356 research outputs found
Substrate specificity of [alpha]-proteobacterial N-end rule adaptors
No full textThesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2016.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student-submitted PDF version of thesis. "June 2016." In title on title page [alpha] appears as lower case Greek letters.Includes bibliographical references (pages 103-118).by Benjamin J. Stein.Ph. D
Global Cicada Sound Collection I: Recordings from South Africa and Malawi by B. W. Price & M. H. Villet and harvesting of BioAcoustica data by GBIF
No full textThe file attached is the published version of the article. © Baker E et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.NHM Repositor
Mapping the Landscape of Acquired Vulnerabilities in Ovarian Cancer
No full textRecent undertakings to identify the genetic lesions associated with ovarian cancer have noted the striking diversity of mutations occurring in this disease. This genetic diversity has complicated the search for novel therapies. However, recent data has suggested that one commonality of ovarian tumors might be ablation of miRNA biogenesis. Here I conducted a broad-scale gain-of-function microRNA (miRNA) screen in 16 ovarian cancer cell lines to annotate the functional landscape present in such a chaotic genetic background. miRNAs function as multigenic perturbations allowing for interrogation of maximal gene space with few experiments. This screen identified multiple miRNAs reducing cell viability with the majority of hits being toxic in only one or two lines screened. This surprising finding reflected the commonality of altered miRNA function in ovarian tumors while also suggesting that specifics of this alteration in function are unique to each tumor. To investigate more public vulnerabilities, I focused mechanistic studies on miRNAs displaying penetrance in greater than 5 cell lines. miR-517a reduced cell viability in over 30% of the panel and also reduced tumor burden in vivo. Functional analysis of the predicted targets of miR-517a revealed that expression of this miRNA reduced protein levels of ARCN1, a member of the coatamer complex, and that knockdown of ARCN1 reduced cell viability similar to miR-517a. Another penetrant miRNA, miR-124a, reduced cell viability in 37.5% of the panel and functional analysis of this miRNA revealed it promoted a cell differentiation program. Analysis of predicted targets revealed that expression of miR-124a reduced expression the homeodomain transcription factor SIX4, resulting in increased signaling along the tumor suppressive AMPK pathway and epithelial differentiation. Furthermore, SIX4 displayed increased expression in ovarian tumors and depletion of SIX4 expression reduced tumor cell viability in vitro and in vivo. Therefore, SIX4 overexpression might function to deflect cell differentiation in tumors. Thus, the common loss of miRNA function observed in ovarian tumors might serve to maintain an undifferentiated state, and engagement of cell fate determination programs via re-expression of miRNAs can result in catastrophic consequences for cancer cell viability
Nucleotide binding and conformational switching in the hexameric ring of a AAA+ machine
No full textThesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, February 2015.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student-submitted PDF version of thesis.Includes bibliographical references.ATP-powered proteases enforce protein quality-control and regulation in all domains of life. ClpX, a AAA+ ring homohexamer, uses the energy of ATP binding and hydrolysis to power conformational changes that unfold and translocate target proteins into the ClpP peptidase for degradation. X-ray crystal structures show that some ClpX subunits occupy nucleotide-loadable conformations and others occupy unloadable conformations. Furthermore, biochemical evidence suggests that multiple classes of nucleotide-loadable subunits exist. How asymmetry among subunits is coordinated to achieve mechanical function has remained unclear. Using a combination of mutagenesis, disulfide crosslinking, and fluorescence methods to assay the conformations and nucleotide-binding properties of individual subunits, we demonstrate dynamic interconversion of loadable and unloadable subunits. Such interconversion is required to couple ATP hydrolysis by ClpX to mechanical work, plays a role in substrate binding and ClpP interaction, and is not strictly coupled to the ATP hydrolysis cycle. ATP binding to different classes of subunits drives allosteric changes in ring conformation to allow hydrolysis and coupled machine function, and we present a subunit-specific single molecule nucleotide occupancy assay to elucidate details of this process.by Benjamin M. Stinson.Ph. D
The later orchestral works of William Walton: a critical and analytical re-evaluation
No full textAlthough the British twentieth-century composer William Walton enJoys a continuing presence in the international canon, the body of scholarship that seriously engages with his life and work is small. The post-war music, which includes the Cello Concerto (1956), Second Symphony (1961), Variations on a Theme of Hindemith (1963), Improvisations on
an Impromptu of Benjamin Britten (1969), and the film score for Battle of Britain (1969), has been particularly underrepresented in critical and analytical writing. In this thesis, I give detailed analyses of these scores, alongside an investigation of the contemporary critical
climate and reception history of these works.
