Defects in materials give rise to fluctuations in electrostatic fields that reflect the local charge density, but imaging this with single atom sensitivity is challenging. However, if possible, this ...provides information about the energetics of adatom binding, localized conduction channels, molecular functionality and their relationship to individual bonds. Here, ultrastable electron-optics are combined with a high-speed 2D electron detector to map electrostatic fields around individual atoms in 2D monolayers using 4D scanning transmission electron microscopy. Simultaneous imaging of the electric field, phase, annular dark field and the total charge in 2D MoS
and WS
is demonstrated for pristine areas and regions with 1D wires. The in-gap states in sulphur line vacancies cause 1D electron-rich channels that are mapped experimentally and confirmed using density functional theory calculations. We show how electrostatic fields are sensitive in defective areas to changes of atomic bonding and structural determination beyond conventional imaging.
Azo-based photoswitches have shown promise as molecular solar–thermal (MOST) materials due to their ability to store energy in their metastable Z isomeric form. The energy is then released, in the ...form of heat, upon photoisomerization to the thermodynamically stable E form. However, obtaining a high energy density and recovering the stored energy with high efficiency requires the materials to be employed in the condensed phase and display a high degree of Z to E switching, both of which are challenging to engineer. Here, we show that arylazopyrazole motifs undergo efficient redox-induced Z to E switching in both the solution and the condensed phase to a higher completeness of switching than achieved photochemically. This redox-initiated pathway lowers the barrier of Z to E isomerization by 27 kJ/mol, while in the condensed phase, the efficiency of electrochemical switching is improved by over an order of magnitude relative to that in the solution state. The influence of the photoswitch’s phase, electrical conductivity, and viscosity on the electrochemical switching in the condensed phase is reported, culminating in a set of design rules to facilitate further investigations. We anticipate the use of an alternative stimulus to light will facilitate the application of MOST materials in situations where phototriggered heat release is unachievable or inefficient, e.g., indoor or at night. Furthermore, exploiting the electrocatalytic mechanism, whereby a catalytic amount of charge triggers Z to E switching via a redox process, bypasses the need for fine tuning of the photoswitching chromophore to achieve complete Z to E switching, thus providing an alternative approach to photoswitch molecular design.
The generally small Gibbs free energy difference between the Z and E isomers of hydrazone photoswitches has so far precluded their use in photon energy storing applications. Here, we report on a ...series of cyclic and acyclic hydrazones, which possess varied degrees of ring strain and, hence, stability of E isomers. The photoinduced isomerization and concurrent phase transition of the cyclic hydrazones from a crystalline to a liquid phase result in the storage of a large quantity of energy, comparable to that of azobenzene derivatives. We demonstrate that the macrocyclic photochrome design in combination with phase transition is a promising strategy for molecular solar thermal energy storage applications.
Structured diffuse auroras are often observed near magnetic local noon (MLN), but their generation mechanisms are poorly understood. We have found that two types of structured diffuse auroras with ...obviously different dynamical properties often coexist near MLN. One type usually drifts from low to high latitude with higher speed and shows pulsation. The other type is always adjacent to the discrete aurora oval and drifts together with nearby discrete aurora with much lower speed. Using coordinated observations from MMS and ground all‐sky imagers, we found that the two types of diffuse auroras are well correlated with number density increase of O+ (from the ionosphere) and of He2+ (from magnetosheath) ions, respectively. These observations indicate that mangetosheath particles penetrated into the magnetosphere also can play an important role for producing the dayside diffuse aurora. In addition, for the first time, electron cyclotron harmonic waves are observed associated with dayside diffuse aurora.
Key Points
Two types of structured diffuse auroras observed near magnetic local noon with obviously different dynamical properties are identified
Types 1 and 2 are associated with number density increase of O+ from the magnetosphere and of He2+ from the magnetosheath, respectively
For the first time, ECH waves, but no whistler mode chorus waves, were observed associated with dayside diffuse auroras
The effect of short range ordering (SRO) on the strain hardening behavior of low solid-solution hardening Ni–Cr alloys with high stacking fault energies (SFEs) was systematically investigated under ...uniaxial compression to a high true strain εt of 0.9 at room temperature. An unexpected four-stage (including Stages A, B, C and D) changing law in strain hardening rate was revealed, which is completely different from the case of conventional high-SFE alloys whose strain hardening rate just monotonously declines as the strain increases. Observations on the deformation microstructures strongly demonstrate that the recovery of strain hardening rate in Ni–Cr alloys (Cr ≥ 20 at.%) at Stages B (0.11 < εt < 0.21) and D (εt ≥ 0.65) should be ascribed to the transformation in dislocation slip mode from wavy slip to planar slip, and the occurrence of the extensive deformation twins (DTs) together with the secondary DTs, respectively. Besides, in the later period of Stage C (0.21 < εt < 0.65), microbands (MBs) and DTs have been locally formed in the Ni–Cr alloys with high SRO degree, which delays the decrease of strain hardening rate to a certain extent. Based on these experimental observations, the impacts of SRO on the formation of planar slip bands, MBs and DTs are analyzed, and the effect of SRO on the four-stage strain hardening behavior is also discussed systematically based on the different deformation mechanisms. In brief, an enhancement of SRO in low solid-solution hardening Ni–Cr alloys with high SFEs has been convincingly confirmed to be capable of improving the strain hardening capacity.
