腺鳞癌转化在肺癌耐药中的功能和机制研究

肺癌是一种高致死率的疾病，具有高度的异质性和可塑性。基于病理学分型，肺癌可分为小细胞肺癌和非小细胞肺癌，后者又可细分为腺癌，鳞癌和大细胞癌。临床上可观察到同一个肿瘤内部混合腺癌和鳞癌(腺鳞癌)，或小细胞肺癌混合腺癌或鳞癌(混合型小细胞肺癌)。其中，腺鳞癌在临床上占非小细胞肺癌的 4%~10%。近几年越来越多的临床案例报道，肺腺癌患者经过化疗、靶向治疗或免疫治疗，肿瘤类型会从腺癌转变成鳞癌，并表现出耐药性。动物模型的研究发现， 肝激酶 B1(Lkb1)缺失会促进小鼠肺腺癌向鳞癌转化，而腺鳞癌是转化过程的中间态。从细胞起源来看，Club 细胞和 AT2 (Alveolar Epithelial Type 2)来源的肺腺癌可以转化成鳞癌。从分子机制来看，肺腺癌向鳞癌转化的过程中，胞外基质重塑以及代谢重编程会导致细胞氧化应激异常，使得活性氧(Reactive Oxygen Species，ROS)水平急剧上升并诱导 p63 上调，最终导致腺鳞癌转化并伴随肿瘤耐药。本综述将总结近年来肺腺鳞癌转化领域的进展并阐述其与耐药的关系，以期为深入理解临床肺癌的可塑性奠定理论基础。     

肥大细胞在肺部感染性疾病中的作用

肺部肥大细胞主要分布于肺部血管周围，支气管以及粘膜组织。病原体入侵时，肥大细胞通过胞吞作用直接摄取病原体，同时通过激活自身受体促进下游细胞介质的释放，增强炎性细胞的募集，直接和间接杀伤病原体。此外，肺部肥大细胞参与病原体的抗原递呈，介导细胞和体液免疫。肥大细胞对肺部病原体感染具有重要的保护功能。     

铁谱术和磨损趋势分析

一、引言——铁谱术航空发动机以及飞机的传动系统都包含有大量的相对运动零部件,包括轴承、齿轮、花键、离合器、封严装置等等。这些零部件在相对运动接触过程中都会产生不同程度的磨损。磨损微粒从这些零件的承载表面产出、而又由于润滑油的冲刷作用而脱离承载表面循环于润滑系统之中。部分颗粒较大的微粒被过滤元件所捕捉,而大量的微小的微粒则自由地活动于整个润滑循环系统。由于不同的材料性能、受力状态、相对运动条件、周围环境等因素的影响,不同的磨损过程中产生的磨损微粒具有不同的数量、大小、形状、颜色、表面特征等等。研究这些不同的特征、分析并确定被润滑零件的磨掼状态可以提供十分宝贵的信息。因     

化学镀SiC／Ni—P功能梯度材料工艺,组织及性能

通过对化学镀Ｎｉ－Ｐ－ＳｉＣ复合镀层的研究，找到了制备ＳｉＣ－Ｎｉ－Ｐ功能梯度材料（ＦＧＭ）的工艺方法。并采用光学显微镜、电子探针分析仪及热震试验等方法和手段对功能梯度材料的组织、形貌、成分与镀层结合力进行了研究。结果表明，功能梯度材料中ＳｉＣ微粒以弥散状态沿镀层厚度方向呈梯度分布，无团聚结块现象，材料致密，组织细小。功能梯度材料较单层Ｎｉ－Ｐ－ＳｉＣ复合镀层以及Ｎｉ－Ｐ／Ｎｉ－Ｐ－ＳｉＣ双层镀层     

水下爆轰燃气泡形态与激波传播过程研究

针对脉冲爆轰发动机在水下工作过程中形成的燃气射流问题,搭建了水下爆轰燃气实验系统,研究了第一个爆轰循环中燃气泡发展变化过程。建立了基于气液两相双流体模型的脉冲爆轰发动机水下喷射模型,采用时-空守恒元和求解元方法,模拟了爆轰波与水相互作用形成的激波的传播及衰减过程。研究结果表明：燃气射流冲击水面时,燃气泡形态在膨胀阶段受到水介质的阻滞作用呈现“豌豆”状,其轴向与径向尺寸有不同的发展规律;同时燃气泡内由于气水冲击作用和燃气扩散受限一直保持较高压力;前导激波传播速度远大于燃气泡发展速度,脱离燃气泡后激波压力值迅速衰减至常压量级,且在中心轴线上的衰减最为剧烈,导致其强度指向性发生改变;前导激波在气液交界面处产生反射,回传的反射激波与后续气流形成的拦截激波碰撞在燃气泡内出现回击现象,使管口附近形成较高的压力峰值。     

