine morphology and compartmentalization

    NARCIS (Netherlands)

    Adrian, Max; Kusters, Remy; Wierenga, Corette J; Storm, Cornelis; Hoogenraad, Casper C; Kapitein, Lukas C

    2014-01-01

    Dendritic spines are micron-sized protrusions that harbor the majority of excitatory synapses in the central nervous system. The head of the spine is connected to the dendritic shaft by a 50-400 nm thin membrane tube, called the spine neck, which has been hypothesized to confine biochemical and

  8. Compartmentalization and ultrastructural alterations induced by chromium in aquatic macrophytes.

    Science.gov (United States)

    Mangabeira, Pedro A; Ferreira, Aluane S; de Almeida, Alex-Alan F; Fernandes, Valéria F; Lucena, Emerson; Souza, Vânia L; dos Santos Júnior, Alberto J; Oliveira, Arno H; Grenier-Loustalot, Marie F; Barbier, Fréderique; Silva, Delmira C

    2011-12-01

    The aim of the present study was to identify the sites of accumulation of Cr in the species of macrophytes that are abundant in the Cachoeira river, namely, Alternanthera philoxeroides, Borreria scabiosoides, Polygonum ferrugineum and Eichhornia crassipes. Plants were grown in nutritive solution supplemented with 0.25 and 50 mg l(-1) of CrCl(3)·6H(2)O. Samples of plant tissues were digested with HNO(3)/HCl in a closed-vessel microwave system and the concentrations of Cr determined using inductively-coupled plasma mass spectrometry (ICP-MS). The ultrastructure of root, stem and leaf tissue was examined using transmission electron microscopy (TEM) and secondary ion mass spectrometry (SIMS) in order to determine the sites of accumulation of Cr and to detect possible alterations in cell organelles induced by the presence of the metal. Chromium accumulated principally in the roots of the four macrophytes (8.6-30 mg kg(-1) dw), with much lower concentrations present in the stems and leaves (3.8-8.6 and 0.01-9.0 mg kg(-1) dw, respectively). Within root tissue, Cr was present mainly in the vacuoles of parenchyma cells and cell walls of xylem and parenchyma. Alterations in the shape of the chloroplasts and nuclei were detected in A. philoxeroides and B. scabiosoides, suggesting a possible application of these aquatic plants as biomarkers from Cr contamination.

  9. Compartmentalized dynamics of cytomegalovirus replication in treated congenital infection.

    Science.gov (United States)

    Luck, S E; Emery, V C; Atkinson, C; Sharland, M; Griffiths, P D

    2016-09-01

    Cytomegalovirus (CMV) is the most prevalent congenital infection in developed countries. A significant number of infected infants develop long-term neurodevelopmental and hearing impairment irrespective of whether disease is detectable at birth. Studies of viral load and replication dynamics have informed the treatment of CMV in adult populations but no similar data exist in neonates. To study CMV virus kinetics in different body fluids of babies treated for congenital infection. CMV virus load was sequentially analyzed in blood, urine and saliva in 17 babies treated for symptomatic congenital CMV infection. Virus was detectable in the urine and saliva of all babies at baseline but in only 15/17 in blood. At the end of 6 weeks of antiviral treatment CMV remained detectable in 9/14 blood samples, 9/12 urine samples and 4/7 salivary swabs. Median half-life (T1/2) of virus decline in blood was 2.4 days (IQR 1.9-3.3) and basic reproductive number (Ro) was 2.3. Although T1/2 values were similar in urine and saliva to those observed in blood, virus dynamics differed both during and after treatment. T1/2 and Ro in blood in this group of neonates were similar to values derived from studies of immunocompromised adults. The persistent viremia observed in treated neonates cannot therefore be adequately explained by the virus dynamics early in treatment. The different dynamics exhibited in blood and urine suggests that studying changes in distinct body compartments may assist in further understanding long-term manifestations of disease. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

  10. Compartmental analysis of metals in waterpipe smoking technique.

    Science.gov (United States)

    Al-Kazwini, Akeel T; Said, Adi J; Sdepanian, Stephanie

    2015-02-18

    The number of waterpipe tobacco smokers has been increasing worldwide. Smokers can be exposed to a number of toxicants, some of which are metals. The aim of this study is to quantitatively determine if the water filtration stage of the waterpipe smoking process successfully decreases exposure to Bi, Cr, Cu, Fe, Mg, Mn, Mo, Ni, Pb, V, and U. Four samples of commercially available tobacco (Moassel) were compared in terms of the total amount of metal contained within the fresh tobacco sample and the amount of metal distributed into each compartment of the waterpipe after a smoking session. For all metals analysed, the concentration of metal 'filtered' out during the water bubbling stage is around 3% (±1%) of the total metal. It can be concluded that this small fraction would not protect the user against exposure to the majority of the potentially toxic metals.

  11. Compartmentalization and transport in beta-lactam antibiotics biosynthesis

    NARCIS (Netherlands)

    Evers, ME; Trip, H; van den Berg, MA; Bovenberg, RAL; Driessen, AJM

    2004-01-01

    Classical strain improvement of beta-lactam producing organisms by random mutagenesis has been a powerful tool during the last century. Current insights in the biochemistry and genetics of beta-lactam production, in particular in the filamentous fungus Penicillium chrysogenum, however, make a more

  12. Fire-scar formation and compartmentalization in oak

    Science.gov (United States)

    Kevin T. Smith; Elaine Kennedy. Sutherland

    1999-01-01

    Fire scars result from the death of the vascular cambium resulting from excessive heating, which exposes sapwood to infection and initiates the wood decay process. In southeastern Ohio, prescribed fires in April 1995 and 1997 scarred Quercus prinus L. and Q. velutina Lam. Low-intensity fires scorched bark and produced scars, primarily on the downslope side of the stem...

  13. Cellular compartmentalization and heavy metal load in the moss ...

    African Journals Online (AJOL)

    ... low compared to Cu, Cr and Cd and these results into low toxicity to B. lambarenensis. It was concluded that moss can be effectively used as biomonitors/bioindicator of environmental pollution due to dust particles from cement factories. Keywords: Bioconcentration, Toxicity, Bioavailability, Biomonitor, transmembrane, ...

  14. Apartment Compartmentalization With an Aerosol-Based Sealing Process

    Energy Technology Data Exchange (ETDEWEB)

    Maxwell, Sean [Consortium for Advanced Residential Buildings (CARB), Norwalk, CT (United States); Berger, David [Consortium for Advanced Residential Buildings (CARB), Norwalk, CT (United States); Harrington, Curtis [Univ. of California, Davis, CA (United States)

    2015-03-01

    The U.S. Department of Energy Building America Team, Consortium for Advanced Residential Buildings, sought to demonstrate this new technology application in a new construction multifamily building in Queens, New York. The effectiveness of the sealing process was evaluated by three methods: air leakage testing of overall apartment before-and-after sealing, point-source testing of individual leaks, and pressure measurements in the walls of an apartment during sealing.

  15. Retinal ganglion cells: Energetics, compartmentation, axonal transport, cytoskeletons and vulnerability.

    Science.gov (United States)

    Yu, Dao-Yi; Cringle, Stephen J; Balaratnasingam, Chandrakumar; Morgan, William H; Yu, Paula K; Su, Er-Ning

    2013-09-01

    Retinal ganglion cells (RGCs) are specialized projection neurons that relay an immense amount of visual information from the retina to the brain. RGC signal inputs are collected by dendrites and output is distributed from the cell body via very thin (0.5-1 μm) and long (∼50 mm) axons. The RGC cell body is larger than other retinal neurons, but is still only a very small fraction (one ten thousandths) of the length and total surface area of the axon. The total distance traversed by RGCs extends from the retina, starting from synapses with bipolar and amacrine cells, to the brain, to synapses with neurons in the lateral geniculate nucleus. This review will focus on the energy demands of RGCs and the relevant tissues that surround them. RGC survival and function unexceptionally depends upon free energy, predominantly adenosine triphosphate (ATP). RGC energy metabolism is vastly different when compared to that of the photoreceptors. Each subcellular component of the RGC is remarkably different in terms of structure, function and extracellular environment. The energy demands and distribution of each component are also distinct as evidenced by the uneven distribution of mitochondria and ATP within the RGC - signifying the presence of intracellular energy gradients. In this review we will describe RGCs as having four subcellular components, (1) Dendrites, (2) Cell body, (3) Non-myelinated axon, including intraocular and optic nerve head portions, and (4) Myelinated axon, including the intra-orbital and intracranial portions. We will also describe how RGCs integrate information from each subcellular component in order achieve intracellular homeostatic stability as well as respond to perturbations in the extracellular environment. The possible cellular mechanisms such as axonal transport and axonal cytoskeleton proteins that are involved in maintaining RGC energy homeostasis during normal and disease conditions will also be discussed in depth. The emphasis of this review will be on energetic mechanisms within RGC components that have the most relevance to clinical ophthalmology. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Differential compartmentalization and distinct functions of GABAB receptor variants

    DEFF Research Database (Denmark)

    Vigot, Réjan; Barbieri, Samuel; Bräuner-Osborne, Hans

    2006-01-01

    GABAB receptors are the G protein-coupled receptors for the main inhibitory neurotransmitter in the brain, gamma-aminobutyric acid (GABA). Molecular diversity in the GABAB system arises from the GABAB1a and GABAB1b subunit isoforms that solely differ in their ectodomains by a pair of sushi repeat...

  17. Linear Theory of Soil Organic Carbon Dynamics: Implications in Modeling Soil Respiration and Carbon Sequestration

    Science.gov (United States)

    Porporato, A.; Manzoni, S.; Katul, G.

    2008-12-01

    The long-term, large-scale soil organic carbon dynamics are typically described by mathematical models based on networks of linear reservoirs. Properties of these networks can be diagnosed from linear system theory (i.e. impulse-response transformations), which is seldom used in soil biogeochemistry, although it can be used to compare and test different models in the context of long-term carbon sequestration in soils. In this work, the general theory of linear impulse-response systems is briefly reviewed and linked to the theory of stochastic point processes. Two characteristic times are considered, the residence time (i.e., the time spent by a molecule in the system) and age (the time elapsed since the molecule entered the system). Both are represented through their probability density functions, which are computed explicitly as a function of model structure. Different cases are analyzed and compared, ranging from a simple individual-pool model, to feedback models involving loops (as in models of soil organic carbon-microbial interactions and physical adsorption-desorption), and to more complex networks often used to simulate in the details the soil organic carbon processes. As examples for these complex networks, the compartmental model CENTURY (Parton et al., 1987), and the continuum-quality Q-model (Agren and Bosatta, 1996) are considered. We assess the relative importance of model structural characteristics to determine the organic carbon residence time and age distributions.

  18. Cross-species comparison of biological themes and underlying genes on a global gene expression scale in a mouse model of colorectal liver metastasis and in clinical specimens

    Directory of Open Access Journals (Sweden)

    Schirmacher Peter

    2008-09-01

    Full Text Available Abstract Background Invasion-related genes over-expressed by tumor cells as well as by reacting host cells represent promising drug targets for anti-cancer therapy. Such candidate genes need to be validated in appropriate animal models. Results This study examined the suitability of a murine model (CT26/Balb/C of colorectal liver metastasis to represent clinical liver metastasis specimens using a global gene expression approach. Cross-species similarity was examined between pure liver, liver invasion, tumor invasion and pure tumor compartments through overlap of up-regulated genes and gene ontology (GO-based biological themes on the level of single GO-terms and of condensed GO-term families. Three out of four GO-term families were conserved in a compartment-specific way between the species: secondary metabolism (liver, invasion (invasion front, and immune response (invasion front and liver. Among the individual GO-terms over-represented in the invasion compartments in both species were "extracellular matrix", "cell motility", "cell adhesion" and "antigen presentation" indicating that typical invasion related processes are operating in both species. This was reflected on the single gene level as well, as cross-species overlap of potential target genes over-expressed in the combined invasion front compartments reached up to 36.5%. Generally, histopathology and gene expression correlated well as the highest single gene overlap was found to be 44% in syn-compartmental comparisons (liver versus liver whereas cross-compartmental overlaps were much lower (e.g. liver versus tumor: 9.7%. However, single gene overlap was surprisingly high in some cross-compartmental comparisons (e.g. human liver invasion compartment and murine tumor invasion compartment: 9.0% despite little histolopathologic similarity indicating that invasion relevant genes are not necessarily confined to histologically defined compartments. Conclusion In summary, cross

  19. A model of spreading of sudden events on social networks

    Science.gov (United States)

    Wu, Jiao; Zheng, Muhua; Zhang, Zi-Ke; Wang, Wei; Gu, Changgui; Liu, Zonghua

    2018-03-01

    Information spreading has been studied for decades, but its underlying mechanism is still under debate, especially for those ones spreading extremely fast through the Internet. By focusing on the information spreading data of six typical events on Sina Weibo, we surprisingly find that the spreading of modern information shows some new features, i.e., either extremely fast or slow, depending on the individual events. To understand its mechanism, we present a susceptible-accepted-recovered model with both information sensitivity and social reinforcement. Numerical simulations show that the model can reproduce the main spreading patterns of the six typical events. By this model, we further reveal that the spreading can be speeded up by increasing either the strength of information sensitivity or social reinforcement. Depending on the transmission probability and information sensitivity, the final accepted size can change from continuous to discontinuous transition when the strength of the social reinforcement is large. Moreover, an edge-based compartmental theory is presented to explain the numerical results. These findings may be of significance on the control of information spreading in modern society.

  20. Biokinetic of plutonium in human beings. Analysis and modification of ICRP 67 model

    International Nuclear Information System (INIS)

    Luciani, A.; Castellani, C. M.

    2001-01-01

    A preliminary research of the available data and empirical functions for the plutonium excretion after injection was carried out. The ICRP model presented in the Publication no. 67 was then analyzed comparing its predictions for the activity in urine and, at a lesser extent, in feces and blood, with the collected data and empirical curves. The model was modified and an optimized age-related compartmental model was developed. A new skeletal model recently developed was also introduced and age depending bone remodelling rates were assumed on the basis of the ICRP Publication 70. This model provides a better agreement with measured urinary excretion data than the current ICRP 67 model, avoiding unphysiological assumptions such as the transfer of activity from soft tissue to urinary bladder, that were part of the ICRP model. The new optimized model predictions of the activity in faeces and in blood after an injection are also closer to the available data than the ICRP 67 estimations. A good agreement with the partitioning factor of plutonium between skeleton and liver obtained from different autopsy studies was also observed [it

  1. Plant Metabolic Modeling: Achieving New Insight into Metabolism and Metabolic Engineering

    Science.gov (United States)

    Baghalian, Kambiz; Hajirezaei, Mohammad-Reza; Schreiber, Falk

    2014-01-01

    Models are used to represent aspects of the real world for specific purposes, and mathematical models have opened up new approaches in studying the behavior and complexity of biological systems. However, modeling is often time-consuming and requires significant computational resources for data development, data analysis, and simulation. Computational modeling has been successfully applied as an aid for metabolic engineering in microorganisms. But such model-based approaches have only recently been extended to plant metabolic engineering, mainly due to greater pathway complexity in plants and their highly compartmentalized cellular structure. Recent progress in plant systems biology and bioinformatics has begun to disentangle this complexity and facilitate the creation of efficient plant metabolic models. This review highlights several aspects of plant metabolic modeling in the context of understanding, predicting and modifying complex plant metabolism. We discuss opportunities for engineering photosynthetic carbon metabolism, sucrose synthesis, and the tricarboxylic acid cycle in leaves and oil synthesis in seeds and the application of metabolic modeling to the study of plant acclimation to the environment. The aim of the review is to offer a current perspective for plant biologists without requiring specialized knowledge of bioinformatics or systems biology. PMID:25344492

  2. Metabolic dynamics in skeletal muscle during acute reduction in blood flow and oxygen supply to mitochondria: in-silico studies using a multi-scale, top-down integrated model.

