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At least 127 records · Page 7Linked to original sources

Modeling the hemodynamic response to dopamine in acute heart failure.

A descriptive incremental nonlinear single-input-multiple-output (SIMO) model of the hemodynamic response [cardiac output (CO) and mean aortic pressure (MAP)] to the inotropic drug dopamine in acute ischemic heart failure was constructed to facilitate the design of closed-loop control systems. The structure of the CO component of the model is a first-order system with a sigmoidal relationship. The MAP component is a first-order system with a threshold. Parameter identification was performed on data collected during positive step (drug on) and negative step (drug off) testing using multiple levels (2-6 mcg/kg/min) of infusion of dopamine in a canine model of acute ischemic heart failure. Parameter estimation utilized a least squares objective function and a linearized form of the step response of the model in the time domain. The model provides good approximations to the mean empirical responses.

Animals↗

In vivo experimental testing and model identification of human scalp skin.

A comprehensive experimental/numerical procedure is formulated and validated for the in vivo characterization of the mechanical properties of human skin and the simulation of reconstructive surgery. The procedure uses in vivo experimental tests on undermined skin flaps, which can be performed during surgery, a numerical model formulated within the framework of nonlinear finite strain elasticity and a nonlinear parameter identification technique for the calibration of the model from indirect measurements. The procedure is applied to characterize the scalp skin tested in Raposio and Nordström (Skin Res. Technol. 4 (1998) 94). The skin is treated as a time independent, isotropic and hyperelastic membrane and the problem is solved through a finite element discretization. The study highlights that the model parameters can be determined with good accuracy using displacement measurements of a few points in the domain.

Biomechanical Phenomena↗

On the design of optimal dynamic experiments for parameter estimation of a Ratkowsky-type growth kinetics at suboptimal temperatures.

It is generally known that accurate model building, i.e., proper model structure selection and reliable parameter estimation, constitutes an essential matter in the field of predictive microbiology, in particular, when integrating these predictive models in food safety systems. In this context, Versyck et al. (1999) have introduced the methodology of optimal experimental design techniques for parameter estimation within the field. Optimal experimental design focuses on the development of optimal input profiles such that the resulting rich (i.e., highly informative) experimental data enable unique model parameter estimation. As a case study, Versyck et al. (1999) [Versyck, K., Bernaerts, K., Geeraerd, A.H., Van Impe, J.F., 1999. Introducing optimal experimental design in predictive modeling: a motivating example. Int. J. Food Microbiol., 51(1), 39-51] have elaborated the estimation of Bigelow inactivation kinetics parameters (in a numerical way). Opposed to the classic (static) experimental approach in predictive modelling, an optimal dynamic experimental setup is presented. In this paper, the methodology of optimal experimental design or parameter estimation is applied to obtain uncorrelated estimates of the square root model parameters [Ratkowsky, D.A., Olley, J., McMeekin, T.A., Ball, A., 1982. Relationship between temperature and growth rate of bacterial cultures. J. Bacteriol. 149, 1-5] describing the effect of suboptimal growth temperatures on the maximum specific growth rate of microorganisms. These estimates are the direct result of fitting a primary growth model to cell density measurements as a function of time. Apart from the design of an optimal time-varying temperature profile based on a sensitivity study of the model output, an important contribution of this publication is a first experimental validation of this innovative dynamic experimental approach for uncorrelated parameter identification. An optimal step temperature profile, within the range of model validity and practical feasibility, is developed for Escherichia coli K12 and successfully applied in practice. The presented experimental validation result illustrates the large potential of the dynamic experimental approach in the context of uncorrelated parameter estimation. Based on the experimental validation result, additional remarks are formulated related to future research in the field of optimal experimental design.

Escherichia coli↗

Model identification of signal transduction networks from data using a state regulator problem.

