Adaptation to Endoplasmic Reticulum Stress Enhances Resistance of Oral Cancer Cells to Cisplatin by Up-Regulating Polymerase η and Increasing DNA Repair Efficiency

Endoplasmic reticulum (ER) stress response is an adaptive program to cope with cellular stress that disturbs the function and homeostasis of ER, which commonly occurs during cancer progression to late stage. Late-stage cancers, mostly requiring chemotherapy, often develop treatment resistance. Chemoresistance has been linked to ER stress response; however, most of the evidence has come from studies that correlate the expression of stress markers with poor prognosis or demonstrate proapoptosis by the knockdown of stress-responsive genes. Since ER stress in cancers usually persists and is essentially not induced by genetic manipulations, we used low doses of ER stress inducers at levels that allowed cell adaptation to occur in order to investigate the effect of stress response on chemoresistance. We found that prolonged tolerable ER stress promotes mesenchymal–epithelial transition, slows cell-cycle progression, and delays the S-phase exit. Consequently, cisplatin-induced apoptosis was significantly decreased in stress-adapted cells, implying their acquisition of cisplatin resistance. Molecularly, we found that proliferating cell nuclear antigen (PCNA) ubiquitination and the expression of polymerase η, the main polymerase responsible for translesion synthesis across cisplatin-DNA damage, were up-regulated in ER stress-adaptive cells, and their enhanced cisplatin resistance was abrogated by the knockout of polymerase η. We also found that a fraction of p53 in stress-adapted cells was translocated to the nucleus, and that these cells exhibited a significant decline in the level of cisplatin-DNA damage. Consistently, we showed that the nuclear p53 coincided with strong positivity of glucose-related protein 78 (GRP78) on immunostaining of clinical biopsies, and the cisplatin-based chemotherapy was less effective for patients with high levels of ER stress. Taken together, this study uncovers that adaptation to ER stress enhances DNA repair and damage tolerance, with which stressed cells gain resistance to chemotherapeutics.     

Photoactive Earth‐Abundant Iron Pyrite Catalysts for Electrocatalytic Nitrogen Reduction Reaction

The generation of ammonia, hydrogen production, and nitrogen purification are considered as energy intensive processes accompanied with large amounts of CO₂ emission. An electrochemical method assisted by photoenergy is widely utilized for the chemical energy conversion. In this work, earth‐abundant iron pyrite (FeS₂) nanocrystals grown on carbon fiber paper (FeS₂/CFP) are found to be an electrochemical and photoactive catalyst for nitrogen reduction reaction under ambient temperature and pressure. The electrochemical results reveal that FeS₂/CFP achieves a high Faradaic efficiency (FE) of ≈14.14% and NH₃ yield rate of ≈0.096 µg min^?1 at ?0.6 V versus RHE electrode in 0.25 m LiClO₄. During the electrochemical catalytic reaction, the crystal structure of FeS₂/CFP remains in the cubic pyrite phase, as analyzed by in situ X‐ray diffraction measurements. With near‐infrared laser irradiation (808 nm), the NH₃ yield rate of the FeS₂/CFP catalyst can be slightly improved to 0.1 µg min^?1 with high FE of 14.57%. Furthermore, density functional theory calculations demonstrate that the N₂ molecule has strong chemical adsorption energy on the iron atom of FeS₂. Overall, iron pyrite‐based materials have proven to be a potential electrocatalyst with photoactive behavior for ammonia production in practical applications.     

Automatic brain tissue segmentation in MR images using hybrid atlas forest based on confidence-weighted probability matrix

The segmentation of specific tissues in an MR brain image for quantitative analysis can assist the disease diagnosis and medical research. Therefore, a robust and accurate method for automatic segmentation is necessary. Atlas-based-method is a common and effective method of automatic segmentation where an atlas refers to a pair of image consist of an intensity image and its corresponding label image. Apart from the general multi-atlas-based methods, which propagate labels through the single atlas then fuse them, we proposed a hybrid atlas forest based on confidence-weighted probability matrix to consider the atlases set as a whole and treat each voxel differently. In the framework, we first register the atlas to the image space of target and calculate the confidence of voxels in the registered atlas. Then, a confidence-weighted probability matrix is generated and it augments to the intensity image of the atlas or target for providing spatial information of the target tissue. Third, a hybrid atlas forest is trained to gather the features and correlation information among the atlases in the dataset. Finally, the segmentation of the target tissues is predicted by the trained hybrid atlas forest. The segment performance and the components efficiency of the proposed method are evaluated on the two public datasets. Based on the experiment results and quantitative comparisons, our method can gather spatial information and correlation among the atlases to obtain an accurate segmentation.     

