Structured Transition of Wind Tunnel Operations Skills from Government-to Contractor-Managed

In 2004, NASA awarded the Research, Operations, Maintenance, and Engineering (ROME) contract at NASA Langley Research Center to a team led by Jacobs Technology, Inc. A key component of the contract was the transitioning of the five large wind tunnel facilities from NASA managed and NASA or NASA/contractor workforces to fully contractor operated. The contractor would manage daily operations while NASA would continue to develop long-term strategies, make decisions regarding commitment of funds and commitment of facilities, and provide oversight of the contractor's performance. A major challenge would be the transition of knowledge of facility operations and maintenance from the incumbent civil servant workforce to the contractor workforce. While the contract has since been modified multiple times, resulting in a blended NASA/ROME workforce across the facilities, the processes developed and implemented to capture and document facility knowledge from the incumbent subject matter experts, build training and certification programs, and grow individual skills across subject areas and across facilities, are worthy of documentation. This is the purpose of this paper

GTTC Future of Ground Testing Meta-Analysis of 20 Documents

National research, development, test, and evaluation ground testing capabilities in the United States are at risk. There is a lack of vision and consensus on what is and will be needed, contributing to a significant threat that ground test capabilities may not be able to meet the national security and industrial needs of the future. To support future decisions, the AIAA Ground Testing Technical Committees (GTTC) Future of Ground Test (FoGT) Working Group selected and reviewed 20 seminal documents related to the application and direction of ground testing. Each document was reviewed, with the content main points collected and organized into sections in the form of a gap analysis current state, future state, major challenges/gaps, and recommendations. This paper includes key findings and selected commentary by an editing team

Immune complex effects on glomerular eicosanoid production and renal hemodynamics

Immune complex effects on glomerular eicosanoid production and renal hemodynamics. We examined the effect of glomerular immune complex (IC) deposition on glomerular eicosanoid synthesis and the role of the eicosanoids in glomerular pathophysiology. Rats received daily 10mg i.v. injections of native bovine gamma–globulin (NBGG) or cationic bovine gamma–globulin (CBGG) for 21 days; age–matched controls were maintained. Immunofluorescence and electron microscopy showed mesangial deposits of IC in the NBGG group and capillary wall deposits in the CBGG group, without light or electron microscopic evidence of leukocyte infiltration. One week after the last antigen dose, GFR was similar in all three groups, but RPF increased in the rats given CBGG; (8.37 ± 0.90 vs. control 5.54 ± 0.56 ml/min, P < 0.05). Glomerular synthesis of prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) was normal in animals that received NBGG. Rats given CBGG had increased glomerular production of PGE2, (2.23 ± 0.37 vs. control 1.03 ± 0.16 ng/mg glomerular dry wt, P < 0.05) and TxB2 (3.12 ± 0.50 vs. control 0.48 ± 0.07 ng/mg glomerular dry wt, P < 0.001). Proteinuria only developed in the rats given CBGG, 86.6 ± 18 mg/24 hr, which correlated with glomerular TxA2 synthesis, r = 0.82, P = 0.01. Acute administration of the TxA2 synthesis inhibitor, UK-38,485, and a TxA2 receptor antagonist, EP-092, to rats given CBGG did not affect GFR or RPF. The cyclo-oxygenase inhibitor, indomethacin, reduced both GFR and RPF by up to 40% in CBGG-immunized rats. Oral administration of UK-38,485 for six days to nephrotic rats did not result in a statistically significant reduction of proteinuria despite 85% inhibition of glomerular TxB2. We conclude that cationic antigen induces a glomerular disease pathologically similar to membranous nephropathy. The increment of RPF is most probably due to increased glomerular PGE2. The increased TxA2 has no effect on glomerular hemodynamics and probably is not a component in the pathogenesis of proteinuria

Evolutionary responses to acquiring a multidrug resistance plasmid are dominated by metabolic functions across diverse <i>Escherichia coli</i> lineages

