NMR-based metabolomic comparative analysis between animal models and patients of pancreatic cancer

胰腺导管腺癌(PDAC)是最致命的肿瘤之一，且其早期诊断困难。作为唯一能无创伤性获得活体组织生化信息的技术，活体磁共振波谱（MRS）技术已被欧洲肿瘤学大会推荐为较好的癌症诊断方法。但目前MRS的应用受到信号灵敏度低、分辨率不足的限制。高分辨魔角旋转核磁共振（HR-MASNMR）技术可以大大提高组织样本的检测分辨率和灵敏度，可以作为MRS技术的离体替代技术。本论文工作利用此技术比较分析胰腺癌患者和动物模型的代谢异同点，增加对PDAC的代谢重构的理解，进一步为胰腺癌的临床诊断提供可靠的实验数据。 本论文第一部分，在裸鼠皮下和胰腺组织分别植入Panc-1和BxPC-3细胞株建立相应的皮下植瘤（SX...Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal carcinomas with a difficult early diagnosis. In vivo magnetic resonance spectroscopy (MRS) has been recommended for diagnosis of brain, prostate and breast cancers by the European Cancer Congress (ECCO). However, it is not feasible and favorable for the clinical diagnosis of PDAC due to its low sensitivity and insufficient resolutio...学位：工程硕士院系专业：物理科学与技术学院_工程硕士(电子与通信工程)学号：3332014115283

A Biocompatible Gadolinium(Ⅲ)-Poly(Aspartic Acid-Co-Phenylalanine) for Liver Magnetic Resonance Imaging Contrast Agent

一种新型的以天门冬氨酸-苯丙氨酸共聚物为载体的大分子生物相容性材料(AP-EdA-dOTA-gd)被制备出来作为磁共振成像造影剂.首先合成了天门冬氨酸-苯丙氨酸共聚物,之后利用乙二胺将1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸(dOTA)连接到共聚物上,最后将钆离子通过配位的作用方式连接到dOTA上,最终得到大分子AP-EdA-dOTA-gd.体外溶血性试验表明AP-EdA-dOTA-gd具有较好的血液相容性.在P H=5.5的组织蛋白酶b的磷酸缓冲液中,AP-EdA-dOTA-gd能够降解.APEdA-dOTA-gd的体外弛豫效率(15.95 MMOl–1·l·S–1)为目前临床应用的gd-dOTA(5.59MMOl–1·l·S–1)的2.9倍.大鼠肝脏成像实验结果表明,AP-EdA-dOTA-gd对于肝组织的成像增强对比度为63.5±6.1%远高于gd-dOTA(24.2±2.9%).A new biocompatible gadolinium(III)-macromolecule(AP-EDA-DOTA-Gd) was developed as a magnetic resonance imaging(MRI) contrast agent.Poly(aspartic acid-cophenylalanine) was synthesized, modified via ethylenediamine, conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid(DOTA) and finally chelated gadolinium(III), yielding gadolinium(III)-based macromolecule(AP-EDA-DOTA-Gd).The hemolytic tests showed the hemocompatibility of this gadolinium(III)-based macromolecular conjugate.In vitro, AP-EDA-DOTA-Gd could be degraded, when it was incubated with cathepsin B in phosphate buffered solution(p H = 5.5).The T1-relaxivity(15.95 mmol–1·L·s–1) of AP-EDA-DOTA-Gd was 2.9 times of that(5.59 mmol–1·L·s–1) of the clinical MRI contrast agent(Gd-DOTA) at 1.5 T and 25 ℃.The liver enhancement of AP-EDA-DOTA-Gd was 63.5±6.1% during the maximum enhancement time(50-80 min), which was much better than that of Gd-DOTA(24.2±2.9%, 10-30 min).AP-EDA-DOTA-Gd was expected to be a potential liver MRI contrast agent.TheNationalNaturalScienceFoundationofChina(20975097and21305134

JUNO Sensitivity on Proton Decay p→νˉK+p\to \bar\nu K^+ Searches

The Jiangmen Underground Neutrino Observatory (JUNO) is a large liquid scintillator detector designed to explore many topics in fundamental physics. In this paper, the potential on searching for proton decay in $p\to \bar\nu K^+$ mode with JUNO is investigated.The kaon and its decay particles feature a clear three-fold coincidence signature that results in a high efficiency for identification. Moreover, the excellent energy resolution of JUNO permits to suppress the sizable background caused by other delayed signals. Based on these advantages, the detection efficiency for the proton decay via $p\to \bar\nu K^+$ is 36.9% with a background level of 0.2 events after 10 years of data taking. The estimated sensitivity based on 200 kton-years exposure is $9.6 \times 10^{33}$ years, competitive with the current best limits on the proton lifetime in this channel

JUNO sensitivity on proton decay p → ν K + searches*

The Jiangmen Underground Neutrino Observatory (JUNO) is a large liquid scintillator detector designed to explore many topics in fundamental physics. In this study, the potential of searching for proton decay in the $p\to \bar{\nu} K^+$ mode with JUNO is investigated. The kaon and its decay particles feature a clear three-fold coincidence signature that results in a high efficiency for identification. Moreover, the excellent energy resolution of JUNO permits suppression of the sizable background caused by other delayed signals. Based on these advantages, the detection efficiency for the proton decay via $p\to \bar{\nu} K^+$ is 36.9% ± 4.9% with a background level of $0.2\pm 0.05({\rm syst})\pm$$0.2({\rm stat})$ events after 10 years of data collection. The estimated sensitivity based on 200 kton-years of exposure is $9.6 \times 10^{33}$ years, which is competitive with the current best limits on the proton lifetime in this channel and complements the use of different detection technologies