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中文摘要
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描述(由申请者提供):儿童医院奥克兰研究所(CHORI)是一个独立的研究所,是奥克兰儿童医院和研究中心的研究机构。根据美国国立卫生研究院(NIH)的资助,我们的研究项目是全国顶级儿科研究部门之一。研究主要集中在健康和疾病中的脂类和脂蛋白。该提案要求提供资金购买安捷伦6490三重四极杆质谱仪(MS),该质谱仪配备1290 Infinity四元液相色谱(LC)系统。这种LC/三重四极杆MS组合系统将取代正在迅速接近其使用寿命的过时的LC/MS系统。LC/MS仪器是涉及代谢组学、疾病和炎症生物标记物的分析、纳米技术药物输送、脂类定量和脂类结合蛋白分析等众多研究项目的关键资源。该仪器将用于定量目标分子,包括鞘脂、维生素D、氨基酸代谢物、硫化和氧化蛋白、磷脂、氧化甾醇和他汀类药物的代谢物。该仪器将支持代表CHORI主要科学中心的12个主要用户,包括癌症研究、镰状细胞疾病和地中海贫血、营养和新陈代谢、免疫学和疫苗开发、肥胖、心血管疾病和糖尿病的预防以及遗传学。6490采用iFunnel技术,能够在传统的高效液相色谱流速下实现齐托莫尔的检测极限。6490仪器为药物化合物、微量营养素、临床样本、药物、代谢物和生物标志物的分析提供了无与伦比的灵敏度。6490 QQQ具有1毫秒的驻留时间和无碰撞单元串扰,与1290超高压/高性能LC(UHPLC)系统完美结合,可实现快速样品分析,即使在1秒宽的UPHLC峰上也可实现可靠的峰积分和定量。对于非常复杂的样品混合物,6490 QQQ允许动态多反应监测(MRM)方法,每种方法最多可转换4000次,极性切换仅需30毫秒。安捷伦6490 QQQ是一款多功能、最先进的仪器,具有高灵敏度、线性度、动态范围、重复性和坚固性,代表了我们的用户群非常熟悉的一项技术。因此,我们从多个相互竞争的MS系统中选择了该系统作为最佳系统。新的LC/MS系统将大大推进当前的项目,并增加CHORI的共享设备池。CHORI的科学家擅长LC/MS;我们在开创MS技术和维护活跃的MS核心设施方面拥有长期的经验。我们还招募了外部科学顾问,以进一步确保该仪器得到正确利用,并使最大数量的CHORI调查人员以及可能通过合作研究努力的外部调查人员的创新研究能力达到最高水平。
英文摘要
DESCRIPTION (provided by applicant): Children's Hospital Oakland Research Institute (CHORI) is a free-standing institute that serves as the research arm of the Children's Hospital & Research Center Oakland. Our research program is among the top pediatric research departments in the nation with regard to funding from the National Institutes of Health (NIH). Research is heavily focused on lipids and lipoproteins in health and disease. This proposal requests funds to purchase an Agilent 6490 Triple Quadrupole mass spectrometer (MS) equipped with 1290 Infinity Quaternary liquid chromatography (LC) system. This LC/triple quadrupole MS combined system would replace an out-of- date LC/MS system that is rapidly approaching the end of its lifespan. LC/MS instrumentation is a critical resource for a large and diverse array of research projects involving metabolomics, analysis of biomarkers of disease and inflammation, drug delivery using nanotechnology, lipid quantitation, and analysis of lipid-binding proteins. The instrument would be used to quantify target molecules including sphingolipids, vitamin D, amino acid metabolites, thiolated and oxidized proteins, phospholipids, oxysterols and metabolites of statin drugs. Twelve major users representing a cross-section of CHORI's major scientific centers, including Cancer Research; Sickle Cell Disease & Thalassemia; Nutrition & Metabolism; Immunology & Vaccine Development; Prevention of Obesity, Cardiovascular Disease & Diabetes; and Genetics will be supported by the instrument. The 6490, with iFunnel Technology, enables zeptomole detection limits at conventional HPLC flow rates. The 6490 instrument provides unsurpassed sensitivity for the analysis of pharmaceutical compounds, trace-level nutrients, clinical samples, drugs, metabolites, and biomarkers. With 1 millisecond dwell times and no collision cell cross talk, the 6490 QqQ is ideally coupled with the 1290 ultra high-pressure/performance LC (UHPLC) system for fast sample analyses, allowing reliable peak integration and quantitation across even 1 second-wide UPHLC peaks. For very complex sample mixtures, the 6490 QqQ allows dynamic multiple reaction monitoring (MRM) methods with up to 4,000 transitions per method and polarity switching in as little as 30 milliseconds. The Agilent 6490 QqQ is a versatile, state-of-the-art instrument with high sensitivity, linearity, dynamic range, reproducibility and robustness and which represents a technology with which our user group is highly familiar. Thus, we have chosen this as the optimal system from a number of competing MS systems. The new LC/MS system will significantly advance the current projects and add to the pool of shared equipment at CHORI. CHORI's scientists are adept at LC/MS; we have long-standing experience in pioneering MS technology and maintaining an active MS Core Facility. We have also recruited external scientific advisors to further insure the instrument is utilized properly and to the highet capacity possible for innovative research by the largest number of CHORI investigators and potentially by external investigators through collaborative research endeavors.
期刊论文(3)
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会议论文
Efficacy of AAV9-mediated SGPL1 gene transfer in a mouse model of S1P lyase insufficiency syndrome.
AAV9 介导的 SGPL1 基因转移在 S1P 裂解酶不足综合征小鼠模型中的功效。
DOI: 10.1172/jci.insight.145936
发表时间: 2021
期刊: JCI insight
影响因子: 8
作者: [Zhao,Piming, Tassew,GizachewB, Lee,JoannaY, Oskouian,Babak, Muñoz,DeniseP, Hodgin,JeffreyB, Watson,GordonL, Tang,Felicia, Wang,Jen-Yeu, Luo,Jinghui, Yang,Yingbao, King,Sarah, Krauss,RonaldM, Keller,Nancy, Saba,JulieD]
通讯作者: Saba,JulieD
DOI: 10.1371/journal.pone.0240437
发表时间: 2020
期刊: PloS one
影响因子: 3.7
作者: [Mietus-Snyder M, Narayanan N, Krauss RM, Laine-Graves K, McCann JC, Shigenaga MK, McHugh TH, Ames BN, Suh JH]
通讯作者: Suh JH
Endogenous and Dietary Sphingolipids as Modulators in Inflammatory Bowel Disease
S1P lyase in colon cancer
海外基金