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At least 901 records · Page 50

Three-Dimensional Cell Culture Models for Infectious Disease and Drug Development

Three-dimensional (3-D) cell cultures hold enormous potential to advance our understanding of infectious disease and to effectively translate basic cellular research into clinical applications. Using novel NASA bioreactor technology, the rotating wall vessel (RWV), we have engineered physiologically relevant 3-D human tissue culture models for infectious disease studies. The design of the RWV is based on the understanding that organs and tissues function in a 3-D environment, and that this 3-D architecture is critical for the differentiated form and function of tissues in vivo. The RWV provides large numbers of cells which are amenable to a wide variety of experimental manipulations and provides an easy, reproducible, and cost-effective approach to enhance differentiated features of cell culture models.

Nickerson, Cheryl A.↗

International Space Station USOS Potable Water Dispenser Development

The International Space Station (ISS) Russian Segment currently provides potable water dispensing capability for crewmember food and beverage rehydration. All ISS crewmembers rehydrate Russian and U.S. style food packages from this location. A new United States On-orbit Segment (USOS) Potable Water Dispenser (PWD) is under development. This unit will provide additional potable water dispensing capability to support an onorbit crew of six. The PWD is designed to provide incremental quantities of hot and ambient temperature potable water to U.S. style food packages. It will receive iodinated water from the Fuel Cell Water Bus in the U.S. Laboratory element. The unit will provide potable-quality water, including active removal of biocidal iodine prior to dispensing. A heater assembly contained within the unit will be able to supply up to 2.0 liters of hot water (65 to 93oC) every thirty minutes. This quantity will allow three to four crewmembers to rehydrate their food and beverages from this location during a single meal. The unit is designed to remain functional for up to ten years with replacement of limited life items such as filters. It will be the size of two stacked Shuttle Middeck lockers (approximately the size of two small suitcases) and integrated into a science payload rack in the U.S. Laboratory element. Providing potable-quality water at the proper temperature for food and beverage reconstitution is critical to maintaining crew health and well-being. The numerous engineering challenges as well as human factors and safety considerations during the concept, design, and prototyping are outlined in this paper.

Shaw, Laura A.↗

The 50 Constellation Priority Sites

The Constellation program (CxP) has developed a list of 50 sites of interest on the Moon which will be targeted by the LRO narrow angle camera. The list has also been provided to the M~ team to supplement their targeting list. This list does not represent a "site selection" process; rather the goal was to find "representative" sites and terrains to understand the range of possible surface conditions for human lunar exploration to aid engineering design and operational planning. The list compilers leveraged heavily on past site selection work (e.g. Geoscience and a Lunar Base Workshop - 1988, Site Selection Strategy for a Lunar Outpost - 1990, Exploration Systems Architecture Study (ESAS) - 2005). Considerations included scientific, resource utilization, and operational merits, and a desire to span lunar terrain types. The targets have been organized into two "tiers" of 25 sites each to provide a relative priority ranking in the event of mutual interference. A LEAG SAT (special action team) was established to validate and recommend modifications to the list. This SAT was chaired by Dr. Paul Lucey. They provided their final results to CxP in May. Dr. Wendell Mendell will organize an on-going analysis of the data as they come down to ensure data quality and determine if and when a site has sufficient data to be retired from the list. The list was compiled using the best available data, however, it is understood that with the flood of new lunar data, minor modifications or adjustments may be required.

Noble, S.↗

Aerocapture Guidance and Performance at Mars for High-Mass Systems

The Mars Entry, Descent, and Landing System Analysis (EDL-SA) project has been tasked with performing systems analysis to identify the optimal technologies required to land a 20-50 MT Exploration-class mission on Mars. It has been shown that it is not possible to safely land these large systems using heritage Mars EDL systems, or analogous Earth or Moon EDL systems. In 2007, NASA conducted a Mars Exploration Architecture Study which included an in depth review of the science motivations and engineering technology requirements for a human Mars mission campaign. This study resulted in an update to the Mars Design Reference Architecture (DRA 5.0). Among the primary findings and recommendations was the conclusion that landing of large payloads (greater than 1 MT) on the surface of Mars remains a key architectural challenge. Additionally, research and system studies of fundamental EDL technologies were highly recommended. The EDL-SA project identified the candidate technologies and assembled them into full capture and EDL sequences so that simulations could be developed to evaluate them. The chosen architectures combine the various technologies of interest in eight different ways. For aerocapture, only two scenarios were considered. The first is a rigid mid-L/D aeroshell (AS), which is represented in architectures 1, 4, 5, and 7. This scenario calls for a vehicle that flies at a 55-degree angle of attack, resulting in ballistic coefficient and L/D values of 490 kg/m 2 and 0.43, respectively. The second is a lifting hypersonic inflatable aerodynamic decelerator (HIAD), which is represented in architectures 2, 6, and 8. This scenario requires the vehicle to fly at a 22.2- degree angle of attack, which correlates to an L/D of 0.3 and was sized to provide a ballistic coefficient of 165 kg/m 2 . Architecture 3 is an all-propulsive sequence, and is not considered in this study.

