1,075 research outputs found

    Investigation of Magnesium Cation-proton Exchange with Transmembrane Electrostatically Localized Protons (TELP) at a Liquid-membrane Interface: Fundamental to Bioenergetics

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    The Lee transmembrane electrostatic proton localization (TELP) theory is a revolutionary scientific theory that has successfully explained decades long-standing quandary in the field of bioenergetics in regards to ATP synthesis in biological systems, specifically alkalophilic bacteria. This study provides experimental support for the TELP theory by further demonstrating evidence of a localized proton layer existing at the liquid-membrane interface in a simulated biological membrane apparatus. Whilst monovalent cations have been studied extensively, divalent cation exchange has not been studied experimentally. A previous study determined equilibrium constant for Na+ and K+ to exchange with localized H+ layer to be (5.07 ± 0.46) x 10-8 and (6.93 ± 0.91) x 10-8 respectively. We discovered that an equilibrium exchange occurs at 0.85 mM Mg2+ concentration. The findings here contributed to the successful determination of the equilibrium constant between Mg2+ and the localized H+ layer to be (1.56 ± 0.46) x 10-5. The equilibrium constant, much smaller than one, thus provides support for Lee’s TELP model since so many more Mg2+ in the bulk liquid phase that are required to even partially delocalize just a single H+ at the liquid-membrane interface. These results are relevant to further understand how water can act as a proton conductor for proton coupling energy transduction and the implications of different biological organisms’ salinity tolerance.https://digitalcommons.odu.edu/gradposters2022_sciences/1012/thumbnail.jp

    A genome-wide association study identifies a susceptibility locus for biliary atresia on 2p16.1 within the gene EFEMP1

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    Biliary atresia (BA) is a rare pediatric cholangiopathy characterized by fibrosclerosing obliteration of the extrahepatic bile ducts, leading to cholestasis, fibrosis, cirrhosis, and eventual liver failure. The etiology of BA remains unknown, although environmental, inflammatory, infectious, and genetic risk factors have been proposed. We performed a genome-wide association study (GWAS) in a European-American cohort of 343 isolated BA patients and 1716 controls to identify genetic loci associated with BA. A second GWAS was performed in an independent European-American cohort of 156 patients with BA and other extrahepatic anomalies and 212 controls to confirm the identified candidate BA-associated SNPs. Meta-analysis revealed three genome-wide significant BA-associated SNPs on 2p16.1 (rs10865291, rs6761893, and rs727878; P < 5 ×10-8), located within the fifth intron of the EFEMP1 gene, which encodes a secreted extracellular protein implicated in extracellular matrix remodeling, cell proliferation, and organogenesis. RNA expression analysis showed an increase in EFEMP1 transcripts from human liver specimens isolated from patients with either BA or other cholestatic diseases when compared to normal control liver samples. Immunohistochemistry demonstrated that EFEMP1 is expressed in cholangiocytes and vascular smooth muscle cells in liver specimens from patients with BA and other cholestatic diseases, but it is absent from cholangiocytes in normal control liver samples. Efemp1 transcripts had higher expression in cholangiocytes and portal fibroblasts as compared with other cell types in normal rat liver. The identification of a novel BA-associated locus, and implication of EFEMP1 as a new BA candidate susceptibility gene, could provide new insights to understanding the mechanisms underlying this severe pediatric disorder

    pp-waves in 11-dimensions with extra supersymmetry

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    The Killing spinor equations for pp-wave solutions of eleven dimensional supergravity are analysed and it is shown that there are solutions that preserve 18,20,22 and 24 supersymmetries, in addition to the generic solution preserving 16 supersymmetries and the Kowalski-Glikman solution preserving 32 supersymmetries.Comment: 13 pages. Reference added, typos corrected, new examples of 7-parameter case presente

    A prospective cohort study comparing the reactogenicity of trivalent influenza vaccine in pregnant and non-pregnant women

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    Background: Influenza vaccination during pregnancy can prevent serious illness in expectant mothers and provide protection to newborns; however, historically uptake has been limited due to a number of factors, including safety concerns. Symptomatic complaints are common during pregnancy and may be mistakenly associated with reactions to trivalent influenza vaccine (TIV). To investigate this, we compared post-vaccination events self-reported by pregnant women to events reported by non-pregnant women receiving TIV. Methods: A prospective cohort of 1,086 pregnant women and 314 non-pregnant female healthcare workers (HCWs) who received TIV between March-May 2014 were followed-up seven days post-vaccination to assess local and systemic adverse events following immunisation (AEFIs). Women were surveyed by text message regarding perceived reactions to TIV. Those reporting an AEFI completed an interview by telephone or mobile phone to ascertain details. Logistic regression models adjusting for age and residence were used to compare reactions reported by pregnant women and non-pregnant HCWs. Results: Similar proportions of pregnant women and non-pregnant, female HCWs reported ≥1 reaction following vaccination with TIV (13.0% and 17.3%, respectively; OR = 1.2 [95% CI: 0.8-1.8]). Non-pregnant, female HCWs were more likely to report fever or headache compared to pregnant women (OR: 4.6 [95% CI 2.1-10.3] and OR: 2.2 [95% CI 1.0-4.6], respectively). No other significant differences in reported symptoms were observed. No serious vaccine-associated adverse events were reported, and less than 2% of each group sought medical advice for a reaction. Conclusions: We found no evidence suggesting pregnant women are more likely to report adverse events following influenza vaccination when compared to non-pregnant female HCWs of similar age, and in some cases, pregnant women reported significantly fewer adverse events. These results further support the safety of TIV administered in pregnant women

