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All sourcesNASA NTRSDOE OSTI
DOE OSTI2025

Optimal Transport as a Tool for Scientific Discovery in Radiation Biology

This report summarizes findings from research conducted for the “Exploration of the Poten tial for Artificial Intelligence and Machine Learning to Advance Low-Dose Radiation Biology Re search” (RadBio-AI) program, supported by the U.S. Department of Energy, Office of Science, Office of Biological and Environmental Research, under Awards KP1601011/FWP CC121 and KP1601017/FWP CC121. The research reported here was undertaken in an effort to assess the potential of optimal measure transport methods as components within the larger scope of a com putational framework envisioned to support research in the radiation biology domain. Within this effort, our interest centered on enabling a unified generic framework where probabilistic modeling, inference, and statistical learning can be carried out for a wide range of data distributions. As described next in Section 1 (and in more detail in our original publication), optimal measure transport offers the possibility of such unified approach.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2025

Physicochemical and biological characterization of a bispecific antibody in a CrossMab/KIH format that targets EGFR and VEGF-A

Introduction Bispecific antibodies (BsAbs) are a class of antibody therapeutics engineered in various molecular formats to bind two distinct antigens and potentially mediate multiple biological effects. These molecular formats are tailored to mediate specific mechanisms of action and possess unique physicochemical and biological properties that are necessary to assure product quality. In ovarian cancer (OC), both EGFR- and VEGF-A-mediated signaling pathways are often upregulated and cooperate to promote tumor growth and angiogenesis. Thus, inhibiting of EGFR- and VEGF-A pathways with a BsAb may provide synergistic anti-tumor activity. Methods Using publicly available sequences and applying immunoglobulin domain crossover (CrossMab) and knobs-into-holes (KIH) technologies, we generated a BsAb to simultaneously bind EGFR and VEGF-A (designated as anti-EGFR/VEGF-A BsAb). This BsAb served as a model for physiochemical and biological characterization of quality attributes that would be critical for the BsAb’s mechanisms of action. Our goal was to gain fundamental insights into BsAbs designed to target a receptor with one arm and a soluble ligand with the other, to support bioassay development and inform quality control strategies. Results Our data demonstrated that the CrossMab/KIH platform successfully produced a correctly assembled BsAb during cell culture. Characterization confirmed that the anti-EGFR/VEGF-A BsAb bound both EGFR and VEGF-A with comparable activity and affinity to the respective parental monoclonal antibodies. Functionally, the BsAb disrupted both EGF/EGFR and VEGF-A/VEGFR2 signaling pathways in OC and human umbilical vein endothelial cell (HUVEC) models. Furthermore, the BsAb effectively blocked angiogenic signaling driven by VEGF-A secreted from OC cells in a paracrine manner. Discussion Based on the combinatorial mechanism of action and our characterization findings, we concluded that two or more bioassays may be needed to accurately assess the activity of both arms of this type of BsAb.

Immunology↗
DOE OSTI2024

Reliability, biological variability, and accuracy of multi-frequency bioelectrical impedance analysis for measuring body composition components

