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At least 19 records

Room temperature crystallography of human acetylcholinesterase bound to a substrate analogue 4K-TMA: Towards a neutron structure

Acetylcholinesterase (AChE) catalyzes hydrolysis of acetylcholine thereby terminating cholinergic nerve impulses for efficient neurotransmission. Human AChE (hAChE) is a target of nerve agent and pesticide organophosphorus compounds that covalently attach to the catalytic Ser203 residue. Reactivation of inhibited hAChE can be achieved with nucleophilic antidotes, such as oximes. Understanding structural and electrostatic (i.e. protonation states) determinants of the catalytic and reactivation processes is crucial to improve design of oxime reactivators. Here we report X-ray structures of hAChE conjugated with a reversible covalent inhibitor 4K-TMA (4K-TMA:hAChE) at 2.8 Å resolution and of 4K-TMA:hAChE conjugate with oxime reactivator methoxime, MMB4 (4K-TMA:hAChE:MMB4) at 2.6 Å resolution, both at physiologically relevant room temperature, as well as cryo-crystallographic structure of 4K-TMA:hAChE at 2.4 Å resolution. 4K-TMA acts as a substrate analogue reacting with the hydroxyl of Ser203 and generating a reversible tetrahedral hemiketal intermediate that closely resembles the first tetrahedral intermediate state during hAChE-catalyzed acetylcholine hydrolysis. Structural comparisons of room temperature with cryo-crystallographic structures of 4K-TMA:hAChE and published mAChE complexes with 4K-TMA, as well as the effect of MMB4 binding to the peripheral anionic site (PAS) of the 4K-TMA:hAChE complex, revealed only discrete, minor differences. The active center geometry of AChE, already highly evolved for the efficient catalysis, was thus indicative of only minor conformational adjustments to accommodate the tetrahedral intermediate in the hydrolysis of the neurotransmitter acetylcholine (ACh). To map protonation states in the hAChE active site gorge we collected 3.5 Å neutron diffraction data paving the way for obtaining higher resolution datasets that will be needed to determine locations of individual hydrogen atoms.

4K-TMA↗

Denver TMA assessment

This report describes the assessment of the Traffic Management Advisor (TMA) conducted at the Denver Center and TRACON, January 11-February 5, 1993. The assessment addressed the effectiveness of TMA for supporting various traffic management activities. At the Center, traffic management coordinators (TMC's) shadowed traffic operations, using TMA to make metering time and internal release decisions. At the TRACON, TMC's accessed TMA in an advisory mode for different planning activities such as staffing, distributing the traffic load, and changing the airport acceptance rate. These different opportunities for assessing TMA provide insight into TMA as a potential communication aid and planning tool. Findings from this assessment indicate that TMA can be used to support traffic management planning and decisions. TMC's at the center were able to use information provided by TMA to determine metering times as well as internal release times. At the TRACON, TMA supported decisions on airport configuration, airport acceptance rate, load distribution, proactive coordination with the center, and staffing. While findings of TMA use are generally positive, it must be kept in mind that this assessment is a snapshot in time. Not all TMA capabilities were assessed, nor were TMC's fully trained and knowledgeable on all features. Feature use will continue to evolve and strategies emerge as the TMC's gain experience with TMA over a variety of traffic situations and their understanding of TMA capabilities broadens with continued training.

Harwood, Kelly↗

Uranyl fluorescence in acidic solution: quenching effects by tetramethylammonium (TMA + )

