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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 271 records · Page 15
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

One-Step Regeneration of Hairy Roots to Induce High Tanshinone Plants in Salvia miltiorrhiza

Salvia miltiorrhiza is a traditional Chinese medicinal plant of Labiatae, which has been widely utilized to treat a variety of cardiovascular and cerebrovascular diseases. However, due to the long growth cycle, low content of active ingredients, and serious quality deterioration of S. miltiorrhiza , the use of biotechnology to improve S. miltiorrhiza to meet the growing demand for clinical applications has become a research hotspot. In this study, a novel one-step hairy root regeneration method was developed, which could rapidly obtain hairy roots and regenerated plants with high tanshinone content. By optimizing the parameters of Agrobacterium rhizogenes transformation in S. miltiorrhiza , it was finally established that the explants were infected in Ar.qual (OD 600 = 0.6) for 10 min, co-cultured for 3 days, and then screened on the screening medium containing 7.5 mg/l hygromycin, the maximum transformation frequency can reach 73.85%. GFP and PCR detection yielded a total of 9 positive transgenic hairy root lines and 11 positive transgenic regenerated plants. SmGGPPS1 was successfully overexpressed in positive transgenic regenerated plants, according to the results of qRT-PCR. The content of tanshinone IIA and cryptotanshinone were dramatically enhanced in transgenic regenerated plants and hairy roots by Ultra Performance Liquid Chromatography analysis. Based on the Agrobacterium-mediated transformation of S. miltiorrhiza , this study developed a new method for regenerating plants with transgenic hairy roots. This method provides a foundation for the breeding of S. miltiorrhiza and the sustainable development of medicinal plant resources, as well as provides a useful reference for the application of other species.

Su, Yuekai↗
DOE OSTI2023

Monte Carlo simulation of shielding designs for a cabinet form factor preclinical MV–energy photon FLASH radiotherapy system

Purpose: A preclinical MV-energy photon FLASH radiotherapy system is being designed at Stanford and SLAC National Accelerator Laboratory. Because of the higher energy and dose rate compared to conventional kV-energy photon laboratory-scale irradiators, adequate shielding in a stand-alone cabinet form factor is more challenging to achieve. We present a Monte Carlo simulation of multilayered shielding for a compact self-shielding system without the need for a radiation therapy vault. Methods: A multilayered shielding approach using multiple alternating layers of high-Z and low-Z materials is applied to the self-shielded cabinet to effectively mitigate the secondary radiation produced and to allow the device to be housed in a Controlled Radiation Area outside of a radiation vault. The multilayered shielding approach takes advantage of the properties of high-Z and low-Z radiation shielding materials such as density, cross-section, atomic number of the shielding elements, and products of radiation interactions within each layer. The Monte Carlo radiation transport code, FLUKA, is used to simulate the total effective dose produced by the operation. Results: The multilayered shielding designs proposed and simulated produced effective dose rates significantly lower than monolayer designs with the same total material thickness at the regulatory boundary; this is accomplished through the manipulation of the locations where secondary radiation is produced and reactions due to material properties such as neutron back reflection in hydrogen. Borated polyethylene at 5 wt% significantly increased the shielding performance as compared to regular polyethylene, with the magnitude of the reduction depending upon the order of the shielding material. Conclusions: The multilayered shielding provides a path for shielding preclinical FLASH systems that deliver MV-energy bremsstrahlung photons. Furthermore, this approach promises to be more efficient with respect to the shielding material mass and space claim as compared to shielded vaults typically required for clinical radiation therapy with MV photons.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2020

Nanoparticles for targeted cancer radiotherapy

Radiotherapy, where ionizing radiation is locally delivered either through an external beam or by surgically implanting radionuclide-based seeds in the tumor, is one of the gold standard treatments for cancer. Due to the non-selective nature of radiation, healthy tissue surrounding the cancerous region is usually affected by the treatment. Hence, new strategies, including targeted alpha therapy, are being studied to improve the selectivity of the treatment and minimize side effects. Several challenges, however, limit the current development of targeted radiotherapy, such as the functionalization of the therapeutic agent with targeting vectors and controlling the release of recoiling daughters. Nanoparticles offer unique opportunities as drug delivery vehicles, since they are biocompatible, enhance the cellular uptake of drugs, and are easily functionalized with targeting molecules. In this review, we examine how nanoparticles can be used for targeted radiotherapy, either as sensitizers of external beams or as delivery vehicles for therapeutic radionuclides. Further, we describe the clinical relevance of different types of nanoparticles, followed by an analysis of how these nanoconstructs can solve some of the main limitations of conventional radiotherapy. Finally, we critically discuss the current situation of nanoparticle-based radiotherapy in clinical settings and challenges that need to be overcome in the future for further development of the field.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2022

