114 research outputs found

    Candidate proof mass actuator control laws for the vibration suppression of a frame

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    The vibration of an experimental flexible space truss is controlled with internal control forces produced by several proof mass actuators. Four candidate control law strategies are evaluated in terms of performance and robustness. These control laws are experimentally implemented on a quasi free-free planar truss. Sensor and actuator dynamics are included in the model such that the final closed loop is self-equilibrated. The first two control laws considered are based on direct output feedback and consist of tuning the actuator feedback gains to the lowest mode intended to receive damping. The first method feeds back only the position and velocity of the proof mass relative to the structure; this results in a traditional vibration absorber. The second method includes the same feedback paths as the first plus feedback of the local structural velocity. The third law is designed with robust H infinity control theory. The fourth strategy is an active implementation of a viscous damper, where the actuator is configured to provide a bending moment at two points on the structure. The vibration control system is then evaluated in terms of how it would benefit the space structure's position control system

    Controlling flexible structures with second order actuator dynamics

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    The control of flexible structures for those systems with actuators that are modeled by second order dynamics is examined. Two modeling approaches are investigated. First a stability and performance analysis is performed using a low order finite dimensional model of the structure. Secondly, a continuum model of the flexible structure to be controlled, coupled with lumped parameter second order dynamic models of the actuators performing the control is used. This model is appropriate in the modeling of the control of a flexible panel by proof-mass actuators as well as other beam, plate and shell like structural numbers. The model is verified with experimental measurements

    Wolverine Gene Flow Across a Narrow Climatic Niche

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    Wolverines (Guio guio) are one of the rarest carnivores in the contiguous United States. Effective population sizes in Montana, Idaho, and Wyoming, where most of the wolverines in the contiguous United States exist, were calculated to be 35 (credible limits, 28 52) suggesting low abundance. Landscape features that influence wolverine population substructure and gene flow are largely unknown. Recent work has identified strong associations between areas with persistent spring snow and wolverine presence and range. We tested whether a dispersal model in which wolverines prefer to disperse through areas characterized by persistent spring snow cover produced least-cost paths among all individuals that correlated with genetic distance among individuals. Models simulating large preferences for dispersing within areas characterized by persistent spring snow explained the data better than a model based on Euclidean distance. Partial Mantel tests separating Euclidean distance from spring snow-cover-based effects indicated that Euclidean distance was not significant in describing patterns of genetic distance. Because these models indicated that successful dispersal paths followed areas characterized by spring snow cover, we used these understandings to derive empirically based least-cost corridor maps in the U.S. Rocky Mountains. These corridor maps largely explain previously published population subdivision patterns based on mitochondrial DNA and indicate that natural colonization of the southern Rocky Mountains by wolverines will be difficult but not impossible

    Complexities in barrier island response to sea level rise : insights from numerical model experiments, North Carolina Outer Banks

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    Author Posting. © American Geophysical Union, 2010. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 115 (2010): F03004, doi:10.1029/2009JF001299.Using a morphological-behavior model to conduct sensitivity experiments, we investigate the sea level rise response of a complex coastal environment to changes in a variety of factors. Experiments reveal that substrate composition, followed in rank order by substrate slope, sea level rise rate, and sediment supply rate, are the most important factors in determining barrier island response to sea level rise. We find that geomorphic threshold crossing, defined as a change in state (e.g., from landward migrating to drowning) that is irreversible over decadal to millennial time scales, is most likely to occur in muddy coastal systems where the combination of substrate composition, depth-dependent limitations on shoreface response rates, and substrate erodibility may prevent sand from being liberated rapidly enough, or in sufficient quantity, to maintain a subaerial barrier. Analyses indicate that factors affecting sediment availability such as low substrate sand proportions and high sediment loss rates cause a barrier to migrate landward along a trajectory having a lower slope than average barrier island slope, thereby defining an “effective” barrier island slope. Other factors being equal, such barriers will tend to be smaller and associated with a more deeply incised shoreface, thereby requiring less migration per sea level rise increment to liberate sufficient sand to maintain subaerial exposure than larger, less incised barriers. As a result, the evolution of larger/less incised barriers is more likely to be limited by shoreface erosion rates or substrate erodibility making them more prone to disintegration related to increasing sea level rise rates than smaller/more incised barriers. Thus, the small/deeply incised North Carolina barriers are likely to persist in the near term (although their long-term fate is less certain because of the low substrate slopes that will soon be encountered). In aggregate, results point to the importance of system history (e.g., previous slopes, sediment budgets, etc.) in determining migration trajectories and therefore how a barrier island will respond to sea level rise. Although simple analytical calculations may predict barrier response in simplified coastal environments (e.g., constant slope, constant sea level rise rate, etc.), our model experiments demonstrate that morphological-behavior modeling is necessary to provide critical insights regarding changes that may occur in environments having complex geometries, especially when multiple parameters change simultaneously.This work was partially supported by the U.S. Geological Survey, Woods Hole Science Center and a sabbatical leave fellowship from Oberlin College to Laura Moore from the Mellon‐8 Consortium