Multidrug resistance (MDR) plasmids drive the spread of antibiotic resistance between bacterial lineages. The immediate impact of MDR plasmid acquisition on fitness and cellular processes varies among bacterial lineages, but how the evolutionary processes enabling the genomic integration of MDR plasmids vary is less well understood, particularly in clinical pathogens. Using diverse Escherichia coli lineages experimentally evolved for ~700 generations, we show that the evolutionary response to gaining the MDR plasmid pLL35 was dominated by chromosomal mutations affecting metabolic and regulatory functions, with both strain-specific and shared mutational targets. The expression of several of these functions, such as anaerobic metabolism, is known to be altered upon acquisition of pLL35. Interactions with resident mobile genetic elements, notably several IS-elements, potentiated parallel mutations, including insertions upstream of hns that were associated with its upregulation and the downregulation of the plasmid-encoded extended-spectrum beta-lactamase gene. Plasmid parallel mutations targeted conjugation-related genes, whose expression was also commonly downregulated in evolved clones. Beyond their role in horizontal gene transfer, plasmids can be an important selective force shaping the evolution of bacterial chromosomes and core cellular functions. IMPORTANCE Plasmids drive the spread of antimicrobial resistance genes between bacterial genomes. However, the evolutionary processes allowing plasmids to be assimilated by diverse bacterial genomes are poorly understood, especially in clinical pathogens. Using experimental evolution with diverse E. coli lineages and a clinical multidrug resistance plasmid, we show that although plasmids drove unique evolutionary paths per lineage, there was a surprising degree of convergence in the functions targeted by mutations across lineages, dominated by metabolic functions. Remarkably, these same metabolic functions show higher evolutionary rates in MDR-lineages in nature and in some cases, like anaerobic metabolism, their expression is directly manipulated by the plasmid. Interactions with other mobile elements resident in the genomes accelerated adaptation by disrupting genes and regulatory sequences that they inserted into. Beyond their role in horizontal gene transfer, plasmids are an important selective force driving the evolution of bacterial genomes and core cellular functions

Mapping gene-by-gene single-nucleotide variation in 8,535 <i>Mycobacterium tuberculosis</i> genomes:a resource to support potential vaccine and drug development

Tuberculosis is an infectious disease caused by the bacterium Mycobacterium tuberculosisMycobacterium bovi

Investigating eye movement patterns, language, and social ability in children with autism spectrum disorder

Although all intellectually high-functioning children with autism spectrum disorder (ASD) display core social and communication deficits, some develop language within a normative timescale and others experience significant delays and subsequent language impairment. Early attention to social stimuli plays an important role in the emergence of language, and reduced attention to faces has been documented in infants later diagnosed with ASD. We investigated the extent to which patterns of attention to social stimuli would differentiate early and late language onset groups. Children with ASD (mean age = 10 years) differing on language onset timing (late/normal) and a typically developing comparison group completed a task in which visual attention to interacting and noninteracting human figures was mapped using eye tracking. Correlations on visual attention data and results from tests measuring current social and language ability were conducted. Patterns of visual attention did not distinguish typically developing children and ASD children with normal language onset. Children with ASD and late language onset showed significantly reduced attention to salient social stimuli. Associations between current language ability and social attention were observed. Delay in language onset is associated with current language skills as well as with specific eye-tracking patterns

Mutations in human immunodeficiency virus type 1 reverse transcriptase that make it sensitive to degradation by the viral protease in virions are selected against in patients

AbstractMutations in the thumb subdomain of reverse transcriptase (RT) of HIV-1 can cause this enzyme to be degraded in virions by the viral protease (PR). Many of these mutations confer a temperature-sensitive phenotype on RT and viral replication. The degradation of RT by PR appears to take place after Gag-Pol has been processed. We show here that mutations in other parts of RT, including the RNase H domain, can make RT PR-sensitive and temperature-sensitive. These data explain why some mutations in the RNase H domain, which had little or no effect on the polymerase activity of purified recombinant RT, had a profound effect on viral titer. Because the PR-sensitive phenotype significantly reduced viral titer, we previously suggested that these mutations would be selected against in patients. We also show that RT mutations that are known to confer a temperature sensitive phenotype are rarely found in the Stanford database

Finite sampling interval effects in Kramers-Moyal analysis

Large sampling intervals can affect reconstruction of Kramers-Moyal coefficients from data. A new method, which is direct, non-stochastic and exact up to numerical accuracy, can estimate these finite-time effects. For the first time, exact finite-time effects are described analytically for special cases; biologically inspired numerical examples are also worked through numerically. The approach developed here will permit better evaluation of Langevin or Fokker-Planck based models from data with large sampling intervals. It can also be used to predict the sampling intervals for which finite-time effects become significant.Comment: Preprin