Endothelial and cancer cells interact with mesenchymal stem cells via both microparticles and secreted factors

Tightly associated with blood vessels in their perivascular niche, human mesenchymal stem cells (MSCs) closely interact with endothelial cells (ECs). MSCs also home to tumours and interact with cancer cells (CCs). Microparticles (MPs) are cell-derived vesicles released into the extracellular environment along with secreted factors. MPs are capable of intercellular signalling and, as biomolecular shuttles, transfer proteins and RNA from one cell to another. Here, we characterize interactions among ECs, CCs and MSCs via MPs and secreted factors in vitro. MPs and non-MP secreted factors (Sup) were isolated from serum-free medium conditioned by human microvascular ECs (HMEC-1) or by the CC line HT1080. Fluorescently labelled MPs were prepared from cells treated with membrane dyes, and cytosolic GFP-containing MPs were isolated from cells transduced with CMV-GFP lentivirus. MSCs were treated with MPs, Sup, or vehicle controls, and analysed for MP uptake, proliferation, migration, activation of intracellular signalling pathways and cytokine release. Fluorescently labelled MPs fused with MSCs, transferring the fluorescent dyes to the MSC surface. GFP was transferred to and retained in MSCs incubated with GFP-MPs, but not free GFP. Thus, only MP-associated cellular proteins were taken up and retained by MSCs, suggesting that MP biomolecules, but not secreted factors, are shuttled to MSCs. MP and Sup treatment significantly increased MSC proliferation, migration, and MMP-1, MMP-3, CCL-2/MCP-1 and IL-6 secretion compared with vehicle controls. MSCs treated with Sup and MPs also exhibited activated NF-κB signalling. Taken together, these results suggest that MPs act to regulate MSC functions through several mechanisms

Perception of aircraft Deviation Cues

To begin to address the need for new displays, required by a future airspace concept to support new roles that will be assigned to flight crews, a study of potentially informative display cues was undertaken. Two cues were tested on a simple plan display - aircraft trajectory and flight corridor. Of particular interest was the speed and accuracy with which participants could detect an aircraft deviating outside its flight corridor. Presence of the trajectory cue significantly reduced participant reaction time to a deviation while the flight corridor cue did not. Although non-significant, the flight corridor cue seemed to have a relationship with the accuracy of participants judgments rather than their speed. As this is the second of a series of studies, these issues will be addressed further in future studies

Flying Schedule-Matching Descents to Explore Flight Crews' Perceptions of Their Load and Task Feasibility

Multiple studies have investigated the development and use of ground-based (controller) tools to manage and schedule traffic in future terminal airspace. No studies have investigated the impacts that such tools (and concepts) could have on the flight-deck. To begin to redress the balance, an exploratory study investigated the procedures and actions of ten Boeing-747-400 crews as they flew eight continuous descent approaches in the Los Angeles terminal airspace, with the descents being controlled using speed alone. Although the study was exploratory in nature, four variables were manipulated: speed changes, route constraints, clearance phraseology, and winds. Despite flying the same scenarios with the same events and timing, there was at least a 50 second difference in the time it took crews to fly the approaches. This variation is the product of a number of factors but highlights potential difficulties for scheduling tools that would have to accommodate this amount of natural variation in descent times. The primary focus of this paper is the potential impact of ground scheduling tools on the flight crews performance and procedures. Crews reported "moderate to low" workload, on average; however, short periods of intense and high workload were observed. The non-flying pilot often reported a higher level of workload than the flying-pilot, which may be due to their increased interaction with the Flight Management Computer, when using the aircraft automation to assist with managing the descent clearances. It is concluded that ground-side tools and automation may have a larger impact on the current-day flight-deck than was assumed and that studies investigating this impact should continue in parallel with controller support tool development

Role of the Controller in an Integrated Pilot-Controller Study for Parallel Approaches

Closely spaced parallel runway operations have been found to increase capacity within the National Airspace System but poor visibility conditions reduce the use of these operations [1]. Previous research examined the concepts and procedures related to parallel runways [2][4][5]. However, there has been no investigation of the procedures associated with the strategic and tactical pairing of aircraft for these operations. This study developed and examined the pilot s and controller s procedures and information requirements for creating aircraft pairs for closely spaced parallel runway operations. The goal was to achieve aircraft pairing with a temporal separation of 15s (+/- 10s error) at a coupling point that was 12 nmi from the runway threshold. In this paper, the role of the controller, as examined in an integrated study of controllers and pilots, is presented. The controllers utilized a pairing scheduler and new pairing interfaces to help create and maintain aircraft pairs, in a high-fidelity, human-in-the loop simulation experiment. Results show that the controllers worked as a team to achieve pairing between aircraft and the level of inter-controller coordination increased when the aircraft in the pair belonged to different sectors. Controller feedback did not reveal over reliance on the automation nor complacency with the pairing automation or pairing procedures

