66 research outputs found

    The Design of an Electro-Mechanical Bicycle for an Immersive Virtual Environment

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    Roughly 50,000 people are injured in bicycle collisions with motor vehicles each year, approximately 6,000 of these injuries involve children less than 14 years old. To better understand which factors put bicycling children at risk for motor vehicle collisions, researchers at the University of Iowa built a virtual environment that simulates the experience of riding through a town and crossing roads with motor vehicles traffic. The stationary bicycle, the focus of this report, replicates the pedal forces experienced by a rider. The stationary bike also provides the simulator with the bicycle’s velocity and steering angle. This report describes the design of the system, which features a flywheel designed to represent the rider and bike inertia, the mechanical linkages between the rider and an electric motor, and a system to measure steering angles. The bicycle has been built and tested and is currently in use in the virtual environment

    Cannabinoid Receptor Involvement in Stress-Induced Cocaine Reinstatement: Potential Interaction with Noradrenergic Pathways

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    This study examined the role of endocannabinoid signaling in stress-induced reinstatement of cocaine seeking and explored the interaction between noradrenergic and endocannabinergic systems in the process. A well-validated preclinical model for human relapse, the rodent conditioned place preference assay, was used. Cocaine-induced place preference was established in C57BL/6 mice using injections of 15 mg/kg cocaine. Following extinction of preference for the cocaine-paired environment, reinstatement of place preference was determined following 6 min of swim stress or cocaine injection (15 mg/kg, i.p.). The role of endocannabinoid signaling was studied using the cannabinoid antagonist AM-251 (3 mg/kg, i.p.). Another cohort of mice was tested for reinstatement following administration of the cannabinoid agonist CP 55,940 (10, 20, or 40 μg/kg, i.p.). The alpha-2 adrenergic antagonist BRL-44408 (5 mg/kg, i.p.) with or without CP 55,940 (20 μg/kg) was administered to a third group of mice. We found that: (1) AM-251 blocked forced swim-induced, but not cocaine-induced, reinstatement of cocaine-seeking behavior; (2) the cannabinoid agonist CP 55,940 did not reinstate cocaine-seeking behavior when administered alone but did synergize with a non-reinstating dose of the alpha-2 adrenergic antagonist BRL-44408 to cause reinstatement. These results are consistent with the hypothesis that stress exposure triggers the endogenous activation of CB1 receptors and that activation of the endocannabinoid system is required for the stress-induced relapse of the mice to cocaine seeking. Further, the data suggest that the endocannabinoid system interacts with noradrenergic mechanisms to influence stress-induced reinstatement of cocaine-seeking behavior

    Chatten gegen die Entfremdung? Eine Untersuchung zu Resonanzerfahrungen in medienvermittelter Kommunikation

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    Die Theorie der Resonanz von Rosa beschreibt intensive, nicht-entfremdete menschliche Weltbeziehungen als Erfahrungen der Resonanz, der Affizierung und Anverwandlung. In der theoretischen Diskussion viel beachtet, blieben empirische Zugänge rar. Diese Studie untersucht, unter welchen Umständen Menschen in medienvermittelter interpersonaler Kommunikation Resonanzerfahrungen erleben, und welchen Einfluss spezifische Medieneigenschaften dabei nehmen. Dafür wird die Resonanztheorie mit Wirkungstheorien wie der Theorie der sozialen Präsenz sowie mit der psychologischen Flow-Theorie in Beziehung gesetzt. Mit einem Mixed-Method-Design aus Experience Sampling und Leitfadeninterviews wurden die alltäglichen Kommunikationserfahrungen von elf Erwachsenen zwischen 18 und 23 Jahren untersucht. Ziel war die Analyse erlebter Resonanzerfahrungen hinsichtlich möglicher beeinflussender Aspekte. Auch Zusammenhänge von Resonanz und Medienwahl wurden betrachtet. Die Untersuchung zeigte, dass die Teilnehmenden Resonanzerfahrungen unterschiedlicher Qualität erlebten. Dabei spielten unterschiedliche mediale Reichhaltigkeiten eine Rolle, starken Einfluss nahmen Aspekte wie Konzentration, Herausforderung und Wohlbefinden. Die Kommunikationsziele Resonanz, Verständnis, Kontrolle und Distanz wurden als Entscheidungsfaktoren für die Medienwahl identifiziert. Auch aufgrund kommunikationsfremder Ziele verzichteten die Teilnehmenden wiederholt auf potenziell intensivere Resonanzerfahrungen.With the theory of resonance Rosa describes intensive, non-alienated human world relations as experiences of resonance, affection and transformation. While this theory has received much attention in theoretical discussions, empirical approaches have so far remained rare. This study investigates the circumstances under which people experience resonance in mediated interpersonal communication, and what influence specific media properties have on this. For this purpose, Rosa's resonance theory is combined, and put into relation with, media effects theories such as the theory of social presence as well as the psychological flow theory. Using a mixed-method design of experience sampling and guided interviews, the everyday communication experiences of eleven young adults between the ages of 18 and 23 were investigated. The study showed that the participants experienced resonance to varying degrees. Media characteristics according to media richness played a role, but aspects such as concentration, challenge and well-being also had a strong influence. The four communication goals resonance, understanding, control and distance could be identified as decision factors for the choice of media. Participants also repeatedly refrained from potentially more intensive experiences of resonance due to goals unrelated to communication

