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.     

Direct Observation of Pure Cu and Cu-Ag Anode Passivation in H2SO4-CuSO4 Aqueous Solution by Channel Flow Double Electrode and Optical Microscopy

Metallurgical and Materials Transactions B - The dissolution and passivation of pure Cu and Cu-5 wt pct Ag anodes in H2SO4-CuSO4 electrolyte were investigated by a direct...     

Multifunctional Hydrophobized Microparticles for Accelerated Wound Healing after Endoscopic Submucosal Dissection

Endoscopic submucosal dissection (ESD) provides strong therapeutic benefits for early gastrointestinal cancer as a minimally invasive treatment. However, there is currently no reliable treatment to prevent scar contracture resulting from ESD which may lead to cicatricial stricture. Herein, a multifunctional colloidal wound dressing to promote tissue regeneration after ESD is demonstrated. This sprayable wound dressing, composed of hydrophobized microparticles, exhibits the multifunctionality necessary for wound healing including tissue adhesiveness, blood coagulation, re‐epithelialization, angiogenesis, and controlled inflammation based on hydrophobic interaction with biological systems. An in vivo feasibility study using swine gastric ESD models reveals that this colloidal wound dressing suppresses fibrosis and accelerates wound healing. Multifunctional colloidal and sprayable wound dressings have an enormous therapeutic potential for use in a wide range of biomedical applications including accelerated wound healing after ESD, prevention of perforation, and the treatment of inflammatory diseases.     

Self-Assembly of Proteinaceous Shells around Positively Charged Gold Nanomaterials Enhances Colloidal Stability in High-Ionic-Strength Buffers

The enzyme lumazine synthase (LS) has been engineered to self-assemble into hollow-shell structures that encapsulate unnatural cargo proteins through complementary electrostatic interactions. Herein, we show that a negatively supercharged LS variant can also form organic–inorganic hybrids with gold nanomaterials. Simple mixing of LS pentamers with positively charged gold nanocrystals in aqueous buffer spontaneously affords protein-shelled gold cores. The procedure works well with differently sized and shaped gold nanocrystals, and the resulting shelled complexes exhibit dramatically enhanced colloidal stability over a wide range of pH (4.0–10.0) and at high ionic strength (up to 1 m NaCl). They are even stable over days upon dilution in buffer. Self-assembly of engineered LS shells in this way offers an easy and attractive alternative to commonly used ligand-exchange methods for stabilizing inorganic nanomaterials.     

A short guide to topological terms in the effective theories of condensed matter

This article is meant as a gentle introduction to the topological terms that often play a decisive role in effective theories describing topological quantum effects in condensed matter systems. We first take up several prominent examples, mainly from the area of quantum magnetism and superfluids/superconductors. We then briefly discuss how these ideas are now finding incarnations in the studies of symmetry-protected topological phases, which are in a sense a generalization of the concept of topological insulators to a wider range of materials, including magnets and cold atoms.     

MISCELA: discovering simultaneous and time-delayed correlated attribute patterns

This article addresses a new pattern mining problem in time series sensor data, which we call correlated attribute pattern mining. The correlated attribute patterns (CAPs for short) are the sets of attributes (e.g., temperature and traffic volume) on sensors that are spatially close to each other and temporally correlated in their measurements. Although the CAPs are useful to accurately analyze and understand spatio-temporal correlation between attributes, the existing mining methods are inefficient to discover CAPs because they extract unnecessary patterns. Therefore, we propose a mining method Miscela to efficiently discover CAPs. Miscela can discover not only simultaneous correlated patterns but also time delayed correlated patterns. Furthermore, we extend Miscela to automatically search for correlated patterns with any time delays. Through our experiments using three real sensor datasets, we show that the response time of Miscela is up to 20.84 times faster compared with the state-of-the-art method. We show that Miscela discovers meaningful patterns for urban managements and environmental studies.

     

Small-angle X-ray scattering studies on melting and recrystallization behaviors of poly(oxyethylene) crystallites in poly(d,l-lactide)/poly(oxyethylene) blends

Direct determination of the discrete distribution for crystalline lamellar thickness has been performed for poly(d,l-lactic acid)/poly(oxyethylene) (PDLLA/PEG) blends by conducting small-angle X-ray scattering (SAXS) measurements using synchrotron radiation. The PDLLA used was an random (racemic) copolymer of bio-based poly(l-lactic acid) (PLLA) and poly(d-lactic acid) (PDLA) with the lactide monomer ratio of l:d = 50:50. It is known that PLA is miscible with PEG in the amorphous state. In the current paper, we report comprehensive results on structural analyses of PDLLA/PEG blends in the course of heating and cooling process using SAXS to elucidate the change in the thickness distribution of the lamellae. As a consequence, it was found that the distribution of the lamellar thickness moves toward the larger value (in other words, lamellar thickening) as temperature approaches the melting point. Typically, the thickness distribution was dispersed in the range of 10–20 nm at room temperature and it changed toward 40 nm in the vicinity of the melting temperature. To the best of our knowledge, this is the first report of direct determination of the discrete distribution for the crystalline lamellar thickness and their in-situ changes in the course of the lamellar thickening process. As a result, the lamellar thickening was found to occur at much lower temperature for the blend samples with 10% and 20% of PDLLA contents as compared to the PEG 100% sample. This phenomenon can be ascribed to the melting point depression owing to the miscibility between PEG and PDLLA. Thereby, thinner lamellae were melted and thicker ones appeared at much lower temperature for the blends than for the PEG 100% sample. As for the average repeating distance (long period) of the lamellar stacks, an abrupt increase similar to the critical divergence was observed (from 25 nm to 50 nm) in the heating process. Not only for the melting behavior but also in the course of recrystallization, change in the lamellar-thickness distribution was uncovered, which shows strong hysteresis depending on what temperature the sample was cooled down from.     

Change in molecular weight distribution by elution of polymers from PVA cast gel

Poly(vinyl alcohol) (PVA) cast gels with high degrees of polymerization and hydrolysis were prepared at room temperature. After sufficient exchange of the outer solvent by fresh pure water, the gel was re-dissolved in pure water at a high temperature. Using this solution, the cast gel was prepared again. This re-dissolution process was repeated again, and a third cast gel was prepared. During each swelling process after each cast-drying process, the amount of elution from the gel was measured and the molecular weight distributions of PVA in the gel as well as in the outer solvent were quantitatively evaluated. The molecular weight distribution of the eluted PVA was found to depend on that of the PVA in the gel; the average molecular weight gradually increased as the re-dissolution process was repeated, while the polydispersity indices of both the PVA from the gel and the eluted PVA decreased.     

以健康理念出发：戴尔医学区景观设计

正戴尔医学院及附属教学医院戴尔塞顿医疗中心地处奧斯汀中部德州大学奥斯汀分校校园。占地逾6.5 hm2的医学区是市内最大的医疗卫生开发区的一部分,不仅为医学院全院师生及访客提供服务,更在校园景观中创造出一片新风貌,立下全新的生态绩效标准。戴尔医学区的景观设计过程是Sasaki及顾问团队过去2年规划工作的延续,项目团队先后在2012—2014年为大学制定了校园总体规划、医学区总体规划以及德州大学奥斯汀分校景观总体规划与设计导则。与之前的总体规划项目一样,戴尔医学区的景观设计同样以多元     

Characterization of the Oxide Scale Formed on T12 Water Wall Tube After Long-term Service in Supercritical Power Plant

Oxidation of Metals - Oxide scale control is one of the critical maintenance issues in fossil fuel power plant. Hence, the water treatment of the feed water has been changed from all-volatile...