1,055 research outputs found

    The Equilateral Pentagon at Zero Angular Momentum: Maximal Rotation Through Optimal Deformation

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    A pentagon in the plane with fixed side-lengths has a two-dimensional shape space. Considering the pentagon as a mechanical system with point masses at the corners we answer the question of how much the pentagon can rotate with zero angular momentum. We show that the shape space of the equilateral pentagon has genus 4 and find a fundamental region by discrete symmetry reduction with respect to symmetry group D_5. The amount of rotation \Delta \theta for a loop in shape space at zero angular momentum is interpreted as a geometric phase and is obtained as an integral of a function B over the region of shape space enclosed by the loop. With a simple variational argument we determine locally optimal loops as the zero contours of the function B. The resulting shape change is represented as a Fourier series, and the global maximum of \Delta \theta \approx 45\degree is found for a loop around the regular pentagram. We also show that restricting allowed shapes to convex pentagons the optimal loop is the boundary of the convex region and gives \Delta \theta \approx 19\degree.Comment: 29 page

    Inverse perturbation method for structural redesign with frequency and mode shape constraints

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76581/1/AIAA-8777-705.pd

    Elevated liver glycogenolysis mediates higher blood glucose during acute exercise in Barth syndrome

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    UNLABELLED: Barth syndrome (BTHS) is an X-linked recessive genetic disorder due to mutations in the Tafazzin (TAFAZZIN) gene that lead to cardiac and skeletal muscle mitochondrial dysfunction. Previous studies in humans with BTHS demonstrate that the defects in muscle mitochondrial oxidative metabolism result in an enhanced reliance on anaerobic metabolism during exercise to meet energy demands of muscular work. During exercise, the liver normally increases glucose production via glycogenolysis and gluconeogenesis to match the elevated rate of muscle glucose uptake and meet the ATP requirements of working muscle. However, the impact of Tafazzin deficiency on hepatic glucose production and the pathways contributing to hepatic glucose production during exercise is unknown. Therefore, the purpose of this study was to quantify in vivo liver gluconeogenesis and glycogenolysis in Tafazzin knockdown mice at rest and during acute exercise. METHODS: Male TAFAZZIN shRNA transgenic (TG) and wild-type (WT) mice completed exhaustive treadmill running protocols to test exercise tolerance. Mice underwent 2H- and 13C-stable isotope infusions at rest and during a 30-minute treadmill running bout to quantify hepatic glucose production and associated nutrient fluxes under sedentary conditions and during acute exercise. Circulating and tissue (skeletal muscle and liver) samples were obtained during and following exercise to assess static metabolite levels. RESULTS: TG mice reached exhaustion sooner during exhaustive treadmill running protocols and exhibited higher plasma lactate concentrations after exhaustive exercise compared to WT mice. Arterial glucose levels were comparable between genotypes at rest, but higher in TG mice compared to WT mice during exercise. Consistent with the higher blood glucose, TG mice showed increased endogenous glucose production owing to elevated glycogenolysis compared to WT mice during exercise. Total gluconeogenesis, gluconeogenesis from glycerol, gluconeogenesis from phosphoenolpyruvate, pyruvate cycling, total cataplerosis, and anaplerotic fluxes were similar between TG and WT mice at rest and during exercise. However, lactate dehydrogenase flux and TCA cycle fluxes trended higher in TG mice during exercise. Liver glycogen content in TG was higher in TG vs. controls. CONCLUSION: Our data in the Tafazzin knockdown mouse suggest that elevated anaerobic metabolism during rest and exercise previously reported in humans with BTHS are supported by the finding of higher hepatic glycogenolysis

    HST NIR Snapshot Survey of 3CR Radio Source Counterparts II: An Atlas and Inventory of the Host Galaxies, Mergers and Companions

