Many solids, including geomaterials and commercially available metallic alloys, can be considered as a porous media. The Gurson-like model has been proposed to describe plastic deformation for such ...type of materials. It has attracted a great deal of attention and various modifications to this model have been proposed. The constitutive equations of Gurson-like model are governed by the first and second stress invariants and the current void volume fraction of the material. Tvergaard and Needleman included void nucleation, growth and coalescence to Gurson model in a phenomenological way Tvergaard V, Needleman A. Analysis of the cup-cone fracture in a round tensile bar. Acta Metall 1984;32(1):157–69 – thus suggesting the so called GTN model. Meanwhile, little attention was given to the dependence of the damage evolution on the third stress invariant. McClintock et al. McClintock FA, Kaplan SM, Berg CA. Ductile fracture by hole growth in shear bands. Int J Fract Mechan 1966;2(4):614–27 proposed damage model based on the void evolution in localized shear banding. In the present paper, a separate internal damage variable which differs from the conventional void volume fraction is introduced. The GTN model is further extended to incorporate the void shearing mechanism of damage, which depends on the third stress invariant. Numerical aspects are addressed concerning the integration of the proposed constitutive relations. A unit cell is studied to illustrate the intrinsic mechanical behavior of the modified model. Computations of the deformation in axisymmetric and transverse plane strain tension are also performed. Realistic crack modes in these simulations are achieved for the modified GTN model.
A damage plasticity model for ductile fracture is proposed. This model is established on the cylindrical coordinate system of principal stress space. Experimental results show that fracture ...initiation in uncracked ductile solids is sensitive to the hydrostatic pressure and dependent on the Lode angle. The joint effects of pressure and Lode angle define a
fracture envelope in principal stress space. Plastic deformation induced damage is calculated by an integral of the damage rate measured at current loading and deformation status with respect to the fracture envelope. A power law damage rule is proposed to characterize the nonlinearity in damage accumulation. A damage-related weakening factor is adopted to describe the material deterioration. The material parameters are calibrated from standard laboratory tests. The proposed model is numerically implemented. Four simulations with emphasis on crack path prediction are presented.
Cryo-electron microscopy (cryo-EM) enables macromolecular structure determination in vitro and inside cells. In addition to aligning individual particles, accurate registration of sample motion and ...three-dimensional deformation during exposures are crucial for achieving high-resolution reconstructions. Here we describe M, a software tool that establishes a reference-based, multi-particle refinement framework for cryo-EM data and couples a comprehensive spatial deformation model to in silico correction of electron-optical aberrations. M provides a unified optimization framework for both frame-series and tomographic tilt-series data. We show that tilt-series data can provide the same resolution as frame-series data on a purified protein specimen, indicating that the alignment step no longer limits the resolution obtainable from tomographic data. In combination with Warp and RELION, M resolves to residue level a 70S ribosome bound to an antibiotic inside intact bacterial cells. Our work provides a computational tool that facilitates structural biology in cells.
The successful development of post‐lithium technologies depends on two key elements: performance and economy. Because sodium‐ion batteries (SIBs) can potentially satisfy both requirements, they are ...widely considered the most promising replacement for lithium‐ion batteries (LIBs) due to the similarity between the electrochemical processes and the abundance of sodium‐based resources. Among various SIB anode materials, metal sulfides are most extensively studied as materials for high‐performance electrodes due to the versatility of their synthesis procedure, utilization potential, and high sodiation capacity. Herein, some of the most effective strategies aimed at effectively alleviating the performance shortcomings of these materials from the materials engineering/design perspective are summarized. In terms of facilitating ion transport in SIBs, which represents one of the most critical aspects of their performance, a specific family of strategies related to a particular operational mechanism is considered rather than categorizing based‐on individual sulfide materials. In the foreseeable future, the development of highly functional SIBs electrode materials and utilization of metal sulfides will become highly relevant due to their stability and performance characteristics. Therefore, it is anticipated that this review will guide further research and facilitate the realization of various applications of sulfide‐based high‐performance rechargeable batteries.
The development of effective material design strategies/methodologies is critical for the practical implementation of transition metal sulfides (TMS), which are versatile high‐performance materials, in sodium‐ion storage. This review highlights and details some of the recent material design and engineering strategies aimed at identifying TMS‐based high‐performance electrode materials.
Antisense oligonucleotides (ASOs) modified with phosphorothioate (PS) linkages and different 2' modifications can be used either as drugs (e.g., to treat homozygous familial hypercholesterolemia and ...spinal muscular atrophy) or as research tools to alter gene expression. PS-ASOs can enter cells without additional modification or formulation and can be designed to mediate sequence-specific cleavage of different types of RNA (including mRNA and non-coding RNA) targeted by endogenous RNase H1. Although PS-ASOs function in both the cytoplasm and nucleus, localization to different subcellular regions can affect their therapeutic potency. Cellular uptake and intracellular distribution of PS ASOs are mediated by protein interactions. The main proteins involved in these processes have been identified, and intracellular sites in which PS ASOs are active, or inactive, cataloged.
