442 research outputs found

    Lift Response of a Stalled Wing to Pulsatile Disturbances

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    The transient lift response of a low-Reynolds-number wing subjected to small amplitude pulsatile disturbances is investigated. The wing has a small aspect ratio and a semicircular planform, and it is fully stalled at a 20 deg angle of attack. Microvalve actuators distributed along the leading edge of the wing produce the transient disturbance. It is shown that the lift response to a single pulse increases with increasing actuator supply pressure and that the lift response curves are similar to each other when scaled by the total impulse. Furthermore, for fixed actuator supply pressure, the amplitude and total impulse of the transient lift response curve increases with increasing external flow speed. In this case, the lift response curves are similar when scaled by the dynamic pressure. The lift response to a single pulse can be treated as a filter kernel, and it can be used to predict the lift time history for the arbitrary actuator input signals. The kernel is similar in shape to transient measurements obtained by other investigators on two-dimensional wings and flaps. Comparisons between the model predictions and the experiments using multiple pulse inputs and square-wave modulated input signals at low frequencies are presented

    Closed-Loop Control of a Wing in an Unsteady Flow

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    The lift response of the separated flow over a wing to different actuator input disturbances is used to obtain linear models useful for closed-loop control design. The wing has a small aspect ratio, a semi-circular planform, and is fully stalled at a 20° angle of attack. Individual pulse-like disturbances and step-input disturbances with randomized frequency were inputs to the actuator, and the lift coefficient increments were output signals. The "prediction error method" system identification technique was used to obtain two linear models of the separated flow. A 4th order model reproduced the non-minimum phase behavior of the pulse input, but did not work well for control purposes. The second model identified was limited to first order. The first order model proved to be useful for designing a proportional-integral feedback controller capable of suppressing lift oscillations in unsteady flows. Good suppression of lift oscillations was observed in the experiment after a step change in wind tunnel flow speed occurred. When the control system was tested with a randomized freestream velocity, it reduced the root-mean-square lift oscillation by 50 percent relative to the uncontrolled case

    Low Reynolds Number Wing Response to an Oscillating Freestream With and Without Feed Forward Control

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    The unsteady lift of a low Reynolds number wing in an oscillating freestream is documented in terms of its amplitude and phase. The phase variation of the lift relative to the freestream velocity shows a larger phase difference than predicted by classical unsteady flow theory. A constant time delay between the lift and the actuator was observed to be τ^+ = t_(delay)U/c = 5.3 when normalized by the freestream speed and chord. Feed forward control of pulsed-jet actuators is used to modulate the lift coefficient of the wing, in an attempt to suppress the lift oscillations. Suppression of the fluctuating lift at the fundamental frequency was partially successful, but additional "noise" was added to harmonics of the lift signal by the controller

    A lipid-anchored neurokinin 1 receptor antagonist prolongs pain relief by a three-pronged mechanism of action targeting the receptor at the plasma membrane and in endosomes

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    G-protein-coupled receptors (GPCRs) are traditionally known for signaling at the plasma membrane, but they can also signal from endosomes after internalization to control important pathophysiological processes. In spinal neurons, sustained endosomal signaling of the neurokinin 1 receptor (NK1R) mediates nociception, as demonstrated in models of acute and neuropathic pain. An NK1R antagonist, Spantide I (Span), conjugated to cholestanol (Span-Chol), accumulates in endosomes, inhibits endosomal NK1R signaling, and causes prolonged antinociception. However, the extent to which the Chol-anchor influences long-term location and activity is poorly understood. Herein, we used fluorescent correlation spectroscopy and targeted biosensors to characterize Span-Chol over time. The Chol-anchor increased local concentration of probe at the plasma membrane. Over time we observed an increase in NK1R-binding affinity and more potent inhibition of NK1R-mediated calcium signaling. Span-Chol, but not Span, caused a persistent decrease in NK1R recruitment of ÎČarrestin and receptor internalization to early endosomes. Using targeted biosensors, we mapped the relative inhibition of NK1R signaling as the receptor moved into the cell. Span selectively inhibited cell surface signaling, whereas Span-Chol partitioned into endosomal membranes and blocked endosomal signaling. In a preclinical model of pain, Span-Chol caused prolonged antinociception (>9 h), which is attributable to a three-pronged mechanism of action: increased local concentration at membranes, a prolonged decrease in NK1R endocytosis, and persistent inhibition of signaling from endosomes. Identifying the mechanisms that contribute to the increased preclinical efficacy of lipid-anchored NK1R antagonists is an important step toward understanding how we can effectively target intracellular GPCRs in disease