First Multimodal, Three-Dimensional, Image-Guided Total Marrow Irradiation Model for Preclinical Bone Marrow Transplantation Studies

Total marrow irradiation (TMI) has significantly advanced radiation conditioning for hematopoietic cell transplantation in hematologic malignancies by reducing conditioning-induced toxicities and improving survival outcomes in relapsed/refractory patients. However, the relapse rate remains high, and the lack of a preclinical TMI model has hindered scientific advancements. To accelerate TMI translation to the clinic, we developed a TMI delivery system in preclinical models.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
NASA NTRS2012

Anaphylaxis, Intra-Abdominal Infections, Skin Lacerations, and Behavioral Emergencies: A Literature Review of Austere Analogs for a near Earth Asteroid Mission

As space exploration is directed towards destinations beyond low-Earth orbit, the consequent new set of medical risks will drive requirements for new capabilities and more resources to ensure crew health. The Space Medicine Exploration Medical Conditions List (SMEMCL), developed by the Exploration Medical Capability element of the Human Research Program, addresses the risk of "unacceptable health and mission outcomes due to limitations of in-flight medical capabilities". It itemizes 85 evidence-based clinical requirements for eight different mission profiles and identifies conditions warranting further research and technology development. Each condition is given a clinical priority for each mission profile. Four conditions -- intra-abdominal infections, skin lacerations, anaphylaxis, and behavioral emergencies -- were selected as a starting point for analysis. A systematic literature review was performed to understand how these conditions are treated in austere, limited-resource, space-analog environments (i.e., high-altitude and mountain environments, submarines, military deployments, Antarctica, isolated wilderness environments, in-flight environments, and remote, resource-poor, rural environments). These environments serve as analogs to spaceflight because of their shared characteristics (limited medical resources, delay in communication, confined living quarters, difficulty with resupply, variable time to evacuation). Treatment of these four medical conditions in austere environments provides insight into medical equipment and training requirements for exploration-class missions.

Chough, Natacha G.↗
DOE OSTI2021

A first-in-human phase 0 clinical study of RNA interference–based spherical nucleic acids in patients with recurrent glioblastoma

Glioblastoma (GBM) is one of the most difficult cancers to effectively treat, in part because of the lack of precision therapies and limited therapeutic access to intracranial tumor sites due to the presence of the blood-brain and blood-tumor barriers. We have developed a precision medicine approach for GBM treatment that involves the use of brain-penetrant RNA interference–based spherical nucleic acids (SNAs), which consist of gold nanoparticle cores covalently conjugated with radially oriented and densely packed small interfering RNA (siRNA) oligonucleotides. On the basis of previous preclinical evaluation, we conducted toxicology and toxicokinetic studies in nonhuman primates and a single-arm, open-label phase 0 first-in-human trial ( NCT03020017 ) to determine safety, pharmacokinetics, intratumoral accumulation and gene-suppressive activity of systemically administered SNAs carrying siRNA specific for the GBM oncogene Bcl2Like12 (Bcl2L12). Patients with recurrent GBM were treated with intravenous administration of siBcl2L12-SNAs (drug moniker: NU-0129), at a dose corresponding to 1/50th of the no-observed-adverse-event level, followed by tumor resection. Safety assessment revealed no grade 4 or 5 treatment–related toxicities. Inductively coupled plasma mass spectrometry, x-ray fluorescence microscopy, and silver staining of resected GBM tissue demonstrated that intravenously administered SNAs reached patient tumors, with gold enrichment observed in the tumor-associated endothelium, macrophages, and tumor cells. NU-0129 uptake into glioma cells correlated with a reduction in tumor-associated Bcl2L12 protein expression, as indicated by comparison of matched primary tumor and NU-0129–treated recurrent tumor. Our results establish SNA nanoconjugates as a potential brain-penetrant precision medicine approach for the systemic treatment of GBM.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Fractionated Radiation Severely Reduces the Number of CD8+ T Cells and Mature Antigen Presenting Cells Within Lung Tumors

