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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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NASA NTRS2013

It's the Heat AND the Humidity -- Assessment of Extreme Heat Scenarios to Enable the Assessment of Climate Impacts on Public Health

In the United States, extreme heat is the most deadly weather-related hazard. In the face of a warming climate and urbanization, which contributes to local-scale urban heat islands, it is very likely that extreme heat events (EHEs) will become more common and more severe in the U.S. In a NASA-funded project supporting the National Climate Assessment, we are providing historical and future measures of extreme heat to enable assessments of the impacts of heat on public health over the coterminous U.S. We use atmospheric temperature and humidity information from meteorological reanalysis and from Global Climate Models (GCMs) to provide data on past and future heat events. The project s emphasis is on providing assessments of the magnitude, frequency and geographic distribution of extreme heat in the U.S. to facilitate public health studies. In our approach, long-term climate change is captured with GCM output, and the temporal and spatial characteristics of short-term extremes are represented by the reanalysis data. Two future time horizons, 2040 and 2090, are the focus of future assessments; these are compared to the recent past period of 1981-2000. We are characterizing regional-scale temperature and humidity conditions using GCM output for two climate change scenarios (A2 and A1B) defined in the Special Report on Emissions Scenarios (SRES). For each future period, 20 years of multi-model GCM output have been analyzed to develop a heat stress climatology based on statistics of extreme heat indicators. Differences between the two future and past periods have been used to define temperature and humidity changes on a monthly time scale and regional spatial scale. These changes, combined with hourly historical meteorological data at a spatial scale (12 km) much finer than that of GCMs, enable us to create future climate realizations, from which we compute the daily heat stress measures and related spatially-specific climatological fields. These include the mean annual number of days above certain thresholds of maximum and minimum air temperatures, heat indices and a new heat stress variable that gives an integrated measure of heat stress (and relief) over the course of a day. Comparisons are made between projected (2040 and 2090) and past (1990) heat stress statistics. All output is being provided at the 12 km spatial scale and will also be aggregated to the county level, which is a popular scale of analysis for public health researchers. County-level statistics will be made available by our collaborators at the Centers for Disease Control and Prevention (CDC) via the Wide-ranging Online Data for Epidemiologic Research (WONDER) system. CDC WONDER makes the information resources of the CDC available to public health professionals and the general public. This addition of heat stress measures to CDC WONDER will allow decision and policy makers to assess the impact of alternative approaches to optimize the public health response to EHEs. It will also allow public health researchers and policy makers to better include such heat stress measures in the context of national health data available in the CDC WONDER system. The users will be able to spatially and temporally query public health and heat-related data sets and create county-level maps and statistical charts of such data across the coterminous U.S.

Crosson, William L↗
NASA NTRS1998

Current concepts in the pathophysiology, evaluation, and diagnosis of compartment syndrome

This article reviews present knowledge of the pathophysiology and diagnosis of acute compartment syndromes. Recent results using compression of legs in normal volunteers provide objective data concerning local pressure thresholds for neuromuscular dysfunction in the anterior compartment. Results with this model indicate that a progression of neuromuscular deficits occurs when IMP increases to within 35 to 40 mm Hg of diastolic blood pressure. These findings provide useful information on the diagnosis and compression thresholds for acute compartment syndromes. Time factors are also important, however, and usually are incompletely known in most cases of acute compartment syndrome. Although the slit catheter is a very good technique for monitoring IMP during rest, these catheters and their associated extracorporeal transducer systems are not ideal. Recently developed miniature transducer-tipped catheters and, perhaps, future development of noninvasive techniques may provide accurate recordings of IMP in patients with acute compartment syndromes.

