Conformance Monitoring Approaches in Current and Future Air Traffic Control Environments

Conformance monitoring is a core task in Air Traffic Control (ATC) operations to determine whether aircraft are adhering to assigned trajectories. This is important for many reasons, including to ensure that tactical collision avoidance maneuvers are properly executed; strategic conflict detection & resolution schemes are valid and security around sensitive locations is maintained. In today’s ATC environment, controllers monitor for conformance via radar systems that primarily provide positional information. As a result, non-conformance criteria are generally based on positional deviations from the assigned trajectory [1] or penetration of restricted airspace such as the No Transgression Zone (NTZ) on PRM approaches [2]. Future ATC surveillance systems such as Automatic Dependant Surveillance (ADS) should provide access to additional aircraft state information which could be used for more effective conformance monitoring. However, at present there is a lack of clear rationale for which states should be surveilled and how they would be used to enable conformance monitoring to be performed at a level appropriate for future operational requirements. This paper describes a framework for this purpose that poses the conformance monitoring task as a model-based fault detection problem.This work was supported by NASA Langley Research Center under grant NAG1-02006

MicroRNA-330-5p as a putative modulator of neoadjuvant chemoradiotherapy sensitivity in oesophageal adenocarcinoma

Oesophageal adenocarcinoma (OAC) is the sixth most common cause of cancer deaths worldwide, and the 5-year survival rate for patients diagnosed with the disease is approximately 17%. The standard of care for locally advanced disease is neoadjuvant chemotherapy or, more commonly, combined neoadjuvant chemoradiation therapy (neo-CRT) prior to surgery. Unfortunately, ~60-70% of patients will fail to respond to neo-CRT. Therefore, the identification of biomarkers indicative of patient response to treatment has significant clinical implications in the stratification of patient treatment. Furthermore, understanding the molecular mechanisms underpinning tumour response and resistance to neo-CRT will contribute towards the identification of novel therapeutic targets for enhancing OAC sensitivity to CRT. MicroRNAs (miRNA/miR) function to regulate gene and protein expression and play a causal role in cancer development and progression. MiRNAs have also been identified as modulators of key cellular pathways associated with resistance to CRT. Here, to identify miRNAs associated with resistance to CRT, pre-treatment diagnostic biopsy specimens from patients with OAC were analysed using miRNA-profiling arrays. In pre-treatment biopsies miR-330-5p was the most downregulated miRNA in patients who subsequently failed to respond to neo-CRT. The role of miR-330 as a potential modulator of tumour response and sensitivity to CRT in OAC was further investigated in vitro. Through vector-based overexpression the E2F1/p-AKT survival pathway, as previously described, was confirmed as a target of miR-330 regulation. However, miR-330-mediated alterations to the E2F1/p-AKT pathway were insufficient to significantly alter cellular sensitivity to chemotherapy (cisplatin and 5-flurouracil). In contrast, silencing of miR-330-5p enhanced, albeit subtly, cellular resistance to clinically relevant doses of radiation. This study highlights the need for further investigation into the potential of miR-330-5p as a predictive biomarker of patient sensitivity to neo-CRT and as a novel therapeutic target for manipulating cellular sensitivity to neo-CRT in patients with OAC

General Relativistic Simulations of Magnetized Plasmas around Merging Supermassive Black Holes

Coalescing supermassive black hole binaries are produced by the mergers of galaxies and are the most powerful sources of gravitational waves accessible to space-based gravitational observatories. Some such mergers may occur in the presence of matter and magnetic fields and hence generate an electromagnetic counterpart. In this Letter, we present the first general relativistic simulations of magnetized plasma around merging supermassive black holes using the general relativistic magnetohydrodynamic code Whisky. By considering different magnetic field strengths, going from non-magnetically dominated to magnetically dominated regimes, we explore how magnetic fields affect the dynamics of the plasma and the possible emission of electromagnetic signals. In particular we observe a total amplification of the magnetic field of ~2 orders of magnitude which is driven by the accretion onto the binary and that leads to much stronger electromagnetic signals, more than a factor of 10^4 larger than comparable calculations done in the force-free regime where such amplifications are not possible.Comment: 7 pages, 5 figures. Minor changes to match version accepted for publication on The Astrophysical Journal Letter

