University of Warwick - Equipment Account

华威大学 - 设备帐户

• 批准号: EP/K011618/1
• 负责人: Caroline Meyer
• 金额: $ 978.26万
• 依托单位: University of Warwick
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FK011618%2F1
• 关键词: University; Warwick; Equipment; Account

This proposal is to design, build, validate and exploit the features of a new Raman spectrometer that will collect Raman, Raman Optical Acitity (ROA), and Raman Linear Difference (RLD) spectra. ROA is well-established, but comparatively under-used as a means of probing secondary and tertiary structures of proteins and other biomacromolecules. RLD is a newly invented technique (Rodger et al. Analytical Chemistry, 2012) that can be used to give relative orientations of subunits of complex molecular assemblies. Raman spectroscopy provides access to the wealth of information available in vibrational spectroscopy without the challenges which confront infra red absorbance where water signals dominate. This project builds on the investigators' acknowledged expertise in developing novel spectroscopies for the study of biomolecules. It follows their success (measured by the increase in publications and linear dichroism (LD) instrument sales triggered by their work over the past 10 years) in making UV-LD an available technology. The motivation for developing a new form of spectroscopy is that the structures and arrangements of molecules, including sugars and lipids, that play key roles in the structures and functions of biomacromolecules are invisible to many techniques. Further, existing techniques do not provide sufficient information for many applications. Atomic-level techniques including crystallography and NMR are not well-suited to large irregular molecular assemblies where the structures of both the macromolecule and surrounding molecules contribute to the function of the components. Circular dichroism, which is currently the most widely used method for determining solution-phase secondary structures of proteins, has comparatively low information content and usable concentration ranges. Thus we need alternative approaches to provide the required information. We believe different forms of Raman spectroscopy can contribute to addressing these issues, but the required instrumentation has not yet been invented. The main applications of the instrument in the lifetime of the funding will be:1. Understand atomic-level structures and functions of biomacromolecules in cellular assemblies which is essential if we wish to control biological processes, such as cell division, for disease control and biotechnology applications. 2. Enhance efficiency in the development and production of pharmaceutical (small molecule) and biopharmaceutical (proteins, nucleic acids, viruses, bacteria) products by improving the approach to Process Analytical Technology (PAT) and helping to enable 'Quality by Design' (QbD). The hypothesis underlying QbD for pharmaceutical drugs, is that quality in production can be planned, and that most quality crises and problems relate to the way in which quality was (or was not) planned in the first place. QbD operates fairly effectively in the pharmaceutical industry. Regulators such as the European Medicines Agency are looking to expand the concept and process of QbD from pharmaceutical products to biopharmaceuticals. However, the analytical methodologies that are possibly sufficient for pharmaceuticals are clearly not adequate for biopharmaceuticals. New challenges are also being brought by the emerging 'Biosimilars' market: most simply, what is 'highly similar'? A wide user community will be established. The applications of the first users will be mainly with proteins, protein fibres, protein assemblies including bacteriophage, and membrane systems.

该建议是设计，构建，验证和利用新的拉曼光谱仪的特征，该功能将收集拉曼，拉曼光学偏见（ROA）和拉曼线性差异（RLD）光谱。 ROA已建立良好，但相对较少的用作探测蛋白质和其他生物百素分子的二级和三级结构的一种手段。 RLD是一种新发明的技术（Rodger等人分析化学，2012年），可用于给出复杂分子组件亚基的相对取向。拉曼光谱法提供了振动光谱中可用的信息的访问，而没有面对水信号占主导地位的红色吸光度的挑战。该项目基于研究人员在开发新的光谱镜研究研究生物分子研究方面的专业知识。它遵循了他们的成功（通过在过去10年中由其工作触发的出版物和线性二色性（LD）仪器销售的增加来衡量），使UV-LD成为可用的技术。开发新的光谱形式的动机是，包括糖和脂质在内的分子的结构和排列在生物乳清分子的结构和功能中起着关键作用，这对于许多技术都是看不见的。此外，现有技术没有为许多应用程序提供足够的信息。包括晶体学和NMR在内的原子级技术不适合大型不规则分子组件，在大型分子组件中，大分子及周围分子的结构都促进了组件的功能。循环二色性是目前使用的最广泛使用的方法来确定蛋白质的溶液 - 二级结构，其信息含量相对较低，可用浓度范围相对较低。因此，我们需要替代方法来提供所需的信息。我们认为，不同形式的拉曼光谱法可以有助于解决这些问题，但是尚未发明所需的仪器。该仪器在资金一生中的主要应用是：1。了解细胞组件中生物ac纤维分子的原子水平结构和功能，这是我们希望控制疾病控制和生物技术应用等生物学过程（例如细胞分裂）至关重要的。 2。通过改善处理分析技术（PAT）的方法并帮助“通过设计质量”（QBD），提高了药物（小分子）和生物药物（蛋白质，核酸，病毒，细菌）产品的效率（蛋白质，核酸，病毒，细菌）。药物的基础QBD的假设是可以计划生产质量，并且大多数质量危机和问题首先与质量（或未）计划的方式有关。 QBD在制药行业中相当有效地运作。欧洲药品局等监管机构正在寻求将QBD的概念和过程从制药产品扩展到生物制药。但是，对于药物的分析方法显然不足以适合生物制药。新兴的“生物仿制药”市场也带来了新的挑战：最简单的是，“高度相似”是什么？将建立广泛的用户社区。第一批用户的应用主要是蛋白质，蛋白质纤维，蛋白质组件，包括噬菌体和膜系统。

项目成果

Towards increased reliability by objectification of Hazard Analysis and Risk Assessment (HARA) of automated automotive systems

• DOI: 10.1016/j.ssci.2017.03.024
• 发表时间: 2017-11-01
• 期刊: SAFETY SCIENCE
• 影响因子: 6.1
• 作者: Khastgir, Siddartha;Birrell, Stewart;Jennings, Paul
• 通讯作者: Jennings, Paul

Calibrating trust through knowledge: Introducing the concept of informed safety for automation in vehicles

• DOI: 10.1016/j.trc.2018.07.001
• 发表时间: 2018-11-01
• 期刊: TRANSPORTATION RESEARCH PART C-EMERGING TECHNOLOGIES
• 影响因子: 8.3
• 作者: Khastgir, Siddartha;Birrell, Stewart;Jennings, Paul
• 通讯作者: Jennings, Paul

Systems Approach to Creating Test Scenarios for Automated Driving Systems

• DOI: 10.1016/j.ress.2021.107610
• 发表时间: 2021-03
• 期刊: Reliab. Eng. Syst. Saf.
• 作者: S. Khastgir;S. Brewerton;John Thomas;P. Jennings