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At least 649 records · Page 36Linked to original sources

Experimental force measurements on a bifurcated endoluminal stent graft model: comparison with theory.

The goal of this study was to experimentally validate a steady-state mathematical model, which can be used to compute the forces acting on a bifurcated endoluminal stent graft. To accomplish this task, an acrylic model of a bifurcated graft was used for the force measurements. The graft model was connected to the inlet piping with a flexible rubber membrane that allowed the graft model to move. This allowed us to measure the force owing to the movement of the graft model with a calibrated load cell. Steady-state blood flow was assumed, and the working fluid was water. The experimental data were found to be consistent with the results from a previously published mathematical model: the graft force is strongly dependent on the proximal or inlet pressure and the inlet area. The force tends to be weakly dependent on flow rate. More research work will be required to determine whether the steady-state force model examined in this article provides a realistic determination of the forces on an endoluminal stent graft that is subject to pulsatile blood flow.

Aortic Aneurysm, Abdominal↗

A spatially varying compton scatter correction for SPECT utilizing the integral Klein-Nishina cross section.

An algorithm correcting for the fraction of scattered events in SPECT and planar imaging is proposed. The algorithm utilizes a pixel-based multi-channel analyser for data acquisition. The method was designed to operate on a local level by three subtraction steps: (a) Subtracting a modified Klein-Nishina single scatter distribution, pixel by pixel, from the events obtained experimentally in the upper half of the photo-peak window. (b) Subtracting a mirrored distribution of the unscattered events hence obtained from that of total events in the lower half of the window, thus giving the scatter distribution in this part of the window. (c) Subtracting the sum of the scatter distributions in both window halves from the corresponding sum of total events in order to obtain the unscattered photons within the photo-peak window. The accuracy of the method was validated experimentally, using a new rCBF phantom allowing for imaging in matter corresponding to soft tissue and approximately in air, respectively. After correction for photon scattering and attenuation, the regional difference in SPECT values in soft tissue equivalent matter and in low-density matter (simulating air) was only 1.5 +/- 7.2% (mean +/- 1 SD), thus indicating a high accuracy of the correction method. Provided that an accurate and stable pixel peak-alignment routine is available, the method can be applied using a minimum of three windows.

Algorithms↗

Predicting subcellular localization via protein motif co-occurrence.

The prediction of subcellular localization of proteins from their primary sequence is a challenging problem in bioinformatics. We have created a Bayesian network localization predictor called PSLT that is based on the combinatorial presence of InterPro motifs and specific membrane domains in human proteins. This probabilistic framework generates a likelihood of localization to all organelles and allows to predict multicompartmental proteins. When used to predict on nine compartments, PSLT achieves an accuracy of 78% as estimated by using a 10-fold cross-validation test and a coverage of 74%. When used to predict the localization of proteins from other closely related species, it achieves a prediction accuracy and a coverage >80%. We compared the localization predictions of PSLT to those determined through GFP-tagging and microscopy for a group of human proteins. We found two general classes of proteins that are mislocalized by the GFP-tagging strategy but are correctly localized by PSLT. This suggests that PSLT can be used in combination with experimental approaches for localization to identify proteins for which additional experimental validation is required. We used our predictor to annotate all 9793 human proteins from SWISS-PROT release 41.25, 16% of which are predicted by PSLT to be present in more than one compartment.

Humans↗

Isokinetic elbow joint torques estimation from surface EMG and joint kinematic data: using an artificial neural network model.

Because the relations between electromyographic signal (EMG) and anisometric joint torque remain unpredictable, the aim of this study was to determine the relations between the EMG activity and the isokinetic elbow joint torque via an artificial neural network (ANN) model. This 3-layer feed-forward network was constructed using an error back-propagation algorithm with an adaptive learning rate. The experimental validation was achieved by rectified, low-pass filtered EMG signals from the representative muscles, joint angle and joint angular velocity and measured torque. Learning with a limited set of examples allowed accurate prediction of isokinetic joint torque from novel EMG activities, joint position, joint angular velocity. Sensitivity analysis of the hidden node numbers during the learning and testing phases demonstrated that the choice of numbers of hidden node was not critical except at extreme values of those parameters. Model predictions were well correlated with the experimental data (the mean root-mean-square-difference and correlation coefficient gamma in learning were 0.0290 and 0.998, respectively, and in three different speed testings were 0.1413 and 0.900, respectively). These results suggested that an ANN model can represent the relations between EMG and joint torque/moment in human isokinetic movements. The effect of different adjacent electrode sites was also evaluated and showed the location of electrodes was very important to produce errors in the ANN model.

