5,727 research outputs found

    Geometry Modeling for Unstructured Mesh Adaptation

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    The quantification and control of discretization error is critical to obtaining reliable simulation results. Adaptive mesh techniques have the potential to automate discretization error control, but have made limited impact on production analysis workflow. Recent progress has matured a number of independent implementations of flow solvers, error estimation methods, and anisotropic mesh adaptation mechanics. However, the poor integration of initial mesh generation and adaptive mesh mechanics to typical sources of geometry has hindered adoption of adaptive mesh techniques, where these geometries are often created in Mechanical Computer- Aided Design (MCAD) systems. The difficulty of this coupling is compounded by two factors: the inherent complexity of the model (e.g., large range of scales, bodies in proximity, details not required for analysis) and unintended geometry construction artifacts (e.g., translation, uneven parameterization, degeneracy, self-intersection, sliver faces, gaps, large tolerances be- tween topological elements, local high curvature to enforce continuity). Manual preparation of geometry is commonly employed to enable fixed-grid and adaptive-grid workflows by reducing the severity and negative impacts of these construction artifacts, but manual process interaction inhibits workflow automation. Techniques to permit the use of complex geometry models and reduce the impact of geometry construction artifacts on unstructured grid workflows are models from the AIAA Sonic Boom and High Lift Prediction are shown to demonstrate the utility of the current approach

    A New Approach toward Transition State Spectroscopy

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    Chirped-Pulse millimetre-Wave (CPmmW) rotational spectroscopy provides a new class of information about photolysis transition state(s). Measured intensities in rotational spectra determine species-isomer-vibrational populations, provided that rotational populations can be thermalized. The formation and detection of S0 vinylidene is discussed in the limits of low and high initial rotational excitation. CPmmW spectra of 193 nm photolysis of Vinyl Cyanide (Acrylonitrile) contain J=0-1 transitions in more than 20 vibrational levels of HCN, HNC, but no transitions in vinylidene or highly excited local-bender vibrational levels of acetylene. Reasons for the non-observation of the vinylidene co-product of HCN are discussed.Comment: Accepted by Faraday Discussion

    Comparative genomics of Australian isolates of the wheat stem rust pathogen Puccinia graminis f. sp. tritici reveals extensive polymorphism in candidate effector genes

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    The wheat stem rust fungus Puccinia graminis f. sp. tritici (Pgt) is one of the most destructive pathogens of wheat. In this study, a draft genome was built for a founder Australian Pgt isolate of pathotype (pt.) 21-0 (collected in 1954) by next generation DNA sequencing. A combination of reference-based assembly using the genome of the previously sequenced American Pgt isolate CDL 75-36-700-3 (p7a) and de novo assembly were performed resulting in a 92 Mbp reference genome for Pgt isolate 21-0. Approximately 13 Mbp of de novo assembled sequence in this genome is not present in the p7a reference assembly. This novel sequence is not specific to 21-0 as it is also present in three other Pgt rust isolates of independent origin. The new reference genome was subsequently used to build a pan-genome based on five Australian Pgt isolates. Transcriptomes from germinated urediniospores and haustoria were separately assembled for pt. 21-0 and comparison of gene expression profiles showed differential expression in ∼10% of the genes each in germinated spores and haustoria. A total of 1,924 secreted proteins were predicted from the 21-0 transcriptome, of which 520 were classified as haustorial secreted proteins (HSPs). Comparison of 21-0 with two presumed clonal field derivatives of this lineage (collected in 1982 and 1984) that had evolved virulence on four additional resistance genes (Sr5, Sr11, Sr27, SrSatu) identified mutations in 25 HSP effector candidates. Some of these mutations could explain their novel virulence phenotypes.Authors wish to thank the Two Blades Foundation for financial support. Part of this work was supported through access to facilities managed by Bioplatforms Australia and funded by the Australian Government National Collaborative Research Infrastructure Strategy and Education Investment Fund Super Science Initiative

    Attenuation of PTEN increases p21 stability and cytosolic localization in kidney cancer cells: a potential mechanism of apoptosis resistance

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    BACKGROUND: The PTEN (Phosphatase and Tensin homolog deleted on chromosome Ten) tumor suppressor gene is frequently mutated or deleted in a wide variety of solid tumors, and these cancers are generally more aggressive and difficult to treat than those possessing wild type PTEN. While PTEN lies upstream of the phosphoinositide-3 kinase signaling pathway, the mechanisms that mediate its effects on tumor survival remain incompletely understood. Renal cell carcinoma (RCC) is associated with frequent treatment failures (~90% in metastatic cases), and these tumors frequently contain PTEN abnormalities. RESULTS: Using the ACHN cell line containing wild type PTEN, we generated a stable PTEN knockdown RCC cell line using RNA interference. We then used this PTEN knockdown cell line to show that PTEN attenuation increases resistance to cisplatin-induced apoptosis, a finding associated with increased levels of the cyclin kinase inhibitor p21. Elevated levels of p21 result from stabilization of the protein, and they are dependent on the activities of phosphoinositide-3 kinase and Akt. More specifically, the accumulation of p21 occurs preferentially in the cytosolic compartment, which likely contributes to both cell cycle progression and resistance to apoptosis. CONCLUSION: Since p21 regulates a decision point between repair and apoptosis after DNA damage, our data suggest that p21 plays a key role in mechanisms used by PTEN-deficient tumors to escape chemotherapy. This in turn raises the possibility to use p21 attenuators as chemotherapy sensitizers, an area under active continuing investigation in our laboratories

