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At least 865 records · Page 48

A Pentavalent HIV-1 Subtype C Vaccine Containing Computationally Selected gp120 Strains Improves the Breadth of V1V2 Region Responses

Background: HIV-1 envelope (Env) variable loops 1 and 2 (V1V2) directed non-neutralizing antibodies were a correlate of decreased transmission risk in the RV144 vaccine trial. Thus, the elicitation and breadth of antibody responses against the V1V2 of HIV-1 Env are important considerations for HIV-1 vaccine candidates. The V1V2 region’s highly variable nature and the extensive diversity of subtype C HIV-1 Envelopes (Envs) make the V1V2 response breadth a high priority for HIV-1 vaccine regimens aiming for V1V2-mediated protection in Southern Africa. Here, we determined whether the breadth of the anti-V1V2 vaccine response can be broadened by including HIV-1 Env strains computationally designed to enhance the coverage of subtype C V1V2 sequence diversity. Methods: Three subtype C Env strains were selected to maximize antibody binding coverage while complementing subtype C vaccine gp120s that were given in human clinical trials in South Africa, as well as to improve epitope accessibility. Humoral immunogenicity of a novel trivalent gp120 vaccine immunogen, a bivalent gp120 boost already in clinical trials (1086C and TV1), and a pentavalent (all five gp120s combined) were evaluated in a preclinical immunization study in guinea pigs. The pentavalent combination was further evaluated with alum versus glucopyranosyl lipid adjuvants formulated in squalene-in-water emulsion (GLA-SE) adjuvants in non-human primates. The breadth of the anti-V1V2 response was assessed using an array of cross-subtype variable loops 1&2 (V1V2) scaffold proteins and linear V2 peptides. Results: The breadth of the IgG response against V1V2 antigens of the trivalent and pentavalent groups was comparable, and both were greater than the breadth of the bivalent group. Linear epitope mapping showed that two linear epitopes in V2 were targeted by the vaccinated animals: the V2 hotspot focused at 169K that potentially correlated with decreased HIV-1 risk in RV144 and the V2.2 site (179LDV/I181) that is part of the integrin α4β7 binding site. The bivalent vaccine elicited a significantly higher magnitude of binding to the V2 hotspot compared to the trivalent vaccine whereas the trivalent vaccine elicited significantly higher binding to the V2.2 epitope compared to the bivalent vaccine, while the pentavalent recognized both regions. Conclusions: These results demonstrate that the three new computationally selected subtype C Envs successfully complemented 1086C and TV1 for broader V1V2 antibody responses, and, in concert with adjuvants that stimulate V1V2 responses, can be considered as part of a rationale immunogen design to improve V1V2 IgG coverage in future vaccine trials in South Africa.

Immunology↗

A porcine ligated loop model reveals new insight into the host immune response against Campylobacter jejuni

The symptoms of infectious diarrheal disease are mediated by a combination of a pathogen’s virulence factors and the host immune system. Campylobacter jejuni is the leading bacterial cause of diarrhea worldwide due to its near-ubiquitous zoonotic association with poultry. One of the outstanding questions is to what extent the bacteria are responsible for the diarrheal symptoms via intestinal cell necrosis versus immune cell initiated tissue damage. To determine the stepwise process of inflammation that leads to diarrhea, we used a piglet ligated intestinal loop model to study the intestinal response to C. jejuni. Pigs were chosen due to the anatomical similarity between the porcine and the human intestine. We found that the abundance of neutrophil related proteins increased in the intestinal lumen during C. jejuni infection, including proteins related to neutrophil migration (neutrophil elastase and MMP9), actin reorganization (Arp2/3), and antimicrobial proteins (lipocalin-2, myeloperoxidase, S100A8, and S100A9). The appearance of neutrophil proteins also corresponded with increases of the inflammatory cytokines IL-8 and TNF-a. Compared to infection with the C. jejuni wild-type strain, infection with the noninvasive C. jejuni ?ciaD mutant resulted in a blunted inflammatory response, with less inflammatory cytokines and neutrophil markers. These findings indicate that intestinal inflammation is driven by C. jejuni virulence and that neutrophils are the predominant cell type responding to C. jejuni infection. We propose that this model can be used as a platform to study the early immune events during infection with intestinal pathogens.

disease model, INNATE IMMUNITY, proteomics, intest↗

Automation effects in a stereotypical multiloop manual control system

The increasing reliance of state-of-the art, high performance aircraft on high authority stability and command augmentation systems, in order to obtain satisfactory performance and handling qualities, has made critical the achievement of a better understanding of human capabilities, limitations, and preferences during interactions with complex dynamic systems that involve task allocation between man and machine. An analytical and experimental study has been undertaken to investigate human interaction with a simple, multiloop dynamic system in which human activity was systematically varied by changing the levels of automation. Task definition has led to a control loop structure which parallels that for any multiloop manual control system, and may therefore be considered a stereotype.

