As a building material with economic potential and various beneficial properties, glass fiber reinforced concrete (GRC) has been rapidly promoted and applied in the field of civil construction. The ...coefficient of thermal expansion (CTE) of fiber-reinforced composites plays a crucial role in the design and analysis of such composites. Therefore, the thermal expansion coefficient of glass fiber reinforced concrete is the focus of this paper. A micromechanics model based on the Mori–Tanaka method is proposed to predict the overall thermal expansion coefficient of GRC. The model considers concrete as a two-phase composite material composed of cement mortar and aggregate. In the derivation process, concrete is treated as the equivalent matrix while glass fiber is treated as the inclusion phase. The present analysis takes into account the effects of glass fiber aspect ratio and reinforcement direction, as well as the volume fractions of aggregate and glass fiber. It is found that the glass fiber aspect ratio and reinforcement direction have a significant effect on the thermal expansion coefficient of concrete. The advantage of this model is that it provides a simple and accurate approach for predicting the CTE of glass fiber reinforced concrete. The developed model is validated by comparison with theoretical and experimental data in the literature.
This article reviews the regulation of production of RBCs at several levels. We focus on the regulated expansion of burst-forming unit-erythroid erythroid progenitors by glucocorticoids and other ...factors that occur during chronic anemia, inflammation, and other conditions of stress. We also highlight the rapid production of RBCs by the coordinated regulation of terminal proliferation and differentiation of committed erythroid colony-forming unit-erythroid progenitors by external signals, such as erythropoietin and adhesion to a fibronectin matrix. We discuss the complex intracellular networks of coordinated gene regulation by transcription factors, chromatin modifiers, and miRNAs that regulate the different stages of erythropoiesis.
The objective of this paper is to discuss the influence of geometric parameters on the performance of the rotational hydrodynamic cavitation reactor (RHCR) using numerical method. The novel RHCR is ...implemented by modifying a centrifugal impeller into a new one using the annular slit constriction (ASC) with circumferentially distributed blind holes. The cavitation intensity and cavitation generation rate are selected to evaluate the cavitation performance, the head is used to assess conveying performance, and the entropy generation theory is used to evaluate the energy loss in the impeller. The effect of the axial width, radial length and radial position of the ASC on the cavitating flow of the RHCR is investigated by CFD method. The results indicate that three patterns of cavitation are induced in the RHCR, including separation cavitation, vortex cavitation and shear cavitation. The axial width, radial length and radial position of the ASC are the important geometric parameter that affect the performance of the RHCR. A small width is superior to a large width in terms of cavitation performance, although the conveying performance suffers as a result. The energy loss in the impeller initially increases and then decreases as the width decreases. Both a reduction in radial length and radial position leads to higher cavitation and conveying capacity, accompanying slight increase in energy loss. Compared to the original model, the RHCR with an axial width of 3 mm, a radial length of 17 mm, and a radial position of 0.541 achieves the highest performance.
FGPMs (functionally gradient porous materials) can satisfy multifold functional constraints with minimizing weights as they are advanced composite materials showing hierarchical mechanical ...properties. However, tailoring the graded relative elasticity distribution of the FGPMs according to demands is still a big trouble, especially for the FGPMs with complex interior structures. In this context, this paper proposes an improved FGPMs design method for tailoring the graded relative elasticity field with stochastic Voronoi structures, which are driven by the FEA (finite element analysis) results. Firstly, a kind of open-cell porous structure is built for FGPMs based on 3D Voronoi diagrams and implicit surfaces. An external frame is generated outside the Voronoi structure to enhance the modeling adaptability and keep geometric and mechanical continuity. Then, two mapping models are established for tailoring the elasticity fields of the FGPMs. One is from the relative elasticity field to the relative density field based on Ashby-Gibson model, wherein, the relative elasticity field is obtained from the FEA results. The other one is from the obtained relative density field to the Voronoi site density field that drives the generation of the open-cell Voronoi porous structure. Finally, the proposed method is experimentally and numerically validated. The results show that both the geometric modeling ability and the elasticity tailoring accuracy are superior, and the FGPMs produced by our method have better mechanical performance compared to other FGPMs.
