Application of interpolation methodology with dynamical constraint to the suspended particulate matter in the Liaodong Bay

IntroductionSuspended Particulate Matter (SPM) influences the primary production and the distributions of pollutants in the ocean. Besides, the regulation mechanisms of SPM in the Liaodong Bay were complicated.MethodTo analyze the distributions and influencing factors of SPM, based on the adjoint assimilation method, an interpolation method with dynamical constraint was established in the Liaodong Bay.ResultIn two ideal experiments, the cost function, Mean Absolute Error (MAE) and Normalized Mean Error (NME) all had reduced by more than 90%, which proved the accuracy of the interpolation method. Based on conventional observations of SPM, the distributions of dynamically constrained, Kriging and radial basis function (RBF) interpolations in March, May, August and October of 2015 were obtained.DiscussionThe cross-validation was carried out to compare the dynamically constrained interpolation and the unconstrained interpolations. Among seven unconstrained interpolation methods, the averaged MAE of RBF interpolation was the lowest, which was 10.976 mg/L. The averaged MAE of dynamically constrained interpolation was 7.703 mg/L, reduced by 29.8% compared with the RBF interpolation. It was indicated that RBF interpolation was the most accurate among the seven unconstrained interpolations and dynamically constrained interpolation was more accurate than unconstrained interpolations at the observation stations. The distributions of dynamically constrained and RBF interpolations were compared with Korean Geostationary Ocean Color Imager (GOCI) satellite-derived distributions of SPM concentrations in the Liaodong Bay. Fully considering the influences of the hydrodynamic processes, the dynamically constrained interpolation provided distributions more consistent with the satellite-derived distributions. However, due to the lack of observations in some areas and ignoring the influences of currents, some high values of SPM concentration were not captured by the distributions of RBF interpolation. Moreover, in accordance with the results of dynamically constrained interpolation, it was found that the SPM concentrations in the bay were affected by the SPM discharge from the Liao River Basin

Construction of a digital fetus library for radiation dosimetry

Purpose: Accurate estimations of fetal absorbed dose and radiation risks are crucial for radiation protection and important for radiological imaging research owing to the high radiosensitivity of the fetus. Computational anthropomorphic models have been widely used in patient-specific radiation dosimetry calculations. In this work, we aim to build the first digital fetal library for more reliable and accurate radiation dosimetry studies. Acquisition and validation methods: Computed tomography (CT) images of abdominal and pelvic regions of 46 pregnant females were segmented by experienced medical physicists. The segmented tissues/organs include the body contour, skeleton, uterus, liver, kidney, intestine, stomach, lung, bladder, gall bladder, spleen, and pancreas for maternal body, and placenta, amniotic fluid, fetal body, fetal brain, and fetal skeleton. Nonuniform rational B-spline (NURBS) surfaces of each identified region was constructed manually using 3D modeling software. The Hounsfield unit values of each identified organs were gathered from CT images of pregnant patients and converted to tissue density. Organ volumes were further adjusted according to reference measurements for the developing fetus recommended by the World Health Organization (WHO) and International Commission on Radiological Protection. A series of anatomical parameters, including femur length, humerus length, biparietal diameter, abdominal circumference (FAC), and head circumference, were measured and compared with WHO recommendations. Data format and usage notes: The first fetal patient-specific model library was developed with the anatomical characteristics of each model derived from the corresponding patient whose gestational age varies between 8 and 35 weeks. Voxelized models are represented in the form of MCNP matrix input files representing the three-dimensional model of the fetus. The size distributions of each model are also provided in text files. All data are stored on Zenodo and are publicly accessible on the following link: https://zenodo.org/record/6471884. Potential applications: The constructed fetal models and maternal anatomical characteristics are consistent with the corresponding patients. The resulting computational fetus could be used in radiation dosimetry studies to improve the reliability of fetal dosimetry and radiation risks assessment. The advantages of NURBS surfaces in terms of adapting fetal postures and positions enable us to adequately assess their impact on radiation dosimetry calculations

