Human pluripotent stem cells (hPSCs), including embryonic stem cells and induced pluripotent stem cells, are potentially useful in regenerative therapies for heart disease. For medical applications, clinical-grade cardiac cells must be produced from hPSCs in a defined, cost-effective manner. Cell-based screening led to the discovery of KY02111, a small molecule that promotes differentiation of hPSCs to cardiomyocytes. Although the direct target of KY02111 remains unknown, results of the present study suggest that KY02111 promotes differentiation by inhibiting WNT signaling in hPSCs but in a manner that is distinct from that of previously studied WNT inhibitors. Combined use of KY02111 and WNT signaling modulators produced robust cardiac differentiation of hPSCs in a xeno-free, defined medium, devoid of serum and any kind of recombinant cytokines and hormones, such as BMP4, Activin A, or insulin. The methodology has potential as a means for the practical production of human cardiomyocytes for regeneration therapies.
The first elastic electron scattering has been successfully performed at the self-confining RI ion target (SCRIT) facility, the world's first electron scattering facility for exotic nuclei. The SCRIT technique achieved high luminosity (over 10 27 cm −2 s −1 , sufficient for determining the nuclear shape) with only 10 8 target ions. While 132 Xe used in this time as a target is stable isotope, the charge density distribution was firstly extracted from the momentum transfer distributions of the scattered electrons by comparing the results with those calculated by a phase shift calculation.The charge density distribution of the nucleus is one of the most important factors in the nuclear structure investigations, as it directly relates to the superimposition of the squared wave functions of all protons in the nucleus. Following the monumental measurements by R. Hofstadter and his colleagues [1] in the latter half of the 20th century, many stable nuclei have been studied by elastic electron scattering experiments. However, with few exceptions, electron scattering from short-lived unstable nuclei has been precluded by the difficulty in preparing the target material for these nuclei. Realizing electron scattering for unstable nuclei has been long waited, as it has been revealed that some of nuclei far from the stability valley exhibit exotic features such as neutron halo, neutron skin, etc.[2] which are totally unknown in stable nuclei.We have invented an internal target-forming technique called self-confining RI ion target (SCRIT) [3] in an electron storage ring, which three-dimensionally traps the target ions along the electron beam axis. The ions are confined by transverse focusing force given by the electron beam itself and an electrostatic potential well provided by electrodes put along the beam axis. After a successful feasibility study [4,5], we have recently completed the construction of the SCRIT electron scattering facility [6] at RIKEN's RI Beam Factory, which is dedicated to the study of exotic nuclei. The luminosity required for elastic electron scattering (10 27 cm −2 s −1 ) was achieved with only 10 8 target ions as available at an conventional isotope separation on line (ISOL) facility. In traditional electron scattering experiments, the number of target nuclei is typically of the order of 10 20 . This advancement enables electron scattering not only from unstable nuclei, but also from stable nuclei that have not been studied to date.In this Letter, we report the first elastic electron scattering results of 132 Xe nuclei obtained at the SCRIT facility. Although 132 Xe is a stable nucleus, it has never been investigated by electron scattering [7]. Interestingly, stable xenon isotopes have been recently utilized as targets for dark matter searches [8][9][10], and in neutrinoless double beta decay experiments [11]. To calculate the cross sections in these experiments, the form factors of the Xe isotopes are required. However, transition X-ray measurements of muonic atoms have yielded only the rootmean-squa...
Formal trimerization of the smallest unit of benzyl imidate leads to 2,4,6-tris(benzyloxy)-1,3,5-triazine (TriBOT), which can be used as an acid-catalyzed O-benzylating reagent. The reaction of various functionalized alcohols with 0.4 equiv of TriBOT in the presence of trifluoromethanesulfonic acid afforded the benzyl ethers in good yields. TriBOT is an inexpensive stable crystalline solid with high atom economy.
Fatostatin, a recently discovered small molecule that inhibits activation of sterol regulatory element-binding protein (SREBP), blocks biosynthesis and accumulation of fat in obese mice. The present study synthesized and evaluated a series of fatostatin derivatives. Our structure-activity relationships led to the identification of N-(4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenyl)methanesulfonamide (24; FGH10019) as the most potent drug-like molecule among the analogs tested. Compound 24 has high aqueous solubility and membrane permeability, and may serve as a seed molecule for further development.
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