NASA Discipline Cardiopulmonary↗
NASA NTRS1998

Rates of ubiquitin conjugation increase when muscles atrophy, largely through activation of the N-end rule pathway

The rapid loss of muscle mass that accompanies many disease states, such as cancer or sepsis, is primarily a result of increased protein breakdown in muscle, and several observations have suggested an activation of the ubiquitin-proteasome system. Accordingly, in extracts of atrophying muscles from tumor-bearing or septic rats, rates of 125I-ubiquitin conjugation to endogenous proteins were found to be higher than in control extracts. On the other hand, in extracts of muscles from hypothyroid rats, where overall proteolysis is reduced below normal, the conjugation of 125I-ubiquitin to soluble proteins decreased by 50%, and treatment with triiodothyronine (T3) restored ubiquitination to control levels. Surprisingly, the N-end rule pathway, which selectively degrades proteins with basic or large hydrophobic N-terminal residues, was found to be responsible for most of these changes in ubiquitin conjugation. Competitive inhibitors of this pathway that specifically block the ubiquitin ligase, E3alpha, suppressed most of the increased ubiquitin conjugation in the muscle extracts from tumor-bearing and septic rats. These inhibitors also suppressed ubiquitination in normal extracts toward levels in hypothyroid extracts, which showed little E3alpha-dependent ubiquitination. Thus, the inhibitors eliminated most of the differences in ubiquitination under these different pathological conditions. Moreover, 125I-lysozyme, a model N-end rule substrate, was ubiquitinated more rapidly in extracts from tumor-bearing and septic rats, and more slowly in those from hypothyroid rats, than in controls. Thus, the rate of ubiquitin conjugation increases in atrophying muscles, and these hormone- and cytokine-dependent responses are in large part due to activation of the N-end rule pathway.

Non-NASA Center↗
NASA NTRS2000

An architecture for a brain-image database

The widespread availability of methods for noninvasive assessment of brain structure has enabled researchers to investigate neuroimaging correlates of normal aging, cerebrovascular disease, and other processes; we designate such studies as image-based clinical trials (IBCTs). We propose an architecture for a brain-image database, which integrates image processing and statistical operators, and thus supports the implementation and analysis of IBCTs. The implementation of this architecture is described and results from the analysis of image and clinical data from two IBCTs are presented. We expect that systems such as this will play a central role in the management and analysis of complex research data sets.

NASA Discipline Neuroscience↗
NASA NTRS1999

Latent Viruses: A Space Travel Hazard??

A major issue associated with long-duration space flight is the possibility of infectious disease causing an unacceptable medical risk to crew members. Our proposal is designed to gain information that addresses several issues outlined in the Immunology/Infectious disease critical path. The major hypothesis addressed is that space flight causes alterations in the immune system that may allow latent viruses which are endogenous in the human population to reactivate and shed to higher levels than normal which can affect the health of crew members during a long term space-flight mission. We will initially focus our studies on the human herpesviruses and human polyomaviruses which are important pathogens known to establish latent infections in the human population. Both primary infection and reactivation from latent infection with this group of viruses can cause a variety of illnesses that result in morbidity and occasionally mortality of infected individuals. Effective vaccines exist for only one of the eight known human herpesviruses and the vaccine itself can still reactivate from latent infection. Available antivirals are of limited use and are effective against only a few of the human herpesviruses. Although most individuals display little if any clinical consequences from latent infection, events which alter immune function such as immunosuppressive therapy following solid organ transplantation are known to increase the risk of developing complications as a result of latent virus reactivation. This proposal will measure both the frequency and magnitude of viral shedding and genome loads in the blood from humans participating in activities that serve as ground based models of space flight conditions. Our initial goal is to develop sensitive quantitative competitive PCR- based assays (QC-PCR) to detect the herpesvirus Epstein-Barr virus (EBV), and the polyomaviruses SV40, BKV, and JCV. Using these assays we will establish baseline patterns of viral genome load in the blood and viral shedding from normal volunteers in a longitudinal study over I year in length. As a comparison, we will measure patterns of viral genome loads and shedding from individuals who are severely immunosuppressed, in whom herpesvirus reactivation or primary infection with a herpesvirus is known to cause complications. In addition, we will proceed to testing ground based analogs in collaboration with Dr. Duane Pierson (Lyndon B. Johnson Space Center). This will include measuring samples obtained from individuals living and working in the extreme environment of Antarctica. We expect to detect viral shedding or reactivation from most of the test groups, although the magnitude of shedding or reactivation cannot be predicted. The data accumulated from studies in this proposal should allow us to evaluate whether events that simulate certain aspects of space flight reactivate viral infections severe enough in nature that they may compromise the success of long-term space flight missions. These studies will also provide a foundation to monitor viral reactivation and shedding from crew members participating in actual space flight missions. We will present data showing the establishment of our QC-PCR assay for detection of EBV.

