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.     

Cyclooxygenase Inhibition Alters Proliferative,Migratory, and Invasive Properties of Human Glioblastoma Cells In Vitro

Prostaglandin E₂ (PGE₂) is known to increase glioblastoma (GBM) cell proliferation and migration while cyclooxygenase (COX) inhibition decreases proliferation and migration. The present study investigated the effects of COX inhibitors and PGE₂ receptor antagonists on GBM cell biology. Cells were grown with inhibitors and dose response, viable cell counting, flow cytometry, cell migration, gene expression, Western blotting, and gelatin zymography studies were performed. The stimulatory effects of PGE₂ and the inhibitory effects of ibuprofen (IBP) were confirmed in GBM cells. The EP2 and EP4 receptors were identified as important mediators of the actions of PGE₂ in GBM cells. The concomitant inhibition of EP2 and EP4 caused a significant decrease in cell migration which was not reverted by exogenous PGE₂. In T98G cells exogenous PGE₂ increased latent MMP2 gelatinolytic activity. The inhibition of COX1 or COX2 caused significant alterations in MMP2 expression and gelatinolytic activity in GBM cells. These findings provide further evidence for the importance of PGE₂ signalling through the EP2 and the EP4 receptor in the control of GBM cell biology. They also support the hypothesis that a relationship exists between COX1 and MMP2 in GBM cells which merits further investigation as a novel therapeutic target for drug development.     

Study of point defects in CuGaSe2 single crystals by means of electron paramagnetic resonance and photoluminescence

Point defects in CuGaSe₂ single crystals as vacancies V_Se, V_Cu and defect pair (2V_Cu⁻+Ga_Cu²⁺) have been studied by means of electron paramagnetic resonance (EPR) and low-temperature photoluminescence (PL). EPR hyperfine structure has been found at temperatures as low as 1.45–45 K and the temperature dependence of EPR line is discussed. Photo-EPR spectrum reveals optically active behavior of intrinsic point defects in CuGaSe₂ crystals. Three bands of PL emission show different origins and two low-energy bands at 1.55 and 1.58 eV have been found to be steady despite H₂-, O₂- and Se₂-annealings. The experimental data added with electric characterization in accordance with the used annealings and together with a defect physics model allow consideration of the point defect ensemble in CuGaSe₂ in more detail.     

Ambient stability of wet chemically passivated germanium wafer for crystalline solar cells

Surface passivation has been recognized as a crucial step in the evaluation of minority carrier lifetime of photovoltaic materials as well as in the fabrication of high efficient solar cells. Dilute acids of HF and HCl are employed for germanium (Ge) surface passivation. An effective lifetime of passivated Ge wafers has been evaluated by a microwave photoconductive decay (μ-PCD) measurement. Surface recombination velocities, S, of H- and Cl-terminated Ge surfaces are 23 and 37 cm/s, respectively. The stability of passivated Ge surfaces against exposure to air has also been examined. The HCl-passivated Ge surfaces are found to be more robust than HF-passivated surfaces.     

Bulk heterojunction organic solar cells utilizing 1,4,8,11,15,18,22,25-octahexylphthalocyanine

Bulk heterojunction solar cells utilizing soluble phthalocyanine derivative, 1,4,8,11,15,18,22,25-octahexylphthalocyanine (C6PcH₂) have been investigated. The active layer was fabricated by spin-coating the mixed solution of C6PcH₂ and 1-(3-methoxy-carbonyl)-propyl-1-1-phenyl-(6,6)C61 (PCBM). The photovoltaic properties of the solar cell with bulk heterojunction of C6PcH₂ and PCBM demonstrated the strong dependence of active layer thickness, and the optimized active layer thickness was clarified to be 120 nm. By inserting MoO₃ hole transport buffer layer between the positive electrode and active layer, the FF and energy conversion efficiency were improved to be 0.50 and 3.2%, respectively. The tandem organic thin-film solar cell has also been studied by utilizing active layer materials of C6PcH₂ and poly(3-hexylthiophene) and the interlayer of LiF/Al/MoO₃ structure, and a high V_oc of 1.27 V has been achieved.     

Formate protects photosynthetic machinery from photoinhibition

In plants, environmental adversity often leads to the formation of reactive oxygen species (ROS) because of excess light energy. We found that incubation of rice leaves under high light intensity together with CO2-depleted air seriously damaged photosynthesis; however, the application of potassium formate (2 mM) before the photoinhibitory treatment protected the photosynthesis of the plant from photoinhibition. Further analysis revealed that formate protects PSII, RuBisCO, and FBPase from photoinhibition. Formate is thought to be involved in endogenous radical scavenging and/or in the supply of CO2, derived from the formate, thereby reducing oxidative damage to the photosystems under photoinhibitory conditions.     

Structural identification and software package for linear multivariable systems

This paper is concerned with the structural identification of linear multivariable systems and an interactive identification package. The structural identification is done by taking the time-invariant subsystem from the realizations of the input-output relations identified using data of disjoint time intervals, and the statistical hypothesis test is employed to determine the order, where the input-output relation is identified based on the generalized least squares method using the possibly larger model for the plant. The identification package is for the identification of the input-output relation of a linear multivariable system, for the structural identification based on the realization and for data management.     

Colorectal Laterally Spreading Tumors by Computed Tomographic Colonography

To date, few reports focused primarily on detecting colorectal laterally spreading tumors (LSTs) have been published. The aim of this study was to determine the visibility of LSTs on computed tomographic colonography (CTC) compared with that on colonoscopy as a standard. We retrospectively reviewed and matched data on endoscopic and CTC reports in 157 patients (161 LSTs) who received a multidetector CT scan using contrast media immediately after total colonoscopy at the National Cancer Center Hospital in Tokyo, Japan, between December 2005 and August 2010. The results of the total colonoscopy were known at the time of the CTC procedure and reading. Of the 161 LSTs detected on colonoscopy, 138 were observed and matched by CTC (86%). Of the 91 granular type LSTs (LST-Gs), 88 (97%) were observed and matched, while of the 70 non-granular type LSTs (LST-NGs), 50 (71%) were observed and matched by CTC (p < 0.0001). CTC enabled observation of 73% (22/30) of 20–29 mm, 83% (35/42) of 30–39 mm, 88% (49/56) of 40–59 mm, and 97% (32/33) of ≥60 mm tumors. The rate of observed LSTs by CTC was 86% (97% of LST-G, 71% of LST-NG) of the LSTs found during total colonoscopy.     

Photosensitized hydrogen evolution from water using a single-walled carbon nanotube/fullerodendron/SiO2 coaxial nanohybrid

A coaxial nanohybrid consisting of a single-walled carbon nanotube (SWCNT), fullerodendron, and SiO(2) shows high-efficiency light-driven hydrogen evolution from water. Upon visible light irradiation, SWCNT/fullerodendron/SiO(2) coaxial nanohybrid shows hydrogen evolution activity in the presence of methyl viologen (MV(2+)), benzyldihydronicotinamide (BNAH), and a colloidal polyvinyl alcohol(PVA)-Pt.