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At least 37 records · Page 2

Probing the subcellular nanostructure of engineered human cardiomyocytes in 3D tissue

Abstract The structural and functional maturation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is essential for pharmaceutical testing, disease modeling, and ultimately therapeutic use. Multicellular 3D-tissue platforms have improved the functional maturation of hiPSC-CMs, but probing cardiac contractile properties in a 3D environment remains challenging, especially at depth and in live tissues. Using small-angle X-ray scattering (SAXS) imaging, we show that hiPSC-CMs matured and examined in a 3D environment exhibit a periodic spatial arrangement of the myofilament lattice, which has not been previously detected in hiPSC-CMs. The contractile force is found to correlate with both the scattering intensity ( R 2 = 0.44) and lattice spacing ( R 2 = 0.46). The scattering intensity also correlates with lattice spacing ( R 2 = 0.81), suggestive of lower noise in our structural measurement than in the functional measurement. Notably, we observed decreased myofilament ordering in tissues with a myofilament mutation known to lead to hypertrophic cardiomyopathy (HCM). Our results highlight the progress of human cardiac tissue engineering and enable unprecedented study of structural maturation in hiPSC-CMs.

36 MATERIALS SCIENCE↗

Handbook of human engineering design data for reduced gravity conditions

A Handbook is presented for the use of engineers, designers, and human factors specialists during the developmental and detailed design phases of manned spacecraft programs. Detailed and diverse quantified data on man's capabilities and tolerances for survival and productive effort in the extraterrestrial environment are provided. Quantified data and information on the space environment as well as the characteristics of the vehicular or residential environment required to support man in outer space are also given.

Marton, T.↗

The Application of the Human Engineering Modeling and Performance Laboratory for Space Vehicle Ground Processing Tasks at Kennedy Space Center

The introduction of United Space Alliance's Human Engineering Modeling and Performance Laboratory began in early 2007 in an attempt to address the problematic workspace design issues that the Space Shuttle has imposed on technicians performing maintenance and inspection operations. The Space Shuttle was not expected to require the extensive maintenance it undergoes between flights. As a result, extensive, costly resources have been expended on workarounds and modifications to accommodate ground processing personnel. Consideration of basic human factors principles for design of maintenance is essential during the design phase of future space vehicles, facilities, and equipment. Simulation will be needed to test and validate designs before implementation.

Woodbury, Sarah K.↗

We Have the Spaceship; But Where's the Start Button: Human Engineering Issues in the Age of Long Duration Space Exploration

As long duration space exploration and habitation becomes more commonplace, a number of Human Engineering factors (Gravitational Adaptation, 2-D to 3-D Movement Adaptation, Design Form/Function, and Space Ergonomics to name a few) will become more pronounced. More research and development is needed in these areas or the explorers may find themselves in painful or dangerous situations.

Hamilton, George S.↗

Human engineering analysis for the high speed civil transport flight deck

The Boeing Company is investigating the feasibility of building a second generation supersonic transport. If current studies support its viability, this airplane, known as the High Speed Civil Transport (HSCT), could be launched early in the next century. The HSCT will cruise at Mach 2.4, be over 300 feet long, have an initial range of between 5000 and 6000 NM, and carry approximately 300 passengers. We are presently involved in developing an advanced flight deck for the HSCT. As part of this effort we are undertaking a human engineering analysis that involves a top-down, mission driven approach that will allow a systematic determination of flight deck functional and information requirements. The present paper describes this work.

Regal, David M.↗

We Have the Spaceship; But Where's the Start Button: Human Engineering Issues in the Age of Long Duration Space Exploration - Presentation

This viewgraph presentation addresses the following considerations for human factors engineering during long duration human space flight: gravitational adaptation, 2-D to 3-D adaptation, handles, exercise posture, and space ergonomics. The presentation argues that there is an urgent need to advance research is these areas in preparation for future manned missions.

