182 research outputs found
Heart-specific Rpd3 downregulation enhances cardiac function and longevity.
No full textDownregulation of Rpd3, a homologue of mammalian Histone Deacetylase 1 (HDAC1), extends lifespan in Drosophila melanogaster. Once revealed that long‐lived fruit flies exhibit limited cardiac decline, we investigated whether Rpd3 downregulation would improve stress resistance and/or lifespan when targeted in the heart. Contested against three different stressors (oxidation, starvation and heat), heart‐specific Rpd3 downregulation significantly enhanced stress resistance in flies. However, these higher levels of resistance were not observed when Rpd3 downregulation was targeted in other tissues or when other long‐lived flies were tested in the heart‐specific manner. Interestingly, the expressions of anti‐aging genes such as sod2, foxo and Thor, were systemically increased as a consequence of heart‐specific Rpd3 downregulation. Showing higher resistance to oxidative stress, the heart‐specific Rpd3 downregulation concurrently exhibited improved cardiac functions, demonstrating an increased heart rate, decreased heart failure and accelerated heart recovery. Conversely, Rpd3 upregulation in cardiac tissue reduced systemic resistance against heat stress with decreased heart function, also specifying phosphorylated Rpd3 levels as a significant modulator. Continual downregulation of Rpd3 throughout aging increased lifespan, implicating that Rpd3 deacetylase in the heart plays a significant role in cardiac function and longevity to systemically modulate the fly’s response to the environment.Peer reviewe
Comment Hollywood figure l'intériorité dans les films " hollywoodiens " de David Lynch, Lost Highway (1997), Mulholland Dr. (2001) et Inland Empire (2006)
No full textInternational audienceThe article takes Zachary Baqué's study of Los Angeles in the films of David Lynch as a starting point to explore David Lynch's Hollywood movies. The author contends that the films offer more than a satirical representation of a corrupt, unhealthy system which threatens dreams and artistic creativity, or a parodic play on Hollywood genre and narrative conventions. Rather, Hollywood is a character, a presence, revealed as both horizontal and vertical, physical and abstract, evoking the city, the studio system, cinema and dreams, so that the satire, the visual motifs and clichés and the topography of Hollywood, and the references to Hollywood films, constitute a complex fabric of subjectivity and interiority.L'article prend comme point de départ les travaux de Zachary Baqué et vise à montrer, à travers une étude diachronique, que les films hollywoodiens de Lynch ne le sont pas uniquement par leur représentation satirique d'un système corrompu qui compromet les ambitions qu'il suscite, ni même par la façon dont il retravaille les conventions génériques et narratives propres au cinéma hollywoodien. Hollywood est une présence à la fois horizontale et verticale, physique et abstraite, réelle et imaginaire, qui renvoie à la ville, au système, au cinéma et au rêve, si bien que la satire, la topographie, les motifs visuels parfois clichés et les références filmiques sont intimement liés en une expression de la subjectivité et de l'intériorité
A Recording, Performance Guide, and Composer Interviews: Six New Original Works for Trios Involving Saxophone, Commissioned for the Rogue Trio and Lotus
No full textabstract: This project includes a recording, composer biographies, performance guides, and composer questionnaires for seven original works commissioned for either the Rogue Trio or Lotus. The members of the Rogue Trio are violinist Kathleen Strahm, saxophonist Justin Rollefson, and pianist Mary Cota. Lotus’s members include Samuel Detweiler, Justin Rollefson, and Kristen Zelenak on saxophone. Both ensembles are based in Tempe, Arizona. All seven original compositions were recorded at Tempest Recording in February of 2018.
The first piece, Four Impersonations (2016), was commissioned by the Rogue Trio and written by Theo Chandler (b.1992) for violin, soprano saxophone and piano. The second piece was written by Spencer Arias (b. 1990) titled He Said There Was No Sound (2015) for violin, alto saxophone, and piano. The final work is titled Cabinet Meeting (2017), composed by Zachary Green (b. 1993) for violin, alto and tenor saxophone, and piano.
