Non-subjective cataract analysis and its application in space radiation risk assessment.

Experimental animal studies and human observations suggest that the question is not whether or not prolonged space missions will cause cataracts to appear prematurely in the astronauts, but when and to what degree. Historically the major impediment to radiation cataract follow-up has been the necessarily subjective nature of assessing the degree of lens transparency. This has spurred the development of instruments which produce video images amenable to digital analysis. One such system, the Zeiss Scheimpflug slit lamp measuring system (SLC), was incorporated into our ongoing studies of radiation cataractogenesis. It was found that the Zeiss SLC measuring system has high resolution and permits the acquisition of reproducible images of the anterior segment of the eye. Our results, based on about 650 images of the rats lens, and followed over a period of 91 weeks of radiation cataract development, showed that the integrated optical density (IOD) of the lens correlated well with conventional assessment with the added advantages of objectivity, permanent and transportable records and linearity as cataracts become more severe. This continuous data acquisition, commencing with cataract onset, can proceed through more advanced stages. The SLC exhibits much greater sensitivity reflected in a continuously progressive severity despite the artifactual plateaus in staging which occur using conventional scoring methods. Systems such as the Zeiss SLC should be used to monitor astronauts frequent visits to low earth orbit to obtain a longitudinal data-base on the influence of this activity on the lens.     

Mice heterozygous for the ATM gene are more sensitive to both X-ray and heavy ion exposure than are wildtypes

Previous studies have shown that the eyes of ATM heterozygous mice exposed to low-LET radiation (X-rays) are significantly more susceptible to the development of cataracts than are those of wildtype mice. The findings, as well as others, run counter to the assumption underpinning current radiation safety guidelines, that individuals are all equally sensitive to the biological effects of radiation. A question, highly relevant to human space activities is whether or not, in similar fashion there may exist a genetic predisposition to high-LET radiation damage.Mice haplodeficient for the ATM gene and wildtypes were exposed to 325 mGy of 1 GeV/amu ⁵⁶Fe ions at the AGS facility of Brookhaven National Laboratory. The fluence was equivalent to 1 ion per lens epithelial cell nuclear area. Controls consisted of irradiated wildtype as well as unirradiated wildtype and heterozygous mice. Prevalence analyses for stage 0.5–3.0 cataracts indicated that not only cataract onset but also progression were accelerated in the mice haplo-deficient for the ATM gene.The data show that heterozygosity for the ATM gene predisposes the eye to the cataractogenic influence of heavy ions and suggest that ATM heterozygotes in the human population may also be radiosensitive. This may have to be considered in the selection of individuals who will be exposed to both HZE particles and low-LET radiation as they may be predisposed to increased late normal tissue damage.     

Radiation effects on late cytopathological parameters in the murine lens relative to particle fluence.

Lenses of mice irradiated with 250 MeV protons, 670 MeV/amu 20Ne, 600 MeV/amu 56Fe, 600 MeV/amu 93Nb and 593 MeV/amu 139La ions were evaluated by analyzing cytopathological indicators which have been implicated in the cataractogenic process. The LETs ranged from 0.40 keV/micrometer to 953 keV/micrometer and fluences from 1.31 10(3)/mm2 to 4.99 x 10(7)/mm2. 60Co gamma-rays were used as the reference radiation. The doses ranged from 10 to 40 cGy. The lenses were assessed 64 weeks post irradiation in order to observe the late effects of LET and dose on the target cell population of the lens epithelium. Our study shows that growth dependent pathological changes occur at the cellular level as a function of dose and LET. The shapes of the RBE-LET and RBE-dose curves are consistent with previous work on eye and other biological systems done in both our laboratory and others. The RBEmax's were estimated, for the most radiation cataract related cytological changes, MN frequency and MR disorganization, by calculating the ratio of the initial slopes of dose effect curve for various heavy ions to that of 60Co gamma-ray. For each ion studied, the RBEmax derived from micronucleus (MN) frequency is similar to that derived from meridional row (MR) disorganization, suggesting that heavy ions are equally efficient at producing each type of damage. Furthermore, on a per particle basis (particle/cell nucleus), both MN frequency and MR disorganization are LET dependent indicating that these classic precataractogenic indicators are multi-gene effects. Poisson probability analysis of the particle number traversing cell nuclei (average area = 24 micrometers2) suggested that single nuclear traversals determine these changes. By virtue of their precataractogenic nature the data on these endpoints intimate that radiation cataract may also be the consequence of single hits. In any case, these observations are consistent with the current theory of the mechanism of radiation cataractogenesis, which proposes that genomic damage to the epithelial cells surviving the exposure is responsible for opacification.     