Hamilton, George↗

Tissue-engineered human bioartificial muscles expressing a foreign recombinant protein for gene therapy

Murine skeletal muscle cells transduced with foreign genes and tissue engineered in vitro into bioartificial muscles (BAMs) are capable of long-term delivery of soluble growth factors when implanted into syngeneic mice (Vandenburgh et al., 1996b). With the goal of developing a therapeutic cell-based protein delivery system for humans, similar genetic tissue-engineering techniques were designed for human skeletal muscle stem cells. Stem cell myoblasts were isolated, cloned, and expanded in vitro from biopsied healthy adult (mean age, 42 +/- 2 years), and elderly congestive heart failure patient (mean age, 76 +/- 1 years) skeletal muscle. Total cell yield varied widely between biopsies (50 to 672 per 100 mg of tissue, N = 10), but was not significantly different between the two patient groups. Percent myoblasts per biopsy (73 +/- 6%), number of myoblast doublings prior to senescence in vitro (37 +/- 2), and myoblast doubling time (27 +/- 1 hr) were also not significantly different between the two patient groups. Fusion kinetics of the myoblasts were similar for the two groups after 20-22 doublings (74 +/- 2% myoblast fusion) when the biopsy samples had been expanded to 1 to 2 billion muscle cells, a number acceptable for human gene therapy use. The myoblasts from the two groups could be equally transduced ex vivo with replication-deficient retroviral expression vectors to secrete 0.5 to 2 microg of a foreign protein (recombinant human growth hormone, rhGH)/10(6) cells/day, and tissue engineered into human BAMs containing parallel arrays of differentiated, postmitotic myofibers. This work suggests that autologous human skeletal myoblasts from a potential patient population can be isolated, genetically modified to secrete foreign proteins, and tissue engineered into implantable living protein secretory devices for therapeutic use.

Non-NASA Center↗

Mechanical stimulation improves tissue-engineered human skeletal muscle

Human bioartificial muscles (HBAMs) are tissue engineered by suspending muscle cells in collagen/MATRIGEL, casting in a silicone mold containing end attachment sites, and allowing the cells to differentiate for 8 to 16 days. The resulting HBAMs are representative of skeletal muscle in that they contain parallel arrays of postmitotic myofibers; however, they differ in many other morphological characteristics. To engineer improved HBAMs, i.e., more in vivo-like, we developed Mechanical Cell Stimulator (MCS) hardware to apply in vivo-like forces directly to the engineered tissue. A sensitive force transducer attached to the HBAM measured real-time, internally generated, as well as externally applied, forces. The muscle cells generated increasing internal forces during formation which were inhibitable with a cytoskeleton depolymerizer. Repetitive stretch/relaxation for 8 days increased the HBAM elasticity two- to threefold, mean myofiber diameter 12%, and myofiber area percent 40%. This system allows engineering of improved skeletal muscle analogs as well as a nondestructive method to determine passive force and viscoelastic properties of the resulting tissue.

Non-NASA Center↗

Multiscale embedded printing of engineered human tissue and organ equivalents

Creating tissue and organ equivalents with intricate architectures and multiscale functional feature sizes is the first step toward the reconstruction of transplantable human tissues and organs. Existing embedded ink writing approaches are limited by achievable feature sizes ranging from hundreds of microns to tens of millimeters, which hinders their ability to accurately duplicate structures found in various human tissues and organs. In this study, a multiscale embedded printing (MSEP) strategy is developed, in which a stimuli-responsive yield-stress fluid is applied to facilitate the printing process. A dynamic layer height control method is developed to print the cornea with a smooth surface on the order of microns, which can effectively overcome the layered morphology in conventional extrusion-based three-dimensional bioprinting methods. Since the support bath is sensitive to temperature change, it can be easily removed after printing by tuning the ambient temperature, which facilitates the fabrication of human eyeballs with optic nerves and aortic heart valves with overhanging leaflets on the order of a few millimeters. The thermosensitivity of the support bath also enables the reconstruction of the full-scale human heart on the order of tens of centimeters by on-demand adding support bath materials during printing. Here, the proposed MSEP demonstrates broader printable functional feature sizes ranging from microns to centimeters, providing a viable and reliable technical solution for tissue and organ printing in the future.