The combination of standard-of-care radiation therapy (RT) with immunotherapy is moving to the mainstream of non-small cell lung cancer treatment. Multiple preclinical studies reported on the CD8{sup +} T cell stimulating properties of RT, resulting in abscopal therapeutic effects. A literature search demonstrates that most preclinical lung cancer studies applied subcutaneous lung tumor models. Hence, in-depth immunologic evaluation of clinically relevant RT in orthotopic lung cancer models is lacking.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2023

Engineering a modular 44 Ti/ 44 Sc generator: eluate evaluation in preclinical models and estimation of human radiation dosimetry

Background: 44 Sc/ 47 Sc is an attractive theranostic pair for targeted in vivo positron emission tomographic (PET) imaging and beta-particle treatment of cancer. The 44 Ti/ 44 Sc generator allows daily onsite production of this diagnostic isotope, which may provide an attractive alternative for PET facilities that lack in-house irradiation capabilities. Early animal and patient studies have demonstrated the utility of 44 Sc. In our current study, we built and evaluated a novel clinical-scale 44 Ti/ 44 Sc generator, explored the pharmacokinetic profiles of 44 ScCl 3 , [ 44 Sc]-citrate and [ 44 Sc]-NODAGA (1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid) in naïve mice, and estimated the radiation burden of 44 ScCl 3 in humans. Methods: 44 Ti/ 44 Sc (101.2 MBq) in 6 M HCl solution was utilized to assemble a modular ZR resin containing generator. After assembly, 44 Sc was eluted with 0.05 M HCl for further PET imaging and biodistribution studies in female Swiss Webster mice. Based on the biodistribution data, absorbed doses of 44 / 47 ScCl 3 in human adults were calculated for 18 organs and tissues using the IDAC-Dose software. Results: 44 Ti in 6 M HCl was loaded onto the organic resin generator with a yield of 99.97%. After loading and initial stabilization, 44 ScCl 3 was eluted with 0.05 M HCl in typical yields of 82.9 ± 5.3% (N = 16), which was normalized to the estimated generator capacity. Estimated generator capacity was computed based on elution time interval and the total amount of 44 Ti loaded on the generator. Run in forward and reverse directions, the 44 Sc/ 44 Ti ratio from a primary column was significantly improved from 1038 ± 440 to 3557 ± 680 (Bq/Bq) when a secondary, replaceable, ZR resin cartridge was employed at the flow outlet. In vivo imaging and ex vivo distribution studies of the reversible modular generator for 44 ScCl 3 , [ 44 Sc]-citrate and [ 44 Sc]-NODAGA show that free 44 Sc remained in the circulation significantly longer than the chelated 44 Sc. The dose estimation of 44 ScCl 3 reveals that the radiation burden is 0.146 mSv/MBq for a 70 kg adult male and 0.179 mSv/MBq for a 57 kg adult female. Liver, spleen and heart wall will receive the highest absorbed dose: 0.524, 0.502, and 0.303 mGy/MBq, respectively, for the adult male. Conclusions: A clinical-scale 44 Ti/ 44 Sc generator system with a modular design was developed to supply 44 ScCl 3 in 0.05 M HCl, which is suitable for further radiolabeling and in vivo use. Our data demonstrated that free 44 ScCl 3 remained in the circulation for extended periods, which resulted in approximately 10 times greater radiation burden than stably chelated 44 Sc. Stable 44 Sc/ 47 Sc-complexation will be more favorable for in vivo use and for clinical utility.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2025

The evolution of analytical techniques for multiplex analysis of protein biomarkers

Introduction: The landscape of biomarker development has evolved with advanced analytical technologies, particularly affinity- and mass spectrometry-based techniques. These advancements have deepened our understanding of disease mechanisms, enabling the development of precise diagnostic tools and personalized medicine. Protein biomarkers, which play pivotal roles in biological processes, have become invaluable in diagnosing and monitoring diseases, aided by their presence in various biological samples and the availability of established detection methods. Areas covered: This review covers the role of protein biomarkers in clinical practice, the development and dimensionality of protein biomarkers, advancements in detection technologies, a comparison of these technologies, and future directions in biomarker discovery and disease mechanism elucidation. Expert opinion: Advances in biomarker technologies have the potential to transform diagnostics and personalized treatment but face challenges such as high costs and technical complexity. Enhancing reproducibility and integrating multi-omics approaches may offer better insights. In conclusion, the field should evolve toward high-throughput, automated methods, continuously adapting research, and clinical practices.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2010

