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41.
Ryusei Terui Yuta Yanase Dr. Hidetomo Yokoo Prof. Yoshitomo Suhara Prof. Makoto Makishima Dr. Yosuke Demizu Dr. Takashi Misawa 《ChemMedChem》2021,16(3):458-462
TGR5, a G-protein-coupled receptor (GPCR), plays an important role in several physiological functions. TGR5 activation through bile acids induces an increase in energy expenditure. Therefore, synthetic TGR5 ligands could be useful for the treatment of obesity or dyslipidemia. In this study, we designed and synthesized a set of TGR5 ligands with a 5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene (TMN) skeleton, and evaluated their TGR5 agonistic activity. We also investigated the selectivity of the synthesized compounds for TGR5 relative to the farnesoid X receptor (FXR) and retinoic acid receptor (RAR). Our results show that compound 4 b [N-(2-chlorophenyl)-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenecarboxamide] exhibited potent TGR5 agonist activity with an IC50 value of 8.4 nM without significant cytotoxicity. In addition, compound 4 b showed only slight agonistic activity toward FXR and RAR at 1 μM treatment. These data indicate that compound 4 b is a selective TGR5 agonist, and could be a promising therapeutic agent for dyslipidemia. 相似文献
42.
Naoki Yamahata Yosuke Toyotake Satomi Kunieda Mamoru Wakayama 《International Journal of Food Science & Technology》2020,55(4):1698-1704
Various fermented whey-based beverages have been developed to reduce waste. However, approaches to increase the preference of whey-based beverages are required because of the low sensory acceptability of whey. Here, we identified the better starting material (whey type), between raw whey (RW) and demineralised whey (DMW), and determined the optimal initial concentration using multiple sensory evaluations to develop acceptable fermented beverages made from sole whey with pure cultured Kluyveromyces marxianus (i.e. without additional ingredients and processing methods). Acceptance tests showed that fermented beverages made from DMW were superior to RW as the starting material. The amounts of ethanol produced were 5.0%, 7.6% and 9.5% v/v from the different initial DMW concentrations of 10%, 15% and 20% w/v, respectively. We observed a significant positive correlation (rs = 0.32, P < 0.05) between the assessment attributes, strength of taste as alcohol beverage and overall acceptability, indicating that higher concentrations of DMW yielded a more desirable product. 相似文献
43.
Rikako Tabata SungGi Chi Junichiro Yuda Yosuke Minami 《International journal of molecular sciences》2021,22(4)
Several immune checkpoint molecules and immune targets in leukemic cells have been investigated. Recent studies have suggested the potential clinical benefits of immuno-oncology (IO) therapy against acute myeloid leukemia (AML), especially targeting CD33, CD123, and CLL-1, as well as immune checkpoint inhibitors (e.g., anti-PD (programmed cell death)-1 and anti-CTLA4 (cytotoxic T-lymphocyte-associated protein 4) antibodies) with or without conventional chemotherapy. Early-phase clinical trials of chimeric antigen receptor (CAR)-T or natural killer (NK) cells for relapsed/refractory AML showed complete remission (CR) or marked reduction of marrow blasts in a few enrolled patients. Bi-/tri-specific antibodies (e.g., bispecific T-cell engager (BiTE) and dual-affinity retargeting (DART)) exhibited 11–67% CR rates with 13–78% risk of cytokine-releasing syndrome (CRS). Conventional chemotherapy in combination with anti-PD-1/anti-CTLA4 antibody for relapsed/refractory AML showed 10–36% CR rates with 7–24 month-long median survival. The current advantages of IO therapy in the field of AML are summarized herein. However, although cancer vaccination should be included in the concept of IO therapy, it is not mentioned in this review because of the paucity of relevant evidence. 相似文献
44.
