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Results for “Experimental validation”

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At least 937 records · Page 52Linked to original sources

PubMed2000

Ultrasonic non-destructive testing of pieces of complex geometry with a flexible phased array transducer

Ultrasonic non-destructive testing of components of complex geometry in the nuclear industry faces several difficulties: sensitivity variations due to unmatched contact, inaccurate localization of defects due to variations of transducer orientation, and uncovered area of the component. To improve the performances of such testing and defect characterization, we propose a new concept of ultrasonic contact phased array transducer. The phased array transducer has a flexible radiating surface able to fit the actual surface of the piece to optimize the contact and thus the sensitivity of the test. To control the transmitted field, and therefore to improve the defect characterization, a delay law optimizing algorithm is developed. To assess the capability of such a transducer, the Champ-Sons model, developed at the French Atomic Energy Commission for predicting field radiated by arbitrary transducers into pieces, has to be extended to sources directly in contact with pieces of complex geometry. The good behavior of this new type of probe predicted by computations is experimentally validated with a jointed transducer positioned on pieces of various profiles.

Journal Article↗

PubMed2000

Experimental investigation of bounded beam reflection from plane interfaces in the vicinity of leaky waves angles

The aim of this work is an experimental validation of the reflected and transmitted fields through a viscoelastic material when a bounded ultrasonic beam is incident at different angles. Special measurements are carried out when incidence is performed at some critical angles of the material used. So the propagation of leaky waves along the solid layer is investigated. The inverse procedure for optimizing model parameters from the noisy input-output data is performed using the maximum likelihood estimator.

Journal Article↗

PubMed2003

Covariation of amino acid positions in HIV-1 protease.

We have examined patterns of sequence variability for evidence of linked sequence changes in HIV-1 subtype B protease using translated sequences from protease inhibitor (PI) treated and untreated subjects downloaded from the Stanford HIV RT and Protease Sequence Database (http://hivdb.stanford.edu). The final data set size was 648 sequences from untreated subjects (notx) and 531 for PI-treated subjects (tx). Each subject was uniquely represented by a single sequence. Mutual information was calculated for all pairwise comparisons of positions with nonconsensus amino acids in at least 5% of sequences; significance of pairwise association was assessed using permutation tests. In addition pairs of positions were assessed for linkage by comparing the observed occurrences of amino acid combinations to expected values. The mutual information statistic indicated linkage between nine pairs of sites in the untreated data set (10:93, 12:19, 35:38, 37:41, 62:71, 63:64, 71:77, 71:93, 77:93). Strong statistical support for linkage in the treated data set was seen for 32 pairs, eight involving position 10:7 involving position 71, with the rest being 12:19, 15:77, 20:36, 30:88, 35:36, 35:37, 36:62, 36:77, 46:82, 46:84, 48:54, 48:82, 54:82, 63:64, 63:90, 73:90, 77:93, and 84:90. Most associations were positive, although negative associations were seen for five pairs of interactions. Structural proximity suggests that numerous pairs may interact within a local environment. These interactions include two distinct clusters around 36/77 and 71/93. While some of these interactions may reflect fortuitous linkage in heavily treated subjects with many resistance mutations, others will likely represent important cooperative interactions that are amenable to experimental validation.

Amino Acid Sequence↗

PubMed2001

Stability analysis of the biodegradation of mixed wastes in a continuous bioreactor with cell recycle.

The stability characteristics of a continuous bioreactor with cell recycle for biodegradation of mixed wastes are investigated. The system involves a pure culture of Pseudomonas putida and media containing phenol and glucose as carbon and energy sources. The model growth kinetics for the two substitutable substrates were experimentally validated in a previous study. The stability analysis carried out using elementary principles of bifurcation theory shows rich dynamics characteristics of the reactor model, including steady-state multiplicity and hysteresis. The effect of the bioreactor operating parameters on the stability behavior of the model is discussed. Practical criteria are also derived for the safe operation of the unit and to prevent the occurrence of wash-out conditions.

Biodegradation, Environmental↗

PubMed1998

Estimates of regional work in the canine left ventricle.

