203 research outputs found

    Neutron scattering study of dipolar spin ice Ho2Sn2O7: Frustrated pyrochlore magnet

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    By means of neutron scattering techniques we have investigated the frustrated pyrochlore magnetHo2Sn2O7, which was found to show ferromagnetic spin-ice behavior below T.1.4 K by susceptibilitymeasurements. High-resolution powder neutron diffraction shows no detectable disorder of the lattice, whichimplies the appearance of a random magnetic state solely by frustrated geometry, i.e., the corner sharingtetrahedra. Magnetic inelastic scattering spectra show that Ho magnetic moments behave as an Ising spinsystem at low temperatures and that the spin fluctuation has static character. The system remains in a shortrange-ordered state down to at least T50.4 K. By analyzing the wave-vector dependence of the magneticscattering using a mean-field theory, it is shown that the Ising spins interact via the dipolar interaction.Therefore we conclude that Ho2Sn2O7 belongs to the dipolar-spin-ice family. Slow spin dynamics is exhibitedas thermal hysteresis and time dependence of the magnetic scattering

    Synergistic Pathogenic Effects of Combined Mouse Monoclonal Anti-Desmoglein 3 IgG Antibodies on Pemphigus Vulgaris Blister Formation

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    Pemphigus vulgaris (PV) is an autoimmune blistering disease caused by anti-desmoglein 3 (Dsg3) IgG antibodies. Previously, we generated an active mouse model for PV by adoptive transfer of splenocytes from immunized or naive Dsg3−/− mice. In this study, we isolated 10 anti-Dsg3 IgG mAbs (NAK-series) from PV model mice generated by transfer of naive Dsg3−/− splenocytes. We characterized their epitopes using domain-swapped and point-mutated Dsg1/Dsg3 molecules and examined their pathogenic activities in blister formation in three different assays. In a passive transfer model using neonatal mice, eight of 10 NAK mAbs showed pathogenic activity when injected together with half the minimum pathogenic dose of anti-Dsg1 IgG autoantibodies from pemphigus foliaceus (PF) patients. None of the mAbs could induce the PV phenotype when individual hybridoma clones were inoculated by peritoneal injection into adult Rag2−/− mice. NAK mAbs displayed a range of potency in an in vitro dissociation assay using primary cultured mouse keratinocytes. Interestingly, when multiple hybridoma clones recognizing different epitopes were inoculated in combination, recipient mice developed the PV phenotype. In vitro dissociation assays confirmed that combined NAK mAbs had synergistic pathogenic effects. These findings indicate that although an individual anti-Dsg3 IgG is not sufficient to cause blistering in adult mice, several together can induce the PV phenotype. These mAbs will provide a valuable tool to investigate the molecular mechanisms of blister formation, mimicking the effects of the polyclonal IgG antibodies found in patients

    The Outline of the High School Trial Corresponding to the University Entrance Selection Reform : Special Examination Subcommittee of the National Six University Collaborative Consortium Education Collaboration Organization

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    6 大学連携事業として,評価したい資質について掘り下げ質問を行う構造化面接と,面接に代わる筆記試験であるペーパーインタビューについて,県内の高等学校の協力を得て2019 年度にトライアルを行った。評価した資質は「新たなこと追究しようとする態度」と「協働して取り組む態度」であり,まず,構造化面接とペーパーインタビューの結果を本学の教員が評価し,その結果を高校教員が個々の受験生に抱いている日常的評価と比較した。トライアルの結果,構造化面接の有効性ならびに,受験者全員に面接を課すことが,時間的,人員的に実施困難な入試におけるペーパーインタビューの有効性が確認された。同時に,測ろうとする資質によっては,面接との評価結果が異なる部分があることも明らかとなった

    Phenyl 2-amino-N,6-O-dibenzyl-2,3-N,O-carbonyl-2-de­oxy-1-thio-β-d-glucopyran­oside

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    In the crystal structure of the title compound, C27H27NO5S, the pyran­ose ring adopts a 4 C 1 chair conformation with puckering parameters Q = 0.639 (2) Å, θ = 174.11 (18) and ϕ = 256 (2)°. The presence of the 2,3-trans-oxazolidinone fixes the conformation of the pyran­ose ring. The phenyl group attached to the S atom and the benzyl group bonding to the N atom are each disordered over two positions with site occupancies of 0.624 (3):0.376 (3) and 0.526 (3):0.474 (3), respectively. An inter­molecular O—H⋯O hydrogen bond is observed

