209 research outputs found

    Employing pre-stress to generate finite cloaks for antiplane elastic waves

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    It is shown that nonlinear elastic pre-stress of neo-Hookean hyperelastic materials can be used as a mechanism to generate finite cloaks and thus render objects near-invisible to incoming antiplane elastic waves. This approach appears to negate the requirement for special cloaking metamaterials with inhomogeneous and anisotropic material properties in this case. These properties are induced naturally by virtue of the pre-stress. This appears to provide a mechanism for broadband cloaking since dispersive effects due to metamaterial microstructure will not arise.Comment: 4 pages, 2 figure

    Kinematics of the Broad Line Region in M81

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    A new model is presented which explains the origin of the broad emission lines observed in the LINER/Seyfert nucleus of M81 in terms of a steady state spherically symmetric inflow, amounting to 1 x 10^-5 Msun/yr, which is sufficient to explain the luminosity of the AGN. The emitting volume has an outer radius of ~1 pc, making it the largest broad line region yet to be measured, and it contains a total mass of ~ 5 x 10^-2 Msun of dense, ~ 10^8 cm^-3, ionized gas, leading to a very low filling factor of ~ 5 x 10^-9. The fact that the BLR in M81 is so large may explain why the AGN is unable to sustain the ionization seen there. Thus, the AGN in M81 is not simply a scaled down quasar.Comment: Accepted for Publication in ApJ 7/21/0

    Comparative Feedstock Analysis in \u3cem\u3eSetaria viridis\u3c/em\u3e L. as a Model for C\u3csub\u3e4\u3c/sub\u3e Bioenergy Grasses and Panicoid Crop Species

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    Second generation feedstocks for bioethanol will likely include a sizable proportion of perennial C4 grasses, principally in the Panicoideae clade. The Panicoideae contain agronomically important annual grasses including Zea mays L. (maize), Sorghum bicolor (L.) Moench (sorghum), and Saccharum officinarum L. (sugar cane) as well as promising second generation perennial feedstocks including Miscanthus × giganteus and Panicum virgatum L. (switchgrass). The underlying complexity of these polyploid grass genomes is a major limitation for their direct manipulation and thus driving a need for rapidly cycling comparative model. Setaria viridis (green millet) is a rapid cycling C4 panicoid grass with a relatively small and sequenced diploid genome and abundant seed production. Stable, transient, and protoplast transformation technologies have also been developed for Setaria viridis making it a potentially excellent model for other C4 bioenergy grasses. Here, the lignocellulosic feedstock composition, cellulose biosynthesis inhibitor response and saccharification dynamics of Setaria viridis are compared with the annual sorghum and maize and the perennial switchgrass bioenergy crops as a baseline study into the applicability for translational research. A genome-wide systematic investigation of the cellulose synthase-A genes was performed identifying eight candidate sequences. Two developmental stages; (a) metabolically active young tissue and (b) metabolically plateaued (mature) material are examined to compare biomass performance metrics

    Stellar Intensity Interferometry with Air Cherenkov Telescope arrays

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    The present generation of ground-based Very High Energy (VHE) gamma-ray observatories consist of arrays of up to four large (> 12m diameter) light collectors quite similar to those used by R. Hanbury Brown to measure stellar diameters by Intensity Interferometry in the late 60's. VHE gamma-ray observatories to be constructed over the coming decade will involve several tens of telescopes of similar or greater sizes. Used as intensity interferometers, they will provide hundreds of independent baselines. Now is the right time to re-assess the potential of intensity interferometry so that it can be taken into consideration in the design of these large facilities.Comment: 11 pages, 9 figures, in procedings of the High Time Resolution Astrophysics conferenc