The quenching of uranyl luminescence by various cation species was studied in aqueous media at low pH. Solutions with different nitrate salts, held at constant uranyl nitrate, nitric acid, and ion concentration, were tested to examine the quenching effects of the cations from the nitrate salts. Alkali metal (Li + , Na + , Rb + ) and quaternary ammonium cations (NH 4 + ), (CH 3 ) 4 N + (TMA + ), (C 2 H 5 ) 4 N + (TEA + ) were investigated. Solutions containing TMA + reduced the lifetime of uranyl fluorescence significantly more than the other cations. Uranyl emission spectra also showed that TMA + increased the complex formation between uranyl and nitrate ions. Fluorescence decay lifetime measurements for most solutions yielded values between 1.4–1.9 μs at 20 °C, while 1.8 M TMA + reduced the lifetime of uranyl fluorescence to 0.6 μs. Decay rate versus concentration data (Stern–Volmer plots) indicated a dynamic quenching process with increasing fluorescence decay rates at higher cation concentrations for Li + , TMA + , and TEA + . The temperature dependencies of the decay rates and the kinetics in D 2 O were also examined.

Persinger, Thomas D. [Argonne National Laboratory ↗

The Challenges of Field Testing the Traffic Management Advisor (TMA) in an Operational Air Traffic Control Facility

The Traffic Management Advisor (TMA), the sequence and schedule tool of the Center/TRACON Automation System (CTAS), was evaluated at the Fort Worth Center (ZFW) in the summer of 1996. This paper describes the challenges encountered during the various phases of the TMA field evaluation, which included system (hardware and software) installation, personnel training, and data collection. Operational procedures were developed and applied to the evaluation process that would ensure air safety. The five weeks of field evaluation imposed minimal impact on the hosting facility and provided valuable engineering and human factors data. The collection of data was very much an opportunistic affair, due to dynamic traffic conditions. One measure of the success of the TMA evaluation is that, rather than remove TMA after the evaluation until it could be fully implemented, the prototype TMA is in continual use at ZFW as the fully operational version is readied for implementation.

Hoang, Ty↗

Literature Review of Thermomechanical Analysis (TMA)

A literature review of thermomechanical analysis (TMA) is presented. A basic introduction to TMA components, theory, and application is followed by an in-depth overview of TMA probes (expansion, penetration, tension, and flexure) and their uses. Sections for calibration and sample preparation are included as a guide for instrumentation usage. The literature review concludes with a section on modulated TMA and a summary of the instrument.

36 MATERIALS SCIENCE↗

Human Factors Report: TMA Operational Evaluations 1996 and 1998

The Traffic Management Advisor (TMA) is a component of the Center-TRACON Automation System (CTAS), a suite of decision-support tools for the air traffic control (ATC) environment which is being developed at NASA Ames Research Center. TMA has been operational at the ATC facilities in Dallas/Fort Worth, Texas, since an operational field evaluation in 1996. The Operational Evaluation demonstrated significant benefits, including an approximately 5 percent increase in airport capacity. This report describes the human factors results from the 1996 Operational Evaluation and an investigation of TMA usage performed two years later, during the 1998 TMA Daily Use Field Survey. The results described are instructive for CTAS focused development, and provide valuable lessons for future research in ATC decision-support tools where it is critical to merge a well-defined, complex work environment with advanced automation.

Lee, Katharine K.↗

User's manual for two dimensional FDTD version TEA and TMA codes for scattering from frequency-independent dielectic materials

The Penn State Finite Difference Time Domain Electromagnetic Scattering Code Versions TEA and TMA are two dimensional numerical electromagnetic scattering codes based upon the Finite Difference Time Domain Technique (FDTD) first proposed by Yee in 1966. The supplied version of the codes are two versions of our current two dimensional FDTD code set. This manual provides a description of the codes and corresponding results for the default scattering problem. The manual is organized into eleven sections: introduction, Version TEA and TMA code capabilities, a brief description of the default scattering geometry, a brief description of each subroutine, a description of the include files (TEACOM.FOR TMACOM.FOR), a section briefly discussing scattering width computations, a section discussing the scattering results, a sample problem set section, a new problem checklist, references and figure titles.

