现代NMR技术在生物医学中的应用－－稀土对大鼠代谢产物的影响及磁共振造影剂性质的研究

近年来，随着脉冲傅里叶变换核磁共振波谱仪灵敏度的提高及计算机技术的进步，使NMR技术在生物领域的应用有了飞速的发展。论文应用NMR技术研究了稀土化合物（硝酸镧）对大鼠体内代谢产物的影响。对Wistar种大鼠按不同剂量给药（灌胃和腹腔注射两种方式）后的尿液和血清中的代谢物质的~1H NMR谱数据进行研究，并结合血清、尿液中生化指标的检测结果，指出稀土作用后大鼠肾脏的肾小管及肝脏线粒体均受到一定程度的损害，随稀土摄入量的增多，损害程度越严重。并提出代谢物中尿素、Suc、Kg、Cit、DMA、DMG、TMAO和氨基酸等可以作为肾脏受损伤的NMR markers，而乙醇、Lac和Tau可作为肝脏受损伤的NMR markers。实验中最小剂量为0.05 mg La(NO_3)_3/kg体重，仍有机体受损的NMR信号，说明稀土的安全剂量小于这一数值。在临床磁共振成像中，造影剂是医学诊断中的一种重要辅助试剂。本文采用NMR水弛豫分析法研究了GdDTPA及Gd(cycle-DTPA-1,2-PN)、Gd(DTPA－BIN)在水溶液和BSA溶液中的弛豫性质，为研究顺磁性金属配合物与蛋白质间相互作用情况提供了有效方法；对配体cycle-DTPA-1,2-pn、DTPA－BIN做了~1H NMR滴定研究，得出其质子解离过程和解离常数，并采用半经验量化计算方法计算了两种配体的质子化过程，得到了与~1H NMR滴定一致的结果。结果表明将NMR实验和量化计算方法结合，是考察复杂配体热力学稳定性的有效方法。

METASTABLE DEFECT IN AMORPHOUS-SILICON SOLAR-CELLS INVESTIGATED BY JUNCTION RECOVERY TECHNIQUE

The effect of metastable defects caused by light soaking and carrier injection on the transport of carriers in undoped a-Si:H has been investigated by a junction recovery technique. The experiments show that after light soaking or carrier injection the product of mu-p-tau-p decreases, but no detectable change in the distribution of shallow valence band tail states was found.

ON THE RATE-EQUATIONS OF SEMICONDUCTOR-LASERS FOR MEASURING SPONTANEOUS EMISSION FACTOR

The rate equations used for measuring spontaneous emission factor beta is examined through the comparison of numerical results, The results show that beta obtained by using total spontaneous emission rate R(sp) = N/tau sp is about double of that using R(sp) = BN2, The magnitude difference between the measured beta and that predicted by classical theory [8] will disappear by using more reasonable R(sp) = BN2. The results also show that the magnitude of beta may be underestimated by ignoring the nonradiative recombination rates.

Optical properties of AIInGaN quaternary alloys

Carrier recombination dynamics in AlInGaN alloy has been studied by photoluminescence (PL) and time-resolved photoluminescence (TRPL). The fast redshift of PL peak energy is observed and well fitted by a physical model considering the thermal activation and transfer processes. This result provides evidence for the exciton localization in the quantum dot (QD)-like potentials in our AlInGaN alloy. The TRPL signals are found to be described by a stretched exponential function of exp[(-t/tau)(beta)], indicating the presence of a significant disorder in the material. The disorder is attributed to a randomly distributed quantum dots or clusters caused by indium fluctuations. By studying the dependence of the dispersive exponent 8 on the temperature and emission energy, we suggest that the exciton hopping dominate the diffusion of carriers localized in the disordered quantum dots. Furthermore, the localized states are found to have OD density of states up to 250 K, since the radiative lifetime remains almost unchanged with increasing temperature.

Small-scale turbulent fluctuations beyond Taylor's frozen-flow hypothesis

The space-time cross-correlation function C-T(r, tau) of local temperature fluctuations in turbulent Rayleigh-Benard convection is obtained from simultaneous two-point time series measurements. The obtained C-T(r, tau) is found to have the scaling form C-T(r(E), 0) with r(E)=[(r-U tau)(2)+ V-2 tau(2)](1/2), where U and V are two characteristic velocities associated with the mean and rms velocities of the flow. The experiment verifies the theory and demonstrates its applications to a class of turbulent flows in which the requirement of Taylor's frozen flow hypothesis is not met.

