1,054 research outputs found
INCREASED EXPRESSION OF THE RAS SUPPRESSOR, RSU-1, INCREASES ERK-2 ACTIVATION AND INHIBITS JUN KINASE ACTIVATION
No full textStudies were undertaken to determine the effect of the Ras suppressor Rsu-1 on Ras signal transduction pathways in two different cell backgrounds. An expression vector containing the mouse rsu-I cDNA under the control of a mouse mammary tumor virus promoter was introduced into NIH 3T3 cells and the pheochromocytoma cell line PC12. Cell lines developed in the NIH 3T3 background expressed p33(rsu-1) at approximately twice the normal endogenous level. However, PC12 cell clones which expressed p33(rsu-1) at an increased level in a regulatable fashion in response to dexamethasone were isolated. Analysis of proteins involved in regulation of Ras and responsive to Ras signal transduction revealed similar changes in the two cell backgrounds in the presence of elevated p33(rsu-1). There was an increase in the level of SOS, the guanine nucleotide exchange factor, and an increase in the percentage of GTP-bound Ras. In addition, there was an increase in the amount of p120 Ras-specific GTPase-activating protein (GAP) and GAP-associated p190. However, a decrease in Ras GTPase-activating activity was detected in lysates of the Rsu-1 transfectants, and immunoprecipitated p120 GAP from the Rsu-1 transfectants showed less Ras GTPase-activating activity than GAP from control cells. Activation of Erk-2 kinase by growth factor and tetradecanyol phorbol acetate was greater in the Rsu-1 transfectants than in control cells. However, c-Jun amino-terminal kinase activity (Jun kinase) was not activatable by epidermal growth factor in Rsu-1 PC12 cell transfectants, in contrast to the PC12 vector control cell line. Transient expression of p33(rsu-1) in Cos1 cells following cotransfection with either hemagglutinin- tagged Jun kinase or hemagglutinin-tagged Erk-2 revealed that Rsu-1 expression inhibited constitutive Jun kinase activity while enhancing Erk-2 activity. Detection of in vitro binding of Rsu-1 to Raf-1 suggested that in Rsu-1 transfectants, increased activation of the Raf-1 pathway occurred at the expense of activation of signal transduction leading to Jun kinase. These results indicate that inhibition of Jun kinase activation was sufficient to inhibit Ras transformation even in the presence of activated Erk-2
The Ras suppressor RSU-1 localizes to 10p13 and its expression in the U251 glioblastoma cell line correlates with a decrease in growth rate and tumorigenic potential.
No full textTHE RAS SUPPRESSOR RSU-1, ENHANCES NGF-INDUCED DIFFERENTIATION OF PC12 CELLS AND INDUCES P21CIP EXPRESSION
No full textThe Rsu-1 Ras suppressor gene was isolated based on its ability to inhibit v-Ras transformation. Using Rsu-1 transfectants of the pheochromocytoma cell line PC12, we demonstrated previously that Rsu-1 expression inhibited Jun kinase activation but enhanced Erk2 activation in response to epidermal growth factor. In the present study, the Rsu-1 PC12 transfectants were used to investigate the role of Rsu-1 in nerve growth factor (NGF)- and v-Ki-ras-mediated neuronal differentiation. NGF-induced neurite extension was enhanced, not inhibited, by the expression of Rsu-1 in PC12 cells. The activation of Erk kinase activity in response to NGF was sustained longer in the Rsu-1 transfectants compared with the vector control cells. During NGF-mediated differentiation, an increase in the expression of specific mRNAs for the early response genes Fos, cJun, and NGF1a was detected in both the vector control and Rsu-1 transfectants. The expression of the differentiation-specific genes VGF8 and SCG10 was similar in Rsu-1 transfectants compared with the vector control cells. The induction of Rsu-1 expression in these cell lines did not inhibit v-Ki-ras-induced differentiation, as measured by neurite extension. These data suggest that although Rsu-1 blocked some Ras-dependent response(s), these responses were not required for differentiation. Moreover, the induction of Rsu-1 expression in the PC12 clones resulted in growth inhibition and p21(WAF/CIP) expression. Hence, Rsu-1 expression enhances NGF-induced differentiation while inhibiting the growth of cells
