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PubMedDate not supplied

In-sewer wastewater characterization and model parameter determination using respirometry.

Experimental determination of wastewater characteristics and model parameters is required for robust modeling of in-sewer processes. Respirometric assays can be used to determine some of the model parameters, thus reducing the number of model parameters to be determined by model calibration and verification. However, the model structure has to be considered for this purpose. The model used consists of three main modules, namely hydrodynamics, advection and dispersion, and biochemical processes, and is applicable in sewers under aerobic dry-weather flow conditions. A procedure is proposed to determine important chemical oxygen demand (COD) fractions and model parameters for biochemical processes. Cumulative oxygen utilization proves to be useful for process identification, providing extra information on substrate availability during the assay. While the values obtained for both COD fractions and parameters depend on the model structure adopted, the procedure used can easily be adapted to other model formulations.

Bacteria, Aerobic↗
PubMed1997

Are pleural fluid parameters related to the development of residual pleural thickening in tuberculosis?

STUDY OBJECTIVE: Identification of predictive factors for the development of residual pleural thickening (RPT). DESIGN: Retrospective study. LOCATION: A 1,500-bed tertiary hospital. PATIENTS: Patients with pleural tuberculosis diagnosed between December 1991 and February 1995 in our Respiratory Disease Service. INTERVENTIONS: The clinical and radiologic characteristics, and measurements of microbiological and biochemical parameters and markers in pleural fluid were studied. RPT was defined in a posteroanterior chest radiograph as a pleural space of >2 mm measured in the lower lateral chest at the level of an imaginary line intersecting the diaphragmatic dome. MEASUREMENTS AND RESULTS: In 56 patients studied, 11 (19.6%) had RPT 10 mm and 24 (42.8%) had RPT >2 mm. The pleural fluid of patients with RPT 10 mm had a significantly lower glucose concentration and pH and higher lysozyme and tumor necrosis factor-alpha levels than the other patients. The pleural fluid of patients with RPT >2 mm showed no significant differences. CONCLUSIONS: The development of RPT 10 mm was related to higher concentrations of lysozyme and tumor necrosis factor-alpha and lower glucose concentration and pH in pleural fluid compared with development of lower measurements of RPT.

Adolescent↗
PubMed1994

Genetic epidemiology of early onset breast cancer.

Risks for breast cancer when there is a family history of the disease are usually calculated using data from segregation analyses which favour a single dominant gene with high penetrance. There are, however, at least three loci known to be associated with familial breast cancer (p53, BRCA1, and an as yet unpublished locus) and the frequencies and penetrances of these genes are not likely to be the same. We have attempted to address the problem of which genetic parameters should be used to calculate risks for different patterns of familial breast cancer. Data from 384 nuclear families ascertained through a proband selected for early onset breast cancer were subjected to complex segregation analysis, correcting for ascertainment bias resulting from selection for severe phenotype. Age of onset of breast cancer, incorporated as severity, provides additional information to the segregation model over and above that given by assigning liability classes on the basis of age at observation. The use of this additional parameter in the analysis is described. There is fair agreement between estimates from this sample and previous predictions from consecutive probands and consultands. The differences suggest more than one rare dominant gene for susceptibility to breast cancer, with different penetrances. Although refinements of segregation analysis will help to delineate these different genes, perfect resolution will require identification of the mutant alleles. Methods to estimate genetic parameters under genotype specific mortality need to be developed. Meanwhile, we suggest that high and low estimates of penetrance be used in risk estimation for genetic counselling, and as a guide to candidates for entry into clinical trials of screening and chemoprevention in breast cancer.

Adult↗
PubMed1997

Linear and nonlinear ARMA model parameter estimation using an artificial neural network.

This paper addresses parametric system identification of linear and nonlinear dynamic systems by analysis of the input and output signals. Specifically, we investigate the relationship between estimation of the system using a feedforward neural network model and estimation of the system by use of linear and nonlinear autoregressive moving-average (ARMA) models. By utilizing a neural network model incorporating a polynomial activation function, we show the equivalence of the artificial neural network to the linear and nonlinear ARMA models. We compare the parameterization of the estimated system using the neural network and ARMA approaches by utilizing data generated by means of computer simulations. Specifically, we show that the parameters of a simulated ARMA system can be obtained from the neural network analysis of the simulated data or by conventional least squares ARMA analysis. The feasibility of applying neural networks with polynomial activation functions to the analysis of experimental data is explored by application to measurements of heart rate (HR) and instantaneous lung volume (ILV) fluctuations.

