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

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

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

Kinetics of Carbamylcholine Binding to Membrane-Bound Acetylcholine Receptor Monitored by Fluorescence Changes of a Covalently Bound Probe

The fluorescent probe 5-(iodoacetamido)salicylic acid has been used to alkylate acetylcholine receptor enriched membrane fragments from Torpedo californica following their reduction with low concentrations of dithiothreitol. This modification did not affect the equilibrium binding of carbamylcholine to the receptor. The fluorescence of bound 5-(iodoacetamido)salicylic acid was enhanced when the labeled membrane fragments were mixed with carbamylcholine. This increase in fluorescence was abolished by preincubation of the membrane fragments with excess ɑ-bungarotoxin and was therefore specific for the acetylcholine receptor. Estimates of dissociation constants obtained from centrifugation experiments with radioactive ligand and from fluorescence titration data were in good agreement, showing that the observed fluorescence enhancement was an accurate reflection of receptor- carbamylcholine complex formation. The kinetics of carbamylcholine binding to labeled membrane fragments have been investigated over a wide range of ligand concentrations by using stopped-flow fluorescence techniques. The kinetic signal was complicated, and four distinct exponential phases were observed. A kinetic mechanism has been proposed to account for this behavior