1983 research outputs found
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Concentration bounds for quantum states with finite correlation length on quantum spin lattice systems
No full textWe consider the problem of determining the energy distribution of quantum states that satisfy exponential decay of correlation and product states, with respect to a quantum local hamiltonian on a spin lattice. For a quantum state on a D-dimensional lattice that has correlation length σ and has average energy e with respect to a given local hamiltonian (with n local terms, each of which has norm at most 1), we show that the overlap of this state with eigenspace of energy f is at most exp(−((e−f)2σ)1D+1/n1D+1Dσ). This bound holds whenever |e−f|>2Dnσ‾‾‾√. Thus, on a one dimensional lattice, the tail of the energy distribution decays exponentially with the energy.
For product states, we improve above result to obtain a Gaussian decay in energy, even for quantum spin systems without an underlying lattice structure. Given a product state on a collection of spins which has average energy e with respect to a local hamiltonian (with n local terms and each local term overlapping with at most m other local terms), we show that the overlap of this state with eigenspace of energy f is at most exp(−(e−f)2/nm2). This bound holds whenever |e−f|>mn‾√.Version of Recor
Control of human telomerase activity by nucleotide metabolism
No full textTelomeres are nucleoprotein structures which flank linear chromosomes and promote genome integrity. Telomere synthesis by the telomerase reverse transcriptase must be tightly controlled to promote cellular function and human health, yet our understanding of the processes which enable telomere length homeostasis is incomplete. Here, I performed the first genome-wide CRISPR-Cas9 screen for telomere length regulating genes in human cells and identified dNTP metabolism as a pathway critical for human telomere length control. Using targeted genetic screening, I found that loss of thymidine nucleotide synthesis or salvage genes led to telomere attrition, whereas loss of the dNTP degrading gene SAMHD1 drove telomere lengthening. Remarkably, I found that supplementation of thymidine nucleoside drove robust telomere lengthening across multiple cell lines, including at doses which had no detectable effects on cell growth, and in a manner which required the presence of telomerase. To further characterize the intersection between dNTP metabolism and telomerase activity control, I developed a method for Telomerase Rapid Assessment in the Cellular Environment, or TRACE. Using TRACE, I identified that guanine nucleotide salvage occupies a critical juncture in telomerase activity control: salvage to form guanosine ribonucleotides drives telomerase inhibition, while salvage to form dGTP stimulates telomerase activation. I propose that dNTP metabolism alters telomere length via the substrate level control of telomerase, adding a new layer to current models of telomerase regulation. Inherited defects in the telomerase components and related genes cause premature telomere shortening and drive a spectrum of fatal disorders called telomere biology disorders (TBDs), manifesting as bone marrow failure, liver and lung fibrosis, and other degenerative diseases throughout the body. There are currently no effective systemic therapies to lengthen telomeres to treat the TBDs, and accordingly the patients diagnosed with these disorders face daunting prognoses. Here, I identify multiple strategies to promote telomere lengthening in TBD patient derived cells by upregulating dNTP metabolism, including supplementation with thymidine, inhibition of the dNTPase SAMHD1, supplementation with deoxyguanosine combined with the PNP inhibitor ulodesine, and expression of an efficient deoxynucleoside kinase from Drosophila melanogaster. Collectively, my work has expanded our understanding of human telomere length control by revealing that telomerase is highly sensitive to manipulations of its dNTP substrates. My findings offer an explanation for emerging human genetic data linking genetic variation in dNTP metabolism genes with telomere length and telomere disease. I propose that the targeted manipulation of dNTP metabolism could provide an avenue to control telomerase activity within a therapeutic window to treat the TBDs. Nucleotide metabolism offers a new lens with which to examine the origins and evolution of telomerase and telomeres.Medical SciencesMedical Science
Investment Feminism and Women's Health
No full textThis essay introduces the term investment feminism to characterize the phenomenon in which financial actors position investment as a powerful lever for advancing gender equity. We offer investment feminism as an analytic tool that illuminates patterns and relations incompletely revealed by existing concepts such as commodity feminism and neoliberal feminism. We develop the concept of investment feminism through a close analysis of its role in the femtech industry, which markets technology and products to promote women's health. Drawing on industry reports, press coverage, and marketing materials, we describe how venture capital firms and femtech startups proffer financial investment as a high-impact means of feminist political action. We argue that while technology has the potential to yield services, tools, diagnostics, and therapies that benefit women, the technological solutions promoted by investment feminism within the women’s health space favor individual self-maintenance rather than structural change. We offer the concept of investment feminism as an analytic tool to support feminist scholars and activists in attending to the role of the financial sector and its ever-increasing influence on gender relations and feminist movements
Artists/Historians: Mauricio Kagel, Musiktheater and the Mobility of (Music) History
No full textThis dissertation explores the circum-Atlantic movement of Musiktheater composition during
the mid-twentieth century, focusing on composers working between Argentine, West German, and
U.S.-American institutions. The dissertation traces how such artists came together from disparate
geographic locales and political circumstances, using the genre of Musiktheater to interrogate cultural
patrimony and negotiate questions of identity and cultural violence. By piecing together unexplored
cross-disciplinary and transnational relations, my research challenges Eurocentric historiography of
avant-garde, postwar musical and operatic composition.
