Cytosolic accumulation of gammaH2AX is associated with tropomyosin-related kinase A-induced cell death in U2OS cells

Tropomyosin-related kinase A (TrkA) plays an important role in cell survival, differentiation, and apoptosis in various neuronal and nonneuronal cell types. Here we show that TrkA overexpression by the Tet-On system mimics NGF-mediated activation pathways in the absence of nerve growth factor (NGF) stimulation in U2OS cells. In addition, p53 upregulation upon DNA damage was inhibited by TrkA, and p21 was upregulated by TrkA in a p53-independent manner. TrkA overexpression caused cell death by interrupting cell cycle progression, and TrkA-induced cell death was diminished in the presence of its specific inhibitor GW441756. Interestingly, TrkA-mediated cell death was strongly related to gammaH2AX production and poly (ADP-ribose) polymerase cleavage in the absence of DNA damage inducer. In this study, we also reveal that gammaH2AX production by TrkA is blocked by TrkA kinase inhibitors K-252a and GW441756, and it is also significantly inhibited by JNK inhibitor SP600125. Moreover, reduction of cell viability by TrkA was strongly suppressed by SP600125 treatment, suggesting a critical role of JNK in TrkA-induced cell death. We also found that gammaH2AX and TrkA were colocalized in cytosol in the absence of DNA damage, and the nuclear localization of gammaH2AX induced by DNA damage was partly altered to cytosol by TrkA overexpression. Our results suggest that the abnormal cytosolic accumulation of gammaH2AX is implicated in TrkA-induced cell death in the absence of DNA damage.     

Photofragmentation of 2‐Deoxy‐D‐Ribose Molecules in the Gas Phase

We have measured the synchrotron‐induced photofragmentation of isolated 2‐deoxy‐D ‐ribose molecules (C₅H₁₀O₄) at four photon energies, namely, 23.0, 15.7, 14.6, and 13.8 eV. At all photon energies above the molecule′s ionization threshold we observe the formation of a large variety of molecular cation fragments, including CH₃⁺, OH⁺, H₃O⁺, C₂H₃⁺, C₂H₄⁺, CH_xO⁺ (x=1,2,3), C₂H_xO⁺ (x=1–5), C₃H_xO⁺ (x=3–5), C₂H₄O₂⁺, C₃H_xO₂⁺ (x=1,2,4–6), C₄H₅O₂⁺, C₄H_xO₃⁺ (x=6,7), C₅H₇O₃⁺, and C₅H₈O₃⁺. The formation of these fragments shows a strong propensity of the DNA sugar to dissociate upon absorption of vacuum ultraviolet photons. The yields of particular fragments at various excitation photon energies in the range between 10 and 28 eV are also measured and their appearance thresholds determined. At all photon energies, the most intense relative yield is recorded for the m/q=57 fragment (C₃H₅O⁺), whereas a general intensity decrease is observed for all other fragments— relative to the m/q=57 fragment—with decreasing excitation energy. Thus, bond cleavage depends on the photon energy deposited in the molecule. All fragments up to m/q=75 are observed at all photon energies above their respective threshold values. Most notably, several fragmentation products, for example, CH₃⁺, H₃O⁺, C₂H₄⁺, CH₃O⁺, and C₂H₅O⁺, involve significant bond rearrangements and nuclear motion during the dissociation time. Multibond fragmentation of the sugar moiety in the sugar–phosphate backbone of DNA results in complex strand lesions and, most likely, in subsequent reactions of the neutral or charged fragments with the surrounding DNA molecules.     

Early Stage UV-B Induced Molecular Modifications of Human Eye Lens γD-Crystallin

In the human eye lenses, the crystallin proteins facilitate transparency, light refraction, as well as UV light protection. A deregulated balanced interplay between α-, β-, and γ-crystallin can cause cataract. γD-crystallin (hγD) is involved in the energy dissipation of absorbed UV light by energy transfer between aromatic side chains. Early UV-B induced damage of hγD with molecular resolution is studied by solution NMR and fluorescence spectroscopy. hγD modifications are restricted to Tyr 17 and Tyr 29 in the N-terminal domain, where a local unfolding of the hydrophobic core is observed. None of the tryptophan residues assisting fluorescence energy transfer is modified and hγD is remained soluble over month. Investigating isotope-labeled hγD surrounded by eye lens extracts from cataract patients reveals very week interactions of solvent-exposed side chains in the C-terminal hγD domain and some remaining photoprotective properties of the extracts. Hereditary E107A hγD found in the eye lens core of infants developing cataract shows under the here used conditions a thermodynamic stability comparable to the wild type but an increased sensitivity toward UV-B irradiation.     

Monte Carlo simulation of radiation damage produced in iron and vanadium by primary knock on atom ‘PKA’

Atomic scale simulation of radiation damage of pure iron and vanadium has been studied using the JA-IPU code based on Monte Carlo simulation. In response to gamma, neutron and any charged particle irradiation, energetic atoms knocked off their lattice position also generate atomic cascades inside the material besides the projectiles. The atomic cascade initiated by the primary knock on atoms (PKAs) of energy in the range 0–50?keV have been simulated in case of iron and vanadium metals. More realistic energy segregation has been achieved by incorporating electronic energy loss (EEL) along with nuclear stopping in the code. It is revealed that the effect of EEL is definite and different at low PKA energy as compared with high energy. The flip over energy is ～8?keV in iron and ～20?keV in the case of vanadium. This difference is found to be more in the case of the displacements than in the case of the defects. Cascade efficiency of vanadium calculated from the JA-IPU code has also been compared with the molecular dynamic simulation and found to be nearly the same.     

