SEARCH · PubMed Health

Results for “Experimental validation”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 487 records · Page 27Linked to original sources

PubMed2002

Quantification of the degree of mineralization of bone in three dimensions using synchrotron radiation microtomography.

The availability of three-dimensional measuring techniques coupled to specific image processing methods opens new opportunities for the analysis of bone structure. In particular, synchrotron radiation microtomography may provide three-dimensional images with spatial resolution as high as one micrometer. Moreover, the use of a monoenergetic synchrotron beam, which avoids beam-hardening effects, allows quantitative measurements of the degree of mineralization in bone samples. Indeed, the reconstructed gray levels of tomographic images correspond directly to a map of the linear attenuation coefficient within the sample. Since the absorption depends on the amount of mineral content, we proposed a calibration method to evaluate the three-dimensional distribution of the degree of mineralization within the sample. First a theoretical linear relationship modeling the linear attenuation coefficient as a function of the hydroxyapatite concentrations was derived. Then, an experimental validation on phantoms confirmed both the accuracy of the image processing tools and the experimental setup used. Finally, the analysis of the degree of mineralization in four iliac crest bone biopsy samples was reported. Our method was compared to the reference microradiography technique, currently used for this quantification in two dimensions. The concentration values of the degree of mineralization were found with both techniques in the range 0.5-1.6 g of mineral per cubic centimeter of bone, both in cortical and in trabecular region. The mean difference between the two techniques was around 4.7%, and was slightly higher in trabecular region than in cortical bone.

Bone Density↗

PubMed1998

Ab initio modeling and molecular dynamics simulation of the alpha 1b-adrenergic receptor activation.

This work describes the ab initio procedure employed to build an activation model for the alpha 1b-adrenergic receptor (alpha 1b-AR). The first version of the model was progressively modified and complicated by means of a many-step iterative procedure characterized by the employment of experimental validations of the model in each upgrading step. A combined simulated (molecular dynamics) and experimental mutagenesis approach was used to determine the structural and dynamic features characterizing the inactive and active states of alpha 1b-AR. The latest version of the model has been successfully challenged with respect to its ability to interpret and predict the functional properties of a large number of mutants. The iterative approach employed to describe alpha 1b-AR activation in terms of molecular structure and dynamics allows further complications of the model to allow prediction and interpretation of an ever-increasing number of experimental data.

Amino Acid Sequence↗

PubMed2003

A strategy for identifying transcription factor binding sites reveals two classes of genomic c-Myc target sites.

Defining the hardwiring of transcription factors to their cognate genomic binding sites is essential for our understanding of biological processes. We used scanning chromatin immunoprecipitation to identify in vivo binding regions (E boxes) for c-Myc in three target genes as a model system. Along with other c-Myc target genes that have been validated by chromatin immunoprecipitation, we used the publicly available genomic sequences to determine whether experimentally derived in vivo binding sites might be predictable from nonexonic sequence conservation across species. Our studies revealed two classes of target genomic binding sites. Although the majority of target genes studied [class I: B23 (NPM1), CAD, CDK4, cyclin D2, ID2, LDH-A, MNT, PTMa, ODC, NM23B, nucleolin, prohibitin, SHMT1, and SHMT2] demonstrate significant sequence conservation of the E boxes and flanking regions, several genes (cyclin B1, JPO1, and PRDX3) belong to a second class (class II) that does not display sequence conservation at and around the site of c-Myc binding. On the basis of our model, we propose a strategy for predicting transcription factor binding sites using phylogenetic sequence comparisons, which will select potential class I target genes among the many emerging candidates from DNA-microarray studies for experimental validation by chromatin immunoprecipitation.

Binding Sites↗

PubMed1994

Estimation of force-activation, force-length, and force-velocity properties in isolated, electrically stimulated muscle.