Grasping at straws: a ratings downgrade for the emerging international financial architecture
No full textFollowing the Asia crisis of 1997-98, policymakers invested a great deal of energy in designing a new international financial architecture. However many of the policy proposals which have emerged from think tanks and the multilateral agencies have proven unworkable or politically unpalatable. The debate focuses on state-led initiatives. But the assumption that public policy is by definition an output of public institutions is difficult to sustain in an era of global change. This paper considers specialized forms of intelligence-gathering and judgment-determination which seem increasingly important as sources of governance in this era of financial market volatility. These agents - embedded knowledge networks (EKNs) - include the major bond rating agencies, Moody’s Investors Service and Standard and Poor’s, the focus of this paper. The Basel Committee has put forward a serious proposal to reform the existing capital adequacy framework which uses banks' own internal ratings and external bond ratings to calculate bank risk-weighted capital requirements. The paper shows that there are potentially unexpected consequences from using private rating agencies as a substitute for state-based regulation, due to the organizational incentives that shape the ratings industry. Cementing these organizational incentives into the emerging financial architecture will give rise to negative social and economic consequences
Letter to Benjamin Clark Cutler from Benjamin Stevens
No full textLetter dated April 14, 1863 to Assistant Adjutant General, Captain Benjamin Clark Cutler, Santa Fe, from First Lieutenant Benjamin Stevens, Fort Wingate, New Mexico, recommending John Murphy and Martin Quintana, in the First New Mexico Volunteers, for military promotion to Second Lieutenant. Letter also signed by First Lieutenant J. L. Barbey, joint author. Civil War. HL introduction page overlaid by document. Letter in English, handwritten, 1pp/fr
Accelerations for global optimization methods that use second derivative information
No full textTwo new improvements for the algorithm of Breiman & Cutler are presented. Better envelopes can be built up using positive definite quadratic forms. Better utilization of first and second derivative information is attained by combining both global aspects of curvature and local aspects nearthe global optimum. The basis of the results is the geometric viewpoint developed by the first author and can be applied to a number of covering type methods. Improvements in convergence rates are demonstrated empirically on standard test functions
Rituximab for prevention and treatment of graft-versus-host disease
No full textGrowing understanding of the important role of B lymphocytes in alloreactivity has paved the way for evaluating anti-B cell therapy with rituximab in patients undergoing allogeneic hematopoietic cell transplantation. Data suggesting a beneficial reduction in incidence and severity of acute graft-versus-host disease (GVHD) are limited to non-randomized studies from single institutions using higher than conventional doses of rituximab. Additionally, rituximab is used as an effective treatment of corticosteroid-refractory chronic GVHD with good responses, particularly in cases of dermatologic and mucosal involvement. Post-transplant administration of rituximab appears to reduce the rate of chronic GVHD in preliminary studies.ARAI S, 2008, ASH ANN M, V112, P466; Canninga-van Dijk MR, 2004, BLOOD, V104, P2603, DOI 10.1182-blood-2004-05-1855; CUTLER C, 2010, ASH ANN M, V116, P214; Cutler C, 2006, BLOOD, V108, P756, DOI 10.1182-blood-2006-01-0233; Do RKG, 2002, CYTOKINE GROWTH F R, V13, P19, DOI 10.1016-S1359-6101(01)00025-9; Eapen M, 2007, BIOL BLOOD MARROW TR, V13, P1461, DOI 10.1016-j.bbmt.2007.08.006; Glass B, 2008, ASH ANN M, V112, P1974; Harris DP, 2000, NAT IMMUNOL, V1, P475, DOI 10.1038-82717; Kapur R, 2008, HAEMATOL-HEMATOL J, V93, P1702, DOI 10.3324-haematol.13311; Kayagaki N, 2002, IMMUNITY, V17, P515, DOI 10.1016-S1074-7613(02)00425-9; KHARFANDABAJA MA, 2010, BIOL BLOOD MARROW TR, V16, pS281, DOI 10.1016-j.bbmt.2009.12.376; Kharfan-Dabaja MA, 2009, BIOL BLOOD MARROW TR, V15, P1005, DOI 