Hess, R. A.↗

HSI Guidelines Outline for the Air Vehicle Control Station. Version 2

This document provides guidance to the FAA and manufacturers on how to develop UAS Pilot Vehicle Interfaces to safely and effectively integrate UASs into the NAS. Preliminary guidelines are provided for Aviate, Communicate, Navigate and Avoid Hazard functions. The pilot shall have information and control capability so that pilot-UA interactions are not adverse, unfavorable, nor compromise safety. Unfavorable interactions include anomalous aircraft-pilot coupling (APC) interactions (closed loop), pilot-involved oscillations (categories I, II or III), and non-oscillatory APC events (e.g., divergence). - Human Systems Integration Pilot-Technology Interface Requirements for Command, Control, and Communications (C3)

Source record↗

Environmental Control and Life Support (ECLS) Systems

Environmental control and life support (ECLS)systems provide the conditions necessary to maintain astronaut's health during a mission. They have been a part of every human-rated vehicle from Mercury onward, from carbon dioxide scrubbers and drink bags, to sophisticated air and water recovery technologies. In order to enable human exploration beyond low Earth orbit for an extended time, such as a mission to Mars, closed-loop life support, the continuous use, reuse, and recycling of air, water, and waste will be necessary. This chapter provides a brief history of air revitalization, wastewater, and solid waste recovery systems from the early spaceflight era to the present, potential technologies in development to facilitate further loop closure, and considerations for future life support system development in support of exploration

Life support↗

Stochastic Verification by Analysis for Autonomous Systems Management Architecture (ASMA)

The Gateway Vehicle Systems Manager (VSM) is the top-level of a distributed, hierarchical software control system. VSM is data-driven and will make decisions related to mission, fault, resource management and vehicle control. These attributes combined with a high degree of autonomy make it susceptible to emergent behavior. In order to achieve the high level of confidence needed in this critical system, the VSM team has developed a multifaceted verification strategy employing traditional verification techniques, simulation, model checking, and runtime verification. Individual algorithms are verified using conventional testing and model checking using assume-guarantee contracts. A discrete event-based simulation approach is being developed to verify timelines. This presentation describes an enhancement to the verification approach using analysis to enhance system robustness by detecting and resolving the potential for emergent behavior. The verification by analysis employs a Software in the Loop (SITL) environment with real flight software executing on emulated processors, simulations of vehicle subsystems, flight dynamics, and human inputs. Since the possible input space and configuration data set are too large for exhaustive testing, a Monte Carlo approach is used to cover feasible scenarios, augmented with corner cases and known higher-risk scenarios. A key problem in using Monte Carlo-based system verification is evaluating test results to ensure that system behavior is correct. The presentation describes the approach the VSM team uses to monitor behavior for compliance with predetermined boundaries and to identify anomalous behavior for further analysis. This presentation describes the multi-level systems approach to verification, and the simulation-based layer that covers the feasible state space: 1. Overview of the Gateway VSM 2. Special challenges due to heterogeneous, hierarchical architecture 3. Modeling and simulation environment using flight software and system simulations 4. Developing input sets to ensure state-space coverage 5. Developing model and data configuration sets to ensure model coverage 6. Interpreting results without predetermined outcomes 7. Lessons learned and future work

Verification and Validation↗

Does man always close the loop in trying to pilot a large ship?

Control of a slowly responding complex dynamic system such as a large supertanker poses special problems for the human. Experienced ship's crew members maneuvered a simulated ship in real time. The simulation was performed using a graphics display run by a DPD 11/40 minicomputer. The maneuvers consisted of piloting a large ship along a narrow waterway. Preliminary results suggest that the human operates as a feedforward controller utilizing the preview information for 'gross changes' in heading, and as a feedback controller for correcting small deviations. The instruments displayed on the deck do not seem to be helpful in all situations. In fact, evidence seems to indicate that some of the displays might even interfere with the pilot's attempt to form a good internal model.

