Identification of mechanisms of toxic action for skin sensitisation using a SMARTS pattern based approach

Skin sensitisation is a key endpoint under REACH as it is costly and its assessment currently has a high dependency on animal testing. In order to reduce both the cost and the numbers of animals tested, it is likely that (quantitative) structure–activity relationships ((Q)SAR) and read-across methods will be utilised as part of intelligent testing strategies. The majority of skin sensitisers elicit their effect via covalent bond formation with skin proteins. These reactions have been understood in terms of well defined nucleophilic–electrophilic reaction chemistry. Thus, a first step in (Q)SAR analysis is the assignment of a chemical's potential mechanism of action enabling it to be placed in an appropriate reactivity domain. The aim of this study was to design a series of SMARTS patterns capable of defining these reactivity domains. This was carried out using a large database of local lymph node assay (LLNA) results that had had potential mechanisms of action assigned to them using expert knowledge. A simple algorithm was written enabling the SMARTS patterns to be used to screen a database of SMILES strings. The SMARTS patterns were then evaluated using a second, smaller, test set of LLNA results which had also had potential mechanisms of action assigned by experts. The results showed that the SMARTS patterns provided an excellent method of identifying potential electrophilic mechanisms. The findings are supported, in part, by molecular orbital calculations which confirm assignment of reactive mechanism of action. The ability to define a chemical's potential reaction mechanism is likely to be of significant benefit to regulators and risk assessors as it enables category formation and subsequent read-across to be performed.     

高压电气设备支架串联体系地震响应半解析法

针对具有集中分布参数柔性节点的多节电瓷型高压电气设备支架串联体系,通过应用分布参数梁振动理论与集中参数通过边界条件的引入,推导出其频率方程,然后通过数值方法求得频率及振型。通过应用Betti定律,推导出具有集中分布参数柔性节点的多节电瓷型高压电气设备支架串联体系振型的正交条件,应用此正交条件对集中参数与分布参数的振动方程解耦,从而得到广义质量及广义荷载,然后通过振型叠加法求解结构的地震响应。最后应用该半解析法与有限元法数值积分法对一330 KV电压互感器支架串联体系地震响应进行分析,分析结果表明,该半解析法求解的地震响应与有限元直接积分法求解的地震响应相一致,从而为具有集中分布参数柔性节点的多节电瓷型高压电气设备支架串联体系的地震响应分析和抗震设计提供了一种新的途径。     

轴辐式枢纽网络系统的关键枢纽设施识别问题研究

作为轴辐式枢纽网络关键因素的节点,尤其是起到中转作用的枢纽节点是网络稳定运行的重要环节。当这些节点被中断时,将对整个网络产生严重的影响。最直接的表现方式即是网络运行成本的急剧上升。因此本文研究如何识别对网络成本具有决定性影响的关键节点。首先,提出枢纽功能性中断问题和模型,并通过禁忌搜索算法进行求解。最后通过中国航空实例验证模型和算法在实际应用中的有效性。结果显示模型和算法能够有效识别出中国航空网络较重要的关键城市以及相对影响较弱的城市。可以为资源有限情况下,中国航空网络中各城市防御设施的合理分级和部署,为重点保护城市的鉴别提供依据和帮助。     

傅里叶变换红外光谱在胃癌淋巴结转移诊断中的应用研究

观察傅里叶变换红外光谱技术无创、原位、快速诊断胃癌淋巴结转移的可行性。联合使用衰减全反射探头及傅里叶变换红外光谱仪测量新鲜离体胃周淋巴结红外光谱,发现每条光谱在吸收波长3 000～1 000 cm-1之间循序出现13条谱带,依据病理检测结果将淋巴结分为转移组及非转移组,比较两组淋巴结红外光谱的峰位和相对峰强等指标结果,最后进行标准统计学分析。36例胃癌患者,共检测淋巴结720枚,其中转移性淋巴结180枚,未转移540枚;与非转移淋巴结相比,转移淋巴结红外光谱有如下特征：(1)与核酸相关的峰强比I_{1 240}/I_{1 460}(p=0.015)和I_{1 080}/I_{1 460}(p=0.034)显著升高,提示转移淋巴结细胞的核酸含量增多;(2)与蛋白相关的I_{1 640}/I_{1 460}(p=0.001)和I_{1 546}/I_{1 460}(p=0.027)峰强比值升高,表明转移淋巴结组织的蛋白质含量明显升高;(3)与脂类相关的I_{2 855}/I_{1 460}和I_{1 740}/I_{1 460}显著降低(p＜0.001),提示癌组织脂类含量相对减少;(4)I_{1 160}/I_{1 460}(p=0.023)显著降低,表明恶性细胞糖类物质的减少。研究结果显示,傅里叶变换红外光谱分析技术有望成为术中原位、在体和快速诊断胃癌淋巴结转移的新方法。     

