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Results for “Experimental validation”

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At least 613 records · Page 34Linked to original sources

PubMed2006

A novel normalization method for effective removal of systematic variation in microarray data.

Normalization of cDNA and oligonucleotide microarray data has become a standard procedure to offset non-biological differences between two samples for accurate identification of differentially expressed genes. Although there are many normalization techniques available, their ability to accurately remove systematic variation has not been sufficiently evaluated. In this study, we performed experimental validation of various normalization methods in order to assess their ability to accurately offset non-biological differences (systematic variation). The limitations of many existing normalization methods become apparent when there are unbalanced shifts in transcript levels. To overcome this limitation, we have proposed a novel normalization method that uses a matching algorithm for the distribution peaks of the expression log ratio. The robustness and effectiveness of this method was evaluated using both experimental and simulated data.

Algorithms↗

PubMed2002

Implications of hormesis for industrial hygiene.

This paper considers hormesis as a valid and potentially valuable alternative hypothesis for low-dose response in the context of occupational health risk assessment. It outlines the current occupational risk assessment paradigm and its use of high-dose toxicological data in setting occupational exposure limits (OELs). This present effort is a call to science to investigate the potential promise of hormesis in providing prima facie experimental evidence for a low-dose threshold of toxic effect to chemical agents. The scientific effort and advancement advised in this piece could also lead to experimentally validated quantitative estimates of the toxic effect extant at occupational exposures in the region of the OEL.

Animals↗

PubMed2006

Factors influencing F-wave latency detection of lumbosacral root lesions using a detection theory based model.

OBJECTIVE: To evaluate the F-wave dilution hypothesis; which implies that absolute F-wave latencies obscure the much smaller delay associated with slow intra-lesion conduction, such is caused by nerve root compression in lumbosacral radiculopathy. A corollary objective is to determine how F-wave measurement and pathological factors influence diagnostic accuracy. METHODS: An analytical model is developed based on signal detection theory and a number of simplifying assumptions. Diagnostic accuracy, quantified by the area under the receiver operating characteristic (ROC) curve, is determined for various model realizations derived from the clinical and experimental neurophysiology literature. A preliminary experimental validation of model predictions is also performed. RESULTS: Absolute F-wave latency does not influence the accuracy of focal lesion detection. F-wave latency variance and lesion pathology are the determinant factors. F-wave latencies and distal latencies are estimated to have qualitatively similar detection characteristics, although distal latencies have quantitatively better diagnostic efficacy for comparable focal pathology. Preliminary experimental results support the modeled dependence of diagnostic accuracy on latency variance and lesion severity. CONCLUSIONS: Absolute F-wave latency does not dilute slow conduction within focal lesions, such as in lumbosacral radiculopathy. The dominant measurement factor is F-wave latency variance. SIGNIFICANCE: To maximize the diagnostic utility of F-wave latencies, focus must be placed on reducing latency variance, such as through correction for demographic covariates. This model calls into question the F-wave dilution hypothesis.

Adolescent↗

PubMed2005

A systems analysis of importin-{alpha}-{beta} mediated nuclear protein import.

Importin-beta (Impbeta) is a major transport receptor for Ran-dependent import of nuclear cargo. Impbeta can bind cargo directly or through an adaptor such as Importin-alpha (Impalpha). Factors involved in nuclear transport have been well studied, but systems analysis can offer further insight into regulatory mechanisms. We used computer simulation and real-time assays in intact cells to examine Impalpha-beta-mediated import. The model reflects experimentally determined rates for cargo import and correctly predicts that import is limited principally by Impalpha and Ran, but is also sensitive to NTF2. The model predicts that CAS is not limiting for the initial rate of cargo import and, surprisingly, that increased concentrations of Impbeta and the exchange factor, RCC1, actually inhibit rather than stimulate import. These unexpected predictions were all validated experimentally. The model revealed that inhibition by RCC1 is caused by sequestration of nuclear Ran. Inhibition by Impbeta results from depletion nuclear RanGTP, and, in support of this mechanism, expression of mRFP-Ran reversed the inhibition.

