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MicroRNAs (miRNAs), useful biomarkers for cancer diagnosis, play an important role in tumorigenesis and progression, but many of the current analysis methods can suffer from excessive protease dependence, being time-consuming and unsatisfactory performance. Therefore, a reliable sensing strategy for the protein-free, ultrasensitive analysis of tumor-associated miRNAs is desired. The proposed dual-walker biosensing strategy based on an entropy-driven catalytic (EDC) walker coupled with a smart-responsive DNAzyme walker was demonstrated for the dual-amplification detection of miRNA-21. Namely, the target miRNA-21 initiates the three-stranded substrate complex of the traditional EDC circuit to release the input trigger of the Dz walker, which recognizes the circular binding domain to restore the cleavage activity of the DzS-AuNP walker. The fluorescence signal continuously released from the AuNPs was recorded by a fluorescence reader for miRNA-21 sensing. The optimized dual-walker exhibited appreciable sensitivity with a detection limit of 70 fM, satisfactory flexibility, fine specificity and ideal stability for clinical serum sample assays. The proposed strategy may open a new avenue for the development of powerful DNA molecular tools for cancer diagnosis. • An entropy-driven catalytic walker switched on DNAzyme walker strategy is proposed. • This dual-walker strategy enables the ultrasensitive analysis of miRNA-21. • This strategy accelerates the signal transduction process and exhibits excellent stability. • The stable and self-locked dual-walker could reduce the background leakage. [ABSTRACT FROM AUTHOR]

• High-speed hail impact experiments are performed on TC4 titanium alloy plate. • The FEM is utilized to simulate the influence of various factors after validation. • The change of hail diameter and velocity has great effect on the response of the plate, and the impact position has little effect on it. • There is a power-law relationship between the impact peak force and the impact velocity with an index of 1.912. This work studied the dynamic response of hail impacting on TC4 titanium alloy plates under different influence factors. Experiments were performed according to China Civil Aviation Regulations Airworthiness Standards. The damage to the plate was recorded by in-situ cameras. The experimental results indicate that the greater the hail velocity, the more severe the damage to the titanium alloy plate. In the simulation, Smoothed Particle Hydrodynamics (SPH) method was used to model the hail. The reliability of numerical model was verified by the comparison with the test results of hail impact response. The numerical results show that the deformation of the plate increases as the impact angle and hail diameter increases. Moreover, the changes in impact angle and position will both alter the displacement and strain distribution within the plate. Through comparative analysis of the impact velocity, hail diameter, impact angle, and impact position on the impact force peak, plastic strain energy, and maximum kinetic energy of the plate, it is found that changes of hail diameter and velocity have great effect on the response of titanium alloy plate, and the impact position has little effect on it. There is a power-law relationship between the hail impact peak force and the hail velocity with an index of 1.912. [ABSTRACT FROM AUTHOR]

Autophagy is well-known to be a lysosome-mediated catabolic process for maintaining cellular and organismal homeostasis, which has been established with many links to a variety of human diseases. Compared with the therapeutic strategy for inhibiting autophagy, activating autophagy seems to be another promising therapeutic strategy in several contexts. Hitherto, mounting efforts have been made to discover potent and selective small-molecule activators of autophagy to potentially treat human diseases. Thus, in this perspective, we focus on summarizing the complicated relationships between defective autophagy and human diseases, and further discuss the updated progress of a series of small-molecule activators targeting autophagy in human diseases. Taken together, these inspiring findings would provide a clue on discovering more small-molecule activators of autophagy as targeted candidate drugs for potential therapeutic purposes. [Display omitted] • Chemical structures of some small-molecule activators of autophagy by targeting specific proteins. • The process of design and optimization is elaborated for the small-molecule activators based on the structure-guided design. • Targeting PPI or covalent ligand activation may be an alternative strategy for small-molecule activators of autophagy. • This article provides a promising therapeutic strategy that could theoretically act on different types of autophagy defects. [ABSTRACT FROM AUTHOR]