The dissertation takes a case study format, focusing on specific constellations of individuals,
relationships, and institutions significant to music and theater history of the postwar era. My
methodology combines close readings; extensive archival research into historical, material,
economic, and institutional contexts; and oral histories I gathered from composers, performers, and
cultural administrators throughout the U.S., Canada, Argentina, Germany, and Switzerland.
The first three case studies of the dissertation focus on the 1960s and 1970s and the work of
composer Mauricio Kagel (1931-2008) and visual artist Ursula Burghardt (1928-2008), opening with
two chapters focused on works by Kagel that address political implications of bourgeois concert
culture and the legacies of colonialism. The first chapter analyzes the 1969 film Ludwig van: A Report,
a commission commemorating the 1970 Beethoven bicentennial that Kagel made in collaboration
with Burghardt and other Fluxus artists, including Joseph Beuys and Robert Filliou. Exploring
notions of collaboration and (music) theater in a filmic medium, I demonstrate how Ludwig van asks
its audience to reflect on the negotiations of the diasporic experiences of avant-garde artists in the
wake of the Holocaust. The second chapter analyzes Kagel’s music-theatrical Mare Nostrum:
Discovery, Pacification and Conversion of the Mediterranean Region by a Tribe from Amazonia (1975).
Borrowing its title from the Roman Empire’s name for the Mediterranean, Mare Nostrum is a farce
of colonialism that narrates an inverted history of the colonization of the Americas. I argue that
Mare Nostrum is in truth a story of the Black Atlantic that deconstructs the near-sacred status of
European narratives of the so-called “discovery” of the Americas. Kagel weaves references to
canonical European music history into a narrative that ultimately, I demonstrate, identifies the birth
of colonialism as the beginnings of a long history of racial, cultural, linguistic, and environmental
genocides.
The third chapter of the dissertation functions as its conceptual center and turning point,
addressing themes of collaboration, authorship, and historiographic erasure. Providing the first
English-language biographical account of Burghardt, the chapter demonstrates the imbalances of
power in the intimate spaces of marriage and artistic partnership that have led to the historiographic
erasure of Burghardt in analysis of Kagel’s oeuvre, and more broadly in histories of mid-century
avant-gardes. I focus on the collaborative work of the nonprofit association Laboratory for
Research on Acoustic and Visual Events (1968-1973) and demonstrate how Burghardt created and
manipulated theatrical, acoustic environments in ways that question traditional definitions of the
musical instrument, instrumentality, and who is allowed to claim the title of “composer.”
The dissertation’s fourth chapter focuses on three composers whose careers have unfolded
between the U.S. and Europe in the twenty-first century. I evaluate how the legacy of mid-century
music-theatrical composition is navigated by contemporary composers, specifically, “The New
Discipline,” founded by Irish composer-performer Jennifer Walshe (b. 1974) in 2016. Through
analysis of Steven Kazuo Takasugi’s (b. 1960) instrumental theater, Sideshow (2015), and Ash Fure’s
(b. 1982) meditation on the Anthropocene, The Force of Things: An Opera for Objects (2016/2017), I
demonstrate how, in the hands of these contemporary composers, Musiktheater is used as a generic
space to interrogate environmental crisis, histories of violence, and circum-Atlantic performance.
