Unsteady Flow and Whirl-Inducing Forces in Axial-Flow Compressors: Part I—Experiment

An experimental and theoretical investigation has been conducted to evaluate the effects seen in axial-flow compressors when the centerline of the rotor is displaced from the centerline of the static structure of the engine. This creates circumferentially nonuniform rotor-tip clearances, unsteady flow, and potentially increased clearances if the rotating and stationary parts come in contact. The result not only adversely affects compressor stall margin, pressure rise capability, and efficiency, but also generates an unsteady, destabilizing, aerodynamic force, called the Thomas/Alford force, which contributes significantly to rotor whirl instabilities in turbomachinery. Determining both the direction and magnitude of this force in compressors, relative to those in turbines, is especially important for the design of mechanically stable turbomachinery components. Part I of this two-part paper addresses these issues experimentally and Part II presents analyses from relevant computational models. Our results clearly show that the Thomas/Alford force can promote significant backward rotor whirl over much of the operating range of modern compressors, although some regions of zero and forward whirl were found near the design point. This is the first time that definitive measurements, coupled with compelling analyses, have been reported in the literature to resolve the long-standing disparity in findings concerning the direction and magnitude of whirl-inducing forces important in the design of modern axial-flow compressors

Evolution of project planning tools in a matrix organization

Until recently, the Corporate Construction Program at Sandia was experiencing difficulties in managing projects: poor planning and cost estimating caused schedule and budget problems. The first step taken was a Microsoft {reg_sign} Project schedule that provides a standard template for scheduling individual construction projects. It is broken down according to the life cycle of the project and prevents the project team from leaving out an important item. A WBS (work breakdown structure) dictionary was also developed that describes how capital and operating funds are used to develop, design, construct, equip, and manage projects. We also developed a matrix chart that maps the planning guide against the major types of construction projects at Sandia. The guide, dictionary, and matrix chart offer enough flexibility that the project manager can make choices about how to structure work, yet ensure that all work rolls up to the cost categories and key DOE WBS elements. As requirements change, the tools can be updated; they also serve as training tools for new project team members

The role of kinetic context in apparent biased agonism at GPCRs

Biased agonism describes the ability of ligands to stabilize different conformations of a GPCR linked to distinct functional outcomes and offers the prospect of designing pathway-specific drugs that avoid on-target side effects. This mechanism is usually inferred from pharmacological data with the assumption that the confounding influences of observational (that is, assay dependent) and system (that is, cell background dependent) bias are excluded by experimental design and analysis. Here we reveal that ‘kinetic context’, as determined by ligand-binding kinetics and the temporal pattern of receptor-signalling processes, can have a profound influence on the apparent bias of a series of agonists for the dopamine D2 receptor and can even lead to reversals in the direction of bias. We propose that kinetic context must be acknowledged in the design and interpretation of studies of biased agonism

Ligand-Induced Modulation of the Free-Energy Landscape of G Protein-Coupled Receptors Explored by Adaptive Biasing Techniques

Extensive experimental information supports the formation of ligand-specific conformations of G protein-coupled receptors (GPCRs) as a possible molecular basis for their functional selectivity for signaling pathways. Taking advantage of the recently published inactive and active crystal structures of GPCRs, we have implemented an all-atom computational strategy that combines different adaptive biasing techniques to identify ligand-specific conformations along pre-determined activation pathways. Using the prototypic GPCR β2-adrenergic receptor as a suitable test case for validation, we show that ligands with different efficacies (either inverse agonists, neutral antagonists, or agonists) modulate the free-energy landscape of the receptor by shifting the conformational equilibrium towards active or inactive conformations depending on their elicited physiological response. Notably, we provide for the first time a quantitative description of the thermodynamics of the receptor in an explicit atomistic environment, which accounts for the receptor basal activity and the stabilization of different active-like states by differently potent agonists. Structural inspection of these metastable states reveals unique conformations of the receptor that may have been difficult to retrieve experimentally

Governing Boards and Profound Organizational Change in Hospitals

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69047/2/10.1177_107755878904600204.pd

Multidisciplinary Consideration of Potential Pathophysiologic Mechanisms of Paradoxical Erythema with Topical Brimonidine Therapy

Rosacea is a chronic inflammatory disease with transient and non-transient redness as key characteristics. Brimonidine is a selective α2-adrenergic receptor (AR) agonist approved for persistent facial erythema of rosacea based on significant efficacy and good safety data. The majority of patients treated with brimonidine report a benefit; however, there have been sporadic reports of worsening erythema after the initial response. A group of dermatologists, receptor physiology, and neuroimmunology scientists met to explore potential mechanisms contributing to side effects as well as differences in efficacy. We propose the following could contribute to erythema after application: (1) local inflammation and perivascular inflammatory cells with abnormally functioning ARs may lead to vasodilatation; (2) abnormal saturation and cells expressing different AR subtypes with varying ligand affinity; (3) barrier dysfunction and increased skin concentrations of brimonidine with increased actions at endothelial and presynaptic receptors, resulting in increased vasodilation; and (4) genetic predisposition and receptor polymorphism(s) leading to different smooth muscle responses. Approximately 80% of patients treated with brimonidine experience a significant improvement without erythema worsening as an adverse event. Attention to optimizing skin barrier function, setting patient expectations, and strategies to minimize potential problems may possibly reduce further the number of patients who experience side effects. Funding: Galderma International S.A.S., Paris, France

The Application of the Probabilistic Collocation Method to a Transonic Axial Flow Compressor

In this paper the Probabilistic Collocation method is used for uncertainty quantification of operational uncertainties in a transonic axial flow compressor (i.e. NASA Rotor 37). Compressor rotors are components of a gas turbine that are highly sensitive to operational and geometrical uncertainties. Validation of the Probabilistic Collocation method with a Monte Carlo simulation using 10,000 Latin Hypercube samples demonstrated that the Probabilistic Collocation method can successfully be applied to a turbomachinery case. The flow through the rotor is characterized by a bow shock in front of the leading edge, which interacts with the boundary layer of the next blade. The total pressure profile at the inlet of the rotor is assumed to be uncertain. A symmetric beta distribution was used for the pressure profile, with the standard deviation such that the uncertainty is in the same order of the measurement accuracy reported in literature. The mass flow was shown to be the most sensitive to the uncertainty, while the efficiency is least affected. It was shown by the compressor maps that is important to take the uncertainty in the total pressure profile at the inlet into account. The standard deviation of the static pressure field showed that the largest variation is present near the shock wave and mainly in the region of the strongest shock, which is near the tip of the blade.Aerospace Engineerin