Mechanically-guided three-dimensional (3D) assembly of mesostructures through controlled compressive buckling represents a promising approach, because of the versatile applicability to a broad set of advanced materials, over length scales from sub-micrometers to centimeters. Based on this approach, a spatial variation of thickness in the initial 2D structures was demonstrated as an effective strategy to produce engineered folding deformations at regions with lower bending stiffness, thereby with an ability to enable autonomous origami assembly. The reliability of this strategy requires the development of a theoretical model as a design reference, such that targeted folding deformations can be achieved without inducing any structural failure. This work presents a finite-deformation model of controlled buckling in straight ribbons with engineered thickness reductions at two or three sites. A comparison of predicted maximum strains and deformed configurations to the finite element analyses (FEA) and experimental results elucidates the validity of the developed model. The results uncover the coupled effect of different geometric parameters on the maximum strain. For relative flexible creases that lead to evident folding deformations, the theoretical model gives approximate analytic solutions to the deformed configurations and maximum strain. Furthermore, the theoretical model was exploited in a design optimization to achieve highly sensitive rotatable micro-mirrors with a desired mechanical tunability of the optical transmittance. This study can be useful in the future designs of 2D precursor structures for the origami-inspired assembly of different 3D mesostructures and micro-devices. [ABSTRACT FROM AUTHOR]

Polyimide hollow fiber membrane module has been tested under low temperature for efficient CO 2 separation. Parametric study was carried out to evaluate separation performance of the designed cryogenic-membrane hybrid system. In detail, the effect of stage cut, feed pressure, operating temperature and CO 2 concentration on gas permeance, CO 2 /N 2 selectivity, CO 2 purity and recovery were investigated. The experimental results indicated that operating temperature played an important role in the separation performance. Reducing stage cut would result in the increase of permeance (up to 302 GPU), CO 2 /N 2 selectivity (up to 20) and CO 2 purity (up to 59%), especially under the low temperature (−20 °C). The variation of gas permeance depended on the competition between the compression and swelling effect of the free volume. When the operating temperature and feed pressure were set at −20 °C and 700 kPa, the CO 2 recovery could be improved to 93%. Although the permeance, CO 2 /N 2 selectivity and recovery adversely decreased with the increase of feed CO 2 concentration, the CO 2 purity could be increased to 40% with the feed pressure of 400 kPa. The cryogenic-membrane hybrid system presented a potential in enhancing the CO 2 removal efficiency. [ABSTRACT FROM AUTHOR]

Canonical interleukin-2 (IL-2) signaling via the high-affinity CD25-containing IL-2 receptor-Janus kinase (JAK)1,3-signal transducer and activator of transcription 5 (STAT5) pathway is essential for development and maintenance of CD4+CD25HiFoxp3+ regulatory T cells (Tregs) that support immune homeostasis. Here, we report that IL-2 signaling via an alternative CD25-chemokine receptor pathway promotes the suppressive function of Tregs. Using an antibody against CD25 that biases IL-2 signaling toward this alternative pathway, we establish that this pathway increases the suppressive activity of Tregs and ameliorates murine experimental autoimmune encephalomyelitis (EAE). Furthermore, heparan sulfate, an IL-2-binding element of cell surfaces and extracellular matrix, or an engineered IL-2 immunocytokine can also direct IL-2 signaling toward this alternative pathway. Overall, these data reveal a non-canonical mechanism for IL-2 signaling that promotes suppressive functions of Tregs, further elucidates how IL-2 supports immune homeostasis, and suggests approaches to promote or suppress Treg functions. [Display omitted] • IL-2 can signal via chemokine receptors (CRs) in addition to the βγ IL-2 receptors • An anti-CD25 induces a CD25-IL-2-CCR7 complex and enforces CR signaling • This non-canonical IL-2 signaling pathway promotes Tregs' suppressive function • A modified form of this anti-CD25 ameliorates experimental autoimmunity IL-2 shapes the immune response. Sun et al. report that IL-2 signaling via a CD25-chemokine receptor pathway promotes increased regulatory T cells' suppressive function. An anti-CD25 or heparan sulfate biases IL-2 signaling toward this chemokine receptor pathway, and administration of a modified form of this anti-CD25 ameliorates murine experimental autoimmune encephalomyelitis. [ABSTRACT FROM AUTHOR]

