Evaluation of High Density Air Traffic Operations with Automation for Separation Assurance, Weather Avoidance and Schedule Conformance

In this paper we discuss the development and evaluation of our prototype technologies and procedures for far-term air traffic control operations with automation for separation assurance, weather avoidance and schedule conformance. Controller-in-the-loop simulations in the Airspace Operations Laboratory at the NASA Ames Research Center in 2010 have shown very promising results. We found the operations to provide high airspace throughput, excellent efficiency and schedule conformance. The simulation also highlighted areas for improvements: Short-term conflict situations sometimes resulted in separation violations, particularly for transitioning aircraft in complex traffic flows. The combination of heavy metering and growing weather resulted in an increased number of aircraft penetrating convective weather cells. To address these shortcomings technologies and procedures have been improved and the operations are being re-evaluated with the same scenarios. In this paper we will first describe the concept and technologies for automating separation assurance, weather avoidance, and schedule conformance. Second, the results from the 2010 simulation will be reviewed. We report human-systems integration aspects, safety and efficiency results as well as airspace throughput, workload, and operational acceptability. Next, improvements will be discussed that were made to address identified shortcomings. We conclude that, with further refinements, air traffic control operations with ground-based automated separation assurance can routinely provide currently unachievable levels of traffic throughput in the en route airspace

A Controller-in-the Loop Simulation of Ground-Based Automated Separation Assurance in a NextGen Environment

A controller-in-the-loop simulation was conducted in the Airspace Operations Laboratory (AOL) at the NASA Ames Research Center to investigate the functional allocation aspects associated with ground-based automated separation assurance in a far-term NextGen environment. In this concept, ground-based automation handled the detection and resolution of strategic and tactical conflicts and alerted the controller to deferred situations. The controller was responsible for monitoring the automation and managing situations by exception. This was done in conditions both with and without arrival time constraints across two levels of traffic density. Results showed that although workload increased with an increase in traffic density, it was still manageable in most situations. The number of conflicts increased similarly with a related increase in the issuance of resolution clearances. Although over 99% of conflicts were resolved, operational errors did occur but were tied to local sector complexities. Feedback from the participants revealed that they thought they maintained reasonable situation awareness in this environment, felt that operations were highly acceptable at the lower traffic density level but were less so as it increased, and felt overall that the concept as it was introduced here was a positive step forward to accommodating the more complex environment envisioned as part of NextGen

GluN2A NMDA Receptor Enhancement Improves Brain Oscillations, Synchrony, and Cognitive Functions in Dravet Syndrome and Alzheimer's Disease Models.

NMDA receptors (NMDARs) play subunit-specific roles in synaptic function and are implicated in neuropsychiatric and neurodegenerative disorders. However, the in vivo consequences and therapeutic potential of pharmacologically enhancing NMDAR function via allosteric modulation are largely unknown. We examine the in vivo effects of GNE-0723, a positive allosteric modulator of GluN2A-subunit-containing NMDARs, on brain network and cognitive functions in mouse models of Dravet syndrome (DS) and Alzheimer's disease (AD). GNE-0723 use dependently potentiates synaptic NMDA receptor currents and reduces brain oscillation power with a predominant effect on low-frequency (12-20 Hz) oscillations. Interestingly, DS and AD mouse models display aberrant low-frequency oscillatory power that is tightly correlated with network hypersynchrony. GNE-0723 treatment reduces aberrant low-frequency oscillations and epileptiform discharges and improves cognitive functions in DS and AD mouse models. GluN2A-subunit-containing NMDAR enhancers may have therapeutic benefits in brain disorders with network hypersynchrony and cognitive impairments

Specificity of Four Laboratory Approaches for Cross-Sectional HIV Incidence Determination: Analysis of Samples from Adults with Known Nonrecent HIV Infection from Five African Countries

Assays to determine cross-sectional HIV incidence misclassify some individuals with nonrecent HIV infection as recently infected, overestimating HIV incidence. We analyzed factors associated with false-recent misclassification in five African countries. Samples from 2197 adults from Botswana, Kenya, South Africa, Tanzania, and Uganda who were HIV infected > 12 months were tested using the (1) BED capture enzyme immunoassay (BED), (2) avidity assay, (3) BED and avidity assays with higher assay cutoffs (BED+ avidity screen), and (4) multiassay algorithm (MAA) that includes the BED+ avidity screen, CD4 cell count, and HIV viral load. Logistic regression identified factors associated with misclassification. False-recent misclassification rates and 95% confidence intervals were BED alone: 7.6% (6.6, 8.8); avidity assay alone: 3.5% (2.7, 4.3); BED+ avidity screen: 2.2% (1.7, 2.9); and MAA: 1.2% (0.8, 1.8). The misclassification rate for the MAA was significantly lower than the rates for the other three methods (each p < 0.05). Misclassification rates were lower when the analysis was limited to subtype C-endemic countries, with the lowest rate obtained for the MAA [0.8% (0.2, 1.9)]. Factors associated with misclassification were for BED alone: country of origin, antiretroviral treatment (ART), viral load, and CD4 cell count; for avidity assay alone: country of origin; for BED+ avidity screen: country of origin and ART. No factors were associated with misclassification using the MAA. In a multivariate model, these associations remained significant with one exception: the association of ART with misclassification was completely attenuated. A MAA that included CD4 cell count and viral load had lower false-recent misclassification than the BED or avidity assays (alone or in combination). Studies are underway to compare the sensitivity of these methods for detection of recent HIV infection