10.1016-j.bbmt.2009.04.003; Kharfan-Dabaja MA, 2008, BIOL BLOOD MARROW TR, V14, P121, DOI 10.1016-j.bbmt.2007.12.340; Khouri IF, 2008, BLOOD, V111, P5530, DOI 10.1182-blood-2008-01-136242; Khouri IF, 2007, BRIT J HAEMATOL, V137, P355, DOI 10.1111-j.1365-2141.2007.06591.x; Khouri IF, 2001, BLOOD, V98, P3595, DOI 10.1182-blood.V98.13.3595; Kim SJ, 2010, HAEMATOL-HEMATOL J, V95, P1935, DOI 10.3324-haematol.2010.026104; McIver Z, 2010, BIOL BLOOD MARROW TR, V16, P1549, DOI 10.1016-j.bbmt.2010.05.004; Mellon-Reppen S, 2010, BONE MARROW TRANSPL, V45, P1758, DOI 10.1038-bmt.2010.58; Mohty M, 2008, BONE MARROW TRANSPL, V41, P909, DOI 10.1038-bmt.2008.12; Okamoto M, 2006, LEUKEMIA, V20, P172, DOI 10.1038-sj.leu.2403996; Pidala J, 2011, INT J HEMATOL, V93, P206, DOI 10.1007-s12185-010-0747-x; Ratanatharathorn V, 2003, BIOL BLOOD MARROW TR, V9, P505, DOI 10.1016-S1083-8791(03)00216-7; Ratanatharathorn V, 2000, ANN INTERN MED, V133, P275; Ratanatharathorn V, 2009, BRIT J HAEMATOL, V145, P816, DOI 10.1111-j.1365-2141.2009.07674.x; RATANATHARATHOR.V, 2007, BLOOD, V110; Sarantopoulos S, 2009, BLOOD, V113, P3865, DOI 10.1182-blood-2008-09-177840; Sarantopoulos S, 2011, BLOOD, V117, P2275, DOI 10.1182-blood-2010-10-307819; Schaerli P, 2000, J EXP MED, V192, P1553, DOI 10.1084-jem.192.11.1553; Schultze JL, 1997, J CLIN INVEST, V100, P2757, DOI 10.1172-JCI119822; Shimabukuro-Vornhagen A, 2009, BLOOD, V114, P4919, DOI 10.1182-blood-2008-10-161638; Teshima T, 2009, INT J HEMATOL, V90, P253, DOI 10.1007-s12185-009-0370-x; van Dorp S, 2009, BIOL BLOOD MARROW TR, V15, P671, DOI 10.1016-j.bbmt.2009.02.005; von Bonin M, 2008, TRANSPLANTATION, V86, P875, DOI 10.1097-TP.0b013e318183f662; Zaja F, 2007, BONE MARROW TRANSPL, V40, P273, DOI 10.1038-sj.bmt.170572511141
The Battle of Leyte Gulf 23 - 26 October 1944
No full textOn the fiftieth anniversary of the Battle of Leyte Gulf, Thomas J. Cutler, author of the highly praised Brown Water, Black Berets, takes a fresh look at the greatest of all naval battles. Using materials not available to previous authors, Cutler captures the milieu, analyzes the strategy and tactics employed, and re-creates the experiences of the participants - from seaman to admiral - both Japanese and AmericanTo describe the Battle of Leyte Gulf as the "greatest of all naval battles" is no exaggeration. The American, Japanese, and Australian ships engaged in the battle numbered 282, and hundreds more were involved in related peripheral operations. Nearly two hundred thousand men participated, in a geographical area spanning more than a hundred thousand square milesDozens of ships were sunk, including some of the largest and most powerful ever built, and thousands of men went to the bottom of the sea with them. Every facet of naval warfare - air, surface, submarine, and amphibious - was involved in this great struggle, and the weapons used included bombs of every type, guns of every caliber, torpedoes, mines, rockets, and even a forerunner of the guided missil
A Late Antique Ivory Plaque and Modern Response
No full textA recently published challenge to the authenticity of the ivory plaque of the Symmachi, now in the Victoria and Albert Museum, is refuted, and its late fourth-century origin is confirmed by comparison with other plaques whose fourth- or fifth-century date is secure. The charge of forgery is related to patterns in recent art historiography, and these are traced to an anachronistic critical vocabulary that entails inappropriate norms of illusionistic depiction. A different vocabulary is proposed, based on a reexamination of the plaque\u27s visible structure and of its artistic sources.
A pendant note by Anthony Cutler scrutinizes the fabric of the Symmachi diptych leaf and the manner in which it was worked. Recognizing both resemblances to and differences from the companion leaf of the Nicomachi, the author argues that these fit a known pattern of Late Antique workshop production and that the technical arguments underlying the claim that SYMMACHORVM is a 19th-century creation are therefore groundless
OTOH
No full textContains the essay “Unsettled Feelings". Funded by SSHRC Institutional Explore Grant. Design by Chloe Brumwell & Randy Lee Cutler.Unsettle
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