Below, explore peer-reviewed journal articles related to ISS National Lab investigations. For a more extensive list of spaceflight-related publications (not limited to ISS National Lab sponsorship), see the International Space Station Research Results Citations on the NASA website.
Remotely sensed data acquired by orbital sensor systems has emerged as a vital tool to identify the extent of damage resulting from a natural disaster, as well as providing near-real time mapping support to response efforts on the ground and humanitarian aid efforts. The International Space Station (ISS) is a unique terrestrial remote sensing platform for acquiring disaster response imagery. Unlike automated remote-sensing platforms it has a human crew; is equipped with both internal and externally-mounted remote sensing instruments; and has an inclined, low-Earth orbit that provides variable views and lighting (day and night) over 90 percent of the inhabited surface of the Earth. As such, it provides a useful complement to autonomous sensor systems in higher altitude polar orbits. NASA remote sensing assets on the station began collecting International Charter, Space and Major Disasters, also known informally as the International Disaster Charter (IDC) response data in May 2012. Since the start of IDC response in 2012, and as of late March 2015, there have been 123 IDC activations; NASA sensor systems have collected data for thirty-four of these events. Of the successful data collections, eight involved two or more ISS sensor systems responding to the same event. Data has also been collected by International Partners in response to natural disasters, most notably JAXA and Roscosmos/Energia through the Urugan program.
Doxorubicin (DOX) is a highly effective anthracycline chemotherapy agent effective in treating a broad range of life-threatening malignancies but it causes cardiotoxicity in many subjects. While the mechanism of its cardiotoxic effects remains elusive, DOX-related cardiotoxicity can lead to heart failure in patients. In this study, we investigated the effects of DOX-induced cardiotoxicity on human cardiomyocytes (CMs) using a three-dimensional (3D) bioprinted cardiac spheroidal droplet based-system in comparison with the traditional two-dimensional cell (2D) culture model. The effects of DOX were alleviated with the addition of N-acetylcysteine (NAC) and Tiron. Caspase-3 activity was quantified, and reactive oxygen species (ROS) production was measured using dihydroethidium (DHE) staining. Application of varying concentrations of DOX (0.4 μM–1 μM) to CMs revealed a dose-specific response, with 1 μM concentration imposing maximum cytotoxicity and 0.22 ± 0.11% of viable cells in 3D samples versus 1.02 ± 0.28% viable cells in 2D cultures, after 5 days of culture. Moreover, a flow cytometric analysis study was conducted to study CMs proliferation in the presence of DOX and antioxidants. Our data support the use of a 3D bioprinted cardiac spheroidal droplet as a robust and high-throughput screening model for drug toxicity. In the future, this 3D spheroidal droplet model can be adopted as a human-derived tissue-engineered equivalent to address challenges in other various aspects of biomedical pre-clinical research.
The Hyperspectral Imager for the Coastal Ocean (HICO) aboard the International Space Station has offered for the first time a dedicated space-borne hyperspectral sensor specifically designed for remote sensing of the coastal environment. However, several processing steps are required to convert calibrated top-of-atmosphere radiances to the desired geophysical parameter(s). These steps add various amounts of uncertainty that can cumulatively render the geophysical parameter imprecise and potentially unusable if the objective is to analyze trends and/or seasonal variability. This research presented here has focused on: (1) atmospheric correction of HICO imagery; (2) retrieval of bathymetry using an improved implementation of a shallow water inversion algorithm; (3) propagation of uncertainty due to environmental noise through the bathymetry retrieval process; (4) issues relating to consistent geo-location of HICO imagery necessary for time series analysis, and; (5) tide height corrections of the retrieved bathymetric dataset. The underlying question of whether a temporal change in depth is detectable above uncertainty is also addressed. To this end, nine HICO images spanning November 2011 to August 2012, over the Shark Bay World Heritage Area, Western Australia, were examined. The results presented indicate that precision of the bathymetric retrievals is dependent on the shallow water inversion algorithm used. Within this study, an average of 70% of pixels for the entire HICO-derived bathymetry dataset achieved a relative uncertainty of less than ± 20%. A per-pixel t-test analysis between derived bathymetry images at successive timestamps revealed observable changes in depth to as low as 0.4 m. However, the present geolocation accuracy of HICO is relatively poor and needs further improvements before extensive time series analysis can be performed.