Introduction Bioelectrical impedance analysis (BIA) systems are gaining popularity for use in research and fitness assessments as the technology improves and becomes more affordable and easier to use. Multifrequency BIA (MF-BIA) may improve accuracy and precision using octopolar contacts for segmental analyses. Purpose Evaluate reliability, biological variability, and accuracy of component measures (total body water, mass, and composition) of commercially available MF-BIA system (InBody 770, Cerritos, California, USA). Methods Fourteen healthy military-age adults were assessed by MF-BIA in duplicate on five laboratory visits across 3 weeks (10 measures each). Participants were evaluated at the same time of day after refraining from strenuous exercise (> 48 h), alcohol consumption (> 24 h), and caffeine, nicotine, and food (> 10 h). Systematic error (test–retest reliability) and biological variability (day-to-day reliability) were summarized by intraclass correlation coefficient (ICC) values determined for body mass (fat, fat-free, total) and body water (extracellular, intracellular, total). Body composition measurements derived from BIA on the second visit were also tested for accuracy compared to dual-energy x-ray absorptiometry (DXA). Results Test–retest reliability was very high for all measurements of whole-body water and mass (ICC ≥ 0.999) and high for regional body water and mass (ICC 0.973–1.000). Biological variability was observable with very minor differences between tests (same day) for total and regional body water (0.0–0.2 L) and total and regional body mass measurements (0.0–0.2 kg); while between day differences were slightly higher (0.0–0.5 L and 0.1–0.7 kg). Compared to DXA, the MF-BIA whole-body measures showed an offset in %BF (Bias −4.0 ± 2.8%; Standard error of the estimate (SEE), 2.6%), an overprediction for total body fat-free mass (Bias 2.8 ± 2.1 kg; SEE 2.2 kg) and an underprediction of total body fat mass (Bias −2.9 ± 2.0 kg; SEE 1.9 kg). Conclusion Under controlled conditions with fit and healthy men and women, this MF-BIA system has high methodological reliability and demonstrates stable day-to-day measurements of major body composition components. Previously reported ~3% body fat offset compared to criterion methods was again confirmed. Precision of the InBody 770 shows consistency and supports further testing of this specific device as a new military standards method and suitability across a wider range of %BF.

Nutrition & Dietetics↗
DOE OSTI2023

The Importance of Sharing Data in Systems Biology

Systems biology research spans a range of biological scales and science domains, and often requires a collaborative effort to collect and share data so that integration is possible. However, sharing data effectively is a challenging task that requires effort and alignment between collaborative partners, as well as coordination between organizations, repositories, and journals. As a community of systems biology researchers, we must get better at efficiently sharing data, and ensuring that shared data comes with the recognition and citations it deserves.

Wood-Charlson, Elisha M. (ORCID:0000000195577715)↗
DOE OSTI2024

Towards Construction of a Novel Nanometer-Resolution MeV-STEM for Imaging Thick Frozen Biological Samples

Driven by life-science applications, a mega-electron-volt Scanning Transmission Electron Microscope (MeV-STEM) has been proposed here to image thick frozen biological samples as a conventional Transmission Electron Microscope (TEM) may not be suitable to image samples thicker than 300–500 nm and various volume electron microscopy (EM) techniques either suffering from low resolution, or low speed. The high penetration of inelastic scattering signals of MeV electrons could make the MeV-STEM an appropriate microscope for biological samples as thick as 10 μm or more with a nanoscale resolution, considering the effect of electron energy, beam broadening, and low-dose limit on resolution. The best resolution is inversely related to the sample thickness and changes from 6 nm to 24 nm when the sample thickness increases from 1 μm to 10 μm. To achieve such a resolution in STEM, the imaging electrons must be focused on the specimen with a nm size and an mrad semi-convergence angle. This requires an electron beam emittance of a few picometers, which is ~1000 times smaller than the presently achieved nm emittance, in conjunction with less than 10 -4 energy spread and 1 nA current. We numerically simulated two different approaches that are potentially applicable to build a compact MeV-STEM instrument: (1) DC (Direct Current) gun, aperture, superconducting radio-frequency (SRF) cavities, and STEM column; (2) SRF gun, aperture, SRF cavities, and STEM column. Beam dynamic simulations show promising results, which meet the needs of an MeV-STEM, a few-picometer emittance, less than 10 -4 energy spread, and 0.1–1 nA current from both options. Also, we designed a compact STEM column based on permanent quadrupole quintuplet, not only to demagnify the beam size from 1 μm at the source point to 2 nm at the specimen but also to provide the freedom of changing the magnifications at the specimen and a scanning system to raster the electron beam across the sample with a step size of 2 nm and the repetition rate of 1 MHz. This makes it possible to build a compact MeV-STEM and use it to study thick, large-volume samples in cell biology.