Lithographically defined interconnects with filamentary, serpentine configurations have been widely used in various forms of stretchable electronic devices, owing to the ultra-high stretchability that can be achieved and the relative simple geometry that facilitates the design and fabrication. Theoretical models of serpentine interconnects developed previously for predicting the performance of stretchability were mainly based on the theory of infinitesimal deformation. This assumption, however, does not hold for the interconnects that undergo large levels of deformations before the structural failure. Here, an analytic model of serpentine interconnects is developed starting from the finite deformation theory of planar, curved beams. Finite element analyses (FEA) of the serpentine interconnects with a wide range of geometric parameters were performed to validate the developed model. Comparisons of the predicted stretchability to the estimations of linear models provide quantitative insights into the effect of finite deformation. Both the theoretical and numerical results indicate that a considerable overestimation (e.g., >50% relatively) of the stretchability can be induced by the linear model for many representative shapes of serpentine interconnects. Furthermore, a simplified analytic solution of the stretchability is obtained by using an approximate model to characterize the nonlinear effect. The developed models can be used to facilitate the designs of serpentine interconnects in future applications. [ABSTRACT FROM AUTHOR]

The re-gasification process plays an important role in the liquefied natural gas (LNG) supply chain. The advantages of an intermediate fluid vaporizer (IFV) include the better energy efficiency, less sensitivity to ambient conditions and no icing or frosting problem. In this paper, the thermal design method has been established for the IFV when vaporizing the subcritical LNG. The typical heat transfer characteristics in the different sections and flow boiling zones have been predicted. The effects of the operating parameters such as the inlet mass flow rate and pressure of LNG and the inlet seawater temperature on the heat transfer coefficients and the required heat transfer areas of the thermolator, evaporator, condenser and the whole IFV have been investigated. The results indicate that the increase in the LNG pressure not only changes the heat transfer coefficient in each flow boiling zone but also influences the transition from one flow boiling zone to another, and ultimately leads to a profitless increase of the required heat transfer area of the condenser. The results reported here would provide insight into the vaporization process of subcritical LNG and give guidance to the potential design optimization of an IFV. [ABSTRACT FROM AUTHOR]

Abstract: High-temperature stress controlled tests for 1.25Cr0.5Mo steel were carried out at different loading conditions to investigate the fatigue–creep interaction behavior. Four fatigue–creep facture character maps have been established. It is found when the stress amplitude is less than the mean stress after a sort, drastic interactions between fatigue and creep will occur, the fracture life will decrease rapidly and the fracture ductility will reach its minimum. As the complex relationships between fracture life and its influencing factors can be well explained by the mean strain rate at half-life, which is considered as the main factor associated with the fracture life. Moreover, based on the ductility exhaustion theory and the effective stress concept, a new model for fatigue–creep life prediction under stress control is proposed. Most of the test data are predicted within a factor of ±×1.5, which is better than the frequency separation method (FS) and the strain energy frequency modified approach (SEFS). [Copyright &y& Elsevier]

Summary Leukocyte adhesion requires β 2 -integrin activation. Resting integrins exist in a bent-closed conformation—i.e., not extended (E−) and not high affinity (H−)—unable to bind ligand. Fully activated E+H+ integrin binds intercellular adhesion molecules (ICAMs) expressed on the opposing cell in trans. E−H− transitions to E+H+ through E+H− or through E−H+, which binds to ICAMs on the same cell in cis. Spatial patterning of activated integrins is thought to be required for effective arrest, but no high-resolution cell surface localization maps of activated integrins exist. Here, we developed Super-STORM by combining super-resolution microscopy with molecular modeling to precisely localize activated integrin molecules and identify the molecular patterns of activated integrins on primary human neutrophils. At the time of neutrophil arrest, E−H+ integrins face each other to form oriented (non-random) nanoclusters. To address the mechanism causing this pattern, we blocked integrin binding to ICAMs in cis , which significantly relieved the face-to-face orientation. Graphical Abstract Highlights • Super-resolution map of β 2 -integrin activation on human neutrophils during arrest • Developed Super-STORM to visualize single-integrin molecules and their conformation • High-affinity bent β 2 -integrin molecules face each other • The face-to-face pattern is held by in cis binding to ICAM dimers Fan et al. introduced STORM imaging to study β 2 -integrin activation in primary human neutrophils during arrest from rolling. Super-STORM further increases the resolution, revealing the spatial orientations and patterns of integrins. [ABSTRACT FROM AUTHOR]