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    We present the second part of an H-band (1.6 microns) atlas of z<0.3 3CR radio galaxies, using the Hubble Space Telescope Near Infrared Camera and Multi-Object Spectrometer (HST NICMOS2). We present new imaging for 21 recently acquired sources, and host galaxy modeling for the full sample of 101 (including 11 archival) -- an 87% completion rate. Two different modeling techniques are applied, following those adopted by the galaxy morphology and the quasar host galaxy communities. Results are compared, and found to be in excellent agreement, although the former breaks down in the case of strongly nucleated sources. Companion sources are tabulated, and the presence of mergers, tidal features, dust disks and jets are catalogued. The tables form a catalogue for those interested in the structural and morphological dust-free host galaxy properties of the 3CR sample, and for comparison with morphological studies of quiescent galaxies and quasar host galaxies. Host galaxy masses are estimated, and found to typically lie at around 2*10^11 solar masses. In general, the population is found to be consistent with the local population of quiescent elliptical galaxies, but with a longer tail to low Sersic index, mainly consisting of low-redshift (z<0.1) and low-radio-power (FR I) sources. A few unusually disky FR II host galaxies are picked out for further discussion. Nearby external sources are identified in the majority of our images, many of which we argue are likely to be companion galaxies or merger remnants. The reduced NICMOS data are now publicly available from our website (http://archive.stsci.edu/prepds/3cr/)Comment: ApJS, 177, 148: Final version; includes revised figures 1, 15b, and section 7.5 (and other minor changes from editing process. 65 pages, inc. 17 figure

    The First Extrasolar Planet Discovered with a New Generation High Throughput Doppler Instrument

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    We report the detection of the first extrasolar planet, ET-1 (HD 102195b), using the Exoplanet Tracker (ET), a new generation Doppler instrument. The planet orbits HD 102195, a young star with solar metallicity that may be part of the local association. The planet imparts radial velocity variability to the star with a semiamplitude of 63.4±2.063.4\pm2.0 m s1^{-1} and a period of 4.11 days. The planetary minimum mass (msinim \sin i) is 0.488±0.0150.488\pm0.015 MJM_J.Comment: 42 pages, 11 figures and 5 tables, Accepted for publication in Ap

    The Effect of Guselkumab on Work Productivity in Biologic-Naïve Patients with Active Psoriatic Arthritis Through Week 52 of the Phase 3, Randomized, Placebo-Controlled DISCOVER-2 Trial

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    Introduction: The phase 3 DISCOVER-2 trial evaluated the effect of guselkumab on impaired work productivity and nonwork activity in biologic-naïve patients with psoriatic arthritis (PsA). Methods: Adults with active PsA were randomized (1:1:1) to guselkumab 100 mg every 4 weeks (Q4W), guselkumab 100 mg at weeks 0 and 4 and then every 8 weeks (Q8W), or placebo (with crossover to guselkumab Q4W at week 24). Least squares mean change from baseline in Work Productivity and Activity Impairment Questionnaire for PsA (WPAI-PsA) domains and employment were assessed by treatment group. Multivariate analysis of data from weeks 0 through 24 assessed independent associations between PsA clinical features and WPAI-PsA domains. Results: In total, 738 patients were evaluated (guselkumab Q4W n = 245; guselkumab Q8W n = 248; placebo n = 245). At week 24, improvements (reduced impairment) in presenteeism (Q4W −20.1%, Q8W −19.6%, placebo −10.5%), work productivity (Q4W −20.1%, Q8W −19.2%, placebo −10.6%), and nonwork activity (Q4W −20.5%, Q8W −21.2%, placebo −9.9%) were greater in guselkumab-treated versus placebo-treated patients. At week 52, following placebo crossover at week 24, improvements were similar among groups. Baseline absenteeism was minimal and did not change in any group. By week 52, 23.1–25.9% of guselkumab-treated patients who were unemployed at baseline were employed. All WPAI-PsA domains were positively associated with C-reactive protein level, fatigue, and pain. All domains except absenteeism were positively associated with enthesitis and Psoriasis Area and Severity Index score. Age was negatively associated with presenteeism and work productivity loss, female sex and tender joint count were positively associated with nonwork activity impairment, and dactylitis was positively associated with presenteeism. Conclusion: Both guselkumab regimens reduced work productivity loss and nonwork activity impairment in patients with active PsA. Association of work productivity loss and nonwork activity impairment with PsA joint and skin features suggests that improvement in both features is beneficial for optimizing improved work productivity loss and nonwork activity impairment. Trial registration: ClinicalTrials.gov identifier, NCT03158285