I argue that the series of significant lifestyle changes that Walton underwent in the years immediately following the Second World War - including exchanging the busy musical life of London and a series of affairs with high-profile figures for the 'dolce far niente' of an isolated Italian island and a stable marriage - are suggestive of a broad shift in the composer's social and cultural values with consequent changes in musical attitudes and compositional tendencies. Walton's later music is differentiated from the pre-war works by the presence of octatonic, twelve-note, hexatonic and other non-diatonic harmonic constructions in the foreground, and a change from teleological to network-based or rotational background structures. My analyses adopt a deliberately eclectic range of analytical strategies, combining aspects of set-class approaches alongside tools from the tonal tradition. This methodological pluralism reflects my argument that the vitality of these scores derives from a tension between modernist and traditional tendencies. I argue that
Walton appropriates a wide range of influences, including to some extent that of the European avant garde, in contradistinction to the assertion prominent in contemporary
reception literature that his music had stagnated into a single outmoded and rarefied style.
I conclude that although Walton's post-war music was indeed conservative in comparison to that of several of his younger contemporaries, his music engages, through opposition and assimilation, with many of the most characteristic trends of twentieth-century concert
music. Nevertheless, I argue that the temptation to label Walton as a 'modernist' should be avoided; his works should be judged on their own terms and not according to the
regressive--progressive axis prominent in much of the contemporary reception literature. These scores may not have been progressive, but they have a distinctive sound-world and an invigorating vitality that makes them exceptionally engaging both as works of art and
objects of study
Questioning modern time with Hannah Arendt and Walter Benjamin
No full textFour texts from Arendt and Benjamin are the scene of our thinking. We enact the question of time as a refusal to abide by the modern conception of time, where the present is the only ground of the real. We argue for a notion of time, in which all that-has-been is considered a site of real experience.
Firstly we discuss Arendt's book On Revolution. Through issues such as history, the eventful and revolt we show the usefulness of the question of time to further our understanding. Secondly in Arendt's 'What is Freedom', freedom is discussed beyond the private individual, as a matter of plurality, of living together. The question of time shows freedom grounded beyond the individual's present, in the historical time of plurality.
With Benjamin's essay 'On some motifs in Baudelaire' we show poetry as a challenge to the symbolic environment of the commodity world. Poetry appears as a keeper of our relation to the time of memory and language that precedes us. In Benjamin's 'The Work of Art in the Age of Its Technological Reproducibility', we distinguish art from technology through the question of time. Art's experience
involves an active relation with what-has-been, with past generations; it challenges the technological way of relating to the world that destroys the depth of human expenence.
Finally, Arendt and Benjamin are presented together, stressing their use of history and tradition to address the problems of modernity. Their effort to think the eventful is related to their negation of historical progression. From the question of time, their thinking teaches us a form of critique that denies the preconception of presence as being the totality of the real. Under their gaze presence is revealed as a changing surface under the sway of history, of time
An analytical study of the Sonata in C for cello and piano by Benjamin Britten
No full textvi, 248 l. charts, music. 28 cm. Appendix: leaves 240-245. Bibliography: leaves 246-248.“…true analysis works through and for the ear. The greatest analysts (like Schenker at his best) are those with the keenest ears; their insights reveal how a piece of music should be heard, which in turn implies how it should be played. An
analysis is a direction for a performance.” In this era of the twentieth century, an age in which technical proficiency is frequently considered the ultimate achievement of the performer, the lack of attention given to the content of the music itself is often evident. The tenor of the ensuing study was provoked by the author's reluctance to accept the performance of music on a purely technical and emotional basis. for it is the conviction of the author that a truly artistic performance is based not only on technical ability and emotion, but also on a sound understanding of the music as well. Such an understanding may begin with a knowledge of the constituent elements of style and a concept of their subsequent
meaning and application to performance. The following outline, based on the premise that the chief elements of style are melody and rhythm, undertakes to show a relationship between style and performance. I. Elements of Style. A. Melody. 1. formal organization (form); 2. Tonal organization (tonality); 3. textural arrangement: (a). homophony (harmony); (b). polyphony (counterpoint). B. Rhythm--the setting of melody. 1. metric basis (meter). II. Application of the elements of melody to performance. A. Formal organization. 1. phrasing (intelligibility); 2. contour (sense of movement both towards and away from points of climax). B. Tonal organization. 1. color (varied between bright and dark by
modality, polytonality, and polymodality). Ill. The control of melody in performance . A. Tempo (faster or slower). B. Dynamics (louder or softer). 1. balance of dynamics (to achieve a proper relationship of the melody with the texture). It is the desire of the author that the following study, based on the above approach to performance, may contribute to a better understanding of the Benjamin Britten Sonata in C for cello and piano.