Adult↗

Enhanced identification of key bacterial motility genes via a cross-species genomic hybrid feature machine learning approach.

Efficient and accurate identification of functional genes is critical to biological research, yet traditional single-species approaches are often limited by low efficiency. Previously, we established a novel method for identifying key genes using cross-species protein domain features and machine learning. However, the high multiplicity of gene members associated with specific domains creates a substantial workload for subsequent experimental validation. To address this, this study proposes an enhanced approach that integrates EggNOG-based protein sequence annotation with domain analysis. Unannotated sequences are subsequently analyzed for protein domains, generating a comprehensive "direct gene annotation plus domain" hybrid feature matrix. While the hybrid matrix model yielded comparable predictive accuracy, it significantly enhanced feature resolution: the top 50 predicted features were all known motility-related genes or domains. Furthermore, among the top 100 ranked features, 58 are confirmed to be directly related to motility based on experimental evidence. Although strict genus-level control still yielded 51 confirmed features, excessive taxonomic restriction drastically reduces the number of training genomes, which may paradoxically impair identification efficiency. These results demonstrate that the new method effectively reduces the subsequent experimental workload and enables high-throughput identification of functional genes in a single analysis. With accuracy and efficiency far exceeding those of existing single-species identification methods, it provides a highly efficient solution for mining key genes underlying other complex bacterial phenotypes.

Machine Learning↗

Combined spectroscopic/computational study of binuclear Fe(I)-Fe(I) complexes: implications for the fully-reduced active-site cluster of Fe-only hydrogenases.

The Fe(I)-Fe(I) dimer complex [Fe2(pdt)(CO)4(CN)2][Et4N]2 (2), where pdt = 1,3-propane dithiolate, serves as a model of the fully reduced [2Fe]H component of the H cluster, which is the active site for catalysis in Fe-only hydrogenases (FeHases). Electronic absorption, magnetic circular dichroism (MCD), and resonance Raman (rR) spectroscopies have been employed to characterize both the ground and excited states of 2 as well as those of the related complex Fe2(pdt)(CO)6 (1). These results have been combined with density functional theory (DFT) computations to produce experimentally validated bonding descriptions of 1 and 2. It is shown that Fe(I)-S covalency is significantly reduced upon dicyano substitution (i.e., conversion of 1 --> 2), while the corresponding Fe(I)-CO/CN pi-backbonding interactions are strengthened, results that are corroborated by normal-coordinate analyses of the vibrational data. Detailed assignments of the features observed in the electronic absorption spectra of 1 and 2 have been developed on the basis of time-dependent DFT (TD-DFT) calculations, which provide remarkably accurate simulations of the experimental data. For both complexes, all bands below 32,000 cm(-1) arise from transitions involving electronic excitation within the binuclear Fe-Fe core, with the most intense feature assigned to the Fe(sigma(b)) --> Fe(sigma*) transition. Analysis of the corresponding rR excitation profiles within the framework of time-dependent Heller theory reveals that in each case the Fe-Fe bond is elongated by approximately 0.3 A in the Fe(sigma(b)) --> Fe(sigma*) excited state. Finally, building upon the insights gained from the spectroscopic/computational studies of 1 and 2, our computational methodology has been extended to the reduced enzyme active site, providing insights into the electronic structure of the [2Fe]H subcluster in the H(red) state and its relationship to catalysis.

Binding Sites↗

Artificial Intelligence-Driven Multi-Omics Analysis Reveals Hydroxytyrosol Targeting of the TXNIP-NLRP3 Inflammasome Axis in Traumatic Brain Injury.