The role of heparan sulfate maturation in cancer: A focus on the 3O-sulfation and the enigmatic 3O-sulfotransferases (HS3STs)

Heparansulfate (HS) modifications are master regulators of the cross-talk between cell and matrix and modulate the biological activity of an array of HS binding proteins, including growth factors and chemokines, morphogens and immunity cell receptors. This review will highlight the importance of HS maturation mediated by N-deactetylase/sulfotransferases, 2O- and 6O-sulfotransferases in cancer biology, and will focus on the 3O-sulfotransferases and on the terminal, rare 3O-sulfation, and their important but still enigmatic impact in cancer progression. The review will also discuss the molecular mechanisms of action of these HS modifications with regards to ligand interactions and signaling in the cancer process and their clinical significance

Effects of cyclic mechanical stretch on thrombin generation at the surface of rat vascular smooth muscle cells

Les cellules musculaires lisses (CML) vasculaires les composants cellulaires principaux de la paroi artérielle, sont exposées constamment aux contraintes mécaniques. Les contraintes mécaniques cycliques régulent de nombreuses fonctions des CML vasculaires via les intégrines. Parmi les intégrines, l'[alpha]v[gamma]3 est non seulement un mécano-transducteur mais aussi le récepteur de la prothrombine à la surface des CML. L?activation de l'intégrine [alpha]v[gamma]3 par les contraintes mécaniques pourrait favoriser l'adhésion des CML à la prothrombine et aussi accélérer la génération de thrombine à la surface des CML. Pour vérifier cette hypothèse, nous avons étudié l'effet des contraintes mécaniques sur la génération de thrombine par les CML et identifié les voies de la signalisation impliquées. Nous avons utilisé un modèle de Flexcell utilisant les CML aortiques de rat, soumises à un étirement cyclique (10%, 1Hz). L'exposition à l'étirement cyclique pendant 1h et 6h induit un phénotype de différenciation et non-apoptotique des CML et une augmentation de l'expression de l'intégrine [alpha]v[gamma]3. Il y a aussi une augmentation de la phosphorylation de Src, FAK, AKT de façon temps dépendant et une augmentation de la phosphorylation de l'ILK à 15 min et du clivage de taline de 5 à 60 min. L'étirement cyclique augmente l'adhésion des CML à la prothrombine et la génération de thrombine avec un effet maximum à 6h de 67% et 30% respectivement. Le peptide mimétique de l'intégrine [alpha]v[gamma]3 (cRGDPV) et le siARN [alpha]v bloquent tous les effets de l'étirement cyclique sur les CML. Le siARN taline inhibe l'expression de la sous-unité [alpha]v et également la phosphorylation de Src, AKT et ILK. Le siARN ILK n'a pas d'effet sur l'expression de l'[alpha]v mais inhibe la phosphorylation d'AKT et le clivage de taline à 6h de l'étirement cyclique. Ainsi, l'étirement cyclique induit une plus forte génération de thrombine par les CML vasculaires via l'activation des voies de signalisation dépendante de l'[alpha]v[gamma]3. Cette étude suggère que la génération de thrombine intravasculaire peut être régulée par des antagonistes de l'intégrine [alpha]v[gamma]3 et peut devenir une nouvelle cible thérapeutique chez les patients avec une pression pulsée élevéeVascular smooth muscle cells (SMC), the main cellular components of the arterial wall, are constantly exposed to mechanical stretch. Cyclic mechanical stress regulates many functions of vascular SMC via integrins. Among the integrins, [alpha]v[gamma]3 is not only a mechanotransducer but also the receptor of prothrombin in the vascular SMC. Activation of integrin [alpha]v[gamma]3 by mechanical stretch may promote SMC adhesion to prothrombin and also accelerate thrombin generation on the surface of SMC. To test this hypothesis, we have studied the effect of mechanical stretch on the generation of thrombin by SMC and identified possible signaling pathway involved. We used a Flexcell model using rat aortic SMC subjected to cyclic stretch (10%, 1Hz). Exposure to cyclic stretch for 1h and 6h induced a phenotype of differentiation and non-apoptosis of SMC and an increased expression of integrin [alpha]v[gamma]3. There was also an increase in phosphorylation of Src, FAK, and AKT in a time dependent manner, increased phosphorylation of ILK at 15min and the cleavage of talin from 5 to 60min. Cyclic stretch increased the adhesion of prothrombin to the SMC, and thrombin generation with a maximum effect of 67% and 30% respectively. A peptide mimetic of integrin [alpha]v[gamma]3 (cRGDPV) and [alpha]v siRNA both blocked all the effects of cyclic stretch on SMC. A talin siRNA inhibited the expression of [alpha]v and the phosphorylation of Src, AKT and ILK. An ILK siRNA has no effect on the expression of [alpha]v but inhibited the phosphorylation of AKT and the cleavage of talin at 6h of stretch. Thus, cyclic stretch induced a higher thrombin generation by vascular SMC via activation of signaling pathways dependant on [alpha]v[gamma]3. This study suggests that intravascular thrombin generation can be regulated by antagonists of integrin [alpha]v[gamma]3 and can become a new therapeutic target for the patients with a high pulse pressur