Countermeasures for space radiation induced adverse biologic effects

Radiation exposure in space is expected to increase the risk of cancer and other adverse biological effects in astronauts. The types of space radiation of particular concern for astronaut health are protons and heavy ions known as high atomic number and high energy (HZE) particles. Recent studies have indicated that carcinogenesis induced by protons and HZE particles may be modifiable. We have been evaluating the effects of proton and HZE particle radiation in cultured human cells and animals for nearly a decade. Our results indicate that exposure to proton and HZE particle radiation increases oxidative stress, cytotoxicity, cataract development and malignant transformation in in vivo and/or in vitro experimental systems. We have also shown that these adverse biological effects can be prevented, at least partially, by treatment with antioxidants and some dietary supplements that are readily available and have favorable safety profiles. Some of the antioxidants and dietary supplements are effective in preventing radiation induced malignant transformation in vitro even when applied several days after the radiation exposure. Our recent progress is reviewed and discussed in the context of the relevant literature.     

Cataract analysis and the assessment of radiation risk in space.

Radiation cataract, a non-stochastic effect on the lens, is readily amenable to non-invasive analysis. Thus, it provides the means to assess radiation risk in space and for long-term monitoring of those who frequent that environment. The importance of such evaluations are underscored by the uncertainties associated with the assignment of quality factors for the effects of heavy charged particles constituting cosmic and solar radiation. Experimental studies were conducted using albino rats to evaluate the cataractogenic potential of 570 MeV/amu Argon ions administered as both single and protracted doses. The cataract studies and investigations of quantitative cytopathological changes associated with them indicate that as the dose of heavy particles decreases, the relative biological effectiveness, compared to X rays, increases. Fractionating the exposures not only failed to reduce the cataractogenic effect but caused a dose-dependent enhancement in the time of onset of opacification. Cytopathologically, the damage caused by heavy particles, when compared to low-LET radiation was found to be quantitatively dissimilar but qualitatively identical. In addition, damage which might be consistent with microlesions was not evident. The data indicates that as regards the cataractogenic potential of heavy particles at low doses an assignment of a Quality Factor (QF) of at least 40 may be in order.     

Cataractogenesis from high-LET radiation and the Casarett model.

Space radiations, especially heavy ions, constitute significant hazards to astronauts. These hazards will increase as space missions lengthen. Moreover, the dangers to astronauts will be enhanced by the persistence, or even the progression, of biological damage throughout their subsequent life spans. To assist in the assessment of risks to astronauts, we are investigating the long-term effects of heavy ions on specific animal tissues. In one study, the eyes of rabbits of various ages were exposed to a single dose of Bragg plateau 20Ne ions (LET infinity approximately equals 30 keV/micrometer). The development of cataracts has shown a pronounced age-related response during the first year after irradiation, and will be followed for two more years. In other studies, mice were exposed to single or fractionated doses of 12C ions (4-cm spread-out Bragg peak; dose-averaged LET infinity = 70-80 keV/micrometer) or 60Co gamma-photons (LET infinity = 0.3 keV/micrometer). Measurements of the frequency of posterior lens opacification have shown that the tissue sparing observed with dose fractionation of gamma-photons was absent when 12C-ion doses were fractionated. Development of posterior lens cataracts was also followed for long periods (up to 21 months) in mice exposed to single doses of Bragg plateau HZE particles (40Ar, 20Ne and 12C ions: LET infinity approximately equals 100, 30 and 10 keV/micrometer, respectively) or 225 kVp X-rays. Based on average cataract levels at the different observation times, the RBE's (RBE = relative biological effectiveness) for the ions were circa 5, 3 and 1-2, respectively, over the range of doses used (0.05-0.9 Gy). Investigations of cataractogenesis are useful for exploring the model of radiation damage proposed by Casarett and by Rubin and Casarett with a tissue not connected directly to the vasculature.     

