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Mondo: integrating disease terminology across communities

Precision medicine aims to enhance diagnosis, treatment, and prognosis by integrating multimodal data at the point of care. However, challenges arise due to the vast number of diseases, differing methods of classification, and conflicting terminological coding systems and practices used to represent molecular definitions of disease. This lack of interoperability artificially constrains the potential for diagnosis, clinical decision support, care outcome analysis, as well as data linkage across research domains to support the development or repurposing of therapeutics. There is a clear and pressing need for a unified system for managing disease entities⁠—including identifiers, synonyms, and definitions. To address these issues, we created the Mondo disease ontology—a community-driven, open-source, unified disease classification system that harmonizes diverse terminologies into a consistent, computable framework. Mondo integrates key medical and biomedical terminologies, including Online Mendelian Inheritance in Man (OMIM), Orphanet, Medical Subject Headings (MeSH), National Cancer Institute Thesaurus (NCIt), and more, to provide a comprehensive and accurate representation of disease concepts with fully provenanced and attributed links back to the sources. Mondo can be used as the handle for curation of gene–disease associations utilized in diagnostic applications, research applications such as computational phenotyping, and in clinical coding systems in clinical decision support by pointing the clinician to the numerous knowledge resources linked to the Mondo identifier. Mondo's community-centric approach, stewarded by the Monarch Initiative's expertise in ontologies, ensures that the ontology remains adaptable to the evolving needs of biomedical research and clinical communities, as well as the knowledge providers.

biomedical informatics↗

Defining the Collision Avoidance Region for DAA Systems

Unmanned aircraft systems (UAS) will be required to equip with a detect-­‐and-­‐avoid (DAA) system in order to satisfy the federal aviation regulations to maintain well clear of other aircraft, some of which may be equipped with a Traffic Collision Avoidance System (TCAS) to mitigate the possibility of mid-­‐air collisions. As such, the minimum operational performance standards (MOPS) for UAS DAA systems are being designed with TCAS interoperability in mind by a group of industry, government, and academic institutions named RTCA Special Committee-228 (SC-228). This document will discuss the development of the spatial-­‐temporal volume known as the collision avoidance region in which the DAA system is not allowed to provide vertical guidance to maintain or regain DAA well clear that could conflict with resolution advisories (RAs) issued by the intruder aircraft's TCAS system. Three collision avoidance region definition candidates were developed based on the existing TCAS RA and DAA alerting definitions. They were evaluated against each other in terms of their interoperability with TCAS RAs and DAA alerts in an unmitigated factorial encounter analysis of 1.3 million simulated pairs.

collision avoidance region↗

Modelling the near-Earth space environment using LDEF data

Near-Earth space is a dynamic environment, that is currently not well understood. In an effort to better characterize the near-Earth space environment, this study compares the results of actual impact crater measurement data and the Space Environment (SPENV) Program developed in-house at POD, to theoretical models established by Kessler (NASA TM-100471, 1987) and Cour-Palais (NASA SP-8013, 1969). With the continuing escalation of debris there will exist a definite hazard to unmanned satellites as well as manned operations. Since the smaller non-trackable debris has the highest impact rate, it is clearly necessary to establish the true debris environment for all particle sizes. Proper comprehension of the near-Earth space environment and its origin will permit improvement in spacecraft design and mission planning, thereby reducing potential disasters and extreme costs. Results of this study directly relate to the survivability of future spacecraft and satellites that are to travel through and/or reside in low Earth orbit (LEO). More specifically, these data are being used to: (1) characterize the effects of the LEO micrometeoroid an debris environment on satellite designs and components; (2) update the current theoretical micrometeoroid and debris models for LEO; (3) help assess the survivability of spacecraft and satellites that must travel through or reside in LEO, and the probability of their collision with already resident debris; and (4) help define and evaluate future debris mitigation and disposal methods. Combined model predictions match relatively well with the LDEF data for impact craters larger than approximately 0.05 cm, diameter; however, for smaller impact craters, the combined predictions diverge and do not reflect the sporadic clouds identified by the Interplanetary Dust Experiment (IDE) aboard LDEF. The divergences cannot currently be explained by the authors or model developers. The mean flux of small craters (approximately 0.05 cm diameter) is overpredicted by Kessler and underpredicted by Cour-Palais. This divergence may be a result of beta-meteoroid fluxes, elliptical orbits or a combination of the two. The results of this study illustrate the definite need for more intensive study of the near-Earth space environment, particularly the small particle regime, as it is the most degrading to spacecraft in LEO.

