Evaluating the Applicability of Fracture Criteria to Predict the Crack Evolution Path of Dolomite Based on SCB Experiments and FEM

Mixed mode fracture tests are conducted under various initial loading combinations of mode I and mode II (from pure mode I to pure mode II) on semicircular bend (SCB) specimens of dolomite rock. Damage zones are observed behind the fracture surfaces of the broken samples. Scanning electron microscope images of the fracture surfaces are used to study the failure manner. Using the conventional remesh method based on the finite element method (FEM), several widely accepted fracture criteria are employed to theoretically predict the fracture paths. These criteria include the maximum tangential stress criterion, minimum strain energy density criterion, maximum energy release rate criterion, maximum dilatational strain energy density criterion, and the distortional strain energy density criterion. The applicability of the five fracture criteria is examined. The results show that none of the criteria are successful in predicting the crack trajectories of the predominately mode II cracks; the differences among the predicted results of the crack growth paths are negligible for each crack inclined angle. The effect of Poisson’s ratio on the fracture criteria is also investigated and the results show that the predicted crack trajectories are not sensitive to Poisson’s ratio

DDColor: Towards Photo-Realistic Image Colorization via Dual Decoders

Image colorization is a challenging problem due to multi-modal uncertainty and high ill-posedness. Directly training a deep neural network usually leads to incorrect semantic colors and low color richness. While transformer-based methods can deliver better results, they often rely on manually designed priors, suffer from poor generalization ability, and introduce color bleeding effects. To address these issues, we propose DDColor, an end-to-end method with dual decoders for image colorization. Our approach includes a pixel decoder and a query-based color decoder. The former restores the spatial resolution of the image, while the latter utilizes rich visual features to refine color queries, thus avoiding hand-crafted priors. Our two decoders work together to establish correlations between color and multi-scale semantic representations via cross-attention, significantly alleviating the color bleeding effect. Additionally, a simple yet effective colorfulness loss is introduced to enhance the color richness. Extensive experiments demonstrate that DDColor achieves superior performance to existing state-of-the-art works both quantitatively and qualitatively. The codes and models are publicly available at https://github.com/piddnad/DDColor.Comment: ICCV 2023; Code: https://github.com/piddnad/DDColo

Targeting Metabolism in Cancer Cells and the Tumour Microenvironment for Cancer Therapy.

Targeting altered tumour metabolism is an emerging therapeutic strategy for cancer treatment. The metabolic reprogramming that accompanies the development of malignancy creates targetable differences between cancer cells and normal cells, which may be exploited for therapy. There is also emerging evidence regarding the role of stromal components, creating an intricate metabolic network consisting of cancer cells, cancer-associated fibroblasts, endothelial cells, immune cells, and cancer stem cells. This metabolic rewiring and crosstalk with the tumour microenvironment play a key role in cell proliferation, metastasis, and the development of treatment resistance. In this review, we will discuss therapeutic opportunities, which arise from dysregulated metabolism and metabolic crosstalk, highlighting strategies that may aid in the precision targeting of altered tumour metabolism with a focus on combinatorial therapeutic strategies

Gene Delivery to Nonhuman Primate Preimplantation Embryos Using Recombinant Adeno-Associated Virus

Delivery of genome editing tools to mammalian zygotes has revolutionized animal modeling. However, the mechanical delivery method to introduce genes and proteins to zygotes remains a challenge for some animal species that are important in biomedical research. Here, an approach to achieve gene delivery and genome editing in nonhuman primate embryos is presented by infecting zygotes with recombinant adeno-associated viruses (rAAVs). Together with previous reports from the authors of this paper and others, this approach is potentially applicable to a broad range of mammals. In addition to genome editing and animal modeling, this rAAV-based method can facilitate gene function studies in early-stage embryos

Adeno-Associated Virus Neutralizing Antibodies in Large Animals and Their Impact on Brain Intraparenchymal Gene Transfer

Pre-existing neutralizing antibody (NAb) against adeno-associated virus (AAV) commonly found in primates is a major host barrier that can severely compromise in vivo gene transfer by AAV vectors. To achieve proof-of-concept success in clinical development of recombinant AAV (rAAV)-based in vivo gene therapy, it is crucial to consider the potential interference of NAb and to enroll serologically compatible study subjects. In this study, we report a large AAV NAb dataset comprising multiple large animal species and AAV serotypes and compare two NAb assays based on in vitro or in vivo transduction inhibition, respectively. Together with previously published AAV seroepidemiology studies, these data can serve as a reference for selecting suitable serotypes, study subjects of large animal species, and potentially human patients for rAAV treatment. In addition, we modeled the intrathalamus rAAV9 delivery in the presence of circulating anti-AAV9 NAb generated by either pre-immunization or passive transfer of NAb-positive large animal serum to mice. The data showed that circulating NAb may not be the sole determinant to inhibit braintransduction. Other aspects of pre-existing AAV immunity following natural infection or rAAV administration may be further studied to establish a more accurate inclusion criterion for clinical studies employing intraparenchymal rAAV9 injections

