422 research outputs found
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Strange times : dissident temporalities and the remaking of history in contemporary fiction
This dissertation argues that a cluster of contemporary novelists experiment with temporalities in order to challenge the still-dominant Enlightenment view that history moves forward in a linear progression. In directing critical attention to the temporal representation of history in recent fiction, I trace a shift in contemporary preoccupations away from the postmodern concerns about the relationship of history to language, narrativity, and knowability and toward the way that temporal adjustment revises historical thinking. I show that a number of contemporary authors eschew the conventional linkages between time and history that normally structure our engagement with the past. Rather than cut the ties between time and history, however, these texts remake them through unusual temporal frameworks. I develop this argument using three case studies, which demonstrate how a particular historiographical concept—traditionally undergirded by progressivist ideologies—changes under the influence of an unconventional representation of time. Using Monique Truong’s The Book of Salt (2003) and Alan Hollinghurst’s The Swimming-Pool Library (1988), I show how queer temporalities, which reject the compulsory rhythms that often govern heteronormative culture, reconfigure archives by considering the inclusion of intentionally falsified documentation. Two works by African American novelists—Colson Whitehead’s The Intuitionist (1999) and Kiese Laymon’s Long Division (2013)—feature a temporality I call the unified now, which envisions time as past, present, and future folded together in a single unit. This temporality allows them to remake the idea of futurity by exploring how future hopes for social improvement might be realized in the present. Finally, Don DeLillo’s Point Omega (2010) and Lydia Millet’s Oh Pure and Radiant Heart (2003) alter the concept of historical scale by considering deep time that requires us to stretch our notion of history from the Big Bang to the death of our planet. They argue that this expansion of scale is the only way to come to terms with humanity’s effect on the natural world. I contend that an exploration of these temporal reorientations is crucial to understanding the contemporary historical imagination and to discovering new ways of perceiving ourselves, defining cultural and social progress, and living responsibly.Englis
DNA Methylation and Transcription Patterns in Intestinal Epithelial Cells From Pediatric Patients With Inflammatory Bowel Diseases Differentiate Disease Subtypes and Associate With Outcome.
BACKGROUND & AIMS: We analyzed DNA methylation patterns and transcriptomes of primary intestinal epithelial cells (IEC) of children newly diagnosed with inflammatory bowel diseases (IBD) to learn more about pathogenesis. METHODS: We obtained mucosal biopsies (N = 236) collected from terminal ileum and ascending and sigmoid colons of children (median age 13 years) newly diagnosed with IBD (43 with Crohn's disease [CD], 23 with ulcerative colitis [UC]), and 30 children without IBD (controls). Patients were recruited and managed at a hospital in the United Kingdom from 2013 through 2016. We also obtained biopsies collected at later stages from a subset of patients. IECs were purified and analyzed for genome-wide DNA methylation patterns and gene expression profiles. Adjacent microbiota were isolated from biopsies and analyzed by 16S gene sequencing. We generated intestinal organoid cultures from a subset of samples and genome-wide DNA methylation analysis was performed. RESULTS: We found gut segment-specific differences in DNA methylation and transcription profiles of IECs from children with IBD vs controls; some were independent of mucosal inflammation. Changes in gut microbiota between IBD and control groups were not as large and were difficult to assess because of large amounts of intra-individual variation. Only IECs from patients with CD had changes in DNA methylation and transcription patterns in terminal ileum epithelium, compared with controls. Colon epithelium from patients with CD and from patients with ulcerative colitis had distinct changes in DNA methylation and transcription patterns, compared with controls. In IECs from patients with IBD, changes in DNA methylation, compared with controls, were stable over time and were partially retained in ex-vivo organoid cultures. Statistical analyses of epithelial cell profiles allowed us to distinguish children with CD or UC from controls; profiles correlated with disease outcome parameters, such as the requirement for treatment with biologic agents. CONCLUSIONS: We identified specific changes in DNA methylation and transcriptome patterns in IECs from pediatric patients with IBD compared with controls. These data indicate that IECs undergo changes during IBD development and could be involved in pathogenesis. Further analyses of primary IECs from patients with IBD could improve our understanding of the large variations in disease progression and outcomes