Atkinson, Dale R.↗

Particle emissions from mobile sources: Discussion of ultrafine particle emissions and definition

There is no universally agreed upon definition for ultrafine particles (UFP). Commonly used definitions for UFP are either particle number below 100 nm or total particle number, but without an agreed upon lower cut point. For example, a lower cut point of 3 nm compared to 10 nm could result in a substantially higher count. Another definition for UFP is total particle mass but without a commonly agreed upon aerodynamic diameter upper cut point, e.g., below 100 nm, 200 nm, 300 nm, etc. Yet another definition is lung deposited surface area weighted by lung deposition fraction, found mainly in the particle mobility diameter range from 20 to 400 nm. It is clear from these definitions that there are inconsistencies in the way UFP is used and defined in the literature. Sometimes these metrics are well correlated, sometimes not. In this paper we suggest three exposure metrics: UFP-N, UFP-M, and UFP-S, that we believe will add clarity. These metrics represent total number, mass, and surface area below 500 nm, respectively. For surface area and mass, the 500 nm cut point can be either aerodynamic or mobility diameter depending upon measurement methodology. For all metrics, this cut point captures nearly all of the primary particle emissions from mobile sources. Furthermore, UFP-N would include a lower cut point of 3–6 nm and would not require an upper size cut point because there is very little particle number above 500 nm or even above 100 nm. Thus, our definition of UFP-N is consistent with the current definition of ultrafine number except for, importantly, the specification of a lower cut point. These exposure metrics can help facilitate consistency in the characterization of both short- and long-term UFP ambient exposures and associated health effects in epidemiological studies.

42 ENGINEERING↗

The ultraviolet spectrum of the planetary nebula Vy 2-2

New ultraviolet short-wavelength (SWP) IUE observations for the proto-planetary nebula Vy 2-2 were obtained in the low-dispersion mode. An exposure of 400-min duration reveals a weak stellar continuum and several definite emission lines as well as a number of absorption features. Emission features of semiforbidden C III, semiforbidden Si III, and forbidden Ne III are clearly observed, while C IV, Si II, and possibly C II appear in absorption. Emission features of He II, semiforbidden O III, and Al III are also indicated, though less certain. The UV spectrum tends to confirm that Vy 2-2 is a young, dense planetary nebula excited by a central star with T(eff) greater than 60,000 K.

Feibelman, Walter A.↗

Memory protection

Accidental overwriting of files or of memory regions belonging to other programs, browsing of personal files by superusers, Trojan horses, and viruses are examples of breakdowns in workstations and personal computers that would be significantly reduced by memory protection. Memory protection is the capability of an operating system and supporting hardware to delimit segments of memory, to control whether segments can be read from or written into, and to confine accesses of a program to its segments alone. The absence of memory protection in many operating systems today is the result of a bias toward a narrow definition of performance as maximum instruction-execution rate. A broader definition, including the time to get the job done, makes clear that cost of recovery from memory interference errors reduces expected performance. The mechanisms of memory protection are well understood, powerful, efficient, and elegant. They add to performance in the broad sense without reducing instruction execution rate.

Denning, Peter J.↗

Workshop on Solar Electric Propulsion

A summary of the discussion at the workshop on solar electric propulsion (SEP) is presented. The purpose of ELITE SEP flight experiment is to demonstrate operation of solar array powered electric thrusters for raising spacecraft from parking orbit to higher altitudes, leading to definition of an operational SEP orbit transfer vehicles (OTV) for Air Force missions. Many of the problems or potential problems that may be associated with SEP are not well understood nor clearly identified, and system level phenomena such as interaction of thruster plume with the solar arrays cannot be simulated in a ground test. Therefore, an end-to-end system flight test is required to demonstrate solar electric propulsion.