Intelligent evolutionary algorithms have been widely used to solve large-scale, complex global optimization problems. Co-evolutionary algorithm (CEA), cultural algorithm (CA), and particle swarm ...optimization (PSO) are all promising methods in the field of intelligent computation. In this paper, a hybrid co-evolutionary cultural algorithm based on particle swarm optimization (CECBPSO) is proposed. In CECBPSO, a novel space called shared global belief space (SGBS) is introduced into the co-evolutionary mechanism, and a new co-evolutionary cultural framework is built. Through the synergistic mechanism, the algorithm has higher probability of avoiding local optima and the whole swarm can find global optima more quickly. Factorial Design (FD) approach is used in this paper in order to get a guideline on how to tune the designed parameters in CECBPSO. Extensive computational studies are also carried out to evaluate the performance of CECBPSO on thirteen benchmark functions and three real-life optimization problems. The results show that the proposed algorithm has superior performance to other compared algorithms in terms of accuracy and convergence speed, especially on high-dimensional problems.
Cancer cells rely on altered metabolism to support abnormal proliferation. We performed a CRISPR/Cas9 functional genomic screen targeting metabolic enzymes and identified PDXK—an enzyme that produces ...pyridoxal phosphate (PLP) from vitamin B6—as an acute myeloid leukemia (AML)-selective dependency. PDXK kinase activity is required for PLP production and AML cell proliferation, and pharmacological blockade of the vitamin B6 pathway at both PDXK and PLP levels recapitulated PDXK disruption effects. PDXK disruption reduced intracellular concentrations of key metabolites needed for cell division. Furthermore, disruption of PLP-dependent enzymes ODC1 or GOT2 selectively inhibited AML cell proliferation and their downstream products partially rescued PDXK disruption induced proliferation blockage. Our work identifies the vitamin B6 pathway as a pharmacologically actionable dependency in AML.
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•CRISPR/Cas9 screen identifies PDXK as an AML selective metabolic dependency•PDXK kinase activity and PLP are selectively required for leukemic cell proliferation•PLP-dependent enzymes ODC1 and GOT2 selectively support leukemic cell proliferation•The vitamin B6 pathway is a therapeutically actionable dependency in leukemia
In a CRISPR/Cas9 functional screen targeting metabolic enzymes, Chen et al. identify PDXK, which produces pyridoxal phosphate (PLP) from vitamin B6, as an AML dependency. PLP-dependent enzymes ODC1 and GOT2 support AML proliferation. Blockade of the vitamin B6 metabolic pathway exhibits anti-leukemic activity.
Stem cells and progenitors in many lineages undergo self-renewing divisions, but the extracellular and intracellular proteins that regulate this process are largely unknown. Glucocorticoids stimulate ...red blood cell formation by promoting self-renewal of early burst-forming unit-erythroid (BFU-E) progenitors. Here we show that the RNA-binding protein ZFP36L2 is a transcriptional target of the glucocorticoid receptor (GR) in BFU-Es and is required for BFU-E self-renewal. ZFP36L2 is normally downregulated during erythroid differentiation from the BFU-E stage, but its expression is maintained by all tested GR agonists that stimulate BFU-E self-renewal, and the GR binds to several potential enhancer regions of ZFP36L2. Knockdown of ZFP36L2 in cultured BFU-E cells did not affect the rate of cell division but disrupted glucocorticoid-induced BFU-E self-renewal, and knockdown of ZFP36L2 in transplanted erythroid progenitors prevented expansion of erythroid lineage progenitors normally seen following induction of anaemia by phenylhydrazine treatment. ZFP36L2 preferentially binds to messenger RNAs that are induced or maintained at high expression levels during terminal erythroid differentiation and negatively regulates their expression levels. ZFP36L2 therefore functions as part of a molecular switch promoting BFU-E self-renewal and a subsequent increase in the total numbers of colony-forming unit-erythroid (CFU-E) progenitors and erythroid cells that are generated.
Using RNA-seq technology, we found that the majority of microRNAs (miRNAs) present in CFU-E erythroid progenitors are down-regulated during terminal erythroid differentiation. Of the developmentally ...down-regulated miRNAs, ectopic overexpression of miR-191 blocks erythroid enucleation but has minor effects on proliferation and differentiation. We identified two erythroid-enriched and developmentally up-regulated genes, Riok3 and Mxi1, as direct targets of miR-191. Knockdown of either Riok3 or Mxi1 blocks enucleation, and either physiological overexpression of miR-191 or knockdown of Riok3 or Mxi1 blocks chromatin condensation. Thus, down-regulation of miR-191 is essential for erythroid chromatin condensation and enucleation by allowing up-regulation of Riok3 and Mxi1.
