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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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At least 73 records · Page 4

Automated CT registration, segmentation, and quantification (AutoCT) v1.0

Processing and analyzing brain imaging is crucial in both scientific development and clinical field. In this software package, we build a pipeline that integrates automatic registration, segmentation, and quantitative analysis for subjects' CT scans. Leveraging diffeomorphic transformations, we enable optimized forward and inverse mappings between an image and the reference. Furthermore, we extract localized features from deformation field based on an online template process, which advances statistical learning downstream. The created templates, atlas as well as our methods provide the brain imaging community tools for AI implementations.

Essiari, Abdelilah↗

Automated CT registration, segmentation, and quantification (AutoCT) v1.1

Processing and analyzing brain imaging is crucial in both scientific development and clinical field. In this software package, we build a pipeline that integrates automatic registration, segmentation, and quantitative analysis for subjects' CT scans. Leveraging diffeomorphic transofrmations, we enable optimized forward and inverse mappings between an image and the reference. Furthermore, we extract localized features from deformation field based on an online template process, which advances statistical learning downstream. The created templates, atlas as well as our methods provide the brain imaging community tools for AI implementations

Bai, Zhe↗

Disease phenotype of classical sheep scrapie is changed upon experimental passage through white-tailed deer

Prion agents occur in strains that are encoded by the structure of the misfolded prion protein (PrP Sc ). Prion strains can influence disease phenotype and the potential for interspecies transmission. Little is known about the potential transmission of prions between sheep and deer. Previously, the classical US scrapie isolate (No.13-7) had a 100% attack rate in white-tailed deer after oronasal challenge. The purpose of this study was to test the susceptibility of sheep to challenge with the scrapie agent after passage through white-tailed deer (WTD scrapie). Lambs of various prion protein genotypes were oronasally challenged with WTD scrapie. Sheep were euthanized and necropsied upon development of clinical signs or at the end of the experiment (72 months post-inoculation). Enzyme immunoassay, western blot, and immunohistochemistry demonstrated PrP Sc in 4 of 10 sheep with the fastest incubation occurring in VRQ/VRQ sheep, which contrasts the original No.13-7 inoculum with a faster incubation in ARQ/ARQ sheep. Shorter incubation periods in VRQ/VRQ sheep than ARQ/ARQ sheep after passage through deer was suggestive of a phenotype change, so comparisons were made in ovinized mice and with sheep with known strains of classical sheep scrapie: No. 13–7 and x-124 (that has a more rapid incubation in VRQ/VRQ sheep). After mouse bioassay, the WTD scrapie and x-124 isolates have similar incubation periods and PrP Sc conformational stability that are markedly different than the original No. 13–7 inoculum. Furthermore, brain tissues of sheep with WTD scrapie and x-124 scrapie have similar patterns of immunoreactivity that are distinct from sheep with No. 13–7 scrapie. Multiple lines of evidence suggest a phenotype switch when No. 13–7 scrapie prions are passaged through deer. This represents one example of interspecies transmission of prions resulting in the emergence or selection of new strain properties that could confound disease eradication and control efforts.

59 BASIC BIOLOGICAL SCIENCES↗

Probing the SARS-CoV-2 main protease active site as a target to inhibit viral replication

SARS-CoV-2 replication involves the synthesis of two large proteins, which are inactive and harmless until the viral main protease enzyme (3CL M pro ) uses them as substrates, cleaving them into many smaller, functional products. Dr Andrey Kovalevsky and his team from Oak Ridge National Laboratory propose a design of novel inhibitors and the repurposing of clinical drugs developed to treat other diseases for the treatment of COVID-19. Finally, the team uses room temperature crystallography with X-rays and neutrons to guide structure-based and computer-assisted drug design and to assess the ability of drugs to inhibit the SARS-CoV-2 main protease, causing virus replication to stop.

Kneller, Daniel↗

X69R Is a Non-Essential Gene That, When Deleted from African Swine Fever, Does Not Affect Virulence in Swine