Bents, David↗

Structural Similitude and Scaling Laws

Aircraft and spacecraft comprise the class of aerospace structures that require efficiency and wisdom in design, sophistication and accuracy in analysis and numerous and careful experimental evaluations of components and prototype, in order to achieve the necessary system reliability, performance and safety. Preliminary and/or concept design entails the assemblage of system mission requirements, system expected performance and identification of components and their connections as well as of manufacturing and system assembly techniques. This is accomplished through experience based on previous similar designs, and through the possible use of models to simulate the entire system characteristics. Detail design is heavily dependent on information and concepts derived from the previous steps. This information identifies critical design areas which need sophisticated analyses, and design and redesign procedures to achieve the expected component performance. This step may require several independent analysis models, which, in many instances, require component testing. The last step in the design process, before going to production, is the verification of the design. This step necessitates the production of large components and prototypes in order to test component and system analytical predictions and verify strength and performance requirements under the worst loading conditions that the system is expected to encounter in service. Clearly then, full-scale testing is in many cases necessary and always very expensive. In the aircraft industry, in addition to full-scale tests, certification and safety necessitate large component static and dynamic testing. Such tests are extremely difficult, time consuming and definitely absolutely necessary. Clearly, one should not expect that prototype testing will be totally eliminated in the aircraft industry. It is hoped, though, that we can reduce full-scale testing to a minimum. Full-scale large component testing is necessary in other industries as well, Ship building, automobile and railway car construction all rely heavily on testing. Regardless of the application, a scaled-down (by a large factor) model (scale model) which closely represents the structural behavior of the full-scale system (prototype) can prove to be an extremely beneficial tool. This possible development must be based on the existence of certain structural parameters that control the behavior of a structural system when acted upon by static and/or dynamic loads. If such structural parameters exist, a scaled-down replica can be built, which will duplicate the response of the full-scale system. The two systems are then said to be structurally similar. The term, then, that best describes this similarity is structural similitude. Similarity of systems requires that the relevant system parameters be identical and these systems be governed by a unique set of characteristic equations. Thus, if a relation or equation of variables is written for a system, it is valid for all systems which are similar to it. Each variable in a model is proportional to the corresponding variable of the prototype. This ratio, which plays an essential role in predicting the relationship between the model and its prototype, is called the scale factor.

Simitses, George J.↗

ACES M and S: Unmitigated Factorial Encounter Study on DAA/TCAS Interoperability

Realization of the expected proliferation of Unmanned Aircraft System (UAS) operations in the National Airspace System (NAS) depends on the development and validation of standards for UAS Detect and Avoid (DAA) Systems. The RTCA Special Committee 228 is charged with leading the development of draft Minimum Operational Performance Standards (MOPS) for UAS DAA Systems. NASA, as a participating member of RTCA SC-228 is committed to supporting the development and validation of draft requirements for DAA alerting and guidance systems. This presentation contains the results of two combinatorial encounter analysis studies using NASA's SAA Control fast-time simulation capability for this purpose. In these studies, encounters between two aircraft were simulated one at a time for the full factorial combination of encounter geometries (e.g., encounter angle, CPA offset) and aircraft performance (e.g., ownership and intruder ground speeds and vertical rates). The first study analyzes the relationships (e.g., timeline) between the different alerting-safety regions in the SC-228 MOPS (in order of increasing severity): 1) DAA warning alert, 2) well clear recovery (WCR) guidance, 3) DAA-Collision Avoidance (CA), and 4) TCAS RA. This study will focus primarily on encounter situations in which TCAS RA occurs prior to any of the other alerting-safety boundaries. In particular, this study will investigate whether using vertical distance or vertical distance at closest point of approach (i.e., vertical miss distance or VMD) is more appropriate for the definition of the DAA-CA region. In addition, cases where transitions between different regions skip an intermediate region will be analyzed. The second study in this presentation explores a proposal to use an altitude rate error threshold to determine if vertical maneuvers are acceptable for DAA WCR guidance against non-cooperative intruders. This study incorporates the radar from the Honeywell sensor model and examines a series of pairwise encounters between a non-cooperative intruder and a UAS ownship, with different combinations of intruder states and ownship performance levels. The study uses SAA Control as a simulation platform and pilot model, and Omnibands to provide DWC recovery guidance. Two simulation sets, one that allows vertical DWC recovery guidance and one that does not, are compared to determine if encounters with altitude rate errors above 250 feet-per-minute are more likely to have more severe losses of well clear, as determined by the Loss of Well-Clear Severity metric.

SaaControl↗

Rocket observations of the diffuse ultraviolet background

The objective of the experiment reported here was to obtain additional information on the absolute intensity level and spatial variation of the diffuse ultraviolet background and thereby gain insight into the origin of this radiation. The experiment used three ultraviolet sensitive photometers placed in the focal plane of a 95-cm, f/2.8 normal incidence telescope flown on board an Aries sounding rocket. The measured intensities clearly refute the hypothesis of an isotropic background, the intensities of the high galactic latitude being definitely lower than the intensities seen at intermediate latitudes. Moreover, the count rates in all three channels along the slow scan exhibit local enhancements as well as an overall trend. In general, the spatial variations exhibited by the data correlate with the line of sight of neutral hydrogen column density as determined from 21-cm radio observations. This fact demonstrates that there is a galactic component to the diffuse ultraviolet radiation field.