Ling, P. D.↗
NASA NTRS2021

Bhutan Agriculture: Developing a Crop Mask for Rice and Creating a Data Collection Protocol Utilizing Remotely Sensed Data in Bhutan

Rice cultivation in Bhutan has been increasingly threatened by deteriorating soil health and outbreaks of diseases and pests associated with the global change in climate patterns. Field surveys, which the national government of Bhutan has relied on to monitor remote agricultural lands, are becoming increasingly overwhelmed by growing threats to agricultural health. To address these concerns, NASA DEVELOP partnered with the Department of Agriculture of Bhutan, the Bhutan Foundation, and the Ugyen Wangchuck Institute of Conservation and Environmental Research (UWICER) and worked to increase the government of Bhutan’s agricultural monitoring capacity. Utilizing Earth observations including Landsat 8 Operational Land Imager (OLI), Sentinel-1 C-band Synthetic Aperture Radar (C-SAR), Shuttle Radar Topography Mission (SRTM), and Planet imagery, the DEVELOP team worked with NASA SERVIR and created a sampling protocol to identify rice plantations and supplement field surveys for more efficient agriculture monitoring. The analysis focused on districts Paro, Punakha, Samtse, Sarpang, Trongsa, Zhemgang, Wangdue Phodrang, and Samdrup Jongkhar in the year 2020 during the period of transplantation (June) to harvesting of rice (November). The team provided the partners with a sampling protocol for integrating NASA Earth observations into their crop monitoring methods, as well as a crop mask for rice identification and to aid crop management. The crop mask for rice was developed using the Random Forest (RF) classifier for the eight districts of Bhutan. Visually, the random forest model has proved to be more accurate and precise than the classification and Regression Tree model. Statistically, the Random Forest model was 91.8% accurate in identifying rice in Bhutan.

Yeshey Seldon↗
NASA NTRS2018

Neutrophil to Lymphocyte Ratio: A Prognostic Indicator for Astronaut Health

Short-term and long-term spaceflight missions can cause immune system dysfunction in astronauts. Recent studies indicate elevated white blood cells (WBC) and polymorphonuclear neutrophils (PMN) in astronaut blood, along with unchanged or reduced lymphocyte counts, and reduced T cell function, during short-(days) and long-(months) term spaceflight. A high PMN to lymphocyte ratio (NLR) can acts as a strong predictor of poor prognosis in cancer, and as a biomarker for subclinical inflammation in humans and chronic stress in mouse models, however, the NLR has not yet been identified as a predictor of astronaut health during spaceflight. For this, complete blood cell count data collected from astronauts and rodents that have flown for short- and long-term missions on board the International Space Station (ISS) was repurposed to determine the NLR pre-, in-, and post-flight. The results displayed that the NLR progressively increased during spaceflight in both human and mice, while a spike in the NLR was observed at post-flight landing, suggesting stress-induced factors may be involved. In addition, the ground-based chronic microgravity analog, hindlimb unloading in mice, indicated an increased NLR, along with induced myeloperoxidase expression, as measured by quantitative (q)PCR. The mechanism for increased NLR was further assessed in vitro using the NASA-developed rotating wall vessel (RWV) cell culture suspension system with human WBCs. The results indicated that simulated microgravity led to increased mature PMN counts, NLR profiles, and production of reactive oxygen species (ROS). Collectively, these studies show that an increased NLR is observed in spaceflight missions, and in chronic microgravity-analog simulation in mice, and that this effect may be potentiated by the oxidative stress response in blood cells under microgravity conditions. Furthermore, these results suggest that a disrupted NLR profile in spaceflight may further disrupt immune homeostasis, potentially causing chronic immune-mediated inflammatory diseases. Thus, we propose that the health status of astronauts during short- and long-term space missions can be monitored by their NLR profile, in addition to utilizing this measurement as a tool for interventions and countermeasure development to restore homeostatic immunity.

biomarker↗
NASA NTRS2024

Conclusions of a Mini Technical Interchange Meeting on New Cross Risk Integration Projects Managed by the NASA Space Radiation Element