    Frameless Image-Guided Radiosurgery for Trigeminal Neuralgia

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    Background: Frameless image-guided radiosurgery (IGRS) is a safe and effective noninvasive treatment for trigeminal neuralgia (TN). This study evaluates the use of frameless IGRS to treat patients with refractory TN. Methods: We reviewed the records of 20 patients diagnosed with TN who underwent frameless IGRS treatments between March 2012 and December 2013. Facial pain was graded using the Barrow Neurological Institute (BNI) scoring system. The initial setup uncertainty from simulation to treatment and the patient intrafraction uncertainty were measured. The median follow-up was 32 months. Results: All patients\u27 pain was BNI Grade IV or V before the frameless IGRS treatment. The mean intrafraction shift was 0.43 mm (0.28-0.76 mm), and the maximum intrafraction shift was 0.95 mm (0.53-1.99 mm). At last follow-up, 8 (40%) patients no longer required medications (BNI 1 or 2), 11 (55%) patients were pain free but required medication (BNI 3), and 1 (5%) patient had no pain relief (BNI 5). Patients who did not have prior surgery had a higher odds ratio for pain relief compared to patients who had prior surgery (14.9, P = 0.0408). Conclusions: Frameless IGRS provides comparable dosimetric and clinical outcomes to frame-based SRS in a noninvasive fashion for patients with medically refractory TN

    Dexamethasone Administration During Definitive Radiation and Temozolomide Renders a Poor Prognosis in a Retrospective Analysis of Newly Diagnosed Glioblastoma Patients

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    BACKGROUND: Dexamethasone (DXM) is commonly used in the management of cerebral edema in patients diagnosed with glioblastoma multiforme (GBM). Bevacizumab (BEV) is FDA-approved for the progression or recurrence of GBM but has not been shown to improve survival when given for newly diagnosed patients concurrently with radiation (RT) and temozolomide (TMZ). Both DXM and BEV reduce cerebral edema, however, DXM has been shown to induce cytokine cascades which could interfere with cytotoxic therapy. We investigated whether DXM would reduce survival of GBM patients in the setting of concurrent TMZ and BEV administration. METHODS: We reviewed the treatment of all 73 patients with GBM who received definitive therapy at our institution from 2005 to 2013 with RT (60 Gy) delivered with concurrent daily TMZ (75 mg/m2). Of these, 34 patients also were treated with concurrent BEV (10 mg/kg every two weeks). Patients received adjuvant therapy (TMZ or TMZ/Bev) until either progression, discontinuation due to toxicity, or 12 months after radiation completion. All patients who had GBM progression with TMZ were offered BEV for salvage therapy, with 19 (56 %) receiving BEV. RESULTS: With a median follow-up of 15.6 months, 67 (91.8 %) patients were deceased. The OS for the entire cohort was 15.9 months, while the PFS was 7.7 months. The extent of resection was a prognostic indicator for OS (p  = .0044). The median survival following gross tumor resection (GTR) was 22.5 months, subtotal resection (STR) was 14.9 months, and biopsy was 12.1 months. The addition of BEV to TMZ with RT was borderline significantly associated with increased PFS (9.4 vs. 5.1 months, p = 0.0574) although was not significantly associated with OS (18.1 vs. 15.3 months respectively, p  = 0.3064). In patients receiving TMZ, DXM use concurrent with RT was a poor prognostic indicator of both OS (12.7 vs. 22.6 months, p = 0.003) and PFS (3.6 vs. 8.4 months, p p = 0.4818). On multivariable analysis, DXM use predicted an unfavorable OS hazard ratio (HR) = 1.72, p = 0.045). CONCLUSIONS: Our results with TMZ, BEV, and RT are similar to previous studies in terms of PFS and OS. DXM use during RT with concurrent TMZ correlated with reduced OS and PFS unless BEV was administered

    Direct evidence of a prey depletion "halo" surrounding a pelagic predator colony

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    Colonially breeding birds and mammals form some of the largest gatherings of apex predators in the natural world and have provided model systems for studying mechanisms of population regulation in animals. According to one influential hypothesis, intense competition for food among large numbers of spatially constrained foragers should result in a zone of prey depletion surrounding such colonies, ultimately limiting their size. However, while indirect and theoretical support for this phenomenon, known as "Ashmole's halo," has steadily accumulated, direct evidence remains exceptionally scarce. Using a combination of vesselbased surveys and Global Positioning System tracking, we show that pelagic seabirds breeding at the tropical island that first inspired Ashmole's hypothesis do indeed deplete their primary prey species (flying fish; Exocoetidae spp.) over a considerable area, with reduced prey density detectable >150 km from the colony. The observed prey gradient was mirrored by an opposing trend in seabird foraging effort, could not be explained by confounding environmental variability, and can be approximated using a mechanistic consumption-dispersion model, incorporating realistic rates of seabird predation and random prey dispersal. Our results provide a rare view of the resource footprint of a pelagic seabird colony and reveal how aggregations of these central-place foraging, marine top predators profoundly influence the oceans that surround them

    Adipocyte lipolysis links obesity to breast cancer growth: adipocyte-derived fatty acids drive breast cancer cell proliferation and migration.