Specific coating processes and materials were investigated in the quest to develop multilayer coatings with greater tolerance to space radiation exposure. Ultraviolet reflection (UVR) and wide-band antireflection (AR) multilayer coatings were deposited on solar cell covers and test substrates and subsequently exposed to simulated space environments and also flown on the Materials International Space Station Experiment-7 (MISSE-7) to determine their space environment stability. Functional solar cells integrated with these coatings underwent simulated UV and MISSE-7 low earth orbit flight exposure. The effects of UV, proton, and atomic oxygen exposure on coatings and on assembled solar cells as related to the implemented deposition processes and material compositions were small. The UVR/AR coatings protected flexible polymer substrate materials that are intended for future flexible multijunction cell arrays to be deployed from rolls. Progress was made toward developing stable and protective coatings for extended space-mission applications. Test results are presented.
This study was initiated as a component of a larger undertaking designed to study bone healing in microgravity aboard the International Space Station (ISS). Spaceflight experimentation introduces multiple challenges not seen in ground studies, especially with regard to physical space, limited resources, and inability to easily reproduce results. Together, these can lead to diminished statistical power and increased risk of failure. It is because of the limited space, and need for improved statistical power by increasing sample size over historical numbers, NASA studies involving mice require housing mice at densities higher than recommended in the Guide for the Care and Use of Laboratory Animals (National Research Council, 2011). All previous NASA missions in which mice were co-housed, involved female mice; however, in our spaceflight studies examining bone healing, male mice are required for optimal experimentation. Additionally, the logistics associated with spaceflight hardware and our study design necessitated variation of density and cohort make up during the experiment. This required the development of a new method to successfully co-house male mice while varying mouse density and hierarchical structure. For this experiment, male mice in an experimental housing schematic of variable density (Spaceflight Correlate) analogous to previously established NASA spaceflight studies was compared to a standard ground based housing schematic (Normal Density Controls) throughout the experimental timeline. We hypothesized that mice in the Spaceflight Correlate group would show no significant difference in activity, aggression, or stress when compared to Normal Density Controls. Activity and aggression were assessed using a novel activity scoring system (based on prior literature, validated in-house) and stress was assessed via body weights, organ weights, and veterinary assessment. No significant differences were detected between the Spaceflight Correlate group and the Normal Density Controls in activity, aggression, body weight, or organ weight, which was confirmed by veterinary assessments. Completion of this study allowed for clearance by NASA of our bone healing experiments aboard the ISS, and our experiment was successfully launched February 19, 2017 on SpaceX CRS-10.
Progressive development of microsatellite technologies has resulted in increased demand for lightweight electrical power subsystems including solar arrays. The use of thin film photovoltaics has been recognized as a key solution to meet the power needs. The lightweight cells can generate sufficient power and still meet critical mass requirements. Commercially available solar cells produced on lightweight substrates are being studied as an option to fulfill the power needs. The commercially available solar cells are relatively inexpensive and have a high payoff potential. Commercially available thin film solar cells are primarily being produced for terrestrial applications. The need to convert the solar cell from a terrestrial to a space compatible application is the primary challenge. Solar cell contacts, grids and interconnects need to be designed to be atomic oxygen resistant and withstand rapid thermal cycling environments. A mechanically robust solar cell interconnect is also required in order to withstand handling during fabrication and survive during launch. The need to produce the solar cell interconnects has been identified as a primary goal of the PowerSphere program and is the topic of this paper. Details of the trade study leading to the final design involving the solar cell wrap around contact, flex blanket, welding process, and frame will be presented at the conference.
Pyridoxal 5 -phosphate (PLP) is a fundamental, multifunc- tional enzyme cofactor used to catalyze a wide variety of chemical reactions involved in amino acid metabolism. PLP-de- pendent enzymes optimize specific chemical reactions by mod- ulating the electronic states of PLP through distinct active site environments. In aspartate aminotransferase (AAT), an extended hydrogen bond network is coupled to the pyridinyl nitrogen of the PLP, influencing the electrophilicity of the cofactor. This network, which involves residues Asp-222, His- 143, Thr-139, His-189, and structural waters, is located at the edge of PLP opposite the reactive Schiff base. We demonstrate that this hydrogen bond network directly influences the proto- nation state of the pyridine nitrogen of PLP, which affects the rates of catalysis. We analyzed perturbations caused by sin- gle- and double-mutant variants using steady-state kinetics, high resolution X-ray crystallography, and quantum chemi- cal calculations. Protonation of the pyridinyl nitrogen to form a pyridinium cation induces electronic delocalization in the PLP, which correlates with the enhancement in cata- lytic rate in AAT. Thus, PLP activation is controlled by the proximity of the pyridinyl nitrogen to the hydrogen bond microenvironment. Quantum chemical calculations indicate that Asp-222, which is directly coupled to the pyridinyl nitro- gen, increases the pKa of the pyridine nitrogen and stabilizes the pyridinium cation. His-143 and His-189 also increase the pKa of the pyridine nitrogen but, more significantly, influ- ence the position of the proton that resides between Asp-222 and the pyridinyl nitrogen. These findings indicate that the second shell residues directly enhance the rate of catalysis in AAT.