Advances in molecular biology provide an opportunity to develop detailed models of biological processes that can be used to obtain an integrated understanding of the system. However, development of useful models from the available knowledge of the system and experimental observations still remains a daunting task. In this work, a model identification strategy for complex biological networks is proposed. The approach includes a state regulator problem (SRP) that provides estimates of all the component concentrations and the reaction rates of the network using the available measurements. The full set of the estimates is utilised for model parameter identification for the network of known topology. An a priori model complexity test that indicates the feasibility of performance of the proposed algorithm is developed. Fisher information matrix (FIM) theory is used to address model identifiability issues. Two signalling pathway case studies, the caspase function in apoptosis and the MAP kinase cascade system, are considered. The MAP kinase cascade, with measurements restricted to protein complex concentrations, fails the a priori test and the SRP estimates are poor as expected. The apoptosis network structure used in this work has moderate complexity and is suitable for application of the proposed tools. Using a measurement set of seven protein concentrations, accurate estimates for all unknowns are obtained. Furthermore, the effects of measurement sampling frequency and quality of information in the measurement set on the performance of the identified model are described.

Algorithms↗

[Quantification study of bone adaptive model based on experiment of rapid-growing rats in different stress environment].

Presented is a method to set up a quantification model of bone growing and remodeling adaptation, which integrates animal experiments, parameter identification of mathematical functions and technique of computer simulation. By designing a new animal experiment, we investigate the effects of growing and remodeling of the rat femurs in different stress environments, gather the bone mineral density (BMD) of proximal femur in the same interval for the unknown parameter (B and K) inversion of bone growing and remodeling equation and create the femur three-dimensional geometrical model based on CT images. The model in this paper can not only numerically measure the relation between outer stimulus and the femur BMD variation of rapid growing rats, but also predict the growth trend of rat femur under different stress environments in its whole lifecycle. The thought and method of creating the model in this paper can be used for reference to modeling human bone growth and remodeling.

Adaptation, Physiological↗

A visualization-based analysis method for multiparameter models of capillary tissue-exchange.

In order to successfully use a model for parameter identification, it must be carefully analyzed. Current analysis methods, however, are ad hoc and provide only partial information. We extended these methods through the application of stacked dimensions, a scientific visualization method. The end result of our extensions are multi-dimensional parametric model-images. These images depict a model as a function of all its parameters in a single graphic. We applied parametric model-images to model verification (behavioral analysis), sensitivity analysis, and identifiability analysis. We applied our methodology to the evaluation of pulmonary vascular capillary-transport models. Results have shown that the visualization-based method provides a more complete view of a model's behavior and its other characteristics. Furthermore, our method has also proven to be more computationally efficient than the traditional approaches.

Capillary Permeability↗

Quantitative genetic models for describing simultaneous and recursive relationships between phenotypes.

Multivariate models are of great importance in theoretical and applied quantitative genetics. We extend quantitative genetic theory to accommodate situations in which there is linear feedback or recursiveness between the phenotypes involved in a multivariate system, assuming an infinitesimal, additive, model of inheritance. It is shown that structural parameters defining a simultaneous or recursive system have a bearing on the interpretation of quantitative genetic parameter estimates (e.g., heritability, offspring-parent regression, genetic correlation) when such features are ignored. Matrix representations are given for treating a plethora of feedback-recursive situations. The likelihood function is derived, assuming multivariate normality, and results from econometric theory for parameter identification are adapted to a quantitative genetic setting. A Bayesian treatment with a Markov chain Monte Carlo implementation is suggested for inference and developed. When the system is fully recursive, all conditional posterior distributions are in closed form, so Gibbs sampling is straightforward. If there is feedback, a Metropolis step may be embedded for sampling the structural parameters, since their conditional distributions are unknown. Extensions of the model to discrete random variables and to nonlinear relationships between phenotypes are discussed.

Bayes Theorem↗

Differential promoter usage for insulin-like growth factor-II gene in Chinese hepatocellular carcinoma with hepatitis B virus infection.