Active Transport, Cell Nucleus↗

PubMed2006

Assessment of a new multileaf collimator concept using GEANT4 Monte Carlo simulations.

The aim of the work was to investigate in advance the dosimetric properties of a new multileaf collimator (MLC) concept with the help of Monte Carlo (MC) simulations prior to the production of a prototype. The geometrical design of the MLC was implemented in the MC code GEANT4. For the simulation of a 6 MV treatment beam, an experimentally validated phase space and a virtual spatial Gaussian-shaped model placed in the origin were used. For the simulation of the geometry in GEANT4, the jaws and the two leaf packages were implemented with the help of computer-aided design data. First, transmission values for different tungsten alloys were extracted using the simulation codes GEANT4 and BEAMnrc and compared to experimental measurements. In a second step, high-resolution simulations were performed to detect the leakage at depth of maximum dose. The 20%-80% penumbra along the travel direction of the leaves was determined using 10 x 10 cm2 fields shifted along the x- and y-axis. The simulated results were compared with measured data. The simulation of the transmission values for different tungsten alloys showed a good agreement with the experimental measurements (within 2.0%). This enabled an accurate estimation of the attenuation coefficient for the various leaf materials. Simulations with varying width of the spatial Gaussian distribution showed that the leakage and the penumbra depend very much on this parameter: for instance, for widths of 2 and 4 mm, the interleaf leakage is below 0.3% and 0.75%, respectively. The results for the leakage and the penumbra (4.7+/-0.5 mm) are in good agreement with the measurements. This study showed that GEANT4 is appropriate for the investigation of the dosimetric properties of a multileaf collimator. In particular, a quantification of the leakage, the penumbra, and the tongue-and-groove effect and an evaluation of the influence of the beam parameters such as the width of the Gaussian distribution was possible.

Body Burden↗

PubMedDate not supplied

Productivity improvement in xanthan gum fermentation using multiple substrate optimization.

A novel and more comprehensive formulation of the optimal control problem that reflects the operational requirements of a typical industrial fermentation has been proposed in this work. This formulation has been applied to a fed-batch bioreactor with three control variables, i.e., feed rates of carbon source, nitrogen source, and an oxygen source, to result in a 148.7% increase in product formation. Xanthan gum production using Xanthomonas campestris has been used as the model system for this optimization study, and the liquid-phase oxygen supply strategy has been used to supply oxygen to the fermentation. The formulated optimization problem has several constraints associated with it due to the nature of the system. A robust stochastic technique, differential evolution, has been used to solve this challenging optimization problem. The infinite dimensional optimization problem has been approximated to a finite dimensional one by control vector parametrization. The state constraints that are path constraints have been addressed by using penalty functions and by integrating them over the total duration to ensure a feasible solution. End point constraints on final working volume of the reactor and on the final residual concentrations of carbon and nitrogen sources have been included in the problem formulation. Further, the toxicity of the oxygen source, H(2)O(2), has been addressed by imposing a constraint on its maximum usable concentration. In addition, the initial volume of the bioreactor contents and feed concentrations have been handled as decision variables, which has enabled a well-grounded choice for their values from the optimization procedure; adhoc values are normally used in the industry. All results obtained by simulation have been validated experimentally with good agreements between experimental and simulated values.

Algorithms↗

PubMed2006

Development of chemical oxygen demand on-line monitoring system based on a photoelectrochemical degradation principle.