• Proposed a Kirigami-based inverse design scheme applicable for mechanically guided assembly methods. • The effectiveness of the scheme is verified through the inverse design of 3D curved ribbons and 3D surfaces. • Based on the proposed inverse design scheme, a microneedle structure is conceptually designed and fabricated. The mechanically guided assembly method utilizes the compressive buckling behavior of thin-film structures to transform two-dimensional (2D) precursors into three-dimensional (3D) structures. Previous research has shown that by inverse designing thickness and width distributions in 2D precursors, various 3D surfaces with target geometries can be accurately assembled. However, the variation in thickness poses significant challenges for the fabrication of the 2D precursor, especially on a small scale. In this paper, we propose a Kirigami-based inverse design framework that utilizes pre-specified incision patterns as critical parameters to control the bending stiffness distribution of 2D precursors. This enables the fabrication of target 3D structures with constant thickness, which greatly simplifies the production of 2D precursors. By studying the deformation characteristics of beam models during pure bending, we have established an analytical relationship between incision patterns and bending stiffness distribution. To validate the effectiveness of our inverse design theory, we conducted a series of simulations and experiments on 3D structures, yielding favorable comparison results. Moreover, guided by this inverse design theory, we have developed a microneedle structure through conceptual design, demonstrating the capability of Kirigami patterns in the inverse design of complex 3D structures, and highlighting the potential application of our method in the biomedical field. [ABSTRACT FROM AUTHOR]

A three-dimensional transient computational fluid dynamics (CFD) model has been established for the simulations of supercritical heat transfer of real liquefied natural gas (LNG) mixture in a single tube and a tube bundle of an intermediate fluid vaporizer (IFV). The influence of chemical composition of LNG on the thermal performance has been analyzed. The results have also been compared with those obtained from the one-dimensional steady-state calculations using the distributed parameter model (DPM). It is found that the current DPM approach can give reasonable prediction accuracy for the thermal performance in the tube bundle but unsatisfactory prediction accuracy for that in a single tube as compared with the corresponding CFD data. As benchmarked against pure methane, the vaporization of an LNG containing about 90% (mole fraction) of methane would lead to an absolute deviation of 5.5 K in the outlet NG temperature and a maximum relative deviation of 11.4% in the tube side HTC in a bundle of about 816 U tubes at the inlet pressure of 12 MPa and mass flux of 200 kg·m −2 ·s −1 . It is concluded that the influence of LNG composition on the thermal performance should be taken into consideration in order to obtain an economic and reliable design of an IFV. [ABSTRACT FROM AUTHOR]

The corrosion fatigue behavior of FV520B steel in water and salt-spray environments at different temperatures is the focus of this study. Temperature has a significant effect on the fatigue behavior of FV520B steel in water and salt-spray environments, but has only a negligible effect in an air environment. Fatigue life decreases as temperature increases in water and salt-spray environments, and this trend is much more remarkable at a low stress amplitude level. As compared to air and water-spray, it was found that the chloride ion in salt-spray accelerated the fatigue damage of FV520B steel. Micro observation revealed that the fatigue cracks were initiated on the surfaces of the specimens in all experimental environments, and significant evidence of corrosion pits and micro cracks was found on the surfaces of the specimens in the salt-spray environment. Based on the pitting corrosion mechanism, a modified fatigue life prediction model that considered the combined effects of stress, temperature and corrosion was proposed. The study results show that the model predictions are in good agreement with the test data. [ABSTRACT FROM AUTHOR]

