Effect of a small molecule inhibitor of nuclear factor-κB nuclear translocation in a murine model of arthritis and cultured human synovial cells

A small cell-permeable compound, dehydroxymethylepoxyquinomicin (DHMEQ), does not inhibit phosphorylation and degradation of IκB (inhibitor of nuclear factor-κB [NF-κB]) but selectively inhibits nuclear translocation of activated NF-κB. This study aimed to demonstrate the antiarthritic effect of this novel inhibitor of the NF-κB pathway in vivo in a murine arthritis model and in vitro in human synovial cells. Collagen-induced arthritis was induced in mice, and after onset of arthritis the mice were treated with DHMEQ (5 mg/kg body weight per day). Using fibroblast-like synoviocyte (FLS) cell lines established from patients with rheumatoid arthritis (RA), NF-κB activity was examined by electrophoretic mobility shift assays. The expression of molecules involved in RA pathogenesis was determined by RT-PCR, ELISA, and flow cytometry. The proliferative activity of the cells was estimated with tritiated thymidine incorporation. After 14 days of treatment with DHMEQ, mice with collagen-induced arthritis exhibited decreased severity of arthritis, based on the degree of paw swelling, the number of swollen joints, and radiographic and histopathologic scores, compared with the control mice treated with vehicle alone. In RA FLS stimulated with tumor necrosis factor-α, activities of NF-κB components p65 and p50 were inhibited by DHMEQ, leading to suppressed expression of the key inflammatory cytokine IL-6, CC chemokine ligand-2 and -5, matrix metalloproteinase-3, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1. The proliferative activity of the cells was also suppressed. This is the first demonstration of an inhibitor of NF-κB nuclear translocation exhibiting a therapeutic effect on established murine arthritis, and suppression of inflammatory mediators in FLS was thought to be among the mechanisms underlying such an effect

A Study on a High Frequency Application of Thyristor

Static switches utilizing thyristor capable of switching at high frequency are described. A brief summary of the experimental operation of the device is included, followed by an analysis of the static switches. Design procedures and graphs are developed that make possible the design of such static switches based upon design criteria.Article信州大学工学部紀要 21: 11-20 (1966)departmental bulletin pape

X-Ray Spectra of the Narrow-Line Seyfert 1 Galaxy Ton S180 in Comparison with Galactic Black Holes

An analysis was made of 0.3-15 keV X-ray spectra of a Narrow-Line Seyfert 1 Galaxy, Ton S180, using archival data from ASCA, RXTE, and XMM-Newton. At energies above 2.5 keV, a power-law with a photon index of ~ 2.3 successfully and consistently reproduced the spectra from all of these observatories. Assuming this power-law component to extend toward lower energies, a soft excess, which is one of the most remarkable features of Narrow-Line Seyfert 1 Galaxies, is explained by another power-law multiplied by a thermal cutoff at ~ 0.4 keV. Some similarities have been observed between this object and Galactic black hole binaries in very high state, the latter being realized under high accretion rates. Attempts have been made to interpret the soft excess in terms of Comptonization of the disk photons by an electron cloud surrounding the accretion disk, like BHBs in a very high state.Comment: 7 pages, 7 figure

Discovery of a bright transient ultraluminous X-ray source Suzaku J1305-4931 in NGC 4945

This paper reports the discovery of a bright X-ray transient source, Suzaku J1305-4913, in the south-west arm of the nearby Seyfert II galaxy NGC 4945. It was detected at a 0.5 -- 10 keV flux of $2.2 \times 10^{-12}$ erg cm$^{-2}$ s$^{-1}$ during the Suzaku observation conducted on 2006 January 15 -- 17, but was undetectable in a shorter observation on 2005 August 22 --23, with an upper limit of $1.7 \times 10^{-14}$ erg cm$^{-2}$ s$^{-1}$ (90% confidence level). At a distance of 3.7 Mpc, the bolometric luminosity of the source becomes $L_{\rm bol} = 4.4 \times 10^{39} \alpha$ erg s$^{-1}$, where $\alpha = (\cos 60^\circ / \cos i)$ and $i$ is the disk inclination. Therefore, the source is classified into so-called ultraluminous X-ray sources (ULXs). The time-averaged X-ray spectrum of the source is described by a multi-color disk model, with the innermost accretion disk temperature of $T_{\rm in} = 1.69_{-0.05}^{+0.06}$ keV. During the 2006 January observation, it varied by a factor of 2 in intensity, following a clear correlation of $L_{\rm bol} \propto T_{\rm in}^4$. It is inferred that the innermost disk radius $R_{\rm in}$ stayed constant at $R_{\rm in} = 79_{-3.9}^{+4.0} \alpha^{1/2}$ km, suggesting the presence of a standard accretion disk. Relating $R_{\rm in}$ with the last stable orbit around a non-rotating black hole yields a rather low black hole mass, $\sim 9 \alpha^{1/2}$ solar masses, which would imply that the source is shining at a luminosity of $\sim3 \alpha^{1/2}$ times the Eddington limit. These results can be better interpreted by invoking sub-Eddington emission from a rapidly spinning black hole with a mass of 20 -- 130 solar masses.Comment: 21 pages, 10 figures, Accepted for PASJ 2nd Suzaku special issu