Arnott, D. R.↗

Experimental discovery of structure–property relationships in ferroelectric materials via active learning

Emergent functionalities of structural and topological defects in ferroelectric materials underpin an extremely broad spectrum of applications ranging from domain wall electronics to high dielectric and electromechanical responses. Many of these functionalities have been discovered and quantified via local scanning probe microscopy methods. However, the search has until now been based on either trial and error, or using auxiliary information such as the topography or domain wall structure to identify potential objects of interest on the basis of the intuition of operator or pre-existing hypotheses, with subsequent manual exploration. Here we report the development and implementation of a machine learning framework that actively discovers relationships between local domain structure and polarization-switching characteristics in ferroelectric materials encoded in the hysteresis loop. The hysteresis loops and their scalar descriptors such as nucleation bias, coercive bias and the hysteresis loop area (or more complex functionals of hysteresis loop shape) and corresponding uncertainties are used to guide the discovery of these relationships via automated piezoresponse force microscopy and spectroscopy experiments. As such, this approach combines the power of machine learning methods to learn the correlative relationships between high-dimensional data, as well as human-based physics insights encoded into the acquisition function. For ferroelectric materials, this automated workflow demonstrates that the discovery path and sampling points of on- and off-field hysteresis loops are largely different, indicating that on- and off-field hysteresis loops are dominated by different mechanisms. Here, the proposed approach is universal and can be applied to a broad range of modern imaging and spectroscopy methods ranging from other scanning probe microscopy modalities to electron microscopy and chemical imaging.

36 MATERIALS SCIENCE↗

Approaches for Synthesis and Deployment of Controller Models on Automated Vehicles for Car-following in Mixed Autonomy

This paper describes the software design patterns and vehicle interfaces that were employed to transition vehicle controllers from simulation environments to open-road field experiments. The approach relies on a life cycle that utilizes model-based design and code generation, along with agile software development, and both software and hardware-in-the-loop testing, with additional safety margins. Autonomous designs should consider the dynamics of mixed autonomy in traffic to safely operate among humans. The software that provides a vehicle’s behavior intelligence is often developed through simulation, which may have a mismatch between dynamics, or as a result of a reinforcement learning workflow, which may be a black box with challenges to analyze. In each of these cases, it is important to have research interfaces that provide strongly typed data streams accessible to researchers who are not software experts while continuing to satisfy safety and liveness constraints. This paper describes how we design the hardware platform interfaces and software design process for a mixed autonomy traffic experiment with a leader-follower scenario. Controller synthesis for these vehicles requires clearly articulated vehicle interfaces and software design patterns for successful onboard deployment. Testing strategies for such controllers are also described before algorithms are transitioned to full-scale field experiments with safety operators for the vehicles. Testing strategies include software-in-the-loop simulation testing, hardware-in-the-loop simulation, ghost-car testing, and read-only testing in live traffic. With our approach, we were not only able to validate our controller synthesized in scripts and simulation, but also able to scale deployment to multiple vehicles.

Bhadani, Rahul↗

Biocybernetic Closed-Loop System for Mitigating Hazardous States of Awareness

The past century of passenger flight has seen continuous improvement in aviation safety by the aerospace industry. However, while commercial aviation accident rates have continued to decline, human error-related incident and accident rates remain remarkably constant across all types of aviation (Shappell, et al., 2007). Unfortunately, this level of human error is unacceptable when considering projections for increased traffic volume (FAA, 2009), and is likely to yield more incidents and accidents unless a more complete understanding of operator error is achieved and remediations are implemented. One area of interest highlighted by researchers is Hazardous States of Awareness (HSAs) that can result from deficiencies in the design and inappropriate use of human-machine interfaces. Identifying and mitigating HSAs is critical for reducing operator errors. One promising approach uses psychophysiological measures which enable automated systems to adapt to the operator?s state and modify modes of operation to support optimal human performance (Scerbo, 2007). This paper will survey previous research and describe future directions for the application of psychophysiological measures of operators derived from cortical and autonomic assessment to perform real-time adaptive modulation of human-automation task mode mixes. The authors will present a summary of previous work done at NASA LaRC and Old Dominion University using a Psychophysiologically Adaptive System (PAS) in which the level of automation of the NASA Multi-Attribute Task Battery was modulated based on Engagement Indices derived from the users? electroencephalogram (Pope, Bogart, & Bartolome, 1995; for review see, Scerbo, Freeman, & Mikulka, 2003). Future theoretical and methodological directions for this type of closed-loop research will be discussed. Specifically, the capacity for this type of PAS to maintain effective operator state and to enable validation of candidate physiological indices will be described. Consideration will also be given to critical system characteristics (e.g., engagement indices, methods for invoking changes among system states, individual differences among users, etc.) that have been or still need to be studied. The potential of the PAS approach for interactive system design and prototyping will also be described. Examples of adaptive automation flight deck concepts in recent experiments will be highlighted and discussed.