Effets des contraintes mécaniques cycliques sur la génération de thrombine à la surface des cellules musculaires lisses de rat

Les cellules musculaires lisses (CML) vasculaires les composants cellulaires principaux de la paroi artérielle, sont exposées constamment aux contraintes mécaniques. Les contraintes mécaniques cycliques régulent de nombreuses fonctions des CML vasculaires via les intégrines. Parmi les intégrines, l'[alpha]v[gamma]3 est non seulement un mécano-transducteur mais aussi le récepteur de la prothrombine à la surface des CML. L?activation de l'intégrine [alpha]v[gamma]3 par les contraintes mécaniques pourrait favoriser l'adhésion des CML à la prothrombine et aussi accélérer la génération de thrombine à la surface des CML. Pour vérifier cette hypothèse, nous avons étudié l'effet des contraintes mécaniques sur la génération de thrombine par les CML et identifié les voies de la signalisation impliquées. Nous avons utilisé un modèle de Flexcell utilisant les CML aortiques de rat, soumises à un étirement cyclique (10%, 1Hz). L'exposition à l'étirement cyclique pendant 1h et 6h induit un phénotype de différenciation et non-apoptotique des CML et une augmentation de l'expression de l'intégrine [alpha]v[gamma]3. Il y a aussi une augmentation de la phosphorylation de Src, FAK, AKT de façon temps dépendant et une augmentation de la phosphorylation de l'ILK à 15 min et du clivage de taline de 5 à 60 min. L'étirement cyclique augmente l'adhésion des CML à la prothrombine et la génération de thrombine avec un effet maximum à 6h de 67% et 30% respectivement. Le peptide mimétique de l'intégrine [alpha]v[gamma]3 (cRGDPV) et le siARN [alpha]v bloquent tous les effets de l'étirement cyclique sur les CML. Le siARN taline inhibe l'expression de la sous-unité [alpha]v et également la phosphorylation de Src, AKT et ILK. Le siARN ILK n'a pas d'effet sur l'expression de l'[alpha]v mais inhibe la phosphorylation d'AKT et le clivage de taline à 6h de l'étirement cyclique. Ainsi, l'étirement cyclique induit une plus forte génération de thrombine par les CML vasculaires via l'activation des voies de signalisation dépendante de l'[alpha]v[gamma]3. Cette étude suggère que la génération de thrombine intravasculaire peut être régulée par des antagonistes de l'intégrine [alpha]v[gamma]3 et peut devenir une nouvelle cible thérapeutique chez les patients avec une pression pulsée élevéeVascular smooth muscle cells (SMC), the main cellular components of the arterial wall, are constantly exposed to mechanical stretch. Cyclic mechanical stress regulates many functions of vascular SMC via integrins. Among the integrins, [alpha]v[gamma]3 is not only a mechanotransducer but also the receptor of prothrombin in the vascular SMC. Activation of integrin [alpha]v[gamma]3 by mechanical stretch may promote SMC adhesion to prothrombin and also accelerate thrombin generation on the surface of SMC. To test this hypothesis, we have studied the effect of mechanical stretch on the generation of thrombin by SMC and identified possible signaling pathway involved. We used a Flexcell model using rat aortic SMC subjected to cyclic stretch (10%, 1Hz). Exposure to cyclic stretch for 1h and 6h induced a phenotype of differentiation and non-apoptosis of SMC and an increased expression of integrin [alpha]v[gamma]3. There was also an increase in phosphorylation of Src, FAK, and AKT in a time dependent manner, increased phosphorylation of ILK at 15min and the cleavage of talin from 5 to 60min. Cyclic stretch increased the adhesion of prothrombin to the SMC, and thrombin generation with a maximum effect of 67% and 30% respectively. A peptide mimetic of integrin [alpha]v[gamma]3 (cRGDPV) and [alpha]v siRNA both blocked all the effects of cyclic stretch on SMC. A talin siRNA inhibited the expression of [alpha]v and the phosphorylation of Src, AKT and ILK. An ILK siRNA has no effect on the expression of [alpha]v but inhibited the phosphorylation of AKT and the cleavage of talin at 6h of stretch. Thus, cyclic stretch induced a higher thrombin generation by vascular SMC via activation of signaling pathways dependant on [alpha]v[gamma]3. This study suggests that intravascular thrombin generation can be regulated by antagonists of integrin [alpha]v[gamma]3 and can become a new therapeutic target for the patients with a high pulse pressureMETZ-SCD (574632105) / SudocNANCY1-Bib. numérique (543959902) / SudocNANCY2-Bibliotheque electronique (543959901) / SudocNANCY-INPL-Bib. électronique (545479901) / SudocSudocFranceF

