287 research outputs found
STOL terminal area operating systems (aircraft and onboard avionics, ATC, navigation aids)
Operational procedures and systems onboard the STOL aircraft which are required to enable the aircraft to perform acceptably in restricted airspace in all types of atmospheric conditions and weather are discussed. Results of simulation and flight investigations to establish operational criteria are presented
Knowledge-based scheduling of arrival aircraft
A knowledge-based method for scheduling arrival aircraft in the terminal area has been implemented and tested in real-time simulation. The scheduling system automatically sequences, assigns landing times, and assigns runways to arrival aircraft by utilizing continuous updates of aircraft radar data and controller inputs. The scheduling algorithms is driven by a knowledge base which was obtained in over two thousand hours of controller-in-the-loop real-time simulation. The knowledge base contains a series of hierarchical 'rules' and decision logic that examines both performance criteria, such as delay reduction, as well as workload reduction criteria, such as conflict avoidance. The objective of the algorithms is to devise an efficient plan to land the aircraft in a manner acceptable to the air traffic controllers. This paper will describe the scheduling algorithms, give examples of their use, and present data regarding their potential benefits to the air traffic system
Airline arrival prioritization in sequencing and scheduling
phone: (650) 604-2545/ fax: (650) 604-0174/ email: [email protected] Abstract The basic objective of arrival sequencing and scheduling in air traffic control automation is t o match traffic demand and airport capacity while minimizing delays. The principle underlying practical sequencing and scheduling algorithms currently in use is referred to as first-come-firstserved (FCFS). While this principle generates fair schedules when delays must be absorbed, it does not take into account airline priorities among individual flights. The development of new scheduling techniques which consider priorities expressed by air carriers will further reduce the economic impact of air traffic management (ATM) restrictions on the airlines. This will also lead to increased airline economic efficiency by allowing airlines to have greater control over their individual arrival banks of aircraft. NASA is exploring the possibility of allowing airlines t o express relative arrival priorities to ATM through the development of new sequencing and scheduling algorithms which take into account airline preferences. This paper introduces a method of scheduling a bank of arrival aircraft according to a preferred order of arrival instead of according t o an FCFS sequence based on estimated time of arrival at the runway. Fast-time simulation is used to evaluate the feasibility of this scheduling method. Results show that when compared with FCFS scheduling, the alternative scheduling method is often successful in reducing deviations from the preferred bank arrival order while causing little or no increase in scheduled delays
Selecting and implementing overview methods: implications from five exemplar overviews
This is the final version of the article. Available from BioMed Central via the DOI in this record.Background
Overviews of systematic reviews are an increasingly popular method of evidence synthesis; there is a lack of clear guidance for completing overviews and a number of methodological challenges. At the UK Cochrane Symposium 2016, methodological challenges of five overviews were explored. Using data from these five overviews, practical implications to support methodological decision making of authors writing protocols for future overviews are proposed.
Methods
Methods, and their justification, from the five exemplar overviews were tabulated and compared with areas of debate identified within current literature. Key methodological challenges and implications for development of overview protocols were generated and synthesised into a list, discussed and refined until there was consensus.
Results
Methodological features of three Cochrane overviews, one overview of diagnostic test accuracy and one mixed methods overview have been summarised. Methods of selection of reviews and data extraction were similar. Either the AMSTAR or ROBIS tool was used to assess quality of included reviews. The GRADE approach was most commonly used to assess quality of evidence within the reviews.
Eight key methodological challenges were identified from the exemplar overviews. There was good agreement between our findings and emerging areas of debate within a recent published synthesis. Implications for development of protocols for future overviews were identified.
Conclusions
Overviews are a relatively new methodological innovation, and there are currently substantial variations in the methodological approaches used within different overviews. There are considerable methodological challenges for which optimal solutions are not necessarily yet known. Lessons learnt from five exemplar overviews highlight a number of methodological decisions which may be beneficial to consider during the development of an overview protocol.The overview conducted by Pollock [19] was supported by a project grant from the Chief Scientist Office of the Scottish Government. The overview conducted by McClurg [21] was supported by a project grant by the Physiotherapy Research Foundation. The overview by Hunt [22] was supported as part of doctoral programme funding by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care South West Peninsula (PenCLAHRC). The overview conducted by Estcourt [20] was supported by an NIHR Cochrane Programme Grant for the Safe and Appropriate Use of Blood Components. The overview conducted by Brunton [23] was commissioned by the Department of Health as part of an ongoing programme of work on health policy research synthesis.