三外涵变循环发动机性能数值模拟

与双外涵模式相比,三外涵变循环技术将使发动机工作范围更广,更易满足未来发动机的自适应要求,及更大提升飞机综合性能。在带核心机驱动风扇级(CDFS)双外涵变循环发动机性能仿真方法基础上,构建了前调节阀门、后调节阀门、第三外涵等的数学模型,开展了三外涵变循环发动机性能模拟方法研究,重点分析了三外涵变循环发动机的稳态性能。结果表明:相比单外涵和双外涵模式,三外涵模式总涵道比调节程度更大,发动机最大状态与亚声速巡航状态间的燃油经济性更明显。     

化学镀SiC/Ni-P功能梯度材料工艺、组织及性能

通过对化学镀Ｎｉ－ Ｐ－ ＳｉＣ复合镀层的研究,找到了制备ＳｉＣ／Ｎｉ－ Ｐ 功能梯度材料（ＦＧＭ） 的工艺方法。并采用光学显微镜、电子探针分析仪及热震试验等方法和手段对功能梯度材料的组织、形貌、成分与镀层结合力进行了研究。结果表明,功能梯度材料中ＳｉＣ微粒以弥散状态沿镀层厚度方向呈梯度分布,无团聚结块现象,材料致密,组织细小。功能梯度材料较单层Ｎｉ－ Ｐ－ ＳｉＣ复合镀层以及Ｎｉ－ Ｐ／Ｎｉ－ Ｐ－ ＳｉＣ 双层镀层具有更好的结合强度。     

FLADE变循环发动机模态转换过程特性分析

为对带FLADE(Fan on Blade)的变循环发动机总体性能进行评估,发展了FLADE部件计算方法以及带FLADE的双外涵变循环发动机稳态性能计算模型,加入反映转子惯性效应和部件容积效应的动力学方程,建立了变循环发动机过渡态性能计算模型。分析了FLADE变循环发动机在双外涵与单外涵模式之间的模态转换过渡态特性,重点研究了几何参数调节及其不同组合形式对FLADE变循环发动机模态转换过程的影响。结果表明,带FLADE的双外涵变循环发动机的模态转换过程只与FLADE导叶角度和FLADE喷管面积有关,且两者应同时放大或关小;FLADE的开/关对风扇外涵气流及核心机的影响较小。     

尾吊模拟失重对小鼠过敏性哮喘的影响及其机制研究

为阐明模拟失重条件下免疫功能变化在过敏性哮喘发生中的作用,在正常条件下和尾吊模拟失重条件下利用卵清蛋白(OVA)刺激诱导小鼠过敏性哮喘,通过小鼠外观、精神、呼吸、擦鼻情况以及肺组织切片、支气管肺泡灌洗液细胞计数评估过敏性哮喘的程度,通过脾细胞计数和淋巴细胞亚群测定小鼠免疫状态。结果表明：小鼠尾吊模拟失重可以改善OVA诱导过敏性哮喘小鼠的外观、精神、呼吸、擦鼻情况,减少OVA诱导小鼠支气管肺组织中炎性细胞浸润,减轻肺泡壁的增厚,降低细胞间质的渗出;与单纯的OVA组相比,尾吊减少了支气管肺泡灌洗液细胞的数目(P<0.001),降低脾细胞的总数(P<0.01),T辅助细胞(Th) 1、Th2和Th17亚群占比降低,调节T细胞(Treg)亚群占比显著升高(P<0.05)。尾吊模拟失重下,OVA诱导条件下,机体免疫功能发生改变,与过敏性哮喘的病情有一定相关性。     

激波串与进气道肩部分离泡相互作用

针对高超声速进气道激波串与肩部分离泡相互作用时的流动振荡问题，在来流马赫数为6的激波风洞中，采用高速纹影拍摄结合壁面动态压力测量，研究了有/无抽吸情况下激波串与肩部分离泡的相互作用过程。结果表明：当激波串前移至肩部附近时，有抽吸进气道也会产生大尺度的分离泡，进而有/无抽吸进气道内的激波串均会与肩部分离泡形成耦合振荡，并造成严重的脉动压力。在激波串的推动下，分离泡能够自由地越过肩部凸拐角，使得其自身的低频振荡特性能够显现。激波串内的压力波动会显著改变分离泡的形态，而分离泡形态的变化又会影响激波串内的压力，两者相互耦合从而维持这种低频振荡。无抽吸进气道具有相同的低频耦合振荡特性；而抽吸缝阻碍了上下游的信息传递，使得有抽吸进气道的分离泡低频振荡显著，而激波串振荡具有一定的宽频特性。经分离激波振荡范围和进气道入口速度无量纲后，有/无抽吸进气道低频耦合振荡的St均处于0.011～0.021，与经典分离泡的低频振荡特性相当。     