    Low-mass bursty galaxies in JADES efficiently produce ionising photons and could represent the main drivers of reionisation

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    © 2023 The Author(s). Published by Oxford University Press on behalf of Royal Astronomical Society. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/We study galaxies in JADES Deep to study the evolution of the ionising photon production efficiency, ξion\xi_{\rm{ion}}, observed to increase with redshift. We estimate ξion\xi_{\rm{ion}} for a sample of 677 galaxies at z49z \sim 4 - 9 using NIRCam photometry. Specifically, combinations of the medium and wide bands F335M-F356W and F410M-F444W to constrain emission lines that trace ξion\xi_{\rm{ion}}: Hα\alpha and [OIII]. Additionally, we use the spectral energy distribution fitting code \texttt{Prospector} to fit all available photometry and infer galaxy properties. The flux measurements obtained via photometry are consistent with FRESCO and NIRSpec-derived fluxes. Moreover, the emission-line-inferred measurements are in tight agreement with the \texttt{Prospector} estimates. We also confirm the observed ξion\xi_{\rm{ion}} trend with redshift and MUV_{\rm{UV}}, and find: logξion(z,MUV)=(0.05±0.02)z+(0.11±0.02)MUV+(27.33±0.37)\log \xi_{\rm{ion}} (z,\text{M}_{\rm{UV}}) = (0.05 \pm 0.02)z + (0.11 \pm 0.02) \text{M}_{\rm{UV}} + (27.33 \pm 0.37). We use \texttt{Prospector} to investigate correlations of ξion\xi_{\rm{ion}} with other galaxy properties. We see a clear correlation between ξion\xi_{\rm{ion}} and burstiness in the star formation history of galaxies, given by the ratio of recent to older star formation, where burstiness is more prevalent at lower stellar masses. We also convolve our ξion\xi_{\rm{ion}} relations with luminosity functions from the literature, and constant escape fractions of 10 and 20\%, to place constraints on the cosmic ionising photon budget. By combining our results, we find that if our sample is representative of the faint low-mass galaxy population, galaxies with bursty star formation are efficient enough in producing ionising photons and could be responsible for the reionisation of the Universe.Peer reviewe

    Integrative analyses identify modulators of response to neoadjuvant aromatase inhibitors in patients with early breast cancer

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    Introduction Aromatase inhibitors (AIs) are a vital component of estrogen receptor positive (ER+) breast cancer treatment. De novo and acquired resistance, however, is common. The aims of this study were to relate patterns of copy number aberrations to molecular and proliferative response to AIs, to study differences in the patterns of copy number aberrations between breast cancer samples pre- and post-AI neoadjuvant therapy, and to identify putative biomarkers for resistance to neoadjuvant AI therapy using an integrative analysis approach. Methods Samples from 84 patients derived from two neoadjuvant AI therapy trials were subjected to copy number profiling by microarray-based comparative genomic hybridisation (aCGH, n = 84), gene expression profiling (n = 47), matched pre- and post-AI aCGH (n = 19 pairs) and Ki67-based AI-response analysis (n = 39). Results Integrative analysis of these datasets identified a set of nine genes that, when amplified, were associated with a poor response to AIs, and were significantly overexpressed when amplified, including CHKA, LRP5 and SAPS3. Functional validation in vitro, using cell lines with and without amplification of these genes (SUM44, MDA-MB134-VI, T47D and MCF7) and a model of acquired AI-resistance (MCF7-LTED) identified CHKA as a gene that when amplified modulates estrogen receptor (ER)-driven proliferation, ER/estrogen response element (ERE) transactivation, expression of ER-regulated genes and phosphorylation of V-AKT murine thymoma viral oncogene homolog 1 (AKT1). Conclusions These data provide a rationale for investigation of the role of CHKA in further models of de novo and acquired resistance to AIs, and provide proof of concept that integrative genomic analyses can identify biologically relevant modulators of AI response
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