To enable deep space exploration and sustained human presence in space, the NASA Human Research Program’s (HRP) Space Radiation Element (SRE) funds research to characterize and mitigate adverse health outcomes from exposure to space radiation that include risks of carcinogenesis, cardiovascular disease, and central nervous system decrements. Recently, the SRE was tasked with supporting multiple HRP Elements with innovative and enabling projects to inform risk characterization, facilitate mitigation activities, and support crew health and performance. These projects, such as precision health initiative, NASA Omics Archive (NOA) and human sample repositories, are agnostic to any HRP Element, hence the name, Cross-Risk Integration Projects (CRIP). CRIP serves 3 broad purposes: - Services: Generate samples and data and manage the receipt, inventory, archive, and ultimate redistribution of biospecimens created in HRP-funded spaceflight and analog research activities—includes NASA Omics Archive project and various human and animal sample repositories. - Method Development: Identify and evaluate new-to-NASA research or analysis methods or techniques that could fundamentally improve existing or planned research efforts—includes the Translational Radiation Research and Countermeasures Project. - Enabling Capabilities: Demonstrate real-world application by adapting, adopting, and/or developing capabilities to benefit crew health and performance and improve risk mitigation—includes Precision Health Initiative (Pharmacogenomics) and advanced biological systems and engineered tissue microsystems initiative (tissue chips, organ-on-a-chip). To identify new technologies, future work, and solicitations, the SRE organizes themed sessions at annual HRP Investigators’ Workshops (IWS). These technical interchange meetings (TIMs) provide a venue for the scientific community to present ongoing work and engage in open discussion of results, limitations of current approaches, and incorporation of novel experimental strategies, model systems, and other innovative techniques. Here, a summary of the studies presented at the SRE-sponsored mini-TIM at the HRP IWS along with the goals and objectives of the CRIP projects is communicated. The 90-min TIM had 6 speakers who presented impressive novel ideas and work, some of which are funded under CRIP by the Space Radiation Element.

Janapriya Saha↗
NASA NTRS2010

Reducing Tick-Borne Disease in Alabama: Linking Health Risk Perception with Spatial Analysis Using the NASA Earth Observing System

Lyme disease (LD) accounts for most vector-borne disease reports in the U.S., and although its existence in Alabama remains controversial, other tick-borne illnesses (TBI) such as Southern Tick-Associated Rash Illness (STARI) pose a health concern in the state. Phase One of the Marshall Space Flight Center-UAB DEVELOP study of TBI identified the presence of the chain of infection for LD (Ixodes scapularis ticks carrying Borrelia burgdorferi bacteria) and STARI (Amblyomma americanum ticks and an as-yet-unconfirmed agent) in Alabama. Both LD and STARI are associated with the development of erythema migrans rashes around an infected tick bite, and while treatable with oral antibiotics, a review of educational resources available to state residents revealed low levels of prevention information. To improve prevention, recognition, and treatment of TBI in Alabama, Phase Two builds a health communication campaign based on vector habitat mapping and risk perception assessment. NASA Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) satellite imagery identified likely tick habitats using remotely sensed measurements of vegetation vigor (Normalized Difference Vegetation Index) and soil moisture. Likely tick habitats, identified as those containing both high vegetation density and soil moisture, included Oak Mountain State Park, Bankhead National Forest, and Talladega National Forest. To target a high-risk group -- outdoor recreation program participants at Alabama universities -- the study developed a behavior survey instrument based on existing studies of LD risk factors and theoretical constructs from the Social Ecological Model and Health Belief Model. The survey instrument was amended to include geographic variables in the assessment of TBI knowledge, attitudes, and prevention behaviors, and the vector habitat model will be expanded to incorporate additional environmental variables and in situ data. Remotely sensed environmental data combined with risk perception assessments inform an ongoing outreach campaign consisting of stakeholder meetings and educational seminars.

