1,519 research outputs found

    How Power Creates Alteration Among Communication for Members Within a Greek Letter Sorority

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    This study aims to address whether or not communication is altered due to hierarchical or seniority status within an all-female base organization such as a sorority. Prior to doing this research, I predicted that the outcome would result in negative alterations within communication. Using a survey method, I was able to obtain 90 participants within female based, National Panhellenic sororities nationwide. Overall, I found that there was more of a positive shift in communication between members who are in power positions, to those that are not

    Selectivity filter mutations shift ion permeation mechanism in potassium channels

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    Potassium (K+) channels combine high conductance with high ion selectivity. To explain this efficiency, two molecular mechanisms have been proposed. The ‘direct knock-on’ mechanism is defined by water-free K+ permeation and formation of direct ion-ion contacts in the highly conserved selectivity filter (SF). The ‘soft knock-on’ mechanism involves co-permeation of water and separation of K+ by water molecules. With the aim to distinguish between these mechanisms, crystal structures of the KcsA channel with mutations in two SF residues - G77 and T75 - were published, where the arrangements of K+ ions and water display canonical soft knock-on configurations. These data were interpreted as evidence of the soft knock-on mechanism in wild-type channels (C. Tilegenova, et al., Structure, function, and ion-binding properties of a K+ channel stabilized in the 2,4-ion–bound configuration. Proceedings of the National Academy of Sciences 116, 16829–16834 (2019)). Here, we test this interpretation using molecular dynamics simulations of KcsA and its mutants. We show that, while a strictly water-free direct knock-on permeation is observed in the wild-type, conformational changes induced by these mutations lead to distinct ion permeation mechanisms, characterized by co-permeation of K+ and water. These mechanisms are characterized by reduced conductance and impaired potassium selectivity, supporting the importance of full dehydration of potassium ions for the hallmark high conductance and selectivity of K+ channels. In general, we present a case where mutations introduced at the critical points of the permeation pathway in an ion channel drastically change its permeation mechanism in a non-intuitive manner

    Improving In Vivo Brain Delivery of Monoclonal Antibody Using Novel Cyclic Peptides

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    This work is licensed under a Creative Commons Attribution 4.0 International License.Many proteins can be used to treat brain diseases; however, the presence of the blood–brain barrier (BBB) creates an obstacle to delivering them into the brain. Previously, various molecules were delivered through the paracellular pathway of the BBB via its modulation, using ADTC5 and HAV6 peptides. This study goal was to design new cyclic peptides with N-to-C terminal cyclization for better plasma stability and modulation of the BBB. Cyclic HAVN1 and HAVN2 peptides were derived from a linear HAV6 peptide. Linear and N-to-C terminal cyclic ADTHAV peptides were designed by combining the sequences of ADTC5 and HAV6. These novel cyclic peptides were used to deliver an IRdye800CW-labeled IgG monoclonal antibody into the brain. Cyclic HAVN1 and HAVN2 peptides deliver IgG into the brain, while the parent linear HAV6 peptide does not. Cyclic and linear ADTHAV and ADTC5 peptides enhanced brain delivery of IgG mAb, in which cyclic ADTHAV peptide was better than linear ADTHAV (p = 0.07). Cyclic ADTHAV and ADTC5 influenced the distribution of IgG mAb in other organs while HAV6, HAVN1 and HAVN2 did not. In summary, the novel cyclic peptides are generally better BBB modulators than their linear counterparts for delivering IgG mAb into the brain

    Screening effects in superconductors

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    The partition function of the Hubbard model with local attraction and long range Coulomb repulsion between electrons is written as a functional integral with an action AA involving a pairing field Δ\Delta and a local potential VV. After integration over VV and over fluctuations in ∣Δ∣2|\Delta|^{2}, the final form of AA involves a Josephson coupling between the local phases of Δ\Delta and a "kinetic energy" term, representing the screened Coulomb interaction between charge fluctuations. The competition between Josephson coupling and charging energy allows to understand the relation between TCT_{C} and composition in high-TCT_{C} materials, in particular superlattices, alloys and bulk systems of low doping.Comment: 4 pages, revtex, no figures, submitted to Physica B (Proceedings of SCES '96 International Conference, held in Zurich from 19th to 21st of August