Toshio Shimoo Masahiro Ito Kiyohito Okamura Michio Takeda 《Journal of the American Ceramic Society》2001,84(1):111-116
Electron-beam-cured polycarbosilane fibers were heat-treated at 673–1773 K in a tube evacuated to 1.3 × 10−1 Pa and then exposed at 1873 K in argon. The effect of vacuum heat treatment on improving the high-temperature stability of low-oxygen SiC fibers was investigated by examining gas evolution, grain growth, surface composition, tensile strength, and morphology. The fibers heat-treated at <1173 K lost strength, because of the vigorous generation of residual hydrogen. A minute amount of oxygen in the atmosphere caused the active oxidation of SiC during heat treatment at >1673 K, resulting in severe strength degradation for the as-heat-treated fibers. Vacuum heat treatment at 1573 K provided the best characteristics in low-oxygen SiC fibers. 相似文献
45.
It has been reported that the major cause of earthquake damage to embankments on level ground surfaces is liquefaction of foundation soil. A few case histories, however, suggest that river levees resting on non-liquefiable foundation soil have been severely damaged if the foundation soil is highly compressible, such as thick soft clay and peat deposits. A large number of such river levees were severely damaged by the 2011 off the Pacific coast of Tohoku earthquake. A detailed inspection of the dissected damaged levees revealed that the base of the levees subsided in a bowl shape due to foundation consolidation. The liquefaction of a saturated zone, formed at the embankment base, is considered the prime cause of the damage. The deformation of the levees, due to the foundation consolidation which may have resulted in a reduction in stress and the degradation of soil density, is surmised to have contributed as an underlying mechanism. In this study, a series of centrifuge tests is conducted to experimentally verify the effects of the thickness of the saturated zone in embankments and of the foundation consolidation on the seismic damage to embankments. It is found that the thickness of the saturated zone in embankments and the drainage boundary conditions of the zone have a significant effect on the deformation of the embankments during shaking. For an embankment on a soft clay deposit, horizontal tensile strain as high as 6% was observed at the zone above the embankment base and horizontal stress was approximately half that of the embankment on stiff foundation soil. Crest settlement and the deformation of the embankment during shaking were larger for the embankment subjected to deformation due to foundation consolidation. 相似文献
46.
Inhibitory Effect of 8‐Halogenated 7‐Deaza‐2′‐deoxyguanosine Triphosphates on Human 8‐Oxo‐2′‐deoxyguanosine Triphosphatase,hMTH1, Activities 下载免费PDF全文
Dr. Yizhen Yin Prof. Dr. Shigeki Sasaki Prof. Dr. Yosuke Taniguchi 《Chembiochem : a European journal of chemical biology》2016,17(7):566-569
hMTH1 (8‐oxo‐2′‐deoxyguanine triphosphatase) hydrolyzes oxidized nucleoside triphosphates; its presence is non‐essential for survival of normal cells but is required for survival of cancer cells. In this study, 8‐halogenated‐7‐deaza‐2′‐deoxyguanosine triphosphate (8‐halogenated‐7‐deazadGTP) derivatives were synthesized. Interestingly, these triphosphates were poor substrates for hMTH1, but exhibited strong competitive inhibition against hMTH1 at nanomolar levels. This inhibitory effect is attributed to slower rate of hydrolysis, possibly arising from enzyme structural changes, specifically different stacking interactions with 8‐halogenated‐7‐deazadGTP. This is the first example of using nucleotide derivatives to inhibit hMTH1, thus demonstrating their potential as antitumor agents. 相似文献
47.
Yosuke Yamazaki Yohei Abe Yukio Hioki Mitsuyoshi Nakatani Akikazu Kitagawa Kazuhiro Nakata 《Welding International》2016,30(10):745-754
Narrow gap welding with an oscillation laser beam is one of the effective processes for thick plate welding. To put this welding process into practical manufacturing, a groove-sensing system using image processing for narrow gap welding with an oscillation laser beam is used. This developed system uses still images of the weld zone taken by a coaxial CMOS camera. It can recognize the position of the groove wall by analysing the brightness distribution in the still image. It can then control the oscillation width and the laser-irradiated area by calculating the groove width and the groove centre position. Some narrow gap welding experiments were performed to evaluate the performance of the developed system. The results revealed that the developed system is effective for narrow gap welding with an oscillation laser beam. Using this system, the narrow gap groove can be welded even if the groove width has changed during the welding process. 相似文献
48.