Traumatic brain injury (TBI) induces secondary neuroinflammation driven by oxidative stress, inflammasome activation, and immune remodeling, yet specific mechanism-guided pharmacological interventions remain limited. This study established an artificial intelligence (AI)-integrated network pharmacology and multi-omics framework to evaluate whether hydroxytyrosol (HT), an olive-derived natural polyphenol, may regulate TBI-related neuroinflammatory targets centered on the TXNIP/NLRP3 inflammasome axis. Starting from the SMILES structure of HT, potential targets were predicted using PharmMapper, SwissTargetPrediction, and the Similarity Ensemble Approach and were standardized to UniProt identifiers. TBI-associated genes were integrated from GeneCards, DisGeNET, OMIM, and the Therapeutic Target Database. The overlapping target set was analyzed using STRING-based protein-protein interaction (PPI) networks, MCODE, CytoHubba, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Public GEO transcriptomic datasets (GSE123831 and GSE104687) were used for cross-platform expression validation, differential expression analysis, and exploratory CIBERSORT-based immune infiltration estimation. Random forest (RF), multilayer perceptron (MLP), graph convolutional network (GCN), graph attention network (GAT), SHAP/LIME explainability analysis, LASSO inflammatory-risk scoring, and two-sample Mendelian randomization (MR) were further applied for target prioritization, immune phenotype mapping, and genetic association analysis. Seventy-three overlapping HT-TBI targets were identified. PPI and topology analyses prioritized TXNIP, NLRP3, CASP1, MAPK1, and TP53 as key hubs enriched in inflammasome activation, oxidative stress, apoptosis, and NOD-like receptor signaling. TXNIP, NLRP3, and CASP1 were consistently upregulated in both TBI transcriptomic datasets. LM22-based immune deconvolution suggested increased pro-inflammatory immune signatures and a positive TXNIP-M1 macrophage association (r&#x202f;=&#x202f;0.63, p < 0.001), which should be interpreted as a transcriptome-derived hypothesis rather than validated murine immune-cell proportions. AI-based models consistently ranked TXNIP/NLRP3 as high-contribution features under internal validation, and removal of these targets reduced model performance. A five-gene inflammatory score achieved an internally evaluated AUC of 0.87, while two-sample MR supported positive genetic associations involving TXNIP expression, TBI risk, NLRP3 and IL-1&#x3b2; expression. Collectively, these findings prioritize the TXNIP/NLRP3/CASP1 module as a computationally supported candidate mechanism through which HT may influence oxidative stress-inflammasome-immune coupling in TBI. This study provides an interpretable drug-target-pathway-phenotype framework and identifies TXNIP, NLRP3, and CASP1 as priority nodes for future experimental validation.

Artificial Intelligence↗

The pseudouridine epitranscriptomic landscape of advanced prostate cancer therapeutic resistance identifies TIMM17A as a key player.

BACKGROUND: Resistance to androgen receptor signaling inhibitors (ARSIs) remains a major barrier of advanced prostate cancer (PCa) treatment. While RNA epitranscriptomic modifications are increasingly recognized as key regulators of tumor biology, the role of pseudouridine (&#x3a8;) in therapeutic resistance is largely unexplored. METHODS: A darolutamide-resistant PCa cell model was established and subjected to integrated multi-omics profiling using bulk RNA sequencing and photo-crosslinking-assisted &#x3a8; sequencing (PA-&#x3a8;-seq). Differential expression and pseudouridylation analyses were combined to identify &#x3a8;-associated genes. Public datasets validated expression and prognosis. Functional assays including RNA knockdown, cell proliferation, colony formation, and xenograft models were conducted. Single-cell RNA sequencing investigated tumor microenvironment (TME) interactions. RESULTS: We identified extensive transcriptomic and pseudouridylation alterations associated with ARSI resistance, with a significant positive correlation between &#x3a8; modification and mRNA expression. Integrated analysis highlighted a subset of "hyper-up" genes enriched in resistance-related pathways. Thus, TIMM17A was identified as a novel candidate. TIMM17A expression was significantly elevated in PCa and correlated with disease progression and poor prognosis. Experimental validations demonstrated that TIMM17A promoted tumor growth and resistance, while its knockdown restored sensitivity to darolutamide both in vitro and in vivo. Mechanistically, TIMM17A expression may be regulated by PUS1&#x2011;mediated pseudouridylation. Single-cell analysis further revealed that TIMM17A is enriched in malignant epithelial cells and associated with enhanced cell-cell communication within the TME. CONCLUSIONS: This study delineates the pseudouridine epitranscriptomic landscape in advanced PCa and identifies TIMM17A as a key mediator of therapeutic resistance. Targeting the &#x3a8;-TIMM17A axis may offer a novel strategy to overcome ARSI resistance.