Radiation risk estimation and its application to human beings in space.

The number of human beings likely to spend time in space will increase as time goes on. While exposures vary according to missions, orbits, shielding, etc., an average space radiation fluence (ignoring solar flares, radiation belts and anomalous regions in space) in locations close to earth is about 10 rad/year with a quality factor of about 5.5. The potential effects of exposure to these fluences include both non-stochastic effects and stochastic effects (cancer and genetic damage). Non-stochastic effects, damage to the lens of the eye, bone marrow or gonads, can be avoided by keeping radiation limits below threshold values. Stochastic effects imply risk at all levels. The magnitude of these risks has been discussed in a number of reports by the UNSCEAR Committee and the BEIR Committee in the USA during 1970-1980. The uncertainties associated with these risks and information which has become available since the last BEIR report is discussed. In considering reasonable limits for exposure in space, acceptable levels for stochastic risks must be based on appropriate comparisons. In view of the limited term of duty of most space workers, a lifetime limit may be appropriate. This lifetime limit might be comparable in terms of risks with limits for radiation workers on the ground but received at a higher annual rate for a shorter time. These and other approaches are expected to be considered by an NCRP Committee currently examining the problem of space radiation hazards.     

聚焦透镜天线焦斑宽度估算

根据惠更斯-菲涅耳原理,通过简单的推导,得出聚焦透镜天线焦平面上焦斑宽度的近似计算公式,并讨论了与焦平面平行的平面上的焦斑场.为证明该方法的计算精度及效率,设计了一个Ka波段聚焦透镜天线,并加工了两个天线样品进行比较.对两天线进行了平面近场扫描测试,采用近似公式计算得到的Ka波段聚焦透镜天线半功率点宽度与实验数据接近,表明文中给出的公式有一定工程参考作用.      

Science strategy for human exploration of Mars.

The scientific objectives of Mars exploration can be framed within the overarching theme of exploring Mars as another home for life, both for evidence of past or present life on Mars, and as a potential future home for human life. The two major areas of research within this theme are: 1) determining the relationship between planetary evolution, climate change, and life, and 2) determining the habitability of Mars. Within this framework, this paper discusses the exploration objectives for exobiology, climatology and atmospheric science, geology, and martian resource assessment. Human exploration will proceed in four major phases: 1) Precursor missions which will obtain environmental knowledge necessary for human exploration, 2) Emplacement phase which includes the first few human landings where crews will explore the local area of the landing site; 3) Consolidation phase missions where a permanent base will be constructed and crews will be capable of detailed exploration over regional scales; 4) Utilization phase, in which a continuously occupied permanent Mars base exists and humans will be capable of detailed global exploration of the martian surface. The phases of exploration differ primarily in the range and capabilities of human mobility. In the emplacement phase, an unpressurized rover, similar to the Apollo lunar rover, will be used and will have a range of a few tens of kilometers. In the Consolidation phase, mobility will be via a pressurized all-terrain vehicle capable of expeditions from the base site of several weeks duration. In the Utilization phase, humans will be capable of several months long expeditions to any point on the surface of Mars using a suborbital rocket equipped with habitat, lab, and return vehicle. Because of human mobility limitations, it is important to extend the range and duration of exploration in all phases by using teleoperated rover vehicles. Site selection for human missions to Mars must consider the multi-decade time frame of these four phases. We suggest that operations in the first two phases be focused in the regional area containing the Coprates Quadrangle and adjacent areas.     