Computer Simulation↗
PubMed2006

Identification of biochemical networks by S-tree based genetic programming.

MOTIVATION: Most previous approaches to model biochemical networks have focused either on the characterization of a network structure with a number of components or on the estimation of kinetic parameters of a network with a relatively small number of components. For system-level understanding, however, we should examine both the interactions among the components and the dynamic behaviors of the components. A key obstacle to this simultaneous identification of the structure and parameters is the lack of data compared with the relatively large number of parameters to be estimated. Hence, there are many plausible networks for the given data, but most of them are not likely to exist in the real system. RESULTS: We propose a new representation named S-trees for both the structural and dynamical modeling of a biochemical network within a unified scheme. We further present S-tree based genetic programming to identify the structure of a biochemical network and to estimate the corresponding parameter values at the same time. While other evolutionary algorithms require additional techniques for sparse structure identification, our approach can automatically assemble the sparse primitives of a biochemical network in an efficient way. We evaluate our algorithm on the dynamic profiles of an artificial genetic network. In 20 trials for four settings, we obtain the true structure and their relative squared errors are <5% regardless of releasing constraints about structural sparseness. In addition, we confirm that the proposed algorithm is robust within +/-10% noise ratio. Furthermore, the proposed approach ensures a reasonable estimate of a real yeast fermentation pathway. The comparatively less important connections with non-zero parameters can be detected even though their orders are below 10(-2). To demonstrate the usefulness of the proposed algorithm for real experimental biological data, we provide an additional example on the transcriptional network of SOS response to DNA damage in Escherichia coli. We confirm that the proposed algorithm can successfully identify the true structure except only one relation.

Algorithms↗
PubMed2003

Neurobehavioral assessment: a survey of use and value in safety assessment studies.

This report describes the results of a survey designed to evaluate the contribution of F1 neurobehavioral testing to hazard identification and characterization in safety assessment studies. (To review the details of the distributed survey, please see the supplementary data for this article on the journal's Web site.) The survey provided information about studies completed in industrial laboratories in the United States, Europe, and Japan since 1990 on 174 compounds. The types of compounds included were pharmaceutical (81%), agricultural (7%), industrial (1%), or were undefined (10%). Information collected included the intended use of the test agent, general study design and methodology, the types and characteristics of F1 behavioral evaluations, and the frequency with which agents affected neurobehavioral parameters in comparison to other F0 and F1 generation parameters. F1 general toxicology parameters such as mortality, pre- and postweaning body weight, and food intake were assessed in most studies and were affected more frequently than other parameters by the test agents. F1 behavioral parameters were assessed less consistently across studies, and were less frequently affected by the agents tested. Although affected by agents less often than general toxicology parameters, F1 behavioral parameters along with other parameters defined the no-observed-effect level (NOEL) in 17/113 (15%) of studies and solely defined the NOEL in 3/113 (2.6%) of studies. Thus, F1 behavioral parameters sometimes improved on the standard toxicological measures of hazard identification. While not detecting agent effects as readily as some measures, the F1 behavioral parameters provide information about agent effects on specialized functions of developing offspring not provided by other standard measures of toxicity. The survey results emphasize the need for further research into the methods of behavioral assessment as well as the mechanisms underlying the neurobehavioral alterations.

Animals↗
PubMed2006

Parameter estimation in models combining signal transduction and metabolic pathways: the dependent input approach.

Biological complexity and limited quantitative measurements pose severe challenges to standard engineering methodologies for modelling and simulation of genes and gene products integrated in a functional network. In particular, parameter quantification is a bottleneck, and therefore parameter estimation, identifiability, and optimal experiment design are important research topics in systems biology. An approach is presented in which unmodelled dynamics are replaced by fictitious 'dependent inputs'. The dependent input approach is particularly useful in validation experiments, because it allows one to fit model parameters to experimental data generated by a reference cell type ('wild-type') and then test this model on data generated by a variation ('mutant'), so long as the mutations only affect the unmodelled dynamics that produce the dependent inputs. Another novel feature of the approach is in the inclusion of a priori information in a multi-objective identification criterion, making it possible to obtain estimates of parameter values and their variances from a relatively limited experimental data set. The pathways that control the nitrogen uptake fluxes in baker's yeast (Saccharomyces cerevisiae) have been studied. Well-defined perturbation experiments were performed on cells growing in steady-state. Time-series data of extracellular and intracellular metabolites were obtained, as well as mRNA levels. A nonlinear model was proposed and was shown to be structurally identifiable given data of its inputs and outputs. The identified model is a reliable representation of the metabolic system, as it could correctly describe the responses of mutant cells and different perturbations.