Multiple-Sulphur Isotope Biosignatures

Variations in sulphur isotope ratios have been used as biosignatures in early rock records and Martian meteorites because some microbial sulphur metabolisms are known to produce large magnitude mass-dependent sulphur isotope fractionation. In order to establish the sulphur isotope biosignature, however, it becomes critically important to evaluate abiogenic processes that fractionate sulphur isotope ratios. A brief review is given here for the fundamental systematics and characteristics of multiple-sulfur isotope effects associated with (1) biological, (2) hydrothermal, and (3) photochemical processes. High-precision analysis of all four isotope abundance of sulphur may provide a unique constraint to establish biosignatures in space exploration.     

Synthesis of Iron-containing Carbon Microparticles from Deoiled Asphalt and Ferrocene

The deoiled asphalt as the carbon source and the ferrocene as the metal source and the catalyst precursor were chosen to synthe-size iron-containing carbon microparticles through co-carbonization at the temperature of about 450 ℃ for 3 h. The resulting products were treated at 2 000 ℃ for 2 h. All samples were examined by high resolution transmission electron microscopy (HRTEM) and X-ray diffraction (XRD). The results show that the iron particles in the heat-treated material are completely coated by carbon. In addition to the fully filled carbon microparticles as well as hollow carbon ones, also form carbon fibers with hollow centers. The formation mechanism of the as-prepared products was discussed briefly.     

一种高可靠长寿命的推进系统

介绍单元肼为推进剂的卫星推进系统，该系统已成功用于我国地球同步轨道通信卫星，高可靠，长寿命。叙述了系统及各部件的主要性能，关键部件的特性与可靠性试验，材料相容性试验，微粒控制及系统热试车。根据多年的飞行试验及地验对系统进行了可靠性计算。     

Error Performance of Two-Channel Phase-Measurement Systems

The problem of measuring a constant phase difference between two sinusoids which have been corrupted by two additive noise processes is investigated. For the case in which both noise processes are Gaussian and the signal-to-noise ratio is high, the variance of the time-averaged phase-difference estimate is found as a single integral over the noise power spectral densities and cross spectral density. Arbitrary cross correlation is allowed between the two noise processes. Two cases of practical interest are considered: 1) the noise processes have identical, rectangular power spectral densities and are statistically independent; 2) an idealized radio direction finding situation in which two spatially separated sensors are immersed in an isotropic, planar noise field. For the statistically independent case, a universal curve is presented which permits determination of phase-estimate standard deviation for arbitrary signal-to-noise ratio and for a wide range of bandwidths and integration times.     

纳米级SiCp/6066Al复合材料的制备与力学性能的研究

采用粉末冶金方法制备了纳米SiCp增强铝基复合材料，研究了增强相尺寸对铝基复合材料性能的影响。结果表明：体积分数为1％的纳米级SiCp／6066Al复合材料的强度与体积分数为12％、尺寸为7μm的SiCp／6066Al复合材料的强度相当，并且前者的塑性高于后者。     

薄壁钛管剪应力本构参数识别方法

不同温度下的薄壁钛管剪应力本构参数识别,是研究薄壁钛管差温剪切弯曲过程管材塑性变形行为迫切需要解决的关键问题。提出了一种管材剪切测试的方法。将不同温度下薄壁钛管等温剪切测试、剪切测试过程模拟有限元模型、以及基于距离函数的响应面模型相结合,提出了薄壁钛管不同温度下剪应力本构参数逆向识别方法。采用该方法,识别了TA2薄壁钛管剪应力本构参数。同时建立了TA2薄壁钛管差温剪切弯曲过程模拟3维弹塑性热力耦合有限元模型。分别采用剪应力本构参数和单拉应力本构参数模拟弯管实验过程,评估了有限元模型的可靠性。结果表明：对于剪应力本构参数,温度越高,管材的K值和n值将减小,m值呈现波动的趋势。与单拉应力本构参数相比,剪应力本构参数对温度的变化更敏感,且剪应力本构参数值较小。与单拉应力本构参数相比,使用剪应力本构参数的有限元模型精度较高,模拟精度最大提高了60%。     