Chad L Stephens↗

V-SUIT Model Validation Using PLSS 1.0 Test Results

The dynamic portable life support system (PLSS) simulation software Virtual Space Suit (V-SUIT) has been under development at the Technische Universitat Munchen since 2011 as a spin-off from the Virtual Habitat (V-HAB) project. The MATLAB(trademark)-based V-SUIT simulates space suit portable life support systems and their interaction with a detailed and also dynamic human model, as well as the dynamic external environment of a space suit moving on a planetary surface. To demonstrate the feasibility of a large, system level simulation like V-SUIT, a model of NASA's PLSS 1.0 prototype was created. This prototype was run through an extensive series of tests in 2011. Since the test setup was heavily instrumented, it produced a wealth of data making it ideal for model validation. The implemented model includes all components of the PLSS in both the ventilation and thermal loops. The major components are modeled in greater detail, while smaller and ancillary components are low fidelity black box models. The major components include the Rapid Cycle Amine (RCA) CO2 removal system, the Primary and Secondary Oxygen Assembly (POS/SOA), the Pressure Garment System Volume Simulator (PGSVS), the Human Metabolic Simulator (HMS), the heat exchanger between the ventilation and thermal loops, the Space Suit Water Membrane Evaporator (SWME) and finally the Liquid Cooling Garment Simulator (LCGS). Using the created model, dynamic simulations were performed using same test points also used during PLSS 1.0 testing. The results of the simulation were then compared to the test data with special focus on absolute values during the steady state phases and dynamic behavior during the transition between test points. Quantified simulation results are presented that demonstrate which areas of the V-SUIT model are in need of further refinement and those that are sufficiently close to the test results. Finally, lessons learned from the modelling and validation process are given in combination with implications for the future development of other PLSS models in V-SUIT.

Olthoff, Claas↗

A Combination of Human Broadly Neutralizing Antibodies against Hepatitis B Virus HBsAg with Distinct Epitopes Suppresses Escape Mutations

Although there is no effective cure for chronic hepatitis B virus (HBV) infection, antibodies are protective and correlate with recovery from infection. To examine the human antibody response to HBV, we screened 124 vaccinated and 20 infected, spontaneously recovered individuals. The selected individuals produced shared clones of broadly neutralizing antibodies (bNAbs) that targeted 3 non-overlapping epitopes on the HBV S antigen (HBsAg). Single bNAbs protected humanized mice against infection but selected for resistance mutations in mice with prior established infection. In contrast, infection was controlled by a combination of bNAbs targeting non-overlapping epitopes with complementary sensitivity to mutations that commonly emerge during human infection. The co-crystal structure of one of the bNAbs with an HBsAg peptide epitope revealed a stabilized hairpin loop. This structure, which contains residues frequently mutated in clinical immune escape variants, provides a molecular explanation for why immunotherapy for HBV infection may require combinations of complementary bNAbs.

59 BASIC BIOLOGICAL SCIENCES↗

The applications of the remote control of the manipulation in manned space exploration

The teleoperator system incorporates many of the advantages of manned systems on the one hand, and mechanical systems on the other. Since man is always in the control loop of a teleoperator system, the system is provided the decision making and adaptive intelligence capabilities which are uniquely human. Conversely, since the actual work is performed by the remotely controlled device, the system incorporates the durability, strength, and the expendable nature of a machine. Use of a teleoperator system is generally safer than placing the man at the worksite, and is generally more flexible and adaptable than an automated mechanical system. Potential earth orbital space missions for teleoperator systems, candidate aerospace teleoperator systems to perform these missions, and the current status of teleoperator technology development within NASA are discussed.

Deutsche, S.↗

Active Sticks: a New Dimension in Controller Design

A smart stick controller was built which actively produces a force to interact with the subject's hand and to aid in tracking. When the human tracks in this situation, the man-machine system can be viewed as the combination of two closed loop feedback paths. The inner loop occurs as a result of a tactile information channel effecting the man-controller interaction through force with this stick in the active mode (the stick generates a force) and the passive mode (the stick not generating a force) are reported. The most noteworthy observation is a significant increase in apparent neuromotor bandwidth and consequently better tracking performance.