Zumwalt, Carlie H.↗

NASA Hazard Analysis Process

This viewgraph presentation reviews The NASA Hazard Analysis process. The contents include: 1) Significant Incidents and Close Calls in Human Spaceflight; 2) Subsystem Safety Engineering Through the Project Life Cycle; 3) The Risk Informed Design Process; 4) Types of NASA Hazard Analysis; 5) Preliminary Hazard Analysis (PHA); 6) Hazard Analysis Process; 7) Identify Hazardous Conditions; 8) Consider All Interfaces; 9) Work a Preliminary Hazard List; 10) NASA Generic Hazards List; and 11) Final Thoughts

Deckert, George↗

Wernher von Braun: Reflections on His Contributions to Space Exploration

In 1950, Dr. Wernher von Braun and approximately 100 of his team members came to Huntsville, Alabama, to begin work with the Army on what would later become America's historic space program. He would later serve as the first director of the Marshall Space Flight Center and led the development of the Saturn V launch vehicle that launched seven crewed American mission to the moon, as well as America s first space station, Skylab. Von Braun is best known for his team s technical achievements. He realized his dream of exploring outer space by helping place humans on the moon. His engineering and managerial talent during the Apollo era had contributed to a technological revolution. He was by all accounts a good engineer, but he was only one among many. What set Von Braun apart were his charisma, his vision, and his leadership skills. He inspired loyalty and dedication in the people around him. He understood the importance of communicating his vision to his team, to political and business leaders and the public. Today, the Marshall Center continues his vision by pursuing engineering and scientific projects that will continue to open space to exploration. This presentation will discuss Von Braun's impact on Huntsville, the Marshall Center, the nation and the world and look at his contributions in context of where world space exploration is today.

Goldman, Arthur E.↗

A Geology Sampling System for Microgravity Bodies

Human exploration of microgravity bodies is being investigated as a precursor to a Mars surface mission. Asteroids, comets, dwarf planets, and the moons of Mars all fall into this microgravity category and some are been discussed as potential mission targets. Obtaining geological samples for return to Earth will be a major objective for any mission to a microgravity body. Currently the knowledge base for geology sampling in microgravity is in its infancy. Humans interacting with non-engineered surfaces in microgravity environment pose unique challenges. In preparation for such missions a team at the NASA Johnson Space Center has been working to gain experience on how to safely obtain numerous sample types in such an environment. This paper describes the type of samples the science community is interested in, highlights notable prototype work, and discusses an integrated geology sampling solution.

Hood, Anthony↗

NASA Human System Risk Assessment Process

NASA utilizes an evidence based system to perform risk assessments for the human system for spaceflight missions. The center of this process is the multi-disciplinary Human System Risk Board (HSRB). The HSRB is chartered from the Chief Health and Medical Officer (OCHMO) at NASA Headquarters. The HSRB reviews all human system risks via an established comprehensive risk and configuration management plan based on a project management approach. The HSRB facilitates the integration of human research (terrestrial and spaceflight), medical operations, occupational surveillance, systems engineering and many other disciplines in a comprehensive review of human system risks. The HSRB considers all factors that influence human risk. These factors include pre-mission considerations such as screening criteria, training, age, sex, and physiological condition. In mission factors such as available countermeasures, mission duration and location and post mission factors such as time to return to baseline (reconditioning), post mission health screening, and available treatments. All of the factors influence the total risk assessment for each human risk. The HSRB performed a comprehensive review of all potential inflight medical conditions and events and over the course of several reviews consolidated the number of human system risks to 30, where the greatest emphasis is placed for investing program dollars for risk mitigation. The HSRB considers all available evidence from human research and, medical operations and occupational surveillance in assessing the risks for appropriate mitigation and future work. All applicable DRMs (low earth orbit for 6 and 12 months, deep space for 30 days and 1 year, a lunar mission for 1 year, and a planetary mission for 3 years) are considered as human system risks are modified by the hazards associated with space flight such as microgravity, exposure to radiation, distance from the earth, isolation and a closed environment. Each risk has a summary two-page assessment representing the state of knowledge/evidence of that risk, available risk mitigations, traceability to the Space Flight Human System Standards (SFHSS) and program requirements, and future work required. These data then can drive coordinated budgets across the Human Research Program, the International Space Station, Crew Health and Safety and Advanced Exploration System budgets to provide the most economical and timely mitigations. The risk assessments were completed for the 6 DRMs and serve as the baseline for which subsequent research and technology development and crew health care portfolios can be assessed. The HSRB reviews each risk at least annually or when new evidence/information is available that adds to the body of evidence. The current status of each risk can be reported to program management for operations, budget reviews and general oversight of the human system risk management program.