毛蕊异黄酮类似物的合成及其对JAK/STAT信号途径调控的构效关系研究

干扰素（IFNs）是最早发现的具有广泛用途的一类细胞因子，IFN-α通过JAK/STAT信号途径调控机体一系列生理和病理反应。至今尚未发现类干扰素的小分子。我们前期研究发现天然产物毛蕊异黄酮可激活干扰素诱导的JAK/STAT信号途径。为发现类干扰素小分子、获得小分子探针，本课题拟建立成熟的JAK/STAT信号途径的筛选模型，合成毛蕊异黄酮及其类似物，研究这些化合物的构效关系，进而尝试通过共价键标记生物素或香豆素来直接研究它们与相关受体的作用。 从异香草醛出发经7步合成反应得到了毛蕊异黄酮。采用平行合成策略得到异黄酮类化合物；采用分支式合成策略，以取代苯乙酸作为合成砌块，获得具有与异黄酮类似结构的香豆素、3-芳基喹诺酮。与分离得到的黄酮类化合物，构建了一个包括异黄酮、黄酮、香豆素、3-芳基喹诺酮在内的化合物库。 建立了包含IFN-α刺激反应元件 (ISRE)的荧光素酶报告基因体系，通过筛选化合物库中的化合物，发现异黄酮骨架为激活JAK/STAT信号途径必须结构、毛蕊异黄酮7-位酚羟基被取代后活性丧失。根据以上结果，对毛蕊异黄酮3′-位标记物的合成进行了初步尝试。 发现山茱萸科植物青荚叶(Helwingia japonica (Thunb.) Dietr.)有抑制蛋白酪氨酸磷酸酯酶1B（PTP1B）的活性。从其地上部分95%乙醇提取物的乙酸乙酯部分分离得到5个化合物,应用波谱方法及与已知品对照的手段鉴定它们为p-menth-2-en-1β, 4β, 8-triol (Z-1)、blumenol A (Z-2)、2′,3′,4′,5′,6′-五羟基查尔酮(Z-3)、洋芹素7-O-β-D-吡喃葡萄糖苷(Z-4)、木犀草素7-O-β-D-吡喃葡萄糖苷(Z-5). Interferons (IFNs) are one kind of cytokines with broad functions. IFN-α mediates series physiological and pathological changes of human body via JAK/STAT pathway. Untill now, no IFNs-like small molecules are discovered. In our preliminary experiment, the natural product calycosin has been observed to activate JAK/STAT pathway. Therefore, we establish a luciferase reporter gene system and synthesize calycosin and its analogues to reveal their structure-activity relationship (SAR). Besides, in order to prove that calycosin activates JAK/STAT pathway through IFN receptor, we attempted to tag it with biotin or coumarin by covalent bonding. Calycosin was synthesized from isovanillin via seven steps. Other isoflavones were obtained by parallel synthesis; coumarins and quinolones were prepared through divergent synthesis, using substituted phenylacetic acids as building blocks. Combing with natural flavones, a small molecule library was established. A luciferase reporter gene system, consisting of 5 copies of the ISRE (interferon-stimulated response element), was used for screening of small molecules from that library. We found that the core-structure of isoflavone was necessary, and if the 7-OH is substituted, the activity slumps. According to our observation, we tried to tag biotin or coumarin at 3′-OH of calycosin. The 95% ethanol extract of the aerial parts of Helwingia japonica (Thunb.) Dietr. showed protein tyrosine phosphatase 1B (PTP1B) inhibitory activity. Five compounds were isolated. On the basis of spectral data or by comparison with authentic samples, they were identified as p-menth-2-en-1β,4β,8-triol (1), blumenol A (2), 2′,3′,4′,5′,6′-pentahydroxychalcone (3), apigenin 7-O-β-D-glucopyranoside (4), and luteolin 7-O-β-D-glucopyranoside (5).

Alterations of immune functions induced by 12C6+ion irradiation in mice

Purpose: To estimate the biological risks to the immune system of the type of space radiation, 12C6+, encountered by cosmonauts during long-term travel in space. Materials and methods: The Kun-Ming strain mice were whole-body irradiated by 12C6+ ion with 0, 0.01, 0.05, 0.075, 0.2, 0.3, 0.5, 0.75, 1 or 2 Gy, at a dose rate of 1 Gy/min. At 35 days after irradiation, the thymus and spleen weights were measured, the natural killer (NK) cells activity of spleen was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT), and the interferon-gamma (IFN-gamma) levels in serum and thymus were detected with enzyme-linked immunosorbent assays (ELISA). Results: The results showed that the thymus weight, IFN-gamma levels in serum and the activity of splenic NK-cells had significantly increased at a dose of 0.05 Gy. With further dose increase, the weight of spleen continued to increase but the weight of thymus, IFN-gamma level and NK-cells activity declined. Conclusions: These results suggest that the dose of 0.05 Gy irradiation has a stimulatory effect on mouse immunity; this effect declined with increasing dose.