Flexible wavelength-, pulse-controlled mode-locked all-fiber laser based on a fiber Lyot filter

In this paper, we report a flexible wavelength-, pulse-controlled mode-locked all-fiber laser based on a novel fiber optic Lyot filter. The wavelength, pulse duration and spectral bandwidth of passive mode-locked lasers can be tuned by controlling the polarization controller. The proposed Lyot filter was constructed by a single-mode fiber insertion between two polarization-maintaining fibers. The filter bandwidth and laser output tunability were based on the birefringence characteristics of the polarization-maintaining fibers. This all-fiber laser is simple and stable and can be used for various applications where width-tunable or wavelength-tunable pulses are necessary

Hierarchical porous TiO2 single crystals templated from partly glassified polystyrene

Hierarchical macro-mesoporous anatase TiO single crystal is one-pot synthesized in an EtOH-H O system using polystyrene (PS) as the single porogen both for macropore and mesopore and TiF as the titanium precursor. The key to the simultaneous growth of single crystal and the introduction of hierarchical pores is the assembly of PS and titania at the glassification temperature of PS (100 °C). During the hydrolytic polymerization of TiF , PS is encapsulated inside titania and gradually glassified. The interference from elastic PS on the oriental growth of TiO crystallite is thus minimized and the final removal of PS through calcination leaves interconnected macropore and mesopore inside the single crystal. According to XPS, EPR and fluorescence analyses, abundant oxygen vacancies are formed on the hierarchical porous single crystal, which presents extraordinary photocatalytic activity and stability in degrading organic pollutants under simulated sunlight irradiation using Rhodamine B as the model. The improved photocatalytic activity is a synergistic effect of improved separation of charge carrier and facilitated interfacial charge transfer benefitting from highly accessible porous single crystal structure. [Abstract copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Targeting codon 158 p53-mutant cancers via the induction of p53 acetylation

Abstract: Gain of function (GOF) DNA binding domain (DBD) mutations of TP53 upregulate chromatin regulatory genes that promote genome-wide histone methylation and acetylation. Here, we therapeutically exploit the oncogenic GOF mechanisms of p53 codon 158 (Arg158) mutation, a DBD mutant found to be prevalent in lung carcinomas. Using high throughput compound screening and combination analyses, we uncover that acetylating mutp53R158G could render cancers susceptible to cisplatin-induced DNA stress. Acetylation of mutp53R158G alters DNA binding motifs and upregulates TRAIP, a RING domain-containing E3 ubiquitin ligase which dephosphorylates IĸB and impedes nuclear translocation of RelA (p65), thus repressing oncogenic nuclear factor kappa-B (NF-ĸB) signaling and inducing apoptosis. Given that this mechanism of cytotoxic vulnerability appears inapt in p53 wild-type (WT) or other hotspot GOF mutp53 cells, our work provides a therapeutic opportunity specific to Arg158-mutp53 tumors utilizing a regimen consisting of DNA-damaging agents and mutp53 acetylators, which is currently being pursued clinically

Dual-confined SeS2 cathode based on polyaniline-assisted double-layered micro/mesoporous carbon spheres for advanced Li-SeS(2 )battery

Selenium-sulfur solid solutions (SexSy) attracts soaring attention owing to its improved electrical conductivity over sulfur and higher theoretical specific capacity than selenium. Herein, high-performance lithium-selenium/sulfur batteries with a dual-confined cathode configuration by encapsulating SeS2 in double-layered hollow micro/mesoporous carbon spheres (DSMCs) with a conductive polyaniline (PANI) protection sheath are proposed. Polysulfides/polyselenides are efficiently restricted in the cathode via physical and chemical entrapment from DSMCs and PANI as well as chemical binding between selenium and sulfur. Benefiting from the distinct advantages of SeS2 and the well-constructed host framework, the cathode achieves high capacity utilization of 1018 mAh g(-1) at 0.2 A g(-1) , together with outstanding rate capability of 619 mAh g(-1) at 2 A g(-1) and excellent cycle life over 500 cycles with almost 100% Coulombic efficiency. The novel SexSy based cathode demonstrates a promising route to surmount some bottlenecks of current lithium-sulfur systems for high-performance rechargeable batteries