Designing advanced controllers for motor neural prosthesis applications requires appropriate models for electrically stimulated muscle. A nonlinear nonisometric muscle model based on a Hill-type structure is presented. Estimation algorithms were derived to parameterize the passive force-length, the passive force-velocity, the active force-length, and the active force-velocity properties, the isometric recruitment curve, and the linear contraction dynamics of the model. All parameters were based on experimental measurements rather than on values taken from the literature. The estimation methods were validated experimentally using isolated hind-limb muscles in two acute animal model preparations. The results demonstrated that the parameterized model is capable of predicting force output with reasonable accuracy for a wide range of simultaneously varying kinematic and stimulation inputs.

Algorithms↗

PubMed2004

Human Neck Finite Element Model Development and Validation against Original Experimental Data.

This study proposes a detailed FEM of a human volunteer's neck and proceeds to an original model validation against experimental data recorded with this human volunteer. In order to evaluate the new model against existing data a successful temporal validation of the model was obtained under frontal, lateral, oblique and rear impact. New validation parameters are based on an experimental test proceeded in the frequency domain in order to extract the volunteer's Head-Neck system's modal characteristics. In depth validation of the head neck FEM is then performed by superposing the numerical and experimental frequency response function. Model optimisation in the frequency domain permitted after significant properties modification to reproduced accurately both, the neck extension mode at 1.4 Hz and the head retraction mode at 8.8 Hz. Finally the "frequency domain optimised" FEM response was superimposed with the temporal corridors provided in the literature. It must be mentioned that the model's response in the temporal domain remains inside existing corridors after this model optimisation in the frequency domain illustrating that the temporal validation is not accurate enough. This study proposes a neck model with improved geometry description and biofidelity with special attention paid to the retraction mode, a phenomenon which is often masked in the temporal domain.

Journal Article↗

PubMed2002

Effectiveness of simultaneous independent realizations at low carrier-to-noise ratio to improve heterodyne Doppler lidar performance. I. Experimental results.

A 1.55-microm continuous-wave heterodyne Doppler lidar (HDL) with three receiver-detector units is used to validate experimentally the findings presented in the Guérit et al. companion paper [Appl. Opt. 41, 2232 (2002)] on the effectiveness of independent realizations to improve HDL performance (velocity or power estimates or both) at a low carrier-to-noise ratio (CNR). In fact, noise has a detrimental effect on the accumulation techniques, so in the Guérit et al. companion paper, the chances of getting "heavy" speckles in HDL signal from many receiver-detector units on a single- or several-shot basis are investigated theoretically and numerically with the Zrnic HDL model. The experimental results enable us to conclude there is a very good agreement (better than 95%) between the performance computed from actual HDL data and from the theoretical prediction.

Comment↗

PubMed2006

Understanding the role of Ti in reversible hydrogen storage as sodium alanate: a combined experimental and density functional theoretical approach.

We report the results of an experimental and theoretical study of hydrogen storage in sodium alanate (NaAlH(4)). Reversible hydrogen storage in this material is dependent on the presence of 2-4% Ti dopant. Our combined study shows that the role of Ti may be linked entirely to Ti-containing active catalytic sites in the metallic Al phase present in the dehydrogenated NaAlH(4). The EXAFS data presented here show that dehydrogenated samples contain a highly disordered distribution of Ti-Al distances with no long-range order beyond the second coordination sphere. We have used density functional theory techniques to calculate the chemical potential of possible Ti arrangements on an Al(001) surface for Ti coverages ranging from 0.125 to 0.5 monolayer (ML) and have identified those that can chemisorb molecular hydrogen via spontaneous or only moderately activated pathways. The chemisorption process exhibits a characteristic nodal symmetry property for the low-barrier sites: the incipient doped surface-H(2) adduct's highest occupied molecular orbital (HOMO) incorporates the sigma antibonding molecular orbital of hydrogen, allowing the transfer of charge density from the surface to dissociate the molecular hydrogen. This work also proposes a plausible mechanism for the transport of an aluminum hydride species back into the NaH lattice that is supported by Car-Parrinello molecular dynamics (CPMD) simulations of the stability and mobility of aluminum clusters (alanes) on Al(001). As an experimental validation of the proposed role of titanium and the subsequent diffusion of alanes, we demonstrate experimentally that AlH(3) reacts with NaH to form NaAlH(4) without any requirement of a catalyst or hydrogen overpressure.