The dissertation demonstrates that writing a history of later twentieth century
experimentalisms with instrumental music theater at its center rather than its periphery requires a
kaleidoscopic turn of music historiography. Such a turn, I argue, produces a history finely attuned
to the experiences of the displaced, of outsiders, culturally, linguistically, methodologically,
religiously, or otherwise. The dissertation illustrates how these individuals formed communities and
worked to negotiate the richly complex, if traumatically violent, social and political world constantly
moving around them
On Chastity: A Lutheran Examination of Chastity in the 21st Century
No full textOne of the most important reforms that Martin Luther made during the Protestant Reformation was to move away from mandatory celibacy for the clergy. Instead, he proposed that all Christians should lead a chaste life — something available to everyone, no matter their office (priest, husband, wife, etc.). This went explicitly against medieval notions of grace, under which people living under vows of celibacy had ‘special grace’ that was unavailable to people who were married. However, in the intervening years, this gift that Luther gave the church has turned into law: no longer something that sets people free to love each other and be in relationship with each other, chastity has become the new celibacy. Through a historical analysis of Luther’s own writings and the Book of Concord and through a contemporary analysis of how chastity functions in both people’s lives and in the Evangelical Lutheran Church in America, this paper argues that Lutherans need to reclaim the original understanding of chastity as a gift. Chastity, far from its original liberatory use in Luther’s time, has instead turned into the theological underpinning of both the church’s understanding of the proper expression of human sexuality and the basis by which the church organizes its discipline for rostered ministers. No longer a gift, chastity has become law; instead of being good news that sets the faithful free to love one another, it constrains them under the fear of punishment and sin
Narrative Carpentry: A Study on Conservation Organisations for Traditional Chinese Timber Structures
No full textThis research focuses on the conservation of historic timber structural buildings in China. Specifically, it examines the various methods, organisations, histories, and approaches to architectural conservation aimed at countering the obsolescence of traditional wooden construction, particularly in terms of its physical characteristics. It also explores geographic adaptation and misadaptation, alongside the craftsmanship and institutional arrangements of conservation. Though relatively scarce, traditional timber structures hold critical importance for modern China. As observed globally, conservation for physically deteriorated buildings is not unique to China, yet in contemporary times, it has become crucial to this nation's identity, cultural heritage, global standing, and economic well-being.
Traditional Chinese timber architecture embodies two distinct construction thinkings: one is the object-oriented approach, which emphasises the buildings' forms and appearances, predominantly observed in official architecture, characterised by a uniformity of form across provinces and strict hierarchical distinctions by function. The other is the process-oriented approach, primarily evident in vernacular architecture, emphasising regional adaptability and the construction process itself. In the pre-industrial era, the forms of both official and vernacular buildings were indirectly produced through carpenters' calculations and manual construction. Moreover, the construction and conservation of buildings are integral to the evolutionary process of architectural forms. Carpenters, pivotal in traditional architectural engineering, established specific social groups around carpentry teams, known in academic circles as 'jiangpai', representing a guild system of apprenticeships, schools of thought, or ideological families.
Over the past century, with the advent of modern architecture in China, traditional timber structures have been progressively supplanted by modern constructions. Modern architectural professionals have largely overshadowed traditional 'jiangpai', though small fractions persist along China's southeastern coast. Regarding wooden structure conservation, traditional artisans and modern architects diverge significantly; the former concentrates on the hands-on construction and maintenance process, while the latter focuses more on representing historic architectural imagery.