In view of the multiple pathological hallmarks of tumors, nanosystems for the sequential delivery of various drugs whose targets are separately located inside and outside tumor cells are desired for ...improved cancer therapy. However, current sequential delivery is mainly achieved through enzyme‐ or acid‐dependent degradation of the nanocarrier, which would be influenced by the heterogeneous tumor microenvironment, and unloading efficiency of the drug acting on the target outside tumor cells is usually unsatisfactory. Here, a light‐triggered sequential delivery strategy based on a liposomal formulation of doxorubicin (DOX)‐loaded small‐sized polymeric nanoparticles (DOX‐NP) and free sunitinib in the aqueous cavity, is developed. The liposomal membrane is doped with photosensitizer porphyrin–phospholipid (PoP) and hybridized with red blood cell membrane to confer biomimetic features. Near‐infrared light‐induced membrane permeabilization triggers the “ultrafast” and “thorough” release of sunitinib (100% release in 5 min) for antiangiogenic therapy and also myeloid‐derived suppressor cell (MDSC) inhibition to reverse the immunosuppressive tumor environment. Subsequently, the small‐sized DOX‐NP liberated from the liposomes is more easily uptaken by tumor cells for improved immunogenic chemotherapy. RNA sequencing and immune‐related assay indicates therapeutic immune enhancement. This light‐triggered sequential delivery strategy demonstrates the potency in cancer multimodal therapy against multiple targets in different spatial positions in tumor microenvironment.
The biomimetic DS@HLipo targets the tumor site, where near‐infrared light‐induced membrane permeation triggers the “ultrafast” and “thorough” release of sunitinib for both antiangiogenic therapy and anti‐MDSC immunotherapy. The liberated doxorubicin (DOX)‐loaded small‐sized polymeric nanoparticles (DOX‐NP) from the liposomes can then be more easily ingested by tumor cells for improved immunogenic chemotherapy.
In this study, novel composite titanium-based metal-organic framework (MOF) beads were synthesized from titanium based metal organic framework MIL-125 and chitosan (CS) and used to remove Pb(II) from ...wastewater. The MIL-125-CS beads were prepared by combining the titanium-based MIL-125 MOF and chitosan using a template-free solvothermal approach under ambient conditions. The surface and elemental properties of these beads were analyzed using scanning electron microscopy, Fourier transform infrared and X-ray photoelectron spectroscopies, as well as thermal gravimetric analysis. Moreover, a series of experiments designed to determine the influences of factors such as initial Pb(II) concentration, pH, reaction time and adsorption temperature was conducted. Notably, it was found that the adsorption of Pb(II) onto the MIL-125-CS beads reached equilibrium in 180 min to a level of 407.50 mg/g at ambient temperature. In addition, kinetic and equilibrium experiments provided data that were fit to the Langmuir isotherm model and pseudo-second-order kinetics. Furthermore, reusability tests showed that MIL-125-CS retained 85% of its Pb(II)-removal capacity after five reuse cycles. All in all, we believe that the developed MIL-125-CS beads are a promising adsorbent material for the remediation of environmental water polluted by heavy metal ions.
RNase H1-dependent antisense oligonucleotides (ASOs) are active in reducing levels of both cytoplasmic mRNAs and nuclear retained RNAs. Although ASO activity in the nucleus has been well ...demonstrated, the cytoplasmic activity of ASOs is less clear. Using kinetic and subcellular fractionation studies, we evaluated ASO activity in the cytoplasm. Upon transfection, ASOs targeting exonic regions rapidly reduced cytoplasmically enriched mRNAs, whereas an intron-targeting ASO that only degrades the nuclear pre-mRNA reduced mRNA levels at a slower rate, similar to normal mRNA decay. Importantly, some exon-targeting ASOs can rapidly and vigorously reduce mRNA levels without decreasing pre-mRNA levels, suggesting that pre-existing cytoplasmic mRNAs can be cleaved by RNase H1-ASO treatment. In addition, we expressed a cytoplasm-localized mutant 7SL RNA that contains a partial U16 small nucleolar RNA (snoRNA) sequence. Treatment with an ASO simultaneously reduced both the nuclear U16 snoRNA and the cytoplasmic 7SL mutant RNA as early as 30 min after transfection in an RNase H1-dependent manner. Both the 5′ and 3′ cleavage products of the 7SL mutant RNA were accumulated in the cytoplasm. Together, these results demonstrate that RNase H1-dependent ASOs are robustly active in both the cytoplasm and nucleus.
Liang et al. show that antisense oligonucleotide (ASO)-directed RNase H1 cleavage is robustly active in both the nucleus and cytoplasm. They found that ASOs can trigger rapid cleavage of both cytoplasmic and nuclear RNAs mediated by RNase H1, which is also present in the cytosol.
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