一个控制超强电离辐射抗性开关基因的研究进展

电离辐射广泛存在于地球和空间,会引起生物体内的DNA损伤,导致机体突变甚至死亡.生物体的DNA损伤响应对于稳定基因组的完整性至关重要.耐辐射奇球菌因其超强的DNA修复能力成为研究DNA损伤修复的模式生物之一.PprI-DdrO系统是近年来发现的一种新型且高效的损伤响应途径,PprI作为响应损伤的重要开关蛋白,通过酶切D...     

New approaches to biochemical radioprotection: antioxidants and DNA repair enhancement.

Chemical repair may be provided by radioprotective compounds present during exposure to ionizing radiation. Considering DNA as the most sensitive target it is feasible to biochemically improve protection by enhancing DNA repair mechanisms. Protection of DNA by reducing the amount of damage (by radical scavenging and chemical repair) followed by enhanced repair of DNA will provide much improved protection and recovery. Furthermore, in cases of prolonged exposure, such as is possible in prolonged space missions, or of unexpected variations in the intensity of radiation, as is possible when encountering solar flares, it is important to provide long-acting protection, and this may be provided by antioxidants and well functioning DNA repair systems. It has also become important to provide protection from the potentially damaging action of long-lived clastogenic factors which have been found in plasma of exposed persons from Hiroshima & Nagasaki, radiation accidents, radiotherapy patients and recently in "liquidators"--persons involved in salvage operations at the Chernobyl reactor. The clastogenic factor, which causes chromatid breaks in non-exposed plasma, might account for late effects and is posing a potential carcinogenic hazard. The enzyme superoxide dismutase (SOD) has been shown to eliminate the breakage factor from cultured plasma of exposed persons. Several compounds have been shown to enhance DNA repair: WR-2721, nicotinamide, glutathione monoester (Riklis et al., unpublished) and others. The right combination of such compounds may prove effective in providing protection from a wide range of radiation exposures over a long period of time.     

Neoplastic cell transformation by high-LET radiation: molecular mechanisms.

Experimental data on molecular mechanisms are essential for understanding the bioeffects of radiation and for developing biophysical models, which can help in determining the shape of dose-response curves at very low doses, e.g., doses less than 1 cGy. Although it has been shown that ionizing radiation can cause neoplastic cell transformation directly, that high-LET heavy ions in general can be more effective than photons in transforming cells, and that the radiogenic cell transformation is a multi-step process [correction of processes], we know very little about the molecular nature of lesions important for cell transformation, the relationship between lethal and transformational damages, and the evolution of initial damages into final chromosomal aberrations which alter the growth control of cells. Using cultured mouse embryo cells (C3H10T1/2) as a model system, we have collected quantitative data on dose-response curves for heavy ions with various charges and energies. An analysis of these quantitative data suggested that two DNA breaks formed within 80 angstroms may cause cell transformation and that two DNA breaks formed within 20 angstroms may be lethal. Through studies with restriction enzymes which produce DNA damages at specific sites, we have found that DNA double strand breaks, including both blunt- and cohesive-ended breaks, can cause cell transformation in vitro. These results indicate that DNA double strand breaks can be important primary lesions for radiogenic cell transformation and that blunt-ended double strand breaks can form lethal as well as transformational damages due to misrepair or incomplete repair in the cell. The RBE-LET relationship is similar for HGPRT gene mutation, chromosomal deletion, and cell transformation, suggesting common lesions may be involved in these radiation effects. The high RBE of high-LET radiation for cell killing and neoplastic cell transformation is most likely related to its effectiveness in producing DNA double strand breaks in mammalian cells. At present the role of oncogenes in radiation cell transformation is unclear.     

Thin film bioreactors in space.

Studies from the Skylab, SL-3 and D-1 missions have demonstrated that biological organisms grown in microgravity have changes in basic cellular functions such as DNA, mRNA and protein synthesis, cytoskeleton synthesis, glucose utilization and cellular differentiation. Since microgravity could affect prokaryotic and eukaryotic cells at a subcellular and molecular level, space offers us an opportunity to learn more about basic biological systems with one important variable removed. The thin film bioreactor will facilitate the handling of fluids in microgravity, under constant temperature and will allow multiple samples of cells to be grown with variable conditions. Studies on cell cultures grown in microgravity would enable us to identify and quantify changes in basic biological function in microgravity which are needed to develop new applications of orbital research and future biotechnology.     

K-ionization and biological effect.

Experimental inactivation cross sections are compared to vacancy production in inner shell (K-shell) of so-called strategic C, N, O atoms of the DNA: in a trial calculation, atoms on the DNA backbone or just contiguous to it are considered as strategic. Various processes are considered: ionization and electron capture by the primary particle, ionization by secondary electrons. The last phenomenon is shown to be important for highly charged and medium velocity ions. A strong similarity is observed between variations versus LET of inactivation and K-vacancy cross sections, especially with regards to LET values for which they maximize: for K-ionization these maxima occur when the ion impact velocity roughly matches the K electron velocity. It is shown that the "K-hypothesis" allows a quantitative fit of experimental inactivation cross sections if a 4% mean lethal efficiency is attributed to ion-induced K-vacancies in strategic C, N, O atoms.     