Ice breaking has become one of the main problems faced by ships and other equipment operating in an ice-covered water region. New methods are always being pursued and studied to improve ice-breaking ...capabilities and efficiencies. Based on the strong damage capability, a high-speed water jet impact is proposed to be used to break an ice plate in contact with water. A series of experiments of water jet impacting ice were performed in a transparent water tank, where the water jets at tens of metres per second were generated by a home-made device and circular ice plates of various thicknesses and scales were produced in a cold room. The entire evolution of the water jet and ice was recorded by two high-speed cameras from the top and front views simultaneously. The focus was the responses of the ice plate, such as crack development and breakup, under the high-speed water jet loads, which involved compressible pressure ${P_1}$ and incompressible pressure ${P_2}$. According to the main cause and crack development sequence, it was found that the damage of the ice could be roughly divided into five patterns. On this basis, the effects of water jet strength, ice thickness, ice plate size and boundary conditions were also investigated. Experiments validated the ice-breaking capability of the high-speed water jet, which could be a new auxiliary ice-breaking method in the future.
The tumor microenvironment (TME) in pancreatic adenocarcinoma (PDAC) is a complex milieu of cellular and non-cellular components. Pancreatic cancer cells (PCC) and cancer-associated fibroblasts (CAF) ...are two major cell types in PDAC TME, whereas the non-cellular components are enriched with extracellular matrices (ECM) that contribute to high stiffness and fast stress-relaxation. Previous studies have suggested that higher matrix rigidity promoted aggressive phenotypes of tumors, including PDAC. However, the effects of dynamic viscoelastic matrix properties on cancer cell fate remain largely unexplored. The focus of this work was to understand the effects of such dynamic matrix properties on PDAC cell behaviors, particularly in the context of PCC/CAF co-culture. To this end, we engineered gelatin-norbornene (GelNB) based hydrogels with a built-in mechanism for simultaneously increasing matrix elastic modulus and viscoelasticity. Two GelNB-based macromers, namely GelNB-hydroxyphenylacetic acid (GelNB-HPA) and GelNB-boronic acid (GelNB-BA), were modularly mixed and crosslinked with 4-arm poly(ethylene glycol)-thiol (PEG4SH) to form elastic hydrogels. Treating the hybrid hydrogels with tyrosinase not only increased the elastic moduli of the gels (due to HPA dimerization) but also concurrently produced 1,2-diols that formed reversible boronic acid-diol bonding with the BA groups on GelNB-BA. We employed patient-derived CAF and a PCC cell line COLO-357 to demonstrate the effect of increasing matrix stiffness and viscoelasticity on CAF and PCC cell fate. Our results indicated that in the stiffened environment, PCC underwent epithelial-mesenchymal transition. In the co-culture PCC and CAF spheroid, CAF enhanced PCC spreading and stimulated collagen 1 production. Through mRNA-sequencing, we further showed that stiffened matrices, regardless of the degree of stress-relaxation, heightened the malignant phenotype of PDAC cells.
The pancreatic cancer microenvironment is a complex milieu composed of various cell types and extracellular matrices. It has been suggested that stiffer matrices could promote aggressive behavior in pancreatic cancer, but the effect of dynamic stiffening and matrix stress-relaxation on cancer cell fate remains largely undefined. This study aimed to explore the impact of dynamic changes in matrix viscoelasticity on pancreatic ductal adenocarcinoma (PDAC) cell behavior by developing a hydrogel system capable of simultaneously increasing stiffness and stress-relaxation on demand. This is achieved by crosslinking two gelatin-based macromers through orthogonal thiol-norbornene photochemistry and post-gelation stiffening with mushroom tyrosinase. The results revealed that higher matrix stiffness, regardless of the degree of stress relaxation, exacerbated the malignant characteristics of PDAC cells.