Probing the medium effect and isospin dependence of the in-medium nucleon-nucleon cross section in heavy ion collisions

Probing in-medium nucleon-nucleon (NN) cross section sigma(1)(NN)(alpha) in heavy ion collisions has been investigated by means of the isospin-dependent quantum molecular dynamics (IQMD) with the isospin- and momentum- dependent interaction (IMDI(tau)). It is found that there are the very obvious medium effect and the sensitive isospin- dependence of nuclear stopping R on the in-medium NN cross section sigma(1)(NN)(alpha) in the nuclear reactions induced by halo-neutron projectile and the same-mass stable projectile. However, R induced by the neutron-halo projectile is obviously lower than that induced by the corresponding stable projectile. In particular, there is a very obvious dependence of R on the medium effect of sigma(1)(NN)(alpha) in the whole beam energy region for the above two kinds of projectiles. Therefore, the comparison between the results of R's in the reactions induced by the neutron-halo projectile and the corresponding same-mass stable projectile is a more favourable probe for extracting the information of sigma(1)(NN)(alpha) because of adding a new judgement.

Power law behavior of the isotope yield distributions in the multifragmentation regime of heavy ion reactions

Isotope yield distributions in the multifragmentation regime were studied with high-quality isotope identification, focusing on the intermediate mass fragments (IMFs) produced in semiviolent collisions. The yields were analyzed within the framework of a modified Fisher model. Using the ratio of the mass-dependent symmetry energy coefficient relative to the temperature, a(sym)/T, extracted in previous work and that of the pairing term, a(p)/T, extracted from this work, and assuming that both reflect secondary decay processes, the experimentally observed isotope yields were corrected for these effects. For a given I = N - Z value, the corrected yields of isotopes relative to the yield of C-12 show a power law distribution Y (N, Z)/Y(C-12) similar to A(-tau) in the mass range 1 <= A <= 30, and the distributions are almost identical for the different reactions studied. The observed power law distributions change systematically when I of the isotopes changes and the extracted tau value decreases from 3.9 to 1.0 as I increases from -1 to 3. These observations are well reproduced by a simple deexcitation model, with which the power law distribution of the primary isotopes is determined to be tau(prim) = 2.4 +/- 0.2, suggesting that the disassembling system at the time of the fragment formation is indeed at, or very near, the critical point.

Influence of Hypericum perforatum Extract on Piglet Infected with Porcine Respiratory and Reproductive Syndrome Virus

To study the influence of Hypericum perforatum extract (HPE) on piglets infected with porcine respiratory and reproductive syndrome virus (PRRSV), enzyme-labeled immunosorbent assay (ELISA) and cytopathic effect (CPE) were used to determine in vitro whether HPE could induce swine pulmonary alveolar macrophages (PAMs) to secrete IFN-gamma, and whether PRRSV titers in PAMs were affected by the levels of HPE-induced IFN-gamma. HPE (200 mg kg(-1)) was administrated by oral gavage to piglets infected with the PRRSV in vivo to observe whether HPE affected the viremia, lung viral titers, and weight gain of piglets infected with PRRSV. The results showed that HPE was capable of inducing PAMs to produce IFN-gamma in a dose dependent manner and HPE pretreatment was capable of significantly reducing PRRSV viral titers in PAMs (P<0.01). Administration of HPE to the PRRSV-infected animals significantly (P<0.05) reduced viremia over time as compared with the PRRSV-infected animals. But there was not significant decrease in lung viral titers at day 21 post-infection between the HPE-treated animals and the PRRSV-infected control piglets. There were no significant differences in weight gain over time among the HPE-treatment animals, the normal control, and the HPE control animals. The PRRSV-infected animals caused significant (P<0.01) growth retardation as compared with the HPE controls and the normal piglets. It suggested that HPE might be an effective novel therapeutic approach to diminish the PRRSV-induced disease in swine.