Air Carrier Flight Operations

Most air carriers operate under a system of prioritized goals including safety, customer service (on-time departures and arrivals) and operating economics. The flight operations department is responsible for the safe and efficient movement of passengers and/or cargo which ultimately generate the revenue for the airline. The major components needing to be coordinated for any given flight include the aircraft and support equipment, cockpit and cabin crews (together known as the “flight crew”), maintenance, and ground service personnel. Although the maintenance and ground crew activities are critical to support flight operations, the emphasis in this document is on the regulation and scheduling of the flight crews to conduct a given flight, followed by a detailed discussion of the activities of flight crews during the phases of a typical revenue flight sequence. Note that this chapter does not attempt to address detailed airmanship and flight maneuvering topics and only includes such information in the context of the overall flight operation. However, specific flight procedures that may have a direct impact on the operational goals are included to aid in understanding the nature and complexity of the factors involved

An Anthropometric Study of 38 Individuals With Prader-Labhart- Willi Syndrome

Weight, height, sitting height, and 24 other anthropometric variables (5 body circumferences, skinfolds at 7 sites, 4 head dimensions, and 8 hand and foot measurements) were obtained on 38 Prader-Labhart-Willi syndrome (PLWS) individuals (21 with apparent chromosome 15 deletions and 17 nondeletion cases) with an age range of 2 weeks to 38½ years. More than half of these individuals were measured on more than one occasion. The measurements confirmed the presence of short stature, small hands and feet, obesity, and narrow bi-frontal diameter in PLWS. No differences were found for the anthropometric measurements between the 2 chromosome subgroups. Inverse correlations were produced with linear measurements (eg, height, hand and foot lengths) and age, which indicated a deceleration of linear growth relative to normal individuals with increasing age

Altered mitochondrial function and energy metabolism is associated with a radioresistant phenotype in oesophageal adenocarcinoma

Neoadjuvant chemoradiation therapy (CRT) is increasingly the standard of care for locally advanced oesophageal cancer. A complete pathological response to CRT is associated with a favourable outcome. Radiation therapy is important for local tumour control, however, radioresistance remains a substantial clinical problem. We hypothesise that alterations in mitochondrial function and energy metabolism are involved in the radioresistance of oesophageal adenocarcinoma (OAC). To investigate this, we used an established isogenic cell line model of radioresistant OAC. Radioresistant cells (OE33 R) demonstrated significantly increased levels of random mitochondrial mutations, which were coupled with alterations in mitochondrial function, size, morphology and gene expression, supporting a role for mitochondrial dysfunction in the radioresistance of this model. OE33 R cells also demonstrated altered bioenergetics, demonstrating significantly increased intracellular ATP levels, which was attributed to enhanced mitochondrial respiration. Radioresistant cells also demonstrated metabolic plasticity, efficiently switching between the glycolysis and oxidative phosphorylation energy metabolism pathways, which were accompanied by enhanced clonogenic survival. This data was supported in vivo, in pre-treatment OAC tumour tissue. Tumour ATP5B expression, a marker of oxidative phosphorylation, was significantly increased in patients who subsequently had a poor pathological response to neoadjuvant CRT. This suggests for the first time, a role for specific mitochondrial alterations and metabolic remodelling in the radioresistance of OAC

Observations of X-rays and Thermal Dust Emission from the Supernova Remnant Kes 75

We present Spitzer Space Telescope and Chandra X-ray Observatory observations of the composite Galactic supernova remnant Kes 75 (G29.7-0.3). We use the detected flux at 24 microns and hot gas parameters from fitting spectra from new, deep X-ray observations to constrain models of dust emission, obtaining a dust-to-gas mass ratio M_dust/M_gas ~0.001. We find that a two-component thermal model, nominally representing shocked swept-up interstellar or circumstellar material and reverse-shocked ejecta, adequately fits the X-ray spectrum, albeit with somewhat high implied densities for both components. We surmise that this model implies a Wolf-Rayet progenitor for the remnant. We also present infrared flux upper limits for the central pulsar wind nebula.Comment: 7 pages, 2 tables, 4 figures, uses emulateapj. Accepted for publication in Ap

Identifying a Novel Role for Fractalkine (CX3CL1) in Memory CD8(+) T Cell Accumulation in the Omentum of Obesity-Associated Cancer Patients