Journal Article↗

PubMed2005

Alternative therapy of earth elements increases the chondroprotective effects of chondroitin sulfate in mice.

The administration of mineral sulphur water is an alternative experimental approach for the treatment of rheumatic diseases, such as osteoarthritis (OA), that cause the degeneration of bone and cartilage and sufferance to the patients. Chondroitin sulfate (CS) is a symptomatic slow acting nutropeucital agent currently used in molecular therapy of OA. Therefore, we have studied the role and efficacy of the selective soil paste from the mineral sulphur enriched spring (mud)-therapy alone or in combination with CS in the treatment of OA. The study was performed on 40 C57 Black 6N mice, an experimental model which spontaneously develop an osteoarthritic process. The animals were divided in 4 groups and were treated with the single agents or with the combination. After 30 days of treatment all the mice were sacrificed and right knees and blood were collected. It was found that CS determined a reduction of radiological and histological features of chondrodegeneration and that mud-therapy increased the effects of CS in the animal group treated with the combination. However, the effects of thermal therapy alone were not statistically significant. Since OA is characterized by an increase of the production of nitric oxide (NO) by chondrocytes in extracellular matrix with its consequent elevation in serum and synovial fluid, we have evaluated the effects of the treatments on serum NO levels. CS alone induced a statistically significant reduction of NO serum levels (90+/-13 micromM vs 219+/-60 microM of control group, P<0.05) while mud-therapy alone induced a not statistically significant reduction of serum NO (170+/-62 microM, P>0.05). However, the latter strongly potentiated the decrease of serum NO induced by CS (31+/-1.5 microM) with a high statistical significance if compared to both the control group (P<0.01) and the CS-treated group (P<0.05). In conclusion, this study demonstrates that mud-therapy with sulphur mineral water could represent an important phase of the therapeutic strategy of OA. This experimental strategy could integrate and potentiate the standard pharmacological tools. Moreover, we have set a valid experimental in vivo model for the study of the thermal effects on the development of OA.

Animals↗

PubMed2006

Diffraction-based density restraints for membrane and membrane-peptide molecular dynamics simulations.

We have recently shown that current molecular dynamics (MD) atomic force fields are not yet able to produce lipid bilayer structures that agree with experimentally-determined structures within experimental errors. Because of the many advantages offered by experimentally validated simulations, we have developed a novel restraint method for membrane MD simulations that uses experimental diffraction data. The restraints, introduced into the MD force field, act upon specified groups of atoms to restrain their mean positions and widths to values determined experimentally. The method was first tested using a simple liquid argon system, and then applied to a neat dioleoylphosphatidylcholine (DOPC) bilayer at 66% relative humidity and to the same bilayer containing the peptide melittin. Application of experiment-based restraints to the transbilayer double-bond and water distributions of neat DOPC bilayers led to distributions that agreed with the experimental values. Based upon the experimental structure, the restraints improved the simulated structure in some regions while introducing larger differences in others, as might be expected from imperfect force fields. For the DOPC-melittin system, the experimental transbilayer distribution of melittin was used as a restraint. The addition of the peptide caused perturbations of the simulated bilayer structure, but which were larger than observed experimentally. The melittin distribution of the simulation could be fit accurately to a Gaussian with parameters close to the observed ones, indicating that the restraints can be used to produce an ensemble of membrane-bound peptide conformations that are consistent with experiments. Such ensembles pave the way for understanding peptide-bilayer interactions at the atomic level.

Birefringence↗

PubMed1998

Asymmetry in placement of bilateral skin markers on horses and effects of asymmetric skin marker placement on kinematic variables.

