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We report in this work a numerical analysis of the sloshing of a squared tank partially filled with a domestic vegetable oil. The tank is subject to controlled motions with a shake table. The free-surface evolution is captured using ultrasonic sensors and an image capturing method. Only confirmed data within the error range is reported. Filling depth, imposed amplitude and frequency effects on the sloshing wave pattern are specifically evaluated. The experiments also reveal the nonlinear wave behavior. The numerical model is based on a stabilized finite element method of the variational multi-scale type. The free-surface is captured using a level set technique developed to be used with adaptive meshes in Arbitrary Lagrangian–Eulerian framework. The numerical results are compared with the experiments for different sloshing conditions near the first sloshing mode. The simulations satisfactorily match the experiments, providing a reliable tool for the analysis of this kind of problems.

This paper investigates the accuracy of Reynolds-averaged Navier-Stokes (RANS) turbulence modelling applied to complex industrial applications. In the context of the increasing instability of the energy market, hydropower plants are frequently working at off-design parameters. Such operation conditions have a strong impact on the efficiency and life span of hydraulic turbines. Therefore, research is currently focused on improving the design and increasing the operating range of the turbines. Numerical simulations represent an accessible and cost efficient alternative to model testing. The presented test case is the Porjus U9 Kaplan turbine model operated at best efficiency point (BEP). Both steady and unsteady numerical simulations are carried out using different turbulence models: k-epsilon, RNG k-epsilon and k-omega Shear Stress Transport (SST). The curvature correction method applied to the SST turbulence model is also evaluated showing nearly no sensitivity to the different values of the production correction coefficient Cscale. The simulations are validated against measurements performed in the turbine runner and draft tube. The numerical results are in good agreement with the experimental time-dependent velocity profiles. The advantages and limitations of RANS modelling are discussed. The most accurate results were provided by the simulations using the k-epsilon and the SST-CC turbulence models but very small differences were obtained between the different tested models. The precision of the numerical simulations decreased towards the outlet of the computational domain. In a companion paper, the pressure profiles obtained numerically are investigated and compared to experimental data.

In this paper, a simplified model of a Polymer Electrolyte Membrane (PEM) water electrolysis cell is presented and compared with experimental data at 60 °C and 80 °C. The model utilizes the same modelling approach used in previous work where the electrolyzer cell is divided in four subsections: cathode, anode, membrane and voltage. The model of the electrodes includes key electrochemical reactions and gas transport mechanism (i.e., H2, O2 and H2O) whereas the model of the membrane includes physical mechanisms such as water diffusion, electro osmotic drag and hydraulic pressure. Voltage was modelled including main overpotentials (i.e., activation, ohmic, concentration). First and second law efficiencies were defined. Key empirical parameters depending on temperature were identified in the activation and ohmic overpotentials. The electrodes reference exchange current densities and change transfer coefficients were related to activation overpotentials whereas hydrogen ion diffusion to Ohmic overvoltages. These model parameters were empirically fitted so that polarization curve obtained by the model predicted well the voltage at different current found by the experimental results. Finally, from the efficiency calculation, it was shown that at low current densities the electrolyzer cell absorbs heat from the surroundings. The model is not able to describe the transients involved during the cell electrochemical reactions, however these processes are assumed relatively fast. For this reason, the model can be implemented in system dynamic modelling for hydrogen production and storage where components dynamic is generally slower compared to the cell electrochemical reactions dynamics.

MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression in both animals and plants. By pairing to microRNA responsive elements (mREs) on target mRNAs, miRNAs play gene-regulatory roles, producing remarkable changes in several physiological and pathological processes. Thus, the identification of miRNA-mRNA target interactions is fundamental for discovering the regulatory network governed by miRNAs. The best way to achieve this goal is usually by computational prediction followed by experimental validation of these miRNA-mRNA interactions. This review summarizes the key strategies for miRNA target identification. Several tools for computational analysis exist, each with different approaches to predict miRNA targets, and their number is constantly increasing. The major algorithms available for this aim, including Machine Learning methods, are discussed, to provide practical tips for familiarizing with their assumptions and understanding how to interpret the results. Then, all the experimental procedures for verifying the authenticity of the identified miRNA-mRNA target pairs are described, including High-Throughput technologies, in order to find the best approach for miRNA validation. For each strategy, strengths and weaknesses are discussed, to enable users to evaluate and select the right approach for their interests.