    Noninvasive Brain Delivery and Efficacy of BDNF to Stimulate Neuroregeneration and Suppression of Disease Relapse in EAE Mice

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    This document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, copyright © 2019 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.molpharmaceut.9b00644.The number of FDA-approved protein drugs (biologics), such as antibodies, antibody–drug conjugates, hormones, and enzymes, continues to grow at a rapid rate; most of these drugs are used to treat diseases of the peripheral body. Unfortunately, most of these biologics cannot be used to treat brain diseases such as Alzheimer’s disease (AD), multiple sclerosis (MS), and brain tumors in a noninvasive manner due to their inability to permeate the blood–brain barrier (BBB). Therefore, there is a need to develop an effective method to deliver protein drugs into the brain. Here, we report a proof of concept to deliver a recombinant brain-derived neurotrophic factor (BDNF) to the brains of healthy and experimental autoimmune encephalomyelitis (EAE) mice via intravenous (iv) injections by co-administering BDNF with a BBB modulator (BBBM) peptide ADTC5. Western blot evaluations indicated that ADTC5 enhanced the brain delivery of BDNF in healthy SJL/elite mice compared to BDNF alone and triggered the phosphorylation of TrkB receptors in the brain. The EAE mice treated with BDNF + ADTC5 suppressed EAE relapse compared to those treated with BDNF alone, ADTC5 alone, or vehicle. We further demonstrated that brain delivery of BDNF induced neuroregeneration via visible activation of oligodendrocytes, remyelination, and ARC and EGR1 mRNA transcript upregulation. In summary, we have demonstrated that ADTC5 peptide modulates the BBB to permit noninvasive delivery of BDNF to exert its neuroregeneration activity in the brains of EAE mice

    Modified ultrafast thermometer UFT-M and temperature measurements during Physics of Stratocumulus Top (POST)

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    A modified UFT-M version of the ultrafast airborne thermometer UFT, aimed at in-cloud temperature measurements, was designed for the Physics of Stratocumulus Top (POST) field campaign. Improvements in its construction resulted in the sensor's increased reliability, which provided valuable measurements in 15 of the 17 flights. Oversampling the data allowed for the effective correction of the artefacts resulting from the interference with electromagnetic transmissions from on-board avionic systems and the thermal noise resulting from the sensor construction. The UFT-M records, when averaged to the 1.4 and 55 m resolutions, compared to the similar records of a thermometer in a Rosemount housing, indicate that the housing distorts even low-resolution airborne temperature measurements. Data collected with the UFT-M during the course of POST characterise the thermal structure of stratocumulus and capping inversion with the maximum resolution of ~1 cm. In this paper, examples of UFT-M records are presented and discussed

    Analysis of time-profiles with in-beam PET monitoring in charged particle therapy

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    Background: Treatment verification with PET imaging in charged particle therapy is conventionally done by comparing measurements of spatial distributions with Monte Carlo (MC) predictions. However, decay curves can provide additional independent information about the treatment and the irradiated tissue. Most studies performed so far focus on long time intervals. Here we investigate the reliability of MC predictions of space and time (decay rate) profiles shortly after irradiation, and we show how the decay rates can give an indication about the elements of which the phantom is made up. Methods and Materials: Various phantoms were irradiated in clinical and near-clinical conditions at the Cyclotron Centre of the Bronowice proton therapy centre. PET data were acquired with a planar 16x16 cm2^2 PET system. MC simulations of particle interactions and photon propagation in the phantoms were performed using the FLUKA code. The analysis included a comparison between experimental data and MC simulations of space and time profiles, as well as a fitting procedure to obtain the various isotope contributions in the phantoms. Results and conclusions: There was a good agreement between data and MC predictions in 1-dimensional space and decay rate distributions. The fractions of 11^{11}C, 15^{15}O and 10^{10}C that were obtained by fitting the decay rates with multiple simple exponentials generally agreed well with the MC expectations. We found a small excess of 10^{10}C in data compared to what was predicted in MC, which was clear especially in the PE phantom.Comment: 9 pages, 5 figures, 1 table. Proceedings of the 20th International Workshop on Radiation Imaging Detectors (iWorid2018), 24-28 June 2018, Sundsvall, Swede
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