OBJECTIVE: To evaluate asymmetry in placement of bilateral skin markers on horses and to determine effect of asymmetric skin marker placement on kinematic variables for trotting horses. ANIMALS: 10 horses for evaluation of asymmetry in marker placement; 1 horse for evaluation of effects on kinematic variables. PROCEDURE: Asymmetry in marker placement was assessed by attaching markers to horses and comparing radiographs of left and right limbs. An experimental model was developed to determine effects on kinematic variables; accuracy of the model was validated experimentally. Using kinematic data from a clinically normal trotting horse as reference data, effects of asymmetric marker placement on vertical displacement-time and joint angle-time diagrams were determined by use of the model. RESULTS: Asymmetry of placement was < 1 cm for markers on the distal portions of the limbs and < 2 cm for markers on the proximal portions. Asymmetric marker placement did not alter general shapes of the vertical displacement-time and joint angle-time curves. In most instances, largest differences in vertical displacement attributable to asymmetric marker placement were equal to or less than magnitude of the asymmetry of placement. Alterations in joint angle-time curves were mainly a result of shifting of the curves on the Y axis. Joint range of motion was only slightly changed by asymmetric marker placement, but maximum flexion and extension angles were greatly altered. CONCLUSIONS AND CLINICAL RELEVANCE: Some kinematic variables can be greatly altered by small differences in skin marker placement. Such effects should be taken into account when evaluating kinematic data for sound and lame horses.

Animals↗

PubMed2005

A dosimetric study of Leipzig applicators.

PURPOSE: To obtain the absolute dose-rate distribution in liquid water for all six cup-shaped Leipzig applicators by means of an experimentally validated Monte Carlo (MC) code. These six applicators were used in high-dose-rate (HDR) afterloaders with the "classic" and v2 (192)Ir sources. The applicators have an inner diameter of 1, 2, and 3 cm, with the source traveling parallel or perpendicular to the contact surface. METHODS AND MATERIALS: The MC GEANT4 code was used to obtain the dose-rate distribution in liquid water for the six applicators and the two HDR source models. To normalize the applicator output factors, a MC simulation for the "classic" and v2 sources in air was performed to estimate the air-kerma strength. To validate this specific application and to guarantee that realistic source-applicator geometry was considered, an experimental verification procedure was implemented in this study, in accordance with the TG43U1 recommendations. Thermolumniscent dosimeter chips and a parallel plate ionization chamber in a polymethyl methacrylate (PMMA) phantom were used to verify the MC results for the six applicators in a microSelectronHDR afterloader with the "classic" source. Dose-rate distributions dependence on phantom size has been evaluated using two different phantom sizes. RESULTS: Percentage depth dose and off-axis profiles were obtained normalized at a depth of 3 mm along the central axis for both phantom sizes. A table of output factors, normalized to 1 U of source kerma strength at this depth, is presented. The dose measured in the PMMA phantom agrees within experimental uncertainties with the dose obtained by the MC GEANT4 code calculations. The phantom size influence on dose-rate distributions becomes significant at depths greater than 5 cm. CONCLUSIONS: MC-detailed simulation was performed for the Nucletron Leipzig HDR applicators. The matrix data obtained, with a grid separation of 0.5 mm, can be used to build a dataset in a convenient format to model these distributions for routine use with a brachytherapy treatment planning system.

Brachytherapy↗

PubMed2002

An approach for developing an experimentally based model for simulating flight-phase dynamics.

This paper presents an approach for developing an experimentally validated dynamic multisegment model to simulate human flight-phase dynamics and multijoint control. Modeling and experimental techniques were integrated to systematically examine the contribution of multiple error sources to the accuracy of the model and to determine the complexity of a model that adequately emulates the dynamic behavior at the total-body and multijoint levels during flight. The accuracy of the model and of the experimental data was assessed using an inverse dynamics simulation of flight-phase motion for two representative cases: (i) a physical model released from a bar and (ii) a gymnast performing a layout dismount from a bar. Multijoint models with varying numbers of segments were assessed in order to determine the complexity of the model that adequately simulates the flight-phase task. A five-segment model was found to adequately simulate the layout dismount performed by the gymnast. The error introduced during modeling and digitizing contributed to an apparent violation of the conservation law manifested as large external forces acting on the nonactuated joints. These results demonstrate the need to reduce sources of error prior to testing hypotheses regarding feedforward and feedback components of the multijoint control system. The proposed approach for quantifying sources of error provides a crucial step that is required in the development of experimentally based dynamic models designed to examine and test hypotheses regarding multijoint control logic.

