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33 records · Page 2
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

Feature Selection Techniques for a Machine Learning Model to Detect Autonomic Dysreflexia

Feature selection plays a crucial role in the development of machine learning algorithms. Understanding the impact of the features on a model, and their physiological relevance can improve the performance. This is particularly helpful in the healthcare domain wherein disease states need to be identified with relatively small quantities of data. Autonomic Dysreflexia (AD) is one such example, wherein mismanagement of this neurological condition could lead to severe consequences for individuals with spinal cord injuries. We explore different methods of feature selection needed to improve the performance of a machine learning model in the detection of the onset of AD. We present different techniques used as well as the ideal metrics using a dataset of thirty-six features extracted from electrocardiograms, skin nerve activity, blood pressure and temperature. The best performing algorithm was a 5-layer neural network with five relevant features, which resulted in 93.4% accuracy in the detection of AD. The techniques in this paper can be applied to a myriad of healthcare datasets allowing forays into deeper exploration and improved machine learning model development. Through critical feature selection, it is possible to design better machine learning algorithms for detection of niche disease states using smaller datasets.

electrocardiography↗
NASA NTRS1994

Human autonomic rhythms: vagal cardiac mechanisms in tetraplegic subjects

1. We studied eight young men (age range: 20-37 years) with chronic, clinically complete high cervical spinal cord injuries and ten age-matched healthy men to determine how interruption of connections between the central nervous system and spinal sympathetic motoneurones affects autonomic cardiovascular control. 2. Baseline diastolic pressures and R-R intervals (heart periods) were similar in the two groups. Slopes of R-R interval responses to brief neck pressure changes were significantly lower in tetraplegic than in healthy subjects, but slopes of R-R interval responses to steady-state arterial pressure reductions and increases were comparable. Plasma noradrenaline levels did not change significantly during steady-state arterial pressure reductions in tetraplegic patients, but rose sharply in healthy subjects. The range of arterial pressure and R-R interval responses to vasoactive drugs (nitroprusside and phenylephrine) was significantly greater in tetraplegic than healthy subjects. 3. Resting R-R interval spectral power at respiratory and low frequencies was similar in the two groups. During infusions of vasoactive drugs, low-frequency R-R interval spectral power was directly proportional to arterial pressure in tetraplegic patients, but was unrelated to arterial pressure in healthy subjects. Vagolytic doses of atropine nearly abolished both low- and respiratory-frequency R-R interval spectral power in both groups. 4. Our conclusions are as follows. First, since tetraplegic patients have significant levels of low-frequency arterial pressure and R-R interval spectral power, human Mayer arterial pressure waves may result from mechanisms that do not involve stimulation of spinal sympathetic motoneurones by brainstem neurones. Second, since in tetraplegic patients, low-frequency R-R interval spectral power is proportional to arterial pressure, it is likely to be mediated by a baroreflex mechanism. Third, since low-frequency R-R interval rhythms were nearly abolished by atropine in both tetraplegic and healthy subjects, these rhythms reflect in an important way rhythmic firing of vagal cardiac motoneurones.

Non-NASA Center↗
DOE OSTI2025

Motion of Molecules in Supramolecular Scaffolds Enhances Bone Regeneration

The regeneration of human tissues is a great scientific challenge and a critical factor to achieve a long healthspan and prevent disabilities due to injury or disease. Materials chemistry can contribute to this goal with the development of bioactive supramolecular systems that can signal cells for regeneration. Recent work in our laboratory using in vivo models of spinal cord injury and cartilage regeneration has demonstrated that the motion of bioactive molecules in supramolecular scaffolds enhances receptor signaling. We report here on a novel molecular strategy to control supramolecular motion in filamentous assemblies using bone regeneration as a functional target. The supramolecular assemblies are composed of monomers that arrange, by design, with either parallel or antiparallel β-sheets, and some of them contain a terminal peptide sequence that binds BMP-2. We found that parallel β-sheet supramolecular assemblies promote greater osteogenic differentiation of progenitor cells in vitro relative to antiparallel assemblies, as well as superior quality of newly regenerated bone in a rat model of spinal fusion. Furthermore, these assemblies drastically reduce the dangerous supraphysiological dose of BMP-2 used clinically for spinal fusion. Here, we attribute the enhanced bioactivity to the weaker nature of hydrogen bonds in parallel relative to antiparallel β-sheet assemblies, which in turn allows greater supramolecular motion and cell signaling of the growth factor-binding molecules.