Advanced prostate cancer↗

A rapid RT-PCR screening assay incorporating multiplexed validated control genes for CBF rearrangements at diagnosis in AML.

AIMS: Our objective was to establish a multiplexed assay using the Biomed 1 primers to detect AML1-ETO transcripts and 10 different CBFB-MYH11 transcripts, using BCR and ABL transcripts as controls. METHODS: Control genes were systematically tested for characteristics of optimal controls. The final assay was validated on 50 AML patient samples. RESULTS: Testing confirmed that the designated control gene criteria were fulfilled. Of 50 patient samples tested, four RT-PCR results were discordant with the cytogenetic result. In three cytogenetically negative cases, RT-PCR detected cryptic CBF rearrangements (one AML1-ETO and two CBFB-MYH11). The fourth case was inv(16) positive but negative by RT-PCR; however, the control gene result revealed suboptimal RNA quality. CONCLUSIONS: We have described a robust multiplex RT-PCR assay that incorporates experimentally validated control genes that are important for accurate interpretation. The assay is more sensitive than cytogenetics in the detection of CBF AML. Application to large patient cohorts will determine the prognostic significance of cryptic CBF rearrangements compared with their cytogenetic counterparts.

Acute Disease↗

Enzyme-like proteins by computational design.

We report the development and initial experimental validation of a computational design procedure aimed at generating enzyme-like protein catalysts called "protozymes." Our design approach utilizes a "compute and build" strategy that is based on the physical/chemical principles governing protein stability and catalytic mechanism. By using the catalytically inert 108-residue Escherichia coli thioredoxin as a scaffold, the histidine-mediated nucleophilic hydrolysis of p-nitrophenyl acetate as a model reaction, and the ORBIT protein design software to compute sequences, an active site scan identified two promising catalytic positions and surrounding active-site mutations required for substrate binding. Experimentally, both candidate protozymes demonstrated catalytic activity significantly above background. One of the proteins, PZD2, displayed "burst" phase kinetics at high substrate concentrations, consistent with the formation of a stable enzyme intermediate. The kinetic parameters of PZD2 are comparable to early catalytic Abs. But, unlike catalytic Ab design, our design procedure is independent of fold, suggesting a possible mechanism for examining the relationships between protein fold and the evolvability of protein function.

Catalytic Domain↗

Quantitative phase-contrast flow MRI measurements in the presence of a second vessel closely positioned to the examined vessel.

PURPOSE: To examine the influence of the truncated sampling of k-space data on the accuracy of phase-contrast (PC) flow quantifications in the presence of nearby vessels. MATERIALS AND METHODS: Computer simulations were performed along with some experimental validations on a flow phantom and a normal subject. RESULTS: The accuracy of the PC flow quantification decreased when a second vessel was positioned closely to the examined vessel. The effect strongly depended on the peak flow velocity in the second vessel relative to the velocity encoding (venc) level of the MRI acquisition, and on the position and area of the second vessel. CONCLUSION: Due to the truncated sampling of the k-space data, signal leaked from nearby vessels and distorted the PC flow quantification in the examined vessel. The presented results suggest specific experimental conditions to minimize this flow quantification error.

Blood Flow Velocity↗

Lack of protection by pneumococcal vaccine after splenectomy in mice challenged with aerosolized pneumococci.

The efficacy of pneumococcal vaccine given after splenectomy lacks experimental validation. Adult CD-1 male mice that received type III pneumococcal capsular polysaccharide vaccine 1 microgram IP, 48 hours postsplenectomy and 7 days before challenge with aerosolized type III Streptococcus pneumoniae had a significantly higher mortality (96%) compared to immunized controls (64%) (p less than 0.002). The vaccine protected immunized sham-operated mice compared to unimmunized controls (p less than 0.015). Mice immunized 7 days before splenectomy were equally protected when compared to immunized sham-operated mice (p = NS). All deaths were secondary to culture-proven pneumococcal infection. These findings corroborate previous experimental and clinical studies demonstrating an impaired immunologic response and increased susceptibility to infection in asplenic individuals. Pneumococcal vaccines should be given before nonemergent splenectomy. Alternatives to splenectomy should be considered for patients with traumatized spleens where possible.