Fast genetic algorithm for roundness evaluation by the minimum zone tolerance (MZT) method

According to ISO 1101, “A geometrical tolerance applied to a feature defines the tolerance zone within which that feature shall be contained”. The main goal of the minimum zone tolerance (MZT) method is to achieve the best estimation of the roundness error, but it is computationally intensive. This paper describes the application of a genetic algorithm (GA) to minimize the computation time in the evaluation of CMM roundness errors of a large cloud of sampled points. Computational experiments have shown that by selecting the optimal GA parameters, namely a combination of the five genetic parameters related to population size, crossover, mutation, stop condition, and search space, the computation time can be reduced by up to one order of magnitude, allowing real-time operation. Optimization has been tested using seven CMM samples, obtained from different machining features. The performance of the optimized algorithm has been validated using four benchmark samples from the literature and with certified samples

HaloTag is an effective expression and solubilisation fusion partner for a range of fibroblast growth factors

The production of recombinant proteins such as the fibroblast growth factors (FGFs) is the key to establishing their function in cell communication. The production of recombinant FGFs in E. coli is limited, however, due to expression and solubility problems. HaloTag has been used as a fusion protein to introduce a genetically-encoded means for chemical conjugation of probes. We have expressed 11 FGF proteins with an N-terminal HaloTag, followed by a tobacco etch virus (TEV) protease cleavage site to allow release of the FGF protein. These were purified by heparin-affinity chromatography, and in some instances by further ion-exchange chromatography. It was found that HaloTag did not adversely affect the expression of FGF1 and FGF10, both of which expressed well as soluble proteins. The N-terminal HaloTag fusion was found to enhance the expression and yield of FGF2, FGF3 and FGF7. Moreover, whereas FGF6, FGF8, FGF16, FGF17, FGF20 and FGF22 were only expressed as insoluble proteins, their N-terminal HaloTag fusion counterparts (Halo-FGFs) were soluble, and could be successfully purified. However, cleavage of Halo-FGF6, -FGF8 and -FGF22 with TEV resulted in aggregation of the FGF protein. Measurement of phosphorylation of p42/44 mitogen-activated protein kinase and of cell growth demonstrated that the HaloTag fusion proteins were biologically active. Thus, HaloTag provides a means to enhance the expression of soluble recombinant proteins, in addition to providing a chemical genetics route for covalent tagging of proteins