Participatory Process for Implementing a Colorectal Cancer Screening Intervention: an Action Plan for Local Sustainability

Background: Rigid protocols can hamper translation of evidence-based interventions from research to real-world settings. This investigation aimed to develop procedures for modifying the study protocol of a community-based participatory research (CBPR) project and to analyze the theoretical constructs that underlie this process. Methods: The research project is a dissemination and implementation study of the Educational Program to Increase Colorectal Cancer Screening (EPICS), an evidence-based intervention targeting African Americans in the United States. The study is being conducted in a partnership with community coalitions in 15 different cities. Each site initially presented unique issues that required modification of the study protocol. Results: In order to honor underlying CBPR theory, it was necessary to negotiate protocol changes with the community coalition at each site, while insuring preservation of the core elements of the intervention. Conclusions: We discuss the ways in which this represents a narrowing of the gap between CBPR and traditional research approaches

Structure of a putative NTP pyrophosphohydrolase: YP_001813558.1 from Exiguobacterium sibiricum 255-15.

The crystal structure of a putative NTPase, YP_001813558.1 from Exiguobacterium sibiricum 255-15 (PF09934, DUF2166) was determined to 1.78 Å resolution. YP_001813558.1 and its homologs (dimeric dUTPases, MazG proteins and HisE-encoded phosphoribosyl ATP pyrophosphohydrolases) form a superfamily of all-α-helical NTP pyrophosphatases. In dimeric dUTPase-like proteins, a central four-helix bundle forms the active site. However, in YP_001813558.1, an unexpected intertwined swapping of two of the helices that compose the conserved helix bundle results in a `linked dimer' that has not previously been observed for this family. Interestingly, despite this novel mode of dimerization, the metal-binding site for divalent cations, such as magnesium, that are essential for NTPase activity is still conserved. Furthermore, the active-site residues that are involved in sugar binding of the NTPs are also conserved when compared with other α-helical NTPases, but those that recognize the nucleotide bases are not conserved, suggesting a different substrate specificity

Structure of the γ-D-glutamyl-L-diamino acid endopeptidase YkfC from Bacillus cereus in complex with L-Ala-γ-D-Glu: insights into substrate recognition by NlpC/P60 cysteine peptidases.

Dipeptidyl-peptidase VI from Bacillus sphaericus and YkfC from Bacillus subtilis have both previously been characterized as highly specific γ-D-glutamyl-L-diamino acid endopeptidases. The crystal structure of a YkfC ortholog from Bacillus cereus (BcYkfC) at 1.8 Å resolution revealed that it contains two N-terminal bacterial SH3 (SH3b) domains in addition to the C-terminal catalytic NlpC/P60 domain that is ubiquitous in the very large family of cell-wall-related cysteine peptidases. A bound reaction product (L-Ala-γ-D-Glu) enabled the identification of conserved sequence and structural signatures for recognition of L-Ala and γ-D-Glu and, therefore, provides a clear framework for understanding the substrate specificity observed in dipeptidyl-peptidase VI, YkfC and other NlpC/P60 domains in general. The first SH3b domain plays an important role in defining substrate specificity by contributing to the formation of the active site, such that only murein peptides with a free N-terminal alanine are allowed. A conserved tyrosine in the SH3b domain of the YkfC subfamily is correlated with the presence of a conserved acidic residue in the NlpC/P60 domain and both residues interact with the free amine group of the alanine. This structural feature allows the definition of a subfamily of NlpC/P60 enzymes with the same N-terminal substrate requirements, including a previously characterized cyanobacterial L-alanine-γ-D-glutamate endopeptidase that contains the two key components (an NlpC/P60 domain attached to an SH3b domain) for assembly of a YkfC-like active site

Report of the first international liver transplantation society expert panel consensus conference on renal insufficiency in liver transplantation

No abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64330/1/21877_ftp.pd

The structure of BVU2987 from Bacteroides vulgatus reveals a superfamily of bacterial periplasmic proteins with possible inhibitory function.

Proteins that contain the DUF2874 domain constitute a new Pfam family PF11396. Members of this family have predominantly been identified in microbes found in the human gut and oral cavity. The crystal structure of one member of this family, BVU2987 from Bacteroides vulgatus, has been determined, revealing a β-lactamase inhibitor protein-like structure with a tandem repeat of domains. Sequence analysis and structural comparisons reveal that BVU2987 and other DUF2874 proteins are related to β-lactamase inhibitor protein, PepSY and SmpA_OmlA proteins and hence are likely to function as inhibitory proteins

Trust, benefit, satisfaction, and burden: A randomized controlled trial to reduce cancer risk through African-American churches

Community-based participatory research (CBPR) approaches that actively engage communities in a study are assumed to lead to relevant findings, trusting relationships, and greater satisfaction with the research process