Role of endogenous thiols in protection.

Aminothiols represent the most important group of radioprotective compounds. The most effective compounds administered at an optimal dose and time before irradiation are able to provide a protection in mice with a dose reduction factor (DRF) of about 2-2.5. The working mechanism can partly be explained as a scavenging process of radicals induced in water and partly as a chemical repair process of injured DNA. The endogenous aminothiol which has far-out the highest intracellular concentration is glutathione (GSH). The importance of intracellular GSH in determining cellular radiosensitivity has been shown by irradiating cells that had very low GSH levels. Such cells appear to have a high radiosensitivity, especially in hypoxic conditions. On the other hand, it has been demonstrated that induction of a high GSH level (100-200% above the normal level) provides only a small protection. In vitro experiments with DNA indicate that thiols with a high positive charge condense in the vicinity of DNA and are effective protectors, whereas thiols with a negative charge are kept away from it and are poor protectors. In comparison with the most effective exogenous aminothiols like cysteamine and WR1065, GSH is not an effective radioprotector. Putative explanations for this relatively poor protective ability of GSH are presented.     

The role of hydration and radiation quality in the induction of DNA damage--chemical aspects.

The mutagenic and lethal effects of ionising radiation are thought to result from chemical modifications induced within DNA. This DNA damage is significantly influenced by the chemical environment and the radiation quality (LET). Water closely associated with the DNA and its immediate environment is involved in the early chemical pathways which lead to the induction of DNA damage and is reflected in the cellular radiosensitivity. For instance, hydration of DNA influences hole migration leading to its localisation at guanine. Changes in the radiation quality are discussed in terms of the complexity of the radical clusters produced. It is inferred that at higher LET, the influence of the chemical environment (O2 etc) decreases with respect to DNA damage and cellular radiosensitivity. It is therefore important to include these effects of environment of the DNA upon the early chemical pathways in models of radiation action.     

飞行综合控制系统空战决策方法

控制决策方法是飞机综合控制系统根据空战对策状态、双方的运动及性能参数等信息产生出机动策略的一种数学方法,是飞机综合控制系统决策层数学模型的重要组成。以空战攻防力学准则建立起的捕获临界条件作为评价函数,采用矩阵博弈数学方法求出离散化机动策略。主要内容：相对运动方程的建立;矩阵博弈策略算法;评价函数的建立等。     

DNA damage and repair in oncogenic transformation by heavy ion radiation.

Energetic heavy ions are present in galactic cosmic rays and solar particle events. One of the most important late effects in risk assessment is carcinogenesis. We have studied the carcinogenic effects of heavy ions at the cellular and molecular levels and have obtained quantitative data on dose-response curves and on the repair of oncogenic lesions for heavy particles with various charges and energies. Studies with repair inhibitors and restriction endonucleases indicated that for oncogenic transformation DNA is the primary target. Results from heavy ion experiments showed that the cross section increased with LET and reached a maximum value of about 0.02 micrometer2 at about 500 keV/micrometer. This limited size of cross section suggests that only a fraction of cellular genomic DNA is important in radiogenic transformation. Free radical scavengers, such as DMSO, do not give any effect on induction of oncogenic transformation by 600 MeV/u iron particles, suggesting most oncogenic damage induced by high-LET heavy ions is through direct action. Repair studies with stationary phase cells showed that the amount of reparable oncogenic lesions decreased with an increase of LET and that heavy ions with LET greater than 200 keV/micrometer produced only irreparable oncogenic damage. An enhancement effect for oncogenic transformation was observed in cells irradiated by low-dose-rate argon ions (400 MeV/u; 120 keV/micrometer). Chromosomal aberrations, such as translocation and deletion, but not sister chromatid exchange, are essential for heavy-ion-induced oncogenic transformation. The basic mechanism(s) of misrepair of DNA damage, which form oncogenic lesions, is unknown.     

Monitoring of environmental UV radiation by biological dosimeters.

As a consequence of the stratospheric ozone layer depletion biological systems can be damaged due to increased UV-B radiation. The aim of biological dosimetry is to establish a quantitative basis for the risk assessment of the biosphere. DNA is the most important target molecule of biological systems having special sensitivity against short wavelength components of the environmental radiation. Biological dosimeters are usually simple organisms, or components of them, modeling the cellular DNA. Phage T7 and polycrystalline uracil biological dosimeters have been developed and used in our laboratory for monitoring the environmental radiation in different radiation conditions (from the polar to equatorial regions). Comparisons with Robertson-Berger (RB) meter data, as well as with model calculation data weighted by the corresponding spectral sensitivities of the dosimeters are presented. Suggestion is given how to determine the trend of the increase in the biological risk due to ozone depletion.     