Hemmings, S.↗
NASA NTRS1989

Specification of parameters for development of a spatial database for drought monitoring and famine early warning in the African Sahel

Parameters were described for spatial database to facilitate drought monitoring and famine early warning in the African Sahel. The proposed system, referred to as the African Drought and Famine Information System (ADFIS) is ultimately recommended for implementation with the NASA/FEMA Spatial Analysis and Modeling System (SAMS), a GIS/Dymanic Modeling software package, currently under development. SAMS is derived from FEMA'S Integration Emergency Management Information System (IEMIS) and the Pacific Northwest Laborotory's/Engineering Topographic Laboratory's Airland Battlefield Environment (ALBE) GIS. SAMS is primarily intended for disaster planning and resource management applications with the developing countries. Sources of data for the system would include the Developing Economics Branch of the U.S. Dept. of Agriculture, the World Bank, Tulane University School of Public Health and Tropical Medicine's Famine Early Warning Systems (FEWS) Project, the USAID's Foreign Disaster Assistance Section, the World Resources Institute, the World Meterological Institute, the USGS, the UNFAO, UNICEF, and the United Nations Disaster Relief Organization (UNDRO). Satellite imagery would include decadal AVHRR imagery and Normalized Difference Vegetation Index (NDVI) values from 1981 to the present for the African continent and selected Landsat scenes for the Sudan pilot study. The system is initially conceived for the MicroVAX 2/GPX, running VMS. To facilitate comparative analysis, a global time-series database (1950 to 1987) is included for a basic set of 125 socio-economic variables per country per year. A more detailed database for the Sahelian countries includes soil type, water resources, agricultural production, agricultural import and export, food aid, and consumption. A pilot dataset for the Sudan with over 2,500 variables from the World Bank's ANDREX system, also includes epidemiological data on incidence of kwashiorkor, marasmus, other nutritional deficiencies, and synergistically-related infectious diseases.

Rochon, Gilbert L.↗
NASA NTRS2009

Traditional Cardiovascular Risk Factors as Predictors of Cardiovascular Events in the U.S. Astronaut Corps

Risk prediction equations from the Framingham Heart Study are commonly used to predict the absolute risk of myocardial infarction (MI) and coronary heart disease (CHD) related death. Predicting CHD-related events in the U.S. astronaut corps presents a monumental challenge, both because astronauts tend to live healthier lifestyles and because of the unique cardiovascular stressors associated with being trained for and participating in space flight. Traditional risk factors may not hold enough predictive power to provide a useful indicator of CHD risk in this unique population. It is important to be able to identify individuals who are at higher risk for CHD-related events so that appropriate preventive care can be provided. This is of special importance when planning long duration missions since the ability to provide advanced cardiac care and perform medical evacuation is limited. The medical regimen of the astronauts follows a strict set of clinical practice guidelines in an effort to ensure the best care. The purpose of this study was to evaluate the utility of the Framingham risk score (FRS), low-density lipoprotein (LDL) and high-density lipoprotein levels, blood pressure, and resting pulse as predictors of CHD-related death and MI in the astronaut corps, using Cox regression. Of these factors, only two, LDL and pulse at selection, were predictive of CHD events (HR(95% CI)=1.12 (1.00-1.25) and HR(95% CI)=1.70 (1.05-2.75) for every 5-unit increase in LDL and pulse, respectively). Since traditional CHD risk factors may lack the specificity to predict such outcomes in astronauts, the development of a new predictive model, using additional measures such as electron-beam computed tomography and carotid intima-media thickness ultrasound, is planned for the future.