    Temporal changes in distributions and the species atlas: how can British and Irish plant data shoulder the inferential burden?

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    Species distribution atlases often rely on volunteer effort to achieve their desired coverage, an activity now typically discussed, at least in academia, under the general theme of “citizen science”. Such data, however, are rarely without complex biases, particularly with respect to the estimation of trends in species’ distributions over many decades. The data of the Botanical Society of Britain and Ireland (BSBI) are no exception to this, and both careful thought in data aggregation (spatial, temporal, and taxonomic) and appropriate modelling procedures are required to overcome these challenges. We discuss these issues, with a primary focus on the statistical models that have been put forward to adjust for such biases. Such models include the Telfer method, various “reporting rate” approaches based on generalised linear models, the frequency scaling using local occupancy (“Frescalo”) model, occupancy models, and spatial smoothing methods. In each case the strengths and limitations in relation to estimating trends from distribution data with important time-varying biases are assessed. Various properties of BSBI data, in particular the increasing numbers of records at fine spatial and temporal scales over the past century, coupled with a general lack of re-visits to sites at such finer scales and the time-varying biases previously mentioned, imply that methods that can be sensibly applied at coarser levels are likely to be most appropriate for estimating accurate long-term trends in distributions. We conclude that Frescalo, which can be seen as a type of occupancy model where an adjustment for overlooked species is made in relation to spatial rather than temporal replication, whilst simultaneously adjusting for variable regional effort, is currently the most sophisticated tool for achieving this. Although recording community-accepted adjustments to data collection practices may allow for a greater application of occupancy modelling or other approaches in the future, methods that seek accurate trends over the long-term are necessarily limited either to scales at which various properties of the data in hand are most likely to be unbiased, or at which the biases are well enough understood to be modelled accurately

    The Testis-Specific Factor CTCFL Cooperates with the Protein Methyltransferase PRMT7 in H19 Imprinting Control Region Methylation

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    Expression of imprinted genes is restricted to a single parental allele as a result of epigenetic regulation—DNA methylation and histone modifications. Igf2/H19 is a reciprocally imprinted locus exhibiting paternal Igf2 and maternal H19 expression. Their expression is regulated by a paternally methylated imprinting control region (ICR) located between the two genes. Although the de novo DNA methyltransferases have been shown to be necessary for the establishment of ICR methylation, the mechanism by which they are targeted to the region remains unknown. We demonstrate that CTCFL/BORIS, a paralog of CTCF, is an ICR-binding protein expressed during embryonic male germ cell development, coinciding with the timing of ICR methylation. PRMT7, a protein arginine methyltransferase with which CTCFL interacts, is also expressed during embryonic testis development. Symmetrical dimethyl arginine 3 of histone H4, a modification catalyzed by PRMT7, accumulates in germ cells during this developmental period. This modified histone is also found enriched in both H19 ICR and Gtl2 differentially methylated region (DMR) chromatin of testis by chromatin immunoprecipitation (ChIP) analysis. In vitro studies demonstrate that CTCFL stimulates the histone-methyltransferase activity of PRMT7 via interactions with both histones and PRMT7. Finally, H19 ICR methylation is demonstrated by nuclear co-injection of expression vectors encoding CTCFL, PRMT7, and the de novo DNA methyltransferases, Dnmt3a, -b and -L, in Xenopus oocytes. These results suggest that CTCFL and PRMT7 may play a role in male germline imprinted gene methylation

    Molecular Cause and Functional Impact of Altered Synaptic Lipid Signaling Due to a \u3cem\u3eprg-1\u3c/em\u3e Gene SNP