Background Diabetic kidney disease (DKD) has been the leading cause of chronic kidney disease in developed countries. Evidence of the benefits of resveratrol (RES) for the treatment of DKD is accumulating. However, comprehensive therapeutic targets and underlying mechanisms through which RES exerts its effects against DKD are limited. Methods Drug targets of RES were obtained from Drugbank and SwissTargetPrediction Databases. Disease targets of DKD were obtained from DisGeNET, Genecards, and Therapeutic Target Database. Therapeutic targets for RES against DKD were identified by intersecting the drug targets and disease targets. GO functional enrichment analysis, KEGG pathway analysis, and disease association analysis were performed using the DAVID database and visualized by Cytoscape software. Molecular docking validation of the binding capacity between RES and targets was performed by UCSF Chimera software and SwissDock webserver. The high glucose (HG)-induced podocyte injury model, RT-qPCR, and western blot were used to verify the reliability of the effects of RES on target proteins. Results After the intersection of the 86 drug targets and 566 disease targets, 25 therapeutic targets for RES against DKD were obtained. And the target proteins were classified into 6 functional categories. A total of 11 cellular components terms and 27 diseases, and the top 20 enriched biological processes, molecular functions, and KEGG pathways potentially involved in the RES action against DKD were recorded. Molecular docking studies showed that RES had a strong binding affinity toward PPARA, ESR1, SLC2A1, SHBG, AR, AKR1B1, PPARG, IGF1R, RELA, PIK3CA, MMP9, AKT1, INSR, MMP2, TTR, and CYP2C9 domains. The HG-induced podocyte injury model was successfully constructed and validated by RT-qPCR and western blot. RES treatment was able to reverse the abnormal gene expression of PPARA, SHBG, AKR1B1, PPARG, IGF1R, MMP9, AKT1, and INSR. Conclusions RES may target PPARA, SHBG, AKR1B1, PPARG, IGF1R, MMP9, AKT1, and INSR domains to act as a therapeutic agent for DKD. These findings comprehensively reveal the potential therapeutic targets for RES against DKD and provide theoretical bases for the clinical application of RES in the treatment of DKD.

Structural resolution of protein interactions enables mechanistic and functional studies as well as interpretation of disease variants. However, structural data is still missing for most protein interactions because we lack computational and experimental tools at scale. This is particularly true for interactions mediated by short linear motifs occurring in disordered regions of proteins. We find that AlphaFold-Multimer predicts with high sensitivity but limited specificity structures of domain-motif interactions when using small protein fragments as input. Sensitivity decreased substantially when using long protein fragments or full length proteins. We delineated a protein fragmentation strategy particularly suited for the prediction of domain-motif interfaces and applied it to interactions between human proteins associated with neurodevelopmental disorders. This enabled the prediction of highly confident and likely disease-related novel interfaces, which we further experimentally corroborated for FBXO23-STX1B, STX1B-VAMP2, ESRRG-PSMC5, PEX3-PEX19, PEX3-PEX16, and SNRPB-GIGYF1 providing novel molecular insights for diverse biological processes. Our work highlights exciting perspectives, but also reveals clear limitations and the need for future developments to maximize the power of Alphafold-Multimer for interface predictions. Synopsis Based on thorough benchmarking of AlphaFold-Multimer a strategy for structure prediction was developed and applied to 62 protein interactions linked to neurological disease. Six novel protein interfaces were further experimentally corroborated. AlphaFold-Multimer (AF) largely fails to predict structures of interacting proteins involving short linear motifs when using full length sequences. A prediction strategy was developed based on protein fragmentation, which boosts AF sensitivity at costs of specificity. Application of this strategy to 62 protein interactions linked to neurological disease resulted in 18 correct or likely correct structural models. Six novel protein interfaces were further supported by experiments. Based on thorough benchmarking of AlphaFold-Multimer a strategy for structure prediction was developed and applied to 62 protein interactions linked to neurological disease. Six novel protein interfaces were further experimentally corroborated.