Beggs, John H.↗

User's manual for two dimensional FDTD version TEA and TMA codes for scattering from frequency-independent dielectric materials

The Penn State Finite Difference Time Domain Electromagnetic Scattering Code Versions TEA and TMA are two dimensional electromagnetic scattering codes based on the Finite Difference Time Domain Technique (FDTD) first proposed by Yee in 1966. The supplied version of the codes are two versions of our current FDTD code set. This manual provides a description of the codes and corresponding results for the default scattering problem. The manual is organized into eleven sections: introduction, Version TEA and TMA code capabilities, a brief description of the default scattering geometry, a brief description of each subroutine, a description of the include files (TEACOM.FOR TMACOM.FOR), a section briefly discussing scattering width computations, a section discussing the scattering results, a sample problem setup section, a new problem checklist, references, and figure titles.

Beggs, John H.↗

X-ray testing of the AXAF Technology Mirror Assembly (TMA) mirror

The X-ray performance of the Advanced X-ray Astrophysics Facility TMA in the 0.277-6.4-keV range. The precise figure and smooth surface originally specified (which were expected from the in-process optical and mechanical measurements) are verified. The paper primarily describes the test equipment and methods used and gives examples of the detailed on-axis and off-axis data.

Schwartz, D. A.↗

Correspondence between AXAF TMA X-ray performance and models based upon mechanical and visible light measurements

The AXAF Technology Mirror Assembly (TMA) was characterized prior to X-ray testing by properties measured mechanically or with visible light; these include alignment offsets, roundness and global-axial-slope errors, axial-figure errors with characteristic lengths greater than about five mm, and surface roughness with scale lengths between about 0.005 and 0.5 mm. The X-ray data of Schwartz et al. (1985) are compared with predictions based upon the mechanical and visible light measurements.

Van Speybroeck, L.↗

The Effects of the Uncertainty of Departures on Multi-Center Traffic Management Advisor (TMA) Scheduling

The Multi-center Traffic Management Advisor (McTMA) provides a platform for regional or national traffic flow management, by allowing long-range cooperative time-based metering to constrained resources, such as airports or air traffic control center boundaries. Part of the demand for resources is made up of proposed departures, whose actual departure time is difficult to predict. For this reason, McTMA does not schedule the departures in advance, but rather relies on traffic managers to input their requested departure time. Because this happens only a short while before the aircraft's actual departure, McTMA is unable to accurately predict the amount of delay airborne aircraft will need to take in order to accommodate the departures. The proportion of demand which is made up by such proposed departures increases as the horizon over which metering occurs gets larger. This study provides an initial analysis of the severity of this problem in a 400-500 nautical mile metering horizon and discusses potential solutions to accommodate these departures. The challenge is to smoothly incorporate departures with the airborne stream while not excessively delaying the departures.' In particular, three solutions are reviewed: (1) scheduling the departures at their proposed departure time; (2) not scheduling the departures in advance; and (3) scheduling the departures at some time in the future based on an estimated error in their proposed time. The first solution is to have McTMA to automatically schedule the departures at their proposed departure times. Since the proposed departure times are indicated in their flight times in advance, this method is the simplest, but studies have shown that these proposed times are often incorrect2 The second option is the current practice, which avoids these inaccuracies by only scheduling aircraft when a confirmed prediction of departure time is obtained from the tower of the departure airport. Lastly, McTMA can schedule the departures at a predicted departure time based on statistical data of past departure time performance. It has been found that departures usually have a wheels-up time after their indicated proposed departure time, as shown in Figure 1. Hence, the departures were scheduled at a time in the future based on the mean error in proposed departure times for their airport.

Thipphavong, Jane↗

Non-invasive Optical End-to-End Test of a Large TMA Telescope (JWST) from the Intermediate Focus

The James Webb Space Telescope (JWST) requires testing of the full optical system in a cryogenic vacuum environment before launch. Challenges with the telescope architecture and the test environment lead to placing removable optical test sources at the Cassegrain intermediate focus of the Telescope. The Science Instrument suite will be used to align the telescope and to verify the wavefront error. The Science Instruments capture test images that are analyzed using focus diverse phase retrieval. The wavefront sensing algorithms have the large dynamic range required to measure the relatively small wavefronts of interest in the presence of the large aberrations resulting from the off-axis source locations at the intermediate focus. These inherent aberrations of the off-axis design are removed analytically from the measured data. The test design and in-situ wavefront sensing process enables a number of tests to verify the alignment and optical quality of the system.