A simple, rapid, and sensitive on-line chemical oxygen demand (COD) determination method has been proposed and experimentally validated. The method is based on a photoelectrochemical oxidative degradation principle and operates under a continuous flow mode. The method employs a specially designed thin-layer photoelectrochemical cell that incorporates a highly effective nanoparticulate TiO2 photoanode. This approach overcomes many problems associated with the conventional COD determination techniques such as long analysis time, consumption of expensive and toxic reagents, production of secondary toxic waste, and poor reproducibility. The effect of important experimental parameters on the analytical signal generation was systematically investigated, and the optimum conditions were obtained. The method was successfully applied to determine the COD of real samples from various industrial wastewaters. The COD value of real samples determined by this method agreed well with the standard dichromate method. The assay time of 1-5 min/sample can be readily achieved. A practical detection limit of 1 mg L(-1) COD with a linear range of 1-100 mg L(-1) was achieved under the optimum conditions.

Electrochemistry↗

PubMed2005

Intravenous selenium modulates L-arginine-induced experimental acute pancreatitis.

CONTEXT: Oxidative stress is understood to have a critical role in the development of acinar injury in experimental acute pancreatitis. We have previously demonstrated that compound multiple antioxidant therapy ameliorates end-organ damage in the intra-peritoneal L-arginine rat model. As the principal co-factor for glutathione, selenium is a key constituent of multiple antioxidant preparations. OBJECTIVE: The intention of this study was to investigate the effect of selenium on pancreatic and remote organ injury in a well-validated experimental model of acute pancreatitis. METHODS: Male Sprague-Dawley rats were randomly allocated to one of 3 groups (n=5/group) and sacrificed at 72 hours. Acute pancreatitis was induced by 250 mg per 100 g body weight of 20% L-arginine hydrochloride in 0.15 mol/L sodium chloride. Group allocations were: Group 1, control; Group 2, acute pancreatitis; Group 3, selenium. MAIN OUTCOME MEASURES: Serum amylase, anti-oxidant levels, bronchoalveolar lavage protein, lung myeloperoxidase activity, and histological assessment of pancreatic injury. RESULTS: L-arginine induced acute pancreatitis characterised by oedema, neutrophil infiltration, acinar cell degranulation and elevated serum amylase. Selenium treatment was associated with reduced pancreatic oedema and inflammatory cell infiltration. Acinar degranulation and dilatation were completely absent. A reduction in bronchoalveolar lavage protein content was also demonstrated. CONCLUSION: Intravenous selenium given 24 hours after induction of experimental acute pancreatitis was associated with a reduction in the histological stigmata of pancreatic injury and a dramatic reduction in broncho-alveolar lavage protein content. Serum selenium fell during the course of experimental acute pancreatitis and this effect was not reversed by exogenous selenium supplementation.

Acute Disease↗

PubMed1990

["Modality shift" paradigms and subjective basic symptoms in schizophrenic patients with various developmental biological risk anamnesis].

Clinical experimental research on schizophrenia does not consider maturation processes of brain function in the majority of cases. In the course of neuronal organization and the differentiation phases of cerebral systems, early traumas in functionally important regions of the brain are accompanied by a facultative impairment of complex systems of information processing. Against the background of the comprehensively coherent "integrative psychobiological model of schizophrenia" (Ciompi) with high construct validity, (experimental) psychology investigations are reported on in the context of the "high-risk" concept in 44 young (20-37 years old) and mainly chronic schizophrenic patients with formation of a specific hypothesis for the developmental biology of the condition. In two homogeneous groups with the same structure, it is checked whether a discriminative appraisal concerning a different organization principle of central information processing systems is possible with "crossmodal" choice-reaction times (cCRT) and certain subscales of the Frankfurt symptom questionnaire (FBF) with regard to alternatively distributed and specially operationalized anamnestic biological risk factors. It can be objectively established in terms of experimental psychology that postpsychotically de-actualized "risk-free" schizophrenics differ from the reference group with a high-risk anamnesis in terms of significantly prolonged cCRT, but not from healthy subjects and an "MBD" control group. In addition, the FBF subscores "weakness of selective attention" and "loss of automatized skills" correlate with poor cCRT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2001

Flow mixing and fluid residence times in a model of a ventricular assist device.

