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.     

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.     

A GIS-based DRASTIC model for assessing aquifer vulnerability in Kakamigahara Heights, Gifu Prefecture, central Japan

Vulnerability assessment to delineate areas that are more susceptible to contamination from anthropogenic sources has become an important element for sensible resource management and land use planning. This contribution aims at estimating aquifer vulnerability by applying the DRASTIC model as well as utilizing sensitivity analyses to evaluate the relative importance of the model parameters for aquifer vulnerability in Kakamigahara Heights, Gifu Prefecture central Japan. An additional objective is to demonstrate the combined use of the DRASTIC and geographical information system (GIS) as an effective method for groundwater pollution risk assessment. The DRASTIC model uses seven environmental parameters (Depth to water, net Recharge, Aquifer media, Soil media, Topography, Impact of vadose zone, and hydraulic Conductivity) to characterize the hydrogeological setting and evaluate aquifer vulnerability. The western part of the Kakamigahara aquifer was dominated by "High" vulnerability classes while the eastern part was characterized by "Moderate" vulnerability classes. The elevated north-eastern part of the study area displayed "Low" aquifer vulnerability. The integrated vulnerability map shows the high risk imposed on the eastern part of the Kakamigahara aquifer due to the high pollution potential of intensive vegetable cultivation. The more vulnerable western part of the aquifer is, however, under a lower contamination risk. In Kakamigahara Heights, land use seems to be a better predictor of groundwater contamination by nitrate. Net recharge parameter inflicted the largest impact on the intrinsic vulnerability of the aquifer followed by soil media, topography, vadose zone media, and hydraulic conductivity. Sensitivity analyses indicated that the removal of net recharge, soil media and topography causes large variation in vulnerability index. Moreover, net recharge and hydraulic conductivity were found to be more effective in assessing aquifer vulnerability than assumed by the DRASTIC model. The GIS technique has provided efficient environment for analyses and high capabilities of handling large spatial data.     

Suppression of phonon‐mediated hot carrier relaxation in type‐II InAs/AlAsxSb1 − x quantum wells: a practical route to hot carrier solar cells

InAs/AlAs_xSb_{1 − x} quantum wells are investigated for their potential as hot carrier solar cells. Continuous wave power and temperature‐dependent photoluminescence indicate a transition in the dominant hot carrier relaxation process from conventional phonon‐mediated carrier relaxation below 90 K to a regime where inhibited radiative recombination dominates the hot carrier relaxation at elevated temperatures. At temperatures below 90 K, photoluminescence measurements are consistent with type‐I quantum wells that exhibit hole localization associated with alloy/interface fluctuations. At elevated temperatures, hole delocalization reveals the true type‐II band alignment, where it is observed that inhibited radiative recombination due to the spatial separation of the charge carriers dominates hot carrier relaxation. This decoupling of phonon‐mediated relaxation results in robust hot carriers at higher temperatures, even at lower excitation powers. These results indicate type‐II quantum wells offer potential as practical hot carrier systems. Copyright © 2016 John Wiley & Sons, Ltd.