    Enjoy! Assertive Language and Consumer Compliance in (Non)Hedonic Contexts

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    This paper is concerned with the tension between consumer persuasion and freedom of choice. We study how assertive language (as in the slogan Just do it!) affects consumer compliance in hedonic vs. utilitarian contexts. Previous literature consistently claimed that forceful language would cause reactance and decreased compliance. However, we find in four studies that assertive persuasion is effective in contexts involving hedonic goods and hedonically framed utilitarian goods. Our hypotheses emerge from sociolinguistic research and confirm the relevance of linguistic research in consumer behavior

    Rationale and design of the Exercise Intensity Trial (EXCITE): A randomized trial comparing the effects of moderate versus moderate to high-intensity aerobic training in women with operable breast cancer

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    <p>Abstract</p> <p>Background</p> <p>The Exercise Intensity Trial (EXcITe) is a randomized trial to compare the efficacy of supervised moderate-intensity aerobic training to moderate to high-intensity aerobic training, relative to attention control, on aerobic capacity, physiologic mechanisms, patient-reported outcomes, and biomarkers in women with operable breast cancer following the completion of definitive adjuvant therapy.</p> <p>Methods/Design</p> <p>Using a single-center, randomized design, 174 postmenopausal women (58 patients/study arm) with histologically confirmed, operable breast cancer presenting to Duke University Medical Center (DUMC) will be enrolled in this trial following completion of primary therapy (including surgery, radiation therapy, and chemotherapy). After baseline assessments, eligible participants will be randomized to one of two supervised aerobic training interventions (moderate-intensity or moderate/high-intensity aerobic training) or an attention-control group (progressive stretching). The aerobic training interventions will include 150 mins.wk<sup>-1 </sup>of supervised treadmill walking per week at an intensity of 60%-70% (moderate-intensity) or 60% to 100% (moderate to high-intensity) of the individually determined peak oxygen consumption (VO<sub>2peak</sub>) between 20-45 minutes/session for 16 weeks. The progressive stretching program will be consistent with the exercise interventions in terms of program length (16 weeks), social interaction (participants will receive one-on-one instruction), and duration (20-45 mins/session). The primary study endpoint is VO<sub>2peak</sub>, as measured by an incremental cardiopulmonary exercise test. Secondary endpoints include physiologic determinants that govern VO<sub>2peak</sub>, patient-reported outcomes, and biomarkers associated with breast cancer recurrence/mortality. All endpoints will be assessed at baseline and after the intervention (16 weeks).</p> <p>Discussion</p> <p>EXCITE is designed to investigate the intensity of aerobic training required to induce optimal improvements in VO<sub>2peak </sub>and other pertinent outcomes in women who have completed definitive adjuvant therapy for operable breast cancer. Overall, this trial will inform and refine exercise guidelines to optimize recovery in breast and other cancer survivors following the completion of primary cytotoxic therapy.</p> <p>Trial Registration</p> <p>NCT01186367</p

    Dendritic Cells in Chronic Mycobacterial Granulomas Restrict Local Anti-Bacterial T Cell Response in a Murine Model

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    Background: Mycobacterium-induced granulomas are the interface between bacteria and host immune response. During acute infection dendritic cells (DCs) are critical for mycobacterial dissemination and activation of protective T cells. However, their role during chronic infection in the granuloma is poorly understood. Methodology/Principal Findings: We report that an inflammatory subset of murine DCs are present in granulomas induced by Mycobacteria bovis strain Bacillus Calmette-guerin (BCG), and both their location in granulomas and costimulatory molecule expression changes throughout infection. By flow cytometric analysis, we found that CD11c + cells in chronic granulomas had lower expression of MHCII and co-stimulatory molecules CD40, CD80 and CD86, and higher expression of inhibitory molecules PD-L1 and PD-L2 compared to CD11c + cells from acute granulomas. As a consequence of their phenotype, CD11c + cells from chronic lesions were unable to support the reactivation of newly-recruited, antigen 85Bspecific CD4 + IFNc + T cells or induce an IFNc response from naĂŻve T cells in vivo and ex vivo. The mechanism of this inhibition involves the PD-1:PD-L signaling pathway, as ex vivo blockade of PD-L1 and PD-L2 restored the ability of isolated CD11c + cells from chronic lesions to stimulate a protective IFNc T cell response. Conclusions/Significance: Our data suggest that DCs in chronic lesions may facilitate latent infection by down-regulating protective T cell responses, ultimately acting as a shield that promotes mycobacterium survival. This DC shield may explai