To provide a reliable tool for predicting the flow in a clinical sac-type ventricular assist device (VAD), a simplified model VAD was developed prior to this study for the purpose of experimental validation of computer simulations of the time-varying flow on a moving grid. At selected locations in the flow field, flow patterns, vortex core trajectories and velocities were compared between the numerical and physical models during one full pumping cycle. The computer simulations showed qualitatively very good agreement with the experiment. Quantitatively, the agreement was less favourable. In order to investigate flow mixing and to evaluate fluid residence times in the model VAD a new tool has been developed: the numerical simulations were extended by injecting a scalar into the flow domain. These simulations allow investigation of the flow mixing qualitatively by visualisation and quantification of fluid residence times. Experimental assessment of the numerical results using dye injection proved to be favourable. The numerical results have been extended to include some prediction of pressure which have been compared with experimental measurements.

Biomedical Engineering↗

PubMed2006

Computational and experimental approaches for assessing the interactions between the model calycin beta-lactoglobulin and two antibacterial fluoroquinolones.

Norfloxacin and levofloxacin, two fluoroquinolones of different bulk, rigidity and hydrophobicity taken as model ligands, were docked to one apo and two holo crystallographic structures of bovine beta-lactoglobulin (BLG) using different computational approaches. BLG is a member of the lipocalin superfamily. Lipocalins show a typical b-barrel structure encompassing an internal cavity where small hydrophobic molecules are usually bound. Our studies allowed the identification of two putative binding sites in addition to the calyx. The rigid docking approximation resulted in strong repulsive forces when the ligands were docked into the calyx of the apo form. On the contrary, hindrance was not experienced in flexible docking protocols whether on the apo or on the holo BLG forms, due to allowance for side chain rearrangement. K(i) between 10(-7) and 10(-6) M were estimated for norfloxacin at pH 7.4, smaller than 10(-5) M for levofloxacin. Spectroscopic and electrophoretic techniques experimentally validated the occurrence of an interaction between norfloxacin and BLG. Changes in chemical shift and dynamic parameters were observed between the (19)F NMR spectra of the complex and of the ligand. A K(i) (ca 10(-7) M) comparable with the docking results was estimated through a NMR relaxation titration. Stabilization against unfolding was demonstrated by denaturant gradient gel electrophoresis on the complex versus apo BLG. NMR experimental evidence points to a very loose interaction for ofloxacin, the racemic mixture containing levofloxacin. Furthermore, we were able to calculate in silico K(i)'s comparable to the published experimental values for the complexes of palmitic and retinoic acid with BLG.

Animals↗

PubMed2026

Integrative Cross-platform Analysis of Kinase Inhibitor Effects on Statin-relevant Cardioprotective Pathways in Human Cardiomyocytes.

BACKGROUND/AIM: Kinase inhibitors (KIs) can cause cardiotoxicity through mechanisms overlapping with statin cardioprotective pathways, yet their effects on these pathways in cardiomyocytes remain uncertain. We evaluated six literature-defined statin-relevant gene sets using transcriptomic and proteomic data. MATERIALS AND METHODS: Pre-ranked gene set enrichment analysis was performed for 23 KIs in primary cardiac cells (GSE146096; n=319) and iPSC-derived cardiomyocytes (GSE217421; n=541), with cross-platform analysis of 21 KIs by shotgun proteomics (PXD014791; n=300). Pathway-specific concordance was assessed by Spearman correlation with Benjamini-Hochberg correction; protein scores were estimated after adjustment for cell line. RESULTS: KI effects were heterogeneous. The anti-fibrotic pathway showed nominal concordance across the two transcriptomic datasets (ρ=0.495, p=0.016, q=0.098; 91% direction concordance) and significant cell-line-adjusted transcriptomic-proteomic concordance (ρ=0.644, p=0.0016, q=0.0081). Nilotinib reproducibly upregulated NF-κB pathway genes [normalized enrichment score (NES)=+2.29 and +2.18 in discovery and validation], with targeted inter-gene-correlation-adjusted testing supporting higher NF-κB expression than under rosuvastatin (CAMERA p=3.54×10-8). No global cross-omics summary remained significant after harmonizing pathway universes and accounting for repeated pathways. CONCLUSION: KI effects on statin-relevant pathways were pathway-specific. Anti-fibrotic concordance and nilotinib-associated NF-κB upregulation are hypothesis-generating candidates for experimental validation.

