On the Convergence of Martingales and the "Littlewood-Paley" Operators

Article信州大学工学部紀要 35: 7-10 (1973)departmental bulletin pape

Fe-K line probing of material around the AGN central engine with Suzaku

We systematically analyzed the high-quality Suzaku data of 88 Seyfert galaxies. We obtained a clear relation between the absorption column density and the equivalent width of the 6.4 keV line above 10$^{23}$ cm$^{-2}$, suggesting a wide-ranging column density of $10^{23-24.5}$ cm$^{-2}$ with a similar solid and a Fe abundance of 0.7--1.3 solar for Seyfert 2 galaxies. The EW of the 6.4 keV line for Seyfert 1 galaxies are typically 40--120 eV, suggesting the existence of Compton-thick matter like the torus with a column density of $>10^{23}$ cm$^{-2}$ and a solid angle of $(0.15-0.4)*4pi$, and no difference of neutral matter is visible between Seyfert 1 and 2 galaxies. An absorber with a lower column density of $10^{21-23}$ cm$^{-2}$ for Compton-thin Seyfert 2 galaxies is suggested to be not a torus but an interstellar medium. These constraints can be understood by the fact that the 6.4 keV line intensity ratio against the 10--50 keV flux is almost identical within a range of 2--3 in many Seyfert galaxies. Interestingly, objects exist with a low EW, 10--30 eV, of the 6.4 keV line, suggesting that those torus subtends only a small solid angle of $<0.2*4pi$. Ionized Fe-K$\alpha$ emission or absorption lines are detected from several percents of AGNs. Considering the ionization state and equivalent width, emitters and absorbers of ionized Fe-K lines can be explained by the same origin, and highly ionized matter is located at the broad line region. The rapid increase in EW of the ionized Fe-K emission lines at $N_{H}>10^{23}$ cm$^{-2}$ is found, like that of the cold material. It is found that these features seem to change for brighter objects with more than several $10^{44}$ erg/s such that the Fe-K line features become weak. We discuss this feature, together with the torus structure.Comment: 32 pages, 20 figures, ApJ accepte

Long-term results of a randomized controlled trial comparing neoadjuvant Adriamycin, cisplatin, and 5-fluorouracil vs docetaxel, cisplatin, and 5-fluorouracil followed by surgery for esophageal cancer (OGSG1003)

Sugimura, K, Yamasaki, M, Yasuda, T, et al. Long‐term results of a randomized controlled trial comparing neoadjuvant Adriamycin, cisplatin, and 5‐fluorouracil vs docetaxel, cisplatin, and 5‐fluorouracil followed by surgery for esophageal cancer (OGSG1003). Ann. Gastroenterol. Surg. 2020; 00: 1– 8. https://doi.org/10.1002/ags3.12388

海氷上のフロストフラワー形成時の化学成分の分別と濃縮

第6回極域科学シンポジウム[OM] 極域気水圏11月16日（月）　統計数理研究所 セミナー室2（D304

Retrograde Transport by Clathrin-Coated Vesicles is Involved in Intracellular Transport of PrPSc in Persistently Prion-Infected Cells

Intracellular dynamics of an abnormal isoform of prion protein (PrPSc) are tightly associated with prion propagation. However, the machineries involved in the intracellular trafficking of PrPSc are not fully understood. Our previous study suggested that PrPSc in persistently prion-infected cells dynamically circulates between endocytic-recycling compartments (ERCs) and peripheral regions of the cells. To investigate these machineries, we focused on retrograde transport from endosomes to the transGolgi network, which is one of the pathways involved in recycling of molecules. PrPSc was co-localized with components of clathrin-coated vesicles (CCVs) as well as those of the retromer complex, which are known as machineries for retrograde transport. Fractionation of intracellular compartments by density gradient centrifugation showed the presence of PrPSc and the components of CCVs in the same fractions. Furthermore, PrPSc was detected in CCVs isolated from intracellular compartments of prioninfected cells. Knockdown of clathrin interactor 1, which is one of the clathrin adaptor proteins involved in retrograde transport, did not change the amount of PrPSc, but it altered the distribution of PrPSc from ERCs to peripheral regions, including late endosomes/lysosomes. These data demonstrated that some PrPSc is transported from endosomes to ERCs by CCVs, which might be involved in the recycling of PrPSc

Comparison of the Anti-Prion Mechanism of Four Different Anti-Prion Compounds, Anti-PrP Monoclonal Antibody 44B1, Pentosan Polysulfate, Chlorpromazine, and U18666A, in Prion-Infected Mouse Neuroblastoma Cells