An Outline of Investigation of Space Medicine Problem and Its Mechanism

The human exploration of space is one of the great voyages of discovery in human history. For over forty years space exploration, human have gotten more profound knowledge about outer space and life phenomena, ranging from understanding and recognizing space to adapting and utilizing space. With these development, space medicine that aimed at studying effect of space environment on human health and ensuring the safety, health and effective working of human in space exploration, will become increasingly improved and matured.The contents of research will develop from the early phenomena observation of the effect of space environment on human physiology and biochemistry, and the effect definition, to the study of the mechanism of changes of cell, molecule, and gene, from the passive adaptation for space environment to taking the initiative countermeasures, in order to ensure the safety, health and effective working of astronauts during space flight.Space practices in the past forty years have confirmed that a variety of physiological and pathological changes have been found for organism exposed to space flight. These changes include cardiovascular dysfunction, bone loss,muscle atrophy, decline of immune function, endocrine function disorder and space motion sickness. In recent years, more attention has been focused on the study of the mechanism of these changes, especially the effects of space environment on cell, molecule and its gene expression. With the demand of China's manned space engineering task and continuous development, a series of studies on medical problem caused by space environment have been carried out.     

Testing a Mars science outpost in the Antarctic dry valleys.

Field research conducted in the Antarctic has been providing insights about the nature of Mars in the science disciplines of exobiology and geology. Located in the McMurdo Dry Valleys of southern Victoria Land (160 degrees and 164 degrees E longitude and 76 degrees 30' and 78 degrees 30' S latitude), research outposts are inhabited by teams of 4-6 scientists. We propose that the design of these outposts be expanded to enable meaningful tests of many of the systems that will be needed for the successful conduct of exploration activities on Mars. Although there are some important differences between the environment in the Antarctic dry valleys and on Mars, the many similarities and particularly the field science activities, make the dry valleys a useful terrestrial analog to conditions on Mars. Three areas have been identified for testing at a small science outpost in the dry valleys; 1) studying human factors and physiology in an isolated environment; 2) testing emerging technologies (e.g., innovative power management systems, advanced life support facilities including partial bioregenerative life support systems for water recycling and food growth, telerobotics, etc.); and 3) conducting basic scientific research that will enhance our understanding of Mars while contributing to the planning for human exploration. We suggest that an important early result of a Mars habitat program will be the experience gained by interfacing humans and their supporting technology in a remote and stressful environment.     

柱面菲涅耳聚光透镜对称折射设计

从分析透镜不同入射高处小棱镜在最小偏向角时具有面形形变容差大的特点出发,给出了柱面菲涅耳太阳聚光透镜对称折射设计的基本原理,并比较了对称折射设计透镜和常规设计透镜的透射特性和会聚特性。采用对称折射设计,菲涅耳透镜柱面形变容差通常可高达15°~20°,且具有比常规设计高的光学效率;对称折射设计透镜虽存在散焦问题,但只要参数选择合理,出射光线均可会聚在太阳电池片上。     

Induction and repair of DNA strand breaks in bovine lens epithelial cells after high LET irradiation.

The lens epithelium is the initiation site for the development of radiation induced cataracts. Radiation in the cortex and nucleus interacts with proteins, while in the epithelium, experimental results reveal mutagenic and cytotoxic effects. It is suggested that incorrectly repaired DNA damage may be lethal in terms of cellular reproduction and also may initiate the development of mutations or transformations in surviving cells. The occurrence of such genetically modified cells may lead to lens opacification. For a quantitative risk estimation for astronauts and space travelers it is necessary to know the relative biological effectiveness (RBE), because the spacial and temporal distribution of initial physical damage induced by cosmic radiation differ significantly from that of X-rays. RBEs for the induction of DNA strand breaks and the efficiency of repair of these breaks were measured in cultured diploid bovine lens epithelial cells exposed to different LET irradiation to either 300 kV X-rays or to heavy ions at the UNILAC accelerator at GSI. Accelerated ions from Z=8 (O) to Z=92 (U) were used. Strand breaks were measured by hydroxyapatite chromatography of alkaline unwound DNA (overall strand breaks). Results showed that DNA damage occurs as a function of dose, of kinetic energy and of LET. For particles having the same LET the severity of the DNA damage increases with dose. For a given particle dose, as the LET rises, the numbers of DNA strand breaks increase to a maximum and then reach a plateau or decrease. Repair kinetics depend on the fluence (irradiation dose). At any LET value, repair is much slower after heavy ion exposure than after X-irradiation. For ions with an LET of less than 10,000 keV micrometers-1 more than 90 percent of the strand breaks induced are repaired within 24 hours. At higher particle fluences, especially for low energetic particles with a very high local density of energy deposition within the particle track, a higher proportion of non-rejoined breaks is found, even after prolonged periods of incubation. At the highest LET value (16,300 keV micrometers-1) no significant repair is observed. These LET-dependencies are consistent with the current mechanistic model for radiation induced cataractogenesis which postulates that genomic damage to the surviving fraction of epithelial cells is responsible for lens opacification.     