African swine fever virus (ASFV) is currently causing devastating outbreaks in Asia and Europe, and the ASFV strain Georgia (ASFV-G) is responsible for these outbreaks. ASFV-G is highly virulent and continues to be maintained in these outbreak areas, apparently without suffering significant genomic or phenotypic changes. When comparing the genome of ASFV-G to other isolates, a thus-far uncharacterized gene, X69R, is highly conserved and, interestingly, is similar to another ASFV uncharacterized gene, J64R. All sequenced ASFV isolates have one or both of these genes, X69R or J64R, suggesting that the presence of at least one of these genes may be necessary for ASFV replication and or virulence. The X69R gene is present in the ASFV-G genome while J64R is absent. To assess the importance of X69R in ASFV-G functionality, we developed a recombinant virus by deleting the X69R gene from the ASFV-G genome (ASFV-G-ΔX69R). ASFV-G-ΔX69R had the same replication kinetics in primary swine macrophage cultures as the parental ASFV-G, indicating that the X69R gene is not essential for ASFV-G viability or efficient replication in the main target cell during in vivo infection. In addition, swine intramuscularly inoculated with a low dose (102 HAD50) of ASFV-G-ΔX69R developed a clinical disease indistinguishable from that induced by the same dose of the virulent parental ASFV-G isolate. Viremia values of ASFV-G-ΔX69R did not significantly differ from those detected in animals infected with parental virus. Therefore, deletion of the X69R gene from ASFV-G does not affect virus replication or virulence in swine.

59 BASIC BIOLOGICAL SCIENCES↗

Evaluation of the Function of ASFV Gene E66L in the Process of Virus Replication and Virulence in Swine

African swine fever virus (ASFV) is the etiological agent of an economically important disease of swine currently affecting large areas of Africa, Eurasia and the Caribbean. ASFV has a complex structure harboring a large dsDNA genome which encodes for more than 160 proteins. One of the proteins, E66L, has recently been involved in arresting gene transcription in the infected host cell. Here, we investigate the role of E66L in the processes of virus replication in swine macrophages and disease production in domestic swine. A recombinant ASFV was developed (ASFV-G-ΔE66L), from the virulent parental Georgia 2010 isolate (ASFV-G), harboring the deletion of the E66L gene as a tool to assess the role of the gene. ASFV-G-ΔE66L showed that the E66L gene is non-essential for ASFV replication in primary swine macrophages when compared with the parental highly virulent field isolate ASFV-G. Additionally, domestic pigs infected with ASFV-G-ΔE66L developed a clinical disease undistinguishable from that produced by ASFV-G. Therefore, E66L is not involved in virus replication or virulence in domestic pigs.

59 BASIC BIOLOGICAL SCIENCES↗

Metabolism and biochemistry in hypogravity

The headward shift of body fluid and increase in stress-related hormones that occur in hypogravity bring about a number of changes in metabolism and biochemistry of the human body. Such alterations may have important effects on health during flight and during a recovery period after return to earth. Body fluid and electrolytes are lost, and blood levels of several hormones that control metabolism are altered during space flight. Increased serum calcium may lead to an increased risk of renal stone formation during flight, and altered drug metabolism could influence the efficacy of therapeutic agents. Orthostatic intolerance and an increased risk of fracturing weakened bones are concerns at landing. It is important to understand biochemistry and metabolism in hypogravity so that clinically important developments can be anticipated and prevented or ameliorated.

Leach, Carolyn S.↗

A Hypothesis on Biological Protection from Space Radiation Through the Use of New Therapeutic Gases

Radiation exposure to astronauts could be a significant obstacle for long duration manned space exploration because of current uncertainties regarding the extent of biological effects. Furthermore, concepts for protective shielding also pose a technically challenging issue due to the nature of cosmic radiation and current mass and power constraints with modern exploration technology. The concern regarding exposure to cosmic radiation is the biological damage it induces. As damage is associated with increased oxidative stress, it is important and would be enabling to mitigate and/or prevent oxidative stress prior to the development of clinical symptoms and disease. This paper hypothesizes a "systems biology" approach in which a combination of chemical and biological mitigation techniques are used conjunctively. It proposes using new, therapeutic, medical gases as both chemical radioprotectors for radical scavenging and biological signaling molecules for management of the body s response to exposure. From reviewing radiochemistry of water, biological effects of CO, H2, NO, and H2S gas, and mechanisms of radiation biology, it is concluded that this approach may have great therapeutic potential for radiation exposure. Furthermore, it also appears to have similar potential for curtailing the pathogenesis of other diseases in which oxidative stress has been implicated including, cardiovascular disease, cancer, chronic inflammatory disease, hypertension, ischemia/reperfusion injury, acute respiratory distress syndrome, parkinson s and alzheimer s disease, cataracts, and aging

Schoenfeld, Michael P.↗

Modeling Acute Health Effects of Astronauts from Exposure to Large Solar Particle Events

