Novel quinazolin-4-one derivatives as potentiating agents of doxorubicin cytotoxicity

We report the design, synthesis and biological evaluation of 17 novel 8-aryl-2-morpholino-3,4-dihydroquinazoline derivatives based on the standard model of DNA-PK and PI3K inhibitors. Novel compounds are sub-divided into two series where the second series of five derivatives was designed to have a better solubility profile over the first one. A combination of in vitro and in silico techniques suggested a plausible synergistic effect with doxorubicin of the most potent compound 14d on cell proliferation via DNA-PK and poly(ADP-ribose) polymerase-1 (PARP-1) inhibition, while alone having a negligible effect on cell proliferation.     

Monte Carlo-based assessment of the trade-off between spatial resolution,field-of-view and scattered radiation in the variable resolution X-ray CT scanner

ObjectiveThe purpose of this work is to evaluate the impact of optimization of magnification on performance parameters of the variable resolution X-ray (VRX) CT scanner.MethodsA realistic model based on an actual VRX CT scanner was implemented in the GATE Monte Carlo simulation platform. To evaluate the influence of system magnification, spatial resolution, field-of-view (FOV) and scatter-to-primary ratio of the scanner were estimated for both fixed and optimum object magnification at each detector rotation angle. Comparison and inference between these performance parameters were performed angle by angle to determine appropriate object position at each opening half angle.ResultsOptimization of magnification resulted in a trade-off between spatial resolution and FOV of the scanner at opening half angles of 90°–12°, where the spatial resolution increased up to 50% and the scatter-to-primary ratio decreased from 4.8% to 3.8% at a detector angle of about 90° for the same FOV and X-ray energy spectrum. The disadvantage of magnification optimization at these angles is the significant reduction of the FOV (up to 50%). Moreover, magnification optimization was definitely beneficial for opening half angles below 12° improving the spatial resolution from 7.5 cy/mm to 20 cy/mm. Meanwhile, the FOV increased by more than 50% at these angles.ConclusionIt can be concluded that optimization of magnification is essential for opening half angles below 12°. For opening half angles between 90° and 12°, the VRX CT scanner magnification should be set according to the desired spatial resolution and FOV.     

Proton microbeam radiotherapy with scanned pencil-beams – Monte Carlo simulations

Irradiation, delivered by a synchrotron facility, using a set of highly collimated, narrow and parallel photon beams spaced by 1 mm or less, has been termed Microbeam Radiation Therapy (MRT). The tolerance of healthy tissue after MRT was found to be better than after standard broad X-ray beams, together with a more pronounced response of malignant tissue. The microbeam spacing and transverse peak-to-valley dose ratio (PVDR) are considered to be relevant biological MRT parameters. We investigated the MRT concept for proton microbeams, where we expected different depth-dose profiles and PVDR dependences, resulting in skin sparing and homogeneous dose distributions at larger beam depths, due to differences between interactions of proton and photon beams in tissue. Using the FLUKA Monte Carlo code we simulated PVDR distributions for differently spaced 0.1 mm (sigma) pencil-beams of entrance energies 60, 80, 100 and 120 MeV irradiating a cylindrical water phantom with and without a bone layer, representing human head. We calculated PVDR distributions and evaluated uniformity of target irradiation at distal beam ranges of 60–120 MeV microbeams. We also calculated PVDR distributions for a 60 MeV spread-out Bragg peak microbeam configuration. Application of optimised proton MRT in terms of spot size, pencil-beam distribution, entrance beam energy, multiport irradiation, combined with relevant radiobiological investigations, could pave the way for hypofractionation scenarios where tissue sparing at the entrance, better malignant tissue response and better dose conformity of target volume irradiation could be achieved, compared with present proton beam radiotherapy configurations.     

Hypersensitivity symptoms associated with exposure to cellular telephones: no causal link

The hypothesis that there exist hypersensitive persons who perceive subjective symptoms from radiofrequency (RF) fields emitted by hand held mobile phones (cellular phones) was tested using double blind provocation experiments. We also tested whether sensitive subjects are able to determine whether the phone is on or off by sensing RF fields. The study group consisted of 20 volunteers (13 women and 7 men) who reported themselves as being sensitive to cellular phones. The RF exposure sources were one analogue NMT phone (900 MHz) and two digital GSM phones (900 and 1800 MHz). The duration of a test session was 30 min, and three or four sessions were performed in random order for each subject during 1 day. The subjects were asked to report symptoms or sensations as soon as they perceived any abnormal feelings. In addition, the subjects' blood pressure, heart rate, and breathing frequency were monitored every 5 min. The results of the study indicated that various symptoms were reported, and most of them appeared in the head region. However, the number of reported symptoms was higher during sham exposure than during real exposure conditions. In addition, none of the test persons could distinguish real RF exposure from sham exposure. Hence, we conclude that adverse subjective symptoms or sensations, though unquestionably perceived by the test subjects, were not produced by cellular phones.     

