Equilibrium Price Dispersion in a Model of Discount Competition

2004-09This paper considers the existence of equilibrium price dispersion in a model of discount competition with perfect information and homogeneous agents. The congestion effect is introduced as the scarcity of good sold at low prices. Consumers take into account not only the prices but also the availability of goods. Firms set their bargain prices and limited supplies. There exists a continuum of asymmetric Nash equilibria in which any kinds of price dispersion exist. The game structure coincides with the proportional-share game which is known in the rent-seeking literature.departmental bulletin pape

ブランド構築と生産者・商業者の社会的分業の再編

departmental bulletin pape

クセノフォン・奥田正造の教育行為に見られる共通性 : 哲学・教育学の盲点を顕在化する側面に着目して<教育科学>

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Observation of B→K*ℓ+ℓ-

journal articl

Effect of the universal prevention program for diverse disorders (Up2-D2) for junior high school students

本研究は中学生を対象としたメンタルヘルス予防プログラムを実施し，その有効性を検討することを目的とした。プログラムは(a)心理教育，(b)行動活性化，(c)社会的スキル訓練，(d)漸進的筋弛緩法，(e)ストレングス，(f)認知再構成法，(g)エクスポージャー，(h)問題解決療法を主な構成要素とし，全12回(1回50分)で行われた。中学1年生76名を対象として，プログラム事前査定（pre），中間査定（mid），事後査定(post)において，抑うつ(DSRS-C)，不安(Short CAS)，怒り感情(ASCA)，友人関係に関する尺度に回答を求めた。分析の結果，いずれの尺度もpre時点と比較してmid時点，post時点で各尺度の得点の有意な変化は見られなかった。また，分析対象者の中からpre時点でDSRS-C得点がカットオフ値を超えていた生徒13名を抽出して分析を行ったところ，DSRS-C得点がpre時点と比較してpost時点で，Short CAS得点がpre時点と比較してmid時点，post時点で有意に減少した。一方，ASCA得点，友人関係尺度(深い－浅い，広い－狭い)得点は有意な結果は得られなかった。これらの結果から，プログラムの実施による不安や怒り感情，友人関係の変容には効果がみられなかったが，学級内に潜在的に在籍する抑うつ症状，不安症状を抱える生徒に有効である可能性が示された。研究論文application/pdfdepartmental bulletin pape

Characterization of the degron/destruction sequence that is essential for NSs-FBXW11 interaction to promote PKR degradation.

<p><b>(A)</b> Description of the NSs degron mutants. The six linear amino acid sequence predicted as the degron sequence of the NSs gene is underlined and the alanine substitution mutations are marked in red. The number in the subscript denotes the amino acid residue number of the NSs protein. <b>(B)</b> Western blot analysis to determine the PKR activation and viral gene expression status in HeLa cells that were infected with rMP-12 encoding wildtype NSs gene or the NSs mutants as indicated in the figure at MOI = 10 for 8h. <b>(C)</b> IFA of NSs (green) filament formation in the nucleus of HeLa cells that were infected with rMP-12 virus expressing wildtype NSs gene or any of the various NSs mutants as indicated in the figure at MOI = 1 for 24h under normal or PKR depleted conditions. The inset shows the magnified image of white box marked in Doxycycline treated cells. Nuclei are stained blue with Hoechst (33342). The panel on the right side is the Western blot showing PKR levels in the HeLa cell line that stable express doxycycline inducible PKR shRNA under untreated or doxycycline treated conditions. <b>(D)</b> Same as C, but the percentage of infected cells was determined by HCA analysis of G expressing cells. Each data point is an average of 3 replicates ±SD. **** indicates a P < 0.0001. <b>(E)</b> Western blot analysis of p-PKR and PKR expression kinetics in HeLa cells that were infected with rMP-12 virus expressing wildtype NSs gene or any of the NSs mutants as indicated in the figure. GAPDH was used as the loading control. <b>(F)</b> Co-immunoprecipitation assay demonstrating binding between NSs mutants and FBXW11 or CUL1. 293T cell lysates transfected with Flag-FBXW11 and myc-CUL1 expression plasmids were combined with mock infected or rMP-12 encoding wildtype or mutant NSs-V5 (MOI = 10 for 8h) under normal or PKR depleted conditions as described in the figure. Lysates were immunoprecipitated with anti-V5 antibodies to test NSs binding to FBXW11, CUL1 and PKR. Western blot of lysates represents 5% of the total cell extracts.</p

D011-2120 depolymerizes microtubules similar to nocodazole.

