LMDA Review, volume 10, issue 1

Contents include: Photo of Conference Participants Annual Conference 1999, Send in your Ballot, A Note to Ourselves, Increase in Dues and New Annual Membership Expiration Date, LMDA Archive, LMDA Administrator; LMDA Interns, Mid-Year Meeting, Early Career Dramaturg Program, Elliot Hayes Award 2000, Report on Canadian Caucus, Script Exchange, Report on the Dramaturgy Focus Group ATHE 1999, Elliot Hayes Award Winners Lue Douthit and Michel Volansky, Acceptance Speech Lue Morgan Douthit, Elliot Hayes Award Presentation to Michele Volansky for Space, On the Elliot Hayes Award Michele Volansky, Day One of the Conference, Day Two of the Conference, Day Three of the Conference, Day Four of the Conference, The Advocacy Caucus Presentation at the Conference, Final Thoughts, Conference 1999 Many Thanks, Arthur Ballet and the Office for Advanced Drama Research, Spotlight on Early Career Dramaturg Vanessa Porteous, A Working History of LMDA The Early Years, From Academia to Arena A Dramaturg\u27s Education in the Real World, Tony Creamer and Death of a Salesman, Two Moments, Jobs and Projects, Scriptseeker.com, LMDA Online Listserv Instructions, Note from James Magruder, Literary Managers and Dramaturgs of the Americas Bibliography 1999, Noted with Pleasure, and Internship Questionnaire.https://soundideas.pugetsound.edu/lmdareview/1020/thumbnail.jp

Vera Fedorovna Kommissarzhevskaia: A life in performance.

Vera Fedorovna Kommissarzhevskaia (1864-1910) is acknowledged as one of the finest actresses in the history of Russian theatre. She began her career in 1891 in a production directed by Stanislavsky and soon blazed across the Russian stage, creating at St. Petersburg's Aleksandrinskii Theatre the role of Nina in the first production of Chekhov's Seagull. In time she opened a theatre of her own, a theatre devoted to finding a new dramatic form. Here some of the most innovative figures in Russian theatrical history--Meyerhold, Tairov, Evreinov, Blok, Khol'mskaia and Gorky--created important work. I am always searching for the new form, the new dramatic idea and the new inspiration Kommissarzhevskaia said in an interview with the New York Times (March 1, 1908). As a result of her search, her theatrical legacy emerged in four ways: one, the quest for a new dramaturgy or style of play writing; two, the casting off of traditional Russian styles of acting; three, the emergence of the profession of the stage director; and four, the emergence of a collaborative style of theatrical production. These contributions were directly related to her performance of self and thus the performance of gender as strategy for survival. All were crucial to the evolution of twentieth-century Russian theatre. Kommissarzhevskaia was not alone in embracing new ideas for she lived during a time of transition. And like the changing times in which she lived, her performance of self changed greatly and frequently during her lifetime. Reacting consciously and subconsciously to a variety of factors in her history and personal makeup, she changed her persona, her perceivable self to optimize her chances of success in life. Critical to Kommissarzhevskaia's performance of self was the idea of progress, of moving forward in new and unexplored directions, and as a result she served as a catalyst for many of the changes that were sweeping the Russian theatre at the turn-of-the-century.Ph.D.BiographiesCommunication and the ArtsLanguage, Literature and LinguisticsSlavic literatureSocial SciencesTheaterUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/130340/2/9722072.pd

Mechanism of MEK inhibition determines efficacy in mutant KRAS- versus BRAF-driven cancers

KRAS and BRAF activating mutations drive tumorigenesis through constitutive activation of the MAPK pathway. As these tumours represent an area of high unmet medical need, multiple allosteric MEK inhibitors, which inhibit MAPK signalling in both genotypes, are being tested in clinical trials. Impressive single-agent activity in BRAF-mutant melanoma has been observed; however, efficacy has been far less robust in KRAS-mutant disease. Here we show that, owing to distinct mechanisms regulating MEK activation in KRAS- versus BRAF-driven tumours, different mechanisms of inhibition are required for optimal antitumour activity in each genotype. Structural and functional analysis illustrates that MEK inhibitors with superior efficacy in KRAS-driven tumours (GDC-0623 and G-573, the former currently in phase I clinical trials) form a strong hydrogen-bond interaction with S212 in MEK that is critical for blocking MEK feedback phosphorylation by wild-type RAF. Conversely, potent inhibition of active, phosphorylated MEK is required for strong inhibition of the MAPK pathway in BRAF-mutant tumours, resulting in superior efficacy in this genotype with GDC-0973 (also known as cobimetinib), a MEK inhibitor currently in phase III clinical trials. Our study highlights that differences in the activation state of MEK in KRAS-mutant tumours versus BRAF-mutant tumours can be exploited through the design of inhibitors that uniquely target these distinct activation states of MEK. These inhibitors are currently being evaluated in clinical trials to determine whether improvements in therapeutic index within KRAS versus BRAF preclinical models translate to improved clinical responses in patients. 2013 Macmillan Publishers Limited. All rights reserve