    Synthetic Molecular Clouds from Supersonic MHD and Non-LTE Radiative Transfer Calculations

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    The dynamics of molecular clouds is characterized by supersonic random motions in the presence of a magnetic field. We study this situation using numerical solutions of the three-dimensional compressible magneto-hydrodynamic (MHD) equations in a regime of highly supersonic random motions. The non-LTE radiative transfer calculations are performed through the complex density and velocity fields obtained as solutions of the MHD equations, and more than 5x10^5 synthetic molecular spectra are obtained. We use a numerical flow without gravity or external forcing. The flow is super-Alfvenic and corresponds to model A of Padoan and Nordlund (1997). Synthetic data consist of sets of 90x90 synthetic spectra with 60 velocity channels, in five molecular transitions: J=1-0 and J=2-1 for 12CO and 13CO, and J=1-0 for CS. Though we do not consider the effects of stellar radiation, gravity, or mechanical energy input from discrete sources, our models do contain the basic physics of magneto-fluid dynamics and non-LTE radiation transfer and are therefore more realistic than previous calculations. As a result, these synthetic maps and spectra bear a remarkable resemblance to the corresponding observations of real clouds.Comment: 33 pages, 12 figures included, 5 jpeg figures not included (fig1a, fig1b, fig3, fig4 fig5), submitted to Ap

    Five Years of Mid-Infrared Evolution of the Remnant of SN 1987A: The Encounter Between the Blast Wave and the Dusty Equatorial Ring

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    We have used the Spitzer satellite to monitor the mid-IR evolution of SN 1987A over a 5 year period spanning the epochs between days 6000 and 8000 since the explosion. The supernova (SN) has evolved into a supernova remnant (SNR) and its radiative output is dominated by the interaction of the SN blast wave with the pre-existing equatorial ring (ER). The mid-IR spectrum is dominated by emission from ~180 K silicate dust, collisionally-heated by the hot X-ray emitting gas with a temperature and density of ~5x10^6 K and 3x10^4 cm-3, respectively. The mass of the radiating dust is ~1.2x10^(-6) Msun on day 7554, and scales linearly with IR flux. The infrared to soft-X-ray flux ratio is roughly constant with a value of 2.5. Gas-grain collisions therefore dominate the cooling of the shocked gas. The constancy of of this ratio suggests that very little grain processing or gas cooling have occurred throughout this epoch. The shape of the dust spectrum remained unchanged during the observations while the total flux increased with a time dependence of t^(0.87), t being the time since the first encounter between the blast wave and the ER. These observations are consistent with the transitioning of the blast wave from free expansion to a Sedov phase as it propagates into the main body of the ER.Comment: Accepted for publication in the ApJ, 11 pages, 11 figure

    Epigenetic suppression of hippocampal calbindin-D28k by ΔFosB drives seizure-related cognitive deficits.

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    The calcium-binding protein calbindin-D28k is critical for hippocampal function and cognition, but its expression is markedly decreased in various neurological disorders associated with epileptiform activity and seizures. In Alzheimer\u27s disease (AD) and epilepsy, both of which are accompanied by recurrent seizures, the severity of cognitive deficits reflects the degree of calbindin reduction in the hippocampal dentate gyrus (DG). However, despite the importance of calbindin in both neuronal physiology and pathology, the regulatory mechanisms that control its expression in the hippocampus are poorly understood. Here we report an epigenetic mechanism through which seizures chronically suppress hippocampal calbindin expression and impair cognition. We demonstrate that ΔFosB, a highly stable transcription factor, is induced in the hippocampus in mouse models of AD and seizures, in which it binds and triggers histone deacetylation at the promoter of the calbindin gene (Calb1) and downregulates Calb1 transcription. Notably, increasing DG calbindin levels, either by direct virus-mediated expression or inhibition of ΔFosB signaling, improves spatial memory in a mouse model of AD. Moreover, levels of ΔFosB and calbindin expression are inversely related in the DG of individuals with temporal lobe epilepsy (TLE) or AD and correlate with performance on the Mini-Mental State Examination (MMSE). We propose that chronic suppression of calbindin by ΔFosB is one mechanism through which intermittent seizures drive persistent cognitive deficits in conditions accompanied by recurrent seizures

    Common peroneal nerve palsy following total knee arthroplasty: prognostic factors and course of recovery.

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    Common peroneal nerve palsy (CPNP) is a serious complication following total knee arthroplasty (TKA). There is little information regarding the clinical course and prognostic factors for recovery. Between January 2000 and December 2008, 44 patients (0.53%) developed CPNP following TKA and were matched to 100 control patients based on year of surgery, type of surgery and surgeon. Regression analysis was performed to identify prognostic factors for recovery. A significant difference was seen in CPNP patients who were on average younger (62.1 years) and had higher BMI (34.5 kg/m(2)) than those who did not have nerve palsy (67.5 years and 31.8 kg/m(2), respectively). Only 37 patients with palsies could be followed, 32 (62.2%) had incomplete nerve palsy, twenty four (75%) of them fully recovered, while only 1 of patients with complete nerve palsy fully recovered. More severe initial injury was a negative prognostic factor for recovery of palsy (P\u3c0.03)
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