Anatomy↗
DOE OSTI2021

Global transcriptome profile of the developmental principles of in vitro iPSC-to-motor neuron differentiation

Abstract Background Human induced pluripotent stem cells (iPSC) have opened new avenues for regenerative medicine. Consequently, iPSC-derived motor neurons have emerged as potentially viable therapies for spinal cord injuries and neurodegenerative disorders including Amyotrophic Lateral Sclerosis. However, direct clinical application of iPSC bears in itself the risk of tumorigenesis and other unforeseeable genetic or epigenetic abnormalities. Results Employing RNA-seq technology, we identified and characterized gene regulatory networks triggered by in vitro chemical reprogramming of iPSC into cells with the molecular features of motor neurons (MNs) whose function in vivo is to innervate effector organs. We present meta-transcriptome signatures of 5 cell types: iPSCs, neural stem cells, motor neuron progenitors, early motor neurons, and mature motor neurons. In strict response to the chemical stimuli, along the MN differentiation axis we observed temporal downregulation of tumor growth factor-β signaling pathway and consistent activation of sonic hedgehog, Wnt/β-catenin, and Notch signaling. Together with gene networks defining neuronal differentiation (neurogenin 2, microtubule-associated protein 2, Pax6, and neuropilin-1), we observed steady accumulation of motor neuron-specific regulatory genes, including Islet-1 and homeobox protein HB9. Interestingly, transcriptome profiling of the differentiation process showed that Ca 2+ signaling through cAMP and LPC was downregulated during the conversion of the iPSC to neural stem cells and key regulatory gene activity of the pathway remained inhibited until later stages of motor neuron formation. Pathways shaping the neuronal development and function were well-represented in the early motor neuron cells including, neuroactive ligand-receptor interactions, axon guidance, and the cholinergic synapse formation. A notable hallmark of our in vitro motor neuron maturation in monoculture was the activation of genes encoding G-coupled muscarinic acetylcholine receptors and downregulation of the ionotropic nicotinic acetylcholine receptors expression. We observed the formation of functional neuronal networks as spontaneous oscillations in the extracellular action potentials recorded on multi-electrode array chip after 20 days of differentiation. Conclusions Detailed transcriptome profile of each developmental step from iPSC to motor neuron driven by chemical induction provides the guidelines to novel therapeutic approaches in the re-construction efforts of muscle innervation.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1974

The National Research Council program on aid to the neurologically handicapped

The multidisciplinary care of neuromuscular disabled patients is reviewed. Described are the activities of occupational and vocational therapists, social workers, clinical psychologists and speech pathologists that are directed toward the major effects of spinal cord injuries, amputations, stroke, cerebral palsy, and rheumatoid arthritis.

Mclaurin, C.↗
NASA NTRS1974

Current therapeutic techniques and rehabilitation from neurological disorders

Rancho Los Amigos Hospital is a 1100-bed teaching hospital that is primarily oriented toward rehabilitation. The individual services that deal with neuromuscular disorders are categorically disease entity oriented: They are directed toward the major problems, such as spinal cord injuries, amputations, stroke, cerebral palsy, and rheumatoid arthritis. The services at Rancho cross many traditional medical specialty barriers.

Nickel, V. L.↗
NASA NTRS1974

The use of objective measurements in the evaluation of therapy programs

The importance of objective measurements is discussed as a means of assessing the efficacy of physical and occupational therapy programs applied to patients recovering from neurological diseases. Considered are three primary categories of neurologically injured patients: patients with hemiplegia, patients with spinal cord injuries, and the heterogeneous group of cerebral palsy patients.