    Physical Health, Media Use, and Mental Health in Children and Adolescents With ADHD During the COVID-19 Pandemic in Australia

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    Objective: To examine the impact of COVID-19 restrictions among children with attention-deficit/hyperactivity disorder (ADHD). Methods: Parents of 213 Australian children (5–17 years) with ADHD completed a survey in May 2020 when COVID-19 restrictions were in place (i.e., requiring citizens to stay at home except for essential reasons). Results: Compared to pre-pandemic, children had less exercise (Odds Ratio (OR) = 0.4; 95% CI 0.3–0.6), less outdoor time (OR = 0.4; 95% 0.3–0.6), and less enjoyment in activities (OR = 6.5; 95% CI 4.0–10.4), while television (OR = 4.0; 95% CI 2.5–6.5), social media (OR = 2.4; 95% CI 1.3–4.5), gaming (OR = 2.0; 95% CI 1.3–3.0), sad/depressed mood (OR = 1.8; 95% CI 1.2–2.8), and loneliness (OR = 3.6; 95% CI 2.3–5.5) were increased. Child stress about COVID-19 restrictions was associated with poorer functioning across most domains. Most parents (64%) reported positive changes for their child including more family time. Conclusions: COVID-19 restrictions were associated with both negative and positive impacts among children with ADHD

    The surface-anchored NanA protein promotes pneumococcal brain endothelial cell invasion

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    In humans, Streptococcus pneumoniae (SPN) is the leading cause of bacterial meningitis, a disease with high attributable mortality and frequent permanent neurological sequelae. The molecular mechanisms underlying the central nervous system tropism of SPN are incompletely understood, but include a primary interaction of the pathogen with the blood–brain barrier (BBB) endothelium. All SPN strains possess a gene encoding the surface-anchored sialidase (neuraminidase) NanA, which cleaves sialic acid on host cells and proteins. Here, we use an isogenic SPN NanA-deficient mutant and heterologous expression of the protein to show that NanA is both necessary and sufficient to promote SPN adherence to and invasion of human brain microvascular endothelial cells (hBMECs). NanA-mediated hBMEC invasion depends only partially on sialidase activity, whereas the N-terminal lectinlike domain of the protein plays a critical role. NanA promotes SPN–BBB interaction in a murine infection model, identifying the protein as proximal mediator of CNS entry by the pathogen

    The CMS Phase-1 pixel detector upgrade

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    The CMS detector at the CERN LHC features a silicon pixel detector as its innermost subdetector. The original CMS pixel detector has been replaced with an upgraded pixel system (CMS Phase-1 pixel detector) in the extended year-end technical stop of the LHC in 2016/2017. The upgraded CMS pixel detector is designed to cope with the higher instantaneous luminosities that have been achieved by the LHC after the upgrades to the accelerator during the first long shutdown in 2013–2014. Compared to the original pixel detector, the upgraded detector has a better tracking performance and lower mass with four barrel layers and three endcap disks on each side to provide hit coverage up to an absolute value of pseudorapidity of 2.5. This paper describes the design and construction of the CMS Phase-1 pixel detector as well as its performance from commissioning to early operation in collision data-taking.Peer reviewe

    MUSiC : a model-unspecific search for new physics in proton-proton collisions at root s=13TeV

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    Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1), are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.Peer reviewe

    Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

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    A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe
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