The production and storage of liquefied petroleum gas (LPG) is gradually becoming larger and more intensive, which greatly increases the risk of the domino effect of an explosion accident in a ...storage tank area while improving production and management efficiency. This paper describes the construction of the domino effect scene of an explosion accident in an LPG storage tank area, the analysis of the characteristics of the LPG tank explosion shock wave and the target storage tank failure, and the creation of an ANSYS numerical model to derive the development trend and expansion law of the domino accident in the LPG storage tank area. The research showed that: 400 m3 tank T1 explosion shock waves spread to T2, T4, T5, T3, and T6, and the tank overpressures of 303 kPa, 303 kPa, 172 kPa, 81 kPa, and 61 kPa respectively. The critical values of the target storage tank failure overpressure-range threshold were 70 kPa and 60 m. After the explosion of the initial unit T1 tank, at 38 ms, the T2 and T4 storage tanks failed and exploded; at 56 ms, the T5 storage tank exploded for the third time; at 82 ms, the T3 storage tank exploded for the fourth time; and at 102 ms, the T6 storage tank exploded for the fifth time. With the increase of explosion sources, the failure overpressure of the target storage tank increased, and the interval between explosions continuously shortened, which reflected the expansion effect of the domino accident. The domino accident situation deduction in the LPG storage tank area provided a scientific basis for the safety layout, accident prevention and control, emergency rescue, and management of a chemical industry park.
•The explosion of the 400 m3 LPG tank was sufficient to cause the tank to fail in the mid near field(10–25 m).•The failure of the target storage tank in the middle and far field is greatly affected by two or more explosion sources.•The maximum superimposed shock wave propagates along the line direction of the source of the explosion.•With the increase of explosion sources, the overpressure of storage tank increases and explosion interval time decreases.
Backgrounds
Epidermal growth factor receptor (EGFR) mutation profiles play a vital role in treatment strategy decisions for non–small cell lung cancer (NSCLC). The purpose of this study was to ...evaluate the predictive efficacy of baseline
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F-FDG PET/CT-based radiomics analysis for EGFR mutation status, mutation site, and the survival benefit of targeted therapy.
Methods
A sum of 313 NSCLC patients with pre-treatment
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F-FDG PET/CT scans and genetic mutations detection were retrospectively studied. Clinical and PET metabolic parameters were incorporated into independent predictors of determining mutation status and mutation site. The dataset was randomly allocated into the training and the validation sets in a 7:3 ratio. Three-dimensional (3D) radiomics features were extracted from each PET- and CT-volume of interests (VOI) singularly, and then a radiomics signature (RS) associated with EGFR mutation profiles is built by feature selection. Three different prediction models based on support vector machine (SVM), decision tree (DT), and random forest (RF) classifiers were established. Furthermore, nomograms for estimation of overall survival (OS) and progression-free survival (PFS) were established by integrating PET/CT radiomics score (Rad-score), metabolic parameters, and clinical factors. Predictive performance was assessed by the receiver operating characteristic (ROC) analysis and the calibration curve analysis. The decision curve analysis (DCA) was applied to estimate and compare the clinical usefulness of nomograms.
Results
Three hundred thirteen NSCLC patients were classified into a training set (n=218) and a validation set (n=95). Multivariate analysis demonstrated that SUVmax and sex were independent indicators of EGFR mutation status and mutation site. Eight CT-derived RS, six PET-derived RS, and two clinical factors were retained to develop integrated models, which exhibited excellent ability to distinguish between EGFR wild type (EGFR-WT), EGFR 19 mutation type (EGFR-19-MT), and EGFR 21 mutation type (EGFR-21-MT). The SVM model outperformed the RF model and the DT model, yielding training area under the curves (AUC) of EGFR-WT, EGFR-19-WT, and EGFR-21-WT, with 0.881, 0.851, and 0.849, respectively, and validation AUCs of 0.926, 0.805 and 0.859, respectively. For prediction of OS, the integrated nomogram is superior to the clinical nomogram and the radiomics nomogram, with C-indexes of 0.80 in the training set and 0.83 in the validation set, respectively.
Conclusions
The PET/CT-based radiomics analysis might provide a novel approach to predict EGFR mutation status and mutation site in NSCLC patients and could serve as useful predictors for the patients’ survival outcome of targeted therapy in clinical practice.
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