Chaplin, H.↗
NASA NTRS1994

Biomedical Use of Aerospace Personal Cooling Garments

Personal thermoregulatory systems are required during extravehicular activity (EVA) to remove the metabolic heat generated by the suited astronaut. The Extravehicular and Protective Systems (STE) Branch of NASA Ames Research Center has developed advanced concepts or liquid cooling garments for both industrial and biomedical applications for the past 25 years. Examples of this work include: (1) liquid cooled helmets for helicopter pilots and race car drivers; (2) vests for fire and mine rescue personnel; (3) bras to increase the definition of tumors during thermography; (4) lower body garments for young women with erythomelaigia; and (5) whole body garments used by patients with multiple sclerosis (MS). The benefits of the biomedical application of artificial thermoregulation received national attention through two recent events: (1) the liquid-cooled garment technology was inducted into the United States Space Foundation's Space Technology Hall of Fame (1993); and (2) NASA has signed a joint Memorandum of Understanding with the Multiple Sclerosis Association (1994) to share this technology for use with MS patient treatment. The STE Branch is currently pursuing a program to refine thermoregulatory design in light of recent technology developments that might be applicable for use by several medical patient populations. Projects have been initiated to apply thermoregulatory technology for the treatment and/or rehabilitation of patients with spinal cord injuries, multiple sclerosis, migraine headaches, and to help prevent the loss of hair during chemotherapy.

Webbon, Bruce W.↗
NASA NTRS1996

Differences in Femoral Geometry and Structure Due to Immobilization

Reduction in bone mass of the lower extremity is well documented in individuals with paralysis resulting from spinal cord injury (SCI). The consequent osteopenia leads to elevated fracture risk with fractures occurring more commonly in the femoral shaft and supracondylar regions than the hip. A model has recently been described to estimate geometry and structure of the femoral midshaft from whole body scans by dual X-ray absorptiometry (DXA). Increases in femoral geometric and structural properties during growth were primarily related to mechanical loading as reflected by body mass. In this study, we investigate the relationship between body mass and femoral geometry and structure in adults with normal habitual mechanical loading patterns and those with severely reduced loading. The subjects were 78 ambulatory men (aged 20-72 yrs) and 113 men with complete paralysis from SCI of more than 4 years duration (aged 21 73 yrs). Subregional analysis was performed on DXA whole body scans to obtain bone mineral content (BMC, g), cortical thickness (cm), crosssectional moment of inertia (CSMI, cm4), and section modulus (cm3) of the femoral midshaft. All measured bone variables were significantly lower in SCI compared with ambulatory subjects: -29% (BMC), -33% (cortical thickness), -23% (CSMI), and -22% (section modulus) while body mass was not significantly different. However, the associations between body mass and bone properties were notably different; r2 values were higher for ambulatory than SCI subjects in regressions of body mass on BMC (0.48 vs 0.20), CSMI (0.59 vs 0.32), and section modulus (0.59 vs 0.31). No association was seen between body mass and cortical thickness for either group. The greatest difference between groups is in the femoral cortex, consistent with reduced bone mass via endosteal expansion. The relatively lesser difference in geometric and structural properties implies that there is less effect on mechanical integrity than would be expected from bone mass results alone. The reduced association in SCI subjects between body mass and bone properties is not unexpected. Although mean body mass differs little between ambulatory and SCI individuals, the association between body mass and in vivo skeletal loading is no longer present, as mechanical influences are removed except for transfer activities. The residual association is probably attributable to the strength of this influence during growth. These results highlight the importance of examining geometry and structure in conjunction with bone mass.