36 MATERIALS SCIENCE↗
DOE OSTI2021

Neutron Radiography and Computed Tomography of Biological Systems at the Oak Ridge National Laboratory's High Flux Isotope Reactor

Neutrons have historically been used for a broad range of biological applications employing techniques such as small-angle neutron scattering, neutron spin echo, diffraction, and inelastic scattering. Unlike neutron scattering techniques that obtain information in reciprocal space, attenuation-based neutron imaging measures a signal in real space that is resolved on the order of tens of micrometers. The principle of neutron imaging follows the Beer-Lambert law and is based on the measurement of the bulk neutron attenuation through a sample. Greater attenuation is exhibited by some light elements (most notably, hydrogen), which are major components of biological samples. Contrast agents such as deuterium, gadolinium, or lithium compounds can be used to enhance contrast in a similar fashion as it is done in medical imaging, including techniques such as optical imaging, magnetic resonance imaging, X-ray, and positron emission tomography. For biological systems, neutron radiography and computed tomography have increasingly been used to investigate the complexity of the underground plant root network, its interaction with soils, and the dynamics of water flux in situ. Moreover, efforts to understand contrast details in animal samples, such as soft tissues and bones, have been explored. This manuscript focuses on the advances in neutron bioimaging such as sample preparation, instrumentation, data acquisition strategy, and data analysis using the High Flux Isotope Reactor CG-1D neutron imaging beamline. The aforementioned capabilities will be illustrated using a selection of examples in plant physiology (herbaceous plant/root/soil system) and biomedical applications (rat femur and mouse lung).

Bilheux, Hassina↗
NASA NTRS1975

Biological indicators for monitoring water quality of MTF canals system

Biological models, diversity indexes, were developed to predict environmental effects of NASA's Mississippi test facility (MTF) chemical operations on canal systems in the area. To predict the effects on local streams, a physical model of unpolluted streams was established. The model is fed by artesian well water free of background levels of pollutants. The species diversity and biota composition of unpolluted MTF stream was determined; resulting information will be used to form baseline data for future comparisons. Biological modeling was accomplished by adding controlled quantities or kinds of chemical pollutants and evaluating the effects of these chemicals on the biological life of the stream.

Sethi, S. L.↗
NASA NTRS1975

Biostack: A study of the biological effects on HZE galactic cosmic radiation

The Biostack experiment designed to study the effect of individual heavy nucleii of the cosmic radiation environment upon biological systems during actual space flight is described. In each Biostack, several thousand biological objects were hit by an HZE particle. The response of the biological objects was studied. Results are discussed in terms of sensitivity to the hit.

Horst Bücker↗
NASA NTRS1976

Publications of the planetary biology program for 1975: A special bibliography

The Planetary Biology Program of the National Aeronautics and Space Administration is the first and only integrated program to methodically investigate the planetary events which may have been responsible for, or related to, the origin, evolution, and distribution of life in the universe. Research supported by this program is divided into the seven areas listed below: (1) chemical evolution, (2) organic geochemistry, (3) life detection, (4) biological adaptation, (5) bioinstrumentation, (6) planetary environments, and (7) origin of life. The arrangement of references in this bibliography follows the division of research described above. Articles are listed alphabetically by author under the research area with which they are most closely related. Only those publications which resulted from research supported by the Planetary Biology Program and which bear a 1975 publication date have been included. Abstracts and theses are not included because of the preliminary and abbreviated nature of the former and the frequent difficulty of obtaining the latter.

Souza, K. A.↗
NASA NTRS1976

The Viking biological investigation - Preliminary results

A preliminary progress report is presented for the Viking biological investigation through its first month. The carbon assimilation, gas exchange, and labeled release experiments are described in detail, and the chronology of the experiments is outlined. For the first experiment, it is found that a small amount of gas was converted into organic material in one sample and that heat treatment of a duplicate sample prevented such conversion. In the second experiment, a substantial amount of O2 was detected along with significant increases in CO2 and small changes in N2. In the third experiment, a significant amount of radioactive gas was evolved from one sample, but not from a duplicate heat-treated sample. Possible biological and nonbiological interpretations are considered for these results. It is concluded that while the experiments provide clear evidence for the occurrence of chemical reactions and while the results do not violate any prima facie criteria for biological processes, a definitive answer cannot yet be given to the question of whether life exists on Mars.

