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This paper proposes a NASA-led investment in a flagship user facility at NASA Ames Research Center for simulating high energy protons and combined exposures to other spaceflight stressors for a wide variety of in vivo, ex vivo, and in vitro biological systems, as well as non-biological models of spacecraft and instruments.
We call for a major dedicated campaign to develop and fly autonomous biological payloads in lunar orbit and on the lunar surface during the next decade, followed by subsequent expansion to Martian orbit. This ambitious goal will require dedicated effort to develop hardware, biological models and data acquisition and processing techniques. We believe that it would be best achieved as a single comprehensive, NASA-led and funded mission project, analogous to planetary science missions. Furthermore, technological developments should be accompanied by collaborations within and between agencies and a robust program for acquisition and retention of talented scientists and engineers.
A wide variety of observations on cells in space, admittedly made under constraining and unnatural conditions in may cases, have led to experimental results that were surprising or unexpected. Reproducibility, freedom from artifacts, and plausibility must be considered in all cases, even when results are not surprising. The papers in symposium on 'Theories and Models on the Biology of Cells in Space' are dedicated to the subject of the plausibility of cellular responses to gravity -- inertial accelerations between 0 and 9.8 m/sq s and higher. The mechanical phenomena inside the cell, the gravitactic locomotion of single eukaryotic and prokaryotic cells, and the effects of inertial unloading on cellular physiology are addressed in theoretical and experimental studies.
The space environment consists of a varying field of radiation particles including high-energy ions, with spacecraft shielding material providing the major protection to astronauts from harmful exposure. Unlike low-LET gamma or X rays, the presence of shielding does not always reduce the radiation risks for energetic charged-particle exposure. Dose delivered by the charged particle increases sharply at the Bragg peak. However, the Bragg curve does not necessarily represent the biological damage along the particle path since biological effects are influenced by the track structures of both primary and secondary particles. Therefore, the ''biological Bragg curve'' is dependent on the energy and the type of the primary particle and may vary for different biological end points. Measurements of the induction of micronuclei (MN) have made across the Bragg curve in human fibroblasts exposed to energetic silicon and iron ions in vitro at two different energies, 300 MeV/nucleon and 1 GeV/nucleon. Although the data did not reveal an increased yield of MN at the location of the Bragg peak, the increased inhibition of cell progression, which is related to cell death, was found at the Bragg peak location. These results are compared to the calculations of biological damage using a stochastic Monte-Carlo track structure model, Galactic Cosmic Ray Event-based Risk Model (GERM) code (Cucinotta, et al., 2011). The GERM code estimates the basic physical properties along the passage of heavy ions in tissue and shielding materials, by which the experimental set-up can be interpreted. The code can also be used to describe the biophysical events of interest in radiobiology, cancer therapy, and space exploration. The calculation has shown that the severely damaged cells at the Bragg peak are more likely to go through reproductive death, the so called "overkill".
The labelled-release and the gas-exchange experiments of the 1976 Mars Viking biology experiment program detected, respectively, C-14 labelled gases and O2 gas. A chemical model is proposed here for these experiments in which the reactants are an inorganic nitrate salt which has been partly photolyzed by ultraviolet light and a sparingly soluble metal carbonate such as calcite. The model reproduces the main effects seen, indicating that nitrates are present in the Martian regolith as well as calcite (or some other carbonate with similar solubility).
Predictive mathematical modeling is an essential part of systems biology and is interconnected with information management. Systems biology information is often stored in specialized formats to facilitate data storage and analysis. These formats are not designed for easy human readability and thus require specialized software to visualize and interpret results. Therefore, comprehending modeling and underlying networks and pathways is contingent on mastering systems biology tools, which is particularly challenging for users with no or little background in data science or system biology. To address this challenge, we investigated the usage of public Artificial Intelligence (AI) tools in exploring systems biology resources in mathematical modeling. We tested public AI’s understanding of mathematics in models, related systems biology data, and the complexity of model structures. Our approach can enhance the accessibility of systems biology for non-system biologists and help them understand systems biology without a deep learning curve.
The organization of a mammalian macular endorgan is interpreted on physical and engineering principles. Having accomplished this task, it is possible to mathematically and symbolically model information processing by the macular neural network. A complex symbolic model is produced through use of mathematical notations that describe the functioning system. The model, consisting of six tiers, is constructed to mimic the neural system. On the basis of initial simulations, it is concluded that the network functions best when some of the detecting elements (i.e., type I hair cells) are weakly inhibitory. The simulations also illustrate the importance of disinhibition of receptors located in the third tier in shaping nerve discharge patterns at the sixth tier in the model system.
An estimated mean thickness of about 1 km of frost in the Martian north polar cap summer remnant, if vaporized, would yield about 1000 g/sq cm of atmosphere over the planet, higher global temperatures through the greenhouse effect, and a greatly increased likelihood of liquid water. Vaporization of such cap remnants may occur twice each equinoctial precession, and Martian organisms may now be in cryptobiotic repose awaiting the end of the long precessional winter. The Viking biology experiments can test this hypothesis.