Compositional and expression analyses of the glideosome during the Plasmodium life cycle reveal an additional myosin light chain required for maximum motility
Myosin A (MyoA) is a Class XIV myosin implicated in gliding motility and host cell and tissue invasion by malaria parasites. MyoA is part of a membrane-associated protein complex called the glideosome, which is essential for parasite motility and includes the MyoA light chain MTIP, and several glideosome-associated proteins (GAPs). However, most studies of MyoA have focused on single stages of the parasite life cycle. We examined MyoA expression throughout the Plasmodium berghei life cycle in both mammalian and insect hosts. In extracellular ookinetes, sporozoites and merozoites, MyoA was located at the parasite periphery. In the sexual stages, zygote formation and initial ookinete differentiation precede MyoA synthesis and deposition, which occurred only in the developing protuberance. In developing intracellular asexual blood stages, MyoA was synthesized in mature schizonts and was located at the periphery of segmenting merozoites, where it remained throughout maturation, merozoite egress and host cell invasion. Besides the known GAPs in the malaria parasite, the complex included GAP40, an additional myosin light chain designated essential light chain (ELC) and several other candidate components. This ELC bound the MyoA neck region adjacent to the MTIP binding site, and both myosin light chains co-located to the glideosome. Co-expression of MyoA with its two light chains revealed that the presence of both light chains enhances MyoA-dependent actin motility. In conclusion, we have established a system to study the interplay and function of the three glideosome components, enabling the assessment of inhibitors that target this motor complex to block host cell invasion
CD32 is expressed on cells with transcriptionally active HIV but does not enrich for HIV DNA in resting T cells
The persistence of HIV reservoirs, including latently infected, resting CD4+ T cells, is the major obstacle to cure HIV infection. CD32a expression was recently reported to mark CD4+ T cells harboring a replication-competent HIV reservoir during antiretroviral therapy (ART) suppression. We aimed to determine whether CD32 expression marks HIV latently or transcriptionally active infected CD4+ T cells. Using peripheral blood and lymphoid tissue of ART-treated HIV+ or SIV+ subjects, we found that most of the circulating memory CD32+ CD4+ T cells expressed markers of activation, including CD69, HLA-DR, CD25, CD38, and Ki67, and bore a TH2 phenotype as defined by CXCR3, CCR4, and CCR6. CD32 expression did not selectively enrich for HIV- or SIV-infected CD4+ T cells in peripheral blood or lymphoid tissue; isolated CD32+ resting CD4+ T cells accounted for less than 3% of the total HIV DNA in CD4+ T cells. Cell-associated HIV DNA and RNA loads in CD4+ T cells positively correlated with the frequency of CD32+ CD69+ CD4+ T cells but not with CD32 expression on resting CD4+ T cells. Using RNA fluorescence in situ hybridization, CD32 coexpression with HIV RNA or p24 was detected after in vitro HIV infection (peripheral blood mononuclear cell and tissue) and in vivo within lymph node tissue from HIV-infected individuals. Together, these results indicate that CD32 is not a marker of resting CD4+ T cells or of enriched HIV DNA–positive cells after ART; rather, CD32 is predominately expressed on a subset of activated CD4+ T cells enriched for transcriptionally active HIV after long-term ART
Planning for Sustainability in Small Municipalities: The Influence of Interest Groups, Growth Patterns, and Institutional Characteristics
How and why small municipalities promote sustainability through planning efforts is poorly understood. We analyzed ordinances in 451 Maine municipalities and tested theories of policy adoption using regression analysis.We found that smaller communities do adopt programs that contribute to sustainability relevant to their scale and context. In line with the political market theory, we found that municipalities with strong environmental interests, higher growth, and more formal governments were more likely to adopt these policies. Consideration of context and capacity in planning for sustainability will help planners better identify and benefit from collaboration, training, and outreach opportunities
Multi-Element Abundance Measurements from Medium-Resolution Spectra. IV. Alpha Element Distributions in Milky Way Dwarf Satellite Galaxies
We derive the star formation histories of eight dwarf spheroidal (dSph) Milky
Way satellite galaxies from their alpha element abundance patterns. Nearly 3000
stars from our previously published catalog (Paper II) comprise our data set.
The average [alpha/Fe] ratios for all dSphs follow roughly the same path with
increasing [Fe/H]. We do not observe the predicted knees in the [alpha/Fe] vs.