In this work, the phase-field approach to fracture is extended to model fatigue failure in high- and low-cycle regime. The fracture energy degradation due to the repeated externally applied loads is introduced as a function of a local energy accumulation variable, which takes the structural loading history into account. To this end, a novel definition of the energy accumulation variable is proposed, allowing the fracture analysis at monotonic loading without the interference of the fatigue extension, thus making the framework generalised. Moreover, this definition includes the mean load influence of implicitly. The elastoplastic material model with the combined nonlinear isotropic and nonlinear kinematic hardening is introduced to account for cyclic plasticity. The ability of the proposed phenomenological approach to naturally recover main features of fatigue, including Paris law and Wöhler curve under different load ratios is presented through numerical examples and compared with experimental data from the author’s previous work. Physical interpretation of additional fatigue material parameter is explored through the parametric study.

Spatio-temporal fusion (STF) aims at fusing (temporally dense) coarse resolution images and (temporally sparse) fine resolution images to generate image series with adequate temporal and spatial resolution. In the last decade, STF has drawn a lot of attention and many STF methods have been developed. However, to date the STF domain still lacks benchmark datasets, which is a pressing issue that needs to be addressed in order to foster the development of this field. In this review, we provide (for the first time in the literature) a robust benchmark STF dataset that includes three important characteristics: (1) diversity of regions, (2) long timespan, and (3) challenging scenarios. We also provide a survey of highly representative STF techniques, along with a detailed quantitative and qualitative comparison of their performance with our newly presented benchmark dataset. The proposed dataset is public and available online.

In this paper, we review and connect the three essential conditions needed by the collapse model to achieve a complete and exact formulation, namely the theoretical, the experimental, and the ontological ones. These features correspond to the three parts of the paper. In any empirical science, the first two features are obviously connected but, as is well known, among the different formulations and interpretations of non-relativistic quantum mechanics, only collapse models, as the paper well illustrates with a richness of details, have experimental consequences. Finally, we show that a clarification of the ontological intimations of collapse models is needed for at least three reasons: (1) to respond to the indispensable task of answering the question ’what are collapse models (and in general any physical theory) about?’; (2) to achieve a deeper understanding of their different formulations; (3) to enlarge the panorama of possible readings of a theory, which historically has often played a fundamental heuristic role.

Background The remarkable growth of genome-wide association studies (GWAS) has created a critical need to experimentally validate the disease-associated variants, 90% of which involve non-coding variants. Methods To determine how the field is addressing this urgent need, we performed a comprehensive literature review identifying 36,676 articles. These were reduced to 1454 articles through a set of filters using natural language processing and ontology-based text-mining. This was followed by manual curation and cross-referencing against the GWAS catalog, yielding a final set of 286 articles. Results We identified 309 experimentally validated non-coding GWAS variants, regulating 252 genes across 130 human disease traits. These variants covered a variety of regulatory mechanisms. Interestingly, 70% (215/309) acted through cis-regulatory elements, with the remaining through promoters (22%, 70/309) or non-coding RNAs (8%, 24/309). Several validation approaches were utilized in these studies, including gene expression (n = 272), transcription factor binding (n = 175), reporter assays (n = 171), in vivo models (n = 104), genome editing (n = 96) and chromatin interaction (n = 33). Conclusions This review of the literature is the first to systematically evaluate the status and the landscape of experimentation being used to validate non-coding GWAS-identified variants. Our results clearly underscore the multifaceted approach needed for experimental validation, have practical implications on variant prioritization and considerations of target gene nomination. While the field has a long way to go to validate the thousands of GWAS associations, we show that progress is being made and provide exemplars of validation studies covering a wide variety of mechanisms, target genes, and disease areas.