Efficiency in European Air Traffic Management -- A Fundamental Analysis of Data, Models, and Methods

We systematically study cornerstones that must be solved to define an air traffic control benchmarking system based on a Data Envelopment Analysis. Primarily, we examine the appropriate decision-making units, what to consider and what to avoid when choosing inputs and outputs in the case that several countries are included, and how we can identify and deal with outliers, like the Maastricht Service Provider. We argue that Air Navigation Service Providers would be a good choice of decision units within the European context. Based on that, we discuss candidates for DEA inputs and outputs and emphasize that monetary values should be excluded. We, further suggest to use super-efficiency DEA for eliminating outliers. In this context, we compare different DEA approaches and find that standard DEA is performing well.Comment: 14 Pages, to be published in JAT

Analysis of Cost-Effectiveness in the Provision of Air Navigation Services at Functional Air Blocks

The Single European Sky (SES) legislation is intended to have a major impact on the fragmentation in the European Air Traffic Management and Communications, Navigation and Surveillance (ATM/ CNS) system. A fundamental aspect of the SES initiative is functional airspace blocks (FABs), which have the goal of reducing the inefficiencies—in terms of safety, capacity, and cost—that result from the fragmentation of European airspace. FABs are seen as an explicit bottom-up first step toward the ultimate integration of European airspace. In this article, we focus on the analysis of the evolution of the cost-effectiveness in the provision of ATM/CNS services at FABs. We proceed in two stages. First, we develop a theoretical framework that allows us to decompose the change in cost-effectiveness of FABs into its basic sources. Second, we use stochastic frontier analysis techniques to estimate the cost equations and decompose the change in the cost-effectiveness of the nine European FABs into several components. Our analysis sheds light on (1) the drivers of changes in the air navigation service providers (ANSPs) and FABs cost-effectiveness from 2006 to 2016, (2) the role that FABs play in enhancing cooperation between ANSPs to obtain operational efficiency gains, and (3) the existence of economies of scale in the European ATM/CNS service provision

Crystal structure of rhodopsin in complex with a mini-G_o sheds light on the principles of G protein selectivity

Selective coupling of G protein (heterotrimeric guanine nucleotide–binding protein)–coupled receptors (GPCRs) to specific Gα-protein subtypes is critical to transform extracellular signals, carried by natural ligands and clinical drugs, into cellular responses. At the center of this transduction event lies the formation of a signaling complex between the receptor and G protein. We report the crystal structure of light-sensitive GPCR rhodopsin bound to an engineered mini-Go protein. The conformation of the receptor is identical to all previous structures of active rhodopsin, including the complex with arrestin. Thus, rhodopsin seems to adopt predominantly one thermodynamically stable active conformation, effectively acting like a “structural switch,” allowing for maximum efficiency in the visual system. Furthermore, our analysis of the well-defined GPCR–G protein interface suggests that the precise position of the carboxyl-terminal “hook-like” element of the G protein (its four last residues) relative to the TM7/helix 8 (H8) joint of the receptor is a significant determinant in selective G protein activation

Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser.

G-protein-coupled receptors (GPCRs) signal primarily through G proteins or arrestins. Arrestin binding to GPCRs blocks G protein interaction and redirects signalling to numerous G-protein-independent pathways. Here we report the crystal structure of a constitutively active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin, determined by serial femtosecond X-ray laser crystallography. Together with extensive biochemical and mutagenesis data, the structure reveals an overall architecture of the rhodopsin-arrestin assembly in which rhodopsin uses distinct structural elements, including transmembrane helix 7 and helix 8, to recruit arrestin. Correspondingly, arrestin adopts the pre-activated conformation, with a ∼20° rotation between the amino and carboxy domains, which opens up a cleft in arrestin to accommodate a short helix formed by the second intracellular loop of rhodopsin. This structure provides a basis for understanding GPCR-mediated arrestin-biased signalling and demonstrates the power of X-ray lasers for advancing the frontiers of structural biology

