585 research outputs found

    Recommendations for Future Efforts in RANS Modeling and Simulation

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    The roadmap laid out in the CFD Vision 2030 document suggests that a decision to move away from RANS research needs to be made in the current timeframe (around 2020). This paper outlines industry requirements for improved predictions of turbulent flows and the cost-barrier that is often associated with reliance on scale resolving methods. Capabilities of RANS model accuracy for simple and complex flow flow fields are assessed, and modeling practices that degrade predictive accuracy are identified. Suggested research topics are identified that have the potential to improve the applicability and accuracy of RANS models. We conclude that it is important that some part of a balanced turbulence modeling research portfolio should include RANS efforts

    Mechanisms of Copper Ion Mediated Huntington's Disease Progression

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    Huntington's disease (HD) is caused by a dominant polyglutamine expansion within the N-terminus of huntingtin protein and results in oxidative stress, energetic insufficiency and striatal degeneration. Copper and iron are increased in the striata of HD patients, but the role of these metals in HD pathogenesis is unknown. We found, using inductively-coupled-plasma mass spectroscopy, that elevations of copper and iron found in human HD brain are reiterated in the brains of affected HD transgenic mice. Increased brain copper correlated with decreased levels of the copper export protein, amyloid precursor protein. We hypothesized that increased amounts of copper bound to low affinity sites could contribute to pro-oxidant activities and neurodegeneration. We focused on two proteins: huntingtin, because of its centrality to HD, and lactate dehydrogenase (LDH), because of its documented sensitivity to copper, necessity for normoxic brain energy metabolism and evidence for altered lactate metabolism in HD brain. The first 171 amino acids of wild-type huntingtin, and its glutamine expanded mutant form, interacted with copper, but not iron. N171 reduced Cu(2+) in vitro in a 1∶1 copper∶protein stoichiometry indicating that this fragment is very redox active. Further, copper promoted and metal chelation inhibited aggregation of cell-free huntingtin. We found decreased LDH activity, but not protein, and increased lactate levels in HD transgenic mouse brain. The LDH inhibitor oxamate resulted in neurodegeneration when delivered intra-striatially to healthy mice, indicating that LDH inhibition is relevant to neurodegeneration in HD. Our findings support a role of pro-oxidant copper-protein interactions in HD progression and offer a novel target for pharmacotherapeutics

    BUMPER v1.0: a Bayesian user-friendly model for palaeo-environmental reconstruction

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    We describe the Bayesian user-friendly model for palaeo-environmental reconstruction (BUMPER), a Bayesian transfer function for inferring past climate and other environmental variables from microfossil assemblages. BUMPER is fully self-calibrating, straightforward to apply, and computationally fast, requiring ~2 s to build a 100-taxon model from a 100-site training set on a standard personal computer. We apply the model’s probabilistic framework to generate thousands of artificial training sets under ideal assumptions.We then use these to demonstrate the sensitivity of reconstructions to the characteristics of the training set, considering assemblage richness, taxon tolerances, and the number of training sites. We find that a useful guideline for the size of a training set is to provide, on average, at least 10 samples of each taxon. We demonstrate general applicability to real data, considering three different organism types (chironomids, diatoms, pollen) and different reconstructed variables. An identically configured model is used in each application, the only change being the input files that provide the training-set environment and taxon-count data. The performance of BUMPER is shown to be comparable with weighted average partial least squares (WAPLS) in each case. Additional artificial datasets are constructed with similar characteristics to the real data, and these are used to explore the reasons for the differing performances of the different training sets

    Development and Use of Engineering Standards for Computational Fluid Dynamics for Complex Aerospace Systems