    Directory of Open Access Journals (Sweden)

    Ranjan K Dash

    Full Text Available Control mechanisms of cellular metabolism and energetics in skeletal muscle that may become evident in response to physiological stresses such as reduction in blood flow and oxygen supply to mitochondria can be quantitatively understood using a multi-scale computational model. The analysis of dynamic responses from such a model can provide insights into mechanisms of metabolic regulation that may not be evident from experimental studies. For the purpose, a physiologically-based, multi-scale computational model of skeletal muscle cellular metabolism and energetics was developed to describe dynamic responses of key chemical species and reaction fluxes to muscle ischemia. The model, which incorporates key transport and metabolic processes and subcellular compartmentalization, is based on dynamic mass balances of 30 chemical species in both capillary blood and tissue cells (cytosol and mitochondria domains. The reaction fluxes in cytosol and mitochondria are expressed in terms of a general phenomenological Michaelis-Menten equation involving the compartmentalized energy controller ratios ATP/ADP and NADH/NAD(+. The unknown transport and reaction parameters in the model are estimated simultaneously by minimizing the differences between available in vivo experimental data on muscle ischemia and corresponding model outputs in coupled with the resting linear flux balance constraints using a robust, nonlinear, constrained-based, reduced gradient optimization algorithm. With the optimal parameter values, the model is able to simulate dynamic responses to reduced blood flow and oxygen supply to mitochondria associated with muscle ischemia of several key metabolite concentrations and metabolic fluxes in the subcellular cytosolic and mitochondrial compartments, some that can be measured and others that can not be measured with the current experimental techniques. The model can be applied to test complex hypotheses involving dynamic regulation of cellular

  3. Modelling primaquine-induced haemolysis in G6PD deficiency.

    Science.gov (United States)

    Watson, James; Taylor, Walter Rj; Menard, Didier; Kheng, Sim; White, Nicholas J

    2017-02-04

    Primaquine is the only drug available to prevent relapse in vivax malaria. The main adverse effect of primaquine is erythrocyte age and dose-dependent acute haemolytic anaemia in individuals with glucose-6-phosphate dehydrogenase deficiency (G6PDd). As testing for G6PDd is often unavailable, this limits the use of primaquine for radical cure. A compartmental model of the dynamics of red blood cell production and destruction was designed to characterise primaquine-induced haemolysis using a holistic Bayesian analysis of all published data and was used to predict a safer alternative to the currently recommended once weekly 0.75 mg/kg regimen for G6PDd. The model suggests that a step-wise increase in daily administered primaquine dose would be relatively safe in G6PDd. If this is confirmed, then were this regimen to be recommended for radical cure patients would not require testing for G6PDd in areas where G6PDd Viangchan or milder variants are prevalent.

  4. Stochastic modeling for magnetic resonance quantification of myocardial blood flow

    Science.gov (United States)

    Seethamraju, Ravi T.; Muehling, Olaf; Panse, Prasad M.; Wilke, Norbert M.; Jerosch-Herold, Michael

    2000-10-01

    Quantification of myocardial blood flow is useful for determining the functional severity of coronary artery lesions. With advances in MR imaging it has become possible to assess myocardial perfusion and blood flow in a non-invasive manner by rapid serial imaging following injection of contrast agent. To date most approaches reported in the literature relied mostly on deriving relative indices of myocardial perfusion directly from the measured signal intensity curves. The central volume principle on the other hand states that it is possible to derive absolute myocardial blood flow from the tissue impulse response. Because of the sensitivity involved in deconvolution due to noise in measured data, conventional methods are sub-optimal, hence, we propose to use stochastic time series modeling techniques like ARMA to obtain a robust impulse response estimate. It is shown that these methods when applied for the optical estimation of the transfer function give accurate estimates of myocardial blood flow. The most significant advantage of this approach, compared with compartmental tracer kinetic models, is the use of a minimum set of prior assumptions on data. The bottleneck in assessing myocardial blood flow, does not lie in the MRI acquisition, but rather in the effort or time for post processing. It is anticipated that the very limited requirements for user input and interaction will be of significant advantage for the clinical application of these methods. The proposed methods are validated by comparison with mean blood flow measurements obtained from radio-isotope labeled microspheres.

  5. Elementary proof of convergence to the mean-field model for the SIR process.

    Science.gov (United States)

    Armbruster, Benjamin; Beck, Ekkehard

    2017-08-01

    The susceptible-infected-recovered (SIR) model has been used extensively to model disease spread and other processes. Despite the widespread usage of this ordinary differential equation (ODE) based model which represents the mean-field approximation of the underlying stochastic SIR process on contact networks, only few rigorous approaches exist and these use complex semigroup and martingale techniques to prove that the expected fraction of the susceptible and infected nodes of the stochastic SIR process on a complete graph converges as the number of nodes increases to the solution of the mean-field ODE model. Extending the elementary proof of convergence for the SIS process introduced by Armbruster and Beck (IMA J Appl Math, doi: 10.1093/imamat/hxw010 , 2016) to the SIR process, we show convergence using only a system of three ODEs, simple probabilistic inequalities, and basic ODE theory. Our approach can also be generalized to many other types of compartmental models (e.g., susceptible-infected-recovered-susceptible (SIRS)) which are linear ODEs with the addition of quadratic terms for the number of new infections similar to the SI term in the SIR model.

  6. Disease mapping based on stochastic SIR-SI model for Dengue and Chikungunya in Malaysia

    International Nuclear Information System (INIS)

    Samat, N. A.; Ma'arof, S. H. Mohd Imam

    2014-01-01

    This paper describes and demonstrates a method for relative risk estimation which is based on the stochastic SIR-SI vector-borne infectious disease transmission model specifically for Dengue and Chikungunya diseases in Malaysia. Firstly, the common compartmental model for vector-borne infectious disease transmission called the SIR-SI model (susceptible-infective-recovered for human populations; susceptible-infective for vector populations) is presented. This is followed by the explanations on the stochastic SIR-SI model which involve the Bayesian description. This stochastic model then is used in the relative risk formulation in order to obtain the posterior relative risk estimation. Then, this relative estimation model is demonstrated using Dengue and Chikungunya data of Malaysia. The viruses of these diseases are transmitted by the same type of female vector mosquito named Aedes Aegypti and Aedes Albopictus. Finally, the findings of the analysis of relative risk estimation for both Dengue and Chikungunya diseases are presented, compared and displayed in graphs and maps. The distribution from risk maps show the high and low risk area of Dengue and Chikungunya diseases occurrence. This map can be used as a tool for the prevention and control strategies for both diseases

  7. Disease mapping based on stochastic SIR-SI model for Dengue and Chikungunya in Malaysia

    Energy Technology Data Exchange (ETDEWEB)

    Samat, N. A.; Ma' arof, S. H. Mohd Imam [Department of Mathematics, Faculty of Science and Mathematics, Universiti Pendidikan Sultan Idris, 35900 Tanjung Malim, Perak (Malaysia)

    2014-12-04

    This paper describes and demonstrates a method for relative risk estimation which is based on the stochastic SIR-SI vector-borne infectious disease transmission model specifically for Dengue and Chikungunya diseases in Malaysia. Firstly, the common compartmental model for vector-borne infectious disease transmission called the SIR-SI model (susceptible-infective-recovered for human populations; susceptible-infective for vector populations) is presented. This is followed by the explanations on the stochastic SIR-SI model which involve the Bayesian description. This stochastic model then is used in the relative risk formulation in order to obtain the posterior relative risk estimation. Then, this relative estimation model is demonstrated using Dengue and Chikungunya data of Malaysia. The viruses of these diseases are transmitted by the same type of female vector mosquito named Aedes Aegypti and Aedes Albopictus. Finally, the findings of the analysis of relative risk estimation for both Dengue and Chikungunya diseases are presented, compared and displayed in graphs and maps. The distribution from risk maps show the high and low risk area of Dengue and Chikungunya diseases occurrence. This map can be used as a tool for the prevention and control strategies for both diseases.

  8. Disease mapping based on stochastic SIR-SI model for Dengue and Chikungunya in Malaysia

    Science.gov (United States)

    Samat, N. A.; Ma'arof, S. H. Mohd Imam

    2014-12-01

    This paper describes and demonstrates a method for relative risk estimation which is based on the stochastic SIR-SI vector-borne infectious disease transmission model specifically for Dengue and Chikungunya diseases in Malaysia. Firstly, the common compartmental model for vector-borne infectious disease transmission called the SIR-SI model (susceptible-infective-recovered for human populations; susceptible-infective for vector populations) is presented. This is followed by the explanations on the stochastic SIR-SI model which involve the Bayesian description. This stochastic model then is used in the relative risk formulation in order to obtain the posterior relative risk estimation. Then, this relative estimation model is demonstrated using Dengue and Chikungunya data of Malaysia. The viruses of these diseases are transmitted by the same type of female vector mosquito named Aedes Aegypti and Aedes Albopictus. Finally, the findings of the analysis of relative risk estimation for both Dengue and Chikungunya diseases are presented, compared and displayed in graphs and maps. The distribution from risk maps show the high and low risk area of Dengue and Chikungunya diseases occurrence. This map can be used as a tool for the prevention and control strategies for both diseases.

  9. A simulation age-specific tuberculosis model for the Cape Town metropole

    Directory of Open Access Journals (Sweden)

    Farai Nyabadza

    2013-09-01

    Full Text Available Tuberculosis (TB continues to present an insurmountable health burden in the Western Cape Province of South Africa. TB dynamics in adults is different from that in children, with the former determining the latter. Because the dynamics of TB are largely dependent on age, planning for interventions requires reasonable and realistic projections of the incidence across ages. It is thus important to model the dynamics of TB using mathematical models as predictive tools. We considered a TB compartmental model that is age dependent and whose parameters are set as functions of age. The model was fitted to the TB incidence data from the Cape Town metropole. The effective contact rate, a function of both age and time, was changed to fit the model to the notification rates of active TB disease cases. Our simulations illustrate that age structure plays an important role in the dynamics of TB. Projections on the future of the epidemic were made for each age group. The projected results show that TB incidence is likely to increase in the lower age groups of the population. It is clearly evident that even very simple models when applied to limited data can actually give valuable insights. Our results show that the age groups who have the highest incidence rates of active TB disease have the highest contribution in the transmission of TB. Furthermore, interventions should be targeted in the age group 25-34 years.

  10. A spatial model of mosquito host-seeking behavior.

    Directory of Open Access Journals (Sweden)

    Bree Cummins

    Full Text Available Mosquito host-seeking behavior and heterogeneity in host distribution are important factors in predicting the transmission dynamics of mosquito-borne infections such as dengue fever, malaria, chikungunya, and West Nile virus. We develop and analyze a new mathematical model to describe the effect of spatial heterogeneity on the contact rate between mosquito vectors and hosts. The model includes odor plumes generated by spatially distributed hosts, wind velocity, and mosquito behavior based on both the prevailing wind and the odor plume. On a spatial scale of meters and a time scale of minutes, we compare the effectiveness of different plume-finding and plume-tracking strategies that mosquitoes could use to locate a host. The results show that two different models of chemotaxis are capable of producing comparable results given appropriate parameter choices and that host finding is optimized by a strategy of flying across the wind until the odor plume is intercepted. We also assess the impact of changing the level of host aggregation on mosquito host-finding success near the end of the host-seeking flight. When clusters of hosts are more tightly associated on smaller patches, the odor plume is narrower and the biting rate per host is decreased. For two host groups of unequal number but equal spatial density, the biting rate per host is lower in the group with more individuals, indicative of an attack abatement effect of host aggregation. We discuss how this approach could assist parameter choices in compartmental models that do not explicitly model the spatial arrangement of individuals and how the model could address larger spatial scales and other probability models for mosquito behavior, such as Lévy distributions.

  11. Comparison of four physiological models for analysis of glucose wash-in curves in the perfused rat liver

    International Nuclear Information System (INIS)

    Le Couteur, D.G.; McLean, A.J.; Yin, Z.L.; Rivory, L.P.

    2001-01-01

    Full text: Oxygen diffusion may be involved in the pathogenesis of impaired drug metabolism by the aged (Le Couteur and McLean 1998) and cirrhotic (McLean and Morgan 1991) liver. To measure the barrier for oxygen transfer between the sinusoid and hepatocyte, we developed a carbon monoxide wash-in technique (Le Couteur et al 1999). The modelling of wash-in curves has been investigated much less intensively than multiple indicator dilution experiments, which utilize bolus injection of substrates. To investigate the effectiveness of various physiological models to fit wash-in curves, we performed wash-in experiments on the livers of male Wistar rats perfused in situ and single-pass with Krebs Henseleit buffer. Test perfusate contained 14 C-sucrose as the extracellular marker and 3 H-glucose. Liver perfusions were performed with background glucose concentrations of 6, 11, 51 or 109 mM. Outflow time-activity curves were analysed using four models. The V max and K m , for the influx of glucose were 1.1±0.03 μg/s/ml and 41.1±3.3 mM using the Crone-Renkin early extraction model; 1.4±0.04 μg/s/ml and 36.3±2.6 mM with dispersion model analysis; 1.8±0.1 μg/s/ml and 24.9±4.2 mM using the Goresky distributed model to fit differentiated wash-in curves; and 2.3±0.5 μg/s/ml and 29.3±16.5 mM using compartmental analysis. There was reasonable agreement between the four models and they yielded results that are similar to those reported for glucose uptake in other preparations. The differences between the models probably reflect differences in assumptions about the effects of efflux, mixing of glucose in the compartments and vascular hetereogeneity. The compartmental model that we used previously to examine gas disposition in the perfused liver gave higher estimates for transport than the other three models. Copyright (2001) Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists

  12. Asymmetric transfer efficiencies between fomites and fingers: Impact on model parameterization.

    Science.gov (United States)

    Greene, Christine; Ceron, Nancy Hernandez; Eisenberg, Marisa C; Koopman, James; Miller, Jesse D; Xi, Chuanwu; Eisenberg, Joseph N S

    2018-01-31

    Healthcare-associated infections (HAIs) affect millions of patients every year. Pathogen transmission via fomites and healthcare workers (HCWs) contribute to the persistence of HAIs in hospitals. A critical parameter needed to assess risk of environmental transmission is the pathogen transfer efficiency between fomites and fingers. Recent studies have shown that pathogen transfer is not symmetric. In this study,we evaluated how the commonly used assumption of symmetry in transfer efficiency changes the dynamics of pathogen movement between patients and rooms and the exposures to uncolonized patients. We developed and analyzed a deterministic compartmental model of Acinetobacter baumannii describing the contact-mediated process among HCWs, patients, and the environment. We compared a system using measured asymmetrical transfer efficiency to 2 symmetrical transfer efficiency systems. Symmetric models consistently overestimated contamination levels on fomites and underestimated contamination on patients and HCWs compared to the asymmetrical model. The magnitudes of these miscalculations can exceed 100%. Regardless of the model, relative percent reductions in contamination declined after hand hygiene compliance reached approximately 60% in the large fomite scenario and 70% in the small fomite scenario. This study demonstrates how healthcare facility-specific data can be used for decision-making processes. We show that the incorrect use of transfer efficiency data leads to biased effectiveness estimates for intervention strategies. More accurate exposure models are needed for more informed infection prevention strategies. Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  13. Cohort effects in dynamic models and their impact on vaccination programmes: an example from Hepatitis A

    Directory of Open Access Journals (Sweden)

    Duval Bernard

    2006-12-01

    Full Text Available Abstract Background Infection rates for many infectious diseases have declined over the past century. This has created a cohort effect, whereby older individuals experienced a higher infection rate in their past than younger individuals do now. As a result, age-stratified seroprevalence profiles often differ from what would be expected from constant infection rates. Methods Here, we account for the cohort effect by fitting an age-structured compartmental model with declining transmission rates to Hepatitis A seroprevalence data for Canadian-born individuals. We compare the predicted impact of universal vaccination with and without including the cohort effect in the dynamic model. Results We find that Hepatitis A transmissibility has declined by a factor of 2.8 since the early twentieth century. When the cohort effect is not included in the model, incidence and mortality both with and without vaccination are significantly over-predicted. Incidence (respectively mortality over a 20 year period of universal vaccination is 34% (respectively 90% higher than if the cohort effect is included. The percentage reduction in incidence and mortality due to vaccination are also over-predicted when the cohort effect is not included. Similar effects are likely for many other infectious diseases where infection rates have declined significantly over past decades and where immunity is lifelong. Conclusion Failure to account for cohort effects has implications for interpreting seroprevalence data and predicting the impact of vaccination programmes with dynamic models. Cohort effects should be included in dynamic modelling studies whenever applicable.