Kiratli, Beatrice Jenny↗
NASA NTRS2002

Skeletal Adaptation to Daily Activity: A Biochemical Perspective

Musculoskeletal forces generated by normal daily activity on Earth maintain the functional and structural properties of muscle and bone throughout most of one's adult life. A reduction in the level of cumulative daily loading caused by space flight, bed rest or spinal cord injury induces rapid muscle atrophy, functional changes in muscle, and bone resorption in regions subjected to the reduced loading. Bone cells in culture and bone tissue reportedly respond to a wide variety of non-mechanical and mechanical stimuli ranging, from electromagnetic fields, and hormones to small amplitude, high frequency vibrations, fluid flow, strain rate, and stress/strain magnitude. However, neither the transduction mechanism that transforms the mechanical input into a muscle or bone metabolic response nor the characteristics, of the loading history that directly or indirectly stimulates the cell is known. Identifying the factors contributing to the input stimulus will have a major impact on the design of effective countermeasures for long duration space flight. This talk will present a brief overview of current theories of bone remodeling and functional adaptation to mechanical loading. Work from our lab will be presented from the perspective of daily cumulative loading on Earth and its relationship to bone density and structure. Our objective is to use the tibia and calcaneus as model bone sites of cortical and cancellous bone adaptation, loaded daily by musculoskeletal forces in equilibrium with the ground reaction force. All materials that will be discussed are in the open scientific literature.

Whalen, Robert T.↗
NASA NTRS2003

Cell Science and Cell Biology Research at MSFC: Summary

The common theme of these research programs is that they investigate regulation of gene expression in cells, and ultimately gene expression is controlled by the macromolecular interactions between regulatory proteins and DNA. The NASA Critical Path Roadmap identifies Muscle Alterations and Atrophy and Radiation Effects as Very Serious Risks and Severe Risks, respectively, in long term space flights. The specific problem addressed by Dr. Young's research ("Skeletal Muscle Atrophy and Muscle Cell Signaling") is that skeletal muscle loss in space cannot be prevented by vigorous exercise. Aerobic skeletal muscles (i.e., red muscles) undergo the most extensive atrophy during long-term space flight. Of the many different potential avenues for preventing muscle atrophy, Dr. Young has chosen to study the beta-adrenergic receptor (betaAR) pathway. The reason for this choice is that a family of compounds called betaAR agonists will preferentially cause an increase in muscle mass of aerobic muscles (i.e., red muscle) in animals, potentially providing a specific pharmacological solution to muscle loss in microgravity. In addition, muscle atrophy is a widespread medical problem in neuromuscular diseases, spinal cord injury, lack of exercise, aging, and any disease requiring prolonged bedridden status. Skeletal muscle cells in cell culture are utilized as a model system to study this problem. Dr. Richmond's research ("Radiation & Cancer Biology of Mammary Cells in Culture") is directed toward developing a laboratory model for use in risk assessment of cancer caused by space radiation. This research is unique because a human model will be developed utilizing human mammary cells that are highly susceptible to tumor development. This approach is preferential over using animal cells because of problems in comparing radiation-induced cancers between humans and animals.

Source record↗
NASA NTRS2000

Invited review: gravitational biology of the neuromotor systems: a perspective to the next era

Earth's gravity has had a significant impact on the designs of the neuromotor systems that have evolved. Early indications are that gravity also plays a key role in the ontogenesis of some of these design features. The purpose of the present review is not to assess and interpret a body of knowledge in the usual sense of a review but to look ahead, given some of the general concepts that have evolved and observations made to date, which can guide our future approach to gravitational biology. We are now approaching an era in gravitational biology during which well-controlled experiments can be conducted for sustained periods in a microgravity environment. Thus it is now possible to study in greater detail the role of gravity in phylogenesis and ontogenesis. Experiments can range from those conducted on the simplest levels of organization of the components that comprise the neuromotor system to those conducted on the whole organism. Generally, the impact of Earth's gravitational environment on living systems becomes more complex as the level of integration of the biological phenomenon of interest increases. Studies of the effects of gravitational vectors on neuromotor systems have and should continue to provide unique insight into these mechanisms that control and maintain neural control systems designed to function in Earth's gravitational environment. A number of examples are given of how a gravitational biology perspective can lead to a clearer understanding of neuromotor disorders. Furthermore, the technologies developed for spaceflight studies have contributed and should continue to contribute to studies of motor dysfunctions, such as spinal cord injury and stroke. Disorders associated with energy support and delivery systems and how these functions are altered by sedentary life styles at 1 G and by space travel in a microgravity environment are also discussed.