Repperger, D. W.↗

Evaluation of Flow Biosensor Technology in a Chronically-Instrumented Non-Human Primate Model

The Physiology Research Branch of Brooks AFB conducts both human and non-human primate experiments to determine the effects of microgravity and hypergravity on the cardiovascular system and to indentify the particular mechanisms that invoke these responses. Primary investigative research efforts in a non-human primate model require the calculation of total peripheral resistance (TPR), systemic arterial compliance (SAC), and pressure-volume loop characteristics. These calculations require beat-to-beat measurement of aortic flow. We have evaluated commercially available electromagnetic (EMF) and transit-time flow measurement techniques. In vivo and in vitro experiments demonstrated that the average error of these techniques is less than 25 percent for EMF and less than 10 percent for transit-time.

SC Koenig↗

Closing the Loop on Space Trash / Is a Circular Economy Possible?

A crew member will nominally consume 2.5 kg of water per crew-member per day, rejectapproximately 0.032 kg of dry fecal solid waste per crew member per day (dry basis)and generate approximately 2,122 kg of logistical waste per year on a long-durationcrewed mission. This topic seeks to push the conversation towards completing a closedloop system and circular economy for all materials and recoverable resources withregard to waste management, regenerative water use, and recycling. In all aspects,reduction of crew maintenance time, mass, power and volume are at the forefront oftechnology development. In addition, the longevity and hardware robustness is important(lasting >3 years). Overall water recovery of >98% is desired, as well as, condensingheat exchangers that remove water from air with collection rates up to 1.45 kg of waterper hour. There are many technologies on the ground being developed for recycling andtrash management or regenerative water use that have yet to introduce themselves forspace development and infusion. Here we look to open the conversation and cross cutthese platforms to bring out some innovation and exposure into the hidden crevasses ofthe waste that humans create and how to minimize it/repurpose it, for all of humanity.

ISRU↗

A psychologist's view of validating aviation systems

All systems, no matter what they are designed to do, have shortcomings that may make them less productive than was hoped during the initial development. Such shortcomings can arise at any stage of development: from conception to the end of the implementation life cycle. While systems failure and errors of a lesser magnitude can occur as a function of mechanical or software breakdown, the majority of such problems, in aviation are usually laid on the shoulders of the human operator and, to a lesser extent, on human factors. The operator bears the responsibility and blame even though, from a human factors perspective, error may have been designed into the system. Human factors is not a new concept in aviation. The name may be new, but the issues related to operators in the loop date back to the industrial revolution of the nineteenth century and certainly to the aviation build-up for World War I. During this first global confrontation, military services from all sides discovered rather quickly that poor selection and training led to drastically increased personnel losses. While hardware design became an issue later, the early efforts were primarily focused on increased care in pilot selection and on their training. This actually involved early labor-intensive simulation, using such devices as sticks and chairs mounted on rope networks which could be manually moved in response to control input. The use of selection criteria and improved training led to more viable person-machine systems. More pilots survived training and their first ten missions in the air, a rule of thumb arrived at by experience which predicted ultimate survival better than any other. This rule was to hold through World War II. At that time, personnel selection and training became very sophisticated based on previous standards. Also, many psychologists were drafted into Army Air Corps programs which were geared towards refining the human factor. However, despite the talent involved in these programs and the tremendous build-up of aviation during the war, there were still aircraft designs that were man killers (no sexism implied since all combat pilots were men). One classic design error that was identified fifty years ago was the multipointer altimeter, which could easily be misread especially by a pilot under considerable task load. It has led to flying fully operational aircraft into the terrain. The authors of the research which formally identified this problem put 'Human Errors' in quotes to express their dissatisfaction with the traditional approach to accident investigation. It traditionally places the burden of guilt on the operator. Some of these altimeters still exist in older aircraft to this day.

Stein, Earl S.↗

Steady-state evoked potentials possibilities for mental-state estimation

The use of the human steady-state evoked potential (SSEP) as a possible measure of mental-state estimation is explored. A method for evoking a visual response to a sum-of-ten sine waves is presented. This approach provides simultaneous multiple frequency measurements of the human EEG to the evoking stimulus in terms of describing functions (gain and phase) and remnant spectra. Ways in which these quantities vary with the addition of performance tasks (manual tracking, grammatical reasoning, and decision making) are presented. Models of the describing function measures can be formulated using systems engineering technology. Relationships between model parameters and performance scores during manual tracking are discussed. Problems of unresponsiveness and lack of repeatability of subject responses are addressed in terms of a need for loop closure of the SSEP. A technique to achieve loop closure using a lock-in amplifier approach is presented. Results of a study designed to test the effectiveness of using feedback to consciously connect humans to their evoked response are presented. Findings indicate that conscious control of EEG is possible. Implications of these results in terms of secondary tasks for mental-state estimation and brain actuated control are addressed.

Junker, Andrew M.↗