  14. Radiation Damage to Nervous System: Designing Optimal Models for Realistic Neuron Morphology in Hippocampus

    Science.gov (United States)

    Batmunkh, Munkhbaatar; Bugay, Alexander; Bayarchimeg, Lkhagvaa; Lkhagva, Oidov

    2018-02-01

    The present study is focused on the development of optimal models of neuron morphology for Monte Carlo microdosimetry simulations of initial radiation-induced events of heavy charged particles in the specific types of cells of the hippocampus, which is the most radiation-sensitive structure of the central nervous system. The neuron geometry and particles track structures were simulated by the Geant4/Geant4-DNA Monte Carlo toolkits. The calculations were made for beams of protons and heavy ions with different energies and doses corresponding to real fluxes of galactic cosmic rays. A simple compartmental model and a complex model with realistic morphology extracted from experimental data were constructed and compared. We estimated the distribution of the energy deposition events and the production of reactive chemical species within the developed models of CA3/CA1 pyramidal neurons and DG granule cells of the rat hippocampus under exposure to different particles with the same dose. Similar distributions of the energy deposition events and concentration of some oxidative radical species were obtained in both the simplified and realistic neuron models.

  15. Translational model to predict pulmonary pharmacokinetics and efficacy in man for inhaled bronchodilators.

    Science.gov (United States)

    Hendrickx, Ramon; Lamm Bergström, Eva; Janzén, David L I; Fridén, Markus; Eriksson, Ulf; Grime, Ken; Ferguson, Douglas

    2018-03-01

    Translational pharmacokinetic (PK) models are needed to describe and predict drug concentration-time profiles in lung tissue at the site of action to enable animal-to-man translation and prediction of efficacy in humans for inhaled medicines. Current pulmonary PK models are generally descriptive rather than predictive, drug/compound specific, and fail to show successful cross-species translation. The objective of this work was to develop a robust compartmental modeling approach that captures key features of lung and systemic PK after pulmonary administration of a set of 12 soluble drugs containing single basic, dibasic, or cationic functional groups. The model is shown to allow translation between animal species and predicts drug concentrations in human lungs that correlate with the forced expiratory volume for different classes of bronchodilators. Thus, the pulmonary modeling approach has potential to be a key component in the prediction of human PK, efficacy, and safety for future inhaled medicines. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  16. ADVAN-style analytical solutions for common pharmacokinetic models.

    Science.gov (United States)

    Abuhelwa, Ahmad Y; Foster, David J R; Upton, Richard N

    2015-01-01

    The analytical solutions to compartmental pharmacokinetic models are well known, but have not been presented in a form that easily allows for complex dosing regimen and changes in covariate/parameter values that may occur at discrete times within and/or between dosing intervals. Laplace transforms were used to derive ADVAN-style analytical solutions for 1, 2, and 3 compartment pharmacokinetic linear models of intravenous and first-order absorption drug administration. The equations calculate the change in drug amounts in each compartment of the model over a time interval (t; t = t2 - t1) accounting for any dose or covariate events acting in the time interval. The equations were coded in the R language and used to simulate the time-course of drug amounts in each compartment of the systems. The equations were validated against commercial software [NONMEM (Beal, Sheiner, Boeckmann, & Bauer, 2009)] output to assess their capability to handle both complex dosage regimens and the effect of changes in covariate/parameter values that may occur at discrete times within or between dosing intervals. For all tested pharmacokinetic models, the time-course of drug amounts using the ADVAN-style analytical solutions were identical to NONMEM outputs to at least four significant figures, confirming the validity of the presented equations. To our knowledge, this paper presents the ADVAN-style equations for common pharmacokinetic models in the literature for the first time. The presented ADVAN-style equations overcome obstacles to implementing the classical analytical solutions in software, and have speed advantages over solutions using differential equation solvers. The equations presented in this paper fill a gap in the pharmacokinetic literature, and it is expected that these equations will facilitate the investigation of useful open-source software for modelling pharmacokinetic data. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Modelling fast spreading patterns of airborne infectious diseases using complex networks

    Science.gov (United States)

    Brenner, Frank; Marwan, Norbert; Hoffmann, Peter

    2017-04-01

    The pandemics of SARS (2002/2003) and H1N1 (2009) have impressively shown the potential of epidemic outbreaks of infectious diseases in a world that is strongly connected. Global air travelling established an easy and fast opportunity for pathogens to migrate globally in only a few days. This made epidemiological prediction harder. By understanding this complex development and its link to climate change we can suggest actions to control a part of global human health affairs. In this study we combine the following data components to simulate the outbreak of an airborne infectious disease that is directly transmitted from human to human: em{Global Air Traffic Network (from openflights.org) with information on airports, airport location, direct flight connection, airplane type} em{Global population dataset (from SEDAC, NASA)} em{Susceptible-Infected-Recovered (SIR) compartmental model to simulate disease spreading in the vicinity of airports. A modified Susceptible-Exposed-Infected-Recovered (SEIR) model to analyze the impact of the incubation period.} em{WATCH-Forcing-Data-ERA-Interim (WFDEI) climate data: temperature, specific humidity, surface air pressure, and water vapor pressure} These elements are implemented into a complex network. Nodes inside the network represent airports. Each single node is equipped with its own SIR/SEIR compartmental model with node specific attributes. Edges between those nodes represent direct flight connections that allow infected individuals to move between linked nodes. Therefore the interaction of the set of unique SIR models creates the model dynamics we will analyze. To better figure out the influence on climate change on disease spreading patterns, we focus on Influenza-like-Illnesses (ILI). The transmission rate of ILI has a dependency on climate parameters like humidity and temperature. Even small changes of environmental variables can trigger significant differences in the global outbreak behavior. Apart from the direct

  18. Labelling, biodistribution and compartmental analysis of N-acetylcysteine labelled with Tc-99m. Comparative investigation with with {sup 99m} Tc-MIBI in an in vivo tumoral model; Estudo de marcacao, biodistribuicao e analise compartimental da N-acetil cisteina marcada com Tc-99m. Investigacao comparativa com MIBI-{sup 99m}Tc em modelo tumoral in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Faintuch, Bluma Linkowski

    1997-07-01

    Labelling and biodistribution studies were done with two different ligands, respectively Methoxy isobutyl isonitrile (MIBI) and N-acetylcysteine (NAC), employing Tc-99m as a tracer. The main objective was to assess the pharmacokinetic properties of the second substance, aiming at its possible application in cancer diagnosis. To this purpose an in vivo investigation was done using healthy and tumor-bearing rats with experimental cancer. Images of tumor-bearing rats registered in a scintillation camera indicated that with {sup 99m} Tc-MIBI none of the two selected times was adequate for visualization of the cancer mass. In contrast, {sup 99m} Tc-NAC permitted clear identification of the humor, four hours after injection. The results have demonstrated that {sup 99m} Tc-NAC is a radiopharmaceutical with affinity for cancer tissue and promising for further investigation concerning imaging diagnosis of tumors. (author)

  19. Method for Modeling High-Temporal-Resolution Stream Inflows in a Long-Term ParFlow.CLM Simulation

    Science.gov (United States)

    Miller, G. R.; Merket, C.

    2017-12-01

    Traditional hydrologic modeling has compartmentalized the water cycle into distinct components (e.g. rainfall-runoff, river routing, or groundwater flow models). An integrated, process-based modeling framework assesses two or more of these components simultaneously, reducing the error associated with approximated boundary conditions. One integrated model, ParFlow.CLM, offers the advantage of parallel computing, but it lacks any mechanism for incorporating time-varying streamflow as an upstream boundary condition. Here, we present a generalized method for applying transient streamflow at an upstream boundary in ParFlow.CLM. Downstream flow values are compared to predictions by traditional runoff and routing methods as implemented in HEC-HMS. Additionally, we define a model spin-up process which includes initialization of steady-state streamflow. The upstream inflow method was successfully tested on two domains - one synthetic tilted V catchment and an idealized small stream catchment in the Brazos River Basin. The stream in the idealized domain is gaged at the upstream and downstream boundaries. Both tests assumed a homogeneous subsurface so that the efficacy of the transient streamflow method could be evaluated with minimal complications by groundwater interactions. In the tilted V catchment, spin-up criteria were achieved within 6 model years. A 25 x 25 x 66 cell model grid was run at a computational efficiency of values early in the simulation.

  20. Population Pharmacokinetic Modeling of a Desmopressin Oral Lyophilisate in Growing Piglets as a Model for the Pediatric Population

    Directory of Open Access Journals (Sweden)

    Elke Gasthuys

    2018-01-01

    Full Text Available Desmopressin is used to treat primary nocturnal enuresis in children. Over the years, various formulations of desmopressin were commercialized of which the sublingual melt tablet is preferred in the pediatric population, despite the lack of full PK studies in this population. A full PK study was performed in growing conventional piglets to evaluate if this juvenile animal model can provide supplementary information to complement the information gap in the pediatric population. A desmopressin sublingual melt tablet (120 μg was administered to 32 male piglets aged 8 days, 4 weeks, 7 weeks, and 6 months (each group n = 8. Population PK (pop-PK analysis was performed to derive the PK parameters, the between- and within-subject variabilities and the effects of covariates. Desmopressin demonstrated two-compartmental PK, with a dual, sequential absorption process, and linear elimination. Body weight was the only significant covariate on clearance and on apparent volume of distribution of the central compartment. In human pediatric trials, no double peak in the absorption phase was observed in the plasma concentration-time curves, possibly due to the sparse sampling strategy applied in those pediatric studies. Therefore, it is recommended to perform additional studies, based on the sampling protocol applied in the current study.

  1. Aquatic pathways model to predict the fate of phenolic compounds

    Energy Technology Data Exchange (ETDEWEB)

    Aaberg, R.L.; Peloquin, R.A.; Strenge, D.L.; Mellinger, P.J.

    1983-04-01

    Organic materials released from energy-related activities could affect human health and the environment. To better assess possible impacts, we developed a model to predict the fate of spills or discharges of pollutants into flowing or static bodies of fresh water. A computer code, Aquatic Pathways Model (APM), was written to implement the model. The computer programs use compartmental analysis to simulate aquatic ecosystems. The APM estimates the concentrations of chemicals in fish tissue, water and sediment, and is therefore useful for assessing exposure to humans through aquatic pathways. The APM will consider any aquatic pathway for which the user has transport data. Additionally, APM will estimate transport rates from physical and chemical properties of chemicals between several key compartments. The major pathways considered are biodegradation, fish and sediment uptake, photolysis, and evaporation. The model has been implemented with parameters for distribution of phenols, an important class of compounds found in the water-soluble fractions of coal liquids. Current modeling efforts show that, in comparison with many pesticides and polyaromatic hydrocarbons (PAH), the lighter phenolics (the cresols) are not persistent in the environment. The properties of heavier molecular weight phenolics (indanols, naphthols) are not well enough understood at this time to make similar judgements. For the twelve phenolics studied, biodegradation appears to be the major pathway for elimination from aquatic environments. A pond system simulation (using APM) of a spill of solvent refined coal (SRC-II) materials indicates that phenol, cresols, and other single cyclic phenolics are degraded to 16 to 25 percent of their original concentrations within 30 hours. Adsorption of these compounds into sediments and accumulation by fish was minor.

  2. Risk methodology for geologic disposal of radioactive waste: asymptotic properties of the environmental transport model

    International Nuclear Information System (INIS)

    Helton, J.C.; Brown, J.B.; Iman, R.L.

    1981-02-01

    The Environmental Transport Model is a compartmental model developed to represent the surface movement of radionuclides. The purpose of the present study is to investigate the asymptotic behavior of the model and to acquire insight with respect to such behavior and the variables which influence it. For four variations of a hypothetical river receiving a radionuclide discharge, the following properties are considered: predicted asymptotic values for environmental radionuclide concentrations and time required for environmental radionuclide concentrations to reach 90% of their predicted asymptotic values. Independent variables of two types are used to define each variation of the river: variables which define physical properties of the river system (e.g., soil depth, river discharge and sediment resuspension) and variables which summarize radionuclide properties (i.e., distribution coefficients). Sensitivity analysis techniques based on stepwise regression are used to determine the dominant variables influencing the behavior of the model. This work constitutes part of a project at Sandia National Laboratories funded by the Nuclear Regulatory Commission to develop a methodology to assess the risk associated with geologic disposal of radioactive waste

  3. Pharmacokinetic Modeling of Manganese I. Dose-Dependencies of Uptake and Elimination

    Energy Technology Data Exchange (ETDEWEB)

    Teeguarden, Justin G.; Dorman, David C.; Covington, Tammie R.; Clewell, III, H. J.; Andersen, Melvin E.

    2007-01-01

    ABSTRACT Homeostatic mechanisms controlling uptake, storage, and elimination of dietary manganese (Mn) afford protection against fluctuations in tissue manganese (Mn) levels. Homeostatic control of inhaled Mn is less well understood, but important in assessing likely risks of Mn inhalation. We have used two compartmental kinetic models to characterize the influence of Mn exposure level and route (oral, inhalation) on uptake, elimination and transport of Mn. The models were fitted to or used to interpret data from five whole body Mn elimination studies, from one dietary Mn balance study, and from two biliary elimination studies, one acute and one chronic. As dietary Mn concentrations increased from low-sufficiency (1.5 ppm) to sufficiency (20 ppm), control of Mn uptake shifts from the intestine (principally), to more proportional control by both intestinal tissues and the liver. Using a 2-compartment distribution model, the increased elimination of 54Mn tracer doses in response to increases in dietary (rats and mice) or inhaled Mn (rats) resulted from increases in Mn elimination rate constants rather than changes in intercompartmental transfer rate constants between a central compartment and deep compartment. The PK analysis also indicated differential control of absorption in single gavage oral dose studies versus continuous high oral doses in the feed. The gavage study indicated increased elimination rate constants and the chronic study had reduced rate constants for absorption. These dose-dependencies in uptake and elimination are necessary inputs for comprehensive PK models guiding human health risk assessments with Mn.