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Androgen receptor (AR) is a transcriptional activator that, in prostate cells, stimulates gene expression required for various cellular functions, including metabolisms and proliferation. AR ...signaling is also essential for the development of hormone-dependent prostate cancer (PCa) and its activity can be blocked by androgen-deprivation therapies (ADTs). Although PCa patients initially respond well to ADTs, the cancer inevitably relapses and progresses to lethal castration-resistant prostate cancer (CRPC). Although AR activity is generally restored in CRPC despite the castrate level of androgens, it is unclear whether AR signaling is significantly reprogrammed. In this study, we examined the AR cistrome in a PCa cell line-derived CRPC model using integrated bioinformatical analyses. Significantly, we found that the AR cistrome is largely retained in the CRPC stage. In particular, AR-mediated lipid biosynthesis is highly conserved and reactivated during the progression to CRPC, and increased level of lipid synthesis is associated with poor prognosis. The restoration of lipid biosynthetic pathways is partially due to the increased expression of AR splice variants. Blocking lipid/cholesterol synthesis in AR variants-expressing CRPC cell line and xenograft models markedly reduces tumor growth through inhibition of mTOR pathway. Silencing the expression of a fatty acid elongase, ELOVL7, also leads to the regression of CRPC xenograft tumors. These results demonstrate the importance of reactivation of AR-regulated lipid biosynthetic pathways in driving CRPC progression, and suggest that ADTs may be therapeutically enhanced by blocking lipid biosynthetic pathways.
We propose a novel centralized and decoupled algorithm, DDM, for solving multi-robot path planning problems in grid graphs, targeting on-demand and automated warehouse-like settings. Two settings are ...studied: a traditional one whose objective is to move a set of robots from their respective initial vertices to the goal vertices as quickly as possible, and a dynamic one which requires frequent re-planning to accommodate for goal configuration adjustments. Among other techniques, DDM is mainly enabled through exploiting two innovative heuristics: path diversification and optimal sub-problem solution databases. The two heuristics attack two distinct phases of a decoupling-based planner: while path diversification allows the more effective use of the entire workspace for robot travel, optimal sub-problem solution databases facilitate the fast resolution of local path conflicts. Extensive evaluation demonstrates that DDM achieves high levels of scalability and solution quality close to the optimum.
Summary
Population-based cohort study of 6,548,784 Korean subjects demonstrates that the risk of fracture was higher in patients with diabetes than in nondiabetic subjects. Furthermore, patients with ...type 1 diabetes were associated with a higher risk of fracture than patients with type 2 diabetes for all measurement sites.
Introduction
Diabetes mellitus is associated with increased fracture risk. Although the pathophysiologic effect on bone metabolism differs according to the type of diabetes, a higher risk of fracture in patients with diabetes than in nondiabetic patients has been consistently demonstrated. Considering the ever-increasing number of patients with diabetes, we aimed to provide updated information on whether this phenomenon remains valid in real-world settings by using large-scale population datasets.
Methods
We conducted a retrospective longitudinal study using data from the Korean National Health Insurance Service dataset of preventive health check-ups between January 2009 and December 2016. The hazard ratios were calculated for any fracture, vertebral fracture, and hip fracture and were analyzed according to the presence and type of diabetes. Among 10,585,818 subjects, 6,548,784 were eligible for the analysis (2418 patients with type 1 diabetes mellitus T1DM and 506,208 patients with type 2 diabetes mellitus T2DM).
Results
The mean follow-up duration (in years) was 7.0 ± 1.3 for subjects without diabetes, 6.4 ± 2.0 for those with T1DM, and 6.7 ± 1.7 for T2DM. Patients with T1DM had a higher incidence rate for all types of fractures per 1000 person-years. The fully adjusted hazard ratios (HRs) for any fracture, vertebral fracture, and hip fracture were higher in T1DM than in T2DM (1.37 95% confidence interval (CI): 1.23–1.52 for any fracture, 1.33 95% CI: 1.09–1.63 for vertebral fracture, and 1.99 95% CI: 1.56–2.53 for hip fracture).
Conclusions
In this large-scale population analysis, diabetes was associated with a higher risk of all types of fractures. Patients with T1DM had a higher risk of fracture than those with T2DM for all measurement sites, and hip fractures had the highest risk. Therefore, fracture prevention training for patients with diabetes is advisable.
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