Early effects of low dose C-12(6+) ion or X-ray irradiation on human peripheral blood lymphocytes

The aim of this study was to estimate the acute effects of low dose C-12(6+) ions or X-ray radiation on human immune function. The human peripheral blood lymphocytes (HPBL) of seven healthy donors were exposed to 0.05 Gy C-12(6+) ions or X-ray radiation and cell responses were measured at 24 h after exposure. The cytotoxic activities of HPBL were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT); the percentages of T and NK cells subsets were detected by flow cytometry; mRNA expression of interleukin (IL)-2, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma were examined by real time quantitative RT-PCR (qRT-PCR); and these cytokines protein levels in supematant of cultured cells were assayed by enzyme-linked immunosorbent assays (ELISA). The results showed that the cytotoxic activity of HPBL, mRNA expression of IL-2, IFN-gamma and TNF-alpha in HPBL and their protein levels in supernatant were significantly increased at 24 h after exposure to 0.05 Gy C-12(6+) ions radiation and the effects were stronger than observed for X-ray exposure. However, there was no significant change in the percentage of T and NK cells subsets of HPBL. These results suggested that 0.05 Gy high linear energy transfer (LET) C-12(6+) radiation was a more effective approach to host immune enhancement than that of low LET X-ray. We conclude that cytokines production might be used as sensitive indicators of acute response to LDL (C) 2009 COSPAR. Published by Elsevier Ltd. All rights reserved.

低剂量12C6+辐射对小鼠免疫系统损伤和抗氧化剂氮乙酰半胱氨酸的保护作用研究

实验目的：随着科技的发展，人类活动范围已经逐渐向外太空扩展，对于人类太空探索的最大威胁是太空中的各种粒子辐射。这些辐射包括太阳辐射（质子和电子）和银河辐射（质子占85%，氦离子占14%，重离子占1%）。众所周知，重离子与常规X和γ射线相比有较高的传能线密度（linear energy transfer, LET）和相对生物学效应（relative biological effectiveness, RBE），对机体组织和器官有较强的影响。放射治疗是肿瘤治疗的重要手段之一，由于肿瘤细胞的异质性，其对放、化疗的反应相差悬殊。本研究的目的是： 1评估辐射对健康机体产生的生物学风险； 2研究抗氧化剂氮乙酰半胱氨酸（NAC）对机体辐射损伤的保护作用 3不同肿瘤细胞辐射敏感性的差异。实验方法： 1 X射线或12C6+离子对小鼠进行不同剂量的全身辐射。NAC处理组小鼠在照射前1小时腹腔注射200mg/kg的NAC，对照组注射等体积的生理盐水。照射后不同时间点取样，利用流式细胞仪检测小鼠免疫细胞周期和凋亡情况，单细胞电泳检测淋巴细胞DNA损伤，MTT法（3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide）检测脾脏NK（natural killer，NK）细胞活性，微核法检测淋巴细胞染色体损伤情况，小鼠体内干扰素－γ（Interferon-γ，IFN-γ）由ELISA方法得到，小鼠血清中超氧化物岐化酶(Surperoxide dismutase SOD）由分光光度法测定，并观察胸腺和脾脏指数变化。 2 不同剂量X射线和12C6+离子辐射人肺腺癌细胞H1299和A549，用细胞克隆法检测照射后细胞存活曲线，流式细胞仪检测细胞周期和凋亡，Western-blot 检测A549 细胞P53蛋白表达。 结果： 1小鼠外周血淋巴细胞、胸腺细胞和脾脏淋巴细胞周期随着X射线照射剂量的增大而被阻滞在了G0/G1期，相同剂量的12C6+离子辐射时外周血淋巴细胞周期被阻滞在S期，分次连续X射线照射时，外周血淋巴细胞周期随着累积剂量的增加被阻滞在G2/M期；细胞凋亡比例随着照射剂量的增加而增加。小鼠血清中IFN-γ水平和脾脏中NK细胞活性在重离子照射剂量为0.05Gy时有显著增加，脾脏NK细胞活性随着照射剂量的增加而减弱。 2重离子照射后，小鼠淋巴细胞DNA和染色体的损伤随辐射剂量和照射后时间的延长而加剧。脾脏NK细胞活性在照射后各个时间点减弱，血清中IFN-γ水平和SOD酶活性随着重离子照射剂量的增加而降低。预防性给予NAC，12C6+离子辐射对淋巴细胞DNA和染色体所致损伤，胸腺细胞周期和凋亡，脾脏NK细胞活性，血清中IFN-γ的水平和SOD酶的活性的损伤与盐水组比较均有显著改善。 3 X射线照射对肺腺癌H1299细胞周期和凋亡率未产生明显影响，重离子照射后随着照射剂量的增加细胞周期被阻滞在G2/M期，细胞凋亡率也呈剂量依赖性；X射线和12C6+离子照射A549细胞后，细胞周期均被阻滞在G2/M期，凋亡率剂量依赖性增加。A549细胞P53蛋白的表达水平随着重离子照射剂量的增加而增加。结论： 1重离子辐射造成细胞DNA和染色体损伤随着照射剂量的增加和照射后时间的延长而增加，比X射线辐射损伤复杂和难以修复，产生这种现象的机理为辐射导致活性氧分子簇的产生，细胞因子和与细胞氧化反应有关的酶活性的变化，同时这种损伤对胸腺细胞周期、凋亡和胸腺、脾脏指数以及机体免疫系统都有影响；低剂量重离子辐射（0.05Gy）对小鼠机体的免疫力有刺激作用，机体免疫能力随着照射剂量增加和照射后时间的推移而减弱，不同的免疫器官对辐射的敏感性也不同； 2 200mg/kg 的NAC对辐射所致小鼠免疫系统损伤有很好的保护作用； 3 肺腺癌细胞H1299比同系A549具有较强的辐射敏感性，A549细胞凋亡的增加与P53蛋白表达水平升高有关