Managing the Risk for Early Onset Osteoporosis in Long-Duration Astronauts Due to Spaceflight

Early Onset Osteoporosis is probably the most recognized but poorly understood long-term health risk due to spaceflight. Osteoporosis management is primarily prophylactic and clinical interventions rely upon the ability to predict fractures which is currently determined by surrogate measures of bone strength. The RMAT for Early Onset Osteoporosis identified some open issues related to the fact that long-duration astronauts compose a unique group of subjects for which clinical approaches for osteoporosis management do not apply. Long-duration astronauts are healthy, young (25 to 55 years of age), predominantly male, and physical fit relative to the typical osteoporosis patient. Moreover, during prolonged space missions (typically 6-month missions) the skeleton not only adapts to weightlessness, but is influenced by numerous risk factors induced by operational constraints, e.g., inability to maintain preflight weight-bearing and aerobic activities, sub-optimal dietary intake (e.g., high sodium content for food stability, lack of fresh fruit and vegetables), suppression of vitamin D metabolism by uv shielding, and remote medicine care. Moreover, adaptation results in novel changes to astronauts bones that cannot be detected by current medically-useful measures. Consequently, a panel of clinicians (recognized leaders and policy-makers in osteoporosis) was convened to review the dataset of bone measures and bone loss risk factors in long-duration astronauts. Driven by the queries in the RMAT, the panel was charged to determine 1) if an intervention is required to prevent this risk, 2) what type and at what time would intervention be optimal, 3) what is the clinical trigger that would require a medical response from flight surgeons and 4) how should research data be used in the clinical care of astronauts. Hence, the RMAT determined that a bone health policy need to be formulated specific for this unique cohort subjected to a novel skeletal condition

Sibonga, Jean D.↗
DOE OSTI2021

Dietary Methionine Supplementation Exacerbates Gastrointestinal Toxicity in a Mouse Model of Abdominal Irradiation

Identification of appropriate dietary strategies for prevention of weight and muscle loss in cancer patients is crucial for successful treatment and prolonged patient survival. High-protein oral nutritional supplements decrease mortality and improve indices of nutritional status in cancer patients; however, high-protein diets are often rich in methionine, and experimental evidence indicates that a methionine-supplemented diet (MSD) exacerbates gastrointestinal toxicity after total body irradiation. Here, we sought to investigate whether MSD can exacerbate gastrointestinal toxicity after local abdominal irradiation, an exposure regimen more relevant to clinical settings.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Clinical Value of Upfront Cranial Radiation Therapy in Osimertinib-Treated Epidermal Growth Factor Receptor–Mutant Non-Small Cell Lung Cancer With Brain Metastases

As a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), osimertinib has a powerful ability to penetrate the blood-brain barrier and a high potency for controlling brain metastases (BMs) from EGFR-mutant non-small cell lung cancer (NSCLC). The clinical value of cranial radiation therapy in osimertinib-treated NSCLC with BMs remains largely unknown.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
NASA NTRS2015