Assessment of the magnitude of regional myocardial work requires knowledge of regional fiber stress and fiber shortening. The theoretical development and experimental validation of a method is presented which used values of estimated active and passive fiber stress according to a fluid-fiber model, and measured fiber strain values. This enables the construction of regional stress-strain diagrams, a regional analog of the pressure-volume area model by Suga and co-investigators, which can be linked to regional oxygen consumption. In the left ventricle, either normally or asynchronously activated, the method yields reliable data on strain and active and passive fiber stress. The relation between estimated regional work and myocardial oxygen demand is in quantitative agreement with previously reported relations between global oxygen demand and measured pressure-volume area. During coronary artery occlusion, however, these values were less reliable, which might be due to inaqdequate knowledge of the (passive) material properties of the myocardium.

Animals↗

PubMed2004

Predicting gene expression from sequence.

We describe a systematic genome-wide approach for learning the complex combinatorial code underlying gene expression. Our probabilistic approach identifies local DNA-sequence elements and the positional and combinatorial constraints that determine their context-dependent role in transcriptional regulation. The inferred regulatory rules correctly predict expression patterns for 73% of genes in Saccharomyces cerevisiae, utilizing microarray expression data and sequences in the 800 bp upstream of genes. Application to Caenorhabditis elegans identifies predictive regulatory elements and combinatorial rules that control the phased temporal expression of transcription factors, histones, and germline specific genes. Successful prediction requires diverse and complex rules utilizing AND, OR, and NOT logic, with significant constraints on motif strength, orientation, and relative position. This system generates a large number of mechanistic hypotheses for focused experimental validation, and establishes a predictive dynamical framework for understanding cellular behavior from genomic sequence.

Animals↗

PubMed1997

The difficulty of identifying genes in anonymous vertebrate sequences.

The identification of genes in newly determined vertebrate genomic sequences can range from a trivial to an impossible task. In a statistical preamble, we show how "insignificant" are the individual features on which gene identification can be rigorously based: promoter signals, splice sites, open reading frames, etc. The practical identification of genes is thus ultimately a tributary of their resemblance to those already present in sequence databases, or incorporated into training sets. The inherent conservatism of the currently popular methods (database similarity search, GRAIL) will greatly limit our capacity for making unexpected biological discoveries from increasingly abundant genomic data. Beyond a very limited subset of trivial cases, the automated interpretation (i.e. without experimental validation) of genomic data, is still a myth. On the other hand, characterizing the 60,000 to 100,000 genes thought to be hidden in the human genome by the mean of individual experiments is not feasible. Thus, it appears that our only hope of turning genome data into genome information must rely on drastic progresses in the way we identify and analyse genes in silico.

Amino Acid Sequence↗

PubMed2001

Neurodegeneration: a failure of neuroregeneration?

Evidence suggests that the brain, like many other tissues, is in a state of dynamic equilibrium. It has an endogenous population of stem cells that proliferate in response to environmental and pharmacological manipulations and that can replace cells lost in some experimental lesions. However, the fact remains that neurodegenerative disorders such as Alzheimer's, Parkinson's, and Huntington's diseases are characterised by continuous loss of neurons that are not replaced. In this hypothesis, we postulate that a primary deficit in neural stem-cell proliferation; migration, or differentiation, or both, might contribute to net cell loss and neuronal circuit disruption in these disorders. Experimental validation of this hypothesis would not only substantially advance understanding of the pathogenesis of these diseases, but could also have profound implications for future treatment of these incurable disorders.

Animals↗

PubMed2001

Dendritic cell discoveries provide new insight into the cellular immunobiology of DNA vaccines.

The evolution of increasingly virulent human pathogens, together with the rapid onset of antimicrobial resistance has created a need for new vaccination strategies. Nucleic acid vaccines, based on recombinant DNA technology are a promising new vaccine formulation capable of eliciting both humoral and cellular immune responses. This technology has been experimentally validated in animal models of pathogen challenge and tumor protection following administration of a DNA vaccine and has led to extensive research into the mechanisms of protective immunity. We focus here on the cellular and molecular mechanisms leading to cell-mediated immune responses to DNA vaccines and discuss these mechanisms in light of recent advances in the field of dendritic cell immunobiology. In particular, the potential involvement of: (i) the CpG pattern-recognition receptor, toll-like receptor-9; (ii) the dendritic cell-specific surface adhesion molecule, DC-SIGN; and (iii) the molecular interactions between CD40 and CD154 in the evolution of protective cell-mediated immunity to DNA vaccines are discussed. An improved understanding of the precise mechanisms leading to protective cellular immunity following DNA vaccination may help in the design of novel DNA constructs containing immunostimulatory features that target one or more of these mechanisms, with the aim of increasing the immunogenic potential and protective efficacy of DNA vaccines.