Negotiating the Principia: the failure of Newton's arguments to persuade his readers, 1684-94
No full textWhen Isaac Newton’s 'Principia Mathematica' was published in the summer of 1687, it met with immediate acclaim. Through a close examination of contemporary reading notes, this thesis aims to establish the extent to which that acclaim was the result of his peers’ assent to the arguments contained in the book.
It will demonstrate that, so far as can be reliably inferred from the extant documentary evidence, early readers were generally not persuaded by the demonstrations in the 'Principia'. Newton’s peers commonly didn’t scrutinise the arguments in his book; when they did scrutinise them, they commonly didn’t understand them; and when they did understand them, they commonly didn’t agree with them. They frequently disputed the composition of his proofs, the validity of his methodology, and the articulation of his foundational concepts. When circumstances allowed, they communicated these misgivings back to Newton, who often altered his text in response, re-working, re-phrasing and re-structuring his demonstrations. They questioned both the formulation of his method of first and last ratios and his mathematisation of force, and none of the readers for whom there is reliable evidence assented to the entirety of Newton’s proof of the inverse-square law. To the extent that they were persuaded by the correctness of Newton’s conclusions, it was either because they were successfully able to reconstruct his arguments within their pre-existing conceptual frameworks; or because they held face-to-face conversations with the author in which they were able to query, contest and negotiate the composition of his text.
In other words, the book was very ineffective at persuading readers of the validity of the arguments it contained. This means that the acclaim 'Principia' received at the moment of publication was unwarranted: it must have had some cause other than readers’ assent to its demonstrations
Piano music. Selections
No full text"Vol. 1 contains biographical sketch of the author by Theo. Baker.
Cult: A Composite Novel
No full textCult (redacted)
The first component of the thesis is a composite novel called Cult which falls into two parts with seven narratives in each. Part 1 tracks the protagonist, Ellen, from her first involvement with the cult through to her eventually leaving it. Although fiction, the first half of the book answers the kinds of questions the author is asked when people discover that she was once a sannyasin (a follower of the guru Bhagwan Shree Rajneesh). While the experiences of meditation, group therapy and communal living are all faithfully rendered within the stories, the need for strong characters, narrative drive and a lightness of touch takes precedence.
Part 2 picks up Ellen’s story some twenty or so years later and explores what becomes of her in middle age. It also looks at other groups in society, such as academia, the law and the internet dating community which each have their own jargon, hierarchies, rituals and rules but are not considered to be cults.
The book examines the question raised in the Epigraph, ‘how do we be together when we feel so alone’ with a focus on relationships other than the familial and the romantic.
Collisions, Chasms and Connections: a Performative Exploration of the Composite Novel Form
The second part of the thesis is both a critical and creative response to three contemporary American books: Olive Kitteridge by Elizabeth Strout; A Visit from the Goon Squad by Jennifer Egan; and Legend of a Suicide by David Vann. The critical element comprises a close reading of the three books; a chronological reconstruction of their overarching storylines; and a consideration of what their authors have said about writing the books. It concludes that, in the composite novel, the simultaneous presentation of multiple views and storylines operate much like a 3D image to give the impression of depth to the characters and situations rendered. The creative element of the essay is a playful and personal response to the texts
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