  4. Computational modeling predicts the ionic mechanism of late-onset responses in unipolar brush cells.

    Science.gov (United States)

    Subramaniyam, Sathyaa; Solinas, Sergio; Perin, Paola; Locatelli, Francesca; Masetto, Sergio; D'Angelo, Egidio

    2014-01-01

    Unipolar Brush Cells (UBCs) have been suggested to play a critical role in cerebellar functioning, yet the corresponding cellular mechanisms remain poorly understood. UBCs have recently been reported to generate, in addition to early-onset glutamate receptor-dependent synaptic responses, a late-onset response (LOR) composed of a slow depolarizing ramp followed by a spike burst (Locatelli et al., 2013). The LOR activates as a consequence of synaptic activity and involves an intracellular cascade modulating H- and TRP-current gating. In order to assess the LOR mechanisms, we have developed a UBC multi-compartmental model (including soma, dendrite, initial segment, and axon) incorporating biologically realistic representations of ionic currents and a cytoplasmic coupling mechanism regulating TRP and H channel gating. The model finely reproduced UBC responses to current injection, including a burst triggered by a low-threshold spike (LTS) sustained by CaLVA currents, a persistent discharge sustained by CaHVA currents, and a rebound burst following hyperpolarization sustained by H- and CaLVA-currents. Moreover, the model predicted that H- and TRP-current regulation was necessary and sufficient to generate the LOR and its dependence on the intensity and duration of mossy fiber activity. Therefore, the model showed that, using a basic set of ionic channels, UBCs generate a rich repertoire of bursts, which could effectively implement tunable delay-lines in the local microcircuit.

  5. Propagation of action potentials along complex axonal trees. Model and implementation.

    Science.gov (United States)

    Manor, Y; Gonczarowski, J; Segev, I

    1991-12-01

    Axonal trees are typically morphologically and physiologically complicated structures. Because of this complexity, axonal trees show a large repertoire of behavior: from transmission lines with delay, to frequency filtering devices in both temporal and spatial domains. Detailed theoretical exploration of the electrical behavior of realistically complex axonal trees is notably lacking, mainly because of the absence of a simple modeling tool. AXONTREE is an attempt to provide such a simulator. It is written in C for the SUN workstation and implements both a detailed compartmental modeling of Hodgkin and Huxley-like kinetics, and a more abstract, event-driven, modeling approach. The computing module of AXONTREE is introduced together with its input/output features. These features allow graphical construction of arbitrary trees directly on the computer screen, and superimposition of the results on the simulated structure. Several numerical improvements that increase the computational efficiency by a factor of 5-10 are presented; most notable is a novel method of dynamic lumping of the modeled tree into simpler representations ("equivalent cables"). AXONTREE's performance is examined using a reconstructed terminal of an axon from a Y cell in cat visual cortex. It is demonstrated that realistically complicated axonal trees can be handled efficiently. The application of AXONTREE for the study of propagation delays along axonal trees is presented in the companion paper (Manor et al., 1991).

  6. Network Thermodynamic Curation of Human and Yeast Genome-Scale Metabolic Models

    Science.gov (United States)

    Martínez, Verónica S.; Quek, Lake-Ee; Nielsen, Lars K.

    2014-01-01

    Genome-scale models are used for an ever-widening range of applications. Although there has been much focus on specifying the stoichiometric matrix, the predictive power of genome-scale models equally depends on reaction directions. Two-thirds of reactions in the two eukaryotic reconstructions Homo sapiens Recon 1 and Yeast 5 are specified as irreversible. However, these specifications are mainly based on biochemical textbooks or on their similarity to other organisms and are rarely underpinned by detailed thermodynamic analysis. In this study, a to our knowledge new workflow combining network-embedded thermodynamic and flux variability analysis was used to evaluate existing irreversibility constraints in Recon 1 and Yeast 5 and to identify new ones. A total of 27 and 16 new irreversible reactions were identified in Recon 1 and Yeast 5, respectively, whereas only four reactions were found with directions incorrectly specified against thermodynamics (three in Yeast 5 and one in Recon 1). The workflow further identified for both models several isolated internal loops that require further curation. The framework also highlighted the need for substrate channeling (in human) and ATP hydrolysis (in yeast) for the essential reaction catalyzed by phosphoribosylaminoimidazole carboxylase in purine metabolism. Finally, the framework highlighted differences in proline metabolism between yeast (cytosolic anabolism and mitochondrial catabolism) and humans (exclusively mitochondrial metabolism). We conclude that network-embedded thermodynamics facilitates the specification and validation of irreversibility constraints in compartmentalized metabolic models, at the same time providing further insight into network properties. PMID:25028891

  7. Modeling survival of juvenile salmon during downriver migration in the Columbia River on a microcomputer

    Energy Technology Data Exchange (ETDEWEB)

    Peloquin, R.A.; McKenzie, D.H.

    1994-10-01

    A compartmental model has been implemented on a microcomputer as an aid in the analysis of alternative solutions to a problem. The model, entitled Smolt Survival Simulator, simulates the survival of juvenile salmon during their downstream migration and passage of hydroelectric dams in the Columbia River. The model is designed to function in a workshop environment where resource managers and fisheries biologists can study alternative measures that may potentially increase juvenile anadromous fish survival during downriver migration. The potential application of the model has placed several requirements on the implementing software. It must be available for use in workshop settings. The software must be easily to use with minimal computer knowledge. Scenarios must be created and executed quickly and efficiently. Results must be immediately available. Software design emphasis vas placed on the user interface because of these requirements. The discussion focuses on methods used in the development of the SSS software user interface. These methods should reduce user stress and alloy thorough and easy parameter modification.

  8. A flexible, interactive software tool for fitting the parameters of neuronal models

    Directory of Open Access Journals (Sweden)

    Péter eFriedrich

    2014-07-01

    Full Text Available The construction of biologically relevant neuronal models as well as model-based analysis of experimental data often requires the simultaneous fitting of multiple model parameters, so that the behavior of the model in a certain paradigm matches (as closely as possible the corresponding output of a real neuron according to some predefined criterion. Although the task of model optimization is often computationally hard, and the quality of the results depends heavily on technical issues such as the appropriate choice (and implementation of cost functions and optimization algorithms, no existing program provides access to the best available methods while also guiding the user through the process effectively. Our software, called Optimizer, implements a modular and extensible framework for the optimization of neuronal models, and also features a graphical interface which makes it easy for even non-expert users to handle many commonly occurring scenarios. Meanwhile, educated users can extend the capabilities of the program and customize it according to their needs with relatively little effort. Optimizer has been developed in Python, takes advantage of open-source Python modules for nonlinear optimization, and interfaces directly with the NEURON simulator to run the models. Other simulators are supported through an external interface. We have tested the program on several different types of problem of varying complexity, using different model classes. As targets, we used simulated traces from the same or a more complex model class, as well as experimental data. We successfully used Optimizer to determine passive parameters and conductance densities in compartmental models, and to fit simple (adaptive exponential integrate-and-fire neuronal models to complex biological data. Our detailed comparisons show that Optimizer can handle a wider range of problems, and delivers equally good or better performance than any other existing neuronal model fitting

  9. Incorporating herd immunity effects into cohort models of vaccine cost-effectiveness.

    Science.gov (United States)

    Bauch, Chris T; Anonychuk, Andrea M; Van Effelterre, Thierry; Pham, Bá Z; Merid, Maraki Fikre

    2009-01-01

    Cohort models are often used in cost-effectiveness analysis (CEA) of vaccination. However, because they cannot capture herd immunity effects, cohort models underestimate the reduction in incidence caused by vaccination. Dynamic models capture herd immunity effects but are often not adopted in vaccine CEA. The objective was to develop a pseudo-dynamic approximation that can be incorporated into an existing cohort model to capture herd immunity effects. The authors approximated changing force of infection due to universal vaccination for a pediatric infectious disease. The projected lifetime cases in a cohort were compared under 1) a cohort model, 2) a cohort model with pseudo-dynamic approximation, and 3) an age-structured susceptible-exposed-infectious-recovered compartmental (dynamic) model. The authors extended the methodology to sexually transmitted infections. For average to high values of vaccine coverage (P > 60%) and small to average values of the basic reproduction number (R(0) vaccination programs for many common infections, the pseudo-dynamic approximation significantly improved projected lifetime cases and was close to projections of the full dynamic model. For large values of R(0) (R(0) > 15), projected lifetime cases were similar under the dynamic model and the cohort model, both with and without pseudo-dynamic approximation. The approximation captures changes in the mean age at infection in the 1st vaccinated cohort. This methodology allows for preliminary assessment of herd immunity effects on CEA of universal vaccination for pediatric infectious diseases. The method requires simple adjustments to an existing cohort model and less data than a full dynamic model.

  10. An insulin infusion advisory system for type 1 diabetes patients based on non-linear model predictive control methods.

    Science.gov (United States)

    Zarkogianni, Konstantia; Mougiakakou, Stavroula G; Prountzou, Aikaterini; Vazeou, Andriani; Bartsocas, Christos S; Nikita, Konstantina S

    2007-01-01

    In this paper, an Insulin Infusion Advisory System (IIAS) for Type 1 diabetes patients, which use insulin pumps for the Continuous Subcutaneous Insulin Infusion (CSII) is presented. The purpose of the system is to estimate the appropriate insulin infusion rates. The system is based on a Non-Linear Model Predictive Controller (NMPC) which uses a hybrid model. The model comprises a Compartmental Model (CM), which simulates the absorption of the glucose to the blood due to meal intakes, and a Neural Network (NN), which simulates the glucose-insulin kinetics. The NN is a Recurrent NN (RNN) trained with the Real Time Recurrent Learning (RTRL) algorithm. The output of the model consists of short term glucose predictions and provides input to the NMPC, in order for the latter to estimate the optimum insulin infusion rates. For the development and the evaluation of the IIAS, data generated from a Mathematical Model (MM) of a Type 1 diabetes patient have been used. The proposed control strategy is evaluated at multiple meal disturbances, various noise levels and additional time delays. The results indicate that the implemented IIAS is capable of handling multiple meals, which correspond to realistic meal profiles, large noise levels and time delays.

  11. Pharmacokinetic-pharmacodynamic modeling of the antihypertensive interaction between azilsartan medoxomil and chlorthalidone in spontaneously hypertensive rats.

    Science.gov (United States)

    Kumar Puttrevu, Santosh; Ramakrishna, Rachumallu; Bhateria, Manisha; Jain, Moon; Hanif, Kashif; Bhatta, Rabi Sankar

    2017-05-01

    A pharmacokinetic-pharmacodynamic (PK-PD) model was developed to describe the time course of blood pressure following oral administration of azilsartan medoxomil (AZM) and/or chlorthalidone (CLT) in spontaneously hypertensive (SH) rats. The drug concentration and pharmacological effects, including systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and tail-cuff manometry, respectively. Sequential PK-PD analysis was performed, wherein the plasma concentration-time data was modeled by one compartmental analysis. Subsequently PD parameters were calculated to describe the time-concentration-response relationship using indirect response (IDR) PK-PD model. The combination of AZ and CLT had greater BP lowering effect compared to AZ or CLT alone, despite of no pharmacokinetic interaction between two drugs. These findings suggest synergistic antihypertensive pharmacodynamic interaction between AZ and CLT noncompetitively, which was simulated by inhibitory function of AZ and stimulatory function of CLT after concomitant administration of the two drugs. The present model was able to capture the turnover of blood pressure adequately at different time points at two different dose levels. The current PK-PD model was successfully utilized in the simulation of PD effect at a dose combination of 0.5 and 2.5 mg/kg for AZ and CLT, respectively. The developed preclinical PK-PD model may provide guidance in the optimization of dose ratio of individual drugs in the combined pharmacotherapy of AZ and CLT at clinical situations.

  12. epidemix-An interactive multi-model application for teaching and visualizing infectious disease transmission.

    Science.gov (United States)

    Muellner, Ulrich; Fournié, Guillaume; Muellner, Petra; Ahlstrom, Christina; Pfeiffer, Dirk U

    2017-12-11

    Mathematical models of disease transmission are used to improve our understanding of patterns of infection and to identify factors influencing them. During recent public and animal health crises, such as pandemic influenza, Ebola, Zika, foot-and-mouth disease, models have made important contributions in addressing policy questions, especially through the assessment of the trajectory and scale of outbreaks, and the evaluation of control interventions. However, their mathematical formulation means that they may appear as a "black box" to those without the appropriate mathematical background. This may lead to a negative perception of their utility for guiding policy, and generate expectations, which are not in line with what these models can deliver. It is therefore important for policymakers, as well as public health and animal health professionals and researchers who collaborate with modelers and use results generated by these models for policy development or research purpose, to understand the key concepts and assumptions underlying these models. The software application epidemix (http://shinyapps.rvc.ac.uk) presented here aims to make mathematical models of disease transmission accessible to a wider audience of users. By developing a visual interface for a suite of eight models, users can develop an understanding of the impact of various modelling assumptions - especially mixing patterns - on the trajectory of an epidemic and the impact of control interventions, without having to directly deal with the complexity of mathematical equations and programming languages. Models are compartmental or individual-based, deterministic or stochastic, and assume homogeneous or heterogeneous-mixing patterns (with the probability of transmission depending on the underlying structure of contact networks, or the spatial distribution of hosts). This application is intended to be used by scientists teaching mathematical modelling short courses to non-specialists - including policy

  13. Pharmacokinetic models relevant to toxicity and metabolism for uranium in humans and animals

    International Nuclear Information System (INIS)

    Wrenn, M.E.

    1989-01-01

    Models to predict short and long term accumulation of uranium in the human kidney are reviewed and summarised. These are generally first order linear compartmental models or pseudo-pharmacokinetic models such as the retention model of the ICRP. Pharmacokinetic models account not only for transfer from blood to organs, but also recirculation from the organ to blood. The most recent information on mammalian and human metabolism of uranium is used to establish a revised model. The model is applied to the short term accumulation of uranium in the human kidney after a single rapid dosage to the blood, such as that obtained by inhaling UF6 or its hydrolysis products. It is shown that the maximum accumulation in the kidney under these conditions is less than the fraction of the material distributed from the blood to kidney if a true pharmacokinetic model is used. The best coefficients applicable to man in the authors' view are summarised in model V. For a half-time of two days in the mammalian kidney, the maximum concentration in kidney is 75% of that predicted by a retention model such as that used by the ICRP following a single acute intake. We conclude that one must use true pharmacokinetic models, which incorporate recirculation from the organs to the blood, in order to realistically predict time dependent uptake in the kidneys and other organs. Information is presented showing that the half-time for urinary excretion of soluble uranium in man after inhalation of UF6 is about one quarter of a day. (author)

  14. A self-organizing state-space-model approach for parameter estimation in hodgkin-huxley-type models of single neurons.

