497 research outputs found
Nonequilibrium steady states in a vibrated-rod monolayer: tetratic, nematic and smectic correlations
We study experimentally the nonequilibrium phase behaviour of a horizontal
monolayer of macroscopic rods. The motion of the rods in two dimensions is
driven by vibrations in the vertical direction. Aside from the control
variables of packing fraction and aspect ratio that are typically explored in
molecular liquid crystalline systems, due to the macroscopic size of the
particles we are also able to investigate the effect of the precise shape of
the particle on the steady states of this driven system. We find that the shape
plays an important role in determining the nature of the orientational ordering
at high packing fraction. Cylindrical particles show substantial tetratic
correlations over a range of aspect ratios where spherocylinders have
previously been shown by Bates et al (JCP 112, 10034 (2000)) to undergo
transitions between isotropic and nematic phases. Particles that are thinner at
the ends (rolling pins or bails) show nematic ordering over the same range of
aspect ratios, with a well-established nematic phase at large aspect ratio and
a defect-ridden nematic state with large-scale swirling motion at small aspect
ratios. Finally, long-grain, basmati rice, whose geometry is intermediate
between the two shapes above, shows phases with strong indications of smectic
order.Comment: 18 pages and 13 eps figures, references adde
Time-Optimized Contextual Information Flow on Unmanned Vehicles
Nowadays, the domain of robotics experiences a significant growth. We focus on Unmanned Vehicles intended for the air, sea and ground (UxV). Such devices are typically equipped with numerous sensors that detect contextual parameters from the broader environment, e.g., obstacles, temperature. Sensors report their findings (telemetry) to other systems, e.g., back-end systems, that further process the captured information while the UxV receives control inputs, such as navigation commands from other systems, e.g., commanding stations. We investigate a framework that monitors network condition parameters including signal strength and prioritizes the transmission of control messages and telemetry. This framework relies on the Theory of Optimal Stopping to assess in real-time the trade-off between the delivery of the messages and the network quality statistics and optimally schedules critical information delivery to back-end systems
Inapproximability of the independent set polynomial in the complex plane
We study the complexity of approximating the value of the independent set polynomial ZG(λ) of a graph G with maximum degree Δ when the activity λ is a complex number. When λ is real, the complexity picture is well-understood, and is captured by two real-valued thresholds λ* and λc, which depend on Δ and satisfy 00, resolving in the affirmative a conjecture of Harvey, Srivastava and Vondrak. Our proof techniques are based around tools from complex analysis — specifically the study of iterative multivariate rational maps
Recapitulation of tumor heterogeneity and molecular signatures in a 3D brain cancer model with decreased sensitivity to histone deacetylase inhibition
INTRODUCTION
Physiologically relevant pre-clinical ex vivo models recapitulating CNS tumor micro-environmental complexity will aid development of biologically-targeted agents. We present comprehensive characterization of tumor aggregates generated using the 3D Rotary Cell Culture System (RCCS).
METHODS
CNS cancer cell lines were grown in conventional 2D cultures and the RCCS and comparison with a cohort of 53 pediatric high grade gliomas conducted by genome wide gene expression and microRNA arrays, coupled with immunohistochemistry, ex vivo magnetic resonance spectroscopy and drug sensitivity evaluation using the histone deacetylase inhibitor, Vorinostat.
RESULTS
Macroscopic RCCS aggregates recapitulated the heterogeneous morphology of brain tumors with a distinct proliferating rim, necrotic core and oxygen tension gradient. Gene expression and microRNA analyses revealed significant differences with 3D expression intermediate to 2D cultures and primary brain tumors. Metabolic profiling revealed differential profiles, with an increase in tumor specific metabolites in 3D. To evaluate the potential of the RCCS as a drug testing tool, we determined the efficacy of Vorinostat against aggregates of U87 and KNS42 glioblastoma cells. Both lines demonstrated markedly reduced sensitivity when assaying in 3D culture conditions compared to classical 2D drug screen approaches.
CONCLUSIONS
Our comprehensive characterization demonstrates that 3D RCCS culture of high grade brain tumor cells has profound effects on the genetic, epigenetic and metabolic profiles of cultured cells, with these cells residing as an intermediate phenotype between that of 2D cultures and primary tumors. There is a discrepancy between 2D culture and tumor molecular profiles, and RCCS partially re-capitulates tissue specific features, allowing drug testing in a more relevant ex vivo system
Improvements in wind speed forecasts for wind power prediction purposes using Kalman filtering
International audienceThis paper studies the application of Kalman filtering as a post-processing method in numerical predictions of wind speed. Two limited-area atmospheric models have been employed, with different options/capabilities of horizontal resolution, to provide wind speed forecasts. The application of Kalman filter to these data leads to the elimination of any possible systematic errors, even in the lower resolution cases, contributing further to the significant reduction of the required CPU time. The potential of this method in wind power applications is also exploited. In particular, in the case of wind power prediction, the results obtained showed a remarkable improvement in the model forecasting skill
Linking Proteomic and Transcriptional Data through the Interactome and Epigenome Reveals a Map of Oncogene-induced Signaling
Cellular signal transduction generally involves cascades of post-translational protein modifications that rapidly catalyze changes in protein-DNA interactions and gene expression. High-throughput measurements are improving our ability to study each of these stages individually, but do not capture the connections between them. Here we present an approach for building a network of physical links among these data that can be used to prioritize targets for pharmacological intervention. Our method recovers the critical missing links between proteomic and transcriptional data by relating changes in chromatin accessibility to changes in expression and then uses these links to connect proteomic and transcriptome data. We applied our approach to integrate epigenomic, phosphoproteomic and transcriptome changes induced by the variant III mutation of the epidermal growth factor receptor (EGFRvIII) in a cell line model of glioblastoma multiforme (GBM). To test the relevance of the network, we used small molecules to target highly connected nodes implicated by the network model that were not detected by the experimental data in isolation and we found that a large fraction of these agents alter cell viability. Among these are two compounds, ICG-001, targeting CREB binding protein (CREBBP), and PKF118–310, targeting β-catenin (CTNNB1), which have not been tested previously for effectiveness against GBM. At the level of transcriptional regulation, we used chromatin immunoprecipitation sequencing (ChIP-Seq) to experimentally determine the genome-wide binding locations of p300, a transcriptional co-regulator highly connected in the network. Analysis of p300 target genes suggested its role in tumorigenesis. We propose that this general method, in which experimental measurements are used as constraints for building regulatory networks from the interactome while taking into account noise and missing data, should be applicable to a wide range of high-throughput datasets.National Science Foundation (U.S.) (DB1-0821391)National Institutes of Health (U.S.) (Grant U54-CA112967)National Institutes of Health (U.S.) (Grant R01-GM089903)National Institutes of Health (U.S.) (P30-ES002109
Comprehensive lung injury pathology induced by mTOR inhibitors
Molecular Targets in Oncology[Abstract] Interstitial lung disease is a rare side effect of temsirolimus treatment in renal cancer patients. Pulmonary fibrosis is characterised by the accumulation of extracellular matrix collagen, fibroblast proliferation and migration, and loss of alveolar gas exchange units. Previous studies of pulmonary fibrosis have mainly focused on the fibro-proliferative process in the lungs. However, the molecular mechanism by which sirolimus promotes lung fibrosis remains elusive. Here, we propose an overall cascade hypothesis of interstitial lung diseases that represents a common, partly underlying synergism among them as well as the lung pathogenesis side effects of mammalian target of rapamycin inhibitors
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