Biomechanical Phenomena↗

PubMed1982

Validity of the Goldman-Hodgkin-Katz equation in paracellular ionic pathways of gallbladder epithelium.

The Goldman-Hodgkin-Katz equation has been extensively used to determine cationic/anionic permeability ratios in the paracellular pathways of the gallbladder epithelium. Nevertheless, new experimental evidence suggests that none of the theoretical assumptions of the equation hold for these pathways. In order to assess the experimental validity of the Goldman equation the permeability ratios were calculated from zero-current diffusion potentials by means of the Goldman equation and compared with the cationic/anionic permeability ratios measured by simultaneous determinations of cation and anion tracer fluxes in the same membranes. The results indicate that the Goldman equation is empirically valid for the tested salts (KCl and RbCl) within the experimental range of concentrations (25 to 200 mM) at an electrochemical-potential difference of zero.

Animals↗

PubMed2006

A validated quantitative assay to detect occult micrometastases by reverse transcriptase-polymerase chain reaction of guanylyl cyclase C in patients with colorectal cancer.

PURPOSE: Guanylyl cyclase C (GCC), a receptor for bacterial diarrheagenic enterotoxins, may be a prognostic and predictive marker to detect occult micrometastases in patients undergoing staging for colorectal cancer. However, quantification of GCC expression in tissues by the quantitative reverse transcription-PCR (qRT-PCR) has not undergone analytic and clinicopathologic validation. EXPERIMENTAL DESIGN: A technique to quantify GCC mRNA in tissues employing RT-PCR was developed and validated employing external calibration standards of RNA complementary to GCC. RESULTS: GCC qRT-PCR exhibited reaction efficiencies >92%, coefficients of variations <5%, linearity >6 orders of magnitude, and a limit of quantification of >25 copies of GCC cRNA. This assay confirmed that GCC mRNA was overexpressed by colorectal tumors from 41 patients, which correlated with increased GCC protein quantified by immunohistochemistry. Analyses obtained with 164 lymph nodes from patients free of cancer and 15 nodes harboring metastases established a threshold for metastatic disease of approximately 200 GCC mRNA copies/mug total RNA, with a sensitivity of 93% and specificity of 97%. GCC mRNA above that threshold was detected in 76 of 367 (approximately 21%) nodes free of disease by histopathology from 6 of 23 (26%) patients, suggesting the presence of occult micrometastases. CONCLUSIONS: Quantifying GCC mRNA in tissues by RT-PCR employing external calibration standards is analytically robust and reproducible, with high clinicopathologic sensitivity and specificity. This validated assay is being applied to approximately 10,000 lymph nodes in a prospective trial to define the sensitivity of GCC qRT-PCR for staging patients with colorectal cancer.

Adult↗

PubMed2004

Phantom validation and in vivo application of an inversion procedure for retrieving the optical properties of diffusive layered media from time-resolved reflectance measurements.

An experimental validation of an inversion procedure for retrieving the optical properties of layered media from multidistance time-resolved reflectance measurements is presented. The results cover a wide range of optical properties, showing excellent effectiveness and reliability of the procedure in reconstructing the optical properties of a two-layered medium. The optical properties of the first layer and the absorption of the second layer could be retrieved with excellent precision, whereas the reduced scattering coefficient of the second layer was reconstructed with a large error. The first layer thickness could be retrieved with an error less than 50%. An example of retrieval of the optical properties of muscle from in vivo measurements during an arterial occlusion is shown.

Algorithms↗

PubMed2026

A reproducible computational transcriptomic framework for cell-type-resolved fibroinflammatory-AKT remodeling in human heart failure.