夏季栾树群落冠层结构对其环境温湿度的调节作用

为探究栾树群落降温增湿作用与其冠层结构参数的相关性在一天中的变化趋势,于天气晴朗的夏季对北京奥林匹克森林公园栾树群落内部和对照点的温度、相对湿度、群落冠层结构参数进行了铡定.结果表明:栾树群落的郁闭度与叶面积指数、平均叶倾角呈显著相关,且叶面积指数与平均叶倾角呈显著相关;在夏季8:00-18:00,栾树群落可降低空气温度0.43～7.53℃,在12:00左右达到降温最大值,增加相对湿度1％ ～ 22％,且在10:00左右增湿作用最显著,而在18:00-次日8:00降温增湿效果不明显;9:00-12:00,郁闭度和叶面积指数显著影响栾树群落的降温增湿作用;12:00-14:00,仅郁闭度与降温增湿作用显著相关;直到18:00,郁闭度和叶面积指数共同决定了栾树群落的降温增湿作用.因此,影响栾树群落降温增湿作用的冠层结构参数在一天中随着时间的推移发生变化.     

生物信息学辅助定位及延伸辐射诱导未知表达序列标签

研究辐射诱导的基因表达调控对于认识细胞对辐射损伤的应激反应有重要意义.在低剂量辐射诱导新基因RIG1表达序列标签(expression sequence tag,EST)片段的基础上,通过非克隆cDNA文库和RACE(rapid amplification of cDNA end)技术获得了其3′末端.依据实验得到的这两段EST序列所提供的信息,通过生物信息学分析将RIG1基因初步定位在20号染色体.对20号染色体RIG1区基因组序列进行外显子扫描,发现预测的外显子正好与实验得到的EST相吻合.利用预测的外显子设计特异引物,成功地克隆了RIG1基因全长序列.同时,对20号染色体RIG1区的生物信息学分析表明,在RIG1基因的上游存在启动子区,从而确定了RIG1基因的基因组序列.因此,通过生物信息学辅助设计实验,快捷地定位及延伸了未知EST片段RIG1,基本完成了RIG1的全基因、基因组序列及染色体定位研究.     

Detection of microwave radiation of cytochrome CYP102 A1 solution during the enzyme reaction

Microwave radiation at 3.4–4.2 GHz frequency of the cytochrome P450 CYP102 A1 (BM3) solution was registered during the lauric acid hydroxylation reaction. The microwave radiation generation was shown to occur following the addition of electron donor NADPH to a system containing an enzyme and a substrate. The radiation occurs for the enzyme solutions with enzyme concentrations of 10^?8 and 10^?9 М. The microwave radiation effect elicited by the aqueous enzyme solution was observed for the first time. The results obtained can be used to elaborate a new approach to enzyme systems research, including studying of the mechanism of interaction of a functioning enzyme system with microenvironment.     

增强UV—B辐射和CO2复合作用对蚕豆幼苗生长和光合作用的影响

在4.52 kJ*m-2*d-1 UV-BBE的UV-B辐射和700 μmol*mol-1的CO2浓度人工模拟复合处理下,研究了对蚕豆(Vicia faba L.)幼苗的生长和光合作用的影响.结果表明,UV-B辐射单因子明显降低蚕豆幼苗的株高、叶面积和生物量,CO2单因子的作用正好相反,二者的作用程度随着处理时间的延长而增大.UV-B辐射和CO2复合作用对蚕豆幼苗的生长影响不明显.同时,增强的UV-B辐射单因子还使蚕豆幼苗的光合速率、气孔导度和水分利用率下降,CO2单因子的作用也相反,且CO2单因子的促进程度大于UV-B辐射单因子的抑制程度.而在UV-B辐射和CO2复合作用下,蚕豆幼苗的光合作用参数基本与对照同步.分析认为,UV-B辐射和CO2复合作用对蚕豆幼苗的影响是一种拮抗作用.