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中文摘要
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描述(由申请人提供):儿童医院奥克兰研究所(CHORI)是一个独立的研究所,作为儿童医院和研究中心奥克兰的研究部门。我们的研究项目是美国国家卫生研究院(NIH)资助的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质和脂蛋白。本提案要求提供资金,用于购买配备1290 Infinity四元液相色谱(LC)系统的Agilent 6490三重四极杆质谱仪(MS)。这种LC/三重四极杆MS组合系统将取代过时的LC/MS系统,该系统正在迅速接近其使用寿命的终点。LC/MS仪器是一个重要的资源,为一个大型和多样化的研究项目,涉及代谢组学,疾病和炎症的生物标志物的分析,药物输送使用纳米技术,脂质定量和脂质结合蛋白的分析。该仪器将用于定量靶分子,包括鞘脂、维生素D、氨基酸代谢物、硫醇化和氧化蛋白质、磷脂、氧化固醇和他汀类药物的代谢物。该仪器将为代表CHORI主要科学中心的12个主要用户提供支持,包括癌症研究;镰状细胞病和地中海贫血;营养与代谢;免疫学和疫苗开发;预防肥胖,心血管疾病和糖尿病;以及遗传学。采用iFunnel技术的6490可在常规HPLC流速下实现zeptomole检测限。6490仪器为药物化合物、微量营养素、临床样品、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的停留时间为1毫秒,无碰撞池串扰,可与1290超高压/高性能LC(UHPLC)系统完美结合,用于快速样品分析,即使是1秒宽的UPHLC峰也能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支持动态多反应监测(MRM)方法,每种方法最多可进行4,000次跃迁,极性切换只需30毫秒。Agilent 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、再现性和鲁棒性,代表了我们用户群非常熟悉的技术。因此,我们从许多竞争的MS系统中选择了这一系统作为最佳系统。新的LC/MS系统将大大推进目前的项目,并增加CHORI的共享设备池。CHORI的科学家擅长LC/MS;我们在开拓MS技术和维护活跃的MS核心设施方面拥有长期的经验。我们还聘请了外部科学顾问,以进一步确保该仪器得到适当利用,并通过合作研究努力,由最多的CHORI研究人员和潜在的外部研究人员进行创新研究。
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