Evalution of a DE-Identification Process for Ocular Imaging

Medical privacy of NASA astronauts requires an organized and comprehensive approach when data are being made available outside NASA systems. A combination of factors, including the uniquely small patient population, the extensive medical testing done on these individuals, and the relative cultural popularity of the astronauts puts them at a far greater risk to potential exposure of personal information than the general public. Therefore, care must be taken to ensure that the astronauts' identities are concealed. Magnetic Resonance Imaging (MRI) medical data is a recent source of interest to researchers concerned with the development of Visual Impairment due to Intracranial Pressure (VIIP) in the astronaut population. Each vision MRI scan of an astronaut includes 176 separate sagittal images that are saved as an "image series" for clinical use. In addition to the medical information these image sets provide, they also inherently contain a substantial amount of non-medical personally identifiable information (PII) such as-name, date of birth, and date of exam. We have shown that an image set of this type can be rendered, using free software, to give an accurate representation of the patient's face. This currently restricts NASA from dispensing MRI data to researchers in a deidentified format. Automated software programs, such as the Brain Extraction Tool, are available to researchers who wish to de-identify MRI sagittal brain images by "erasing" identifying characteristics such as the nose and jaw on the image sets. However, this software is not useful to NASA for vision research because it removes the portion of the images around the eye orbits, which is the main area of interest to researchers studying the VIIP syndrome. The Lifetime Surveillance of Astronaut Health program has resolved this issue by developing a protocol to de-identify MRI sagittal brain images using Showcase Premier, a DICOM (Digital Imaging and Communications in Medicine) software package. The software allows manual editing of one image from a patient's image set to be automatically applied to the entire image series. This new approach would allow a new level of access to untapped medical imaging data relating to VIIP that can be utilized by researchers while protecting the privacy of the astronauts. In the next step toward finalizing this technique, NASA clinical radiology consultants will test the images to verify removal of all metadata and PII.

LaPelusa, Michael B.↗
DOE OSTI2026

Hadron Therapy For Cancer Treatment

The biological and physical rationale for hadron therapy is well understood by the research community, but hadron therapy is not well established in mainstream medicine. This talk will describe the biological advantage of neutron therapy and the dose distribution advantage of proton therapy, followed by a discussion of the challenges to be met before hadron therapy can play a significant role in treating cancer. A proposal for a new research-oriented hadron clinic will be presented.

Lennox, Arlene Judith [Fermilab]↗
DOE OSTI2020

Protein Factory on a Chip for Rapid Therapeutics

The potential for new, re-emerging, or engineered pandemic threats could challenge our nation's biosecurity, requiring rapid and flexible countermeasure development platforms. In healthcare, one of the main hindrances to the timely development of protein-based therapeutics for cancer, infectious disease, and other diseases has been a slow and expensive quality-controlled production stage. We present a protein-based technology that has the potential to address these crucial problems in biosecurity and healthcare by maximizing protein production and system portability, while minimizing production latency and cost. Specifically, we have developed a reusable, portable first-generation platform that leverages the advantages of cell-free protein synthesis (CFPS) and flow cells to create practical amounts of clinically relevant therapeutics. We have demonstrated that this technology is reusable and programmable, enabling a single platform that can synthesize multiple dosages of various therapeutics and vaccine in the field. Implementing this technology could mitigate pandemic threats by providing a rapidly-deployable (just-in-time), versatile (precision medicine) production of biologic therapeutics to the infected patient’s locale (point-of-care). In drug development, once promising drug variations are identified, the platform can be scaled to quickly produce practical amounts of protein for patient testing in the matter of days (vs. months) at a fraction of the cost of existing technology.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Clinical pharmacology information in regulatory submissions and labeling: A comparative analysis of orphan and non-orphan drugs approved by the FDA

Clinical pharmacology is an integral discipline supporting the development, regulatory evaluation, and clinical use of drugs for the treatment of both common and rare diseases. Here, we evaluated the recommendations and information available from select clinical pharmacology studies in the therapeutic product labeling of new molecular entities (NMEs) approved from 2017 to 2019 for both common and rare diseases. A total of 151 NMEs, including 72 orphan and 79 non-orphan drugs, were analyzed for recommendations and information available related to food–drug interaction, drug–drug interaction, renal impairment, hepatic impairment, QT assessment, and human radiolabeled mass balance studies using data collected from the original labeling and other regulatory documents. The analysis showed no statistically significant difference in the recommendations between orphan and non-orphan drugs except for renal impairment related recommendations in section 8 of the labeling. Although not significant, fewer hepatic impairment labeling recommendations were available for orphan drugs when compared with non-orphan drugs. At the time of initial approval, 79 postmarketing requirements (PMRs) and postmarketing commitments (PMCs) for 33 orphan drugs and 39 PMRs and PMCs for 19 non-orphan drugs were established; with most difference observed for drug–drug interaction, hepatic impairment, and QT assessment. Overall, although there was a trend for more labeling recommendations and fewer postmarketing studies and clinical trials for non-orphan drugs, there appeared to be no substantial differences in how these select clinical pharmacology studies are leveraged during the development and approval of orphan and non-orphan drugs.

60 APPLIED LIFE SCIENCES↗