170 research outputs found

    An Experimental Investigation of the Effect of Narrowband Freestream Noise on Fundamental Transitional Shockwave-Boundary Layer Interaction Mechanisms

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    Recent work at the University of Tennessee Space Institute has demonstrated that the resonant behavior observed in the spectra of cylinder- and blunt-fin-generated XSBLIs is connected to fundamental fluid mechanisms within the boundary layer. Therefore, a test campaign was conducted to characterize the fundamental mechanisms that drive the low-frequency unsteadiness in cylinder- and blunt-fin-generated shockwave-boundary layer interactions, specifically shockwave-boundary layer interactions in which the incoming boundary layer is undergoing a laminar-to-turbulent transition. This research aims to develop a deeper understanding of such interactions and characterize the resonant behavior observed in past work by varying the sweepback angle of a hemicylindrical blunt fin in the UTSI Mach 2 Blowdown Facility. A z-type schlieren setup provided a qualitative understanding of the flowfield. Quantitative results were extracted from the qualitative images using image processing techniques developed within MATLAB. Previously reported freestream narrowband noise in the University of Tennessee Space Institute Mach 2 Blowdown Facility was measured in the spectral content of the leading-edge shockwave and in the boundary layer. The unswept case showed excellent agreement with previously reported results. However, the swept blunt-fins did not exhibit the same narrowband spectral content as the unswept blunt-fin, but instead showed a broadening of the spectral content as the sweep angle was increased. Additionally, the scale of the interactions decreased, as expected, with the reduction in shock strength. Furthermore, the calculated Strouhal numbers for the swept fins showed excellent agreement with prior research

    NBOMe Toxicity and Fatalities: A Review of the Literature

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    In the decade since the introduction of the novel synthetic hallucinogen NBOMe into the consumer market, this drug has become an increasingly prevalent, yet poorly understood cause of altered mental status (AMS) resulting in hospitalization. In this literature review, we conducted a PubMed query for mentions of NBOMe ingestion since Suzuki et al.’s publication of their 2015 review. Among English language publications published between October 2014 and June 8, 2021, were sixteen case reports and six case series detailing a total of 42 cases of NBOMe toxicity. Notably, 26 (62%) patients experienced tachycardia, 22 (52%) had hypertension, 34 (81%) experienced hallucinations. Nine of 42 cases ended in fatality, including six cases of apparent direct NBOMe toxicity, one death by suicide, and two cases of fatalities from trauma after “excited delirium.” At least seven individuals believed that they had purchased and consumed LSD. This updated review of the literature underlines the high prevalence of fatality associated with NBOMe ingestion, as well as the need for increased knowledge among law enforcement and emergency medical providers of the toxidrome of NBOMe when responding to cases of AMS

    Arab-Israeli conflict 1947-1967: a view through the public speeches of U.S. secretaries of state

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    Due to the character of the original source materials and the nature of batch digitization, quality control issues may be present in this document. Please report any quality issues you encounter to [email protected], referencing the URI of the item.Includes bibliographical references (leaves 62-64).This project is a re-visitation of the 20-year period of Arab-Israeli conflict immediately following the United Nations' creation of the state of Israel. It focuses on U.S. policy towards the Arab-Israeli dispute by examining the public speeches of the U.S. secretaries of state. When necessary, the scope of documents is widened to include internal State Department papers, the memoirs of the secretaries of state, public speeches by other Department of State officials, and general historical accounts of Arab-Israeli and Middle Eastern events. The written materials are used to determine the different pressures that cause U.S. policy shifts, to evaluate any static or evolving policy trends, and to generate an historical sketch of U.S. involvement. The pressures on U.S. policy that are examined include communism, the United Nations, the economic effects of Middle Eastern oil, arms shipments to Arab and Israeli interests, the Palestinian refugees, and the domestic political influence on U.S. officials. After the initial establishment of U.S. policy in 1947 and 1948, the secretaries of state attempted to maintain a consistent tone towards Arab-Israeli issues. The role of the Cold War, however, made this endeavor increasingly difficult as the U.S. and the Soviet Union inched closer to armed conflict. This factor would weigh just as heavily as economic concerns on U.S. policy in the Middle East over the twenty year span. The other factors examined, while important in the overall scheme, did not substantially impact U.S. policy as much as the Cold War and economic interests. While each secretary of state and subsequent presidential administration did try to make progress in removing the Arab-Israeli disputes, the consistency of the pressures on U.S. policy produced a stagnant atmosphere not conducive to change or improvement. All of these pressures, with the exception of the role of communism, still exist today, along with a newer, more intense threat of Arab resentment towards the United States; their existence continues to plague U.S. policymaking towards the Arab-Israeli conflicts

    The Diversity of Life by E.O. Wilson

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    In The Diversity of Life, E. O. Wilson tells a tale about how our earth is on track for another extinction event and humans are at fault. Wilson discusses various topics such as environmental preservation, biodiversity and its importance, and how life has evolved over time. Wilson views biodiversity differently than many as he focuses on all species found in the ecosystem rather than narrowing his focus on one. He mentions how new species can be created by groups evolving and developing new skills or existing in new environments. Species are going extinct and being created constantly; these extinctions don\u27t have to be large; they can exist on small scales yet still cause an impact on the entire ecosystem. Wilson goes on to explain that humans have existed for a small period of time yet we are the number one cause of extinction events within species. Ultimately, humans will be the cause of our own downfall as the environment is a reflection and product of human actions.https://scholarworks.moreheadstate.edu/celebration_posters_2023/1008/thumbnail.jp