A new window on the cosmos: The Stratospheric Observatory for Infrared Astronomy (SOFIA)

The Stratospheric Observatory for Infrared Astronomy (SOFIA) is a joint US/German Project to develop and operate a gyrostabilized 2.5-m telescope in a Boeing 747-SP. This observatory will allow astronomical observations from 0.3 μm to sub-millimeter wavelengths at stratospheric altitudes as high as 45,000 ft where the atmosphere is not only cloud-free, but largely transparent at infrared wavelengths. The dynamics and chemistry of interstellar matter, and the details of embedded star formation will be key science goals. In addition, SOFIA’s unique portability will enable large-telescope observations at sites required to observe transient phenomena and location specific events. SOFIA will offer the convenient accessibility of a ground-based telescope for servicing, maintenance, and regular technology upgrades, yet will also have many of the performance advantages of a space-based telescope. Initially, SOFIA will fly with nine first-generation focal plane instruments that include broad-band imagers, moderate resolution spectrographs that will resolve broad features from dust and large molecules, and high resolution spectrometers capable of studying the chemistry and detailed kinematics of molecular and atomic gas. First science flights will begin in 2010, leading to a full operations schedule of about 120 8–10 h flights per year by 2014. The next call for instrument development that can respond to scientifically exciting new technologies will be issued in 2010. We describe the SOFIA facility and outline the opportunities for observations by the general scientific community with cutting edge focal plane technology. We summarize the operational characteristics of the first-generation instruments and give specific examples of the types of fundamental scientific studies these instruments are expected to make.     

Planetary Protection Policy (U.S.A.).

Through existing treaty obligations of the United States, NASA is committed to exploring space while avoiding biological contamination of the planets, and to the protection of the Earth against harm from materials returned from space. Because of the similarities between Mars and Earth, plans for the exploration of Mars evoke discussions of these Planetary Protection issues. US Planetary Protection Policy will be focused on the preservation of these goals in an arena that will change with the growth of scientific knowledge about the martian environment. Early opportunities to gain the appropriate data will be used to guide later policy implementation. Because human presence on Mars will result in the end of Earth's separation from the martian environment, it is expected that precursor robotic missions will address critical planetary protection concerns before humans arrive.     

Investigation of dose and flux dynamics in the Liulin-5 dosimeter of the tissue-equivalent phantom onboard the Russian segment of the International Space Station.

Described is the Liulin-5 active dosimetric telescope designed for measurement of the space radiation dose depth-distribution in a human phantom on the Russian Segment of the International Space Station (ISS). The Liulin-5 experiment is a part of the international project MATROSHKA-R on ISS. The MATROSHKA-R project is aimed to study the depth-dose distribution at the sites of critical organs of the human body, using models of human body-anthropomorphic and spherical tissue-equivalent phantoms. The aim of Liulin-5 experiment is a long term (4-5 years) investigation of the radiation environment dynamics inside the spherical tissue-equivalent phantom, mounted in different compartments. Energy deposition spectra, linear energy transfer spectra, and flux and dose rates for charged particles will be measured simultaneously with near real time resolution at different depths of the phantom by means of three silicon detectors. Data obtained together with data from other active and passive dosimeters will be used to estimate the radiation risk to the crewmembers, which verify the models of radiation environment in low Earth orbit. Presented are the test results of the prototype unit. Liulin-5 will be flown on the ISS in the year 2003.     