神经元电生理学等效电路模型及参数特性研究

从考虑神经元轴突朗飞结的电缆模型入手,根据脑磁图和电磁场理论的“场路一致性”原理,讨论了应该从著名的Hodgkin-Huxley一阶静态等效电路扩展为二阶动态电路的合理性和必要性,并通过具体的计算实例进一步研究电生理学材料参数膜电容C 和电感L的频率特性,实验结果表明,有髓神经元纤维轴向信号传递速度越快,其电容和电感值就越小.     

2(1/2)维等离子体粒子模拟分布式并行程序设计

设计了两种粒子模拟的并行算法,并对其进行了比较,基于消息传递环境开发2(1/2)维粒子模拟并行程序,测试并分析了并行性能.粒子模拟算法中,给出了一个初始化粒子三维Maxwell速度分布的算法,并对常用的电磁场的Lindman吸收边界作了推广.最后对激光钻孔问题作了粒子模拟计算,验证了该并行程序.     

非匹配结点的有限单元等参插值方法及其应用研究

针对两零件的异构网格单元结点在接触界面不能相互匹配导致结点属性不能连续过渡和传递的问题,提出非匹配结点的有限单元等参插值方法,通过构建非匹配结点的形函数和修正原结点的形函数,将结点属性值的影响范围限制在可控的局部区域,从而实现两异构网格结点属性在接触界面的连续过渡和传递。通过两个异构的四边形单元网格的结点属性在接触界面的过渡实例和啮合齿轮的接触分析应用,验证了该方法的正确性和有效性。     

Highly Bright and Photostable Li(Gd,Y)F4:Yb,Er/LiGdF4 Core/Shell Upconversion Nanophosphors for Bioimaging Applications

Intense green‐emitting Li(Gd,Y)F₄:Yb,Er/LiGdF₄ core/shell (C/S) upconversion nanophosphors (UCNPs) with a tetragonal bipyramidal morphology are synthesized. The morphology and UC luminescence of the Li(Gd,Y)F₄:Yb,Er UCNPs are significantly affected by the Li precursors, and bright UC green‐emitting Li(Gd,Y)F₄:Yb,Er UCNPs with a tetragonal bipyramidal shape, i.e., UC tetragonal bipyramids (UCTBs), are synthesized using LiOH·H₂O as a Li precursor. A LiGdF₄ shell is grown on the Li(Gd,Y)F₄:Yb,Er UCTBs, and the C/S UCNPs exhibit 4.7 times higher luminescence intensity than core UCTBs. The C/S UCNPs show a high absolute UC quantum yield of 4.6% under excitation with 980 nm near infrared (NIR) light, and the UC luminescence from the C/S UCNPs is stable under continuous irradiation with the 980 nm NIR laser for 1 h. The hydrophobic surfaces of the as‐synthesized C/S UCNPs are modified to hydrophilic surfaces by using poly(acrylic acid) (PAA) for bioimaging applications. They are applied to human cervical adenocarcinoma (HeLa) cell imaging and SK‐MEL‐2 melanoma cell imaging and in vivo imaging, including subcutaneous and intramuscular imaging, and UC luminescence images with high signal‐to‐noise ratio are obtained. Furthermore, sentinel‐lymph‐node imaging is successfully conducted with the PAA‐capped Li(Gd,Y)F₄:Yb,Er/LiGdF₄ C/S UCNPs under illumination with NIR light.     

On Some Classical Methods to Improve Algebraic Curves and Surfaces

First, a modern presentation of the theory of the Halphen transform is given. This method associates to a plane projective curve C, once a general conic has been chosen, another birationally equivalent plane curve, whose singularities are simpler than those of C. Repeating, a curve is obtained whose only singularities are nodes. Next, it is studied how to apply this process to a family of plane curves. With this technique it is possible to transform a given family (with irreducible general member) into one where, generically, the curves are nodal. Finally, it is studied a similar process, called the Halphen–Picard transformation, for surfaces in three-space. By suitably reiterating this procedure, a surface can be transformed into a birationally equivalent one (in the same projective space), such that the sections with planes in a general pencil are, generically, nodal curves.