Animals↗

PubMed2001

Structural features of a snake venom thrombin-like enzyme: thrombin and trypsin on a single catalytic platform?

The Lachesis muta thrombin-like enzyme (LM-TL) is a single chain serine protease that shares 38% sequence identity with the serine protease domain of thrombin and also displays similar fibrinogen-clotting activity. In addition, the 228 amino acid residue LM-TL is 52% identical to trypsin, and cleaves chromogenic substrates with similar specificity. Herein we report a three-dimensional (3D) model validated experimentally for LM-TL based on these two homologous proteins of known 3D structure. Spatial modeling of LM-TL reveals a serine protease with a chymotrypsin fold presenting a hydrophobic pocket on its surface, involved in substrate recognition, and an important 90's loop, involved in restricting the LM-TL catalytic site cleft. Docking analysis showed that LM-TL would not form a stable complex with basic pancreatic trypsin inhibitor and wild-type ecotin since its 90's loop would restrict the access to the catalytic site. LM-TL formed acceptable interactions with fibrinopeptide A and a variant of ecotin; ecotin-TSRR/R in which both the primary and secondary binding sites are mutated Val81Thr, Thr83Ser, Met84Arg, Met85Arg and Asp70Arg. Furthermore, analysis of the primary structures of LM-TL and of the seven snake venom thrombin-like enzymes (SVTLEs) family reveals a subgroup formed by LM-TL, crotalase, and bilineobin, both closely related to thrombin. Therefore, LM-TL provides an initial point to compare SVTLEs with their counterparts, e.g. the mammalian serine proteases, and a basis for the localization of important residues within the little known SVTLEs family.

Amino Acid Sequence↗

PubMed1999

Modelling the interactions between Lactobacillus curvatus and Enterobacter cloacae. II. Mixed cultures and shelf life predictions.

The modelling approach presented in this study can be used to predict when interactions between microorganisms in homogenous systems occur. It was tested for the interaction between Lactobacillus curvatus and Enterobacter cloacae. In this binary system, L. curvatus produces lactic acid which decreases the pH in the system. The pH decrease was found to be the main limiting factor of growth of both E. cloacae and L. curvatus. This resulted in E. cloacae reaching its final concentration earlier when compared to its growth in pure culture. The models consisted of a set of first order ordinary differential equations describing the growth, consumption and production rates of both microorganisms. The parameters for these equations were obtained from pure culture studies and from literature. These equations were solved using a combination of analytical and numerical methods. The prediction of growth in mixed culture using parameters from pure culture experiments and literature were close to the experimental data. Both model predictions and experimental validation indicated that interaction occurs when the concentration of L. curvatus reaches 10(8) cfu/ml. At that moment in time, the pH had decreased to inhibiting levels. These concentrations of microorganisms (10(8) cfu/ml) do occur in fermented products where interactions obviously are important. In nonfermented foods however, this level of microorganisms indicate that spoilage has occurred or is about to start. Microbial interactions can therefore be neglected when predicting shelf life or safety of food products in most cases.

Colony Count, Microbial↗

PubMed1999

Thermal inactivation of Alicyclobacillus acidoterrestris spores under different temperature, soluble solids and pH conditions for the design of fruit processes.

Alicyclobacillus acidoterrestris, a thermoacidophilic, non-pathogenic and spore-forming bacterium has been detected in several spoiled commercial pasteurised fruit juices. A. acidoterrestris spores, besides being resistant to the pasteurisation treatment conditions normally applied to acidic fruit products, can germinate and grow causing spoilage. Therefore, this microorganism was suggested as the target to be used in the design of adequate pasteurisation processes. The objectives of this work were to investigate the influence of temperature (T: 85-97 degrees C), total soluble solids (SS: 5-60 degrees Brix or % by weight) and pH (2.5-6.0) on D-values (decimal reduction time) of Alicyclobacillus acidoterrestris (type strain, NCIMB 13137) spores, and to fit a model using response surface methodology. A central composite face-centred experimental design was used, and the response, D-value determined in malt extract broth, ranged between 0.498+/-0.045 and 94.9+/-6.7 min. Within the factor ranges studied, temperature was the parameter that most affected the D-value. Following this was the SS and, lastly, the pH value. A linear decrease in D-value was observed with decreasing SS and pH, and a non-linear decrease in D-value was noticed with increasing temperature. A second order polynomial was successfully fitted to the data (R2 = 0.98). In general, D-values measured in real fruit systems, such as orange, apple and grape juices, blackcurrant concentrates, cupuaçu (exotic fruit) extract and orange juice drink, were higher than those predicted by the malt extract broth model. This result emphasises the importance of experimental validation of any model-derived process.

