Design,Synthesis, and Biological Evaluation of Lysine Demethylase 5 C Degraders

Lysine demethylase 5 C (KDM5C) controls epigenetic gene expression and is attracting great interest in the field of chemical epigenetics. KDM5C has emerged as a therapeutic target for anti-prostate cancer agents, and recently we identified triazole 1 as an inhibitor of KDM5C. Compound 1 exhibited highly potent KDM5C-inhibitory activity in in vitro enzyme assays, but did not show strong anticancer effects. Therefore, a different approach is needed for the development of anticancer agents targeting KDM5C. Here, we attempted to identify KDM5C degraders by focusing on a protein-knockdown strategy. Compound 3 b , which was designed based on compound 1 , degraded KDM5C and inhibited the growth of prostate cancer PC-3 cells more strongly than compound 1 . These findings suggest that KDM5C degraders are more effective as anticancer agents than compounds that only inhibit the catalytic activity of KDM5C.     

Automation trust increases under high-workload multitasking scenarios involving risk

Cognition, Technology & Work - Trust is a critical construct that influences human–automation interaction in multitasking workspaces involving imperfect automation. Karpinsky et al. (Appl...     

The World robot summit disaster robotics category – achievements of the 2018 preliminary competition

The World Robot Summit is a robot Olympics and aims to be held in a different country every four years from 2020. The concept of the Plant Disaster Prevention challenge is daily inspections, checks, and emergency response in industrial plants, and in this competition, robots must carry out these types of missions in a mock-up plant. The concept of the Tunnel Disaster Response and Recovery challenge is emergency response to tunnel disasters, and is a simulation competition whereby teams compete to show their ability to deal with disasters, by collecting information and removing debris. The Standard Disaster Robotics challenge assesses, in the form of a contest, the standard performance levels of a robot that are necessary for disaster prevention and emergency response. The World Robot Summit Preliminary Competition was held at Tokyo Big Sight in October 2018, and 36 teams participated in the Disaster Robotics Category. UGVs and UAVs contended the merits of new technology for solving complex problems, using core technologies such as mobility, sensing, recognition, performing operations, human interface, autonomous intelligence etc., as well as system integration and implementation of strategies for completing missions, gaining high-level results.     

A highly transparent and thermally stable copolymer of 1‐adamantyl methacrylate and styrene

Thermal and optical properties of copolymers of 1‐adamantyl methacrylate (AdMA) and styrene (St) prepared by free radical polymerization in the bulk are investigated. The copolymer forms an azeotrope when the composition is AdMA/St = 55/45 mol%. The glass transition temperature and decomposition temperature of the azeotropic copolymer are 170 and ca 340 °C, respectively. The refractive index increases nonlinearly with St content from 1.522 to 1.591. The light scattering loss at 633 nm is 28.1 dB km^?1, which is less than half of that of polystyrene. The total optical loss including molecular vibrational absorption, which is evaluated using a copolymer‐based optical fiber, is 292–645 dB km^?1 at 500–700 nm. These values correspond to transmittances of 86–93% for a 1 m optical path length. © 2014 Society of Chemical Industry     

Molecular Mechanisms to Control Post-Transplantation Hepatitis B Recurrence

Hepatitis B often progresses to decompensated liver cirrhosis requiring orthotopic liver transplantation (OLT). Although newer nucleos(t)ide analogues result in >90% viral and hepatitis activity control, severely decompensated patients still need OLT because of drug-resistant virus, acute exacerbation, or hepatocellular carcinoma. Acute hepatitis B is also an indication for OLT, because it can progress to fatal acute liver failure. After OLT, the hepatitis B recurrence rate is >80% without prevention, while >90% of transplant recipients are clinically controlled with combined hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogue treatment. However, long-term HBIG administration is associated with several unresolved issues, including limited availability and extremely high cost; therefore, several treatment protocols with low-dose HBIG, combined with nucleos(t)ide analogues, have been investigated. Another approach is to induce self-producing anti-hepatitis B virus (HBV) antibodies using an HBV envelope (HBs) antigen vaccine. Patients who are not HBV carriers, such as those with acutely infected liver failure, are good candidates for vaccination. For chronic HBV carrier liver cirrhosis patients, a successful vaccine response can only be achieved in selected patients, such as those treated with experimentally reduced immunosuppression protocols. The present protocol for post-OLT HBV control and the future prospects of newer treatment strategies are reviewed.     

Characterization of Cu Nanoparticles on TiO2 Photocatalysts Fabricated by Electroless Plating Method

Cu-modified TiO₂ photocatalysts (Cu/TiO₂) were fabricated by electroless plating and wet impregnation methods. Photocatalytic activity for H₂ production over Cu/TiO₂ by electroless plating method was higher than that over Cu/TiO₂ by impregnation method. Characterization of Cu nanoparticles by HRTEM, STEM-EDX, XRD and XAFS was studied. As compared to the wet impregnation method, the electroless plating method resulted in the formation of Cu nanoparticles with small size and uniform distribution on the TiO₂ surface, which caused the enhancement of H₂ production. XAFS measurement provided the evidences for the chemical state change of Cu species during the photocatalytic reaction. The process that Cu species varied from Cu²⁺ into Cu⁰ via Cu¹⁺ as the intermediate under photoirradiation is very important for the H₂ production, which indicates that the metallic Cu nanoparticles acted as the active sites and restrained the photogenerated charges recombination.     

Ultimate strength of compressed stiffened plates and minimum stiffness ratio of their stiffeners

A theoretical investigation into the effectiveness of a stiffener against the ultimate strength of a stiffened plate is carried out. Series of the buckling analyses, the elastic large deflection analyses and the elastic-plastic large deflection analyses are performed by the analytical method and the finite element method on the stiffened plate under thrust. Experiments are also carried out on the stiffened plate under thrust to confirm the theoretical results.On buckling of a stiffened plate, it is well known that ther exxists a minimum stiffness ratio of a stiffener to the plate, $\text{λ}{}^{\mathrm{B}}{}_{\min }$, which gives the maximum limiting value of the buckling strength. Concerning the ultimate strength it was confirmed that there exists a significant stiffness ratio of a st stiffener to the plate, $\text{λ}{}^{\mathrm{U}}{}_{\min }$ similar to $\text{λ}{}^{\mathrm{B}}{}_{\min }$ for the buckling strength.It was also found that there are three typical collapse modes for the stiffened plate under thrust, that is: (1) MODE OO, overall collapse after overall buckling; (2) MODE LO, overall collapse after local buckling; (3) MODE LL, local collapse after local buckling.Approximatelmethods are proposed to evaluate the ultimate strength and $\text{λ}{}^{\mathrm{U}}{}_{\min }$ of a multi-stiffened plate under thrust.The effects of initial imperfections such as welding residual stresses and initial deflection on ultimate strength and $\text{λ}{}^{\mathrm{U}}{}_{\min }$ of a stiffened plate under thrust are also discussed.