基于石英晶体天平和微纳光纤的有机污染物在线监测

为了监测高功率激光驱动器中有机污染物的挥发特性以及其在光学元件表面的沉积特性,研究了基于石英晶体微量天平和微纳光纤传感器的真空腔体内有机物在线监测技术.首先测试了不同分子态污染物浓度时石英晶体天平的响应性能,然后采用视角因子等分法对微纳光纤传感器和石英晶体天平进行对比实验,模拟有机污染物在光学表面沉积的特性.实验结果表明,石英晶体天平和微纳光纤测试有机物在光学表面沉积时响应一致,均可用于高功率激光驱动器有机污染物的在线监测;当污染物面密度大于0.5×10-5g/cm2时,微纳光纤传感器有较高精度和响应速度;有机污染物浓度越高,其更容易吸附沉积在光学元件表面.     

GaN高电子迁移率晶体管强电磁脉冲损伤效应与机理

提出了一种新型GaN异质结高电子迁移率晶体管在强电磁脉冲下的二维电热模型,模型引入材料固有的极化效应,高场下电子迁移率退化、载流子雪崩产生效应以及器件自热效应,分析了栅极注入强电磁脉冲情况下器件内部的瞬态响应,对其损伤机理和损伤阈值变化规律进行了研究.结果表明,器件内部温升速率呈现出"快速-缓慢-急剧"的趋势.当器件局部温度足够高时(2000 K),该位置热电子发射与温度升高形成正反馈,导致温度急剧升高直至烧毁.栅极靠近源端的柱面处是由于热积累最易发生熔融烧毁的部位,严重影响器件的特性和可靠性.随着脉宽的增加,损伤功率阈值迅速减小而损伤能量阈值逐渐增大.通过数据拟合得到脉宽τ与损伤功率阈值P和损伤能量阈值E的关系.     

高功率微波作用下高电子迁移率晶体管的损伤机理

本文针对高电子迁移率晶体管在高功率微波注入条件下的损伤过程和机理进行了研究,借助SentaurusTCAD仿真软件建立了晶体管的二维电热模型,并仿真了高功率微波注入下的器件响应.探索了器件内部电流密度、电场强度、温度分布以及端电流随微波作用时间的变化规律.研究结果表明,当幅值为20 V,频率为14.9 GHz的微波信号由栅极注入后,器件正半周电流密度远大于负半周电流密度,而负半周电场强度高于正半周电场.在强电场和大电流的共同作用下,器件内部的升温过程同时发生在信号的正、负半周内.又因栅极下靠近源极侧既是电场最强处,也是电流最密集之处,使得温度峰值出现在该处.最后,对微波信号损伤的高电子迁移率晶体管进行表面形貌失效分析,表明仿真与实验结果符合良好.     

Low-velocity impact damage characterization of carbon fiber reinforced polymer (CFRP) using infrared thermography

Carbon fiber reinforced polymer (CFRP) after low-velocity impact is detected using infrared thermography, and different damages in the impacted composites are analyzed in the thermal maps.The thermal conductivity under pulse stimulation, frictional heating and thermal conductivity under ultrasonic stimulation of CFRP containing low-velocity impact damage are simulated using numerical simulation method. Then, the specimens successively exposed to the low-velocity impact are respectively detected using the pulse infrared thermography and ultrasonic infrared thermography. Through the numerical simulation and experimental investigation, the results obtained show that the combination of the above two detection methods can greatly improve the capability for detecting and evaluating the impact damage in CFRP. Different damages correspond to different infrared thermal images. The delamination damage, matrix cracking and fiber breakage are characterized as the block-shape hot spot, line-shape hot spot, and “

” shape hot spot respectively.     

双重孔隙渗流作用井眼围岩损伤力学模型研究

考虑双重介质建立了井眼围岩力学模型,考虑井眼围岩岩体为孔隙、裂缝双重介质,将围岩区域分为破坏区、损伤区和弹性区,建立双重介质渗流作用下的井壁围岩不同区域的损伤力学计算模型和井眼损伤区域的计算方法,计算结果表明理论计算模型与有限元模拟结果吻合较好.     

A Supramolecular Gel Approach to Minimize the Neural Cell Damage during Cryopreservation Process

The storage method for living cells is one of the major challenges in cell‐based applications. Here, a novel supramolecular gel cryopreservation system (BDTC gel system) is introduced, which can observably increase the neural cell viability during cryopreservation process because this system can (1) confine the ice crystal growth in the porous of BDTC gel system, (2) decrease the amount of ice crystallization and cryopreservation system's freezing point, and (3) reduce the change rates of cell volumes and osmotic shock. In addition, thermoreversible BDTC supramolecular gel is easy to be removed after thawing so it does not hinder the adherence, growth, and proliferation of cells. The results of functionality assessments indicate that BDTC gel system can minimize the neural cell damage during cryopreservation process. This method will be potentially applied in cryopreservation of other cell types, tissues, or organs and will benefit cell therapy, tissue engineering, and organs transplantation.