Algorithms↗
PubMed2004

Identification of complex systems based on neural and Takagi-Sugeno fuzzy model.

The paper describes a neuro-fuzzy identification approach, which uses numerical data as a starting point. The proposed method generates a Takagi-Sugeno fuzzy model, characterized with transparency, high accuracy and a small number of rules. The process of self-organizing of the identification model consists of three phases: clustering of the input-output space using a self-organized neural network; determination of the parameters of the consequent part of a rule from over-determined batch least-squares formulation of the problem, using singular value decomposition algorithm; and on-line adaptation of these parameters using recursive least-squares method. The verification of the proposed identification approach is provided using four different problems: two benchmark identification problems, speed estimation for a dc motor drive, and estimation of the temperature in a tunnel furnace for clay baking.

Journal Article↗
PubMed1989

Communicative profiles of preschool children with handicaps: implications for early identification.

The purpose of this study was to compare the communicative profiles of preschool children with handicaps to those of normal children functioning in the prelinguistic and one-word stage using standard sampling procedures. The children with handicaps included 4 with Down syndrome, 4 with specific language impairments, and 3 with autism. Measures obtained from the communication samples included rates of intentional communication and proportions of communicative functions, discourse structure, communicative means, and syllabic shape. The results of the children with Down syndrome fell within the normal range on all parameters. The common pattern displayed by the children with specific language impairments was a deviation in syllabic shape. The children with autism displayed adequate rates of communicating but fell outside of the normal range for their language stage on the other communicative parameters. Clinical implications of these findings for the early identification of children with communicative impairments are discussed.

Autistic Disorder↗
PubMed1998

Construction of a directed hammerhead ribozyme library: towards the identification of optimal target sites for antisense-mediated gene inhibition.

Antisense-mediated gene inhibition uses short complementary DNA or RNA oligonucleotides to block expression of any mRNA of interest. A key parameter in the success or failure of an antisense therapy is the identification of a suitable target site on the chosen mRNA. Ultimately, the accessibility of the target to the antisense agent determines target suitability. Since accessibility is a function of many complex factors, it is currently beyond our ability to predict. Consequently, identification of the most effective target(s) requires examination of every site. Towards this goal, we describe a method to construct directed ribozyme libraries against any chosen mRNA. The library contains nearly equal amounts of ribozymes targeting every site on the chosen transcript and the library only contains ribozymes capable of binding to that transcript. Expression of the ribozyme library in cultured cells should allow identification of optimal target sites under natural conditions, subject to the complexities of a fully functional cell. Optimal target sites identified in this manner should be the most effective sites for therapeutic intervention.

Base Sequence↗
PubMed1993

Critical analysis of the signal-averaged electrocardiogram. Improved identification of late potentials.

BACKGROUND: This study performed a critical analysis of signal-averaging methods. The objective was to optimize detection of late potentials. METHODS AND RESULTS: We studied two patient populations: a low-arrhythmia-risk group with no evidence of heart disease and a group with clinically documented ventricular tachycardia (VT). Filtered QRS duration (QRSD) and terminal QRS amplitude (RMS40) were measured from the vector magnitude. A QRS duration based on the latest detectable ventricular activity in any of the three individual XYZ leads was also measured. Because of improved signal-to-noise ratio, both individual lead analysis and extended (600-versus 200-beat) averaging yielded significant changes in signal-averaged ECG parameters. Both approaches gave an increased sensitivity for VT identification. Sensitivity, specificity, and accuracy were evaluated as functions of critical values of QRSD and RMS40. RMS measurements in the terminal QRS, ranging from 20 to 100 msec and including RMS40, did not contribute to maximizing sensitivity and were highly correlated with QRSD. Our results from the low-arrhythmia-risk group suggest that age and sex should be considered in the definition of late potentials. CONCLUSIONS: We propose a VT risk stratification scheme using signal-averaged ECG parameters obtained from both individual lead and vector magnitude analysis. This allows definition of four categories of VT risk derived statistically from the study data. This definition is based on combined measures of sensitivity, specificity, and negative and positive predictive value.

Aged↗
PubMedDate not supplied

[Consideration of a priori information and type of an experimental error using the method of system identification based on the minimal quadratic discrepancy criterion].

The variants of the identification method were considered that take the a priori information about the evolution of a system under study and the type of experimental errors of the dynamic parameters of the system into account. An example of using this method for the identification of a biochemical reaction is given where the error in measuring the dynamic parameters (concentration of substances) has both an absolute and a relative components.