    Epigenetic Small Molecules Rescue Nucleocytoplasmic Transport and DNA Damage Phenotypes in C9ORF72 ALS/FTD

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    Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease with available treatments only marginally slowing progression or improving survival. A hexanu-cleotide repeat expansion mutation in the C9ORF72 gene is the most commonly known genetic cause of both sporadic and familial cases of ALS and frontotemporal dementia (FTD). The C9ORF72 expansion mutation produces five dipeptide repeat proteins (DPRs), and while the mechanistic determinants of DPR-mediated neurotoxicity remain incompletely understood, evidence suggests that disruption of nucleocytoplasmic transport and increased DNA damage contributes to pathology. Therefore, characterizing these disturbances and determining the relative contribution of different DPRs is needed to facilitate the development of novel therapeutics for C9ALS/FTD. To this end, we generated a series of nucleocytoplasmic transport “biosensors”, composed of the green fluorescent protein (GFP), fused to different classes of nuclear localization signals (NLSs) and nuclear export signals (NESs). Using these biosensors in conjunction with automated microscopy, we investigated the role of the three most neurotoxic DPRs (PR, GR, and GA) on seven nuclear import and two export pathways. In addition to other DPRs, we found that PR had pronounced inhibitory effects on the classical nuclear export pathway and several nuclear import pathways. To identify compounds capable of counteracting the effects of PR on nucleocytoplasmic transport, we developed a nucleocy-toplasmic transport assay and screened several commercially available compound libraries, totaling 2714 compounds. In addition to restoring nucleocytoplasmic transport efficiencies, hits from the screen also counteract the cytotoxic effects of PR. Selected hits were subsequently tested for their ability to rescue another C9ALS/FTD phenotype—persistent DNA double strand breakage. Overall, we found that DPRs disrupt multiple nucleocytoplasmic transport pathways and we identified small molecules that counteract these effects—resulting in increased viability of PR-expressing cells and decreased DNA damage markers in patient-derived motor neurons. Several HDAC inhibitors were validated as hits, supporting previous studies that show that HDAC inhibitors confer therapeutic effects in neurodegenerative models

    Prospects for Pulsar Studies at MeV Energies

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    Enabled by the Fermi Large Area Telescope, we now know young and recycled pulsars fill the gamma-ray sky, and we are beginning to understand their emission mechanism and their distribution throughout the Galaxy. However, key questions remain: Is there a large population of pulsars near the Galactic center? Why do the most energetic pulsars shine so brightly in MeV gamma rays but not always at GeV energies? What is the source and nature of the pair plasma in pulsar magnetospheres, and what role does the polar cap accelerator play? Addressing these questions calls for a sensitive, wide-field MeV telescope, which can detect the population of MeV-peaked pulsars hinted at by Fermi and hard X-ray telescopes and characterize their spectral shape and polarization.Comment: 8 pages, 4 figures, Astro2020 Science White Paper submitted to the National Academies of Science

    The novel BET inhibitor UM-002 reduces glioblastoma cell proliferation and invasion

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    Bromodomain and extraterminal domain (BET) proteins have emerged as therapeutic targets in multiple cancers, including the most common primary adult brain tumor glioblastoma (GBM). Although several BET inhibitors have entered clinical trials, few are brain penetrant. We have generated UM-002, a novel brain penetrant BET inhibitor that reduces GBM cell proliferation in vitro and in a human cerebral brain organoid model. Since UM-002 is more potent than other BET inhibitors, it could potentially be developed for GBM treatment. Furthermore, UM-002 treatment reduces the expression of cell-cycle related genes in vivo and reduces the expression of invasion related genes within the non-proliferative cells present in tumors as measured by single cell RNA-sequencing. These studies suggest that BET inhibition alters the transcriptional landscape of GBM tumors, which has implications for designing combination therapies. Importantly, they also provide an integrated dataset that combines in vitro and ex vivo studies with in vivo single-cell RNA-sequencing to characterize a novel BET inhibitor in GBM

    Magnetars as Astrophysical Laboratories of Extreme Quantum Electrodynamics: The Case for a Compton Telescope

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    A next generation of Compton and pair telescopes that improve MeV-band detection sensitivity by more than a decade beyond current instrumental capabilities will open up new insights into a variety of astrophysical source classes. Among these are magnetars, the most highly magnetic of the neutron star zoo, which will serve as a prime science target for a new mission surveying the MeV window. This paper outlines the core questions pertaining to magnetars that can be addressed by such a technology. These range from global magnetar geometry and population trends, to incisive probes of hard X-ray emission locales, to providing cosmic laboratories for spectral and polarimetric testing of exotic predictions of QED, principally the prediction of the splitting of photons and magnetic pair creation. Such fundamental physics cannot yet be discerned in terrestrial experiments. State of the art modeling of the persistent hard X-ray tail emission in magnetars is presented to outline the case for powerful diagnostics using Compton polarimeters. The case highlights an inter-disciplinary opportunity to seed discovery at the interface between astronomy and physics.Comment: 11 pages, 4 figures, Astro2020 Science White Paper submitted to the National Academies of Science
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