La lutte contre l'abstraction : La signification de l'acte de voir dans La Peste d'Albert Camus

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Generation of Seed Magnetic Field around First Stars: the Biermann Battery Effect

We investigate generation processes of magnetic fields around first stars. Since the first stars are expected to form anisotropic ionization fronts in the surrounding clumpy media, magnetic fields are generated by effects of radiation force as well as the Biermann battery effect. We have calculated the amplitude of magnetic field generated by the effects of radiation force around the first stars in the preceding paper, in which the Biermann battery effects are not taken into account.In this paper, we calculate the generation of magnetic fields by the Biermann battery effect as well as the effects of radiation force, utilizing the radiation hydrodynamics simulations. As a result, we find that the generated magnetic field strengths are ~ 10^{-19}G-10^{-17}G at ~ 100pc-1kpc scale mainly by the Biermann battery, which is an order of magnitude larger than the results of our previous study. We also find that this result is insensitive to various physical parameters including the mass of the source star, distance between the source and the dense clump, unless we take unlikely values of these parameters.Comment: 19 pages, 7 figures, Accepted for publications in Ap

Superconductor derived from a topological insulator heterostructure

Topological superconductors (TSCs) are of significant current interest because they offer promising platforms for finding Majorana fermions. Here we report on a superconductor synthesized by intercalating Cu into a naturally formed topological insulator (TI) heterostructure consisting of Bi₂Se₃ TI units separated by nontopological PbSe units. Interestingly, in this TI-based superconductor, the specific-heat behavior suggests the occurrence of unconventional superconductivity with gap nodes. The existence of gap nodes in a strongly spin-orbit coupled superconductor would give rise to spin-split Andreev bound states that are the hallmark of topological superconductivity. Hence, this superconductor emerges as an intriguing candidate TSC

Discovery of soticlestat, a potent and selective inhibitor for cholesterol 24-hydroxylase (CH24H)

Cholesterol 24-hydroxylase (CH24H, CYP46A1), a brain-specific cytochrome P450 (CYP) family enzyme, plays a role in the homeostasis of brain cholesterol by converting cholesterol to 24S-hydroxycholesterol (24HC). Despite a wide range of potential of CH24H as a drug target, no potent and selective inhibitors have been identified. Here, we report on the structure-based drug design (SBDD) of novel 4-arylpyridine derivatives based on the X-ray co-crystal structure of hit derivative 1b. Optimization of 4-arylpyridine derivatives led us to identify 3v ((4-benzyl-4-hydroxypiperidin-1-yl)­(2,4′-bipyridin-3-yl)­methanone, IC50 = 7.4 nM) as a highly potent, selective, and brain-penetrant CH24H inhibitor. Following oral administration to mice, 3v resulted in a dose-dependent reduction of 24HC levels in the brain (1, 3, and 10 mg/kg). Compound 3v (soticlestat, also known as TAK-935) is currently under clinical investigation for the treatment of Dravet syndrome and Lennox-Gastaut syndrome as a novel drug class for epilepsies

The first total synthesis of N1999-A2: absolute stereochemistry and stereochemical implications into DNA cleavage

Enediyne antitumor antibiotics have attracted immense attention among chemists and biologists alike because of their unique chemical structures, potent antitumor activities, and fascinating biological modes of action. As a novel addition to this family, the nonprotein and extremely strained nine-membered enediyne antibiotic N1999-A2 strongly inhibits the growth of various tumor cell lines and bacteria, and cleaves DNA in a base-specific manner. The attractive features of this molecule lie not only within the chemical structure being analogous to the neocarzinostatin chromophore, itself a potent anticancer agent, but also in that it can invoke remarkably strong biological activities even without a stabilizing apoprotein carrier and a glycoside functionality that can accelerate the rate of DNA cleavage. In this regard, N1999-A2 serves as a leading enediyne-based antitumor agent with minimal functionality that is able to act on DNA selectively. We therefore focused on this unique, unstable, and stereochemically unknown compound and undertook the formidable challenge of devising an efficient strategy that would be flexible enough to ultimately construct a series of related highly strained systems