Bacillaceae↗

PubMed2003

A program based on a 'selective' least-squares method for respiratory mechanics monitoring in ventilated patients.

This paper proposes a program for continuous estimation of respiratory mechanics parameters in ventilated patients. This program can be used with any ventilator providing airway pressure and flow signals without additional equipment. Overall breathing resistance, dynamic elastance (E) and positive end expiratory pressure (P(0)) are periodically estimated by multiple linear regression on selected parts of breathing cycles. Experimental validation together with justification of the selection procedure are based on signals obtained while ventilating a lung mechanical analogue with various intensive care ventilators. Clinical validity has been tested on 12 ventilated patients. The quality of estimation has been assessed by mean square difference between measured and reconstituted pressure (MSE), coefficient of determination (R(2)) and the condition number (a confidence index), and by comparison of E and P(0) with corresponding static values. The high R(2) and the low MSE obtained on most clinical cycles indicate that selected parts of cycles obey closely the model underlying parameter estimation. Agreement between static and dynamic parameters demonstrates the clinical validity of our program.

Aged↗

PubMed2000

Noninvasive measurements for studying the tumoral pharmacokinetics of platinum anticancer drugs in solid tumors.

An effective methodology to determine the amount of cisplatin or carboplatin at the solid tumor site in a noninvasive manner may enable clinicians to design drug regimens based on an individual's in situ pharmacokinetics. Such noninvasive methods may allow optimization of an individual's drug exposure at the target site, as well as provide a screening measure to determine individual efficacy based on exposure to these platinated drugs. 195mPt appears to be the radionuclide of platinum most suitable for radiolabeling cisplatin or carboplatin, and an analysis is presented of the methods available for preparing such radiolabeled drugs. The use of this methodology is illustrated in detail in studies in animals, as well as some preliminary studies in humans. The animals used were Sprague Dawley rats bearing the Walker 256 carcinoma, and drug biodistribution was studied following administration of cisplatin or carboplatin radiolabeled with 195mPt. This radionuclide permitted noninvasive imaging of the drug and its metabolites at the tumor site and at selected organs. The results obtained show an ability to estimate the amount of platinated drug species in the tumor environment using a noninvasive methodology. Various compartmental models were tested, some of which could be validated experimentally. This noninvasive method is able to provide individual estimates of the active component of the drug at the target site, and is therefore a method that can be implemented in human studies.

Animals↗

PubMed2001

Biomechanics of the cervical spine Part 2. Cervical spine soft tissue responses and biomechanical modeling.

OBJECTIVE: The responses and contributions of the soft tissue structures of the human neck are described with a focus on mathematical modeling. Spinal ligaments, intervertebral discs, zygapophysial joints, and uncovertebral joints of the cervical spine are included. Finite element modeling approaches have been emphasized. Representative data relevant to the development and execution of the model are discussed. A brief description is given on the functional mechanical role of the soft tissue components. Geometrical characteristics such as length and cross-sectional areas, and material properties such as force-displacement and stress-strain responses, are described for all components. Modeling approaches are discussed for each soft tissue structure. The final discussion emphasizes the normal and abnormal (e.g., degenerative joint disease, iatrogenic alteration, trauma) behaviors of the cervical spine with a focus on all these soft tissue responses. A brief description is provided on the modeling of the developmental biomechanics of the pediatric spine with a focus on soft tissues. Relevance. Experimentally validated models based on accurate geometry, material property, boundary, and loading conditions are useful to delineate the clinical biomechanics of the spine. Both external and internal responses of the various spinal components, a data set not obtainable directly from experiments, can be determined using computational models. Since soft tissues control the complex structural response, an accurate simulation of their anatomic, functional, and biomechanical characteristics is necessary to understand the behavior of the cervical spine under normal and abnormal conditions such as facetectomy, discectomy, laminectomy, and fusion.

Adult↗

PubMed2002

Response of fluctuating asymmetry to arsenic toxicity: support for the developmental selection hypothesis.

