535 research outputs found

    Inequity in the OCR Interview Process

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    The present study explores the question of whether there is an advantage to interviewing at a certain time of day, or in a certain position relative to others. Field data was cross-examined with survey data from 409 Penn students, which indicated if the individual had received a second round, and thus had been successful, after their first round interview. We found that individuals who interviewed (1) with an interviewer who had conducted fewer interviews prior to the given interview and (2) at an earlier time during the day had higher success rates. Rates of success declined as prior interviews increased and as the time of the interview became later. Prior research suggests that ego depletion, discrimination, and/or endogeneity may be at play in affecting these results. The results of this study indicate an answer to our research question, as well as the mechanisms affecting interview success as related to time of day, may benefit from further experimental research

    PolĪ·, PolĪ¶ and Rev1 together are required for G to T transversion mutations induced by the (+)- and (āˆ’)-trans-anti-BPDE-N(2)-dG DNA adducts in yeast cells

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    Benzo[a]pyrene is an important environmental mutagen and carcinogen. Its metabolism in cells yields the mutagenic, key ultimate carcinogen 7R,8S,9S,10R-anti-benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide, (+)-anti-BPDE, which reacts via its 10-position with N(2)-dG in DNA to form the adduct (+)-trans-anti-BPDE-N(2)-dG. To gain molecular insights into BPDE-induced mutagenesis, we examined in vivo translesion synthesis and mutagenesis in yeast cells of a site-specific 10S (+)-trans-anti-BPDE-N(2)-dG adduct and the stereoisomeric 10R (āˆ’)-trans-anti-BPDE-N(2)-dG adduct. In wild-type cells, bypass products consisted of 76% C, 14% A and 7% G insertions opposite (+)-trans-anti-BPDE-N(2)-dG; and 89% C, 4% A and 4% G insertions opposite (āˆ’)-trans-anti-BPDE-N(2)-dG. Translesion synthesis was reduced by āˆ¼26ā€“37% in rad30 mutant cells lacking PolĪ·, but more deficient in rev1 and almost totally deficient in rev3 (lacking PolĪ¶) mutants. C insertion opposite the lesion was reduced by āˆ¼24ā€“33% in rad30 mutant cells, further reduced in rev1 mutant, and mostly disappeared in the rev3 mutant strain. The insertion of A was largely abolished in cells lacking either PolĪ·, PolĪ¶ or Rev1. The insertion of G was not detected in either rev1 or rev3 mutant cells. The rad30 rev3 double mutant exhibited a similar phenotype as the single rev3 mutant with respect to translesion synthesis and mutagenesis. These results show that while the PolĪ¶ pathway is generally required for translesion synthesis and mutagenesis of the (+)- and (āˆ’)-trans-anti-BPDE-N(2)-dG DNA adducts, PolĪ·, PolĪ¶ and Rev1 together are required for Gā†’T transversion mutations, a major type of mutagenesis induced by these lesions. Based on biochemical and genetic results, we present mechanistic models of translesion synthesis of these two DNA adducts, involving both the one-polymerase one-step and two-polymerase two-step models

    Localization of sterols and oxysterols in mouse brain reveals distinct spatial cholesterol metabolism

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    Dysregulated cholesterol metabolism is implicated in a number of neurological disorders. Many sterols, including cholesterol and its precursors and metabolites, are biologically active and important for proper brain function. However, spatial cholesterol metabolism in brain and the resulting sterol distributions are poorly defined. To better understand cholesterol metabolism in situ across the complex functional regions of brain, we have developed on-tissue enzyme-assisted derivatization in combination with microliquid extraction for surface analysis and liquid chromatography-mass spectrometry to locate sterols in tissue slices (10 Āµm) of mouse brain. The method provides sterolomic analysis at 400-Āµm spot diameter with a limit of quantification of 0.01 ng/mm2. It overcomes the limitations of previous mass spectrometry imaging techniques in analysis of low-abundance and difficult-to-ionize sterol molecules, allowing isomer differentiation and structure identification. Here we demonstrate the spatial distribution and quantification of multiple sterols involved in cholesterol metabolic pathways in wild-type and cholesterol 24S-hydroxylase knockout mouse brain. The technology described provides a powerful tool for future studies of spatial cholesterol metabolism in healthy and diseased tissues

    Impact of Ionic Liquids on Silver Thermoplastic Composite Membrane Polyurethane for Propane/Propylene Separation

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    This work describes newly synthesized composite polymeric membranes and their utilization in propane/propylene separation in a gas mixture. The nonporous composite polymers were successfully synthesized by using thermoplastic polyurethane (TPU) and several silver salts/silver salts with ionic liquids (ILs). Our studies showed that silver bis(trifluoromethanesulfonyl)imide (Ag[Tf2N]) containing membranes outperformed other silver salt containing membranes in terms of selectivity. In addition, to this finding, ILs, as additives for the membranes, enhanced the selectivity by facilitating improved coordination of the olefin with the silver ions in the dense composite polymers.Scopu

    Dwarf AGNs from Variability for the Origins of Seeds (DAVOS): Intermediate-mass black hole demographics from optical synoptic surveys