In this session, Session JP3, the discussion focuses on the following topics: Morphology of brain, pituitary and thyroid in the rats exposed to altered gravity; Biochemical Properties of B Adrenoceptors After Spaceflight (LMS-STS78) or Hindlimb Suspension in Rats; Influence of Hypergravity on the Development of Monoaminergic Systems in the Rat Spinal Cord; A Vestibular Evoked Potentials (VsEPs) Study of the Function of the Otolith Organs in Different Head Orientations with respect to Earth Gravity Vector in the Rat; Quantitative Observations on the Structure of Selected Proprioceptive Components in Adult Rats that Underwent About Half of their Fetal Development in Space; Effects of a Nine-Day Shuttle Mission on the Development of the Neonatal Rat Nervous System, A Behavioral Study; Muscle Atrophy Associated to Microgravity in Rat, Basic Data For Countermeasures; Simulated Weightlessness by Unloading in the Rat, Results of a Time Course Study of Biochemical Events Occurring During Unloading and Lack of Effect of a rhBNP-2 Treatment on Bone Formation and Bone Mineral Content in Unloading Rats; and Cytological Mechanism of the Osteogenesis Under Microgravity Conditions.
The World Space Congress 1992 took place after two Spacelab flights with important biological payloads on board, the SLS-1 (June 1991) and IML-1 (January 1992) missions respectively. Interesting experiments were carried out in 1991 also on the Shuttle middeck and on the sounding rocket MASER 4. The highlights of the investigations on these missions together with the results of relevant ground-based research were presented at the symposium.
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The track structure model of heavy ion cross sections was developed by Katz and co-workers in the 1960s. In this model the action cross section is evaluated by mapping the dose-response of a detector to gamma rays (modeled from biological target theory) onto the radial dose distribution from delta rays about the path of the ion. This is taken to yield the radial distribution of probability for a "hit" (an interaction leading to an observable end-point). Radial integration of the probability yields the cross section. When different response from ions of different Z having the same stopping power is observed this model may be indicated. Since the 1960s there have been several developments in the computation of the radial dose distribution, in the measurement of these distributions, and in new radiobiological data against which to test the model. The earliest model, by Butts and Katz made use of simplified delta ray distribution functions, of simplified electron range-energy relations, and neglected angular distributions. Nevertheless it made possible the calculation of cross sections for the inactivation of enzymes and viruses, and allowed extension to tracks in nuclear emulsions and other detectors and to biological cells. It set the pattern for models of observable effects in the matter through which the ion passed. Here we outline subsequent calculations of radial dose which make use of improved knowledge of the electron emission spectrum, the electron range-energy relation, the angular distribution, and some considerations of molecular excitation, of particular interest both close to the path of the ion and the outer limits of electron penetration. These are applied to the modeling of action cross sections for the inactivation of several strains of E-coli and B. subtilis spores where extensive measurements in the "thin-down" region have been made with heavy ion beams. Such calculations serve to test the radial dose calculations at the outer limit of electron penetration. We lack data from which to test these calculations in regions close to the path of the ion aside from our earliest work on latent tracks in plastics, though it appears that the criterion then suggested for the threshold of track formation, of a minimal dose at a minimal distance (of about 20 angstroms, in plastics), remains valid.
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The space program is faced with two difficult radiation protection issues for future long-term operations. First, retrofit of shield material or conservatism in shield design is prohibitively expensive and often impossible. Second, shielding from the cosmic heavy ions is faced with limited knowledge on the physical properties and biological responses of these radiations. The current status of space shielding technology and its impact on radiation health is discussed herein in terms of conventional protection practice and a test biological response model. The impact of biological response on the selection of optimum materials for cosmic ray shielding is presented in terms of the transmission characteristics of the shield material. Although the systematics of nuclear cross sections are able to demonstrate the relation of exposure risk to shield-material composition, the current uncertainty in-nuclear cross sections will not allow an accurate evaluation of risk reduction. This paper presents a theoretical study of risk-related factors and a pilot experiment to study the effectiveness of choice of shield materials to reduce the risk in space operations.
When shielding from cosmic heavy ions, one is faced with limited knowledge about the physical properties and biological responses of these radiations. Herein, the current health is discussed in terms of conventional protection practice and a test biological response model. The impact of biological response on optimum materials selection for cosmic ray shielding is presented in terms of the transmission characteristics of the shield material. Although liquid hydrogen is an optimum shield material, evaluation of the effectiveness of polymeric structural materials must await improvement in our knowledge of both the biological response and the nuclear processes.
With shielding from cosmic heavy ions, one is faced with limited knowledge about the physical properties and biological responses of these radiations. Herein, the current status of space shielding technology and its impact on radiation health is discussed in terms of conventional protection practice and a test biological response model. The impact of biological response on optimum materials selection for cosmic ray shielding is presented in terms of the transmission characteristics of the shield material. Although liquid hydrogen gas is an optimum shield material, evaluation of the effectiveness of polymeric structural materials must await improvement in our knowledge of both the biological response and the nuclear processes.
The biological effects of heavy charged particle (HZE) radiation are of particular interest to travellers and planners for long-duration space flights where exposure levels represent a potential health hazard. The unique feature of HZE radiation is the structured pattern of its energy deposition in targets. There are many consequences of this feature to biological endpoints when compared with effects of ionizing photons. Dose vs response and dose-rate kinetics may be modified, DNA and cellular repair systems may be altered in their abilities to cope with damage, and the qualitative features of damage may be unique for different ions. The nematode Caenorhabditis elegans is being used to address these and related questions associated with exposure to radiation. HZE-induced mutation, chromosome aberration, cell inactivation and altered organogenesis are discussed along with plans for radiobiological experiments in space.