Whitman, Tony↗

A Novel Application of TMA to Converging Runway Operations in a Simulated NextGen Environment

In 2013, the Airspace Operations Laboratory at NASA Ames Research Center conducted a human-in-the-loop simulation that examined the feasibility of applying a number of Next Generation Air Transportation System (NextGen) solutions to complex arrival operations in and around the New York metroplex. The delivery of arrivals to Newark Liberty International Airport (EWR) was the focus of this simulation, which involved extending the Terminal Sequencing and Spacing (TSS) scheduling capability to precisely schedule arrivals to intersecting runways 22 Left and 11. An important enabler for the concept was the availability of a dependent runway scheduler that was able to coordinate arrival times between aircraft landing on intersecting runways. At the time of the study, there was no functionality within the TSS scheduler to automatically create the dependent runway schedules. Instead, a Traffic Management Coordinator (TMC) manually created a de-conflicted schedule, which allowed for the concept to be tested as well as provided valuable insight into the tool requirements for a dependent runway scheduler. Throughout the course of preparations for the simulation, the individual serving as the TMC developed a number of strategies and procedures for manually adjusting the Scheduled Time of Arrival (STA) of the EWR arrivals in order to ensure that adequate spacing was provided between runway 22L and 11 arrival pairs. This paper describes the strategies and procedures that were developed and details how they were successfully applied during the simulation. Results will also be presented that shed additional light on exactly how the schedules were manipulated and their impact on delivery performance and safety. Ideas for additional TSS enhancements and next steps, based on participant feedback, will also be presented.

Homola, Jeffrey↗

Analyzing Double Delays at Newark Liberty International Airport (EWR)

When weather or congestion impacts the National Airspace System, multiple different Traffic Management Initiatives can be implemented, sometimes with unintended consequences. One particular perceived inequity that is commonly identified is in the interaction between Ground Delay Programs (GDPs) and time based scheduling of internal departures by the Traffic Management Advisor (TMA) (now operationally superseded by the FAA's the Time-Based Flow Management system). Internal departures under TMA scheduling can take large GDP delays, followed by large TMA scheduling delays, because they cannot easily fit into the arrival flow at the runway. In this paper we examine the causes of these double delays through an analysis of arrival operations at Newark Liberty International Airport (EWR) from June to August 2010. TMA scheduling delays are found to be generally higher than TMA airborne metering delays, regardless of prior GDP delays. Depending on how the double delay is defined, between 42 and 62 of all internal departures in GDP and TMA scheduling experienced double delays in this period. A deep dive into the data reveals that contributors to double delays include upstream flights departing before their Expect Departure Clearance Times (EDCTs); differences in the rates used for setting EDCTs and TMA Scheduled Times of Arrival; differences in the arrival demand expected based on EDCTs and the arrival demand entering TMA; and shorter en route times between takeoff and entry into TMA than assumed in the calculation of flight EDCTs, all of which undermine the sequencing and spacing underlying flight EDCTs. Double delays are also found to coincide with periods in which the virtual runway arrival queue being served by a TMA is large, there are periods of high demand relative to capacity, and there are high airborne metering delays. Data mining techniques are used to confirm that each of these factors contribute to the occurrence of double delay andor high internal departure scheduling delay across three months of data from June to August 2010. Predictors of the occurrence of double delay and high TMA scheduling delay are built using logistic regression, providing prediction accuracies of 69 and 73, respectively.

traffic flow management↗

Thiohalorhabdus methylotropha sp. nov., an extremely halophilic autotrophic methylotiotroph from hypersaline lakes