The first piece commissioned by Lotus and composed by Spencer Arias is titled As I escape, the water calms (2017) for soprano saxophone, alto saxophone, and tenor saxophone. The second piece was composed by Graham Cohen (b. 1999), titled Introduction and Toccata (2017), written for soprano, alto, and baritone saxophones. The third piece, titled Everything that rises, was written by David “Clay” Mettens (b. 1990) in 2014 for three soprano saxophones. Samuel Detweiler, Justin Rollefson and Tyler Flowers originally commissioned this piece. The final piece commissioned by Lotus was written by Matthew Kennedy (b. 1987) titled Triceratops: tasty grooves for saxophone trio (2017) for alto, tenor, and baritone saxophones.Dissertation/ThesisFour Impersonations, Movement I: An outwardly-confident adolescent demanding recognition - Theo ChandlerFour Impersonations, Movement II: A grumpy hermit ignoring the attention of a suitor - Theo ChandlerFour Impersonations, Movement III: A skinny, shy boy standing in the rain - Theo ChandlerFour Impersonations, Movement IV: Subordinates mocking an authority figure - Theo ChandlerHe Said There Was No Sound - Spencer AriasCabinet Meeting, Movement I: Introduction - Zachary GreenCabinet Meeting, Movement II: Jared Kushner, mysterious robot - Zachary GreenCabinet Meeting, Movement III: Secretary of State Rex Tillerson, lonesome cowboy - Zachary GreenCabinet Meeting, Movement IV: Anthony "The Mooch" Scaramucci, in candid conversation with the New Yorker - Zachary GreenCabinet Meeting, Movement V: Betsy DeVos Secretary of Education - Zachary GreenCabinet Meeting, Movement VI: Ben Carson Secretary of Housing and Urban Development - Zachary GreenCabinet Meeting, Movement VII: Attorney General Jeff Sessions, responding to questions from the Senate Intelligence Committee - Zachary GreenAs I escape, the water calms - Spencer AriasIntroduction and Toccata - Graham CohenEverything that rises - David “Clay” MettensTriceratops - Matthew KennedyDoctoral Dissertation Music 201
Flow cytometry quantitation of dopamine receptor D2 loss as a sensitive measure of Huntington's Disease progression in mouse neurons
No full textThesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2013.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.Mouse models of Huntington's Disease (HD) are often used for testing potential therapeutic compounds. These experiments require substantial investments in time and resources, and have yet to produce any intervention that has made a significant impact on disease progression in the clinic. In evaluating potential therapeutics, there is an unmet need for a rapid, highly quantitative measure of disease progression in the HD mouse model brain. Such an assay would help make preclinical trials more efficient. To address this need, I have developed a novel technique for measuring the progression of transcriptional dysregulation, a phenotype with substantial similarities between mouse models and patients. Specifically, utilizing mice that drive GFP expression under the control of one such dysregulated gene (Drd2), I have improved on previous protocols for the isolation and characterization of adult neurons by flow cytometry. Drd2 is a well-studied marker of a particularly vulnerable population in HD patients, the indirect medium spiny neurons of the striatum. Using this technique, I have demonstrated the ability to accurately and rapidly quantitate Drd2 transcript levels, as measured by Drd2 GFP (D2GFP) fluorescence, in several strains of HD model mice. This D2GFP loss is particularly robust, with sufficient power to allow subtle, statistically significant alterations to be observed with very small cohorts. Furthermore, the introduction of this D2GFP transgene does not alter the classic HD pathology in these mice. Finally, I show that D2GFP dysregulation can be either induced or ameliorated genetically by delivering transgenes via adeno associated viral vectors, and that a small molecule with only subtle transcriptional effects (cystamine) fails to rescue D2GFP loss. I hope that this system can be of great utility in the validation of effective therapeutic interventions for HD.by Zachary R. Crook.Ph.D
Indentation of Solid Nitrogen Between 30 K and 40 K