Klein, H. P.↗
NASA NTRS1977

Site Alteration Effects from Rocket Exhaust Impingement During a Simulated Viking Mars Landing. Part 2: Chemical and Biological Site Alteration

Chemical and biological alteration of a Mars landing site was investigated experimentally and analytically. The experimental testing was conducted using a specially designed multiple nozzle configuration consisting of 18 small bell nozzles. The chemical test results indicate that an engine using standard hydrazine fuel will contaminate the landing site with ammonia (50-500ppm), nitrogen (5-50ppm), aniline (0.01-0.5ppm), hydrogen cyanide (0.01-0.5ppm), and water. A purified fuel, with impurities (mostly aniline) reduced by a factor of 50-100, limits the amount of hydrogen cyanide and aniline to below detectable limits for the Viking science investigations and leaves the amounts of ammonia, nitrogen, and water in the soil unchanged. The large amounts of ammonia trapped in the soil will make interpretation of the organic analysis investigation results more difficult. The biological tests indicate that the combined effects of plume gases, surface heating, surface erosion, and gas composition resulting from the retrorockets will not interfere with the Viking biology investigation.

Husted, R. R.↗
NASA NTRS1976

Biology on the outer planets

A brief review is given of information on the structure and composition of the outer planets and the organic reactions that may be occurring on them. The possibility of life arising or surviving in the atmospheres of these planets is considered, and the problem of contamination during future unmanned missions is assessed. Atmospheric models or available atmospheric data are reviewed for Jupiter, Saturn, Uranus, Neptune, Pluto, the Galilean satellites, and Titan. The presence of biologically interesting gases on Jupiter and Saturn is discussed, requirements for life on Jupiter are summarized, and possible sources of biological energy are examined. Proposals are made for protecting these planets and satellites from biological contamination by spacecraftborne terrestrial organisms.

Young, R. S.↗
NASA NTRS1978

Before the long journey: Development of Soviet space biology and medicine

Academician O. Gazenko, Chief of the Institute of Biomedical Problems, USSR Ministry of Public Health, reviewed the short but intense history of Soviet research in space biology and medicine. The solid academic approach of the Soviet Academy of Sciences in giving a good start at the very beginning of the space age is stressed and key people and institutions who initiated these studies are named. The basic feature of the first period of space biology is seen as the search for answers to a few fundamental questions of survival in space. It is pointed out that the initiated investigations were replaced by refined, in-depth studies of the biological, biophysical, and biochemical processes in human organism in the space environment and the search for methods which should enable cosmonaut crews to live in space for several years during interplanetary journeys. Discussing the typical problems of this effort, Gazenko each time showed how they benefit medical science and practice in general.

Gazenko, O. G.↗
NASA NTRS1977

The Viking biological investigation - General aspects

The Viking biological investigation has tested four different hypotheses regarding the possible nature of Martian organisms. While significant results were obtained for each of these, tests of three of the hypotheses appear to indicate the absence of biology in the samples used, while the fourth is consistent with a biological interpretation. The original assumptions for each experiment and the experimental procedures that were utilized to test these assumptions are reviewed.

Klein, H. P.↗
NASA NTRS1982

Controlled ecological life support system - biological problems

The general processes and controls associated with two distinct experimental paradigms are examined. Specific areas for research related to biotic production (food production) and biotic decomposition (waste management) are explored. The workshop discussions were directed toward Elemental cycles and the biological factors that affect the transformations of nutrients into food, of food material into waste, and of waste into nutrients were discussed. To focus on biological issues, the discussion assumed that (1) food production would be by biological means (thus excluding chemical synthesis), (2) energy would not be a limiting factor, and (3) engineering capacity for composition and leak rate would be adequate.

Moore, B., III↗
NASA NTRS1981

Design and control strategies for CELSS - Integrating mechanistic paradigms and biological complexities

Systems analysis and control theory consideration are given to simulations of both individual components and total systems, in order to develop a reliable control strategy for a Controlled Ecological Life Support System (CELSS) which includes complex biological components. Because of the numerous nonlinearities and tight coupling within the biological component, classical control theory may be inadequate and the statistical analysis of factorial experiments more useful. The range in control characteristics of particular species may simplify the overall task by providing an appropriate balance of stability and controllability to match species function in the overall design. The ultimate goal of this research is the coordination of biological and mechanical subsystems in order to achieve a self-supporting environment.

Moore, B., III↗