FPGA implementations of feed forward neural network by using floating point hardware accelerators

This paper documents the research towards the analysis of different solutions to implement a Neural Network architecture on a FPGA design by using floating point accelerators. In particular, two different implementations are investigated: a high level solution to create a neural network on a soft processor design, with different strategies for enhancing the performance of the process; a low level solution, achieved by a cascade of floating point arithmetic elements. Comparisons of the achieved performance in terms of both time consumptions and FPGA resources employed for the architectures are presented

Using Neural Networks to Explore Air Traffic Controller Workload

When a new system, concept, or tool is proposed in the aviation domain, one concern is the impact that this will have on operator workload. As an experience, workload is difficult to measure in a way that will allow comparison of proposed systems with those already in existence. Chatterji and Sridhar (2001) suggested a method by which airspace parameters can be translated into workload ratings, using a neural network. This approach was employed, and modified to accept input from a non-real time airspace simulation model. The following sections describe the preparations and testing work that will enable comparison of a future airspace concept with a current day baseline in terms of workload levels

Flight-Deck Strategies and Outcomes When Flying Schedule-Matching Descents

Recent studies at NASA Ames Research Center have investigated the development and use of ground-based (air traffic controller) tools to manage and schedule air traffic in future terminal airspace. An exploratory study was undertaken to investigate the impacts that such tools (and concepts) could have on the flight-deck. Ten Boeing 747-400 crews flew eight optimized profile descents in the Los Angeles terminal airspace, while receiving scripted current day and futuristic speed clearances, to ascertain their ability to fly schedulematching descents without prior training. Although the study was exploratory in nature, four variables were manipulated: route constraints, winds, speed changes, and clearance phraseology. Despite flying the same scenarios with the same events and timing, there were significant differences in the time it took crews to fly the approaches. This variation is the product of a number of factors but highlights potential difficulties for scheduling tools that would have to accommodate this amount of natural variation in descent times. The focus of this paper is the examination of the crews' aircraft management strategies and outcomes. This includes potentially problematic human-automation interaction issues that may negatively impact arrival times, speed and altitude constraint compliance, and energy management efficiency

An Investigation of Flight Deck Data Link in the Terminal Area

The Next Generation Air Transportation System (NextGen) and Europe's Single European Sky ATM Research (SESAR) concepts require an increased use of trajectory-based operations, including extensive strategic air traffic control clearances. The clearances are lengthy and complex, which necessitate data link communications to allow for message permanence and integration into the autoflight systems (i.e., autoload capability). This paper examines the use of flight deck data link communications for strategic and tactical clearance usage in the terminal area. A human-in-the-loop simulation was conducted using a high-fidelity flight deck simulator, with ten commercial flight crews as participants. Data were collected from six flight scenarios in the San Francisco terminal airspace. The variables of interest were ATC message modality (voice v. data link), temporal quality of the message (tactical v. strategic) and message length. Dependent variables were message response times, communication clarifications, communication-related errors, and pilot workload. Response time results were longer in data link compared to voice, a finding that has been consistently revealed in a number of other simulations [1]. In addition, strategic clearances and longer messages resulted in a greater number of clarifications and errors, suggesting an increase in uncertainty of message interpretation for the flight crews when compared to tactical clearances. The implications for strategic and compound clearance usage in NextGen and SESAR are discusse

Preliminary Human-in-the-Loop Assessment of Procedures for Very-Closely-Spaced Parallel Runways

Demand in the future air transportation system concept is expected to double or triple by 2025 [1]. Increasing airport arrival rates will help meet the growing demand that could be met with additional runways but the expansion airports is met with environmental challenges for the surrounding communities when using current standards and procedures. Therefore, changes to airport operations can improve airport capacity without adding runways. Building additional runways between current ones, or moving them closer, is a potential solution to meeting the increasing demand, as addressed by the Terminal Area Capacity Enhancing Concept (TACEC). TACEC requires robust technologies and procedures that need to be tested such that operations are not compromised under instrument meteorological conditions. The reduction of runway spacing for independent simultaneous operations dramatically exacerbates the criticality of wake vortex incursion and the calculation of a safe and proper breakout maneuver. The study presented here developed guidelines for such operations by performing a real-time, human-in-the-loop simulation using precision navigation, autopilot-flown approaches, with the pilot monitoring aircraft spacing and the wake vortex safe zone during the approach