3D bioprinting↗

The NASA Ames integral aircraft passenger seat concept - A human engineering approach

A new NASA Ames concept for an aircraft passenger seat has been under research and development since 1968. It includes many human-factor features that will provide protection to the passenger from vibration, jostle, and high impact. It is comfortable and safer than any of the seats presently in use. An in-depth design, fabrication, and impact analysis was conducted in order to design a seat that will maximize passenger protection in high g impacts (20 g horizontal -Gx, 36 g vertical +Gz, 16 g lateral Gy). The method for absorbing impact energy was accomplished with a combination of stretching stainless steel cables, thread breaking of stitches, hydraulic mechanism and the special Temper Form cushions. The restraint system for the seat consisted of a lap belt and shoulder harness inertia reel combination.

Kubokawa, C. C.↗

Engineered human vascular models to study endothelial dysfunction in infectious disease

Vascular involvement plays a pivotal role in the pathogenesis of numerous emerging viral threats, with climate changes amplifying the likelihood of these diseases evolving into pandemics. Establishing an infectable and physiologically relevant human in vitro model holds immense importance in comprehending the pathogenesis of these threats and devising effective countermeasures. Although in vivo models provide valuable insight into disease, their application is restricted by interspecies variations, particularly concerning pathogens exclusive to humans. Moreover, animal models often fail to replicate comorbidities prevalent in patient populations, thus limiting our understanding of disease behavior in humans. In this study, we have devised a testing platform aimed at exploring pathogen interactions with innate immunity within the vasculature, encompassing both healthy and dysfunctional endothelial conditions.

42 ENGINEERING↗

Engineered human antibodies for the opsonization and killing of Staphylococcus aureus

Gram-positive organisms with their thick envelope cannot be lysed by complement alone. Nonetheless, antibody-binding on the surface can recruit complement and mark these invaders for uptake and killing by phagocytes, a process known as opsonophagocytosis. The crystallizable fragment of immunoglobulins (Fcγ) is key for complement recruitment. The cell surface of S. aureus is coated with Staphylococcal protein A (SpA). SpA captures the Fcγ domain of IgG and interferes with opsonization by anti-S. aureus antibodies. In principle, the Fcγ domain of therapeutic antibodies could be engineered to avoid the inhibitory activity of SpA. However, the SpA-binding site on Fcγ overlaps with that of the neonatal Fc receptor (FcRn), an interaction that is critical for prolonging the half-life of serum IgG. This evolutionary adaptation poses a challenge for the exploration of Fcγ mutants that can both weaken SpA–IgG interactions and retain stability. Here, we use both wild-type and transgenic human FcRn mice to identify antibodies with enhanced half-life and increased opsonophagocytic killing in models of S. aureus infection and demonstrate that antibody-based immunotherapy can be improved by modifying Fcγ. Our experiments also show that by competing for FcRn-binding, staphylococci effectively reduce the half-life of antibodies during infection. These observations may have profound impact in treating cancer, autoimmune, and asthma patients colonized or infected with S. aureus and undergoing monoclonal antibody treatment.

59 BASIC BIOLOGICAL SCIENCES↗

Education, training, and human engineering in aerospace; SAE Aerotech '93, Costa Mesa, CA, Sep. 27-30, 1993

Advances in simulation technology are discussed by a number of government and industry experts, for both training and research and development applications. Advanced techniques, such as helmet-mounted information displays, neurocontrollers, automated training systems, and simulation for space-based systems are included. Advances in training methodology for air transportation are covered by a group of experts in that field, including discussions of advanced flight deck transition training, new training tools, and effective low cost alternatives for part-task training. With the ever-increasing emphasis on human factors in cockpit and cabin design, the section on research, advances, and certification criteria in that field is pertinent. NASA, aircraft manufacturing, and FAA representatives have compiled an informative group of presentations concerning active topics and considerations in human factors design.

Shapiro, Diane C.↗

Collaborative Human Engineering Work in Space Exploration Extravehicular Activities (EVA)

A viewgraph presentation on extravehicular activities in space exploration in collaboration with other NASA centers, industries, and universities is shown. The topics include: 1) Concept of Operations for Future EVA activities; 2) Desert Research and Technology Studies (RATS); 3) Advanced EVA Walkback Test; 4) Walkback Subjective Results; 5) Integrated Suit Test 1; 6) Portable Life Support Subsystem (PLSS); 7) Flex PLSS Design Process; and 8) EVA Information System; 9)

DeSantis, Lena↗