Purification and In Vitro Growth of Human Epidermal Basal Keratinocytes Using a Monoclonal Antibody

We have made a new monoclonal antibody, EL-2, and used it with an immunorosetting procedure combined with Ficoll-Hypaque gradient centrifugation to purify and culture basal keratinocytes. Immunofluorescence of cell suspensions and immunoperoxidase staining of tissue sections demonstrate that EL-2 reacts with malignant cell lines, activated lymphocytes and monocytes, and basal keratinocytes. Sequential immunoprecipitation studies demonstrate that monoclonal antibodies EL-2 and 4F2 detect the same membrane protein. However, we have extended previous studies by making the new observation that both EL-2 and 4F2 react with cultured melanocytes. Basal keratinocytes were purified from single-cell epidermal suspensions by incubation with EL-2 followed by rosetting with rabbit antimouse IgG antibodies covalently linked to bovine red blood cells. Rosetting (basal) keratinocytes were separated from EL-2 negative cells by Ficoll gradient centrifugation. We obtained basal keratinocyte populations of >90% purity as assessed by reactivity with EL-2 and another basal keratinocyte-specific monoclonal antibody, HCl. Langerhans cell, fibroblast, and melanocyte contamination was negligible. Cultures of basal keratinocytes were enriched in EL-2-reactive cells throughout the entire 19 days of culture studied. EL-2 is being used to characterize disorders of keratinocyte proliferation; EL-2 reacted with both squamous and basal cell carcinomas. EL-2 stained only the basal layer of lesional skin from patients with psoriasis, pityriasis rubra pilaris, and Darier's disease. Purification of basal keratinocytes will be important in biochemical and functional studies of normal skin and in establishing long-term keratinocyte lines from normal cells

A Multi-Armed Bandit to Smartly Select a Training Set from Big Medical Data

With the availability of big medical image data, the selection of an adequate training set is becoming more important to address the heterogeneity of different datasets. Simply including all the data does not only incur high processing costs but can even harm the prediction. We formulate the smart and efficient selection of a training dataset from big medical image data as a multi-armed bandit problem, solved by Thompson sampling. Our method assumes that image features are not available at the time of the selection of the samples, and therefore relies only on meta information associated with the images. Our strategy simultaneously exploits data sources with high chances of yielding useful samples and explores new data regions. For our evaluation, we focus on the application of estimating the age from a brain MRI. Our results on 7,250 subjects from 10 datasets show that our approach leads to higher accuracy while only requiring a fraction of the training data.Comment: MICCAI 2017 Proceeding

The Nature of Starbursts : II. The Duration of Starbursts in Dwarf Galaxies

The starburst phenomenon can shape the evolution of the host galaxy and the surrounding intergalactic medium. The extent of the evolutionary impact is partly determined by the duration of the starburst, which has a direct correlation with both the amount of stellar feedback and the development of galactic winds, particularly for smaller mass dwarf systems. We measure the duration of starbursts in twenty nearby, ongoing, and "fossil" starbursts in dwarf galaxies based on the recent star formation histories derived from resolved stellar population data obtained with the Hubble Space Telescope. Contrary to the shorter times of 3-10 Myr often cited, the starburst durations we measure range from 450 - 650 Myr in fifteen of the dwarf galaxies and up to 1.3 Gyr in four galaxies; these longer durations are comparable to or longer than the dynamical timescales for each system. The same feedback from massive stars that may quench the flickering SF does not disrupt the overall burst event in our sample of galaxies. While five galaxies present fossil bursts, fifteen galaxies show ongoing bursts and thus the final durations may be longer than we report here for these systems. One galaxy shows a burst that has been ongoing for only 20 Myr; we are likely seeing the beginning of a burst event in this system. Using the duration of the starbursts, we calculate that the bursts deposited 10^(53.9)-10^(57.2) ergs of energy into the interstellar medium through stellar winds and supernovae and produced 3%-26% of the host galaxy's mass.Comment: 28 pages, 4 figure

A Keck HIRES Doppler Search for Planets Orbiting Metal-Poor Dwarfs. II. On the Frequency of Giant Planets in the Metal-Poor Regime

We present an analysis of three years of precision radial velocity measurements of 160 metal-poor stars observed with HIRES on the Keck 1 telescope. We report on variability and long-term velocity trends for each star in our sample. We identify several long-term, low-amplitude radial-velocity variables worthy of follow-up with direct imaging techniques. We place lower limits on the detectable companion mass as a function of orbital period. Our survey would have detected, with a 99.5% confidence level, over 95% of all companions on low-eccentricity orbits with velocity semi-amplitude K > 100 m/s, or M_p*sin(i) > 3.0 M_JUP*(P/yr)^(1/3), for orbital periods P< 3 yr. None of the stars in our sample exhibits radial-velocity variations compatible with the presence of Jovian planets with periods shorter than the survey duration. The resulting average frequency of gas giants orbiting metal-poor dwarfs with -2.0 < [Fe/H] < -0.6 is f_p<0.67% (at the 1-sigma confidence level). We examine the implications of this null result in the context of the observed correlation between the rate of occurrence of giant planets and the metallicity of their main-sequence solar-type stellar hosts. By combining our dataset with the Fischer & Valenti (2005) uniform sample, we confirm that the likelihood of a star to harbor a planet more massive than Jupiter within 2 AU is a steeply rising function of the host's metallicity. However, the data for stars with -1.0 < [Fe/H] < 0.0 are compatible, in a statistical sense, with a constant occurrence rate f_p~1%. Our results can usefully inform theoretical studies of the process of giant planet formation across two orders of magnitude in metallicity.Comment: 59 pages, 7 tables, 8 figures. Accepted for publication in the Astrophysical Journa

Impact of the COVID-19 pandemic on chronic disease management and patient reported outcomes in patients with pulmonary hypertension: The Pulmonary Hypertension Association Registry

To better understand the impact of the COVID-19 pandemic on the care of patients with pulmonary hypertension, we conducted a retrospective cohort study evaluating health insurance status, healthcare access, disease severity, and patient reported outcomes in this population. Using the Pulmonary Hypertension Association Registry (PHAR), we defined and extracted a longitudinal cohort of pulmonary arterial hypertension (PAH) patients from the PHAR\u27s inception in 2015 until March 2022. We used generalized estimating equations to model the impact of the COVID-19 pandemic on patient outcomes, adjusting for demographic confounders. We assessed whether insurance status modified these effects via covariate interactions. PAH patients were more likely to be on publicly-sponsored insurance during the COVID-19 pandemic compared with prior, and did not experience statistically significant delays in access to medications, increased emergency room visits or nights in the hospital, or worsening of mental health metrics. Patients on publicly-sponsored insurance had higher healthcare utilization and worse objective measures of disease severity compared with privately insured individuals irrespective of the COVID-19 pandemic. The relatively small impact of the COVID-19 pandemic on pulmonary hypertension-related outcomes was unexpected but may be due to pre-established access to high quality care at pulmonary hypertension comprehensive care centers. Irrespective of the COVID-19 pandemic, patients who were on publicly-sponsored insurance seemed to do worse, consistent with prior studies highlighting outcomes in this population. We speculate that previously established care relationships may lessen the impact of an acute event, such as a pandemic, on patients with chronic illness