Gene Transfer and the Reconstruction of Life’s Early History from Genomic Data

The metaphor of the unique and strictly bifurcating tree of life, suggested by Charles Darwin, needs to be replaced (or at least amended) to reflect and include processes that lead to the merging of and communication between independent lines of descent. Gene histories include and reflect processes such as gene transfer, symbioses and lineage fusion. No single molecule can serve as a proxy for the tree of life. Individual gene histories can be reconstructed from the growing molecular databases containing sequence and structural information. With some simplifications these gene histories can be represented by furcating trees; however, merging these gene histories into web-like organismal histories, including the transfer of metabolic pathways and cell biological innovations from now-extinct lineages, has yet to be accomplished. Because of these difficulties in interpreting the record retained in molecular sequences, correlations with biochemical fossils and with the geological record need to be interpreted with caution. Advances to detect and pinpoint transfer events promise to untangle at least a few of the intertwined histories of individual genes within organisms and trace them to the organismal ancestors. Furthermore, analysis of the shape of molecular phylogenetic trees may point towards organismal radiations that might reflect early mass extinction events that occurred on a planetary scale.     

Biological implications of the Viking mission to Mars

A central purpose of Viking was to search for evidence that life exists on Mars or may have existed in the past. The missions carried three biology experiments the prime purpose of which was to seek for existing microbial life. In addition the results of a number of the other experiments have biological implications: (1) The elemental analyses of the atmosphere and the regolith showed or implied that the elements generally considered essential to terrestrial biology are present. (2) But unexpectedly, no organic compounds were detected in Martian samples by an instrument that easily detected organic materials in the most barren of terrestrial soils. (3) Liquid water is believed to be an absolute requisite for life. Viking obtained direct evidence for the presence of water vapor and water ice, and it obtained strong inferential evidence for the existence of large amounts of subsurface permafrost now and in the Martain past. However it obtained no evidence for the current existence of liquid water possessing the high chemical potential required for at least terrestrial life, a result that is consistent with the known pressure-temperature relations on the planet's surface. On the other hand, the mission did obtain strong indications from both atmospheric analyses and orbital photographs that large quantities of liquid water flowed episodically on the Martian surface 0.5 to 2.5 G years ago.The three biology experiments produced clear evidence of chemical reactivity in soil samples, but it is becoming increasingly clear that the chemical reactions were nonbiological in origin. The unexpected release of oxygen by soil moistened with water vapor in the Gas Exchange experiment together with the negative findings of the organic analysis experiment lead to the conclusion that the surface contains powerful oxidants. This conclusion is consistent with models of the atmosphere. The oxidants appear also to have been responsible for the decarboxylation of the organic nutrients that were introduced in the Label Release experiment. The major results of the GEX and LR experiments have been simulated at least qualitatively on Earth. The third, Pyrolytic Release, experiment obtained evidence for organic synthesis by soil samples. Although the mechanism of the synthesis is obscure, the thermal stability of the reaction makes a biological explanation most unlikely. Furthermore, the response of soil samples in all three experiments to the addition of water is not consistent with a biological interpretation.The conditions now known to exist at and below the Martian surface are such that no known terrestrial organism could grow and function. Although the evidence does not absolutely rule out the existence of favourable oases, it renders their existence extremely unlikely. The limiting conditions for the functioning of terrestrial organisms are not the limits for conceivable life elsewhere, and accordingly one cannot exclude the possibility that indigenous life forms may currently exist somewhere on Mars or may have existed sometime in the past. Nevertheless, the available information about the present Martian environment puts severe constraints and presents formidable challenges to any putative Martian organisms. The Martian environment in the past, on the other hand, appears to have been considerably less hostile biologically, and it might possibly have permitted the origin and transient establishment of a biota.     