The effect of exposure to sodium arsenite during development was tested on adult fluctuating asymmetry (FA) in sternopleural bristle number, bristle number, body size and survivorship in Drosophila melanogaster. Three genetic strains of flies were used, CT-106, PVM and Oregon-R, and arsenite concentrations ranged from relatively mild, sub-lethal doses, to concentrations with pronounced negative effects on survivorship. At arsenite concentrations of 1.0 and 0.125 mM, mortality was on average 38% greater than in controls, and surviving flies emerged significantly smaller and had fewer bristles than controls. Neither the effect of arsenite or the genotype x environment interaction on asymmetry were significant. However, given the high mortality, any increase in FA could have been masked by the outcome of developmental selection against developmentally unstable phenotypes. We tested for this effect by contrasting FA values between (1) flies reared at the highest concentrations used previously, (2) flies reared at sub-lethal dosage, and (3) controls. Positional fluctuating asymmetry (PFA), which is expected to be a sensitive indicator of underlying developmental stability, was significantly reduced among flies reared at the highest concentration, and at which flies suffered significant mortality. Moreover, the slope of the regression relating mean PFA to emergence per bottle was significantly positive. These data support the hypothesis that developmental selection occurred in this experiment, and that the expected positive relationship between asymmetry and stress may be altered when the stressor eliminates individuals from the population. In contrast, FA of flies reared at sub-lethal dosage did not differ from that in controls, a result that fails to support the hypothesis that arsenite disrupts developmental stability. Our results call for caution in FA-based biomonitoring, especially of potentially lethal forms of stress, because in the presence of developmental selection, and under the common assumption that FA should increase under stress, erroneous conclusions may be drawn about the health and well being of a population. It is suggested that FA-based biomonitoring efforts integrate the use of FA with other bioindicators, and experimentally validate any expected FA-stress relationship before attempting to infer the presence of environmental stress.

Animals↗

PubMedDate not supplied

Experimental designs and risk assessment in combination toxicology: panel discussion.

Advancing our knowledge on the toxicology of combined exposures to chemicals and implementation of this knowledge in guidelines for health risk assessment of such combined exposures are necessities dictated by the simple fact that humans are continuously exposed to a multitude of chemicals. A prerequisite for successful research and fruitful discussions on the toxicology of combined exposures (mixtures of chemicals) is the use of defined terminology implemented by an authoritative international body such as, for example, the International Union of Pure and Applied Chemistry (IUPAC) Toxicology Committee. The extreme complexity of mixture toxicology calls for new research methodologies to study interactive effects, taking into account limited resources. Of these methodologies, statistical designs and mathematical modelling of toxicokinetics and toxicodynamics seem to be most promising. Emphasis should be placed on low-dose modelling and experimental validation. The scientifically sound so-called bottom-up approach should be supplemented with more pragmatic approaches, focusing on selection of the most hazardous chemicals in a mixture and careful consideration of the mode of action and possible interactive effects of these chemicals. Pragmatic approaches may be of particular importance to study and evaluate complex mixtures; after identification of the 'top ten' (most risky) chemicals in the mixture they can be examined and evaluated as a defined (simple) chemical mixture. In setting exposure limits for individual chemicals, the use of an additional safety factor to compensate for potential increased risk due to simultaneous exposure to other chemicals, has no clear scientific justification. The use of such an additional factor is a political rather than a scientific choice.

Hazardous Substances↗

PubMed2003

A kinetic model of the cyclin E/Cdk2 developmental timer in Xenopus laevis embryos.

Early cell cycles of Xenopus laevis embryos are characterized by rapid oscillations in the activity of two cyclin-dependent kinases. Cdk1 activity peaks at mitosis, driven by periodic degradation of cyclins A and B. In contrast, Cdk2 activity oscillates twice per cell cycle, despite a constant level of its partner, cyclin E. Cyclin E degrades at a fixed time after fertilization, normally corresponding to the midblastula transition. Based on published data and new experiments, we constructed a mathematical model in which: (1) oscillations in Cdk2 activity depend upon changes in phosphorylation, (2) Cdk2 participates in a negative feedback loop with the inhibitory kinase Wee1; (3) cyclin E is cooperatively removed from the oscillatory system; and (4) removed cyclin E is degraded by a pathway activated by cyclin E/Cdk2 itself. The model's predictions about embryos injected with Xic1, a stoichiometric inhibitor of cyclin E/Cdk2, were experimentally validated.

Algorithms↗