Mapping the core regulatory circuitry of embryonic stem cells

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2008.Includes bibliographical references.Embryonic stem (ES) cells are of tremendous biological interest because they have the capacity, termed pluripotency, to generate any cell type of the adult organism. Our lab is interested in understanding the genetic circuitry that governs pluripotency. For my thesis work I have contributed to a team effort to deduce the transcriptional regulatory circuitry of ES cells. This collaborative effort first sought to define the genes that are regulated by the key pluripotency regulators, Oct4, Sox2 and Nanog. We then determined the genes targeted by the Polycomb Repressive Complex in ES cells. These datasets allowed us to define the core transcriptional regulatory circuitry for these cells and demonstrated that pluripotency is mediated through the repression of developmental regulators. Finally, an effort to understand how Wnt signaling modifies this circuitry led to the discovery that the Wnt signaling component Tcf3 is a core component of the transcriptional regulatory circuitry and serves to repress the pluripotency regulators, contributing to the balance between pluripotency and differentiation.by Sarah E. Johnstone.Ph.D

An ALMA Search for Substructure, Fragmentation, and Hidden Protostars in Starless Cores in Chamaeleon I

We present an Atacama Large Millimeter/submillimeter Array (ALMA) 106 GHz (Band 3) continuum survey of the complete population of dense cores in the Chamaeleon I molecular cloud. We detect a total of 24 continuum sources in 19 different target fields. All previously known Class 0 and Class I protostars in Chamaeleon I are detected, whereas all of the 56 starless cores in our sample are undetected. We show that the Spitzer+Herschel census of protostars in Chamaeleon I is complete, with the rate at which protostellar cores have been misclassified as starless cores calculated as <1/56, or < 2%. We use synthetic observations to show that starless cores collapsing following the turbulent fragmentation scenario are detectable by our ALMA observations when their central densities exceed ~10^8 cm^-3, with the exact density dependent on the viewing geometry. Bonnor-Ebert spheres, on the other hand, remain undetected to central densities at least as high as 10^10 cm^-3. Our starless core non-detections are used to infer that either the star formation rate is declining in Chamaeleon I and most of the starless cores are not collapsing, matching the findings of previous studies, or that the evolution of starless cores are more accurately described by models that develop less substructure than predicted by the turbulent fragmentation scenario, such as Bonnor-Ebert spheres. We outline future work necessary to distinguish between these two possibilities.Comment: Accepted by Ap

Very Large Array Observations of Ammonia in Infrared-Dark Clouds II: Internal Kinematics

Infrared-dark clouds (IRDCs) are believed to be the birthplaces of rich clusters and thus contain the earliest phases of high-mass star formation. We use the Green Bank Telescope (GBT) and Very Large Array (VLA) maps of ammonia (NH3) in six IRDCs to measure their column density and temperature structure (Paper 1), and here, we investigate the kinematic structure and energy content. We find that IRDCs overall display organized velocity fields, with only localized disruptions due to embedded star formation. The local effects seen in NH3 emission are not high velocity outflows but rather moderate (few km/s) increases in the line width that exhibit maxima near or coincident with the mid-infrared emission tracing protostars. These line width enhancements could be the result of infall or (hidden in NH3 emission) outflow. Not only is the kinetic energy content insufficient to support the IRDCs against collapse, but also the spatial energy distribution is inconsistent with a scenario of turbulent cloud support. We conclude that the velocity signatures of the IRDCs in our sample are due to active collapse and fragmentation, in some cases augmented by local feedback from stars.Comment: 15 pages, 12 figures, accepted for publication in Ap

Health behaviours and mental and physical health status in older adults with a history of homelessness: a cross-sectional population-based study in England

Objectives: This study compared (i) levels of engagement in lifestyle risk behaviours and (ii) mental and physical health status in individuals who have previously been homeless to those of individuals who have not. Design: Cross-sectional. Participants: Data were from participants (n=6,931) of the English Longitudinal Study of Ageing. Measures: Participants reported whether they had ever been homeless. We used regression models to analyse associations between homelessness and (i) cigarette smoking, daily alcohol consumption and physical inactivity, adjusting for sociodemographic covariates (age, sex, ethnicity, highest level of education, marital status, and household non-pension wealth), and (ii) self-rated health, limiting long-standing illness, depressive symptoms, life satisfaction, quality of life and loneliness, adjusting for sociodemographics and health behaviours. Results: 104 participants (1.5%) reported having been homeless. Individuals who had been homeless were significantly more likely to be physically inactive (OR=1.62, 95% CI 1.44 to 2.52), report fair/bad/very bad self-rated health (OR=1.75, 95% CI 1.07 to 2.86), have a limiting long-standing illness (OR=2.66, 95% CI 1.65 to 4.30) and be depressed (OR=3.06, 95% CI 1.85 to 5.05), and scored lower on measures of life satisfaction (17.34 vs. 19.96, p<0.001) and quality of life (39.02 vs. 41.21, p=0.013). Rates of smoking (20.2% vs. 15.4%, p=0.436), daily drinking (27.6% vs. 22.8%, p=0.385), and loneliness (27.1% vs. 21.0%, p=0.080) were also elevated. Conclusions: Those who were once homeless have poorer mental and physical health outcomes and are more likely to be physically inactive. Interventions to improve their health and quality of life are required