    Directory of Open Access Journals (Sweden)

    Dimitrios V Vavoulis

    Full Text Available Traditional approaches to the problem of parameter estimation in biophysical models of neurons and neural networks usually adopt a global search algorithm (for example, an evolutionary algorithm, often in combination with a local search method (such as gradient descent in order to minimize the value of a cost function, which measures the discrepancy between various features of the available experimental data and model output. In this study, we approach the problem of parameter estimation in conductance-based models of single neurons from a different perspective. By adopting a hidden-dynamical-systems formalism, we expressed parameter estimation as an inference problem in these systems, which can then be tackled using a range of well-established statistical inference methods. The particular method we used was Kitagawa's self-organizing state-space model, which was applied on a number of Hodgkin-Huxley-type models using simulated or actual electrophysiological data. We showed that the algorithm can be used to estimate a large number of parameters, including maximal conductances, reversal potentials, kinetics of ionic currents, measurement and intrinsic noise, based on low-dimensional experimental data and sufficiently informative priors in the form of pre-defined constraints imposed on model parameters. The algorithm remained operational even when very noisy experimental data were used. Importantly, by combining the self-organizing state-space model with an adaptive sampling algorithm akin to the Covariance Matrix Adaptation Evolution Strategy, we achieved a significant reduction in the variance of parameter estimates. The algorithm did not require the explicit formulation of a cost function and it was straightforward to apply on compartmental models and multiple data sets. Overall, the proposed methodology is particularly suitable for resolving high-dimensional inference problems based on noisy electrophysiological data and, therefore, a

  15. Modelagem comparativa da cinética da fase sólida do capim-elefante picado, suplementado ou não com concentrados, e fornecido a vacas Holandês x Zebu em lactação Comparative modeling of chopped elephantgrass particulate kinectics in crossbred lactating cows receiving or not concentrate supplement

    Directory of Open Access Journals (Sweden)

    F.C.F. Lopes

    2008-06-01

    Full Text Available Foram comparadas as estimativas da cinética da fase sólida do capim-elefante (Pennisetum purpureum, Schum. picado, mordentado com cromo (Cr, obtidas do ajuste de dois modelos não-lineares (bicompartimental tempo-independente e multicompartimental tempo-dependente a resultados de excreção fecal de vacas Holandês x Zebu em lactação. Utilizaram-se dados de dois experimentos realizados em anos diferentes com capim-elefante cortado aos 60 e 45 dias, e suplementado, 3,3kg/vaca/dia, base matéria natural, ou não com concentrados. Foram utilizadas quatro e três vacas, respectivamente, no primeiro e no segundo ano de experimentação, havendo sempre duas fases de coleta de dados, necessárias para permitir que cada vaca pudesse ser avaliada em cada tratamento. As taxas de passagem ruminal estimadas variaram de 3,0 a 3,2%/h no modelo bicompartimental tempo-independente, e de 2,6 a 3,0%/h no modelo multicompartimental tempo-dependente, enquanto as respectivas taxas de passagem pós-ruminal variaram de 4,9 a 7,4%/h e de 7,4 a 10,9%/h. Os tempos médios de retenção do capim-elefante no trato gastrintestinal das vacas variaram de 66,0 a 76,2h no modelo bicompartimental tempo-independente, e de 48,1 a 57,8h no modelo multicompartimental tempo-dependente. O processo de dependência de tempo imposto pelo modelo multicompartimental permitiu melhor ajuste aos dados de excreção fecal do Cr, em relação ao modelo bicompartimental.Particulate kinetics estimates of chopped elephantgrass (Pennisetum purpureum, Schum. mordanted with Chromium (Cr were obtained and compared by the adjustment of two nonlinear models - age-independent double-compartmental model and age-dependent multicompartmental model - to a Cr faecal excretion dates of lactating crossbred Holstein x Zebu cows. Results from two trials carried out in different years with elephantgrass cut at 60 and 45 days of growth and supplemented, 3,3 kg/cow/day, wet basis, or not with concentrates were

  16. Development of risk-based computer models for deriving criteria on residual radioactivity and recycling

    International Nuclear Information System (INIS)

    Chen, S.Y.

    1994-01-01

    Argonne National Laboratory (ANL) is developing multimedia environmental pathway and health risk computer models to assess radiological risks to human health and to derive cleanup guidelines for environmental restoration, decommissioning, and recycling activities. These models are based on the existing RESRAD code, although each has a separate design and serves different objectives. Two such codes are RESRAD-BUILD and RESRAD-PROBABILISTIC. The RESRAD code was originally developed to implement the US Department of Energy's (DOE's) residual radioactive materials guidelines for contaminated soils. RESRAD has been successfully used by DOE and its contractors to assess health risks and develop cleanup criteria for several sites selected for cleanup or restoration programs. RESRAD-BUILD analyzes human health risks from radioactive releases during decommissioning or rehabilitation of contaminated buildings. Risks to workers are assessed for dismantling activities; risks to the public are assessed for occupancy. RESRAD-BUILD is based on a room compartmental model analyzing the effects on room air quality of contaminant emission and resuspension (as well as radon emanation), the external radiation pathway, and other exposure pathways. RESRAD-PROBABILISTIC, currently under development, is intended to perform uncertainty analysis for RESRAD by using the Monte Carlo approach based on the Latin-Hypercube sampling scheme. The codes being developed at ANL are tailored to meet a specific objective of human health risk assessment and require specific parameter definition and data gathering. The combined capabilities of these codes satisfy various risk assessment requirements in environmental restoration and remediation activities

  17. Development of risk-based computer models for deriving criteria on residual radioactivity and recycling

    International Nuclear Information System (INIS)

    Chen, Shih-Yew

    1995-01-01

    Argonne National Laboratory (ANL) is developing multimedia environmental pathway and health risk computer models to assess radiological risks to human health and to derive cleanup guidelines for environmental restoration, decommissioning, and recycling activities. These models are based on the existing RESRAD code, although each has a separate design and serves different objectives. Two such codes are RESRAD-BUILD and RESRAD-PROBABILISTIC. The RESRAD code was originally developed to implement the U.S. Department of Energy's (DOE's) residual radioactive materials guidelines for contaminated soils. RESRAD has been successfully used by DOE and its contractors to assess health risks and develop cleanup criteria for several sites selected for cleanup or restoration programs. RESRAD-BUILD analyzes human health risks from radioactive releases during decommissioning or rehabilitation of contaminated buildings. Risks to workers are assessed for dismantling activities; risks to the public are assessed for occupancy. RESRAD-BUILD is based on a room compartmental model analyzing the effects on room air quality of contaminant emission and resuspension (as well as radon emanation), the external radiation pathway, and other exposure pathways. RESRAD-PROBABILISTIC, currently under development, is intended to perform uncertainty analysis for RESRAD by using the Monte Carlo approach based on the Latin-Hypercube sampling scheme. The codes being developed at ANL are tailored to meet a specific objective of human health risk assessment and require specific parameter definition and data gathering. The combined capabilities of these codes satisfy various risk assessment requirements in environmental restoration and remediation activities. (author)

  18. A confidence building exercise in data and identifiability: Modeling cancer chemotherapy as a case study.

    Science.gov (United States)

    Eisenberg, Marisa C; Jain, Harsh V

    2017-10-27

    Mathematical modeling has a long history in the field of cancer therapeutics, and there is increasing recognition that it can help uncover the mechanisms that underlie tumor response to treatment. However, making quantitative predictions with such models often requires parameter estimation from data, raising questions of parameter identifiability and estimability. Even in the case of structural (theoretical) identifiability, imperfect data and the resulting practical unidentifiability of model parameters can make it difficult to infer the desired information, and in some cases, to yield biologically correct inferences and predictions. Here, we examine parameter identifiability and estimability using a case study of two compartmental, ordinary differential equation models of cancer treatment with drugs that are cell cycle-specific (taxol) as well as non-specific (oxaliplatin). We proceed through model building, structural identifiability analysis, parameter estimation, practical identifiability analysis and its biological implications, as well as alternative data collection protocols and experimental designs that render the model identifiable. We use the differential algebra/input-output relationship approach for structural identifiability, and primarily the profile likelihood approach for practical identifiability. Despite the models being structurally identifiable, we show that without consideration of practical identifiability, incorrect cell cycle distributions can be inferred, that would result in suboptimal therapeutic choices. We illustrate the usefulness of estimating practically identifiable combinations (in addition to the more typically considered structurally identifiable combinations) in generating biologically meaningful insights. We also use simulated data to evaluate how the practical identifiability of the model would change under alternative experimental designs. These results highlight the importance of understanding the underlying mechanisms

  19. A probabilistic modeling approach to assess human inhalation exposure risks to airborne aflatoxin B 1 (AFB 1)

    Science.gov (United States)

    Liao, Chung-Min; Chen, Szu-Chieh

    To assess how the human lung exposure to airborne aflatoxin B 1 (AFB 1) during on-farm activities including swine feeding, storage bin cleaning, corn harvest, and grain elevator loading/unloading, we present a probabilistic risk model, appraised with empirical data. The model integrates probabilistic exposure profiles from a compartmental lung model with the reconstructed dose-response relationships based on an empirical three-parameter Hill equation model, describing AFB 1 cytotoxicity for inhibition response in human bronchial epithelial cells, to quantitatively estimate the inhalation exposure risks. The risk assessment results implicate that exposure to airborne AFB 1 may pose no significance to corn harvest and grain elevator loading/unloading activities, yet a relatively high risk for swine feeding and storage bin cleaning. Applying a joint probability function method based on exceedence profiles, we estimate that a potential high risk for the bronchial region (inhibition=56.69% with 95% confidence interval (CI): 35.05-72.87%) and bronchiolar region (inhibition=44.93% with 95% CI: 21.61 - 66.78%) is alarming during swine feeding activity. We parameterized the proposed predictive model that should encourage a risk-management framework for discussion of carcinogenic risk in occupational settings where inhalation of AFB 1-contaminated dust occurs.

  20. Theoretical Compartment Modeling of DCE-MRI Data Based on the Transport across Physiological Barriers in the Brain

    Directory of Open Access Journals (Sweden)

    Laura Fanea

    2012-01-01

    Full Text Available Neurological disorders represent major causes of lost years of healthy life and mortality worldwide. Development of their quantitative interdisciplinary in vivo evaluation is required. Compartment modeling (CM of brain data acquired in vivo using magnetic resonance imaging techniques with clinically available contrast agents can be performed to quantitatively assess brain perfusion. Transport of 1H spins in water molecules across physiological compartmental brain barriers in three different pools was mathematically modeled and theoretically evaluated in this paper and the corresponding theoretical compartment modeling of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI data was analyzed. The pools considered were blood, tissue, and cerebrospinal fluid (CSF. The blood and CSF data were mathematically modeled assuming continuous flow of the 1H spins in these pools. Tissue data was modeled using three CMs. Results in this paper show that transport across physiological brain barriers such as the blood to brain barrier, the extracellular space to the intracellular space barrier, or the blood to CSF barrier can be evaluated quantitatively. Statistical evaluations of this quantitative information may be performed to assess tissue perfusion, barriers' integrity, and CSF flow in vivo in the normal or disease-affected brain or to assess response to therapy.

  1. Direction selectivity in a model of the starburst amacrine cell.

    Science.gov (United States)

    Tukker, John J; Taylor, W Rowland; Smith, Robert G

    2004-01-01

    The starburst amacrine cell (SBAC), found in all mammalian retinas, is thought to provide the directional inhibitory input recorded in On-Off direction-selective ganglion cells (DSGCs). While voltage recordings from the somas of SBACs have not shown robust direction selectivity (DS), the dendritic tips of these cells display direction-selective calcium signals, even when gamma-aminobutyric acid (GABAa,c) channels are blocked, implying that inhibition is not necessary to generate DS. This suggested that the distinctive morphology of the SBAC could generate a DS signal at the dendritic tips, where most of its synaptic output is located. To explore this possibility, we constructed a compartmental model incorporating realistic morphological structure, passive membrane properties, and excitatory inputs. We found robust DS at the dendritic tips but not at the soma. Two-spot apparent motion and annulus radial motion produced weak DS, but thin bars produced robust DS. For these stimuli, DS was caused by the interaction of a local synaptic input signal with a temporally delayed "global" signal, that is, an excitatory postsynaptic potential (EPSP) that spread from the activated inputs into the soma and throughout the dendritic tree. In the preferred direction the signals in the dendritic tips coincided, allowing summation, whereas in the null direction the local signal preceded the global signal, preventing summation. Sine-wave grating stimuli produced the greatest amount of DS, especially at high velocities and low spatial frequencies. The sine-wave DS responses could be accounted for by a simple mathematical model, which summed phase-shifted signals from soma and dendritic tip. By testing different artificial morphologies, we discovered DS was relatively independent of the morphological details, but depended on having a sufficient number of inputs at the distal tips and a limited electrotonic isolation. Adding voltage-gated calcium channels to the model showed that their

  2. Infection dynamics on spatial small-world network models

    Science.gov (United States)

    Iotti, Bryan; Antonioni, Alberto; Bullock, Seth; Darabos, Christian; Tomassini, Marco; Giacobini, Mario

    2017-11-01

    The study of complex networks, and in particular of social networks, has mostly concentrated on relational networks, abstracting the distance between nodes. Spatial networks are, however, extremely relevant in our daily lives, and a large body of research exists to show that the distances between nodes greatly influence the cost and probability of establishing and maintaining a link. A random geometric graph (RGG) is the main type of synthetic network model used to mimic the statistical properties and behavior of many social networks. We propose a model, called REDS, that extends energy-constrained RGGs to account for the synergic effect of sharing the cost of a link with our neighbors, as is observed in real relational networks. We apply both the standard Watts-Strogatz rewiring procedure and another method that conserves the degree distribution of the network. The second technique was developed to eliminate unwanted forms of spatial correlation between the degree of nodes that are affected by rewiring, limiting the effect on other properties such as clustering and assortativity. We analyze both the statistical properties of these two network types and their epidemiological behavior when used as a substrate for a standard susceptible-infected-susceptible compartmental model. We consider and discuss the differences in properties and behavior between RGGs and REDS as rewiring increases and as infection parameters are changed. We report considerable differences both between the network types and, in the case of REDS, between the two rewiring schemes. We conclude that REDS represent, with the application of these rewiring mechanisms, extremely useful and interesting tools in the study of social and epidemiological phenomena in synthetic complex networks.

  3. Current crisis or artifact of surveillance: insights into rebound chlamydia rates from dynamic modelling

    Directory of Open Access Journals (Sweden)

    Vickers David M

    2010-03-01

    Full Text Available Abstract Background After initially falling in the face of intensified control efforts, reported rates of sexually transmitted chlamydia in many developed countries are rising. Recent hypotheses for this phenomenon have broadly focused on improved case finding or an increase in the prevalence. Because of many complex interactions behind the spread of infectious diseases, dynamic models of infection transmission are an effective means to guide learning, and assess quantitative conjectures of epidemiological processes. The objective of this paper is to bring a unique and robust perspective to observed chlamydial patterns through analyzing surveillance data with mathematical models of infection transmission. Methods This study integrated 25-year testing volume data from the Canadian province of Saskatchewan with one susceptible-infected-treated-susceptible and three susceptible-infected-treated-removed compartmental models. Calibration of model parameters to fit observed 25-year case notification data, after being combined with testing records, placed constraints on model behaviour and allowed for an approximation of chlamydia prevalence to be estimated. Model predictions were compared to observed case notification trends, and extensive sensitivity analyses were performed to confirm the robustness of model results. Results Model predictions accurately mirrored historic chlamydial trends including an observed rebound in the mid 1990s. For all models examined, the results repeatedly highlighted that increased testing volumes, rather than changes in the sensitivity and specificity of testing technologies, sexual behaviour, or truncated immunological responses brought about by treatment can, explain the increase in observed chlamydia case notifications. Conclusions Our results highlight the significant impact testing volume can have on observed incidence rates, and that simple explanations for these observed increases appear to have been dismissed in

  4. Mixed Effects Modeling Using Stochastic Differential Equations: Illustrated by Pharmacokinetic Data of Nicotinic Acid in Obese Zucker Rats.