The Geology of Mercury: The View Prior to the MESSENGER Mission

Mariner 10 and Earth-based observations have revealed Mercury, the innermost of the terrestrial planetary bodies, to be an exciting laboratory for the study of Solar System geological processes. Mercury is characterized by a lunar-like surface, a global magnetic field, and an interior dominated by an iron core having a radius at least three-quarters of the radius of the planet. The 45% of the surface imaged by Mariner 10 reveals some distinctive differences from the Moon, however, with major contractional fault scarps and huge expanses of moderate-albedo Cayley-like smooth plains of uncertain origin. Our current image coverage of Mercury is comparable to that of telescopic photographs of the Earth’s Moon prior to the launch of Sputnik in 1957. We have no photographic images of one-half of the surface, the resolution of the images we do have is generally poor (∼1 km), and as with many lunar telescopic photographs, much of the available surface of Mercury is distorted by foreshortening due to viewing geometry, or poorly suited for geological analysis and impact-crater counting for age determinations because of high-Sun illumination conditions. Currently available topographic information is also very limited. Nonetheless, Mercury is a geological laboratory that represents (1) a planet where the presence of a huge iron core may be due to impact stripping of the crust and upper mantle, or alternatively, where formation of a huge core may have resulted in a residual mantle and crust of potentially unusual composition and structure; (2) a planet with an internal chemical and mechanical structure that provides new insights into planetary thermal history and the relative roles of conduction and convection in planetary heat loss; (3) a one-tectonic-plate planet where constraints on major interior processes can be deduced from the geology of the global tectonic system; (4) a planet where volcanic resurfacing may not have played a significant role in planetary history and internally generated volcanic resurfacing may have ceased at ∼3.8 Ga; (5) a planet where impact craters can be used to disentangle the fundamental roles of gravity and mean impactor velocity in determining impact crater morphology and morphometry; (6) an environment where global impact crater counts can test fundamental concepts of the distribution of impactor populations in space and time; (7) an extreme environment in which highly radar-reflective polar deposits, much more extensive than those on the Moon, can be better understood; (8) an extreme environment in which the basic processes of space weathering can be further deduced; and (9) a potential end-member in terrestrial planetary body geological evolution in which the relationships of internal and surface evolution can be clearly assessed from both a tectonic and volcanic point of view. In the half-century since the launch of Sputnik, more than 30 spacecraft have been sent to the Moon, yet only now is a second spacecraft en route to Mercury. The MESSENGER mission will address key questions about the geologic evolution of Mercury; the depth and breadth of the MESSENGER data will permit the confident reconstruction of the geological history and thermal evolution of Mercury using new imaging, topography, chemistry, mineralogy, gravity, magnetic, and environmental data.     

Mercury’s Weather-Beaten Surface: Understanding Mercury in the Context of Lunar and Asteroidal Space Weathering Studies

Mercury’s regolith, derived from the crustal bedrock, has been altered by a set of space weathering processes. Before we can interpret crustal composition, it is necessary to understand the nature of these surface alterations. The processes that space weather the surface are the same as those that form Mercury’s exosphere (micrometeoroid flux and solar wind interactions) and are moderated by the local space environment and the presence of a global magnetic field. To comprehend how space weathering acts on Mercury’s regolith, an understanding is needed of how contributing processes act as an interactive system. As no direct information (e.g., from returned samples) is available about how the system of space weathering affects Mercury’s regolith, we use as a basis for comparison the current understanding of these same processes on lunar and asteroidal regoliths as well as laboratory simulations. These comparisons suggest that Mercury’s regolith is overturned more frequently (though the characteristic surface time for a grain is unknown even relative to the lunar case), more than an order of magnitude more melt and vapor per unit time and unit area is produced by impact processes than on the Moon (creating a higher glass content via grain coatings and agglutinates), the degree of surface irradiation is comparable to or greater than that on the Moon, and photon irradiation is up to an order of magnitude greater (creating amorphous grain rims, chemically reducing the upper layers of grains to produce nanometer-scale particles of metallic iron, and depleting surface grains in volatile elements and alkali metals). The processes that chemically reduce the surface and produce nanometer-scale particles on Mercury are suggested to be more effective than similar processes on the Moon. Estimated abundances of nanometer-scale particles can account for Mercury’s dark surface relative to that of the Moon without requiring macroscopic grains of opaque minerals. The presence of nanometer-scale particles may also account for Mercury’s relatively featureless visible–near-infrared reflectance spectra. Characteristics of material returned from asteroid 25143 Itokawa demonstrate that this nanometer-scale material need not be pure iron, raising the possibility that the nanometer-scale material on Mercury may have a composition different from iron metal [such as (Fe,Mg)S]. The expected depletion of volatiles and particularly alkali metals from solar-wind interaction processes are inconsistent with the detection of sodium, potassium, and sulfur within the regolith. One plausible explanation invokes a larger fine fraction (grain size <45 μm) and more radiation-damaged grains than in the lunar surface material to create a regolith that is a more efficient reservoir for these volatiles. By this view the volatile elements detected are present not only within the grain structures, but also as adsorbates within the regolith and deposits on the surfaces of the regolith grains. The comparisons with findings from the Moon and asteroids provide a basis for predicting how compositional modifications induced by space weathering have affected Mercury’s surface composition.