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    Loss of plasticity‐related gene 1 (PRG‐1), which regulates synaptic phospholipid signaling, leads to hyperexcitability via increased glutamate release altering excitation/inhibition (E/I) balance in cortical networks. A recently reported SNP in prg‐1 (R345T/mutPRG‐1) affects ~5 million European and US citizens in a monoallelic variant. Our studies show that this mutation leads to a loss‐of‐PRG‐1 function at the synapse due to its inability to control lysophosphatidic acid (LPA) levels via a cellular uptake mechanism which appears to depend on proper glycosylation altered by this SNP. PRG‐1+/− mice, which are animal correlates of human PRG‐1+/mut carriers, showed an altered cortical network function and stress‐related behavioral changes indicating altered resilience against psychiatric disorders. These could be reversed by modulation of phospholipid signaling via pharmacological inhibition of the LPA‐synthesizing molecule autotaxin. In line, EEG recordings in a human population‐based cohort revealed an E/I balance shift in monoallelic mutPRG‐1 carriers and an impaired sensory gating, which is regarded as an endophenotype of stress‐related mental disorders. Intervention into bioactive lipid signaling is thus a promising strategy to interfere with glutamate‐dependent symptoms in psychiatric diseases

    Urgent need for a non-discriminatory and non-stigmatizing nomenclature for monkeypox virus

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    Free PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9451062/We propose a novel, non-discriminatory classification of monkeypox virus diversity. Together with the World Health Organization, we named three clades (I, IIa and IIb) in order of detection. Within IIb, the cause of the current global outbreak, we identified multiple lineages (A.1, A.2, A.1.1 and B.1) to support real-time genomic surveillance.info:eu-repo/semantics/publishedVersio

    Single-molecule in vivo imaging of bacterial respiratory complexes indicates delocalized oxidative phosphorylation

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    Chemiosmotic energy coupling through oxidative phosphorylation (OXPHOS) is crucial to life, requiring coordinated enzymes whose membrane organization and dynamics are poorly understood. We quantitatively explore localization, stoichiometry, and dynamics of key OXPHOS complexes, functionally fluorescent protein-tagged, in Escherichia coli using low-angle fluorescence and superresolution microscopy, applying single-molecule analysis and novel nanoscale co-localization measurements. Mobile 100-200nm membrane domains containing tens to hundreds of complexes are indicated. Central to our results is that domains of different functional OXPHOS complexes do not co-localize, but ubiquinone diffusion in the membrane is rapid and long-range, consistent with a mobile carrier shuttling electrons between islands of different complexes. Our results categorically demonstrate that electron transport and proton circuitry in this model bacterium are spatially delocalized over the cell membrane, in stark contrast to mitochondrial bioenergetic supercomplexes. Different organisms use radically different strategies for OXPHOS membrane organization, likely depending on the stability of their environment

    Global disparities in SARS-CoV-2 genomic surveillance

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    Genomic sequencing is essential to track the evolution and spread of SARS-CoV-2, optimize molecular tests, treatments, vaccines, and guide public health responses. To investigate the global SARS-CoV-2 genomic surveillance, we used sequences shared via GISAID to estimate the impact of sequencing intensity and turnaround times on variant detection in 189 countries. In the first two years of the pandemic, 78% of high-income countries sequenced >0.5% of their COVID-19 cases, while 42% of low- and middle-income countries reached that mark. Around 25% of the genomes from high income countries were submitted within 21 days, a pattern observed in 5% of the genomes from low- and middle-income countries. We found that sequencing around 0.5% of the cases, with a turnaround time <21 days, could provide a benchmark for SARS-CoV-2 genomic surveillance. Socioeconomic inequalities undermine the global pandemic preparedness, and efforts must be made to support low- and middle-income countries improve their local sequencing capacity

    Global disparities in SARS-CoV-2 genomic surveillance

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    Genomic sequencing is essential to track the evolution and spread of SARS-CoV-2, optimize molecular tests, treatments, vaccines, and guide public health responses. To investigate the global SARS-CoV-2 genomic surveillance, we used sequences shared via GISAID to estimate the impact of sequencing intensity and turnaround times on variant detection in 189 countries. In the first two years of the pandemic, 78% of high-income countries sequenced >0.5% of their COVID-19 cases, while 42% of low- and middle-income countries reached that mark. Around 25% of the genomes from high income countries were submitted within 21 days, a pattern observed in 5% of the genomes from low- and middle-income countries. We found that sequencing around 0.5% of the cases, with a turnaround time <21 days, could provide a benchmark for SARS-CoV-2 genomic surveillance. Socioeconomic inequalities undermine the global pandemic preparedness, and efforts must be made to support low- and middle-income countries improve their local sequencing capacity
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