Enzymes dependent on pyridoxal 5?-phosphate (PLP, the active form of vitamin B6) perform a myriad of diverse chemical transformations. They promote various reactions by modulating the electronic states of PLP through weak interactions in the active site. Neutron crystallography has the unique ability of visualizing the nuclear positions of hydrogen atoms in macromolecules. Here we present a room-temperature neutron structure of a homodimeric PLP-dependent enzyme, aspartate aminotransferase, which was reacted in situ with ?-methylaspartate. In one monomer, the PLP remained as an internal aldimine with a deprotonated Schiff base. In the second monomer, the external aldimine formed with the substrate analog. We observe a deuterium equidistant between the Schiff base and the C-terminal carboxylate of the substrate, a position indicative of a low-barrier hydrogen bond. Quantum chemical calculations and a low-pH room-temperature X-ray structure provide insight into the physical phenomena that control the electronic modulation in aspartate aminotransferase.
Moving contact-lines (CLs) dissipate. Sessile droplets, mechanically driven into resonance by plane-normal forcing of the contacting substrate, can exhibit oscillatory CL motions with CL losses dominating bulk dissipation. Conventional practice measures CL dissipation based on the rate of mechanical work of the unbalanced Young’s force at the CL. Typical approaches require measurements local to the CL and assumptions about the “equilibrium” contact angle (CA). This paper demonstrates how to use scanning of forcing frequency to characterize CL dissipation without any dependence on measurements from the vicinity of the CL. The results are of immediate relevance to an International Space Station (ISS) experiment and of longer-term relevance to Earth-based wettability applications. Experiments reported here use various concentrations of a water-glycerol mixture on a low-hysteresis non-wetting substrate.
Understanding molecules involved in differentiation of human pluripotent stem cells (hPSCs) into cardiomyocytes and endothelial cells is important in advancing hPSCs for cell therapy and drug testing. Here, we report that LGR5, a leucine-rich repeat-containing G-protein-coupled receptor, plays a critical role in hPSC differentiation into cardiomyocytes and endothelial cells. LGR5 expression was transiently upregulated during the early stage of cardiomyocyte differentiation, and knockdown of LGR5 resulted in reduced expression of cardiomyocyte-associated markers and poor cardiac differentiation. In contrast, knockdown of LGR5 promoted differentiation of endothelial-like cells with increased expression of endothelial cell markers and appropriate functional characteristics, including the ability to form tube-like structures and to take up acetylated low-density lipoproteins. Furthermore, knockdown of LGR5 significantly reduced the proliferation of differentiated cells and increased the nuclear translocation of ?-catenin and expression of Wnt signaling-related genes. Therefore, regulation of LGR5 may facilitate efficient generation of cardiomyocytes or endothelial cells from hPSCs.
Drawing parallels to the symmetry breaking of atomic orbitals used to explain the periodic table of chemical elements; here we introduce a periodic table of droplet motions, also based on symmetry breaking but guided by a recent droplet spectral theory. By this theory, higher droplet mode shapes are discovered and a wettability spectrometer is invented. Motions of a partially wetting liquid on a support have natural mode shapes, motions ordered by kinetic energy into the periodic table, each table characteristic of the spherical-cap drop volume and material parameters. For water on a support having a contact angle of about 60°, the first 35 predicted elements of the periodic table are discovered. Periodic tables are related one to another through symmetry breaking into a two-parameter family tree.
A colloidal motor driven by surface tension forces is theoretically designed by encapsulating an active Janus particle in a liquid drop which is immiscible in the suspending medium. The Janus particle produces an asymmetric flux of a solute species which induces surface tension gradients along the liquid–liquid interface between the drop and the surrounding fluid. The resulting Marangoni forces at the interface propel the compound drop/Janus particle system. The propulsion speeds of the motor are evaluated for a range of relative sizes and positions of the drop and the particle and across a range of transport properties of the drop and the suspending medium. It is demonstrated that the proposed design can produce higher propulsion velocities than the traditional Janus-particle-based colloidal motors propelled by neutral diffusiophoresis.