Aerosols↗

Finite element analysis of cervical facetectomy.

STUDY DESIGN: Moment-rotation responses and disc anulus stresses of intact and facetectomized C4-C6 cervical spinal units were analyzed using detailed, three-dimensional, finite element models. OBJECTIVES: To evaluate biomechanical effects of progressive unilateral and bilateral facet resections on cervical spine segmental mobility (external response) and disc anulus stress (internal response). SUMMARY OF BACKGROUND DATA: Experimental studies have demonstrated that facetectomy significantly increases segmental mobility of the cervical spine. The biomechanical effects of facetectomy on the internal response, however, have not been investigated. METHODS: Moment-rotation responses of C4 with respect to C6 and von Mises stress in the disc anulus were examined using finite element models of a 0% (intact), 25%, 50%, 75%, and 100% unilaterally and bilaterally facetectomized cervical spinal unit. The model simulations were conducted under the pure-moment loading of 1.8 Nm in flexion, extension, lateral bending, and axial torsion. The intact model also was validated experimentally under the same conditions. RESULTS: The moment-rotation responses of the intact unit were within the ranges of experimental data. Cervical rotations increased with the increased degree of facet resection. The greatest change occurred between 50% and 75% facet resections in bilateral facetectomy. Similar patterns were found for disc anulus stresses, but to a greater extent. The maximum increase in rotation (11%) and in anulus stress (30%) occurred in lateral bending. Torsion was the least affected loading mode. The effects of unilateral facetectomy were considerably less than those of 75% bilateral facetectomy. CONCLUSIONS: Facetectomy has a greater effect on anulus stress than on intervertebral joint stiffness. Significant increase in anulus stresses and segmental mobility may occur when bilateral facet resection exceeds 50%.

Adult↗

Correction of photoresponse nonuniformity for matrix detectors based on prior compensation for their nonlinear behavior.

What we believe to be a novel procedure to correct the nonuniformity that is inherent in all matrix detectors has been developed and experimentally validated. This correction method, unlike other nonuniformity-correction algorithms, consists of two steps that separate two of the usual problems that affect characterization of matrix detectors, i.e., nonlinearity and the relative variation of the pixels' responsivity across the array. The correction of the nonlinear behavior remains valid for any illumination wavelength employed, as long as the nonlinearity is not due to power dependence of the internal quantum efficiency. This method of correction of nonuniformity permits the immediate calculation of the correction factor for any given power level and for any illuminant that has a known spectral content once the nonuniform behavior has been characterized for a sufficient number of wavelengths. This procedure has a significant advantage compared with other traditional calibration-based methods, which require that a full characterization be carried out for each spectral distribution pattern of the incident optical radiation. The experimental application of this novel method has achieved a 20-fold increase in the uniformity of a CCD array for response levels close to saturation.

Journal Article↗

Simulation of the Adhesion of Particles to Surfaces.

The removal of micrometer and submicrometer particles from dielectric and metal films represents a challenge in postchemical mechanical polishing cleaning. Proper modeling of the adhesive force between contaminant particles and these films is needed to develop optimal solutions to postchemical mechanical polishing cleaning. We have previously developed and experimentally validated a model to describe the adhesion between spherical particles and thin films. This simulation expands previous models to characterize the adhesive interaction between asymmetrical particles, characteristic of a polishing slurry, and various films. Our simulation accounts for the contact area between particles and substrates, as well as the morphology of the surfaces. Previous models fail to accurately describe the contact of asymmetrical particles interacting with surfaces. By properly accounting for nonideal and geometry and morphology, the simulation predicts a more accurate adhesive force than predictions based upon an ideal van der Waals model. The simulation is compared to experimental data taken for both semi-ideal particle-substrate systems (polystyrene latex spheres in contact with silicon films) and asymmetrical systems (alumina particles in contact with various films). Copyright 2001 Academic Press.

Journal Article↗

Surgical navigation display system using volume rendering of intraoperatively scanned CT images.