Algorithms↗
PubMedDate not supplied

[Play olfactometry for children].

The method presented includes recording of motor responses to odor stimulation reinforced by electric games. Game olfactometry was performed in 34 young children before and after adenotomy using a specially designed olfactometer which measured an increase in the threshold concentration of odor stimulation. As an olfactory stimulus we used 50% aqueous solution of dimethoxybenzene on identification threshold values. In parallel, we recorded the following physiological parameters: galvanic-skin response, pneumography and ECG. In order to develop a stable reflex, 23 children needed from 7 to 9 reinforcements and 8 children needed from 11 to 12 reinforcements. It was found that the level of identification threshold olfactory stimulation was directly proportional to the number of reinforcements. Our findings allow us to recommend the above method for clinical application.

Adenoidectomy↗
PubMedDate not supplied

Impaired processing of famous faces in Alzheimer's disease is related to neurofibrillary tangle densities in the prefrontal and anterior cingulate cortex.

To examine the neuroanatomical correlates of impaired processing of famous faces in Alzheimer's disease (AD), we performed an anterograde clinicopathological study of 25 patients with clinically and neuropathologically confirmed AD. Famous face recognition, identification and naming was assessed using the Famous Face Test. The assessment of neurofibrillary tangle (NFT) and senile plaque (SP) densities was performed in ten cortical areas in both hemispheres, and statistical analysis was made using forward stepwise logistic regression models. A statistically significant relationship was found between NFT densities in Brodmann's areas 9 and 24 in both hemispheres and impaired famous face naming and identification. SP counts did not correlate with any of the neuropsychological parameters. These data suggest that NFT formation in prefrontal and anterior cingulate cortex, two areas involved in semantic memory processes, is a key event in famous face naming and identification deficits. In agreement with previous studies, they also indicate that SP densities are not a good pathological correlate of neuropsychological deficits in AD.

Aged↗
PubMed1994

Assessing glycosidic linkage flexibility: conformational analysis of the repeating trisaccharide unit of Aeromonas salmonicida.

A detailed conformational analysis was performed for the synthetic branched trisaccharide beta-D-ManNAc-(1-->4)-[alpha-D-Glc-(1-->3)]-L-Rha 1 which represents the repeating unit of the O-antigenic polysaccharide of Aeromonas salmonicida. The study was based on 26 experimental NOE curves from 1D transient NOE experiments, employing Gaussian-shaped inversion pulses at 600 MHz. Eight of the NOE curves were interglycosidic and thus useful for an analysis of glycosidic linkage orientations. Metropolis Monte Carlo (MMC) simulations and minimum-energy calculations with the program GEGOP were used to obtain theoretical NOE curves which were compared to the experimental ones. MMC simulations with different temperature parameters of 310, 600, 900 and 2000 K allowed identification of NOEs which are sensitive towards different conformation distributions--not only different conformations--at both glycosidic linkages in 1. A comparison of trisaccharide 1 with the constituent disaccharides beta-D-ManNAc-(1-->4)-L-Rha 2 and alpha-D-Glc-(1-->3)-L-Rha 3 revealed effects of branching on glycosidic linkage flexibility. A quantitative evaluation was facilitated by the introduction of entropy-related flexibility parameters. Our study indicates a notable restriction of flexibility, especially at the (1-->3) linkage in 1. Although overall flexibility in 1 is reduced as compared to the constituent disaccharides 2 and 3, it cannot be neglected altogether. In summary, combined transient NOE experiments and MMC simulations provide a simple approach to analyse glycosidic linkage flexibility.

Aeromonas↗
PubMed2005

Characterization of cells with different mitochondrial membrane potential during apoptosis.