Promoting physical activity in vulnerable adults “at risk” of homelessness: A Randomised Controlled Trial Protocol

Introduction: People who are homeless, or at risk of homelessness, have substantially poorer health. Sustained and regular participation in physical activity is beneficial for both mental and physical health. Limited data suggests that levels of physical activity in the homeless and those at risk of homelessness are low, and access to community-based exercise is limited or non-existent for this population. Nonetheless, exercise programs for the homeless could provide a feasible and scalable intervention for providing beneficial effects on physical and mental health in this population. The primary aim of this studyis to evaluate the impact of a group exercise intervention on activity levels in people who are homeless or at risk of homelessness in central London, UK. The secondary aim is to evaluate the impact of the intervention on mental and physical health outcomes. Method and analysis: A 2-arm, individually randomised controlled trial in people who are homeless and those vulnerable and at risk of homelessness in central London, UK. Participants will be recruited through a London-based homeless charity, Single Homeless Project. Following baseline assessments and allocation to intervention (exercise classes) or control (usual care), participants will be followed up at 3, 6, 9 and 12 months. The primary outcomes will be change in objective physical activity. The secondary outcomes will includechange in fitness assessments and mental health parameters. Changes in drug use and alcohol dependency will also be explored. Ethics and dissemination: Ethical approval was obtained through the Anglia Ruskin University Department of Sport and Exercise Sciences Research Ethics Committee. Results of this study will be disseminated through peer-reviewed publications and scientific presentations

Awesome SOSS: Transmission Spectroscopy of WASP-96b with NIRISS/SOSS

The future is now - after its long-awaited launch in December 2021, JWST began science operations in July 2022 and is already revolutionizing exoplanet astronomy. The Early Release Observations (ERO) program was designed to provide the first images and spectra from JWST, covering a multitude of science cases and using multiple modes of each on-board instrument. Here, we present transmission spectroscopy observations of the hot-Saturn WASP-96b with the Single Object Slitless Spectroscopy (SOSS) mode of the Near Infrared Imager and Slitless Spectrograph, observed as part of the ERO program. As the SOSS mode presents some unique data reduction challenges, we provide an in-depth walk-through of the major steps necessary for the reduction of SOSS data: including background subtraction, correction of 1/f noise, and treatment of the trace order overlap. We furthermore offer potential routes to correct for field star contamination, which can occur due to the SOSS mode's slitless nature. By comparing our extracted transmission spectrum with grids of atmosphere models, we find an atmosphere metallicity between 1x and 5x solar, and a solar carbon-to-oxygen ratio. Moreover, our models indicate that no grey cloud deck is required to fit WASP-96b's transmission spectrum, but find evidence for a slope shortward of 0.9$\mu$m, which could either be caused by enhanced Rayleigh scattering or the red wing of a pressure-broadened Na feature. Our work demonstrates the unique capabilities of the SOSS mode for exoplanet transmission spectroscopy and presents a step-by-step reduction guide for this new and exciting instrument.Comment: MNRAS, in press. Updated to reflect published versio

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

The JCMT BISTRO Survey: The Magnetic Field Strength in the Orion A Filament

We determine the magnetic field strength in the OMC 1 region of the Orion A filament via a new implementation of the Chandrasekhar-Fermi method using observations performed as part of the James Clerk Maxwell Telescope (JCMT) B-Fields In Star-Forming Region Observations (BISTRO) survey with the POL-2 instrument. We combine BISTRO data with archival SCUBA-2 and HARP observations to find a plane-of-sky magnetic field strength in OMC 1 of B_pos=6.6±4.7 mG, where δB_pos=4.7 mG represents a predominantly systematic uncertainty. We develop a new method for measuring angular dispersion, analogous to unsharp masking. We find a magnetic energy density of ~1.7×10^-7 Jm^-3 in OMC 1, comparable both to the gravitational potential energy density of OMC 1 (~10^-7 Jm^-3), and to the energy density in the Orion BN/KL outflow (~10^-7 Jm^-3). We find that neither the Alfvén velocity in OMC 1 nor the velocity of the super-Alfvénic outflow ejecta is sufficiently large for the BN/KL outflow to have caused large-scale distortion of the local magnetic field in the ~500-year lifetime of the outflow. Hence, we propose that the hour-glass field morphology in OMC 1 is caused by the distortion of a primordial cylindrically-symmetric magnetic field by the gravitational fragmentation of the filament and/or the gravitational interaction of the BN/KL and S clumps. We find that OMC 1 is currently in or near magnetically-supported equilibrium, and that the current large-scale morphology of the BN/KL outflow is regulated by the geometry of the magnetic field in OMC 1, and not vice versa