Ultrafast structural changes direct the first molecular events of vision

視覚に関わるタンパク質の超高速分子動画 --薄暗いところで光を感じる仕組み--. 京都大学プレスリリース. 2023-03-23.Vision is initiated by the rhodopsin family of light-sensitive G protein-coupled receptors (GPCRs). A photon is absorbed by the 11-cis retinal chromophore of rhodopsin, which isomerizes within 200 femtoseconds to the all-trans conformation, thereby initiating the cellular signal transduction processes that ultimately lead to vision. However, the intramolecular mechanism by which the photoactivated retinal induces the activation events inside rhodopsin remains experimentally unclear. Here we use ultrafast time-resolved crystallography at room temperature to determine how an isomerized twisted all-trans retinal stores the photon energy that is required to initiate the protein conformational changes associated with the formation of the G protein-binding signalling state. The distorted retinal at a 1-ps time delay after photoactivation has pulled away from half of its numerous interactions with its binding pocket, and the excess of the photon energy is released through an anisotropic protein breathing motion in the direction of the extracellular space. Notably, the very early structural motions in the protein side chains of rhodopsin appear in regions that are involved in later stages of the conserved class A GPCR activation mechanism. Our study sheds light on the earliest stages of vision in vertebrates and points to fundamental aspects of the molecular mechanisms of agonist-mediated GPCR activation

Structure of the human κ-opioid receptor in complex with JDTic

Opioid receptors mediate the actions of endogenous and exogenous opioids on many physiological processes, including the regulation of pain, respiratory drive, mood, and—in the case of κ-opioid receptor (κ-OR)—dysphoria and psychotomimesis. Here we report the crystal structure of the human κ-OR in complex with the selective antagonist JDTic, arranged in parallel dimers, at 2.9 Å resolution. The structure reveals important features of the ligand-binding pocket that contribute to the high affinity and subtype selectivity of JDTic for the human κ-OR. Modelling of other important κ-OR-selective ligands, including the morphinan-derived antagonists norbinaltorphimine and 5′-guanidinonaltrindole, and the diterpene agonist salvinorin A analogue RB-64, reveals both common and distinct features for binding these diverse chemotypes. Analysis of site-directed mutagenesis and ligand structure–activity relationships confirms the interactions observed in the crystal structure, thereby providing a molecular explanation for κ-OR subtype selectivity, and essential insights for the design of compounds with new pharmacological properties targeting the human κ-OR

Estimating the Volatility of Flights and Risk of Saturation of Airspaces in the European Core Area: A Methodological Proposal

Despite having some fluctuations and the impact of the COVID-19 crisis, the demand for flights had a general growing trend for the past years. As the airspace is limited, efforts to better manage the total number of flights are noteworthy. In addition, volatility (i.e., unpredicted changes) in the number of flights has been observed to be increasing. Efforts to improve flight forecasting are thus necessary to improve air traffic efficiency and reduce costs. In this study, volatility in the number of flights is estimated based on past trends, and the outcomes are used to project future levels. This enables risk situations such as having to manage unexpectedly high numbers of flights to be predicted. The methodological approach analyses the Functional Airspace Block of Central Europe (FABEC). Based on the number of flights for 2015–2019, the following are calculated: historic mean, variance, volatility, 95th percentile, flights per hour and flights per day of the week in different time zones in six countries. Due to the nature of air traffic and the overdispersion observed, this study uses counting data models such as negative binomial regressions. This makes it possible to calculate risk measures including expected shortfall (ES) and value at risk (VaR), showing for each hour that the number of flights can exceed planned levels by a certain number. The study finds that in Germany and Belgium at 13:00 h there is a 5% worst-case possibility of having averages of 683 and 246 flights, respectively. The method proposed is useful for planning under uncertainties. It is conducive to efficient airspace management, so risk indicators help Air Navigation Service Providers (ANSPs) to plan for low-probability situations in which there may be large numbers of flights