A series of Fas receptor agonist antibodies that demonstrate an inverse correlation between affinity and potency

Receptor agonism remains poorly understood at the molecular and mechanistic level. In this study, we identified a fully human anti-Fas antibody that could efficiently trigger apoptosis and therefore function as a potent agonist. Protein engineering and crystallography were used to mechanistically understand the agonistic activity of the antibody. The crystal structure of the complex was determined at 1.9 Å resolution and provided insights into epitope recognition and comparisons with the natural ligand FasL (Fas ligand). When we affinity-matured the agonist antibody, we observed that, surprisingly, the higher-affinity antibodies demonstrated a significant reduction, rather than an increase, in agonist activity at the Fas receptor. We propose and experimentally demonstrate a model to explain this non-intuitive impact of affinity on agonist antibody signalling and explore the implications for the discovery of therapeutic agonists in general

Improving the efficiency and effectiveness of an industrial SARS-CoV-2 diagnostic facility.

On 11th March 2020, the UK government announced plans for the scaling of COVID-19 testing, and on 27th March 2020 it was announced that a new alliance of private sector and academic collaborative laboratories were being created to generate the testing capacity required. The Cambridge COVID-19 Testing Centre (CCTC) was established during April 2020 through collaboration between AstraZeneca, GlaxoSmithKline, and the University of Cambridge, with Charles River Laboratories joining the collaboration at the end of July 2020. The CCTC lab operation focussed on the optimised use of automation, introduction of novel technologies and process modelling to enable a testing capacity of 22,000 tests per day. Here we describe the optimisation of the laboratory process through the continued exploitation of internal performance metrics, while introducing new technologies including the Heat Inactivation of clinical samples upon receipt into the laboratory and a Direct to PCR protocol that removed the requirement for the RNA extraction step. We anticipate that these methods will have value in driving continued efficiency and effectiveness within all large scale viral diagnostic testing laboratories

iDROP, an Innovative Software Program to Design Decommissioning Scenarios

International audienceMany historic nuclear facilities have reached the end of their lifetimes and are now being decontaminated and dismantled. Our institute has been working on innovative solutions for these huge and complex decommissioning projects. These include remote handling tools, in situ characterization, and the simulation of intervention scenarios. The latter is a valuable means of visualizing and gathering information on highly radioactive environments that humans cannot enter. Various treatment techniques can be compared and workers can be trained before operating on site. For the past 10 years, our institute has been developing a virtual reality tool that simulates all the key elements of a dismantling project, including the remote handling, and the accessibility of the site for humans, and the dose assessment associated. This tool allows all these parameters to be computed in a single interactive environment, allowing pre-defined scenarios to be verified and alternative solutions to be designed. This software is presented in the following paper; we here illustrate that it is particularly well-suited to dismantling projects. We also describe a first application of the tool to investigate radiological exposure scenarios; the STEL (a contaminated effluents treatment facility) decommissioning project is presented and the data preparation, configuration of the simulation, and results are described. The advantages of this software include its user-friendliness, responsiveness, speed, and usefulness for the preparation of complex dismantling operations. The perspectives of this project include the simulation in Virtual Reality of human interventions

Fatty Acid Esters in Europe: Market Trends and Technological Perspectives

Based on strong governmental incentives, biodiesel from transesterification of Fatty Acids (FAE) production is rapidly increasing mainly in Europe and is starting to expand worldwide. A closer look at the complex European incentives scheme and an update of the planned FAE capacity expansion helps to explain the key economic factors in this sharp raise in FAE activity. Based on this economic background, key factors for FAE technology selection will be explored to demonstrate alternatives for biofuels production. Increasing biodiesel consumption in a sustainable way requires optimizing production processes compatible with high production capacities, high yields and low environmental impact, especially regarding wastes streams. This paper highlights a commercially proven technology available for meeting these challenges, focusing on a new continuous FAE production process where the transesterification reaction is promoted by a heterogeneous catalyst. This process employs methanolysis of vegetable oils by passing the reactants through two consecutive fixed-bed reactors followed by methanol and glycerin separation stages. The Axens process requires neither catalyst recovery nor aqueous treatment. It achieves very high methyl esters yields with a high purity glycerin byproduct. At least 98% purity glycerin is directly recovered in the total absence of any mineral (salts) contaminants thereby offering an alternative for a real “Green Process”