Halm, M. K.↗
NASA NTRS1999

Molecular Signaling in Muscle Plasticity

Extended spaceflight under microgravity conditions leads to significant atrophy of weight-bearing muscles. Atrophy and hypertrophy are the extreme outcomes of the high degree of plasticity exhibited by skeletal muscle. Stimuli which control muscle plasticity include neuronal, hormonal, nutritional, and mechanical inputs. The mechanical stimulus for muscle is directly related to the work or exercise against a load performed. Little or no work is performed by weight-bearing muscles under microgravity conditions. A major hypothesis is that focal adhesion kinase (FAK) which is associated with integrin at the adherens junctions and costa meres of all skeletal muscles is an integral part of the major mechanism for molecular signaling upon mechanical stimulation in all muscle fibers. Additionally, we propose that myotonic protein kinase (DMPK) and dystrophin (DYSTR) also participate in distinct mechanically stimulated molecular signaling pathways that are most critical in type I and type II muscle fibers, respectively. To test these hypotheses, we will use the paradigms of hindlimb unloading and overloading in mice as models for microgravity conditions and a potential exercise countermeasure, respectively, in mice. We expect that FAK loss-of-function will impair hypertrophy and enhance atrophy in all skeletal muscle fibers whereas DYSTR and DMPK loss-of-function will have similar but more selective effects on Type IT and Type I fibers, respectively. Gene expression will be monitored by muscle-specific creatine kinase M promoter-reporter construct activity and specific MRNA and protein accumulation in the soleus (type I primarily) and plantaris (type 11 primarily) muscles. With these paradigms and assays, the following Specific Project Aims will be tested in genetically altered mice: 1) identify the roles of DYSTR and its pathway; 2) evaluate the roles of the DMPK and its pathway; 3) characterize the roles of FAK and its pathway and 4) genetically analyze the mechanisms and interactions between the FAK, DYSTR, and DMPK-associated pathways in single and specific combinations of mutants. The identification of potential signaling mechanisms may permit future development of pharmacological countermeasures for amelioration and prevention of the microgravity-induced atrophy in extended spaceflight, and the analysis of both overloading and unloading paradigms may provide further support for development of exercise-based countermeasures. Understanding the basic mechanisms of molecular signaling in muscle plasticity may aid our understanding and treatment of skeletal muscle atrophy not only in spaceflight but in similar problems of the aging population, in prolonged bed rest, and in cachexia associated with chronic disease.

Epstein, Henry F.↗
NASA NTRS1999

Fluid shear stress as a regulator of gene expression in vascular cells: possible correlations with diabetic abnormalities

Diabetes mellitus is associated with increased frequency, severity and more rapid progression of cardiovascular diseases. Metabolic perturbations from hyperglycemia result in disturbed endothelium-dependent relaxation, activation of coagulation pathways, depressed fibrinolysis, and other abnormalities in vascular homeostasis. Atherosclerosis is localized mainly at areas of geometric irregularity at which blood vessels branch, curve and change diameter, and where blood is subjected to sudden changes in velocity and/or direction of flow. Shear stress resulting from blood flow is a well known modulator of vascular cell function. This paper presents what is currently known regarding the molecular mechanisms responsible for signal transduction and gene regulation in vascular cells exposed to shear stress. Considering the importance of the hemodynamic environment of vascular cells might be vital to increasing our understanding of diabetes.

Review, Tutorial↗
NASA NTRS2002

Tackling a Hot Paradox: Laminar Soot Processes-2 (LSP-2)

The last place you want to be in traffic is behind the bus or truck that is belching large clouds of soot onto your freshly washed car. Besides looking and smelling bad, soot is a health hazard. Particles range from big enough to see to microscopic and can accumulate in the lungs, potentially leading to debilitating or fatal lung diseases. Soot is wasted energy, and therein lies an interesting paradox: Soot forms in a flame's hottest regions where you would expect complete combustion and no waste. Soot enhances the emissions of other pollutants (carbon monoxide and polyaromatic hydrocarbons, etc.) from flames and radiates unwanted heat to combustion chambers (a candle's yellowish glow is soot radiating heat), among other effects. The mechanisms of soot formation are among the most important unresolved problems of combustion science because soot affects contemporary life in so many ways. Although we have used fire for centuries, many fundamental aspects of combustion remain elusive, in part because of limits imposed by the effects of gravity on Earth. Hot or warm air rises quickly and draws in fresh cold air behind it, thus giving flames the classical teardrop shape. Reactions occur in a very small zone, too fast for scientists to observe, in detail, what is happening inside the flame. The Laminar Soot Processes (LSP-2) experiments aboard STS-107 will use the microgravity environment of space to eliminate buoyancy effects and thus slow the reactions inside a flame so they can be more readily studied. 'Laminar' means a simple, smooth fuel jet burning in air, somewhat like a butane lighter. This classical flame approximates combustion in diesel engines, aircraft jet propulsion engines, and furnaces and other devices. LSP-2 will expand on surprising results developed from its first two flights in 1997. The data suggest the existence of a universal relationship, the soot paradigm, that, if proven, will be used to model and control combustion systems on Earth. STS-107 experiments also will help set the stage for extended combustion experiments aboard the International Space Station.