BACKGROUND: Until now, the simultaneous analysis of several parameters during apoptosis, including DNA content and mitochondrial membrane potential (DeltaPsi), has not been possible because of the spectral characteristics of the commonly used dyes. Using polychromatic flow cytometry based upon multiple laser and UV lamp excitation, we have characterized cells with different DeltaPsi during apoptosis. METHODS: U937 cells were treated with the flavonoid quercetin (Qu) and stained with JC-1 to detect DeltaPsi, propidium iodide (PI) for cell viability, Hoechst 33342 for DNA content, Annexin V conjugated with Alexa Fluor-647 for detection of phosphatidilserine (PS) exposure, marker of early apoptosis, or Mitotracker Deep Red for the determination of mitochondrial mass. RESULTS: Treatment with Qu provoked the onset of three cell populations with different DeltaPsi: (1) healthy cells, with normal DeltaPsi, DNA content and physical parameters, high mitochondrial mass, PI- and Annexin V-negative; (2) cells with intermediate DeltaPsi and normal DNA content, but with physical parameters typical of apoptotic cells and low mitochondrial mass; most of them were PI+ and Annexin V+; (3) cells with collapsed DeltaPsi that had low mitochondrial mass and were Annexin-V+, PI+; half of them showed diminished DNA content. Similar results, i.e. the presence of cells with intermediate DeltaPsi, were observed in other models of apoptosis. CONCLUSIONS: During Qu-induced apoptosis, loss of DeltaPsi, PS exposure, and decrease of mitochondrial mass are early events that precede permeability to PI and loss of DNA. Populations of cells with different DeltaPsi, as revealed by flow cytometry after JC-1 staining, differed also for other parameters associated to apoptosis. Thus, the simultaneous analysis of several parameters by polychromatic flow cytometry permits a better identification of many stages of cell death, and, more in general, allows to evaluate the eventual heterogenic sensibility of the population under study to a given compound.

Apoptosis↗
PubMed1992

Continuous, on-line DNA sequencing using a versatile infrared laser scanner/electrophoresis apparatus.

A new apparatus for continuously detecting fluorescently labeled DNA fragments is based on infrared fluorescence technology. This technology combines state-of-the-art developments in chemistry, laser technology, and detection, while achieving improved reliability, sensitivity, and flexibility for applications including DNA sequencing. DNA molecules labeled with a novel infrared fluorophore are detected during electrophoresis using a scanning infrared fluorescence microscope. The microscope consists of a laser diode for exciting the fluorophore and a silicon avalanche photodiode for detecting the infrared emission. Optimum conditions for detection and throughput are obtained by adjusting electrophoresis, scanning and imaging parameters. Typical DNA sequencing runs (test templates) allow identification of over 500 bases per sample with greater than 99% accuracy.

Base Sequence↗
PubMed1995

Correlation of anoxic neuronal responses and calbindin-D28k localization in stratum pyramidale of rat hippocampus.

Immunohistochemical staining for the calcium-binding protein calbindin-D28k (CaBP) was combined with Lucifer Yellow (LY) identification and intracellular recording of changes in membrane parameters of pyramidal neurons in CA2, CA1, and the subiculum of rat hippocampal slices during brief exposure (4.0 +/- 0.19 min) to N2. Anoxia evoked either a depolarization or hyperpolarization of membrane potential (VM) (+21.5 +/- 2.79 mV above VM = -70.5 +/- 1.50 mV, n = 30 and -7.2 +/- 0.72 mV below VM = -68.2 +/- 1.34 mV, n = 24, respectively) and a fall in membrane resistance of approximately 20%. Differences in the response could be correlated with the presence or absence of CaBP and the localization of neurons in different layers of stratum pyramidale and sectors of the hippocampus. For neurons immunopositive for calbindin (CaBP(+)), depolarization was observed more frequently (83%) than hyperpolarization (17%); in contrast, 44% of responses of calbindin-negative (CaBP(-)) neurons were depolarizing and 56% were hyperpolarizing. Depolarizations of CaBP(+) neurons were more gradual in slope, and more rapidly reached a plateau in comparison with those recorded in CaBP(-) neurons. Responses of neurons in the superficial layer of stratum pyramidale (in which 79% of CaBP(+) pyramidal neurons were situated) were mainly depolarizing (91%), while for those in the deep layer (which contained 89% of the CaBP(-) cells) such responses were observed less often (45%). Depolarization was also more common than hyperpolarization for cells located in CA2/CA1c/CA1b (63%) than in the CA1a/subicular region (37%). The depolarizing response of the majority of pyramidal neurons which are CaBP(+), superficial, and closer to CA3 may reflect an efficient buffering of intracellular Ca2+, which maintains a low [Ca2+]i, steep gradient for Ca2+ influx and may facilitate the movement of Ca2+ away from points of entry. The neurons which are CaBP(-), deep, and closer to subiculum and in which N2 evokes hyperpolarization, on the other hand, may have a sustained elevation/accumulation of cytosolic Ca2+ which could activate K+ conductance, inhibit Ca2+ influx, and stabilize the membrane potential. These experiments provide a functional correlate for CaBP and suggest that it may have a significant role in Ca2+ homeostasis and the determination of selective neuronal vulnerability.

Animals↗