Effect of Air and Root Temperatures on the Development of Flower Cluster Borne on the Forced Lateral Shoot of Muscat of Alexandria Grapes

ブドウ,Muscat of Alexandriaの2期作栽培において,2期作目の花穂は1期作目にくらべて発育が著しく劣るが,これは2期作目の発芽から開花までが夏期にあたるため,この時期の気温が高すぎることも大きく影饗している. そこで本実験では,気温条件が高すぎる場合に地温を人為的に操作することによって花穂の発育不良を回復することができるかどうかを確めるために,ポット植えのMuscat of Alexandriaの2番枝の発芽直前から気温(30℃,25℃,自然)と地温(30℃,25℃,20℃)をかえて,2番枝上の花穂の発育を比較した. (1)2番枝の生長はいずれの気温の場合にも地温20℃区で劣ったが,とくに気温が高いほどこの傾向が著しかった. 花穂の伸長もこれとほぼ同様な傾向がみられ,とくに30℃-20℃(気温-地温)区では,すべての花穂が発育を停止し,発芽後約20日目には枯死した. (2)気温が30℃でも地温25℃および30℃の両区では気温25℃あるいは自然気温(平均23.4℃）の場合と同じように花穂は発育して開花に至ったが,この両区では開花初期から落花が著しく,満開後約10日目における結実率は最も低かった. いっぽう,25℃-25℃区では第2次花穂数,花らい数ともに最も多く花穂の発育はすぐれ,また,この区の結実率は高かった. (3)以上の結果から,Muscat of Alexandriaの2番枝に着生した花穂の高温による発育不良は地温を下げることによって回復することは不可能で,気温が高いほど地面も高温を必要としたが,気温が30℃恒温では地温をどのように調整しても結実が悪く,気温条件としては高すぎると思われた

Effects of Root Temperature on Development of Flower Cluster, Berry Set and Berry Growth of Muscat of Alexandria Grapes

ブドウ“マスカット・オブ・アレキサンドリア"のつぎ木苗(H.F.台)について,発芽約3週前から落果終了期まで(実験I)と,開花約10日前から果肉細胞の分裂終了期まで(実験II)地温処理を行い,花穂の発育,結実,果粒の発育等に及ぼす影饗を調査した. またこの時期までの処理が収穫果に及ぼす影響についても調査した. 1) 実験Iにおいて,花穂の伸長は30℃区ですぐれ,花穂当りの小花数もこの区で最も多かったが,これ以下の地温では小花数に大きな差はみられなかった. 一方,33℃区では花穂の発育異常がみられ,花穂当りの小花数は著しく少なく,小花分化期の地温条件としては高温すぎると思われた. 2) 結実率は実験Iでは18,20,25,30℃の各区で､また実験IIでは20,25,30℃の各区で高く,一方,15℃区では実験I,IIともに最も低かった. 花穂の発育異常がみられた33℃区でも結実率はすぐれた. 結実率と人工培地上での花粉の発芽率との間には明確な関連は認められなかった. 3) 処理終了時の果粒の大きさは,実験I,IIともに25,30℃の両区ですぐれ,15℃区で劣った. 15℃区では果肉の外壁及び内壁の細胞数は他の区よりもいく分少ない程度であったが,その大きさ,とくに内壁細胞の大きさは著しく小さかった. また実験Iの33℃区と実験IIの35℃区では,外壁及び内壁の細胞数が少ない傾向であった. 4) 収穫果の大きさは,実験Iでは18,20,25℃の各区で,また実験IIでは25,30,35℃の各区ですぐれたのに対し,15℃区では実験I,IIともに最も小さかった. 果粒中の種子数は15℃区で著しく少なく,とくに実験Iの15℃区では果粒当り2個以下のものが70%以上を占めた. 果汁の屈折計示度及び酸含量には実験I,IIともに処理区間での差は認められなかった