BACKGROUND: Human insulin-like growth factor-II (IGF-II) gene contains nine exons and four different promoters (P1-P4). Expression of the gene is elevated in the preneoplastic hepatic foci and hepatocellular carcinoma (HCC) of experimental animals and humans. To gain insight into transcriptional regulation of the gene in HCC, we analyzed the relative usage of the P1-P4 promoters and its correlation with the clinical and pathological characteristics in Chinese hepatocellular carcinoma with hepatitis B virus (HBV) infection. METHODS: P1-P4 usage levels of the gene in tumorous and matched adjacent nontumorous tissues from 23 HCC patients and 7 normal liver tissues were evaluated using a semiquantitative reverse-transcription polymerase chain reaction (RT-PCR) assay. The mutation status of p53 gene in HCC tissues was analyzed by PCR and sequencing. RESULTS: Transcripts from P1 were not detectable in 65.2% HCC tissues, and were expressed at low levels or not expressed in all nontumorous tissues compared with normals, but P2 usage levels showed no differences. P3 and P4 expression was significantly increased in most of HCC and almost all adjacent nontumorous tissues. There was a positive association of expression levels of both P3 and P4 transcripts in HCC tissues with the p53 mutation and presence of tumor embolus of portal vein, and expression of P3 were negatively related to differentiation of HCC. However, expression of both P3 and P4 was not associated with other parameters. CONCLUSIONS: Loss of P1 activity and reactivation of P3 and P4 are important characteristics in most of Chinese HCC with HBV infection, and increased IGF-II expression from P3 and P4 may play an active role in early proliferation of precancerous liver cells and hepatocarcinogenesis of these cases. Significant increase in fetal transcripts is associated with the p53 mutation and poor prognosis of the HCC patients and might serve as one of identification parameters of poor HCC prognosis.

Adult↗

Tendency modeling: a new approach to obtain simplified kinetic models of metabolism applied to Saccharomyces cerevisiae.

A novel approach to construct kinetic models of metabolic pathways, to be used in metabolic engineering, is presented: the tendency modeling approach. This approach greatly facilitates the construction of these models and can easily be applied to complex metabolic networks. The resulting models contain a minimal number of parameters; identification of their values is straightforward. Use of in vitro obtained information in the identification of the kinetic equations is minimized. The tendency modeling approach has been used to derive a dynamic model of primary metabolism for aerobic growth of Saccharomyces cerevisiae on glucose, in which compartmentation is included. Simulation results obtained with the derived model are satisfying for most of the carbon metabolites that have been measured. Compared to a more detailed model, the simulations of our model are less accurate, but taking into account the much smaller number of kinetic parameters (35 instead of 84), the tendency the modeling approach is considered promising.

Biomedical Engineering↗

Identification of a non-linear model as a new method to detect expiratory airflow limitation in mechanically ventilated patients.

Expiratory flow limitation (EFL) can occur in mechanically ventilated patients with chronic obstructive pulmonary disease and other disorders. It leads to dynamic hyperinflation with ensuing deleterious consequences. Detecting EFL is thus clinically relevant. Easily applicable methods however lack this detection being routinely made in intensive care. Using a simple mathematical model, we propose a new method to detect EFL that does not require any intervention or modification of the ongoing therapeutic. The model consists in a monoalveolar representation of the respiratory system, including a collapsible airway that is submitted to periodic changes in pressure at the airway opening: EFL provokes a sharp expiratory increase in the resistance Rc of the collapsible airway. The model parameters were identified via the Levenberg-Marquardt method by fitting simulated data on the airway pressure and the flow signals recorded in 10 mechanically ventilated patients. A sensitivity study demonstrated that only 8/11 parameters needed to be identified, the remaining three being given reasonable physiological values. Flow-volume curves built at different levels of positive expiratory pressure, PEEP, during "PEEP trials" (stepwise increases in positive end-expiratory pressure to optimize ventilator settings) have shown evidence of EFL in three cases. This was concordant with parameter identification (high Rc during expiration for EFL patients). We conclude from these preliminary results that our model is a potential tool for the non-invasive detection of EFL in mechanically ventilated patients.