    Science.gov (United States)

    Leander, Jacob; Almquist, Joachim; Ahlström, Christine; Gabrielsson, Johan; Jirstrand, Mats

    2015-05-01

    Inclusion of stochastic differential equations in mixed effects models provides means to quantify and distinguish three sources of variability in data. In addition to the two commonly encountered sources, measurement error and interindividual variability, we also consider uncertainty in the dynamical model itself. To this end, we extend the ordinary differential equation setting used in nonlinear mixed effects models to include stochastic differential equations. The approximate population likelihood is derived using the first-order conditional estimation with interaction method and extended Kalman filtering. To illustrate the application of the stochastic differential mixed effects model, two pharmacokinetic models are considered. First, we use a stochastic one-compartmental model with first-order input and nonlinear elimination to generate synthetic data in a simulated study. We show that by using the proposed method, the three sources of variability can be successfully separated. If the stochastic part is neglected, the parameter estimates become biased, and the measurement error variance is significantly overestimated. Second, we consider an extension to a stochastic pharmacokinetic model in a preclinical study of nicotinic acid kinetics in obese Zucker rats. The parameter estimates are compared between a deterministic and a stochastic NiAc disposition model, respectively. Discrepancies between model predictions and observations, previously described as measurement noise only, are now separated into a comparatively lower level of measurement noise and a significant uncertainty in model dynamics. These examples demonstrate that stochastic differential mixed effects models are useful tools for identifying incomplete or inaccurate model dynamics and for reducing potential bias in parameter estimates due to such model deficiencies.

  5. A mathematical model to evaluate the routine use of fecal microbiota transplantation to prevent incident and recurrent Clostridium difficile infection.

    Science.gov (United States)

    Lofgren, Eric T; Moehring, Rebekah W; Anderson, Deverick J; Weber, David J; Fefferman, Nina H

    2014-01-01

    Fecal microbiota transplantation (FMT) has been suggested as a new treatment to manage Clostridium difficile infection (CDI). With use of a mathematical model of C. difficile within an intensive care unit (ICU), we examined the potential impact of routine FMT. A mathematical model of C. difficile transmission, supplemented with prospective cohort, surveillance, and billing data from hospitals in the southeastern United States. Cohort, surveillance, and billing data as well as data from the literature were used to construct a compartmental model of CDI within an ICU. Patients were defined as being in 1 of 6 potential health states: uncolonized and at low risk; uncolonized and at high risk; colonized and at low risk; colonized and at high risk; having CDI; or treated with FMT. The use of FMT to treat patients after CDI was associated with a statistically significant reduction in recurrence but not with a reduction in incident cases. Treatment after administration of high-risk medications, such as antibiotics, did not result in a decrease in recurrence but did result in a statistically significant difference in incident cases across treatment groups, although whether this difference was clinically relevant was questionable. Our study is a novel mathematical model that examines the effect of FMT on the prevention of recurrent and incident CDI. The routine use of FMT represents a promising approach to reduce complex recurrent cases, but a reduction in CDI incidence will require the use of other methods to prevent transmission.

  6. A deterministic model for one-dimensional excluded flow with local interactions.

    Directory of Open Access Journals (Sweden)

    Yoram Zarai

    Full Text Available Natural phenomena frequently involve a very large number of interacting molecules moving in confined regions of space. Cellular transport by motor proteins is an example of such collective behavior. We derive a deterministic compartmental model for the unidirectional flow of particles along a one-dimensional lattice of sites with nearest-neighbor interactions between the particles. The flow between consecutive sites is governed by a "soft" simple exclusion principle and by attracting or repelling forces between neighboring particles. Using tools from contraction theory, we prove that the model admits a unique steady-state and that every trajectory converges to this steady-state. Analysis and simulations of the effect of the attracting and repelling forces on this steady-state highlight the crucial role that these forces may play in increasing the steady-state flow, and reveal that this increase stems from the alleviation of traffic jams along the lattice. Our theoretical analysis clarifies microscopic aspects of complex multi-particle dynamic processes.

  7. A physiological biokinetic model for the [7(N)-{sup 3}H]-cholesterol dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Adriano dos Santos; Martins, Joao Francisco Trencher; Velo, Alexandre Franca; Hamada, Margarida M.; Mesquita, Carlos Henrique de, E-mail: adriano_oliveira@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2015-07-01

    Cardiovascular diseases (CVD) are a major source of deaths worldwide according to WHO (World Health Organization). It is well-known that the change of the level of plasma lipoproteins, which are responsible for the cholesterol transport in the bloodstream, is a main cause of these diseases. For this reason, to know the biokinetic parameters of plasma lipoproteins and quantifies them is important to correct and deepen the understanding of associated diseases. The main objective of this work is to provide a biokinetic model in order to estimate the radiometric dose, due to the intake of [7(N){sup -3}H] –Cholesterol in physiological issues, in metabolic studies. The internal dosimetry is important to know the biological effects of radiation. The model was based on Schwartz et al (2004), using parameters for the plasmatic lipoproteins and ICRP 30 (1979) gastrointestinal tract; the dose in the compartments were calculated using the MIRD methodology and the compartmental analysis by Matlab® software. The coefficients were estimated for an adult phantom with a body mass of 73.3 kg. (author)

  8. Peptide-nucleotide microdroplets as a step towards a membrane-free protocell model

    Science.gov (United States)

    Koga, Shogo; Williams, David S.; Perriman, Adam W.; Mann, Stephen

    2011-09-01

    Although phospholipid bilayers are ubiquitous in modern cells, their impermeability, lack of dynamic properties, and synthetic complexity are difficult to reconcile with plausible pathways of proto-metabolism, growth and division. Here, we present an alternative membrane-free model, which demonstrates that low-molecular-weight mononucleotides and simple cationic peptides spontaneously accumulate in water into microdroplets that are stable to changes in temperature and salt concentration, undergo pH-induced cycles of growth and decay, and promote α-helical peptide secondary structure. Moreover, the microdroplets selectively sequester porphyrins, inorganic nanoparticles and enzymes to generate supramolecular stacked arrays of light-harvesting molecules, nanoparticle-mediated oxidase activity, and enhanced rates of glucose phosphorylation, respectively. Taken together, our results suggest that peptide-nucleotide microdroplets can be considered as a new type of protocell model that could be used to develop novel bioreactors, primitive artificial cells and plausible pathways to prebiotic organization before the emergence of lipid-based compartmentalization on the early Earth.

  9. A physiological biokinetic model for the [7(N)-3H]-cholesterol dosimetry

    International Nuclear Information System (INIS)

    Oliveira, Adriano dos Santos; Martins, Joao Francisco Trencher; Velo, Alexandre Franca; Hamada, Margarida M.; Mesquita, Carlos Henrique de

    2015-01-01

    Cardiovascular diseases (CVD) are a major source of deaths worldwide according to WHO (World Health Organization). It is well-known that the change of the level of plasma lipoproteins, which are responsible for the cholesterol transport in the bloodstream, is a main cause of these diseases. For this reason, to know the biokinetic parameters of plasma lipoproteins and quantifies them is important to correct and deepen the understanding of associated diseases. The main objective of this work is to provide a biokinetic model in order to estimate the radiometric dose, due to the intake of [7(N) -3 H] –Cholesterol in physiological issues, in metabolic studies. The internal dosimetry is important to know the biological effects of radiation. The model was based on Schwartz et al (2004), using parameters for the plasmatic lipoproteins and ICRP 30 (1979) gastrointestinal tract; the dose in the compartments were calculated using the MIRD methodology and the compartmental analysis by Matlab® software. The coefficients were estimated for an adult phantom with a body mass of 73.3 kg. (author)

  10. Biowaiver approach for biopharmaceutics classification system class 3 compound metformin hydrochloride using in silico modeling.

    Science.gov (United States)

    Crison, John R; Timmins, Peter; Keung, Anther; Upreti, Vijay V; Boulton, David W; Scheer, Barry J

    2012-05-01

    The dependency of metformin in vivo disposition on the rate and extent of dissolution was studied. The analysis includes the use of fundamental principles of drug input, permeability, and intestinal transit time within the framework of a compartmental absorption transit model to predict key pharmacokinetic (PK) parameters and then compare the results to clinical data. The simulations show that the maximum plasma concentration (C(max) ) and area under the curve (AUC) are not significantly affected when 100% of drug is released within 2 h of oral dosing, which was confirmed with corresponding human PK data. Furthermore, in vitro dissolution profiles measured in aqueous buffers at pH values of 1.2, 4.5, and 6.8 were slower than in vivo release profiles generated by deconvolution of metformin products that were bioequivalent. On the basis of this work, formulations of metformin that release 100% in vitro in a   time period equal to or less than two hours are indicated to be bioequivalent. The use of modeling offers a mechanistic-based approach for demonstrating acceptable bioperformance for metformin formulations without having to resort to in vivo bioequivalence studies and may be more robust than statistical comparison of in vitro release profiles. This work further provides a strategy for considering Biopharmaceutics Classification System (BCS) Class 3 compounds to be included under biowaiver guidelines as for BCS Class 1 compounds. Copyright © 2012 Wiley Periodicals, Inc.

  11. The development of the model for recognition of prior learning for nurses in South Africa

    Directory of Open Access Journals (Sweden)

    T Khanyile

    2005-09-01

    Full Text Available The National Qualifications Framework (NQF was established to address the compartmentalization of education and training, the absence of norms and standards and the need for international recognition. According to the South African Qualifications Authority (1996,this framework was aimed at developing a comprehensive qualifications structure and an integrated approach to education and training in the country (NCHE, 1996:46. Educational institutions, including those for nursing, were challenged with a view to rethink the whole culture of teaching and learning and was counted as knowledge. The major principle of the NQF was the Recognition of Prior Learning (RPL, which had to be pursued across all sectors (Musker, 1998: 8. RPL was seen as a means to widen access into learning programs for those who had been historically denied this. The challenge for educational institutions was how to ensure that RPL systems once implemented did not compromise academic standards. Research into methodologies to implement the NF in the absence of mechanisms was then essential. The purpose of the study was to develop and test a RPL model for nurses in South Africa. The study adopted a multi phase decisions oriented evaluation research design. Stuffelbeam’s educational evaluation model was used to guide data collection and analysis. The research questions were incorporated under the different phases of evaluation. The model was development at six levels: level one was at the policy makers level; level two was at the stakeholders; levels three to six were at institutional level where three institutions participated at pilot site for the RPL model development. These levels are presented as tiers in the figure 1. This article present the results of the model development at the first two levels, which according to Stuffelbeam ‘s model is the context evaluation for boundary setting. Part two will present the model development at institutional level, involving the input

  12. Examining rainfall and cholera dynamics in Haiti using statistical and dynamic modeling approaches.

    Science.gov (United States)

    Eisenberg, Marisa C; Kujbida, Gregory; Tuite, Ashleigh R; Fisman, David N; Tien, Joseph H

    2013-12-01

    Haiti has been in the midst of a cholera epidemic since October 2010. Rainfall is thought to be associated with cholera here, but this relationship has only begun to be quantitatively examined. In this paper, we quantitatively examine the link between rainfall and cholera in Haiti for several different settings (including urban, rural, and displaced person camps) and spatial scales, using a combination of statistical and dynamic models. Statistical analysis of the lagged relationship between rainfall and cholera incidence was conducted using case crossover analysis and distributed lag nonlinear models. Dynamic models consisted of compartmental differential equation models including direct (fast) and indirect (delayed) disease transmission, where indirect transmission was forced by empirical rainfall data. Data sources include cholera case and hospitalization time series from the Haitian Ministry of Public Health, the United Nations Water, Sanitation and Health Cluster, International Organization for Migration, and Hôpital Albert Schweitzer. Rainfall data was obtained from rain gauges from the U.S. Geological Survey and Haiti Regeneration Initiative, and remote sensing rainfall data from the National Aeronautics and Space Administration Tropical Rainfall Measuring Mission. A strong relationship between rainfall and cholera was found for all spatial scales and locations examined. Increased rainfall was significantly correlated with increased cholera incidence 4-7 days later. Forcing the dynamic models with rainfall data resulted in good fits to the cholera case data, and rainfall-based predictions from the dynamic models closely matched observed cholera cases. These models provide a tool for planning and managing the epidemic as it continues. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Investigation of nonlinear models to describe long-term egg production in Japanese quail.

    Science.gov (United States)

    Narinc, Dogan; Karaman, Emre; Aksoy, Tulin; Firat, Mehmet Ziya

    2013-06-01

    In this study, long-term egg production was monitored in a Japanese quail flock, which had not undergone any genetic improvement, for 52 wk as of the age of sexual maturity. The study aimed to detect some traits with respect to egg production, to determine the cumulative hen-housed egg numbers, and to compare goodness of fit of different nonlinear models for the percentage of hen-day egg production. The mean age at first egg was 38.9 d and the age at 50% egg production was 45.3 d. The quail reached peak production at 15 wk of age (wk 9 of egg production period) when the percentage of hen-day egg production was found to be 94%. The cumulative hen-housed egg number for 52 wk as of the age of sexual maturity was 253.08. The monomolecular function, a nonsigmoid model, was used in the nonlinear regression analysis of the cumulative egg numbers. Parameters a, b, and c of the monomolecular model were estimated to be 461.70, 473.31, and 0.065, respectively. Gamma, McNally, Adams-Bell, and modified compartmental models, widely used in hens previously, were used in the nonlinear regression analysis of the percentages of hen-day egg production. The goodness of fit for these models was compared using the values of pseudo-R², Akaike's information criterion, and Bayesian information criterion. It was determined that all the models are adequate but that the Adams-Bell model displayed a slightly better fit for the percentage of hen-day egg production in Japanese quail than others.

  14. Quantification of a pharmacological perturbation in the radiopharmacokinetic models of cisplatin

    International Nuclear Information System (INIS)

    Dahalan, R.