The dynamic fracture assessment method applied to a cracked centrifugal impeller subjected to dynamic loading is the focus of this study. J -integral histories and loading rates at crack tips were evaluated by numerical simulation through ABAQUS and Zencrack software. True stress–strain relations, fracture mechanism and fracture toughness of the impeller material FV520B steel were investigated over a wide range of loading rates by experimental and theoretical methods. Fracture assessment with consideration to rate effects was then conducted based on the CEGB R6 procedure. The present method demonstrated advantages over existing methods evaluated by an equivalent static load. [ABSTRACT FROM AUTHOR]

Highlights: [•] The failure of the slot-welded impeller can be attributed to SSC accelerated by HIC. [•] FV520B steel with banded δ ferrite does not match the optimal heat treatment. [•] The corrosive environment is caused by hydrogen sulfide and condensed water vapor. [•] The stress in the impeller strongly depends on shrink fit and centrifugal force. [Copyright &y& Elsevier]

Deep understanding of mass diffusion controlled chemomechanical behaviors of composites with local mass flux discontinuities between inclusions and matrixes are of great significance in modern advanced technology and engineering applications. This work develops a finite-deformation chemomechanical model for particle-enforced composites when under mass diffusion. A general chemomechanical cohesive model is developed for chemo-mechanically imperfect interfaces between the inclusions and matrixes. In the developed cohesive model, both of the displacement jump, the chemical potential jump as well as the mass flux jump are considered. A interfacial potential is developed upon the consideration that the diffusant permeation deteriorate interfacial fracture and degrade the interface strength. Applying standard variations procedure on total energy of the coupled chemomechanical system, the associated weak formulations are developed, and then implemented in finite element method software ABAQUS through subroutine UELs. To validate the proposed cohesive model, the mass-diffusion-driven crack propagation is simulated and compared with the published works. A series of numerical examples are conducted to elucidate the key features of chemo-mechanically imperfect interface model. The results show that the jump of mass flux across interface results in a normal swelling of interface even no mechanical load is applied. An increase of interface diffusion coefficient causes a lower chemical potential jump. Parametric analysis show that the interface properties, such as the cohesive strength, fracture energy and degradation parameter, affect the diffusion rate through controlling the mechanical performance of interface. A strong interface can restrict effectively the mass spread across the interface. This research provides a theoretical reference for a wide applications of particle-reinforced composites in chemical environment. [ABSTRACT FROM AUTHOR]

Abstract: Fatigue–creep interaction is the main reason for the failures of many engineering components under high temperature and cyclic loading. In this paper a new model for the life prediction of fatigue–creep interaction has been developed. In this model, the law of energy conservation and the momentum conservation principle are used to describe the process of fatigue–creep interaction. By mathematical technique, the expressions of these two rules are transformed into a simple function, which can describe the relationship between the internal energy and life. This function supposes that the internal energy change of a specimen is a constant from the initial state to the failure one under certain conditions. It should be pointed out that the new model mentioned above is applicable to the life prediction of strain-controlled tests and stress-controlled tests. Moreover, owning to its simple expression, it is very easy to use this model to predict the life of fatigue–creep interaction. To check the validity of the new model proposed in this paper, the assessments for fatigue–creep interaction tests of 1.25Cr0.5Mo steel under stress control at 540°C have been performed. The predicted results are in a good agreement with the experimental data. [Copyright &y& Elsevier]