<p>(<b>A</b>) IFA of HeLa cells that were mock infected of infected with MP12 virus for 12 h and either were mock treated or treated with vehicle control (0.5% DMSO), Brefeldin A (100 ng/ml) nocodazole (33 µM), and D011-2120 (50 µM) for 15 min, 4 h or 10 h respectively prior to stopping infection. Cells were immunostained to detect tubulin (green) or RVFV Gn (red). (<b>B</b>) HeLa cells in a 96 well plate were treated with D011-2120 or reference compounds for 4 h and immunostained with tubulin antibody. Acquired images were subjected to pattern and ridge analysis (Columbus software) to evaluate differences in microtubulin organization within the cells. Each data point is derived from eight replicates. Percent ridge values were obtained by normalizing each data point with 0.5% DMSO treated cells, which was considered 100%.</p

Golgi disruption properties of the four hit compounds and reference compounds derived from HCI-based analysis of HeLa-G cells.

<p>GC₅₀, effective concentration of compound that disrupts 50% of the Golgi complexes.</p><p>% GN_L, which is the lowest % of Golgi number achievable at the compound's highest concentration.</p><p>ND, not determined.</p

NSs binds to CUL1 most efficiently and regulates PKR degradation.

<p><b>(A)</b> Co-immunoprecipitation (Co-IP) of the NSs protein shows that CUL1 bound most efficiently to NSs among the 8 cullin family members, including CUL1 to 3, CUL4A-4B, CUL5, CUL7 or CUL9. Lysates of 293T cells that were transfected to express the vector alone or <i>myc</i>-tagged CUL1, -2, -3, -4A, -4B, -5 or -7 or HA tagged CUL9 proteins were combined with rMP-12-NSs-V5 infected cell lysates and immunoprecipitated with the anti-<i>myc</i> or anti-HA antibodies. The bound proteins were detected by Western blot analysis as shown in the figure. Lysate controls represent 5% of the lysate used in co-IP. <b>(B)</b> NSs protein binding to various CUL1 mutant proteins that were transiently expressed in 293T was determined as described above in A. αA represents IP using all three: HA, <i>myc</i> and Flag antibodies in the control <b>(C)</b> Tentative model of PKR degradation by SCF complex: CUL1 forms a molecular scaffold to organize the SCF by forming two distinct functional modules. The C terminal domain (CTD) of CUL1 (green) binds to RBX1 (R, grey), that recruits ubiquitin (U, brown) loading E2 enzyme (light green) for catalysis while the N terminus binds to SKP1 (S, grey), which recruits substrate in this case NSs (red)-PKR (blue),) <i>via</i> substrate recognizing F-box protein (yellow). PKR is presumably poly-ubiquitinated (UUU, brown) by the E2 enzyme and subjected to proteasome degradation. CUL1 is conjugated with NEDD8 (purple) and is essential for SCF E3 ligase activity.</p

Protein Kinase R Degradation Is Essential for Rift Valley Fever Virus Infection and Is Regulated by SKP1-CUL1-F-box (SCF)^FBXW11-NSs E3 Ligase

<div><p>Activated protein kinase R (PKR) plays a vital role in antiviral defense primarily by inhibiting protein synthesis and augmenting interferon responses. Many viral proteins have adopted unique strategies to counteract the deleterious effects of PKR. The NSs (Non-structural s) protein which is encoded by Rift Valley fever virus (RVFV) promotes early PKR proteasomal degradation through a previously undefined mechanism. In this study, we demonstrate that NSs carries out this activity by assembling the SCF (SKP1-CUL1-F-box)^FBXW11 E3 ligase. NSs binds to the F-box protein, FBXW11, <i>via</i> the six amino acid sequence DDGFVE called the degron sequence and recruits PKR through an alternate binding site to the SCF^FBXW11 E3 ligase. We further show that disrupting the assembly of the SCF^FBXW11-NSs E3 ligase with MLN4924 (a small molecule inhibitor of SCF E3 ligase activity) or NSs degron viral mutants or siRNA knockdown of FBXW11 can block PKR degradation. Surprisingly, under these conditions when PKR degradation was blocked, NSs was essential and sufficient to activate PKR causing potent inhibition of RVFV infection by suppressing viral protein synthesis. These antiviral effects were antagonized by the loss of PKR expression or with a NSs deleted mutant virus. Therefore, early PKR activation by disassembly of SCF^FBXW11-NSs E3 ligase is sufficient to inhibit RVFV infection. Furthermore, <i>FBXW11</i> and <i>BTRC</i> are the two homologues of the <i>βTrCP</i> (Beta-transducin repeat containing protein) gene that were previously described to be functionally redundant. However, in RVFV infection, among the two homologues of βTrCP, FBXW11 plays a dominant role in PKR degradation and is the limiting factor in the assembly of the SCF^FBXW11 complex. Thus, FBXW11 serves as a master regulator of RVFV infection by promoting PKR degradation. Overall these findings provide new insights into NSs regulation of PKR activity and offer potential opportunities for therapeutic intervention of RVFV infection.</p></div