So far, there have been no reports of trimethylamine (TMA)-utilizing extremely halophilic microorganisms in hypersaline habitats. Our aerobic enrichments at 4 M total Na + with 5 mM TMA inoculated with surface sediments from hypersaline soda (at pH 9.5) or chloride-sulfate (at pH 7) lakes in southwestern Siberia were successful only for the latter. The initial enrichment included both bacteria and haloarchaea but only the bacterial component was able to grow as a pure culture with TMA. Strain Cl-TMA forms a new-species lineage within the genus Thiohalorhabdus which includes extremely halophilic and obligate lithoautotrophic sulfur-oxidizing gammaproteobacteria. Cl-TMA can grow methyloautotrophically utilizing TMA, dimethylamine (DMA) and methanol (MeOH) as the electron donors or chemolithoautotrophically with thiosulfate. Mixotrophic growth was also observed with the three methyl compounds and thiosulfate. Carbon is assimilated autotrophically via the Calvin-Benson-Basham pathway. Unlike the type species of Thiohalorhabdus, T. denitrificans , Cl-TMA was incapable of anaerobic growth via denitrification. The isolate belongs to extreme halophiles growing between 2.5 and 5 M NaCl with an optimum at 3–3.5 M. Genome analysis identified two gene clusters coding for PQQ-dependent methanol dehydrogenases (MxaFI and XoxF), four homologues of the formaldehyde activating enzymes (Faes), a TMA/DMA oxidation locus, and two cluster of genes encoding an N-methylglutamate dehydrogenase pathway (NMGP) for methylamine oxidation. The first steps of C 1 -subtrate conversions are followed by the tetrahydrofolate (THF)-linked and tetrahydromethanopterin (H4MPT)-linked formaldehyde oxidation pathways and two formate dehydrogenases. All of those signatures of methylotrophy were absent in T. denitrificans . In contrast, genes for two key sulfur oxidation enzymes, thiosulfate dehydrogenase TsdAB and sulfide dehydrogenase FccAB, that are present in the type species are missing in Cl-TMA. Thiosulfate is oxidized to sulfate by a combination of an incomplete Sox cycle and an sHdr system. Strain Cl-TMA T (JCM 35977 = UQM 41915) is proposed to be classified as Thiohalorhabdus methylotrophus sp. nov.

59 BASIC BIOLOGICAL SCIENCES↗

Analyzing Double Delays at Newark Liberty International Airport

When weather or congestion impacts the National Airspace System, multiple different Traffic Management Initiatives can be implemented, sometimes with unintended consequences. One particular inefficiency that is commonly identified is in the interaction between Ground Delay Programs (GDPs) and time based metering of internal departures, or TMA scheduling. Internal departures under TMA scheduling can take large GDP delays, followed by large TMA scheduling delays, because they cannot be easily fitted into the overhead stream. In this paper we examine the causes of these double delays through an analysis of arrival operations at Newark Liberty International Airport (EWR) from June to August 2010. Depending on how the double delay is defined between 0.3 percent and 0.8 percent of arrivals at EWR experienced double delays in this period. However, this represents between 21 percent and 62 percent of all internal departures in GDP and TMA scheduling. A deep dive into the data reveals that two causes of high internal departure scheduling delays are upstream flights making up time between their estimated departure clearance times (EDCTs) and entry into time based metering, which undermines the sequencing and spacing underlying the flight EDCTs, and high demand on TMA, when TMA airborne metering delays are high. Data mining methods (currently) including logistic regression, support vector machines and K-nearest neighbors are used to predict the occurrence of double delays and high internal departure scheduling delays with accuracies up to 0.68. So far, key indicators of double delay and high internal departure scheduling delay are TMA virtual runway queue size, and the degree to which estimated runway demand based on TMA estimated times of arrival has changed relative to the estimated runway demand based on EDCTs. However, more analysis is needed to confirm this.

traffic management advisor↗