    Efficacy of Intravesical Nadofaragene Firadenovec for Patients With Bacillus Calmette-Guérin-Unresponsive Nonmuscle-Invasive Bladder Cancer: 5-Year Follow-Up From a Phase 3 Trial

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    Purpose: Nadofaragene firadenovec-vncg is a nonreplicating adenoviral vector–based gene therapy for bacillus Calmette-GuĂ©rin (BCG)–unresponsive carcinoma in situ (CIS) with/without high-grade Ta/T1. We report outcomes following 5 years of planned follow-up. Materials and Methods: This open-label phase 3 trial (NCT02773849) enrolled patients with BCG-unresponsive nonmuscle-invasive bladder cancer in 2 cohorts: CIS ± Ta/T1 (CIS; n = 107) and Ta/T1 without CIS (Ta/T1 cohort; n = 50). Patients received 75 mL (3 × 1011 vp/mL) nadofaragene firadenovec intravesically once every 3 months with cystoscopy and cytology assessments, with continued treatment offered to those remaining high grade recurrence–free (HGRF). Results: One hundred fifty-seven patients were enrolled from 33 US sites (n = 151 included in efficacy analyses). Median follow-up was 50.8 months (interquartile range 39.1-60.0), with 27% receiving ≄ 5 instillations and 7.6% receiving treatment for ≄ 57 months. Of patients with CIS 5.8% (95% CI 2.2-12.2) were HGRF at month 57, and 15% (95% CI 6.1-27.8) of patients with high-grade Ta/T1 were HGRF at month 57. Kaplan-Meier–estimated HGRF survival at 57 months was 13% (95% CI 6.9-21.5) and 33% (95% CI 19.5-46.6) in the CIS and Ta/T1 cohorts, respectively. Cystectomy-free survival at month 60 was 49% (95% CI 40.0-57.1): 43% (95% CI 32.2-53.7) in the CIS cohort and 59% (95% CI 43.1-71.4) in the Ta/T1 cohort. Overall survival at 60 months was 80% (71.0, 86.0): 76% (64.6-84.5) and 86% (70.9-93.5) in the CIS and Ta/T1 cohorts, respectively. Only 5 patients (4 with CIS and 1 with Ta/T1) experienced clinical progression to muscle-invasive disease. Conclusions: At 60 months, nadofaragene firadenovec-vncg allowed bladder preservation in nearly half of the patients and proved to be a safe option for BCG-unresponsive nonmuscle-invasive bladder cancer

    Increased Abundance of M cells in the Gut Epithelium Dramatically Enhances Oral Prion Disease Susceptibility

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    Many natural prion diseases of humans and animals are considered to be acquired through oral consumption of contaminated food or pasture. Determining the route by which prions establish host infection will identify the important factors that influence oral prion disease susceptibility and to which intervention strategies can be developed. After exposure, the early accumulation and replication of prions within small intestinal Peyer's patches is essential for the efficient spread of disease to the brain. To replicate within Peyer's patches, the prions must first cross the gut epithelium. M cells are specialised epithelial cells within the epithelia covering Peyer's patches that transcytose particulate antigens and microorganisms. M cell-development is dependent upon RANKL-RANK-signalling, and mice in which RANK is deleted only in the gut epithelium completely lack M cells. In the specific absence of M cells in these mice, the accumulation of prions within Peyer's patches and the spread of disease to the brain was blocked, demonstrating a critical role for M cells in the initial transfer of prions across the gut epithelium in order to establish host infection. Since pathogens, inflammatory stimuli and aging can modify M cell-density in the gut, these factors may also influence oral prion disease susceptibility. Mice were therefore treated with RANKL to enhance M cell density in the gut. We show that prion uptake from the gut lumen was enhanced in RANKL-treated mice, resulting in shortened survival times and increased disease susceptibility, equivalent to a 10-fold higher infectious titre of prions. Together these data demonstrate that M cells are the critical gatekeepers of oral prion infection, whose density in the gut epithelium directly limits or enhances disease susceptibility. Our data suggest that factors which alter M cell-density in the gut epithelium may be important risk factors which influence host susceptibility to orally acquired prion diseases
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