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    BACKGROUND: Obesity is associated with increased recurrence and reduced survival of breast cancer. Adipocytes constitute a significant component of breast tissue, yet their role in provisioning metabolic substrates to support breast cancer progression is poorly understood. RESULTS: Here, we show that co-culture of breast cancer cells with adipocytes revealed cancer cell-stimulated depletion of adipocyte triacylglycerol. Adipocyte-derived free fatty acids were transferred to breast cancer cells, driving fatty acid metabolism via increased CPT1A and electron transport chain complex protein levels, resulting in increased proliferation and migration. Notably, fatty acid transfer to breast cancer cells was enhanced from "obese" adipocytes, concomitant with increased stimulation of cancer cell proliferation and migration. This adipocyte-stimulated breast cancer cell proliferation was dependent on lipolytic processes since HSL/ATGL knockdown attenuated cancer cell responses. CONCLUSIONS: These findings highlight a novel and potentially important role for adipocyte lipolysis in the provision of metabolic substrates to breast cancer cells, thereby supporting cancer progression

    Mitochondrial mutations and metabolic adaptation in pancreatic cancer.

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    BACKGROUND: Pancreatic cancer has a five-year survival rate of ~8%, with characteristic molecular heterogeneity and restricted treatment options. Targeting metabolism has emerged as a potentially effective therapeutic strategy for cancers such as pancreatic cancer, which are driven by genetic alterations that are not tractable drug targets. Although somatic mitochondrial genome (mtDNA) mutations have been observed in various tumors types, understanding of metabolic genotype-phenotype relationships is limited. METHODS: We deployed an integrated approach combining genomics, metabolomics, and phenotypic analysis on a unique cohort of patient-derived pancreatic cancer cell lines (PDCLs). Genome analysis was performed via targeted sequencing of the mitochondrial genome (mtDNA) and nuclear genes encoding mitochondrial components and metabolic genes. Phenotypic characterization of PDCLs included measurement of cellular oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) using a Seahorse XF extracellular flux analyser, targeted metabolomics and pathway profiling, and radiolabelled glutamine tracing. RESULTS: We identified 24 somatic mutations in the mtDNA of 12 patient-derived pancreatic cancer cell lines (PDCLs). A further 18 mutations were identified in a targeted study of ~1000 nuclear genes important for mitochondrial function and metabolism. Comparison with reference datasets indicated a strong selection bias for non-synonymous mutants with predicted functional effects. Phenotypic analysis showed metabolic changes consistent with mitochondrial dysfunction, including reduced oxygen consumption and increased glycolysis. Metabolomics and radiolabeled substrate tracing indicated the initiation of reductive glutamine metabolism and lipid synthesis in tumours. CONCLUSIONS: The heterogeneous genomic landscape of pancreatic tumours may converge on a common metabolic phenotype, with individual tumours adapting to increased anabolic demands via different genetic mechanisms. Targeting resulting metabolic phenotypes may be a productive therapeutic strategy

    Bringing plant-based veterinary vaccines to market: Managing regulatory and commercial hurdles

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    AbstractThe production of recombinant vaccines in plants may help to reduce the burden of veterinary diseases, which cause major economic losses and in some cases can affect human health. While there is abundant research in this area, a knowledge gap exists between the ability to create and evaluate plant-based products in the laboratory, and the ability to take these products on a path to commercialization. The current report, arising from a workshop sponsored by an Organisation for Economic Co-operation and Development (OECD) Co-operative Research Programme, addresses this gap by providing guidance in planning for the commercialization of plant-made vaccines for animal use. It includes relevant information on developing business plans, assessing market opportunities, manufacturing scale-up, financing, protecting and using intellectual property, and regulatory approval with a focus on Canadian regulations
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