No full textThis research was completed in support of the proposed NASA mission, Triton Hopper, whose intended mission is to land on Triton, a moon of Neptune. Flight over Tritons surface is to be provided by repurposing in situ resources; where solidified nitrogen is gathered, heated, and used as a gaseous propellant. Mechanical property data of solid nitrogen at Triton surface conditions is almost nonexistent. A system was designed to gather hardness data via flat punch indentation of cryocooler formed solidified nitrogen samples. The system was used to collect data at temperatures between 30 and 40K at 1-degree increments. Hardness averages ranged from 0.35 Mpa to 2.26 Mpa as temperature decreased, the data were approximately 3 to 4 times harder than prior data. The system was modified and used to conduct rotary shear testing. Based on the results, suggestions for further work are provided.masters, M.S., Mechanical Engineering -- University of Idaho - College of Graduate Studies, 2021-1
Diuretic Therapy for Patients With Heart Failure JACC State-of-the-Art Review
No full textExpansion of extracellular fluid volume is central to the pathophysiology of heart failure. Increased extracellular fluid leads to elevated intracardiac filling pressures, resulting in a constellation of signs and symptoms of heart failure referred to as congestion. Loop diuretics are one of the cornerstones of treatments for heart failure, but in contrast to other therapies, robust clinical trial evidence to guide the use of diuretics is sparse. A nuanced understanding of renal physiology and diuretic pharmacokinetics is essential for skillful use of diuretics in the management of heart failure in both the inpatient and outpatient settings. Diuretic resistance, defined as an inadequate quantity of natriuresis despite an adequate diuretic regimen, is a major clinical challenge that generally portends a poor prognosis. In this review, the authors discuss the fundamental mechanisms and physiological principles that underlie the use of diuretic therapy and the available data on the optimal use of diuretics.Felker, GM (reprint author), Duke Clin Res Inst, 200 Morris St, Durham, NC 27705 USA.
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God’s Faithfulness to Promise: The Hortatory Use of Commissive Language in Hebrews
No full textDavid Worley\u27s 1981 Yale University dissertation--revised with foreword by James Thompson and bibliographical addendum by Lee Zachary Maxey--explores the use commissive language, promises, and hortatory literature in the book of Hebrews. The author concludes that the use of commissive language in the book of Hebrews was not prompted by criticisms within the church over a delay in God’s promise keeping; rather that our author seized upon God’s commissive activity and the behavior of promisees of scripture as a way of emboldening a people tempted to withdraw from one another and from God to endure social and financial difficulties and to remain confident in the face of threats to the promise.https://digitalcommons.acu.edu/acu_library_books/1000/thumbnail.jp
Temporal interference for dual site transcranial magnetic stimulation
No full textDual-site Transcranial Magnetic Stimulation (ds-TMS) is a TMS protocol that involves stimulating two areas of the brain in close succession. This method is useful for studying the connections between two physical parts of the brain. TMS coils are generally designed for use on a single target area in the brain. When ds-TMS targets are in close proximity to one another, using traditional coils in a limited space increases the possibility of errors associated with positioning, resulting in inconsistent pulse strength and trajectory. We developed a single TMS coil that uses temporal interference (TI) to stimulate multiple targets within close proximity without compromising the ideal positioning of either location. TI TMS operates based on the frequency difference of two magnetic fields delivered simultaneously. The frequency difference between the two fields results in an envelope which can be steered to target a different location without moving the coil. We designed a TI-TMS coil and show that the peak induced electric field can be steered 4 cm in either direction (8 cm range) from the center point of the coil while delivering a peak field of 120 V/m, which is above the minimum 100 V/m needed to activate neurons. An experimental model was built using the same dimensions as the simulation model and validated that the physical model is able to steer the magnetic pulse using TI.This article is published as Boldrey, Joseph, Zachary Higgs, and David C. Jiles. "Temporal interference for dual site transcranial magnetic stimulation." AIP Advances 13, no. 2 (2023): 025242.
