Disruption of glycerol metabolism by RNAi targeting of genes encoding glycerol kinase results in a range of phenotype severity in Drosophila.

In Drosophila, RNAi targeting of either dGyk or dGK can result in two alternative phenotypes: adult glycerol hypersensitivity or larval lethality. Here we compare these two phenotypes at the level of glycerol kinase (GK) phosphorylation activity, dGyk and dGK-RNA expression, and glycerol levels. We found both phenotypes exhibit reduced but similar levels of GK phosphorylation activity. Reduced RNA expression levels of dGyk and dGK corresponded with RNAi progeny that developed into glycerol hypersensitive adult flies. However, quantification of dGyk/dGK expression levels for the larval lethality phenotype revealed unexpected levels possibly due to a compensatory mechanism between dGyk and dGK or RNAi inhibition. The enzymatic role of glycerol kinase converts glycerol to glycerol 3-phosphate. As expected, elevated glycerol levels were observed in larvae that went on to develop into glycerol hypersensitive adults. Interestingly, larvae that died before eclosion revealed extremely low glycerol levels. Further characterization identified a wing phenotype that is enhanced by a dGpdh null mutation, indicating disrupted glycerol metabolism underlies the wing phenotype. In humans, glycerol kinase deficiency (GKD) exhibits a wide range of phenotypic variation with no obvious genotype-phenotype correlations. Additionally, disease severity often does not correlate with GK phosphorylation activity. It is intriguing that both human GKD patients and our GKD Drosophila model show a range of phenotype severity. Additionally, the lack of correlation between GK phosphorylation and dGyk/dGK-RNA expression with phenotypic severity suggests further study including understanding the alternative functions of the GK protein, could provide insights into the complex pathogenic mechanism observed in human GKD patients

The Outer Limits of Galaxy Clusters: Observations to the Virial Radius with Suzaku, XMM, and Chandra

The outskirts of galaxy clusters, near the virial radius, remain relatively unexplored territory and yet are vital to our understanding of cluster growth, structure, and mass. In this presentation, we show the first results from a program to constrain the state of the outer intracluster medium (ICM) in a large sample of galaxy clusters, exploiting the strengths of three complementary X-ray observatories: Suzaku (low, stable background), XMM-Newton (high sensitivity), and Chandra (good spatial resolution). By carefully combining observations from the cluster core to beyond r_200, we are able to identify and reduce systematic uncertainties that would impede our spatial and spectral analysis using a single telescope. Our sample comprises nine clusters at z ~ 0.1-0.2 fully covered in azimuth to beyond r_200, and our analysis indicates that the ICM is not in hydrostatic equilibrium in the cluster outskirts, where we see clear azimuthal variations in temperature and surface brightness. In one of the clusters, we are able to measure the diffuse X-ray emission well beyond r_200, and we find that the entropy profile and the gas fraction are consistent with expectations from theory and numerical simulations. These results stand in contrast to recent studies which point to gas clumping in the outskirts; the extent to which differences of cluster environment or instrumental effects factor in this difference remains unclear. From a broader perspective, this project will produce a sizeable fiducial data set for detailed comparison with high-resolution numerical simulations.Comment: 8 pages, 6 figures. To appear in the proceedings of the Suzaku 2011 Conference, "Exploring the X-ray Universe: Suzaku and Beyond.

Annual Survey of Virginia Law: Civil Practice and Procedure

This article reviews some of the recent developments and changes effected by the Supreme Court of Virginia and the Virginia General Assembly which affect and involve civil litigation. The scope of this paper does not extend to criminal procedure. This paper is not intended to be an all inclusive compilation, but rather a sampling of case law and legislative enactments of interest to the civil litigation attorney

A SENSITIVE, COUPLED ASSAY FOR PLASMINOGEN ACTIVATOR USING A THIOL ESTER SUBSTRATE FOR PLASMIN *

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75243/1/j.1749-6632.1981.tb29768.x.pd

Design and Validation of an Autonomous Mission Manager towards Coordinated Multi-Spacecraft Missions

For ambitious upcoming aerospace missions, autonomy will play a crucial role in achieving complex mission goals and reducing the burden for ground operations. Standalone spacecraft can leverage autonomy concepts to optimize data collection and ensure robust operation. For spacecraft clusters, autonomy can additionally provide a feasible method of ensuring coordination through onboard peer-to-peer scheduling. However, in exchange for providing flexible mission capabilities and operational convenience, autonomy introduces additional uncertainty and software complexity, which complicates the mission assurance process. This research presents a framework for designing and testing schedules consisting of heavily constrained tasks. The core of this framework, the Schedule Manager (SM), manages tasks by associating constraints with each task including time windows, task priority, conflict categories, and resource requirements, which assures that tasks will only run when capable. This increased control over individual tasks also improves the modularity of the overall mission plan, and provides a built-in fail-safe in the event of unexpected task failure through the loading of predefined contingency schedules. The SM can use estimated task durations and resource requirements to simulate schedules ahead of time, which can be used on the ground for schedule validation and onboard as a method of prognostics and to calculate resource availability windows. The ability to predict availability windows onboard and dynamically adjust depending upon currently scheduled tasks enables peer-to-peer tasking and scheduling. For example, a spacecraft can schedule a coordinated action by broadcasting the task requirements in an availability window request to all applicable spacecraft. Then, based upon the availability windows received from each spacecraft, the coordinating spacecraft can then issue a final task scheduling command with a much lower probability of conflict. The SM has been integrated with the core Flight System (cFS) from NASA, which has flight heritage on previous successful large-scale missions such as the Lunar and Dust Environment Explorer (LADEE). This integration is in the form of a cFS application called the cFS Schedule Manager (CSM), which will manage the operations for the Space Test Program Houston 7 Configurable and Autonomous Sensor Processing Research (STP-H7-CASPR) experiment that is planned for launch on SpaceX-24 to the International SpaceStation (ISS) in December 2021. Software validation was achieved with cFS unit tests, functional tests, and code analysis tools. Demonstrations were built using the COSMOS ground station and the 42 spacecraft simulator, and these were tested with a cluster of development boards in the loop as representative flight hardware

RISK PERCEPTIONS AND MANAGEMENT RESPONSES: PRODUCER-GENERATED HYPOTHESES FOR RISK MODELING

Farm level risk analyses have used price and yield variability almost exclusively to represent risk. Results from a survey of 149 agricultural producers in 12 states indicate that producers consider a broader range of sources of variability in their operations. Significant differences exist among categories with respect to the importance of the sources of variability in crop and livestock production. Producers also used a variety of management responses to variability. There were significant difference among categories in the importance given to particular responses and their use of them. These results have implications for research, extension, and policy programs.Risk and Uncertainty,