The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project. ?? 2013 Elsevier B.V. All rights reserved
For production of different monoclonal antibodies (mAbs), biopharmaceutical companies often use related upstream and downstream manufacturing processes. Such platforms are typically characterized regarding influence of upstream and downstream process (DSP) parameters on critical quality attributes (CQAs). CQAs must be monitored strictly by an adequate control strategy. One such process-related CQA is the content of host cell protein (HCP) which is typically analyzed by immunoassay methods (e.g., HCP-ELISA). The capacity of the immunoassay to detect a broad range of HCPs, relevant for the individual mAb-production process should be proven by orthogonal proteomic methods such as 2D gel electrophoresis or mass spectrometry (MS). In particular MS has become a valuable tool to identify and quantify HCP in complex mixtures. We evaluate up-and DSP parameters of four different biopharmaceutical products, two different process variants, and one mock fermentation on the HCP pattern by shotgun MS analysis and ELISA. We obtained a similar HCP pattern in different cell culture fluid harvests compared to the starting material from the downstream process. During the downstream purification process of the mAbs, the HCP level and the number of HCP species significantly decreased, accompanied by an increase in diversity of the residual HCP pattern. Based on this knowledge, we suggest a control strategy that combines multi product ELISA for in-process control and release analytics, and MS testing for orthogonal HCP characterization, to attain knowledge on the HCP level, clusters and species. This combination supports a control strategy for HCPs addressing safety and efficacy of biopharmaceutical products. K E Y W O R D S biopharmaceuticals, ELISA, host cell protein, mass spectrometry, proteomics 1 | INTRODUCTION Recombinant monoclonal antibodies (mAbs) produced in Chinese Hamster Ovarian cells are among the most important biopharmaceutical drugs. Different sub-populations of the Chinese hamster ovary (CHO) cell line are commonly used in biopharmaceutical processes for mAbs 1 . mAbs are steadily secreted into the cell culture fluid (CCF) during the fermentation process. During different steps of the DSP mAbs are purified and concentrated from CCF by separating DNA, RNA, lipids, other cell and process derived components,
Our research goals are to understand the nature of, construct and evaluate intelligent interfaces as knowledge-based systems. In this paper we demonstrate the need for help systems as an essential part of human-computer communication. Help strategies are based on a model of the task (to understand what the user is doing or which goals he/she 1 wants to achieve) and a model of the user (to guarantee that these systems are non-intrusive and that they pay attention to the needs of individual users). We illustrate that passive and active help systems have to be constructed as knowledge-based systems. Two operational systems (PASSIVIST and ACTIVIST) are described to show the usefulness of this approach.
© 1985 ACM0-89791-149-0/85/004/0161 $00.75~: the mental model (Norman 82; Fischer 84) of the user, i.e. the set of concepts which he thinks exist in the system. A passive help (see section i.i) system is needed to gradually master the commands in D 2 and D 3.
The Cherenkov Telescope Array ( ) is a future gamma-ray observatory that is planned to significantly improve upon the sensitivity and precision of the current generation of Cherenkov telescopes. The observatory will consist of several dozens of telescopes with different sizes and equipped with different types of cameras. Of these, the FlashCam camera system is the first to implement a fully digital signal processing chain which allows for a traceable, configurable trigger scheme and flexible signal reconstruction. As of autumn , a prototype FlashCam camera for the medium-sized telescopes of nears completion. First results of the ongoing system tests demonstrate that the signal chain and the readout system surpass requirements. The stability of the system is shown using long-term temperature cycling.
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