Jakobsen, P.↗

Analysis of Igniter/Promoter Material Effects on Burn Length Variability in Astm G124 Standard Testing

ASTM G124 refers to the “Standard Test Method for Determining the Combustion Behavior of Metallic Materials in Oxygen Enriched Atmospheres”. Major test parameters are well defined in the standard and a detailed description of how to set up and conduct the test is also included. However, one variable - the igniter/promoter system - is not clearly restricted or specified. Due to the fact that this igniter/promoter system is not definitively specified, multiple materials have been used. This lack of specificity in igniter/promoter material was identified as a potential source of variability in test results, and as such has been selected for this study as a parameter to analyze and identify if the igniters/promoters should be standardized. For that purpose, several igniter/promoter systems have been selected (that were currently in use at various laboratories) which would be tested via ASTM G124 with Inconel 718 test rods. Testing was conducted over two phases – the first for screening promoter effects in the transition region of the material, and the second for comparing measured flammability thresholds identified through testing by each igniter/promoter type. The results of this study have found that igniter/promoter material is not a statistically significant factor in the variability of burn length in test samples. Initial results showing variability was likely due to small sample size, as the issue became less pronounced once more samples were tested and more data generated. Each of the igniter/promoter systems tested were effective at determining flammability thresholds and so it is concluded that no specific igniter/promoter needs to be identified in the ASTM G124 test standard.

oxygen compatibility↗

Microbiome definition re-visited: old concepts and new challenges

The field of microbiome research has evolved rapidly over the past few decades, and has become a topic of great scientific and public interest. As a result of this rapid growth in interest covering different fields, we are lacking a clear commonly agreed definition of the term ‘microbiome’. Moreover, a consensus on best practices in microbiome research is missing. Recently, a panel of international experts discussed the current gaps in the frame of the European-funded MicrobiomeSupport project. The meeting brought together about 40 leaders from diverse microbiome areas, while more than a hundred experts from all over the world took part in an online survey accompanying the workshop. This article excerpts the outcomes of the workshop and the corresponding online survey embedded in a short historical introduction and uture outlook. We propose a definition of microbiome based on the compact, clear and comprehensive description of the term provided by Whipps et al. in 1988, amended with a set of novel recommendations considering the latest technological developments and research findings. We clearly separate the terms microbiome and microbiota, and provide a comprehensive discussion considering the composition of microbiota, the heterogeneity and dynamics of microbiomes in time and space, the stability and resilience of microbial networks, the definition of core microbiomes and functionally relevant keystone species as well as co-evolutionary principles of microbe-host and inter-species interactions within the microbiome. These broad definitions together with the suggested unifying concepts will help to improve standardization of microbiome studies in the future, and could be the starting point for an integrated assessment of data resulting in a more rapid transfer of knowledge from basic science into practice.

54 ENVIRONMENTAL SCIENCES↗

A General Simulator Using State Estimation for a Space Tug Navigation System

A general simulation program is presented (GSP) involving nonlinear state estimation for space vehicle flight navigation systems. A complete explanation of the iterative guidance mode guidance law, derivation of the dynamics, coordinate frames, and state estimation routines are given so as to fully clarify the assumptions and approximations involved so that simulation results can be placed in their proper perspective. A complete set of computer acronyms and their definitions as well as explanations of the subroutines used in the GSP simulator are included. To facilitate input/output, a complete set of compatable numbers, with units, are included to aid in data development. Format specifications, output data phrase meanings and purposes, and computer card data input are clearly spelled out. A large number of simulation and analytical studies were used to determine the validity of the simulator itself as well as various data runs.

Boland, J. S., III↗

A High-Level Formalization of Floating-Point Number in PVS

We develop a formalization of floating-point numbers in PVS based on a well-known formalization in Coq. We first describe the definitions of all the needed notions, e.g., floating-point number, format, rounding modes, etc.; then, we present an application to polynomial evaluation for elementary function evaluation. The application already existed in Coq, but our formalization shows a clear improvement in the quality of the result due to the automation provided by PVS. We finally integrate our formalization into a PVS hardware-level formalization of the IEEE-854 standard previously developed at NASA.