Cyclic stretch-induced thrombin generation by rat vascular smooth muscle cells is mediated by the integrin alpha(v)beta(3) pathway

International audienceVascular smooth muscle cell (VSMC) phenotypic modulation plays a pivotal role in atherothrombotic diseases. Thrombin generation at the surface of VSMCs and activation of integrin mechanotransduction pathways represent potential mechanisms. Here, we examine whether mechanical stretch increases thrombin generation on cultured rat aortic VSMCs. The integrin (v3) antagonist peptide (cRGDPV) dose-dependently decreased thrombin generation without stretch. Static stretch (5, 1 Hz) failed to modify the thrombin-forming capacity of VSMCs, whereas 10 cyclic stretch during 60 and 360 min enhanced integrin (v3) expression and thrombin generation at the surface of VSMCs by 30 without inducing apoptosis. Cyclic stretch also stimulated Src phosphorylation, cleavage of talin, and binding of prothrombin to VSMCs. Upregulation of (v3) expression, Src phosphorylation, and enhanced thrombin generation by cyclic stretch were abolished by cRGDPV and silencing RNA (siRNA) against (v) as well as by selective inhibition of integrin (v3) inside-out signalling by a talin-siRNA. Complete abolition of stretch-induced VSMC-supported thrombin generation by the RGT peptide, which disrupts the interaction of Src with the (3) cytoplasmic tail, demonstrates the link between outside-in pathways involving (3)-Src interaction and thrombin activity dependent on inside-out signalling. These data show that the contribution of cyclic stretch to VSMC-supported thrombin generation is driven by the integrin (v3) signalling pathway and suggest a role for pulsatility-induced intramural thrombin in VSMC-dependent vascular remodelling

Integrated Metabolomics and Transcriptomics Analyses Reveal the Metabolic Differences and Molecular Basis of Nutritional Quality in Landraces and Cultivated Rice

Rice (Oryza sativa L.) is one of the most globally important crops, nutritionally and economically. Therefore, analyzing the genetic basis of its nutritional quality is a paramount prerequisite for cultivating new varieties with increased nutritional health. To systematically compare the nutritional quality differences between landraces and cultivated rice, and to mine key genes that determine the specific nutritional traits of landraces, a seed metabolome database of 985 nutritional metabolites covering amino acids, flavonoids, anthocyanins, and vitamins by a widely targeted metabolomic approach with 114 rice varieties (35 landraces and 79 cultivars) was established. To further reveal the molecular mechanism of the metabolic differences in landrace and cultivated rice seeds, four cultivars and six landrace seeds were selected for transcriptome and metabolome analysis during germination, respectively. The integrated analysis compared the metabolic profiles and transcriptomes of different types of rice, identifying 358 differentially accumulated metabolites (DAMs) and 1982 differentially expressed genes (DEGs), establishing a metabolite–gene correlation network. A PCA revealed anthocyanins, flavonoids, and lipids as the central differential nutritional metabolites between landraces and cultivated rice. The metabolite–gene correlation network was used to screen out 20 candidate genes postulated to be involved in the structural modification of anthocyanins. Five glycosyltransferases were verified to catalyze the glycosylation of anthocyanins by in vitro enzyme activity experiments. At the same time, the different mechanisms of the anthocyanin synthesis pathway and structural diversity in landrace and cultivated rice were systematically analyzed, providing new insights for the improvement and utilization of the nutritional quality of rice landrace varieties