Adult↗

The NoH value in EPR spin trapping: a new parameter for the identification of 5,5-dimethyl-1-pyrroline-N-oxide spin adducts.

The ratio of the nitrogen to hydrogen hyperfine splittings (aN/aH) of spin adducts derived from the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) has been found to be a useful parameter for adduct identification. For example, this parameter makes it possible to distinguish between the superoxide (aN/aH = 1.22-1.26) and peroxyl (aN/aH = 1.33-1.40) radical adducts of DMPO in aqueous solution. Since the aN to aH ratio corrects for minor differences in EPR spectrometer calibration, it is a more reproducible parameter than the aN and aH values themselves.

Cyclic N-Oxides↗

[Validation of a new interactive software monitoring a controlled-flow infusion pump for cisplatin dosage regimen adjustment].

Adaptive dosing of cisplatin (CDDP) results in reduced haematological and renal toxicity but it has never been clearly shown that it affects the tumoral response rate. Before undertaking a clinical randomized study of CDDP monitoring versus standard dose, a comparative study was performed between a new software dedicated to the interactive adjustments--the AJI software--and the APIS software for clinical pharmacokinetics which incorporates a bayesian procedure and a population information computed according to a three compartment model. CDDP was administered by continuous infusion at variable rates with a controlled flow pump during four days in order to reach the target of 1.3 mg/L at the end of the first day, and to maintain this level during the whole treatment. This study was carried out on two groups of patients. Group 1 (12 patients; 27 courses) received CDDP with sequential flow rates in order to obtain a population information to be used with AJI. For patients in group 2 (14 patients; 26 courses), doses (flows) were adapted in a prospective study using the AJI software two to three times the first day, then daily. They could have been adapted (retrospective study) after platin pharmacokinetic parameters identification by APIS. The dosage recommendations proposed by APIS the first day, from 12 hours to 24 hours, to reach the target of 1.3 mg/L at 24 hours, and then daily up to D4 (AAPT at Di) to maintain this level were compared to those which were really administered during the interactive treatment (DA at Di). There were no statistically significant difference for D2, D4 and for the total dose (118.7 +/- 20.1 mg and 118.5 +/- 45.1 mg). The difference was statistically significant for D1 and D3 (P < 0.05). The inter-individual variability was less important with AJI (CV = 16.9% for DA total) than with APIS (CV = 38.0% for ADAPT total). The platin pharmacokinetic parameters identified the first day by APIS were not statistically different from those identified from the whole treatment for clearance (5.92 and 5.63 l/d) and Vtotal 87.8 and 93.1 L); the difference was statistically significant for Vinitial (34.7 and 42.5 L; P < 0.05) and the terminal half-life (13.1 and 15.5 days; P < 0.05).

Adolescent↗

Identitag, a relational database for SAGE tag identification and interspecies comparison of SAGE libraries.