    1987-01-01

    Radiopharmacokinetics, a new approach to pharmacokinetics that combines the techniques of quantitative radionuclide imaging, knowledge of the drug's metabolism, and advanced modeling techniques, has enabled identification of various anatomic and biochemical states of cisplatin as it traverses the physiological system. This approach has been employed in analyzing various organ compartmental models of this drug, using such models to quantify the modulating effect of a pharmacological agent, mannitol, on the radiopharmacokinetics of cisplatin. Our work has documented that such a novel approach is possible and that pharmacological perturbations may be quantitated so as to exercise control over the pharmacokinetics of the drug and help to develop strategies to achieve optimum therapeutic effect. The study shows a need for further improvement in the quality of the data gathered noninvasively from the kidneys and the tissues, and a more accurate method to collect urine samples. Simulation experiments were conducted using perfect data and either a 10% or 40% error in the kidney and tissue data, and a 5% error in the blood and urine data. These simulations suggest that a 40% error is too high to analyze our data using the original 8-multicompartmental system and that data collection must be improved to obtain close to 10% precision. Understanding the effects of the pharmacological modulator on the kinetics of the drug of interest and representing the drug model in a manner which will reflect this effect of the modulator is an important step in quantifying its effect. This was shown in the present study by testing various 1-compartment, 2-compartment, 3-compartment, and 5-compartment models, all of them subsystems of the 8-compartment model of cisplatin and representing sectors of the model where the pharmacological modulator, mannitol, was thought to exert its effect

  15. A model of population dynamics of TB in a prison system and application to South Africa.

    Science.gov (United States)

    Witbooi, Peter; Vyambwera, Sibaliwe Maku

    2017-11-29

    Tuberculosis (TB) continues to spread in South African prisons in particular, as prisons are over-capacitated and have poor ventilation. The awaiting trial detainees are not screened on admission and are at high risk of getting infected with TB. We propose a compartmental model to describe the population dynamics of TB disease in prisons. Our model considers the inflow of susceptible, exposed and TB infectives into the prison population. Removal of individuals out of the prison population can be either by death or by being released from prison, as compared to a general population in which removal is only by death. We describe conditions, including non-inflow of infectives into the prison, which will ensure that TB can be eradicated from the prison population. The model is calibrated for the South African prison system, by using data in existing literature. The model can be used to make quantitative projections of TB prevalence and to measure the effect of interventions. Illustrative simulations in this regard are presented. The model can be used for other prison populations too, if data is available to calculate the model parameters. Various simulations generated with our model serve to illustrate how it can be utilized in making future projections of the levels of prevalence of TB, and to quantify the effect of interventions such as screening, treatment or reduction of transmission parameter values through improved living conditions for inmates. This makes it particularly useful as there are various targets set by the World Health Organization and by governments, for reduction of TB prevalence and ultimately its eradication. Towards eradication of TB from a prison system, the theorem on global stability of the disease-free state is a useful indicator.

  16. Computational Modeling of Space Physiology for Informing Spaceflight Countermeasure Design and Predictions of Efficacy

    Science.gov (United States)

    Lewandowski, B. E.; DeWitt, J. K.; Gallo, C. A.; Gilkey, K. M.; Godfrey, A. P.; Humphreys, B. T.; Jagodnik, K. M.; Kassemi, M.; Myers, J. G.; Nelson, E. S.; hide

    2017-01-01

    MOTIVATION: Spaceflight countermeasures mitigate the harmful effects of the space environment on astronaut health and performance. Exercise has historically been used as a countermeasure to physical deconditioning, and additional countermeasures including lower body negative pressure, blood flow occlusion and artificial gravity are being researched as countermeasures to spaceflight-induced fluid shifts. The NASA Digital Astronaut Project uses computational models of physiological systems to inform countermeasure design and to predict countermeasure efficacy.OVERVIEW: Computational modeling supports the development of the exercise devices that will be flown on NASAs new exploration crew vehicles. Biomechanical modeling is used to inform design requirements to ensure that exercises can be properly performed within the volume allocated for exercise and to determine whether the limited mass, volume and power requirements of the devices will affect biomechanical outcomes. Models of muscle atrophy and bone remodeling can predict device efficacy for protecting musculoskeletal health during long-duration missions. A lumped-parameter whole-body model of the fluids within the body, which includes the blood within the cardiovascular system, the cerebral spinal fluid, interstitial fluid and lymphatic system fluid, estimates compartmental changes in pressure and volume due to gravitational changes. These models simulate fluid shift countermeasure effects and predict the associated changes in tissue strain in areas of physiological interest to aid in predicting countermeasure effectiveness. SIGNIFICANCE: Development and testing of spaceflight countermeasure prototypes are resource-intensive efforts. Computational modeling can supplement this process by performing simulations that reduce the amount of necessary experimental testing. Outcomes of the simulations are often important for the definition of design requirements and the identification of factors essential in ensuring

  17. Effects of soft interactions and bound mobility on diffusion in crowded environments: a model of sticky and slippery obstacles.

    Science.gov (United States)

    Stefferson, Michael W; Norris, Samantha L; Vernerey, Franck J; Betterton, Meredith D; Hough, Loren E

    2017-06-29

    Crowded environments modify the diffusion of macromolecules, generally slowing their movement and inducing transient anomalous subdiffusion. The presence of obstacles also modifies the kinetics and equilibrium behavior of tracers. While previous theoretical studies of particle diffusion have typically assumed either impenetrable obstacles or binding interactions that immobilize the particle, in many cellular contexts bound particles remain mobile. Examples include membrane proteins or lipids with some entry and diffusion within lipid domains and proteins that can enter into membraneless organelles or compartments such as the nucleolus. Using a lattice model, we studied the diffusive movement of tracer particles which bind to soft obstacles, allowing tracers and obstacles to occupy the same lattice site. For sticky obstacles, bound tracer particles are immobile, while for slippery obstacles, bound tracers can hop without penalty to adjacent obstacles. In both models, binding significantly alters tracer motion. The type and degree of motion while bound is a key determinant of the tracer mobility: slippery obstacles can allow nearly unhindered diffusion, even at high obstacle filling fraction. To mimic compartmentalization in a cell, we examined how obstacle size and a range of bound diffusion coefficients affect tracer dynamics. The behavior of the model is similar in two and three spatial dimensions. Our work has implications for protein movement and interactions within cells.

  18. 3D gravity modeling of the Corrientes province (NE Argentina) and its importance to the Guarani Aquifer System

    Science.gov (United States)

    Mira, Andrés; Gómez Dacal, María Laura; Tocho, Claudia; Vives, Luis

    2013-11-01

    This paper presents a geological model of Corrientes province (Argentina) based on Bouguer gravity anomaly data, obtained in 2073 measurement points. To build the model, the IGMAS + interactive program was used. Two areas of approximately 135,000 km2 were modeled in this study. The selection of these areas was based on the sectors where the largest number of gravity anomaly measurements was made and other type of data was available to perform the parameterization (i.e, lithology profiles in boreholes, seismic profiles and audio-magnetotelluric AMT soundings). The initial geological configuration proposed was composed by four layers: basement, sediments (Paleozoic-Lower Cretaceous), basalts (Serra Geral Group, Lower Cretaceous) and post-basaltic sediments. The result shows a basement compartmentalized in structural blocks separated by large faults. The connection of Asunción and Río Grande Arches is confirmed along a structural high that crosses Corrientes province from SE to NW. The basaltic layer shows lateral changes in its thickness, due to faulting, almost disappearing on the NW of Corrientes. This structural configuration has a special hydrogeological importance because it produces the rise of the Guaraní Aquifer System sedimentary series near the surface and the intense fracture network makes this area prone to local recharge and regional discharge.

  19. Influence of demographic changes on the impact of vaccination against varicella and herpes zoster in Germany - a mathematical modelling study.

    Science.gov (United States)

    Horn, Johannes; Damm, Oliver; Greiner, Wolfgang; Hengel, Hartmut; Kretzschmar, Mirjam E; Siedler, Anette; Ultsch, Bernhard; Weidemann, Felix; Wichmann, Ole; Karch, André; Mikolajczyk, Rafael T

    2018-01-09

    Epidemiological studies suggest that reduced exposure to varicella might lead to an increased risk for herpes zoster (HZ). Reduction of exposure to varicella is a consequence of varicella vaccination but also of demographic changes. We analyzed how the combination of vaccination programs and demographic dynamics will affect the epidemiology of varicella and HZ in Germany over the next 50 years. We used a deterministic dynamic compartmental model to assess the impact of different varicella and HZ vaccination strategies on varicella and HZ epidemiology in three demographic scenarios, namely the projected population for Germany, the projected population additionally accounting for increased immigration as observed in 2015/2016, and a stationary population. Projected demographic changes alone result in an increase of annual HZ cases by 18.3% and a decrease of varicella cases by 45.7% between 1990 and 2060. Independently of the demographic scenario, varicella vaccination reduces the cumulative number of varicella cases until 2060 by approximately 70%, but also increases HZ cases by 10%. Unlike the currently licensed live attenuated HZ vaccine, the new subunit vaccine candidate might completely counteract this effect. Relative vaccine effects were consistent across all demographic scenarios. Demographic dynamics will be a major determinant of HZ epidemiology in the next 50 years. While stationary population models are appropriate for assessing vaccination impact, models incorporating realistic population structures allow a direct comparison to surveillance data and can thus provide additional input for immunization decision-making and resource planning.

  20. Population pharmacokinetic modelling of the enterohepatic recirculation of diclofenac and rofecoxib in rats

    Science.gov (United States)

    Huntjens, D R H; Strougo, A; Chain, A; Metcalf, A; Summerfield, S; Spalding, D J M; Danhof, M; Della Pasqua, O

    2008-01-01

    Background and purpose: Enterohepatic recirculation (EHC) is a common pharmacokinetic phenomenon that has been poorly modelled in animals. The presence of EHC leads to the appearance of multiple peaks in the concentration-time profile and increased exposure, which may have implications for drug effect and extrapolation across species. The aim of this investigation was to develop a population pharmacokinetic model for diclofenac and rofecoxib that describes EHC and to assess its consequence for the pharmacodynamics of both drugs. Experimental approach: The pharmacokinetics of diclofenac and rofecoxib was characterized in male rats following intravenous, intraperitoneal and oral administration. Blood samples were collected at pre-defined time points after dosing to determine plasma concentrations over time. A parametric approach using nonlinear mixed effects modelling was applied to describe EHC, whilst simulations were used to evaluate its impact on PGE2 inhibition. Key results: For diclofenac, EHC was described by a compartmental model with periodic transfer rate and metabolite formation rate. For rofecoxib, EHC modelling required a conversion compartment with first-order recycling rate and lag time. Based on model predictions, EHC causes an increase of 95% in the systemic exposure to diclofenac and of 15% in the exposure to rofecoxib. In addition, EHC prolongs the inhibition of PGE2 and increases the duration of the anti-inflammatory effect (24 h for rofecoxib 10 mg kg−1) without affecting maximum inhibition. Conclusions and implications: Our findings show the relevance of exploring EHC in a quantitative manner to accurately interpret pharmacodynamic findings in vivo, in particular when scaling across species. PMID:18193075

  1. GRAPHICAL USER INTERFACE WITH APPLICATIONS IN SUSCEPTIBLE-INFECTIOUS-SUSCEPTIBLE MODELS.

    Science.gov (United States)

    Ilea, M; Turnea, M; Arotăriţei, D; Rotariu, Mariana; Popescu, Marilena

    2015-01-01

    Practical significance of understanding the dynamics and evolution of infectious diseases increases continuously in contemporary world. The mathematical study of the dynamics of infectious diseases has a long history. By incorporating statistical methods and computer-based simulations in dynamic epidemiological models, it could be possible for modeling methods and theoretical analyses to be more realistic and reliable, allowing a more detailed understanding of the rules governing epidemic spreading. To provide the basis for a disease transmission, the population of a region is often divided into various compartments, and the model governing their relation is called the compartmental model. To present all of the information available, a graphical user interface provides icons and visual indicators. The graphical interface shown in this paper is performed using the MATLAB software ver. 7.6.0. MATLAB software offers a wide range of techniques by which data can be displayed graphically. The process of data viewing involves a series of operations. To achieve it, I had to make three separate files, one for defining the mathematical model and two for the interface itself. Considering a fixed population, it is observed that the number of susceptible individuals diminishes along with an increase in the number of infectious individuals so that in about ten days the number of individuals infected and susceptible, respectively, has the same value. If the epidemic is not controlled, it will continue for an indefinite period of time. By changing the global parameters specific of the SIS model, a more rapid increase of infectious individuals is noted. Using the graphical user interface shown in this paper helps achieving a much easier interaction with the computer, simplifying the structure of complex instructions by using icons and menus, and, in particular, programs and files are much easier to organize. Some numerical simulations have been presented to illustrate theoretical

  2. A theoretical model for substance abuse in the presence of treatment

    Directory of Open Access Journals (Sweden)

    Farai Nyabadza

    2012-03-01

    Full Text Available The production and use of addictive stimulants has been a major problem in South Africa. Although research has shown increased demand for drug abuse treatment, the actual size of the drug-abusing population remains unknown. Thus the prevalence of drug abuse requires estimation through available tools. Many questions remain unanswered with regard to interventions, new cases of substance abuse and relapse in recovering persons. A six-state compartmental model including a core and non-core group, with fast and slow progression to addiction, was formulated with the aim of qualitatively investigating the dynamics of substance abuse and predicting drug abuse trends. The analysis of the model was presented in terms of the substance abuse epidemic threshold R0. Numerical simulations were performed to fit the model to available data for methamphetamine use in the Western Cape and to determine the role played by some key parameters. The model was also fitted to data on methamphetamine users who enter rehabilitation using the least squares curve fitting method. It was shown that the model exhibits a backward bifurcation where a stable drug-free equilibrium coexists with a stable drug-persistent equilibrium for a certain defined range of values of R0. The stabilities of the model equilibria were ascertained and persistence conditions established. It was found that it is not sufficient to reduce R0 below unit to control the substance abuse epidemic. The reproduction number should be brought below a determined threshold, R0c. The results also suggested that the substance abuse epidemic can be reduced by intervention programmes targeted at light drug users and by increasing the uptake rate into treatment for those addicted. Projected trends showed a steady decline in the prevalence of methamphetamine abuse until 2015.

  3. A new, fully coupled, reaction-transport-mechanical approach to modeling the evolution of natural gas reservoirs in the Piceance Basin

    Science.gov (United States)

    Payne, Dorothy Frances

    The Piceance Basin is highly compartmented, and predicting the location and characteristics of producible reservoirs is difficult. Gas generation is an important consideration in quality and size of natural gas reserves, but it also may contribute to fracturing, and hence the creation of the reservoirs in which it is contained. The purpose of this dissertation is to use numerical modeling to study the evolution of these unconventional natural gas reservoirs in the Piceance Basin. In order to characterize the scale and structure of compartmentation in the Piceance Basin, a set of in-situ fluid pressure data were interpolated across the basin and the resulting fluid pressure distribution was analyzed. Results show complex basin- and field-scale compartmentation in the Upper Cretaceous units. There are no simple correlations between compartment location and such factors as stratigraphy, basin structure, or coal thickness and maturity. To account for gas generation in the Piceance Basin, a new chemical kinetic approach to modeling lignin maturation is developed, based primarily on structural transformations of the lignin molecule observed in naturally matured samples. This model calculates mole fractions of all species, functional group fractions, and elemental weight percents. Results show reasonable prediction of maturities at other sites in the Piceance Basin for vitrinite reflectance up to about 1.7 %Ro. The flexible design of the model allows it to be modified to account for compositionally heterogeneous source material. To evaluate the role of gas generation in this dynamical system, one-dimensional simulations have been performed using the CIRFB reaction-transport-mechanical (RTM) simulator. CIRFB accounts for compaction, fracturing, hydrocarbon generation, and multi-phase flow. These results suggest that by contributing to overpressure, gas generation has two important implications: (1) gas saturation in one unit affects fracturing in other units, thereby

  4. Model(ing) Law

    DEFF Research Database (Denmark)

    Carlson, Kerstin

    The International Criminal Tribunal for the former Yugoslavia (ICTY) was the first and most celebrated of a wave of international criminal tribunals (ICTs) built in the 1990s designed to advance liberalism through international criminal law. Model(ing) Justice examines the case law of the ICTY...