Francisco, D.↗

A Geology Sampling System for Small Bodies

Human exploration of Small Bodies is being investigated as a precursor to a Mars surface mission. Asteroids, comets, dwarf planets, and the moons of Mars all fall into this Small Bodies category and some are being discussed as potential mission tar-gets. Obtaining geological samples for return to Earth will be a major objective for any mission to a Small Body. Currently the knowledge base for geology sampling in microgravity is in its infancy. Furthermore, humans interacting with non-engineered surfaces in a microgravity environment poses unique challenges. In preparation for such missions, a team at the National Aeronautics and Space Administration (NASA) John-son Space Center (JSC) has been working to gain experience on how to safely obtain numerous sample types in such an environment. This abstract briefly summarizes the type of samples the science community is interested in, discusses an integrated geology sampling solution, and highlights some of the unique challenges associated with this type of exploration.

Hood, A. D.↗

A Geology Sampling System for Small Bodies

Human exploration of microgravity bodies is being investigated as a precursor to a Mars surface mission. Asteroids, comets, dwarf planets, and the moons of Mars all fall into this microgravity category and some are being discussed as potential mission targets. Obtaining geological samples for return to Earth will be a major objective for any mission to a small body. Currently, the knowledge base for geology sampling in microgravity is in its infancy. Humans interacting with non-engineered surfaces in microgravity environment pose unique challenges. In preparation for such missions a team at the NASA Johnson Space Center has been working to gain experience on how to safely obtain numerous sample types in such an environment. This paper describes the type of samples the science community is interested in, highlights notable prototype work, and discusses an integrated geology sampling solution.

Naids, Adam J.↗

Simplified one-pot synthesis of [.sup.18F]SFB for radiolabeling

A non-aqueous single pot synthesis of [.sup.18F]SFB is set forth. The [.sup.18F]SFB produced with this method is then used, for example, to label a peptide or an engineered antibody fragment (diabody) targeting human epidermal growth factor receptor 2 (HER2) as representative examples of labeled compounds for use as an injectable composition to locate abnormal tissue, specifically tumors within an animal or human using a PET scan.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Argonne News Brief: Making Sense of Noise

The Argonne Leadership Computing Facility at Argonne National Laboratory helped Joe Nichols, of the University of Minnesota, to create high fidelity simulations of jet turbulence to determine how and where noise is produced. The results may lead to novel engineering designs that reduce noise over commercial flight paths and on aircraft carrier decks.

42 ENGINEERING↗

Environmental Engineering for the 21st Century: Addressing Grand Challenges

Environmental engineers support the well-being of people and the planet in areas where the two intersect. Over the decades the field has improved countless lives through innovative systems for delivering water, treating waste, and preventing and remediating pollution in air, water, and soil. These achievements are a testament to the multidisciplinary, pragmatic, systems-oriented approach that characterizes environmental engineering. The future holds daunting challenges for human society and our environment. Populations are expanding, demand for resources is increasing, the climate is changing, and humanity’s impacts on the planet continue to mount. Will we be able to achieve a better quality of life for our growing population without compromising the ability of future generations to achieve the same? This study, authored by 18 of the nation’s leading environmental engineers, scientists, and policy experts under the auspices of the National Academies of Sciences, Engineering, and Medicine, outlines the crucial role for environmental engineers in this period of dramatic growth and change. The report identifies five pressing challenges of the 21st century that environmental engineers are uniquely poised to help advance: 1: Sustainably supply food, water, and energy, 2: Curb climate change and adapt to its impacts, 3: Design a future without pollution and waste, 4: Create efficient, healthy, resilient cities, and 5: Foster informed decisions and actions. The report’s vision is ambitious. The challenges ahead are substantial. Yet every day, environmental engineers are making progress, both by applying existing knowledge and skills and by advancing research and innovation to generate new insights and achievements. By refocusing and redoubling its efforts to advance practical, impactful solutions for humanity’s multifaceted, vexing problems, the field of environmental engineering can build on its past successes—and chart new territory—in the decades ahead.

42 ENGINEERING↗

New Window into the Human Body

Michael Vannier, MD, a former NASA engineer, recognized the similarity between NASA's computerized image processing technology and nuclear magnetic resonance. With technical assistance from Kennedy Space Center, he developed a computer program for Mallinckrodt Institute of Radiology enabling Nuclear Magnetic Resonance (NMR) to scan body tissue for earlier diagnoses. Dr. Vannier feels that "satellite imaging" has opened a new window into the human body.