[Fe/H] diagram, corresponding to the metallicity at which Type Ia supernovae
begin to explode. Instead, we find that Type Ia supernova ejecta contribute to
the abundances of all but the most metal-poor ([Fe/H] < -2.5) stars. We have
also developed a chemical evolution model that tracks the star formation rate,
Types II and Ia supernova explosions, and supernova feedback. Without metal
enhancement in the supernova blowout, massive amounts of gas loss define the
history of all dSphs except Fornax, the most luminous in our sample. All six of
the best-fit model parameters correlate with dSph luminosity but not with
velocity dispersion, half-light radius, or Galactocentric distance.Comment: 28 pages, 14 figures; accepted for publication in ApJ; very minor
editorial corrections in v
PTF11eon/SN2011dh: Discovery of a Type IIb Supernova From a Compact Progenitor in the Nearby Galaxy M51
On May 31, 2011 UT a supernova (SN) exploded in the nearby galaxy M51 (the
Whirlpool Galaxy). We discovered this event using small telescopes equipped
with CCD cameras, as well as by the Palomar Transient Factory (PTF) survey, and
rapidly confirmed it to be a Type II supernova. Our early light curve and
spectroscopy indicates that PTF11eon resulted from the explosion of a
relatively compact progenitor star as evidenced by the rapid shock-breakout
cooling seen in the light curve, the relatively low temperature in early-time
spectra and the prompt appearance of low-ionization spectral features. The
spectra of PTF11eon are dominated by H lines out to day 10 after explosion, but
initial signs of He appear to be present. Assuming that He lines continue to
develop in the near future, this SN is likely a member of the cIIb (compact
IIb; Chevalier and Soderberg 2010) class, with progenitor radius larger than
that of SN 2008ax and smaller than the eIIb (extended IIb) SN 1993J progenitor.
Our data imply that the object identified in pre-explosion Hubble Space
Telescope images at the SN location is possibly a companion to the progenitor
or a blended source, and not the progenitor star itself, as its radius (~10^13
cm) would be highly inconsistent with constraints from our post-explosion
photometric and spectroscopic data
Knowledge as quality non-conformance : A critical case study of ISO 9000 and adult education in the workplace.
The study focused on the impact of the process seeking ISO 9000 registration and the way in which learning processes come to be defined as defective
Declining Public Awareness of Heart Attack Warning Symptoms in the Years Following an Australian Public Awareness Campaign: A Cross-Sectional Study
Background: The National Heart Foundation of Australia's (NHFA) Warning Signs campaign ran between 2010 and 2013. This study examines trends in Australian adults’ ability to name heart attack symptoms during the campaign and in the years following. Methods: Using the NHFA's HeartWatch data (quarterly online surveys) for adults aged 30–59 years, we conducted an adjusted piecewise regression analysis comparing trends in the ability to name symptoms during the campaign period plus one year lag (2010–2014) to the post-campaign period (2015–2020) Results: Over the study period, there were 101,936 Australian adults surveyed. Symptom awareness was high or increased during the campaign period. However, there was a significant downward trend in each year following the campaign period for most symptoms (e.g., chest pain: adjusted odds ratio [AOR] =0.91, 95%CI: 0.56–0.80; arm pain: AOR=0.92, 95%CI: 0.90–0.94). Conversely, the inability to name any heart attack symptom increased in each year following the campaign (3.7% in 2010 to 19.9% in 2020; AOR=1.13, 95%CI: 1.10–1.15); these respondents were more likely to be younger, male, have less than 12 years of education, identify as Aboriginal and/or Torres Strait Islander Peoples, speak a language other than English at home and have no cardiovascular risk factors. Conclusion: Awareness of heart attack symptoms has decreased in the years since the Warning Signs campaign in Australia, with 1 in 5 adults currently unable to name a single heart attack symptom. New approaches are needed to promote and sustain this knowledge, and to ensure people act appropriately and promptly if symptoms occur
Recruitment to the “Breast—Activity and Healthy Eating After Diagnosis”(B-AHEAD) Randomized Controlled Trial
Excess weight at breast cancer diagnosis and weight gain during treatment are linked to increased breast cancer specific and
all-cause mortality. The Breast—Activity and Healthy Eating After Diagnosis (B-AHEAD) trial tested 2 weight loss diet and
exercise programmes versus a control receiving standard written advice during adjuvant treatment. This article identifies
differences in characteristics between patients recruited from the main trial site to those of the whole population from
that site during the recruitment period and identifies barriers to recruitment. A total of 409 patients with operable breast
cancer were recruited within 12 weeks of surgery. We compared demographic and treatment factors between women
recruited from the main trial coordinating site (n = 300) to the whole breast cancer population in the center (n = 532).
Uptake at the coordinating site was 42%, comparable to treatment trials in the unit (47%). Women recruited were younger
(55.9 vs 61.2 years, P < .001), more likely to live in least deprived postcode areas (41.7% vs 31.6%, P = .004), and more likely
to have screen-detected cancers (55.3% vs 48.7%, P = .026) than the whole breast cancer population. The good uptake
highlights the interest in lifestyle change around the time of diagnosis, a challenging time in the patient pathway, and shows
that recruitment at this time is feasible. Barriers to uptake among older women and women with a lower socioeconomic
status should be understood and overcome in order to improve recruitment to future lifestyle intervention programs
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