BACKGROUND: Serial Analysis of Gene Expression (SAGE) is a method of large-scale gene expression analysis that has the potential to generate the full list of mRNAs present within a cell population at a given time and their frequency. An essential step in SAGE library analysis is the unambiguous assignment of each 14 bp tag to the transcript from which it was derived. This process, called tag-to-gene mapping, represents a step that has to be improved in the analysis of SAGE libraries. Indeed, the existing web sites providing correspondence between tags and transcripts do not concern all species for which numerous EST and cDNA have already been sequenced. RESULTS: This is the reason why we designed and implemented a freely available tool called Identitag for tag identification that can be used in any species for which transcript sequences are available. Identitag is based on a relational database structure in order to allow rapid and easy storage and updating of data and, most importantly, in order to be able to precisely define identification parameters. This structure can be seen like three interconnected modules : the first one stores virtual tags extracted from a given list of transcript sequences, the second stores experimental tags observed in SAGE experiments, and the third allows the annotation of the transcript sequences used for virtual tag extraction. It therefore connects an observed tag to a virtual tag and to the sequence it comes from, and then to its functional annotation when available. Databases made from different species can be connected according to orthology relationship thus allowing the comparison of SAGE libraries between species. We successfully used Identitag to identify tags from our chicken SAGE libraries and for chicken to human SAGE tags interspecies comparison. Identitag sources are freely available on http://pbil.univ-lyon1.fr/software/identitag/ web site. CONCLUSIONS: Identitag is a flexible and powerful tool for tag identification in any single species and for interspecies comparison of SAGE libraries. It opens the way to comparative transcriptomic analysis, an emerging branch of biology.

Animals↗

Mathematical modeling of elution curves for a protein mixture in ion exchange chromatography and for the optimal selection of operational conditions.

Elution curves in ionic exchange chromatography (IEC) for a three-protein mixture (alpha-lactoalbumin, ovalbumin, and beta-lactoglobulin), carried out under different flow rates and ionic strength conditions, were simulated using two different mathematical models. These models were the Plate Model and the more fundamentally based Rate Model. Relatively low protein concentrations were used to avoid protein-protein interactions. Simulated elution curves were compared with experimental data not used for parameter identification. Deviation between experimental data and the simulated curves using the Plate Model was less than 0.0189 (absorbance units); a slightly higher deviation [0.0252 (absorbance units)] was obtained when the Rate Model was used. A cost function was built that included the effect of the different production stages, namely fermentation, purification, and concentration. These considered the effect on the performance of IEC; yield, purity, concentration and the time needed to accomplish the separation. Operational conditions in the IEC such as flow rate, ionic strength gradient and the operational time can be selected using this model in order to find the minimum cost for the protein production process depending on the characteristics of the final product desired such as purity and yield. This cost function was successfully used for the selection of the operational conditions as well as the fraction of the product to be collected (peak cutting) in IEC. It can be used for protein products with different characteristics and qualities, such as purity and yield, by choosing the appropriate parameters.

Chromatography, Ion Exchange↗

[Concept and interim result of the ALL-BFM 90 therapy study in treatment of acute lymphoblastic leukemia in children and adolescents: the significance of initial therapy response in blood and bone marrow].

In the ongoing trial ALL-BFM 90 for the treatment of childhood non-B cell acute lymphoblastic leukemia (ALL) 1468 unselected patients (pts) were enrolled from 84 centers in Germany and Switzerland from 4/90 to 12/93. Based on the results of the previous trial ALL/NHL-BFM 86 this treatment program focused especially on therapy modifications for average (MRG) and high risk (HRG) pts, on the evaluation of therapy response for prognosis, and on the identification of high risk pts by molecular genetics. For average risk pts consolidation therapy was intensified by the addition of L-asparaginase (L-ASP) on a randomized basis. In HRG induction and consolidation therapy was modified by introduction of early intensification elements that had proved to be effective in relapsed pts. This patient group was randomized for the evaluation of the effects of G-CSF administered in the intervals between the intensification elements. Distribution of the 1376 eligible pts into the three treatment arms SRG (standard risk), MRG, and HRG was as expected (17 pts not yet assigned): 385 pts (28.0%), 834 pts (60.6%), and 140 pts (10.2%), respectively. Treatment consisted of the 8-drug induction (Protocol I), consolidation (Protocol M), reinduction (Protocol II), and maintenance therapy (total therapy duration 24 months). The drug doses and combinations were only slightly modified compared to the previous study ALL-BFM 86 with the exception of the randomized L-ASP containing arm MRG-2 (Protocol M-A) and group HRG. Preventive cranial irradiation was reduced to 12 Gy and applied to MRG and HRG pts only. As in study ALL-BFM 86, the initial response to a 7-day exposure to prednisone and to the first intrathecal injection of MTX at diagnosis was evaluated at day 8 of treatment with regard to blast count in peripheral blood (PB). In addition, pts were now investigated for the presence of blasts in the bone marrow (BM) at day 15 of treatment to compare the prognostic power of both response parameters. Identification of translocation t(9; 22) and/or BCR-ABL rearrangement characterized a small subgroup of pts that were not detected by poor initial therapy response. These pts were enrolled in HRG for more intensive treatment including allogeneic bone marrow transplantation (BMT). After a median observation time of 22 months, the overall probability for event-free survival (p-EFS) is 82 +/- 2%. 11 pts (0.8%) died before complete remission (CR) was achieved, 15 pts (1.1%) died while in CR for reasons other than relapse.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Rapid monitoring for the enhanced definition and control of a selective cell homogenate purification by a batch-flocculation process.