Humans↗

PubMedDate not supplied

[Carbohydrate-dependent lipidogenesis. Review of the literature and experimental study].

The literature on glycide-induced lipidogenesis is reviewed. This is an important question also because of its relation to the pathogenesis of pathological conditions such as ketoacidosis, obesity and hypertriglyceridaemia. Doubt is expressed concerning the interpretation of some experimental procedures used in determining the extent of lipidogenesis in man. The questions raised are fully discussed. Their solution is sought via an experiment on the rat involving the comparison of tissue and plasma lipid metabolites values following infusion of a labelled glucose bolus. Little correlation was noted, low plasma levels being found with high tissue radioactivity. It is emphasized that it is very difficult to ideate a valid experimental approach in order to investigate the extent of lipidogenesis in man in vivo: in this respect, the long term risk arising from the use of tracers with a very long half-life (e.g. 14C) in man must be carefully valuated.

Adipose Tissue↗

PubMed2005

Sequencing of Aspergillus nidulans and comparative analysis with A. fumigatus and A. oryzae.

The aspergilli comprise a diverse group of filamentous fungi spanning over 200 million years of evolution. Here we report the genome sequence of the model organism Aspergillus nidulans, and a comparative study with Aspergillus fumigatus, a serious human pathogen, and Aspergillus oryzae, used in the production of sake, miso and soy sauce. Our analysis of genome structure provided a quantitative evaluation of forces driving long-term eukaryotic genome evolution. It also led to an experimentally validated model of mating-type locus evolution, suggesting the potential for sexual reproduction in A. fumigatus and A. oryzae. Our analysis of sequence conservation revealed over 5,000 non-coding regions actively conserved across all three species. Within these regions, we identified potential functional elements including a previously uncharacterized TPP riboswitch and motifs suggesting regulation in filamentous fungi by Puf family genes. We further obtained comparative and experimental evidence indicating widespread translational regulation by upstream open reading frames. These results enhance our understanding of these widely studied fungi as well as provide new insight into eukaryotic genome evolution and gene regulation.

Aspergillus fumigatus↗

PubMed1987

Comparison of measured and calculated internal absorbed doses in a heterogeneous phantom.

The experimental validity of the MIRD (Medical Internal Radiation Dose Committee of the Society of Nuclear Medicine) internal-dose calculations was investigated. Internal radiation doses were measured in a phantom representing the MIRD mathematical phantom using a newly developed volumetric tissue-equivalent dose meter that could be moulded to reproduce the geometry of the phantom's mathematical organs. The MIRD Monte Carlo computer code ALGAM was adapted to simulate the experimental conditions and was run for each calculation with 60,000 photon histories. The experimental data and the theoretical calculations were compared for different combinations of six source organs and seven target organs using 60Co as the source of radiation. The results of this comparison indicated agreement between measured and calculated doses when the uncertainties associated with both techniques are considered. However, statistical analysis of the data also gave an indication that the Monte Carlo method might overestimate the internal absorbed doses since the agreement with the experimental data was found to be in one direction.

Cobalt Radioisotopes↗

PubMed2006

EGASP: the human ENCODE Genome Annotation Assessment Project.