DOI: 10.1063/9.0000448.
Copyright 2023 The Author(s).
Attribution 4.0 International (CC BY 4.0).
Posted with permission
Slavery beyond slavery: the American South, British imperialism, and the circuits of capital, 1833-1873
No full text“Slavery Beyond Slavery: The American South, British Imperialism, and the Circuits of Capital, 1833-1873” expands upon W.E.B. Du Bois’s insight that U.S. slavery intensified and transformed the exploitation of labor on a global scale. In places of intense colonial conflict and breakdown—India’s North-Western Provinces, British Honduras, and Queensland, Australia— U.S. settler slavery informed planters and colonial officials in pursuits to reorganize production and transform colonial practices. I argue that in the mid-nineteenth century, the economic dynamism of U.S. settler slavery had broader implications than what is commonly recognized.
While imperialists, planters, and capitalists sought to manage the contradictions of empire, race, and capital, those subjected to expropriation often tried and sometimes succeeded in creating alternatives. In response to settler imperial crisis in British Honduras, landholding interests turned first toward bringing emancipated African Americans to the colony. Yet, when African Americans refused to leave the United States, landholders turned toward former white slaveholders to manage Chinese laborers brought to the colony in 1865. In response to planter abuse, Chinese laborers abandoned plantations and joined with the Santa Cruz Maya. The Santa Cruz Maya refused to return laborers to British Honduras stating, according to one frustrated colonial official, that Chinese laborers were “Indians like themselves.”
In contrast to such racial remaking in the service of anti-colonial and anti-plantation commonality, in Queensland during the same decade, white settlers developed a white supremacist discourse that argued that Chinese and South Asian exclusion and Aboriginal removal were necessary to stabilize the territory as a racially homogenous white man’s country. This argument depended heavily upon anti-African American racism and often concluded that Black presence had doomed United States democracy. In India’s North-Western Provinces,famine caused by food scarcity was rendered comparable to the experiences that Lancashire cotton workers suffered from due to increased cotton prices brought about by disrupted access to enslaved labor. By considering what binds these histories together, “Slavery Beyond Slavery” takes seriously W.E.B. Du Bois’s contention that slavery ultimately won the Civil War, not just in the United States but in the world. This victory did not depend upon the triumph or failure of planters in Belize or even the American South. Rather, slavery’s triumph after abolition was in the expansion of a racially ordered global economy.Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2019-08-01The student, Zachary Sell, accepted the attached license on 2017-05-24 at 19:03.The student, Zachary Sell, submitted this Dissertation for approval on 2017-05-24 at 19:13.This Dissertation was approved for publication on 2017-05-25 at 14:51.DSpace SAF Submission Ingestion Package generated from Vireo submission #11178 on 2017-09-29 at 11:13:19Made available in DSpace on 2017-09-29T16:39:03Z (GMT). No. of bitstreams: 2
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A trade space model for robotic lunar exploration
No full textThesis (S.M.)--Massachusetts Institute of Technology, Dept. of Aeronautics and Astronautics, 2010.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 (p. 147-152).The last decade has seen a resurgence of interest in the moon as a target for planetary exploration. In light of the growing interest in the robotic exploration of the moon, this thesis presents a quantitative methodology for exploring the trade space of potential in situ robotic lunar spacecraft designs. A science value model was developed, using Multi-Attribute Utility Theory (MAUT), to estimate the effectiveness of a spacecraft design towards assessing a set of specified science objectives. An engineering model was developed to estimate the masses of spacecraft designs within the trade space. These models were integrated together to explore the objectives of minimizing mass and maximizing science return. Two methods for exploration of the trade space were presented: a stochastic design space search method, and a multi-objective simulated annealing method. Using these techniques, the optimality of a reference mission was investigated, and ways to improve science utility performance were shown. The exploration of a trade space under uncertainty, using an -Pareto search method, was investigated, and recommendations for designers were presented.by Zachary James Bailey.S.M
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