基于马尔可夫链的空间站推进1553B通信系统可靠性分析

推进功能的正常实现为空间站长期在轨运行提供重要保障。1553B通信系统作为推进功能的重要组成部分,承担着推进系统与外界进行数据交互的任务,其可靠性设计至关重要。为提高1553B通信系统可靠性,分别对包含数据隔离芯片在内的远程终端及其处理器进行双余度冗余设计。通过建立故障树对1553B通信系统可靠性进行分析,并引入平均无故障时间、可靠度等定量指标,基于马尔可夫链建立可靠性模型进行定量计算。结果表明,1553B通信系统平均无故障时间增加1.947倍,可靠度增长3.89%,故障概率则下降超98%,由此验证了双余度冗余设计能够有效地提升1553B通信系统的可靠性。     

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.     

On a possible ring current effect in the density of the neutral upper atmosphere

The neutral post-storm effect is reconsidered by means of accelerometric data. Since Δρ has proved to be different function of Kp during and outside recovery phases, but a unique function of Dst, the latter is considered as a better index for correcting the effect of geomagnetic activity in models, i.e. it seems that the ring current plays an important role in the geomagnetic effect of the equatorial thermosphere.     

高精度位置跟踪自适应增益调度滑模控制算法

影响位置跟踪精度最重要的因素之一是系统不可避免地存在内外不确定性。由于具备很强的鲁棒性,滑模控制能有效消除系统不确定性的影响,然而也会带来抖振这一顽疾。因此,有效削弱滑模控制系统的抖振是提升系统跟踪精度的关键。为此,本文提出一种误差主导的自适应增益调度算法,该算法利用等效原理准确判断系统滑动模态是否建立,并以此来调度切换函数增益值的增减;同时,为克服因利用低通滤波器获取切换函数等效输出而引起的时间延迟,在增益调度中采用误差主导的增益变化率,确保了增益调度的实时性。理论和仿真实验证明,在滑动模态建立前,该增益调度策略能加快滑模变量的收敛速度;而在滑动模态建立后,该增益调度策略能使增益值在有限时间内趋近于系统不确定的绝对值,降低了系统抖振幅值,从而获取更高的跟踪精度。直流力矩电机伺服系统位置跟踪对比实验结果表明,该增益调度方案有效,能使系统获得更高的跟踪精度。     

气膜孔图像对焦评价函数的实验研究

为了使工业影像测头能够正确对焦于气膜孔的出口表面,开展了对焦评价函数选取的实验研究。首先,分析了各类对焦评价函数的特性、要求及优缺点,并确定选择灰度梯度函数用于图像序列的清晰度评价;然后,考察了Brenner梯度函数、Tenengrad梯度函数和Laplacian梯度函数等5种具有代表性的灰度梯度函数,通过实验获得了它们的函数曲线,并进行归一化处理和比较分析,最终确定Laplacian梯度函数作为系统的对焦评价函数,并进行了重复性验证。实验结果表明,Laplacian梯度函数可以正确判别出被测气膜孔的对焦位置,且对焦重复性小于0.005mm,满足气膜孔形位参数的检测要求。     

气膜孔图像对焦评价函数的实验研究

为了使工业影像测头能够正确对焦于气膜孔的出口表面,开展了对焦评价函数选取的实验研究。首先,分析了各类对焦评价函数的特性、要求及优缺点,并确定选择灰度梯度函数用于图像序列的清晰度评价;然后,考察了Brenner梯度函数、Tenengrad梯度函数和Laplacian梯度函数等5种具有代表性的灰度梯度函数,通过实验获得了它们的函数曲线,并进行归一化处理和比较分析,最终确定Laplacian梯度函数作为系统的对焦评价函数,并进行了重复性验证。实验结果表明,Laplacian梯度函数可以正确判别出被测气膜孔的对焦位置,且对焦重复性小于0.005mm,满足气膜孔形位参数的检测要求。     

一个二次可积系统在二次保守扰动下的分支

研究了一个具有同宿轨的二次可积系统在二次保守扰动下的分支现象.此时一阶Melnikov函数恒等于零,必须考虑二阶Melnikov函数,而在一阶Melnikov函数中不起作用的扰动参数在二阶Melnikov函数中却起着非常重要的作用,因此扰动部分极为复杂.在此借助于二阶Melnikov函数的计算公式及理论分析,建立了极限环分支定理,得到了在一阶Melnikov函数恒等于零,而二阶Melnikov函数不恒等于零时,可能分支出的极限环个数最大为2的结论.     

采用Loh近似假设的最优气动力辅助异面变轨研究

提出了一种Ｌｏｈ近似模型,并在此基础上导出了最优气动力辅助异面变轨的控制规律,以及相应的最优轨迹的近似解析解。给出了Ｌｏｈ近似模型中各系数的求解方法。通过对最优控制律及轨迹近似解的分析,得到一些有益的结论。     

热流效应对场向电流确定的影响

给出了任意速度分布函数条件下复频率的介电函数和色散关系的求解方法. 讨论了16矩近似条件下, 场向热流对电子速度分布函数, 介电函数实部与虚部, 以及离子与电子谐振频率和阻尼率的影响, 并与平衡态时麦克斯韦分布等离子体的计算结果进行了比较. 忽略场向热流效应, 正向电子漂移速度条件下, 上行等离子线探测, 会过高估计场向电流; 负向电子漂移速度条件下, 上行等离子线探测会过低估计场向电流. 对上下行等离子线同时探测情况, 忽略热流效应同样会过高估计场向电流.