Source record↗

A Methodology for Investigating Adaptive Postural Control

Our research on postural control and human-environment interactions provides an appropriate scientific foundation for understanding the skill of mass handling by astronauts in weightless conditions (e.g., extravehicular activity or EVA). We conducted an investigation of such skills in NASA's principal mass-handling simulator, the Precision Air-Bearing Floor, at the Johnson Space Center. We have studied skilled movement-body within a multidisciplinary context that draws on concepts and methods from biological and behavioral sciences (e.g., psychology, kinesiology and neurophysiology) as well as bioengineering. Our multidisciplinary research has led to the development of measures, for manual interactions between individuals and the substantial environment, that plausibly are observable by human sensory systems. We consider these methods to be the most important general contribution of our EVA investigation. We describe our perspective as control theoretic because it draws more on fundamental concepts about control systems in engineering than it does on working constructs from the subdisciplines of biomechanics and motor control in the bio-behavioral sciences. At the same time, we have attempted to identify the theoretical underpinnings of control-systems engineering that are most relevant to control by human beings. We believe that these underpinnings are implicit in the assumptions that cut across diverse methods in control-systems engineering, especially the various methods associated with "nonlinear control", "fuzzy control," and "adaptive control" in engineering. Our methods are based on these theoretical foundations rather than on the mathematical formalisms that are associated with particular methods in control-systems engineering. The most important aspects of the human-environment interaction in our investigation of mass handling are the functional consequences that body configuration and stability have for the pick up of information or the achievement of overt goals. It follows that an essential characteristic of postural behavior is the effective maintenance of the orientation and stability of the sensory and motor "platforms" (e.g., head or shoulders) over variations in the human, the environment and the task. This general skill suggests that individuals should be sensitive to the functional consequences of body configuration and stability. In other words, individuals should perceive the relation between configuration, stability, and performance so that they can adaptively control their interaction with the surroundings. Human-environment interactions constitute robust systems in that individuals can maintain the stability of such interactions over uncertainty about and variations in the dynamics of the interaction. Robust interactions allow individuals to adopt orientations and configurations that are not optimal with respect to purely energetic criteria. Individuals can tolerate variation in postural states, and such variation can serve an important function in adaptive systems. Postural variability generates stimulation which is "textured" by the dynamics of the human-environment system. The texture or structure in stimulation provides information about variation in dynamics, and such information can be sufficient to guide adaption in control strategies. Our method were designed to measure informative patterns of movement variability.

McDonald, P. V.↗

Development of trophoblast cystic structures from human induced pluripotent stem cells in limited-area cell culture

Highlights: • Limited-area culture of iPSs induced trophectoderm-like cyst structures. • Trophectoderm-like cyst structures exhibited trophoblast function. • These cysts provide a 3D model for the study of differentiation and morphogenesis. We developed a novel engineering technique to induce differentiation of human induced pluripotent stem cells (hiPSCs) into organoids mimicking the trophectoderm (TE). Here, hiPSCs were cultured on a limited area of 2–4 mm in diameter. After 15–20 days, spherical cysts appeared on the surface of the limited area. Secretion of human chorionic gonadotrophin (hCG) began to increase after ∼ 20 days and remained dramatically elevated over the next 20 days. Limited-area-cultured cysts exhibited expression of hCG, which was a result of epithelial differentiation. Low expression levels of pluripotent genes and high expression levels of trophoblast lineage-specific genes were detected in the cells of spherical cysts. Multinucleated syncytia trophoblast was observed in the reseeded cystic cells. We observed hiPSC-derived cysts that morphologically resembled trophectoderm in vivo. The limited-area cell culture induced a three-dimensional (3D) trophectoderm organoid, which has potential for use in the study of human trophoblast differentiation and placental morphogenesis.

60 APPLIED LIFE SCIENCES↗

Mitigation of chromosome loss in clinical CRISPR-Cas9-engineered T cells

CRISPR-Cas9 genome editing has enabled advanced T cell therapies, but occasional loss of the targeted chromosome remains a safety concern. To investigate whether Cas9-induced chromosome loss is a universal phenomenon and evaluate its clinical significance, we conducted a systematic analysis in primary human T cells. Arrayed and pooled CRISPR screens revealed that chromosome loss was generalizable across the genome and resulted in partial and entire loss of the targeted chromosome, including in preclinical chimeric antigen receptor T cells. T cells with chromosome loss persisted for weeks in culture, implying the potential to interfere with clinical use. A modified cell manufacturing process, employed in our first-in-human clinical trial of Cas9-engineered T cells (NCT03399448), reduced chromosome loss while largely preserving genome editing efficacy. Expression of p53 correlated with protection from chromosome loss observed in this protocol, suggesting both a mechanism and strategy for T cell engineering that mitigates this genotoxicity in the clinic.

59 BASIC BIOLOGICAL SCIENCES↗