Molecules that inhibit the formation of an abnormal　isoform of prion protein (PrPSc) in prion-infected　cells are candidate therapeutic agents for prion　diseases. Understanding how these molecules inhibit　PrPSc formation provides logical basis for proper　evaluation of their therapeutic potential. In this study, we extensively analyzed the effects of the anti-PrP monoclonal antibody (mAb) 44B1, pentosan polysulfate (PPS), chlorpromazine (CPZ) and U18666A on the intracellular dynamics of a cellular isoform of prion protein (PrPC) and PrPSc in prion-infected mouse neuroblastoma cells to re-evaluate the effects of those agents. MAb 44B1 and PPS rapidly reduced PrPSc levels without altering intracellular distribution of PrPSc. PPS did not change the distribution and levels of PrPC, whereas mAb 44B1 appeared to inhibit the trafficking of cell surface PrPC to organelles in the endocytic-recycling pathway that are thought to be one of the sites for PrPSc formation. In contrast, CPZ and U18666A initiated the redistribution of PrPSc from organelles in the endocytic-recycling pathway to late　endosomes/lysosomes without apparent changes in the distribution of PrPC. The inhibition of lysosomal function by monensin or bafilomycin A1 after the occurrence of PrPSc redistribution by CPZ or U18666A partly antagonized PrPSc degradation, suggesting that the transfer of PrPSc to late endosomes/lysosomes, possibly via alteration of the membrane trafficking machinery of cells, leads to PrPSc degradation. This study revealed that precise analysis of the　intracellular dynamics of PrPC and PrPSc provides important information for understanding the mechanism of anti-prion agents

Temporary upregulation of anti-inflammatory cytokine IL-13 expression in the brains of CD14 deficient mice in the early stage of prion infection

CD14 deficient (CD14(-/-)) mice survived longer than wild-type (WT) C57BL/6J mice when inoculated with prions intracerebrally, accompanied by increased expression of anti-inflammatory cytokine IL-10 by microglia in the early stage of infection. To assess the immune regulatory effects of CD14 in detail, we compared the gene expression of pro- and anti-inflammatory cytokines in the brains of WT and CD14(-/-) mice infected with the Chandler strain. Gene expression of the anti-inflammatory cytokine IL-13 in prion-infected CD14(-/-) mice was temporarily upregulated at 75 dpi, whereas IL-13 gene expression was not upregulated in prion-infected WT mice. Immunofluorescence staining showed that IL-13 was mainly expressed in neurons of the thalamus at 75 dpi. These results suggest that CD14 can suppress IL-13 expression in neurons during the early stage of prion infection. (C) 2014 Elsevier Inc. All rights reserved

Characterization of intracellular dynamics of inoculated PrP-res and newly generated PrPSc during early stage prion infection in Neuro2a cells

To clarify the cellular mechanisms for the establishment of prion infection, we analyzed the intracellular dynamics of inoculated and newly generated abnormal isoform of prion protein (PrPSc) in Neuro2a cells. Within 24 h after inoculation, the newly generated PrPSc was evident at the plasma membrane, in early endosomes, and in late endosomes, but this PrPSc was barely evident in lysosomes; in contrast, the majority of the inoculated PrPSc was evident in late endosomes and lysosomes. However, during the subsequent 48 h, the newly generated PrPSc increased remarkably in early endosomes and recycling endosomes. Overexpression of wild-type and mutant Rab proteins showed that membrane trafficking along not only the endocytic-recycling pathway but also the endo-lysosomal pathway is involved in de novo PrPSc generation. These results suggest that the trafficking of exogenously introduced PrPSc from the endo-lysosomal pathway to the endocytic-recycling pathway is important for the establishment of prion infection. (C) 2013 Elsevier Inc. All rights reserved

Listeria monocytogenes serotype 4b strains replicate in monocytes/macrophages more than the other serotypes

We analyzed the pathogenicity of various serotypes of Listeria monocytogenes using a Balb/c mouse intravenous injection model. The survival rates of mice inoculated with strains NS1/2b (serotype 1/2b), NS3b (serotype 3b) and NS 4b (serotype 4b) were 60, 63.6 and 63.6%, respectively. Although the survival rates were similar, the bacterial growth in the liver of NS3b-infected mice was 144.5-fold higher than that in the liver of NS4b-infected mice. Histopathological analyses suggest that the NS4b strain replicated more in monocytes/macrophages, whereas the NS3b strain replicated more in hepatocytes. These results raise a possibility that the serotype 4b strains replicated more in monocytes/macrophages compared to the other serotype strains. To assess this, we isolated CD11b-positive cells from mouse livers infected with EGDe (serotype 1/2a), NS1/2b, NS3b, NS4b and the serotype 4b strains 51414 and F17 and counted the number of live bacteria in these cells. CD11b-positive cells from the NS4b-, 51414- and F17-infected mice possessed 24.4- to 42.7-fold higher numbers of live bacteria than those from mice infected with EGDe and NS3b strains. These results suggest that serotype 4b strains replicated more in monocytes/macrophages than the other serotypes, and this may be involved in the pathogenicity of serotype 4b strains, particularly in the dissemination of L. monocytogenes through the host body