Faeth, Gerard M.↗
NASA NTRS2001

Extending unbiased stereology of brain ultrastructure to three-dimensional volumes

OBJECTIVE: Analysis of brain ultrastructure is needed to reveal how neurons communicate with one another via synapses and how disease processes alter this communication. In the past, such analyses have usually been based on single or paired sections obtained by electron microscopy. Reconstruction from multiple serial sections provides a much needed, richer representation of the three-dimensional organization of the brain. This paper introduces a new reconstruction system and new methods for analyzing in three dimensions the location and ultrastructure of neuronal components, such as synapses, which are distributed non-randomly throughout the brain. DESIGN AND MEASUREMENTS: Volumes are reconstructed by defining transformations that align the entire area of adjacent sections. Whole-field alignment requires rotation, translation, skew, scaling, and second-order nonlinear deformations. Such transformations are implemented by a linear combination of bivariate polynomials. Computer software for generating transformations based on user input is described. Stereological techniques for assessing structural distributions in reconstructed volumes are the unbiased bricking, disector, unbiased ratio, and per-length counting techniques. A new general method, the fractional counter, is also described. This unbiased technique relies on the counting of fractions of objects contained in a test volume. A volume of brain tissue from stratum radiatum of hippocampal area CA1 is reconstructed and analyzed for synaptic density to demonstrate and compare the techniques. RESULTS AND CONCLUSIONS: Reconstruction makes practicable volume-oriented analysis of ultrastructure using such techniques as the unbiased bricking and fractional counter methods. These analysis methods are less sensitive to the section-to-section variations in counts and section thickness, factors that contribute to the inaccuracy of other stereological methods. In addition, volume reconstruction facilitates visualization and modeling of structures and analysis of three-dimensional relationships such as synaptic connectivity.

NASA Discipline Neuroscience↗
NASA NTRS2020

Let Dependent Low Dose and Synergistic Inhibition of Human Angiogenesis by Charged Particles: Validation of Micrornas That Drive Inhibition

The microvasculature permeates all tissues at the microscopic level making the whole body a target for Space Radiation. Depending on the trajectory a single heavy ion particle would traverse many micro-vessels as it passes through the body causing a widespread response. Studies on the effects of charged particles on the development of human 3D micro-vessel models show that angiogenesis is inhibited by all ions detectible at a dose of 1.25c Gy. However, there are two distinct mechanisms of inhibition depending on the linear energy transfer (LET). We show here that the inhibition of angiogenesis is demarcated into two groups. The blockage of the early motile stage of micro-vessel development occurs after exposure to light ions (LET 3 KeV/n or lower) whereas the prevention of the later stages of development when the microvessels widen into tubes occurs after exposure to heavy ions (LET 8 KeV/n or higher). Strikingly, the combined effect of each ion has a synergistic effect detectible as low as 0.6 cGy. The low fluence of these doses indicates a bystander effect where the response is transmitted to other cells by the secretion of molecules by targeted cells. Prime candidates are microRNAs (miRNAs) and we have previously identified three angiogenesis-associated miRNA regulators from serum, cardiac tissue, and micro-vessels exposed to a simplified Galactic Cosmic Radiation (GCR) simulation – a mixture of heavy and light ions found in Space. Synthetic molecules (Antagomirs) designed to inhibit the predicted miRNAs were successfully used to reverse the inhibition of angiogenesis by Space Radiation. With the simple application of the antagomirs as a countermeasure we have for the first time shown an amelioration of the complex response(s) of angiogenesis to Space Radiation. This opens a new avenue of possible mitigation strategies based on the regulation and understanding of master regulators. These results not only have impact with Space Radiation research, but also provide clues of possible therapeutics for terrestrial diseases in the clinical setting.