As operative procedures become more complicated, simply increasing the number of devices will not facilitate such operations. It is necessary to consider the ergonomics of the operating environment, especially with regard to the provision of navigation data, the prevention of technical difficulties, and the comfort of the operating room staff. We have designed and created a data-fusion interface that enables volumetric Maximum Intensity Projection (MIP) image navigation using intra-operative mobile 3D-CT data in the OR. The 3D volumetric data reflecting a patient's inner structure is directly displayed on the monitor through video images of the surgical field using a 3D optical tracking system, a ceiling-mounted articulating monitor, and a small-size video camera mounted at the back of the monitor. The system performance and accuracy was validated experimentally. This system provides a novel interface for a surgeon with volume rendering of intra-operatively scanned CT images, as opposed to preoperative images.

Computer Graphics↗

Spectroscopic and computational studies of Co3+-corrinoids: spectral and electronic properties of the B12 cofactors and biologically relevant precursors.

The B(12) cofactors methylcobalamin (MeCbl) and 5'-deoxyadenosylcobalamin (AdoCbl) have long fascinated chemists because of their complex structures and unusual reactivities in biological systems; however, their electronic absorption (Abs) spectra have remained largely unassigned. In this study, we have used Abs, circular dichroism (CD), magnetic CD (MCD), and resonance Raman spectroscopic techniques to probe the electronic excited states of Co(3+)Cbl species that differ with respect to their upper axial ligand, including MeCbl, AdoCbl, aquacobalamin (H(2)OCbl(+)), and vitamin B(12) (cyanocobalamin, CNCbl). Also included to probe the effect of the lower axial ligand on the electronic properties of Cbls is Ado-cobinamide (AdoCbi(+)), an AdoCbl derivative that lacks the tethered base 5,6-dimethylbenzimidazole (DMB) and instead binds a water molecule in the lower axial position. Spectroscopic data for each species are analyzed within the framework of time-dependent density functional theory (TD-DFT) to assign the major spectral features (the so-called alpha/beta, D/E, and gamma bands) and to generate experimentally validated electronic-structure descriptions. These studies reveal that the "unique" Abs spectra of MeCbl and AdoCbl, which differ considerably from the "typical" Abs spectra of H(2)OCbl(+) and CNCbl, reflect the high degree of sigma-donation from the alkyl ligand to the Co center and the consequent destabilization of all Co 3d orbitals. They reveal further that with increasing sigma-donor strength of the upper axial ligand, the contribution from the formally unoccupied Co 3d(z(2)) orbital to the HOMO increases, which induces a strong Co[bond]N(DMB) sigma-antibonding interaction, consistent with the experimentally observed lengthening of this bond from H(2)OCbl(+) to CNCbl and MeCbl. Alternatively, our spectroscopic and computational data for MeCbl and MeCbi(+) reveal that substitution of the DMB by a water molecule in the lower axial position has negligible effects on the Co[bond]C. A simple model is presented that explains why the identity of the upper axial ligand has a major effect on the Co[bond]N(ax) strength, whereas the lower axial ligand does not appreciably modulate the nature of the Co[bond]C. Implications of these results with respect to enzymatic Co[bond]C activation are discussed.

Circular Dichroism↗

Construction and application of a multispecific competitor to quantify mRNA of matrix metalloproteinases and their tissue inhibitors in small human biopsies.

Accurate quantitation of mRNA levels of a number of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in very small samples such as human biopsy material has not been generally possible. This paper describes the development, validation and application of a quantitative RT-PCR (Q-RT-PCR) assay that allows the detection and quantitation of mRNAs encoding genes of three MMPs (MMP-1, MMP-2, MMP-3), three TIMPs (TIMP-1, TIMP-2, TIMP-3) and GAPDH simultaneously from small amounts of RNA (< 4 microg). A multispecific competitor which shares the same primer-binding sequences as the cellular mRNA of all seven genes, but yields different sized PCR products, was constructed by adding primers specific for the MMPs and TIMPs to a core molecule (mutated GAPDH) by sequential PCR and cloning, and its multispecificity was experimentally validated. Application of the technique to measurement of transcriptional levels of MMPs and TIMPs in cultured human endometrial stromal cells provided support to the hypothesis that progesterone withdrawal alters the ratio of MMPs to TIMPs in favor of MMPs. This Q-RT-PCR method is a relatively simple, highly specific and nonradioactive procedure and is widely applicable.

Base Sequence↗