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    Computational fluid dynamics (CFD) and other advanced modeling and simulation (M&S) methods are increasingly relied on for predictive performance, reliability and safety of engineering systems. Analysts, designers, decision makers, and project managers, who must depend on simulation, need practical techniques and methods for assessing simulation credibility. The AIAA Guide for Verification and Validation of Computational Fluid Dynamics Simulations (AIAA G-077-1998 (2002)), originally published in 1998, was the first engineering standards document available to the engineering community for verification and validation (V&V) of simulations. Much progress has been made in these areas since 1998. The AIAA Committee on Standards for CFD is currently updating this Guide to incorporate in it the important developments that have taken place in V&V concepts, methods, and practices, particularly with regard to the broader context of predictive capability and uncertainty quantification (UQ) methods and approaches. This paper will provide an overview of the changes and extensions currently underway to update the AIAA Guide. Specifically, a framework for predictive capability will be described for incorporating a wide range of error and uncertainty sources identified during the modeling, verification, and validation processes, with the goal of estimating the total prediction uncertainty of the simulation. The Guide's goal is to provide a foundation for understanding and addressing major issues and concepts in predictive CFD. However, this Guide will not recommend specific approaches in these areas as the field is rapidly evolving. It is hoped that the guidelines provided in this paper, and explained in more detail in the Guide, will aid in the research, development, and use of CFD in engineering decision-making

    Thigh-Derived Inertial Sensor Metrics to Assess the Sit-to-Stand and Stand-to-Sit Transitions in the Timed Up and Go (TUG) Task for Quantifying Mobility Impairment in Multiple Sclerosis

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    INTRODUCTION: Inertial sensors generate objective and sensitive metrics of movement disability that may indicate fall risk in many clinical conditions including multiple sclerosis (MS). The Timed-Up-And-Go (TUG) task is used to assess patient mobility because it incorporates clinically-relevant submovements during standing. Most sensor-based TUG research has focused on the placement of sensors at the spine, hip or ankles; an examination of thigh activity in TUG in multiple sclerosis is wanting. METHODS: We used validated sensors (x-IMU by x-io) to derive transparent metrics for the sit-to-stand (SI-ST) transition and the stand-to-sit (ST-SI) transition of TUG, and compared effect sizes for metrics from inertial sensors on the thighs to effect sizes for metrics from a sensor placed at the L3 level of the lumbar spine. 23 healthy volunteers were compared to 17 ambulatory persons with MS (PwMS, HAI <= 2). RESULTS: During the SI-ST transition, the metric with the largest effect size comparing healthy volunteers to PwMS was the Area Under the Curve of the thigh angular velocity in the pitch direction -- representing both thigh and knee extension; the peak of the spine pitch angular velocity during SI-ST also had a large effect size, as did some temporal measures of duration of SI-ST, although less so. During the ST-SI transition the metric with the largest effect size in PwMS was the peak of the spine angular velocity curve in the roll direction. A regression was performed. DISCUSSION: We propose for PwMS that the diminished peak angular velocities during SI-ST directly represents extensor weakness, while the increased roll during ST-SI represents diminished postural control. CONCLUSIONS: During the SI-ST transition of TUG, angular velocities can discriminate between healthy volunteers and ambulatory PwMS better than temporal features. Sensor placement on the thighs provides additional discrimination compared to sensor placement at the lumbar spine

    Teaching Mathematics with Technology: TPACK and Effective Teaching Practices

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    This paper examines how 17 secondary mathematics teacher candidates (TCs) in four university teacher preparation programs implemented technology in their classrooms to teach for conceptual understanding in online, hybrid, and face to face classes during COVID-19. Using the Professional Development: Research, Implementation, and Evaluation (PrimeD) framework, TCs, classroom mentor teachers, field experience supervisors, and university faculty formed a Networked Improvement Community (NIC) to discuss a commonly agreed upon problem of practice and a change idea to implement in the classroom. Through Plan-Do-Study-Act cycles, participants documented their improvement efforts and refinements to the change idea and then reported back to the NIC at the subsequent monthly meeting. The Technology Pedagogical Content Knowledge framework (TPACK) and the TPACK levels rubric were used to examine how teacher candidates implemented technology for Mathematics conceptual understanding. The Mathematics Classroom Observation Protocol for Practices (MCOP2) was used to further examine how effective mathematics teaching practices (e.g., student engagement) were implemented by TCs. MCOP2 results indicated that TCs increased their use of effective mathematics teaching practices. However, growth in TPACK was not significant. A relationship between TPACK and MCOP2 was not evident, indicating a potential need for explicit focus on using technology for mathematics conceptual understanding
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