    Quiet Eye Duration and Gun Motion in Elite Shotgun Shooting

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    INTRODUCTION: No literature exists to document skill-related differences in shotgun shooting and whether these may be a function of eye movements and control of gun motion. We therefore conducted an exploratory investigation of the visual search behaviors and gun barrel kinematics used by elite and subelite shooters across the three shotgun shooting subdisciplines. METHODS: Point of gaze and gun barrel kinematics were recorded in groups of elite (n = 24) and subelite (n = 24) shooters participating in skeet, trap, and double trap events. Point of gaze was calculated in relation to the scene, while motion of the gun was captured by two stationary external cameras. Quiet eye (final fixation or tracking gaze that is located on a specific location/object in the visual display for a minimum of 100 ms) duration and onset were analyzed as well as gun motion profiles in the horizontal and vertical planes. RESULTS: In skeet, trap, and double trap disciplines, elite shooters demonstrated both an earlier onset and a longer relative duration of quiet eye than their subelite counterparts did. Also, in all three disciplines, quiet eye duration was longer and onset earlier during successful compared with unsuccessful trials for elite and subelite shooters. Kinematic analyses indicated that a slower movement of the gun barrel was used by elite compared with subelite shooters. CONCLUSIONS: Overall, stable gun motion and a longer quiet eye duration seem critical to a successful performance in all three shotgun disciplines

    Error mitigation, optimization, and extrapolation on a trapped ion testbed

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    Current noisy intermediate-scale quantum (NISQ) trapped-ion devices are subject to errors around 1% per gate for two-qubit gates. These errors significantly impact the accuracy of calculations if left unchecked. A form of error mitigation called Richardson extrapolation can reduce these errors without incurring a qubit overhead. We demonstrate and optimize this method on the Quantum Scientific Computing Open User Testbed (QSCOUT) trapped-ion device to solve an electronic structure problem. We explore different methods for integrating this error mitigation technique into the Variational Quantum Eigensolver (VQE) optimization algorithm for calculating the ground state of the HeH+ molecule at 0.8 Angstrom. We test two methods of scaling noise for extrapolation: time-stretching the two-qubit gates and inserting two-qubit gate identity operations into the ansatz circuit. We find the former fails to scale the noise on our particular hardware. Scaling our noise with global gate identity insertions and extrapolating only after a variational optimization routine, we achieve an absolute relative error of 0.363% +- 1.06 compared to the true ground state energy of HeH+. This corresponds to an absolute error of 0.01 +- 0.02 Hartree; outside chemical accuracy, but greatly improved over our non error mitigated estimate. We ultimately find that the efficacy of this error mitigation technique depends on choosing the right implementation for a given device architecture and sampling budget.Comment: 16 pages, 11 figure

    Delays in Leniency Application: Is There Really a Race to the Enforcer's Door?

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    This paper studies cartels’ strategic behavior in delaying leniency applications, a take-up decision that has been ignored in the previous literature. Using European Commission decisions issued over a 16-year span, we show, contrary to common beliefs and the existing literature, that conspirators often apply for leniency long after a cartel collapses. We estimate hazard and probit models to study the determinants of leniency-application delays. Statistical tests find that delays are symmetrically affected by antitrust policies and macroeconomic fluctuations. Our results shed light on the design of enforcement programs against cartels and other forms of conspiracy

    Characterization of Antibodies against Receptor Activity-Modifying Protein 1 (RAMP1): A Cautionary Tale

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    Calcitonin gene-related peptide (CGRP) is a key component of migraine pathophysiology, yielding effective migraine therapeutics. CGRP receptors contain a core accessory protein subunit: receptor activity-modifying protein 1 (RAMP1). Understanding of RAMP1 expression is incomplete, partly due to the challenges in identifying specific and validated antibody tools. We profiled antibodies for immunodetection of RAMP1 using Western blotting, immunocytochemistry and immunohistochemistry, including using RAMP1 knockout mouse tissue. Most antibodies could detect RAMP1 in Western blotting and immunocytochemistry using transfected cells. Two antibodies (844, ab256575) could detect a RAMP1-like band in Western blots of rodent brain but not RAMP1 knockout mice. However, cross-reactivity with other proteins was evident for all antibodies. This cross-reactivity prevented clear conclusions about RAMP1 anatomical localization, as each antibody detected a distinct pattern of immunoreactivity in rodent brain. We cannot confidently attribute immunoreactivity produced by RAMP1 antibodies (including 844) to the presence of RAMP1 protein in immunohistochemical applications in brain tissue. RAMP1 expression in brain and other tissues therefore needs to be revisited using RAMP1 antibodies that have been comprehensively validated using multiple strategies to establish multiple lines of convincing evidence. As RAMP1 is important for other GPCR/ligand pairings, our results have broader significance beyond the CGRP field
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