BACKGROUND: Human heart failure involves multicellular transcriptional remodeling, but public transcriptomic studies often remain disconnected from cell-type localization and perturbational interpretation. METHODS: We developed a reproducible computational workflow integrating human left-ventricular bulk transcriptomes, donor-level cell-type pseudobulk results from a human heart-failure single-cell/single-nucleus atlas, external snRNA-seq support, curated module scoring, focused ligand-receptor prioritization and LINCS/L1000 perturbational matching. RESULTS: Cross-cohort analysis identified 14,358 same-direction HF-associated genes, including 1633 replicated HF-up and 785 replicated HF-down genes. Donor-level pseudobulk analysis localized disease remodeling to cardiomyocyte, fibroblast and myeloid compartments. Activated fibroblast and inflammatory myeloid programs defined a fibroinflammatory remodeling axis connected to context-dependent AKT-associated transcriptional shifts. External snRNA-seq support was strongest for fibroblast activation and AKT-associated remodeling, with etiology-dependent heterogeneity across validation resources. L1000FWD screening prioritized safety-aware perturbational hypotheses, including glimepiride and simvastatin as interpretable candidates requiring experimental validation. CONCLUSIONS: This study provides a computational transcriptomic framework linking reproducible human HF signatures, cell-type-resolved fibroinflammatory remodeling and perturbational genomic prioritization without claiming drug efficacy or AKT causality.

Humans↗

PubMed2025

Automating candidate gene prioritization with large language models: from naive scoring to literature-grounded validation.

MOTIVATION: Identifying promising therapeutic targets from thousands of genes in transcriptomic studies remains a major bottleneck in biomedical research. While large language models (LLMs) show potential for gene prioritization, they suffer from hallucination and lack systematic validation against expert knowledge. RESULTS: The framework identified 609 sepsis-relevant genes with >94% filtering efficiency, demonstrating strong enrichment for inflammatory pathways including TNF-α signaling, complement activation, and interferon responses. Literature validation yielded 30 ultra-high confidence therapeutic candidates, including both established sepsis genes (IL10, TREM1, S100A9, NLRP3) and novel targets warranting investigation. Benchmark validation against expert-curated databases achieved 71.2% recall, with systematic correlation between computational confidence and evidence quality. The final candidate set balanced discovery (11 novel genes) with validation (19 known genes), maintaining biological coherence throughout the filtering process. This framework demonstrates that rigorous methodology can transform unreliable LLM outputs into systematically validated biological insights. By combining computational efficiency with literature grounding, the approach provides a practical tool for prioritizing experimental validation efforts. The modular design enables adaptation to other diseases through knowledge base substitution, offering a systematic approach to literature-guided biomarker discovery. AVAILABILITY AND IMPLEMENTATION: We developed a two-stage computational framework that combines LLM-based screening with literature validation for systematic gene prioritization. Starting with 10 824 genes from the BloodGen3 repertoire, we applied multi-criteria evaluation for sepsis relevance, followed by retrieval-augmented generation using 6346 curated sepsis publications. A novel faithfulness evaluation system verified that LLM predictions aligned with retrieved literature evidence. Source code and implementation details are available at https://github.com/taushifkhan/llm-geneprioritization-framework, vector database at https://doi.org/10.5281/zenodo.15802241, and Interactive demonstration at https://llm-geneprioritization.streamlit.app/.

Humans↗

PubMed2006

Robustness and stability of flow-and-diffusion structures.

Reaction-diffusion-advection systems have revealed an interesting variety of pattern formation mechanism during the last years. Inside this field, flow-and-diffusion structures (FDSs) appear as a generalization of the mechanism of spatial symmetry breaking for different diffusion coefficients and flow rates of activator and inhibitor. The recent experimental validation of FDSs situates these structures in the focus of the actual research. We will report here an experimental and numerical analysis of the theoretically predicted robustness of these flow-and-diffusion structures by using different boundary profiles of illumination used to obtain FDSs. The results here shown reveal important characteristics related with the coexistence and interaction between these structures.

Journal Article↗