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    We present a phenomenological forward Monte Carlo model for forecasting the population of active galactic nuclei (AGNs) in dwarf galaxies observable via their optical variability. Our model accounts for expected changes in the spectral energy distribution of AGNs in the intermediate-mass black hole (IMBH) mass range and uses observational constraints on optical variability as a function of black hole (BH) mass to generate mock light curves. Adopting several different models for the BH occupation function, including one for off-nuclear IMBHs, we quantify differences in the predicted local AGN mass and luminosity functions in dwarf galaxies. As a result, we are able to model the variable fraction of AGNs as a function of physical host properties, such as host galaxy stellar mass, in the presence of complex selection effects. We find that our adopted occupation fractions for the "heavy" and "light" initial BH seeding scenarios can be distinguished with variability data at the 2āˆ’3Ļƒ2-3 \sigma level for galaxy host stellar masses below āˆ¼108MāŠ™\sim 10^8 M_\odot with the Vera C. Rubin Observatory. We demonstrate the prevalence of a selection bias whereby recovered IMBH masses fall, on average, above the predicted value from the local host galaxy - BH mass scaling relation with the strength of the bias dependent on the survey sensitivity. The methodology developed in this work can be used more broadly to forecast and correct for selection effects for AGN demographic studies in synoptic surveys. Finally, we show that a targeted āˆ¼\sim hourly cadence program over a few nights with the Rubin Observatory can provide strong constraints on IMBH masses given their expected rapid variability timescales.Comment: 26 pages, 16 figures incl. 5 appendices; re-submitted to MNRAS following referee repor

    Drug Delivery Implants in the Treatment of Vitreous Inflammation

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    The eye is a model organ for the local delivery of therapeutics. This proves beneficial when treating vitreous inflammation and other ophthalmic pathologies. The chronicity of certain diseases, however, limits the effectiveness of locally administered drugs. To maintain such treatments often requires frequent office visits and can result in increased risk of infection and toxicity to the patient. This paper focuses on the implantable devices and particulate drug delivery systems that are currently being implemented and investigated to overcome these challenges. Implants currently on the market or undergoing clinical trials include those made of nonbiodegradable polymers, containing ganciclovir, fluocinolone acetonide, triamcinolone acetonide, and ranibizumab, and biodegradable polymers, containing dexamethasone, triamcinolone acetonide, and ranibizumab. Investigational intravitreal implants and particulate drug delivery systems, such as nanoparticles, microparticles, and liposomes, are also explored in this review article

    GPS Tracking in Dementia Caregiving: Social Norm, Perceived Usefulness, and Behavioral Intent to Use Technology

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    Remote monitoring technology has taken a place in dementia caregiving by providing assistive tools such as tracking devices using Global Positioning Systems (GPS). Nevertheless, caregiversā€™ attitudes toward this technology are still inconclusive, and the factors leading up to their behavioral intent to use the technology remain unclear. Based on a survey of 202 dementia caregivers, our analysis with structural equation modeling demonstrates that care recipientsā€™ (i.e., persons with dementia) wandering, caregiversā€™ concern, as well as caregiversā€™ smartphone usage positively predict caregiversā€™ behavioral intent to use GPS tracking devices. Meanwhile, social norm and perceived usefulness of technology mediate the relationship between individual attributes and behavioral intent. Theoretical and practical implications are discussed

    Genetic models of apoptosis-induced proliferation decipher activation of JNK and identify a requirement of EGFR signaling for tissue regenerative responses in Drosophila

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    Recent work in several model organisms has revealed that apoptotic cells are able to stimulate neighboring surviving cells to undergo additional proliferation, a phenomenon termed apoptosis-induced proliferation. This process depends critically on apoptotic caspases such as Dronc, the Caspase-9 ortholog in Drosophila, and may have important implications for tumorigenesis. While it is known that Dronc can induce the activity of Jun N-terminal kinase (JNK) for apoptosis-induced proliferation, the mechanistic details of this activation are largely unknown. It is also controversial if JNK activity occurs in dying or in surviving cells. Signaling molecules of the Wnt and BMP families have been implicated in apoptosis-induced proliferation, but it is unclear if they are the only ones. To address these questions, we have developed an efficient assay for screening and identification of genes that regulate or mediate apoptosis-induced proliferation. We have identified a subset of genes acting upstream of JNK activity including Rho1. We also demonstrate that JNK activation occurs both in apoptotic cells as well as in neighboring surviving cells. In a genetic screen, we identified signaling by the EGFR pathway as important for apoptosis-induced proliferation acting downstream of JNK signaling. These data underscore the importance of genetic screening and promise an improved understanding of the mechanisms of apoptosis-induced proliferation

    Clinical, Cytogenetic, and Molecular Findings in Two Cases of Variant t(8;21) Acute Myeloid Leukemia (AML).

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    t(8;21)(q22;q22) is present in ~5ā€“10% of patients with de novo acute myeloid leukemia (AML) and is associated with a better overall prognosis. Variants of the t(8;21) have been described in the literature, however, their clinical and prognostic significance has not been well-characterized. Molecular profiling of these cases has not previously been reported but may be useful in better defining the prognosis of this subset of patients. We present two cases of variant t(8;21) AML including clinical, cytogenetic, and molecular data
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