Structure and crystallization behavior of complex mold flux glasses in the system CaO-Na2O-Li2O-CaF2-B2O3-SiO2: A multi-nuclear NMR spectroscopic study

The structure of mold flux glasses in the system CaO-(Na,Li)₂O-SiO₂-CaF₂ with unusually high modifier contents, stabilized by the addition of ∼4 mol% B₂O₃, is studied using ⁷Li, ²³Na, ¹⁹F, ¹¹B, and ²⁹Si magic-angle-spinning (MAS), and ⁷Li{¹⁹F} and ²³Na{¹⁹F} rotational echo double-resonance (REDOR) nuclear magnetic resonance (NMR) spectroscopy. When taken together, the spectroscopic results indicate that the structure of these glasses consists primarily of dimeric [Si₂O₇]⁻⁶ units that are linked to the (Ca,Na,Li)-O coordination polyhedra, and are interspersed with chains of corner-shared BO₃ units. The F atoms in the structure are exclusively bonded to Ca atoms, forming Ca(O,F)_n coordination polyhedra. This structural scenario is shown to be consistent with the crystallization of cuspidine (3CaO·2SiO₂·CaF₂) from the parent melts on slow supercooling. The progressive addition of Li to a Na-containing base composition results in a corresponding increase in the undercooling required for the nucleation of cuspidine in the melt, which is attributed to the frustrated local structure caused by the mixing of alkali ions.     

Physical,mechanical and thermal properties of cross laminated timber made with coconut wood

European Journal of Wood and Wood Products - The fundamental material properties of coconut wood cross-laminated timber (CLT) were experimentally evaluated with a focus on the effect of the...     

Three-dimensional finite element analysis of geosynthetic-reinforced soil walls with turning corners

The paper presents in-depth three-dimensional finite element analyses investigating geosynthetic-reinforced soil walls with turning corners. Validation of the 3D numerical procedure was first performed via comparisons between the simulated and reported results of a benchmark physical modeling built at the Royal Military College of Canada. GRS walls with corners of 90°, 105°, 120°, 135°, 150°, and 180° were simulated adopting the National Concrete Masonry Association guidelines. The behaviors of the GRS walls with corners, including the lateral facing displacement, maximum reinforcement load, factor of safety, potential failure surface, vertical separation of facing blocks, and types of corners were carefully evaluated. Our comprehensive results show (i) minimum lateral displacement occurs at the corner; (ii) lower strength of reinforcements are required at the corner; (iii) higher corner angles lead to lower stability; (iv) potential failure surface forms earlier at the end walls; (v) deeper potential failure surfaces are found at the corners; (vi) larger numbers of vertical separations are found at walls with smaller corner angles. The paper highlighted the salient influence of the corners on the behaviors of GRS walls and indicated that a 3D analysis could reflect the required reinforcement length and the irregular formation of the potential failure surfaces.     

ALLSTEPS: Curriculum-driven Learning of Stepping Stone Skills

Humans are highly adept at walking in environments with foot placement constraints, including stepping-stone scenarios where footstep locations are fully constrained. Finding good solutions to stepping-stone locomotion is a longstanding and fundamental challenge for animation and robotics. We present fully learned solutions to this difficult problem using reinforcement learning. We demonstrate the importance of a curriculum for efficient learning and evaluate four possible curriculum choices compared to a non-curriculum baseline. Results are presented for a simulated humanoid, a realistic bipedal robot simulation and a monster character, in each case producing robust, plausible motions for challenging stepping stone sequences and terrains.     

A triple (e−/O2−/H+) conducting perovskite BaCo0.4Fe0.4Zr0.1Y0.1O3-δ for low temperature solid oxide fuel cell

Low-temperature solid oxide fuel cells (LT-SOFCs) have recently gained enormous attention worldwide with a new research trend focusing on single layer fuel cells (SLFC), which have better cell performance than traditional SOFCs at low operating temperatures. In this study, a triple (e^?/O^2?/H⁺) conducting perovskite BaCo_0.4Fe_0.4Zr_0.1Y_0.1O_3-δ (BCFZY) is used as the intermediate layer material for SLFC. A high current density of 994 mA/cm² at 0.6 V and a peak power density of 610 mW/cm² with an OCV of 1.01 V has been achieved with a cell operating temperature of 550 °C, confirming the application feasibility of BCFZY in SLFCs. Furthermore, a typical proton conductor BaZr_0.8Y_0.2O_3-δ (BZY) is introduced into BCFZY to enhance the cell performance. By adjusting the mass ratio of the BCFZY-BZY layer, an optimal power density is obtained, achieving 703 mW/cm² with an OCV of 1.03 V at 550 °C with an 8BCFZY:2BZY (wt%) ratio. These findings prove that the proposed BCFZY-BZY holds great promise for developing SLFCs to realize low-temperature operation.