  5. Models and role models

    NARCIS (Netherlands)

    ten Cate, J.M.

    2015-01-01

    Developing experimental models to understand dental caries has been the theme in our research group. Our first, the pH-cycling model, was developed to investigate the chemical reactions in enamel or dentine, which lead to dental caries. It aimed to leverage our understanding of the fluoride mode of

  6. Field Demonstration of Horizontal Infill Drilling Using Cost-effective Integrated Reservoir Modeling--Mississippian Carbonates, Central Kansas

    Energy Technology Data Exchange (ETDEWEB)

    Saibal Bhattacharya

    2005-08-31

    data constraints afflicting mature Mississippian fields. A publicly accessible databank of representative petrophysical properties and relationships was developed to overcome the paucity of such data that is critical to modeling the storage and flow in these reservoirs. Studies in 3 Mississippian fields demonstrated that traditional reservoir models built by integrating log, core, DST, and production data from existing wells on 40-acre spacings are unable to delineate karst-induced compartments, thus making 3D-seismic data critical to characterize these fields. Special attribute analyses on 3D data were shown to delineate reservoir compartments and predict those with pay porosities. Further testing of these techniques is required to validate their applicability in other Mississippian reservoirs. This study shows that detailed reservoir characterization and simulation on geomodels developed by integrating wireline log, core, petrophysical, production and pressure, and 3D-seismic data enables better evaluation of a candidate field for horizontal infill applications. In addition to reservoir compartmentalization, two factors were found to control the economic viability of a horizontal infill well in a mature Mississippian field: (a) adequate reservoir pressure support, and (b) an average well spacing greater than 40-acres.

  7. Development of a zoning-based environmental-ecological-coupled model for lakes to assess lake restoration effect

    Science.gov (United States)

    Xu, Mengjia; Zou, Changxin; Zhao, Yanwei

    2017-04-01

    Environmental/ecological models are widely used for lake management as they provide a means to understand physical, chemical and biological processes in highly complex ecosystems. Most research focused on the development of environmental (water quality) and ecological models, separately. Limited studies were developed to couple the two models, and in these limited coupled models, a lake was regarded as a whole for analysis (i.e., considering the lake to be one well-mixed box), which was appropriate for small-scale lakes and was not sufficient to capture spatial variations within middle-scale or large-scale lakes. This paper seeks to establish a zoning-based environmental-ecological-coupled model for a lake. The Baiyangdian Lake, the largest freshwater lake in Northern China, was adopted as the study case. The coupled lake models including a hydrodynamics and water quality model established by MIKE21 and a compartmental ecological model used STELLA software have been established for middle-sized Baiyangdian Lake to realize the simulation of spatial variations of ecological conditions. On the basis of the flow field distribution results generated by MIKE21 hydrodynamics model, four water area zones were used as an example for compartmental ecological model calibration and validation. The results revealed that the developed coupled lake models can reasonably reflected the changes of the key state variables although there remain some state variables that are not well represented by the model due to the low quality of field monitoring data. Monitoring sites in a compartment may not be representative of the water quality and ecological conditions in the entire compartment even though that is the intention of compartment-based model design. There was only one ecological observation from a single monitoring site for some periods. This single-measurement issue may cause large discrepancies particularly when sampled site is not representative of the whole compartment. The

  8. The Potential for Zinc Stable Isotope Techniques and Modelling to Determine Optimal Zinc Supplementation

    Science.gov (United States)

    Tran, Cuong D.; Gopalsamy, Geetha L.; Mortimer, Elissa K.; Young, Graeme P.

    2015-01-01

    It is well recognised that zinc deficiency is a major global public health issue, particularly in young children in low-income countries with diarrhoea and environmental enteropathy. Zinc supplementation is regarded as a powerful tool to correct zinc deficiency as well as to treat a variety of physiologic and pathologic conditions. However, the dose and frequency of its use as well as the choice of zinc salt are not clearly defined regardless of whether it is used to treat a disease or correct a nutritional deficiency. We discuss the application of zinc stable isotope tracer techniques to assess zinc physiology, metabolism and homeostasis and how these can address knowledge gaps in zinc supplementation pharmacokinetics. This may help to resolve optimal dose, frequency, length of administration, timing of delivery to food intake and choice of zinc compound. It appears that long-term preventive supplementation can be administered much less frequently than daily but more research needs to be undertaken to better understand how best to intervene with zinc in children at risk of zinc deficiency. Stable isotope techniques, linked with saturation response and compartmental modelling, also have the potential to assist in the continued search for simple markers of zinc status in health, malnutrition and disease. PMID:26035248

  9. Controlling measles using supplemental immunization activities: a mathematical model to inform optimal policy.

    Science.gov (United States)

    Verguet, Stéphane; Johri, Mira; Morris, Shaun K; Gauvreau, Cindy L; Jha, Prabhat; Jit, Mark

    2015-03-03

    The Measles & Rubella Initiative, a broad consortium of global health agencies, has provided support to measles-burdened countries, focusing on sustaining high coverage of routine immunization of children and supplementing it with a second dose opportunity for measles vaccine through supplemental immunization activities (SIAs). We estimate optimal scheduling of SIAs in countries with the highest measles burden. We develop an age-stratified dynamic compartmental model of measles transmission. We explore the frequency of SIAs in order to achieve measles control in selected countries and two Indian states with high measles burden. Specifically, we compute the maximum allowable time period between two consecutive SIAs to achieve measles control. Our analysis indicates that a single SIA will not control measles transmission in any of the countries with high measles burden. However, regular SIAs at high coverage levels are a viable strategy to prevent measles outbreaks. The periodicity of SIAs differs between countries and even within a single country, and is determined by population demographics and existing routine immunization coverage. Our analysis can guide country policymakers deciding on the optimal scheduling of SIA campaigns and the best combination of routine and SIA vaccination to control measles. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. The Potential for Zinc Stable Isotope Techniques and Modelling to Determine Optimal Zinc Supplementation

    Directory of Open Access Journals (Sweden)

    Cuong D. Tran

    2015-05-01

    Full Text Available It is well recognised that zinc deficiency is a major global public health issue, particularly in young children in low-income countries with diarrhoea and environmental enteropathy. Zinc supplementation is regarded as a powerful tool to correct zinc deficiency as well as to treat a variety of physiologic and pathologic conditions. However, the dose and frequency of its use as well as the choice of zinc salt are not clearly defined regardless of whether it is used to treat a disease or correct a nutritional deficiency. We discuss the application of zinc stable isotope tracer techniques to assess zinc physiology, metabolism and homeostasis and how these can address knowledge gaps in zinc supplementation pharmacokinetics. This may help to resolve optimal dose, frequency, length of administration, timing of delivery to food intake and choice of zinc compound. It appears that long-term preventive supplementation can be administered much less frequently than daily but more research needs to be undertaken to better understand how best to intervene with zinc in children at risk of zinc deficiency. Stable isotope techniques, linked with saturation response and compartmental modelling, also have the potential to assist in the continued search for simple markers of zinc status in health, malnutrition and disease.

  11. Modelling fuel consumption in kerbside source segregated food waste collection: separate collection and co-collection.

    Science.gov (United States)

    Chu, T W; Heaven, S; Gredmaier, L

    2015-01-01

    Source separated food waste is a valuable feedstock for renewable energy production through anaerobic digestion, and a variety of collection schemes for this material have recently been introduced. The aim of this study was to identify options that maximize collection efficiency and reduce fuel consumption as part of the overall energy balance. A mechanistic model was developed to calculate the fuel consumption of kerbside collection of source segregated food waste, co-mingled dry recyclables and residual waste. A hypothetical city of 20,000 households was considered and nine scenarios were tested with different combinations of collection frequencies, vehicle types and waste types. The results showed that the potential fuel savings from weekly and fortnightly co-collection of household waste range from 7.4% to 22.4% and 1.8% to 26.6%, respectively, when compared to separate collection. A compartmentalized vehicle split 30:70 always performed better than one with two compartments of equal size. Weekly food waste collection with alternate weekly collection of the recyclables and residual waste by two-compartment collection vehicles was the best option to reduce the overall fuel consumption.

  12. Trophic modeling of Eastern Boundary Current Systems: a review and prospectus for solving the “Peruvian Puzzle”

    Directory of Open Access Journals (Sweden)

    Marc H. Taylor

    2013-04-01

    Full Text Available Eastern Boundary Current systems (EBCSs are among the most productive fishing areas in the world. High primary and secondary productivity supports a large biomass of small planktivorous pelagic fish, “small pelagics”, which are important drivers of production to the entire system whereby they can influence both higher and lower trophic levels. Environmental variability causes changes in plankton (food quality and quantity, which can affect population sizes, distribution and domi-nance among small pelagics. This variability combined with impacts from the fishery complicate the development of management strategies. Consequently, much recent work has been in the development of multispecies trophic models to better understand interdependencies and system dynamics. Despite similarities in extent, structure and primary productivity between EBCSs, the Peruvian system greatly differs from the others in the magnitude of fish catches, due mainly to the incredible production of the anchovy Engraulis ringens. This paper reviews literature concerning EBCSs dynamics and the state-of-the-art in the trophic modeling of EBCSs. The objective is to critically analyze the potential of this approach for system understanding and management and to adapt existing steady-state models of the Peruvian system for use in (future dynamic simulations. A guideline for the construction of trophodynamic models is presented taking into account the important trophic and environmental interactions. In consideration of the importance of small pelagics for the system dynamics, emphasis is placed on developing appropriate model compartmentalization and spatial delineation that facilitates dynamic simulations. Methods of model validation to historical changes are presented to support hypotheses concerning EBCS dynamics and as a critical step to the development of predictive models. Finally, the identification of direct model links to easily obtainable abiotic parameters is

  13. Seismicity and coupled deformation modeling at the Coso Geothermal Field

    Science.gov (United States)

    Kaven, J. O.; Hickman, S. H.; Davatzes, N. C.

    2015-12-01

    Micro-seismicity in geothermal reservoirs, in particular in enhanced geothermal systems (EGS), is a beneficial byproduct of injection and production, as it can indicate the generation of high-permeability pathways on either pre-existing or newly generated faults and fractures. The hazard of inducing an earthquake large enough to be felt at the surface, however, is not easily avoided and has led to termination of some EGS projects. To explore the physical processes leading to permeability creation and maintenance in geothermal systems and the physics of induced earthquakes , we investigated the evolution of seismicity and the factors controlling the migration, moment release rate, and timing of seismicity in the Coso Geothermal Field (CGF). We report on seismicity in the CGF that has been relocated with high precision double-difference relocation techniques and simultaneous velocity inversions to understand hydrologic reservoir compartmentalization and the nature of subsurface boundaries to fluid flow. We find that two distinct compartments are present within the CGF, which are divided by an aseismic gap showing a relatively low Vp/Vs ratio, likely indicating lower temperatures or lower pore pressures within the gap than in the adjacent reservoir compartments. Well-located events with Mw> 3.5 tend to map onto reactivated fault structures that were revealed when imaged by the relocated micro-seismicity. We relate the temporal and spatial migration of moment release rate to the injection and production histories in the reservoir by employing a thermo-poro-elastic finite element model that takes into account the compartment boundaries defined by the seismicity. We find that pore pressure effects alone are not responsible for the migration of seismicity and that poro-elastic and thermo-elastic stress changes are needed in addition to fluid pressure effects to account for the observed moment release rates.

  14. Predictive features of persistent activity emergence in regular spiking and intrinsic bursting model neurons.

    Directory of Open Access Journals (Sweden)

    Kyriaki Sidiropoulou

    Full Text Available Proper functioning of working memory involves the expression of stimulus-selective persistent activity in pyramidal neurons of the prefrontal cortex (PFC, which refers to neural activity that persists for seconds beyond the end of the stimulus. The mechanisms which PFC pyramidal neurons use to discriminate between preferred vs. neutral inputs at the cellular level are largely unknown. Moreover, the presence of pyramidal cell subtypes with different firing patterns, such as regular spiking and intrinsic bursting, raises the question as to what their distinct role might be in persistent firing in the PFC. Here, we use a compartmental modeling approach to search for discriminatory features in the properties of incoming stimuli to a PFC pyramidal neuron and/or its response that signal which of these stimuli will result in persistent activity emergence. Furthermore, we use our modeling approach to study cell-type specific differences in persistent activity properties, via implementing a regular spiking (RS and an intrinsic bursting (IB model neuron. We identify synaptic location within the basal dendrites as a feature of stimulus selectivity. Specifically, persistent activity-inducing stimuli consist of activated synapses that are located more distally from the soma compared to non-inducing stimuli, in both model cells. In addition, the action potential (AP latency and the first few inter-spike-intervals of the neuronal response can be used to reliably detect inducing vs. non-inducing inputs, suggesting a potential mechanism by which downstream neurons can rapidly decode the upcoming emergence of persistent activity. While the two model neurons did not differ in the coding features of persistent activity emergence, the properties of persistent activity, such as the firing pattern and the duration of temporally-restricted persistent activity were distinct. Collectively, our results pinpoint to specific features of the neuronal response to a given

  15. Noninvasive estimation of bound and mobile platinum compounds in the kidney using a radiopharmacokinetic model

    International Nuclear Information System (INIS)

    Brechner, R.R.; D'Argenio, D.Z.; Dahalan, R.; Wolf, W.

    1986-01-01

    Nephrotoxicity remains a major limitation in the use of cisplatin [cis-diamminedichloroplatinum(II)]. Although several strategies are in use to limit this serious side effect, none is fully satisfactory. Classical pharmacokinetic studies of cisplatin have been based on blood and urine samples. As nephrotoxicity plays a significant role in the design of the therapeutic strategy, the kidneys should be considered as a separate state in any model formulated for ultimate control purposes. Previous studies of organ pharmacokinetics have relied on population measurements. The authors have developed an organ compartmental model from individual animal data obtained noninvasively. The eight-compartment model used to represent the distribution of cisplatin considers free and bound platinum in plasma, platinum in the erythrocytes, mobile and bound platinum in the kidneys, mobile and bound platinum in the tissues, and platinum in the urine. Data were collected from experiments with anesthetized female rats, after intravenous administration of [195mPt]cisplatin. Both arterial and bladder samples, and multiple images obtained with an Anger camera interfaced to a microcomputer were used. The model was estimated from individual data obtained after injection of a bolus of cisplatin (six animals). The model was validated by using it to predict data obtained from forcing the system with a different input function, a 0.5-h intravenous infusion (three animals). The results of this work show that it is possible to noninvasively study drug kinetics in organs that are not readily accessible to direct measurements in an individual, rather than relying on invasive measurements performed on a population.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Dynamical modeling of the moth pheromone-sensitive olfactory receptor neuron within its sensillar environment.

    Directory of Open Access Journals (Sweden)

    Yuqiao Gu

    Full Text Available In insects, olfactory receptor neurons (ORNs, surrounded with auxiliary cells and protected by a cuticular wall, form small discrete sensory organs--the sensilla. The moth pheromone-sensitive sensillum is a well studied example of hair-like sensillum that is favorable to both experimental and modeling investigations. The model presented takes into account both the molecular processes of ORNs, i.e. the biochemical reactions and ionic currents giving rise to the receptor potential, and the cellular organization and compartmentalization of the organ represented by an electrical circuit. The number of isopotential compartments needed to describe the long dendrite bearing pheromone receptors was determined. The transduction parameters that must be modified when the number of compartments is increa