Failure analyses of five centrifugal casting ethylene cracking furnace tubes within one year and eight months during 2014 to 2017 were investigated through the electro-hydraulic servo universal testing machine, the high temperature endurance testing machine and the scanning electron microscope method, etc. The results showed that the cracking failure parts of five ethylene cracking furnace tubes had microporosity cavities (circa 10–50 μm size). The distribution of the microporosity cavities had a local characteristic (usually within the range of 300 mm). The microporosity cavities connected into microcracks in a relatively short time. The furnace tube is accelerated into the third stage of creep, and eventually failed during service in short term. So the microporosity affects the life of the furnace tube, but does not need to become macroporosity during service. The microporosity is harmful, and it is hard to detect by the existing nondestructive testing method. Prevention measures are put forward from solidification rate, pouring temperature and cylinder rotating speed to prevent microporosity from the manufacturing process of furnace tubes. • The dense microporous cavity accelerated the tube into the third stage of creep, resulting in cracking failure in short-term. • The microporosity was not needed to develop into macroporosity and would have impact on the life of furnace tube. • Reducing solidification rate and increasing pouring temperature could reduce the possibility of microporosity formation. [ABSTRACT FROM AUTHOR]

For a type IV hydrogen storage vessel, the complexity of the mechanical system is a result of the increased number of thin-layered composites and geometrical details at dome parts, which significantly prolongs the computation time for traditional numerical analysis and optimal design. In this work, a framework couples machine learning (ML) and finite element (FE) analysis is proposed for a 70 MPa type IV vessel. Providing an approach that allows the winding parameters optimization process to include the corresponded feasible dome geometry. High-fidelity FE models are established and different failure modes are included. The artificial neural network (ANN) is developed and coupled with the FE models, where the irregularity of directional material distribution on both cylindrical and dome regions is adequately considered during the optimization process. Winding parameters extended by practical production modifications such as transition areas and layer ending adjustments are introduced to the modified input layer of ANN, to ensure the integrality of the complex geometrical details. The computational cost is greatly reduced with satisfying accuracy compared to FE analysis, where the optimized lay-up scheme could be obtained with a prediction error of less than 2% on the damage state function. The associated simulation results show an obvious improvement in mechanical response under designed burst pressure. Particularly, the prototypical vessels are further produced to carry out comparative experiments, which indicate that the burst pressure of the type IV vessel has been improved from 145 MPa to 157.74 MPa. This is also consistent with the numerical prediction of burst pressure using Hashin failure criteria and progressive damage analysis. [Display omitted] • ANN-based machine learning (ML) algorithms is used to optimize 70 MPa type IV vessel. • The irregularity of directional material distribution in dome regions is well considered. • Transition areas and layer-ending adjustments are introduced to the modified input layer of ANN. • Multiple failure modes and mechanical performances are considered to evaluate the outputs. [ABSTRACT FROM AUTHOR]

Cladding stainless steel layer on the inner surface of ferrite pressure vessel is a common method to improve the corrosion resistance and save the economic cost. However, the movement of heat source and temperature gradient in the process of cladded welding will lead to the anisotropy of cladded layer material. When measuring the residual stress of pressure vessel steel plate with stainless steel cladded layers (SSCL) by contour method, it is necessary to know the elastic mechanical properties of stainless steel cladded layers accurately. The assumption of transversely isotropy (TI) was employed, and the relationship between the material compliance matrix and the elastic modulus of transversely isotropic material was utilized. Based on the elastic modulus of each cladded layer and the whole steel plate from the longitudinal direction (0°) until the transverse direction (90°) measured by the experiment, the independent constants S11 , S13 , S33 and S44 in the compliance matrix of each cladded layer and the whole steel plate were obtained by regression analysis method. Furthermore, by using the relationship between the independent constants of the stiffness matrix of the transversely isotropic material and the single crystal material, the independent constant S12 in the compliance matrix of each stainless steel cladded layer and the whole steel plate were obtained. And then the independent constants of the stiffness matrix of each cladded layer and the whole steel plate were acquired. Hence, a method for calculating the anisotropic elastic constants of the stainless steel cladded layer and the whole steel plate was proposed. The results will provide material data support for measuring residual stress of pressure vessel steel plate with stainless steel cladded layers by contour method. • Transversely isotropy assumption was used to calculate elastic constants of the SSCL. • Four independent constants of each SSCL were obtained by regression analysis method. • The last constant was obtained using relationship of TI and single crystal material. • A method to calculate the anisotropic elastic constants of SSCL was proposed. [ABSTRACT FROM AUTHOR]