Microgravity is a unique environment to elucidate host–parasite biology. Entomopathogenic nematodes (EPNs), model parasites, kill host insects with mutualistic bacteria and provide environmentally friendly pest control. It is unknown how microgravity affects a multistep insect invasion by parasites with mutualistic bacteria. EPNs respond directionally to electromagnetic cues and their sinusoidal locomotion is affected by various physical factors. Therefore, we expected microgravity to impact EPN functionality. Microgravity experiments during space flight on the International Space Station (ISS) indicated that EPNs successfully emerged from consumed insect host cadavers, moved through soil, found and infected bait insects in a manner equivalent to Earth controls. However, nematodes that developed entirely in space, from the egg stage, died upon return to Earth, unlike controls in microgravity and on Earth. This agricultural biocontrol experiment in space gives insight to long-term space flight for symbiotic organisms, parasite biology, and the potential for sustainable crop protection in space.
Cerium oxide (CeO2) was prepared using a controlled-precipitation method under microgravity at the International Space Station (ISS). For comparison, ceria was also synthesized under normal-gravity conditions (referred as control). The Brunauer-Emmett-Teller (BET) surface area, pore volume and pore size analysis results indicated that the ceria particles grown in space had lower surface area and pore volume compared to the control samples. Furthermore, the space samples had a broader pore size distribution ranging from 30–600 Å, whereas the control samples consisted of pore sizes from 30–50 Å range. Structural information of the ceria particles were obtained using TEM and XRD. Based on the TEM images, it was confirmed that the space samples were predominantly nano-rods, on the other hand, only nano-polyhedra particles were seen in the control ceria samples. The average particle size was larger for ceria samples synthesized in space. XRD results showed higher crystallinity as well as larger mean crystal size for the space samples. The effect of sodium hydroxide concentration on synthesis of ceria was also examined using 1 M and 3 M solutions. It was found that the control samples, prepared in 1 M and 3 M sodium hydroxide solutions, did not show a significant difference between the two. However, when the ceria samples were prepared in a more basic medium (3 M) under microgravity, a decrease in the particle size of the nano-rods and appearances of nano-polyhedra and spheres were observed.
To evaluate effects of microgravity on virulence, we studied the ability of four common clinical pathogens: Klebsiella, Streptococcus, Proteus, and Pseudomonas to kill wild type Caenorhabditis elegans (C. elegans) nematodes at the larval and adult stages. Simultaneous studies were performed utilizing spaceflight, rotation in a 2D clinorotation device, and static ground controls. Nematodes, microbes and growth media were separated until exposed to true or modeled microgravity, then mixed and grown for 48 hours. Experiments were terminated by paraformaldehyde fixation and optical density measurements were used to assay residual microorganisms. Spaceflight was associated with reduced virulence for Klebsiella and Streptococcus but had negligible effect on Enterococcus and Pseudomonas. Clinorotation generated very different results with all four organisms showing significantly reduced virulence. We conclude that clinorotation is not a consistent model of the changes that actually occur under microgravity conditions. Further, bacteria virulence is unchanged or reduced, not increased during spaceflight.
To evaluate effects of microgravity on virulence, we studied the ability of four common clinical pathogens—Listeria monocytogenes, methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus faecalis, and Candida albicans—to kill wild type Caenorhabditis elegans (C. elegans) nematodes at the larval and adult stages. Simultaneous studies were performed utilizing spaceflight, clinorotation in a 2-D clinorotation device, and static ground controls. The feeding rate of worms for killed E. coli was unaffected by spaceflight or clinorotation. Nematodes, microbes, and growth media were separated until exposed to true or modeled microgravity, then mixed and grown for 48 h. Experiments were terminated by paraformaldehyde fixation, and optical density measurements were used to assay residual microorganisms. Spaceflight was associated with reduced virulence for Listeria, Enterococcus, MRSA, and Candida for both larval and adult C. elegans. These are the first data acquired with a direct in vivo assay system in space to demonstrate virulence. Clinorotation reproduced the effects of spaceflight in some, but not all, virulence assays: Candida and Enterococcus were less virulent for larval worms but not adult worms, whereas virulence of MRSA and Listeria were unaffected by clinorotation in tests with both adult and larval worms. We conclude that four common clinical microorganisms are all less virulent in space.