Dynamics of excited OCS investigated by resonance-enhanced multiphoton ionization

The predissociation decay behavior of molecule carbonyl sulfide (OCS) has been investigated by resonance-enhanced multiphoton ionization spectroscopy using the pump-probe technique of dichroic femtosecond lasers in real time. The lifetime of excited OCS around 74 720 cm(-1) by two-photon absorption of 268 nm, corresponding to upsilon(1)=1 of the Rydberg state [(2)Pi(1/2)]4ppi((1)Sigma(+)), is directly determined to be tau(D)=1071+/-11 fs. This picosecond decay process indicates that the excited state is predissociative. The temporal information of dissociation enriches the knowledge of the potential-energy surface of the associative excited state.

Stability shear stress and equilibrium cross-sectional geometry of sheltered tidal channels

This study relates tidal channel cross-sectional area (A) to peak spring discharge (Q) via a physical mechanism, namely the stability shear stress ( tau sub(S)) just necessary to maintain a zero gradient in net along-channel sediment transport. It is assumed that if bed shear stress ( tau ) is greater than tau sub(S), net erosion will occur, increasing A, and reducing tau similar to (Q/A) super(2) back toward tau sub(S). If tau < tau sub(S) there will be net deposition, reducing A and increasing tau toward tau sub(S). A survey of the literature allows estimates of Q and A at 242 sections in 26 separate sheltered tidal systems. Assuming a single value of tau sub(S) characterizes the entire length of a given tidal channel, it is predicted that along-channel geometry will follow the relation Ah sub(R) super(1) super(/) super(6) similar to Q. Along-channel regressions of the form Ah sub(R) super(1) super(/) super(6) similar to Q super( beta ) give a mean observed value for beta of 1.00 plus or minus 0.06, which is consistent with this concept. Results indicate that a lower bound on tau sub(S) (and an upper bound on A) for stable channels is provided by the critical shear stress ( tau sub(C)) just capable of initiating sediment motion. Observed tau sub(S) is found to vary among all systems as a function of spring tidal range (R sub(sp)) according to the relation tau sub(S) approximately 2.3 R sub(sp) super(0.79) tau sub(C). Observed deviations from uniform tau sub(S) along individual channels are associated with along-channel variation in the direction of maximum discharge (i.e., flood-versus ebb-dominance).

The dewetting dynamics of the polymer thin film by solvent annealing

The slippage effect of the polymer chains is investigated in the dewetting process of the polymer solution film. The solvent-induced dewetting is used in our experiments to study the dynamics of hole growth in the dewetting process of the polymer solution film. Our results show that in the case of the low molecular weight polystyrene (PS) film, the slippage effect of the polymer chains is not displayed and the radius of the holes is R similar to exp(t/tau); in the case of the higher molecular weight PS film, the slippage effect of the polymer chain is not valid in the case of the thin film and that is valid in the case of the thick film, and the dynamic process of hole growth divides into three stages (R similar to t, and then R similar to t(x) (2/3 < x < 1), finally, R similar to t). Besides, the solvent and substrate properties also influence the dewetting dynamics of the polymer solution film.