Downstream-bioprocess operations, for example, selective flocculation, are inherently variable due to fluctuations in feed material, equipment performance, and quality of additives such as flocculating agents. Due to these fluctuations in operating conditions, some form of process control is essential for reproducible and satisfactory process performance and hence, product quality. Both product (alcohol dehydrogenase) and key contaminants (RNA, protein, cell debris) within a Saccharomyces cerevisiae system were monitored in real-time adopting an at-line enzymatic reaction and rapid UV-VIS spectral-analysis technique every 135 seconds. The real-time measurements were implemented within two control configurations to regulate the batch-flocculation process according to prespecified control objectives, using the flocculant dose as the sole manipulative variable. An adaptive, model-based control arrangement was studied, which combined the rapid measurements with a process model and two model parameter-identification techniques for real-time prediction of process behavior. Based on an up-to-date mathematical description of the flocculation system, process optimization was attained and subsequent feedback control to this optimum operating set point was reproducibly demonstrated with a 92% accuracy. A simpler control configuration was also investigated adopting the cell debris concentration as the control variable. Both control arrangements resulted in superior flocculation-process performances in terms of contaminant removal, product recovery, and excess flocculant usage compared to an uncontrolled system.

Alcohol Dehydrogenase↗

Hydraulics of laboratory and full-scale upflow anaerobic sludge blanket (UASB) reactors.

Laboratory-scale upflow anaerobic sludge blanket (UASB) reactors are often used as test platforms to evaluate full-scale applications. However, for a given volume specific hydraulic loading rate and geometry, the gas and liquid flows increase proportionally with the cube root of volume. In this communication, we demonstrate that a laboratory-scale reactor had plug-flow hydraulics, while a full-scale reactor had mixed flow hydraulics. The laboratory-scale reactor could be modeled using an existing biochemical model, and parameters identified, but because of computational speed with plug-flow hydraulics, mixed systems are instead recommended for parameter identification studies. Because of the scaling issues identified, operational data should not be directly projected from laboratory-scale results to the full-scale design.

Anaerobiosis↗

Wheat gliadin: digital imaging and database construction using a 4-band reference system of agarose isoelectric focusing patterns.

An isoelectric focusing method using thin-layer agarose gel has been developed for wheat gliadin. Using flat-bed units with a third electrode, up to 72 samples per gel may be analyzed. Advantages over traditional acid polyacrylamide gel electrophoresis methodology include: faster run times, nontoxic media, and greater sample capacity. The method is suitable for fingerprinting or purity testing of wheat varieties. Using digital images captured by a flat-bed scanner, a 4-band reference system using isoelectric points was devised. Software enables separated bands to be assigned pI values based upon reference tracks. Precision of assigned isoelectric points is shown to be on the order of 0.02 pH units. Captured images may be stored in a computer database and compared to unknown patterns to enable an identification. Parameters for a match with a stored pattern may be adjusted for pI interval required for a match, and number of best matches.

Databases, Factual↗