In space exploration outside the Earth s geomagnetic field, radiation exposure from solar particle events (SPE) presents a health concern for astronauts, that could impair their performance and result in possible failure of the mission. Acute risks are of special concern during extra-vehicular activities because of the rapid onset of SPE. However, most SPEs will not lead to acute risks but can lead to mission disruption if accurate projection methods are not available. Acute Radiation Sickness (ARS) is a group of clinical syndromes developing acutely (within several seconds to 3 days) after high dose whole-body or significant partial-body ionizing radiation exposures. The manifestation of these syndromes reflects the disturbance of physiological processes of various cellular groups damaged by radiation. Hematopoietic cells, skin, epithelium, intestine, and vascular endothelium are among the most sensitive tissues of human body to ionizing radiation. Most ARS symptoms are directly related to these tissues and other systems (nervous, endocrine, and cardiovascular, etc.) with coupled regulations. Here we report the progress in bio-mathematical models to describe the dose and time-dependent early human responses to ionizing radiation. The responses include lymphocyte depression, granulocyte modulation, fatigue and weakness syndrome, and upper gastrointestinal distress. The modest dose and dose-rates of SPEs are predicted to lead to large sparing of ARS, however detailed experimental data on a range of proton dose-rates for organ doses from 0.5 to 2 Gy is needed to validate the models. We also report on the ARRBOD code that integrates the BRYNTRN and SUMDOSE codes, which are used to estimate the SPE organ doses for astronauts under various space travel scenarios, with our models of ARS. The more recent effort is to provide easy web access to space radiation risk assessment using the ARRBOD code.

Hu, Shaowen↗

An Integrated Musculoskeletal Countermeasure Battery for Long-Duration Lunar Missions

During extended periods of skeletal unloading, losses in strength and density of the proximal femur will occur. In long-duration spaceflight, resistive exercise is used to replace the normal loads exerted on the spine and hip. At the present time, there is no conclusive evidence that hip bone loss has been prevented in this scenario. Our group has recently developed and clinically evaluated a multifunctional exercise system, the Combined Countermeasure Device (CCD). The CCD comprises a low-footprint Stuart Platform for lower-body resistance exercise and balance training, and a cardiovascular exercise bicycle. A consideration for resistance exercise was targeting of the hip abductor and adductor muscles, which attach directly at the hip and which should subject it to the largest loads. In our training study, we found that CCD exercise increased hip adductor and abductor strength, and modeling results suggest that this exercise exerts forces on the hip of approx. 4-6 body weights at 1g, compared to forces of approx.2.5 body weight y squatting exercise. In our current study, we hypothesize that abductor and adductor exercise will increase the density and strength of the proximal femur.

Lang, T. F.↗

A Hypothesis on Biological Protection from Space Radiation Through the Use of New Therapeutic Gases as Medical Counter Measures

Radiation exposure to astronauts could be a significant obstacle for long duration manned space exploration because of current uncertainties regarding the extent of biological effects. Furthermore, concepts for protective shielding also pose a technically challenging issue due to the nature of cosmic radiation and current mass and power constraints with modern exploration technology. The concern regarding exposure to cosmic radiation is the biological damage it induces. As damage is associated with increased oxidative stress, it is important and would be enabling to mitigate and/or prevent oxidative stress prior to the development of clinical symptoms and disease. This paper hypothesizes a "systems biology" approach in which a combination of chemical and biological mitigation techniques are used conjunctively. It proposes using new, therapeutic, medical gases as both chemical radioprotectors for radical scavenging and biological signaling molecules for management of the body s response to exposure. From reviewing radiochemistry of water, biological effects of CO, H2, NO, and H2S gas, and mechanisms of radiation biology, it is concluded that this approach may have great therapeutic potential for radiation exposure. Furthermore, it also appears to have similar potential for curtailing the pathogenesis of other diseases in which oxidative stress has been implicated including cardiovascular disease, cancer, chronic inflammatory disease, hypertension, ischemia/reperfusion injury, acute respiratory distress syndrome, Parkinson s and Alzheimer s disease, cataracts, and aging.

Schoenfeld, Michael P.↗

A Hypothesis on Biological Protection from Space Radiation Through the Use of New Therapeutic Gases

Radiation exposure to astronauts could be a significant obstacle for long duration manned space exploration because of current uncertainties regarding the extent of biological effects. Furthermore, concepts for protective shielding also pose a technically challenging issue due to the nature of cosmic radiation and current mass and power constraints with modern exploration technology. The concern regarding exposure to cosmic radiation is the biological damage it induces. As damage is associated with increased oxidative stress, it is important and would be enabling to mitigate and/or prevent oxidative stress prior to the development of clinical symptoms and disease. This paper hypothesizes a "systems biology" approach in which a combination of chemical and biological mitigation techniques are used conjunctively. It proposes using new, therapeutic, medical gases as both chemical radioprotectors for radical scavenging and biological signaling molecules for management of the body s response to exposure. From reviewing radiochemistry of water, biological effects of CO, H2, NO, and H2S gas, and mechanisms of radiation biology, it is concluded that this approach may have great therapeutic potential for radiation exposure. Furthermore, it also appears to have similar potential for curtailing the pathogenesis of other diseases in which oxidative stress has been implicated including cardiovascular disease, cancer, chronic inflammatory disease, hypertension, ischemia/reperfusion injury, acute respiratory distress syndrome, Parkinson s and Alzheimer s disease, cataracts, and aging.