Review, Tutorial↗
NASA NTRS2003

Integrated Electrode Arrays for Neuro-Prosthetic Implants

Arrays of electrodes integrated with chip-scale packages and silicon-based integrated circuits have been proposed for use as medical electronic implants, including neuro-prosthetic devices that might be implanted in brains of patients who suffer from strokes, spinal-cord injuries, or amyotrophic lateral sclerosis. The electrodes of such a device would pick up signals from neurons in the cerebral cortex, and the integrated circuit would perform acquisition and preprocessing of signal data. The output of the integrated circuit could be used to generate, for example, commands for a robotic arm. Electrode arrays capable of acquiring electrical signals from neurons already exist, but heretofore, there has been no convenient means to integrate these arrays with integrated-circuit chips. Such integration is needed in order to eliminate the need for the extensive cabling now used to pass neural signals to data-acquisition and -processing equipment outside the body. The proposed integration would enable progress toward neuro-prostheses that would be less restrictive of patients mobility. An array of electrodes would comprise a set of thin wires of suitable length and composition protruding from and supported by a fine-pitch micro-ball grid array or chip-scale package (see figure). The associated integrated circuit would be mounted on the package face opposite the probe face, using the solder bumps (the balls of the ball grid array) to make the electrical connections between the probes and the input terminals of the integrated circuit. The key innovation is the insertion of probe wires of the appropriate length and material into the solder bumps through a reflow process, thereby fixing the probes in place and electrically connecting them with the integrated circuit. The probes could be tailored to any distribution of lengths and made of any suitable metal that could be drawn into fine wires. Furthermore, the wires could be coated with an insulating layer using anodization or other processes, to achieve the correct electrical impedance. The probe wires and the packaging materials must be biocompatible using such materials as lead-free solders. For protection, the chip and package can be coated with parylene.

Brandon, Erik↗
DOE OSTI2023

Supramolecular polymers: Dynamic assemblies of “dancing” monomers

The objective of this perspective on supramolecular polymers is to highlight how their dynamic nature based on noncovalent bonding among monomers can have a profound impact on their functions. We focus here on peptide amphiphile supramolecular polymers developed in our laboratory and use recent results on their dynamic behavior to reflect on the exciting functions that might emerge in these systems. We are greatly motivated by recent results that demonstrate unprecedented bioactivity in supramolecular polymers to address the enormous scientific challenge of finding strategies to reverse paralysis caused by traumatic injuries or disease. We suggest that future opportunities exist for novel functions in supramolecular polymers by tuning dynamic behavior through the chemical design of monomers, and also by gaining an understanding of the precise spatiotemporal mechanisms linked to supramolecular motion in these emerging polymers.

36 MATERIALS SCIENCE↗
NASA NTRS2001

Crosstalk between p38, Hsp25 and Akt in spinal motor neurons after sciatic nerve injury

The p38 stress-activated protein kinase pathway is involved in regulation of phosphorylation of Hsp25, which in turn regulates actin filament dynamic in non-neuronal cells. We report that p38, Hsp25 and Akt signaling pathways were specifically activated in spinal motor neurons after sciatic nerve axotomy. The activation of the p38 kinase was required for induction of Hsp25 expression. Furthermore, Hsp25 formed a complex with Akt, a member of PI-3 kinase pathway that prevents neuronal cell death. Together, our observations implicate Hsp25 as a central player in a complex system of signaling that may both promote regeneration of nerve fibers and prevent neuronal cell death in the injured spinal cord.

NASA Discipline Developmental Biology↗