To evaluate the effects of microgravity on virulence genes in Salmonella, we studied the ability of various Salmonella deletion mutants to kill wild-type Caenorhabditis elegans nematodes at the larval and adult stages. Simultaneous studies were performed utilizing spaceflight, clinorotation, and static ground controls. Nematodes, Salmonella, and growth media were separated until exposed to true or simulated microgravity, and then mixed and grown for 48?h. Experiments were terminated by paraformaldehyde fixation, and optical density measurements were used to assay residual microorganisms. Prior flight in space led to reduced virulence of wild-type Salmonella when subsequently evaluated in a ground-based virulence assay with carefully matched inocula for never-flown Salmonella controls. However, when the virulence assay was conducted in spaceflight, there was only a minimal change in the virulence of wild-type Salmonella toward C. elegans. Deletion of pipA, a gene in Salmonella pathogenicity island-5, reduced Salmonella virulence toward wild-type and Tol1-deletion L2 larvae in spaceflight but had no effect on virulence for Tol1-deletion adult worms in spaceflight. PipA-deletion Salmonella were also less virulent toward wild-type L2 larvae in clinorotation, but showed a paradoxical increased virulence toward Tol1-deletion L2 larvae in clinorotation.
Spaceflight alters many processes of the human body including cardiac function and cardiac progenitor cell behavior. The mechanism behind these changes remains largely unknown; however, simulated microgravity devices are making it easier for researchers to study the effects of microgravity. To study the changes that take place in cardiac progenitor cells in microgravity environments, adult cardiac progenitor cells were cultured aboard the International Space Station (ISS) as well as on a clinostat and examined for changes in Hippo signaling, a pathway known to regulate cardiac development. Cells cultured under microgravity conditions, spaceflight-induced or simulated, displayed upregulation of downstream genes involved in the Hippo pathway such as YAP1 and SOD2. YAP1 is known to play a role in cardiac regeneration which led us to investigate YAP1 expression in a sheep model of cardiovascular repair. Additionally, to mimic the effects of microgravity, drug treatment was used to induce Hippo related genes as well as a regulator of the Hippo pathway, miRNA-302a. These studies provide insight into the changes that occur in space and how the effects of these changes relate to cardiac regeneration studies.
With extended stays aboard the International Space Station (ISS) becoming commonplace, there is a need to better understand the effects of microgravity on cardiac function. We utilized human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to study the effects of microgravity on cell-level cardiac function and gene expression. The hiPSC-CMs were cultured aboard the ISS for 5.5 weeks and their gene expression, structure, and functions were compared with ground control hiPSC-CMs. Exposure to microgravity on the ISS caused alterations in hiPSC-CM calcium handling. RNA-sequencing analysis demonstrated that 2,635 genes were differentially expressed among flight, post-flight, and ground control samples, including genes involved in mitochondrial metabolism. This study represents the first use of hiPSC technology to model the effects of spaceflight on human cardiomyocyte structure and function.
Spaceflight-induced remodeling of the skull is characterized by greater bone volume, mineral density, and mineral content. To further investigate the effects of spaceflight on other non-weight bearing bones of the head, as well as to gain insight into potential factors mediating the remodeling of the skull, the purpose of the present study was to determine the effects of spaceflight on mandibular bone properties. Female C57BL/6 mice were flown 15 d on the STS-131 Space Shuttle mission (n = 8) and 13 d on the STS-135 mission (n = 5) or remained as ground controls (GC). Upon landing, mandibles were collected and analyzed via micro-computed tomography for tissue mineralization, bone volume (BV/TV), and distance from the cemento–enamel junction to the alveolar crest (CEJ–AC). Mandibular mineralization was not different between spaceflight (SF) and GC mice for either the STS-131 or STS-135 missions. Mandibular BV/TV (combined cortical and trabecular bone) was lower in mandibles from SF mice on the STS-131 mission (80.7 ± 0.8%) relative to that of GC (n = 8) animals (84.2 ± 1.2%), whereas BV/TV from STS-135 mice was not different from GC animals (n = 7). The CEJ–AC distance was shorter in mandibles from STS-131 mice (0.217 ± 0.004 mm) compared to GC animals (0.283 ± 0.009 mm), indicating an anabolic (or anti-catabolic) effect of spaceflight, while CEJ–AC distance was similar between STS-135 and GC mice. These findings demonstrate that mandibular bones undergo skeletal changes during spaceflight and are susceptible to the effects of weightlessness. However, adaptation of the mandible to spaceflight is dissimilar to that of the cranium, at least in terms of changes in BV/TV.