BACKGROUND: We present the results of EGASP, a community experiment to assess the state-of-the-art in genome annotation within the ENCODE regions, which span 1% of the human genome sequence. The experiment had two major goals: the assessment of the accuracy of computational methods to predict protein coding genes; and the overall assessment of the completeness of the current human genome annotations as represented in the ENCODE regions. For the computational prediction assessment, eighteen groups contributed gene predictions. We evaluated these submissions against each other based on a 'reference set' of annotations generated as part of the GENCODE project. These annotations were not available to the prediction groups prior to the submission deadline, so that their predictions were blind and an external advisory committee could perform a fair assessment. RESULTS: The best methods had at least one gene transcript correctly predicted for close to 70% of the annotated genes. Nevertheless, the multiple transcript accuracy, taking into account alternative splicing, reached only approximately 40% to 50% accuracy. At the coding nucleotide level, the best programs reached an accuracy of 90% in both sensitivity and specificity. Programs relying on mRNA and protein sequences were the most accurate in reproducing the manually curated annotations. Experimental validation shows that only a very small percentage (3.2%) of the selected 221 computationally predicted exons outside of the existing annotation could be verified. CONCLUSION: This is the first such experiment in human DNA, and we have followed the standards established in a similar experiment, GASP1, in Drosophila melanogaster. We believe the results presented here contribute to the value of ongoing large-scale annotation projects and should guide further experimental methods when being scaled up to the entire human genome sequence.

Alternative Splicing↗

PubMed2005

Molar mass distributions by gradient liquid chromatography: predicting and tailoring selectivity.

Interactive liquid chromatography (iLC) for polymer analysis is usually applied to the characterisation of distributions other than molar mass. In particular, its use for the determination of chemical-composition, functionality-type and tacticity distributions has been demonstrated. The application of iLC for the determination of molar mass distributions (MMDs), however, has not yet been fully explored. An expanded version of the reversed-phase liquid chromatography model has been developed to describe and predict how the retention behaviour of polydisperse polystyrene samples changes with molar mass. The relationship between molar mass and the parameters of the model has been investigated in some detail and non-linear correlations were found. From the model and the relationships between the model parameters and molar mass, calibration curves (retention time versus molar mass) were constructed to predict changes in chromatographic selectivity across a given molar mass range. These calibration curves were compared to experimentally obtained curves and, in most cases, excellent agreement was found. The dramatic enhancement in selectivity that can be obtained with iLC in comparison to size-exclusion chromatography (SEC) was illustrated by measuring matrix-assisted laser desorption ionisation (MALDI) MS spectra of fractions collected during a gradient-LC separation. In the low-molar mass range, essentially monodisperse fractions were obtained. Calibration curves, predicted by the model and validated experimentally using narrow-dispersity standards and MALDI-MS spectra of fractions, were used to determine the molar mass distribution of some narrowly distributed polystyrene samples. Molar mass distributions for such standards were found to be somewhat lower than the values reported by the manufacturers. The results also deviated from those obtained by MALDI-MS.

Calibration↗

PubMed2005

Validation of q-ball imaging with a diffusion fibre-crossing phantom on a clinical scanner.

Magnetic resonance (MR) diffusion imaging provides a valuable tool used for inferring structural anisotropy of brain white matter connectivity from diffusion tensor imaging. Recently, several high angular resolution diffusion models were introduced in order to overcome the inadequacy of the tensor model for describing fibre crossing within a single voxel. Among them, q-ball imaging (QBI), inherited from the q-space method, relies on a spherical Radon transform providing a direct relationship between the diffusion-weighted MR signal and the orientation distribution function (ODF). Experimental validation of these methods in a model system is necessary to determine the accuracy of the methods and to optimize them. A diffusion phantom made up of two textile rayon fibre (comparable in diameter to axons) bundles, crossing at 90 degrees , was designed and dedicated to ex vivo q-ball validation on a clinical scanner. Normalized ODFs were calculated inside regions of interest corresponding to monomodal and bimodal configurations of underlying structures. Three-dimensional renderings of ODFs revealed monomodal shapes for voxels containing single-fibre population and bimodal patterns for voxels located within the crossing area. Principal orientations were estimated from ODFs and were compared with a priori structural fibre directions, validating efficiency of QBI for depicting fibre crossing. In the homogeneous regions, QBI detected the fibre angle with an accuracy of 19 degrees and in the fibre-crossing region with an accuracy of 30 degrees .

Anisotropy↗