This research centres on one official artisan collective and two grassroots artisan groups. It investigates the histories, organisational structures, distinctive building techniques, and the transmission of knowledge among these jiangpai. Additionally, the study contrasts modern architects and scholars in the architectural field with traditional artisans, analysing disparities in conservation approaches through specific case studies. The research finds that conservation strategies centred on representing historical information in heritage buildings, typically advocated by contemporary architects, are prevalent in government-led conservation initiatives. In contrast, process-driven conservation practices, espoused by traditional artisan groups, are more common in community-led construction and conservation projects. There is increasing interaction and convergence between these two groups of practitioners. The co-existence of design-led and process-led conservation methods is evident in contemporary conservation practice. Moreover, traditional building techniques remain valuable for future conservation efforts
Leveraging Geographic Information for Causal Inference in Pharmacoepidemiology
No full textRandomized trials (RCT) with major adverse cardiovascular event (MACE) outcomes found no effect of dipeptidyl-peptidase-4 inhibitors (DPP-4i) medications compared to placebo or second-generation sulfonylureas (SU) while non-randomized database studies suggested a benefit of DPP-4i versus SU. Residual confounding by socioeconomic factors were thought to be a main reason.
Aim 1 characterized the geospatial distribution of the adoption of DPP-4i antidiabetics versus SU. Aim 2 evaluated whether incorporation of small-area-level socioeconomic measures can reduce confounding in non-randomized comparisons of DPP-4i to SU as second-line antidiabetic therapies in the prevention of MACE. Aim 3 compared area-level prescribing density (APD) and physician prescribing preference (PPP) as instrumental variables (IVs) with the objective of finding a strategy for control of previously unmeasured confounders.
Using Medicare claims data from 2012 to 2017, two cohorts were built emulating RCTs of sitagliptin or saxagliptin starters each compared to SU starters.
For each ZCTA, the proportion DPP-4i prescribing in relation to total ZCTA cohort members was calculated and used for a local indicator of spatial association cluster analysis. Multilevel logistic models were used to quantify the variation in medication use at the individual, ZCTA, state, and region levels.
DPP-4i utilization proportion was low (sitagliptin median = 0.22; interquartile range 0.15 to 0.33; saxagliptin median = 0.025; 0.00 to 0.069). High amounts of clustering were observed for sitagliptin proportion (Moran’s I = 0.32) and saxagliptin proportion (Moran’s I = 0.20). Sitagliptin utilization was high in the New York metro area and urban southern California. Saxagliptin had similar patterns with additional clusters in the upper Midwest. Regions, states, and ZCTAs accounted for 8.1% of variation in sitagliptin prescribing and 13.3% of saxagliptin prescribing. Variation across ZCTAs suggests neighborhood factors may have been important determinants of prescribing. Removing high co-payments may have improved equity in access to safer antidiabetics.
Area-level covariates were obtained for ZCTAs from the American Community Survey. ZCTA-level socioeconomic covariates were incorporated into propensity scores for Cox proportional hazards models. Cox models stratified by ZCTAs were also fit.
Adding area covariates improved propensity score model fit and treatment discrimination. Unadjusted associations for receiving sitagliptin or saxagliptin compared to SU showed a decreased hazard of MACE occurrence (sitagliptin hazard ratio (HR) = 0.86; 95% confidence interval 0.83 to 0.88; saxagliptin HR = 0.68; 0.64 to 0.73). Adjusting for individual-level covariates moved estimates towards the null (sitagliptin HR = 0.89; 0.86 to 0.92; saxagliptin HR = 0.78; 0.73 to 0.83). Adding area covariates moved estimates minimally closer to the null. Adjusted stratified Cox models produced similar results (sitagliptin HR = 0.90; 0.87 to 0.93; saxagliptin HR = 0.76; 0.71 to 0.81). Incorporation of area-level covariates in survival analyses did not meaningfully reduce confounding beyond individual-level covariates.
The proportion of DPP-4i prescribing in relation to all cohort members in a zip code tabulation area defined the APD IV at various cutoffs (0% vs. 100% to % vs. ≥50%). The same proportions were calculated for each patient’s physician prescribing history as the PPP IV. An instantaneous physician preference (iPPP) IV used a physician’s most recent prescription. Two-stage IV regression models were adjusted for propensity score quintiles.