Yen-Ruh Wuu↗
NASA NTRS2017

Bone and Cartilage Degeneration in Mice Following Long-Duration Spaceflight: The Role of Bone Marrow Stem Cells

The detrimental effects of mechanical unloading in microgravity, including the musculo-skeletal system, are well documented. However, the effects of mechanical unloading on joint health and the interaction between bone and cartilage specifically, are less well known. Our ongoing studies with the mouse bone model have identified the failure of normal stem cell-based tissue regeneration, in addition to tissue degeneration, as a significant concern for long-duration spaceflight, especially in the mesenchymal and hematopoietic tissue lineages. Furthermore, we have identified the cell cycle arrest molecule, CDKN1ap21, as specifically up-regulated during spaceflight exposure and localized to osteoprecursors on the bone surface and chondroprogenitors in articular cartilage that are both required for normal tissue regeneration. The 30-day BionM1 and 37-day Rodent Research 1 (RR1) missions enabled the possibility of studying these effects in long-duration microgravity experiments. We hypothesized that the inhibition of stem cell-based tissue regeneration in short-duration spaceflight would continue during long-duration spaceflight resulting in significant tissue alterations and we specifically studied the hip joint (pelvis and proximal femur) to elucidate these effects. To test this hypothesis we analyzed bone and bone marrow stem cells using techniques including high-resolution Microcomputed Tomography (MicroCT), in-vivo differentiation and migration assays, and whole transcriptome expression profiling. We found that exposure to spaceflight for 30 days results in a significant decrease in bone volume fraction (-31), trabecular thickness (-14) and trabecular number (-20). Similar decrements in bone volume fraction (-27), trabecular number (-13) and trabecular thickness (-17) were found in female mice exposed to 37 days spaceflight. Furthermore, high-resolution MicroCT and immunohistochemical analysis of spaceflight tissues revealed a severe disruption of the epiphyseal boundary, resulting in endochondral ossification of the femoral head and perforation of articular cartilage by bone. This suggests that spaceflight in microgravity may cause rapid induction of an aging-like phenotype with signs of osteoarthritic disease in the hip joint. Microarray analysis also revealed that the top pathways altered during spaceflight include activation of matrix metalloproteinases, oxidative stress signaling and inflammation in both whole bone tissue and isolated bone marrow stem cells. In conclusion, the observed inhibition of stem cell-based tissue regeneration persists during long-duration spaceflight. Furthermore, spaceflight mice exhibit disruption of the epiphyseal boundary and endochondral ossification of the femoral head, and an inhibition of stem cell based tissue regeneration, which, taken together, may indicate onset of an accelerated aging phenotype with signs of osteoarthritic disease.

Cartilage↗
NASA NTRS2009

The Urban Environmental Monitoring/100 Cities Project: Legacy of the First Phase and Next Steps

The Urban Environmental Monitoring (UEM) project, now known as the 100 Cities Project, at Arizona State University (ASU) is a baseline effort to collect and analyze remotely sensed data for 100 urban centers worldwide. Our overarching goal is to use remote sensing technology to better understand the consequences of rapid urbanization through advanced biophysical measurements, classification methods, and modeling, which can then be used to inform public policy and planning. Urbanization represents one of the most significant alterations that humankind has made to the surface of the earth. In the early 20th century, there were less than 20 cities in the world with populations exceeding 1 million; today, there are more than 400. The consequences of urbanization include the transformation of land surfaces from undisturbed natural environments to land that supports different forms of human activity, including agriculture, residential, commercial, industrial, and infrastructure such as roads and other types of transportation. Each of these land transformations has impacted, to varying degrees, the local climatology, hydrology, geology, and biota that predate human settlement. It is essential that we document, to the best of our ability, the nature of land transformations and the consequences to the existing environment. The focus in the UEM project since its inception has been on rapid urbanization. Rapid urbanization is occurring in hundreds of cities worldwide as population increases and people migrate from rural communities to urban centers in search of employment and a better quality of life. The unintended consequences of rapid urbanization have the potential to cause serious harm to the environment, to human life, and to the resulting built environment because rapid development constrains and rushes decision making. Such rapid decision making can result in poor planning, ineffective policies, and decisions that harm the environment and the quality of human life. Slower, more thought-out, decision making could result in more favorable outcomes. The harm to the environment includes poor air quality, soil erosion, polluted rivers and aquifers, and loss of wildlife habitat. Human life is then threatened because of increased potential for disease spreading, human conflict, environmental hazards, and diminished quality of life. The built environment is potentially threatened when cities are built in areas that can be impacted by events such as hurricanes, tsunamis, earthquakes, fires, and landslides. Our goals include assessing the threat of such events on cities and the people living there.

Stefanov, William L.↗