Boldo, Sylvie↗

Experiment K-6-22. Growth hormone regulation, synthesis and secretion in microgravity. Part 1: Somatotroph physiology. Part 2: Immunohistochemical analysis of hypothalamic hormones. Part 3: Plasma analysis

The objectives of the 1887 mission were: (1) to determine if the results of the SL-3 pituitary gland experiment (1) were repeatable; and (2) to determine what effect a longer mission would have on the rat pituitary gland growth hormone (GH) system. In the 1887 experiment two issues were considered especially important. First, it was recognized that cells prepared from individual rat pituitary glands should be considered separately so that the data from the 5 glands could be analyzed in a statistically meaningful way. Second, results of the SL-3 flight involving the hollow fiber implant and HPLC GH-variant experiments suggested that the biological activity of the hormone had been negatively affected by flight. The results of the 1887 experiment documented the wisdom of addressing both issues in the protocol. Thus, the reduction in secretory capacity of flight cells during subsequent extended cell culture on Earth was documented statistically, and thereby established the validity of the SL-3 result. The results of both flight experiments thus support the contention that there is a secretory lesion in pituitary GH cells of flight animals. The primary objective of both missions was a clear definition of the effect of spaceflight on the GH cell system. There can no longer be any reasonable doubt that this system is affected in microgravity. One explanation for the reason(s) underlying the better known effects of spaceflight on organisms, viz. changes in bone, muscle and immune systems may very well rest with such changes in bGH. In spite of the fact that rats in the Cosmos 1887 flight were on Earth for two days after flight, the data show that the GH system had still not recovered from the effects of flight. Many questions remain. One of the more important concerns the GRF responsiveness of somatotrophs after flight. This will be tested in an upcoming experiment.

Grindeland, R.↗

Cirrus cloud spectra and layers observed during the FIRE and GASP projects

A general characterization is developed for cirrus clouds in terms of their spectra, shapes, optical thicknesses, and radiative properties for use in numerical models. Data sets from the Global Atmospheric Sampling Project (GASP) of the upper troposphere and the First ISCCP Regional Experiment (FIRE) are combined and analyzed to study general traits of cirrus clouds. A definition is given for 2D turbulence, and the GASP and FIRE data sets are examined with respect to cirrus layers and entrainment and to dominant turbulent scales. The approach employs conditional sampling in cloudy and clear air, power-spectral analysis, and mixing-line-type diagrams. Evidence is given for a well mixed cloud deck and for the tendency of cirrus to be formed in multilayer structures. The results are of use in mesoscale and global circulation models which predict cirrus, in small-scale cirrus modeling, and in studying the role of gravity waves in the horizontal structure of upper tropospheric clouds.

Flatau, Piotr J.↗

Interpretation and Formalization of the Right-of-Way Rules

This paper presents an interpretation and mathematical definition of the right-of-way rules as stated in USA, Title 14 of the Code of Federal Regulations, Part 91, Section 91.113 (14 CFR 91.113). In an encounter between two aircraft, the right-of-way rules defines which aircraft, if any, has the right-of-way and which AQ2 aircraft must maneuver to stay well clear of the other aircraft. The objective of the work presented in this paper is to give an unambiguous interpretation of the rules. From the interpretation, a precise mathematical formulation is created that can be used for analysis and proof of properties. The mathematical formulation has been defined in the Prototype Verification System (PVS) and properties of well formedness and core properties of the formalization have been mechanically proved. This mathematical formulation can be implemented digitally, so that right-of-way rules can be used in simulation or in future autonomous operations.

Right-of-Way↗

Development of an Interoperable GNSS Space Service Volume

Global Navigation Satellite Systems (GNSS), now routinely used for navigation by spacecraft in low Earth orbit, are being used increasingly by high-altitude users in geostationary orbit and high eccentric orbits as well, near to and above the GNSS constellations themselves. Available signals in these regimes are very limited for any single GNSS constellation due to the weak signal strength, the blockage of signals by the Earth, and the limited number of satellites. But with the recent development of multiple GNSS constellations and ongoing upgrades to existing constellations, multi-GNSS signal availability is set to improve significantly. This will only be achieved if these signals are designed to be interoperable and are clearly documented and supported.All satellite navigation constellation providers are working together through the United Nations International Committee on GNSS (ICG) to establish an interoperable multi-GNSS Space Service Volume (SSV) for the benefit of all GNSS space users. The multi-GNSS SSV represents a common set of baseline definitions and assumptions for high-altitude service in space, documents the service provided by each constellation, and provides a framework for continued support for space users. This paper provides an overview of the GNSS SSV concept, development, status, and achievements within the ICG. It describes the final adopted definition and performance characteristics of the GNSS SSV, as well as the numerous benefits and use cases enabled by this development. Extensive technical analysis was also performed to illustrate these benefits in terms of signal availability, both on a global scale, and for multiple distinct mission types. This analysis is summarized here and presented in detail in a companion paper by Enderle, et al.

Positioning↗