The omentum is enriched with pro-inflammatory effector memory CD8+ T cells in patients with the obesity-associated malignancy, esophagogastric adenocarcinoma (EAC) and we have identified the chemokine macrophage inflammatory protein-1alpha as a key player in their active migration to this inflamed tissue. More recently, others have established that subsets of memory CD8+ T cells can be classified based on their surface expression of CX3CR1; the specific receptor for the inflammatory chemokine fractalkine. CD8+ T cells expressing intermediate levels (CX3CR1INT) are defined as peripheral memory, those expressing the highest levels (CX3CR1HI) are effector memory/terminally differentiated and those lacking CX3CR1 (CX3CR1NEG) are classified as central memory. To date, the fractalkine:CX3CR1 axis has not been examined in the context of CD8+ T cell enrichment in the omentum and here we examine this chemokines involvement in the accumulation of memory CD8+ T cells in the omentum of EAC patients. Our data show that fractalkine is significantly enriched in the omentum of EAC patients and drives migration of T cells derived from EAC patient blood. Furthermore, CX3CR1 is endocytosed specifically by CD8+ T cells upon encountering fractalkine, which is consistent with the significantly diminished frequencies of CX3CR1INT and CX3CR1HI CD8+ T cells in the fractalkine-rich environment of omentum in EAC, relative to matched blood. Fractalkine-mediated endocytosis of CX3CR1 by CD8+ T cells is sustained and is followed by enhanced surface expression of L-selectin (CD62L). These novel data align with our findings that circulating CX3CR1NEG CD8+ T cells express higher levels of L-selectin than CX3CR1INT CD8+ T cells. This is consistent with previous reports and implicates fractalkine in the conversion of CX3CR1INT CD8+ T cells to a CX3CR1NEG phenotype characterized by alterations in the migratory capacity of these T cells. For the first time, these findings identify fractalkine as a driver of T cell migration to the omentum in EAC and indicate that CD8+ T cells undergo sequenced fractalkine-mediated alterations in CX3CR1 and L-selectin expression. These data implicate fractalkine as more than a chemotactic cytokine in obesity-associated meta-inflammation and reveal a role for this chemokine in the maintenance of the CX3CR1NEG CD8+ T cell populations

Nonthermal X-Rays from Supernova Remnant G330.2+1.0 and the Characteristics of its Central Compact Object

We present results from our X-ray data analysis of the SNR G330.2+1.0 and its CCO, CXOU J160103.1--513353 (J1601). Using our XMM-Newton and Chandra observations, we find that the X-ray spectrum of J1601 can be described by neutron star atmosphere models (T ~ 2.5--3.7 MK). Assuming the distance of d ~ 5 kpc for J1601 as estimated for SNR G330.2+1.0, a small emission region of R ~ 1--2 km is implied. X-ray pulsations previously suggested by Chandra are not confirmed by the XMM-Newton data, and are likely not real. However, our timing analysis of the XMM-Newton data is limited by poor photon statistics, and thus pulsations with a relatively low amplitude (i.e., an intrinsic pulsed-fraction < 40%) cannot be ruled out. Our results indicate that J1601 is a CCO similar to that in the Cassiopeia A SNR.X-ray emission from SNR G330.2+1.0 is dominated by power law continuum (Gamma ~ 2.1--2.5) which primarily originates from thin filaments along the boundary shell. This X-ray spectrum implies synchrotron radiation from shock-accelerated electrons with an exponential roll-off frequency ~ 2--3 x 10^17 Hz. For the measured widths of the X-ray filaments (D ~ 0.3 pc) and the estimated shock velocity (v_s ~ a few x 10^3 km s^-1), a downstream magnetic field B ~ 10--50 $\mu$G is derived. The estimated maximum electron energy E_max ~ 27--38 TeV suggests that G330.2+1.0 is a candidate TeV gamma-ray source. We detect faint thermal X-ray emission in G330.2+1.0. We estimate a low preshock density n_0 ~ 0.1 cm^-3, which suggests a dominant contribution from an inverse Compton mechanism (than the proton-proton collision) to the prospective gamma-ray emission. Follow-up deep radio, X-ray, and gamma-ray observations will be essential to reveal the details of the shock parameters and the nature of particle accelerations in this SNR.Comment: 26 pages, 3 tables, 7 figures (4 color figures), Accepted by Ap