    Marmoset Cytochrome P450 3A4 Ortholog Expressed in Liver and Small-Intestine Tissues Efficiently Metabolizes Midazolam, Alprazolam, Nifedipine, and Testosterone

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    ABSTRACT Common marmosets (Callithrix jacchus), small New World primates, are increasingly attracting attention as potentially useful animal models for drug development. However, characterization of cytochrome P450 (P450) 3A enzymes involved in the metabolism of a wide variety of drugs has not investigated in marmosets. In this study, sequence homology, tissue distribution, and enzymatic properties of marmoset P450 3A4 ortholog, 3A5 ortholog, and 3A90 were investigated. Marmoset P450 3A forms exhibited high amino acid sequence identities (88-90%) to the human and cynomolgus monkey P450 3A orthologs and evolutionary closeness to human and cynomolgus monkey P450 3A orthologs compared with other P450 3A enzymes. Among the five marmoset tissues examined, P450 3A4 ortholog mRNA was abundant in livers and small intestines where P450 3A4 ortholog proteins were immunologically detected. Three marmoset P450 3A proteins heterologously expressed in Escherichia coli membranes catalyzed midazolam 19-and 4-hydroxylation, alprazolam 4-hydroxylation, nifedipine oxidation, and testosterone 6b-hydroxylation, similar to cynomolgus monkey and human P450 3A enzymes. Among the marmoset P450 3A enzymes, P450 3A4 ortholog effectively catalyzed midazolam 19-hydroxylation, comparable to microsomes from marmoset livers and small intestines. Correlation analyses with 23 individual marmoset liver microsomes suggested contributions of P450 3A enzymes to 19-hydroxylation of both midazolam (human P450 3A probe) and bufuralol (human P450 2D6 probe), similar to cynomolgus monkey P450 3A enzymes. These results indicated that marmoset P450 3A forms had functional characteristics roughly similar to cynomolgus monkeys and humans in terms of tissue expression patterns and catalytic activities, suggesting marmosets as suitable animal models for P450 3A-dependent drug metabolism

    High-energy-resolution XANES of layered oxides for sodium-ion battery

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    The 3d transition metal oxides with layered structures, Na x MO2 (M = Mn, Co), are promising cathode materials for Na-ion secondary batteries. Here, we investigate the electronic structure of the M of four layered oxides (Na0.91CoO2, Na0.66CoO2, Na1.00MnO2, and Na0.54MnO2) by means of high energy resolution fluorescence detected X-ray absorption near-edge structure, which utilizes the 1s core-hole lifetime-broadening reduction. The highly energy-resolved spectroscopy reveals a shoulder structure in the pre-edge regions of the Co K-edge spectra in Na0.91CoO2. The structure is ascribed to the transition to the Co 3d/4p states via slight hybridization with the Na 3s state

    Serologic Markers in Relation to Parasite Exposure History Help to Estimate Transmission Dynamics of Plasmodium vivax

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    Plasmodium vivax infection has been gaining attention because of its re-emergence in several parts of the world. Southeastern Turkey is one of the places in which persistent focal malaria caused exclusively by P. vivax parasites occurs. Although control and elimination studies have been underway for many years, no detailed study has been conducted to understand the mechanisms underlying the ineffective control of malaria in this region. Here, for the first time, using serologic markers we try to extract as much information as possible in this region to get a glimpse of P. vivax transmission. We conducted a sero-immunological study, evaluating antibody responses of individuals living in Sanliurfa to four different P. vivax antigens; three blood-stage antigens (PvMSP119, PvAMA1-ecto, and PvSERA4) and one pre-erythrocytic stage antigen (PvCSP). The results suggest that a prior history of malaria infection and age can be determining factors for the levels and sustainability of naturally acquired antibodies. Significantly higher antibody responses to all the studied antigens were observed in blood smear-negative individuals with a prior history of malaria infection. Moreover, these individuals were significantly older than blood smear-negative individuals with no prior history of infection. These data from an area of sole P. vivax-endemic region may have important implications for the global malaria control/elimination programs and vaccine design
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