Alex Pollock is employed by the Nursing, Midwifery and Allied Health Professions (NMAHP) Research Unit, which is supported by the Chief Scientist Office of the Scottish Government. Pauline Campbell is supported by the Chief Nurses Office of the Scottish Government
The role of the conserved phenylalanine in the σ54-interacting GAFTGA motif of bacterial enhancer binding proteins
σ54-dependent transcription requires activation by bacterial enhancer binding proteins (bEBPs). bEBPs are members of the AAA+ (ATPases associated with various cellular activities) protein family and typically form hexameric structures that are crucial for their ATPase activity. The precise mechanism by which the energy derived from ATP hydrolysis is coupled to biological output has several unknowns. Here we use Escherichia coli PspF, a model bEBP involved in the transcription of stress response genes (psp operon), to study determinants of its contact features with the closed promoter complex. We demonstrate that substitution of a highly conserved phenylalanine (F85) residue within the L1 loop GAFTGA motif affects (i) the ATP hydrolysis rate of PspF, demonstrating the link between L1 and the nucleotide binding pocket; (ii) the internal organization of the hexameric ring; and (iii) σ54 interactions. Importantly, we provide evidence for a close relationship between F85 and the −12 DNA fork junction structure, which may contribute to key interactions during the energy coupling step and the subsequent remodelling of the Eσ54 closed complex. The functionality of F85 is distinct from that of other GAFTGA residues, especially T86 where in contrast to F85 a clean uncoupling phenotype is observed
Structural basis of nucleosome assembly by the Abo1 AAA+ ATPase histone chaperone
The fundamental unit of chromatin, the nucleosome, is an intricate structure that requires histone chaperones for assembly. ATAD2 AAA+???ATPases are a family of histone chaperones that regulate nucleosome density and chromatin dynamics. Here, we demonstrate that the fission yeast ATAD2 homolog, Abo1, deposits histone H3???H4 onto DNA in an ATP-hydrolysis-dependent manner by in vitro reconstitution and single-tethered DNA curtain assays. We present cryo-EM structures of an ATAD2 family ATPase to atomic resolution in three different nucleotide states, revealing unique structural features required for histone loading on DNA, and directly visualize the transitions of Abo1 from an asymmetric spiral (ATP-state) to a symmetric ring (ADP- and apo-states) using high-speed atomic force microscopy (HS-AFM). Furthermore, we find that the acidic pore of ATP-Abo1 binds a peptide substrate which is suggestive of a histone tail. Based on these results, we propose a model whereby Abo1 facilitates H3???H4 loading by utilizing ATP
Molecular Landscape of the Ribosome Pre-initiation Complex during mRNA Scanning: Structural Role for eIF3c and Its Control by eIF5
Citation: Obayashi, E., Luna, R. E., Nagata, T., Martin-Marcos, P., Hiraishi, H., Singh, C. R., . . . Asano, K. (2017). Molecular Landscape of the Ribosome Pre-initiation Complex during mRNA Scanning: Structural Role for eIF3c and Its Control by eIF5. Cell Reports, 18(11), 2651-2663. doi:10.1016/j.celrep.2017.02.052During eukaryotic translation initiation, eIF3 binds the solvent-accessible side of the 40S ribosome and recruits the gate-keeper protein eIF1 and eIF5 to the decoding center. This is largely mediated by the N-terminal domain (NTD) of eIF3c, which can be divided into three parts: 3c0, 3c1, and 3c2. The N-terminal part, 3c0, binds eIF5 strongly but only weakly to the ribosome-binding surface of eIF1, whereas 3c1 and 3c2 form a stoichiometric complex with eIF1. 3c1 contacts eIF1 through Arg-53 and Leu-96, while 3c2 faces 40S protein uS15/S13, to anchor eIF1 to the scanning pre-initiation complex (PIC). We propose that the 3c0:eIF1 interaction diminishes eIF1 binding to the 40S, whereas 3c0:eIF5 interaction stabilizes the scanning PIC by precluding this inhibitory interaction. Upon start codon recognition, interactions involving eIF5, and ultimately 3c0:eIF1 association, facilitate eIF1 release. Our results reveal intricate molecular interactions within the PIC, programmed for rapid scanning-arrest at the start codon
False discovery rate estimation and heterobifunctional cross-linkers
<div><p>False discovery rate (FDR) estimation is a cornerstone of proteomics that has recently been adapted to cross-linking/mass spectrometry. Here we demonstrate that heterobifunctional cross-linkers, while theoretically different from homobifunctional cross-linkers, need not be considered separately in practice. We develop and then evaluate the impact of applying a correct FDR formula for use of heterobifunctional cross-linkers and conclude that there are minimal practical advantages. Hence a single formula can be applied to data generated from the many different non-cleavable cross-linkers.</p></div
Association of the Chromosome Replication Initiator DnaA with the Escherichia coli Inner Membrane In Vivo: Quantity and Mode of Binding
DnaA initiates chromosome replication in most known bacteria and its activity is controlled so that this event occurs only once every cell division cycle. ATP in the active ATP-DnaA is hydrolyzed after initiation and the resulting ADP is replaced with ATP on the verge of the next initiation. Two putative recycling mechanisms depend on the binding of DnaA either to the membrane or to specific chromosomal sites, promoting nucleotide dissociation. While there is no doubt that DnaA interacts with artificial membranes in vitro, it is still controversial as to whether it binds the cytoplasmic membrane in vivo. In this work we looked for DnaA-membrane interaction in E. coli cells by employing cell fractionation with both native and fluorescent DnaA hybrids. We show that about 10% of cellular DnaA is reproducibly membrane-associated. This small fraction might be physiologically significant and represent the free DnaA available for initiation, rather than the vast majority bound to the datA reservoir. Using the combination of mCherry with a variety of DnaA fragments, we demonstrate that the membrane binding function is delocalized on the surface of the protein’s domain III, rather than confined to a particular sequence. We propose a new binding-bending mechanism to explain the membrane-induced nucleotide release from DnaA. This mechanism would be fundamental to the initiation of replication
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