Space telescope studies of Jupiter and Saturn simulated by Voyager observations

Space Telescope (ST) observations of Jupiter and Saturn will offer a unique opportunity for monitoring their changing meteorological characteristics. They will provide higher spatial and temporal resolution for composition and vertical structure studies than have been available to date. We have simulated the planetary camera observations of Jupiter and Saturn by Voyager images of the appropriate spatial scale. With this data set we have investigated the meteorological properties of these atmospheres which can be studied at these scales. In addition we have considered the advances obtainable with the high resolution spectrometer on ST compared with observations from ground-based and other Earth-orbiting satellites. These studies will provide insight into the scientific gain and possible problems in the use of ST for planetary studies.     

Regeneration of organs and tissues in lower vertebrates during and after space flight.

In this paper most important data obtained in studies on the effect of space flight conditions on regeneration in the adult newt are summarized. We demonstrate a phenomenon of synchronization of limb and lens regeneration and increase in its rate during and after space flight. We also describe a peculiarities of cell proliferation in lens, limb and tail regenerates and of the process of minced muscle regeneration.     

The biological component of the life support system for a Martian expedition.

Ground-based experiments at RF SSC-IBMP RAS (State Science Center of Russian Federation--Institute of Biomedical Problems of Russian Academia of Science) were aimed at overall studies of a human-unicellular algae-mineralization LSS (life support system) model. The system was 15 m3 in volume. It contained 45 L of algal suspension with a dry substance density of 10-12 g per liter; water volume, including the algal suspension, was 59 L. More sophisticated model systems with partial substitution of unicellular algae with higher plates (crop area of 15 m2) were tested in three experiments from 1.5 to 2 months in duration. The experiments demonstrated that LSS employing the unicellular algae play not only a macrofunction (regeneration of atmosphere and water) but also carry some other functions (purification of atmosphere, formation of microbial cenosis etc.) providing an adequate human environment. It is also important that functional reliability of the algal regenerative subsystem is secured by a huge number of cells able, in the event of death of a part of population, to recover in the shortest possible time the size of population and, hence, functionality of the LSS autotrophic component. For a long period of time a Martian crew will be detached from Earth's biosphere and for this reason LSS of their vehicle must be highly reliable, robust and redundant. One of the approaches to LSS redundancy is installation of two systems with different but equally efficient regeneration technologies, i.e. physical-chemical and biological. At best, these two systems should operate in parallel sharing the function of regeneration of the human environment. In case of failure or a sharp deterioration in performance of one system the other will, by way of redundancy, increase its throughput to make up for the loss. This LSS design will enable simultaneous handling of a number of critical problems including adequate satisfaction of human environmental needs.     

Planetary protection issues in advance of human exploration of Mars.

Current planetary quarantine considerations focus on robotic missions and attempt a policy of no biological contamination. The presence of humans on Mars, however, will inevitably result in biological contamination and physical alteration of the local environment. The focus of planetary quarantine must therefore shift toward defining and minimizing the inevitable contamination associated with humans. This will involve first determining those areas that will be affected by the presence of a human base, then verifying that these environments do not harbor indigenous life nor provide sites for Earth bacteria to grow. Precursor missions can provide salient information that can make more efficient the planning and design of human exploration missions. In particular, a robotic sample return mission can help to eliminate the concern about returning samples with humans or the return of humans themselves from a planetary quarantine perspective. Without a robotic return the cost of quarantine that would have to be added to a human mission may well exceed the cost of a robotic return mission. Even if the preponderance of scientific evidence argues against the presence of indigenous life, it must be considered as part of any serious planetary quarantine analysis for missions to Mars. If there is life on Mars, the question of human exploration assumes an ethical dimension.