All IVs were strong and reduced covariate imbalance. APD IV analyses found no meaningful difference for sitagliptin (0% vs. 100% HR = 1.11; 0.79 to 1.57). PPP IV analyses showed reduced risk for sitagliptin (% vs. ≥50% HR = 0.69; 0.48 to 0.98). iPPP analyses showed little to no difference for sitagliptin (HR = 0.86; 0.60 to 1.10) and saxagliptin (HR = 0.98; 0.56 to 1.72). Instruments focusing on short-term prescribing preference like the iPPP IV hold promise over area-based instruments to improve confounding control in comparative effectiveness analyses
When Witches Mourn the Dead: Grieving Rituals of Contemporary Witchcraft in New England
No full textThis project is underpinned by ethnographic and phenomenological methods used to analyze the grieving rituals of contemporary witches in New England through the lens of anthropology, ritual studies, and grief counseling. The results of this study will fill in the gap in the literature on the anthropology of witchcraft and contemporary American death rites, which currently lack studies on personal grieving rituals. The scholarly backdrop of my research traces recent trends in the anthropology of death that reflect a movement toward noninstitutionalized death-related coping strategies along with psychotherapeutic literature on bereavement that similarly shows a shift toward private and individualized rituals of death and grieving while addressing changes in institutional authorities on mourning and individual responses in the contemporary United States. This undertaking aims to answer the following critical questions: How does the magic worldview of contemporary witchcraft inform the way witches create grieving rituals? How do these rituals enable contemporary witches to process and heal from the critical experience of loss
Redefining Foreign Correspondence
No full textAlong with American journalism generally, foreign correspondence has evolved in the last 250 years so that it scarcely resembles its colonial origins. Not the least of these differences is that it never occurred to colonial printers to have a newsroom, let alone pay anyone to report from abroad. Colonial printers published travelers’ letters and unabashedly lifted stories from European publications because they were free and tended to be non-controversial. Today, in contrast, the foreign correspondent for traditional news media enjoys prestige among professional peers and is a figure to be reckoned with by public policy makers.
At the same time, paradoxically, establishment news media have de-emphasized foreign news. Critics have described the trend in Darwinian terms. The international news hole -- the space and time devoted to foreign affairs – is an “endangered species,” journalism historian Michael Emery lamented in the late 1980s. “Where there are still correspondents based abroad,” former diplomatic correspondent and media critic Marvin Kalb noted, “the genre known as ‘foreign correspondent’ is becoming extinct.”Version of Recor
Nanoparticle Clearance: A Regulatory Summary Recommending Strengthening of the Current FDA Guidance in Assuring Long Term Safety of Nanoparticle Therapies in Cancer Patients
No full textCancer has complicated pathogenesis, making it one of the leading causes of mortality and morbidity. Traditional cancer treatments include targeted therapy, immunotherapy, chemotherapy, and radiation therapy. The development of nanotechnology has led to a revolution in the treatment and detection of cancer. Nanoparticles can be a better option for cancer because they have unique advantages like biocompatibility, less drug related toxicity, better stability, higher permeability and retention impact, and precise targeting. This overview discusses the factors that could affect the biodistribution and blood circulation half-life of nanoparticles (NPs) used in drug delivery systems. These variables include adjustable nanoparticle parameters such as composition, size, core characteristics, surface modifications like PEGylation and surface charge, targeted ligand functionalization, and interactions with biological barriers. Cancer currently presents a challenge to effective treatment due to its complicated pathogenesis and the drawbacks of traditional treatments such as multi-drug resistance, cytotoxicity, and lack of selectivity. Nanoparticles have unique advantages such as biocompatibility, less toxicity, better stability, higher permeability and retention effect, and precise targeting. Furthermore, drug delivery systems based on nanoparticles can help reduce cancer-related treatment resistance, which is caused by impaired apoptotic pathways, overexpression of drug efflux transporters, and hypoxic environments. Nanoparticles are also being investigated for their potential use in immunotherapy. This overview examines how NPs can be utilized to deliver drugs, how they are cleared from the body, and proposes how the FDA has set guidance for the industry for nanomaterials and the gaps for where they can do more to keep these therapies safe for use in human