Schoenfeld, Michael P.↗

A Hypothesis on Biological Protection from Space Radiation Through the Use of New Therapeutic Gases as Medical Counter Measures

Exposure to astronauts could be a significant obstacle for long duration manned space exploration because of current uncertainties regarding the extent of biological effects. Furthermore, concepts for protective shielding also pose a technically challenging issue due to the nature of cosmic radiation and current mass and power constraints with modern exploration technology. As biological damage from exposure is associated with increased oxidative stress, it would be enabling to mitigate and/or prevent stress prior to the development of clinical symptoms and disease. This paper hypothesizes a "systems biology" approach in which a combination of chemical and biological mitigation techniques are used conjunctively. It proposes using new, therapeutic, medical gases as both chemical radioprotectors for radical scavenging and biological promoters for management of the body s response to exposure. From reviewing radiochemistry of water, biological effects of CO, H2, NO, and H2S gas, and mechanisms of radiation biology, it is concluded that this approach may have great therapeutic potential for exposure. Furthermore, it also appears to have potential for curtailing the pathogenesis of other diseases in which oxidative stress has been implicated including cardiovascular disease, cancer, chronic inflammatory disease, hypertension, ischemia/reperfusion injury, acute respiratory distress syndrome, Parkinson s and Alzheimer s disease, cataracts, and aging.

Schoenfeld, Michael P.↗

Miniaturized, Portable Sensors Monitor Metabolic Health

In order to measure astronauts' metabolic rates in space, Glenn Research Center partnered with Case Western University and the Cleveland Clinic to develop the Portable Unit for Metabolic Analysis (PUMA). Cleveland-based Orbital Research licensed and then modified PUMA to help the US Navy assess pilot oxygen problems and is now designing a device that can be used in hospitals.

Source record↗

Developing Mission Segment-Specific Clinical Data for Impact

Space exploration missions represent a significant future objective for NASA’s human spaceflight operations for the near and long term. By operating missions during longer periods and over further distances, NASA’s mission planning models, hardware systems, and medical capabilities will be stretched beyond their original design constraints. The necessity of medical training and medical supply manifesting for such missions is likely to become incredibly intricate as trade-space analysis is performed over varying mission profiles. For this purpose, IMPACT was created to extend and improve the Integrated Medical Model (IMM) which is used for International Space Station (ISS) medical predications and consists of a probabilistic risk assessment tool that simulates missions to calculate risks given the constraints on crew complement, mission duration and activity (such as Extravehicular Activities), power, communication, mass, volume, and evacuation consideration as well as to predict mission outcomes. Currently, the medical evidence used to support IMPACT remains static, addressing risks of a medical condition and the impacts of the condition during spaceflight only, but is only calculated for a small number of mission parameters. Extended missions will consist of new and varied living environments, changing gravitational loads, and dynamic working requirements. Medical risks are not typically constant but will change depending upon the physical and physiological environment of the body during all phases of a mission. Risks are likely to shift during different mission segments, and understanding how components of a mission profile change risks will assist mission planners to increase chances for mission success.

Christopher Zahner↗

Overcoming Barriers to Radiopharmaceutical Therapy (RPT): An Overview From the NRG-NCI Working Group on Dosimetry of Radiopharmaceutical Therapy

Radiopharmaceutical therapy (RPT) continues to demonstrate tremendous potential in improving the therapeutic gains in radiation therapy by specifically delivering radiation to tumors that can be well assessed in terms of dosimetry and imaging. Dosimetry in external beam radiation therapy is standard practice. This is not the case, however, in RPT. This NRG (acronym formed from the first letter of the 3 original groups: National Surgical Adjuvant Breast and Bowel Project, the Radiation Therapy Oncology Group, and the Gynecologic Oncology Group)-National Cancer Institute Working Group review describes some of the challenges to improving RPT. The main priorities for advancing the field include (1) developing and adopting best practice guidelines for incorporating patient-specific dosimetry for RPT that can be used at both large clinics with substantial resources and more modest clinics that have limited resources, (2) establishing and improving strategies for introducing new radiopharmaceuticals for clinical investigation, (3) developing approaches to address the radiophobia that is associated with the administration of radioactivity for cancer therapy, and (4) solving the financial and logistical issues of expertise and training in the developing field of RPT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