The liquefaction resistance of sand increases with cyclic pre-shearing and pre-shaking as a result of earthquakes if the strain level in the pre-shearing is small. When larger shear strains are imposed, liquefaction resistance decreases. These complicated effects of pre-shearing histories on the liquefaction resistance are investigated in this study through a series of cyclic triaxial tests. Various combinations of cyclic stress amplitude and number of cycles of pre-shearing are examined. The tested sand is Toyoura Sand at 45% relative density, under a confining pressure of 50 kPa. Test results indicate that for the range of shear strain amplitude in pre-shearing smaller than 0.35%, the liquefaction resistance increases with pre-shearing. The increase in the liquefaction resistance depends strongly on the volumetric strain in the pre-shearing, and several effects of the shear stress amplitude and number of cycles can be negligible. Small volumetric strain of the order of 1% doubled the liquefaction resistance. Meanwhile, in the range of shear strain amplitude larger than 0.6%, the liquefaction resistance decreases. The liquefaction resistance decreases as the shear strain amplitude increases. Shear strain amplitude is one of the factors dominating this degrading effect, and the volumetric strain exerts beneficial effects to a certain extent. In this study, another series of tests are conducted to investigate the combined effects of small and large strain amplitude pre-shearing. It is observed that small shear strain pre-shearing cycles subsequent to large shear strain cycles erased the degrading effect of the latter. However, a large shear strain pre-shearing after small strain cycles degrades the beneficial effect of the small shear strain pre-shearing cycles previously applied to the specimens; however, the effects of the former small strain pre-shearing remains. 相似文献
49.
Takeshi Kikutani J. Radhakrishnan Sadaaki Arikawa Akira Takaku Norimasa Okui Xia Jin Fumio Niwa Yosuke Kudo 《应用聚合物科学杂志》1996,62(11):1913-1924
High-speed bicomponent spinning of poly(ethylene terephthalate)(PET)(core) and poly-propylene (PP) (sheath) was carried out and the structure development in the individual components, PET and PP, was investigated. The orientation and crystallinity development in the PET component was enhanced as compared to that of the single-component spinning while the PP component remained in a low orientation state and had a pseudohexagonal crystal structure even at high take-up speeds. To clarify the mutual interaction between the two components in bicomponent spinning, a semiquantitative numerical simulation was performed. The simulation results obtained using the Newtonian fluid model showed that the solidification stress in the PET component was enhanced while that of the PP component was decreased in comparison with the corresponding single-component spinning. This is due to the difference in the temperature dependence of their elongational viscosity. Simulation with an upper-convected Maxwell model as the constitutive equation suggested that significant stress relaxation of the PP component can occur in the spinline if the PET component solidifies earlier than does PP. Based on the structural characterization results, and the simulation results, it was concluded that the difference in the activation energy of the elongational viscosity and solidification temperature between the two polymers are the main factors influencing the mutual interaction in the bicomponent spinning process. © 1996 John Wiley & Sons, Inc. 相似文献
50.
Gel permeation chromatography of polyoxymethylene has been studied using N,N-dimethylformamide as the solvent. Polyoxymethylene samples used here are a copolymer of tetraoxane with 1,3-dioxolane and a commercial polyoxymethylene whose molecular weight distributions are moderately broad. Their intrinsic viscosities [η] range from 1.4 to 2.8 dl/g. Factors affecting chromatograms are discussed, and the operating conditions were determined by using the analytical scale GPC. On the basis of these operating conditions, the molecular weight fractionation of polyoxymethylene was carried out by using the preparative scale GPC. It was found that polyoxymethylene can be effectively fractionated to give seven to ten fractions each of them containing the fractionated polymer ranging in weight from 0.2 to 8 mg when 40 mg polymer sample was used for a run of the measurement. The fractionated polymers were also found to have a narrow molecular weight distribution within a single peak, and their Mw/Mn values decrease with increasing molecular weight. 相似文献