Iterative approach to computational enzyme design

A general approach for the computational design of enzymes to catalyze arbitrary reactions is a goal at the forefront of the field of protein design. Recently, computationally designed enzymes have been produced for three chemical reactions through the synthesis and screening of a large number of variants. Here, we present an iterative approach that has led to the development of the most catalytically efficient computationally designed enzyme for the Kemp elimination to date. Previously established computational techniques were used to generate an initial design, HG-1, which was catalytically inactive. Analysis of HG-1 with molecular dynamics simulations (MD) and X-ray crystallography indicated that the inactivity might be due to bound waters and high flexibility of residues within the active site. This analysis guided changes to our design procedure, moved the design deeper into the interior of the protein, and resulted in an active Kemp eliminase, HG-2. The cocrystal structure of this enzyme with a transition state analog (TSA) revealed that the TSA was bound in the active site, interacted with the intended catalytic base in a catalytically relevant manner, but was flipped relative to the design model. MD analysis of HG-2 led to an additional point mutation, HG-3, that produced a further threefold improvement in activity. This iterative approach to computational enzyme design, including detailed MD and structural analysis of both active and inactive designs, promises a more complete understanding of the underlying principles of enzymatic catalysis and furthers progress toward reliably producing active enzymes

Three-dimensional flushing times of the Persian Gulf

2000 FLORIDA AVE NW, WASHINGTON, USA, DC, 2000

Experience unbound: The effects of coworking on workplace design practice

This thesis uses the typology of coworking and the values associated with it as a lens through which to look at the design of the broader workplace. It examines the ways in which people behave in these new working environments and how these designed spaces are planned, briefed, commissioned and evaluated. The study responds to a continuing gap in the knowledge around the spatial constitution and behaviours of coworking despite a growing interest from corporate organisations. Taking an inter-disciplinary approach that draws on environmental psychology, design practice and the social sciences, the thesis is rooted in both academia and industry, presenting four design studies that map the development and spatial manifestations of coworking and explore user behaviour in space. The thesis explores the values and spatial strategies of coworking through the quantitative analysis of 100 coworking home pages and 73 floor plans, and places coworking in the wider context of historical and current workplace development. Alongside this, it adopts design ethnography techniques to explore user behaviour in space at three different sites: the Impact Hub in Birmingham and Second Home in London - both coworking spaces - and Sony PlayStation in London, a commercial workplace seeking to build a more creative community. Each site uses different strategies for managing change and co-creation, but with the same aims of prioritising user experience and building and supporting collaborative relationships. In the original design study, new user-centred design tools for brief making and evaluation are developed and applied at the Impact Hub and Sony PlayStation. With relatively little academic research into the spaces of coworking, these design studies provide a platform to explore the values, infrastructures and spatial strategies associated with coworking, identify points of departure from established models, and identify whether there are central ideas within coworking that might be applied to the wider workplace. Six original contributions to knowledge are presented: a new definitional model of coworking, quantitative coworking spatial analysis, a design taxonomy of coworking spaces, an adapted framework for considering user experience, a user-centred design toolkit, and recommendations for incorporating aspects of coworking into wider workplace design. The study identifies that the success of a coworking space depends on the experience that they create. This relies on complex and evolving interactions between space, support and service infrastructures, brand identification and community management, and the thesis highlights that simply adopting the spatial strategies or aesthetics of coworking without acknowledging its careful curation of space and relationships is unlikely to produce the desired results. This presents new challenges for the briefing, design and ongoing management of the workplace, which are discussed in the thesis. This PhD concludes with insights into how the essential qualities of coworking might be used to reshape spaces for creative knowledge work alongside a set of practical tools and recommendations that relate to briefing, design and post-occupancy evaluation processes

Evaluating MIKE & PIKE: The Relationship Trend Between Elephant Carcasses & The Illegal Trade in Endangered Elephants

African and Asian elephants face many threats to their population numbers, including habitat loss, climate change, and interactions with humans. However, poaching and the illegal wildlife trade are the largest threats to these species. The first step in the illegal trade is taking or poaching of the elephant – typically the bulls with the largest tusks. Tusk ivory, whether African or Asian, is then exported to transit hubs in Asian countries. Final exported products, either carved or raw, enter the illegal markets located in many Asian countries and cities. Monitoring the Illegal Killing of Elephants (MIKE) and Proportion of Illegally Killed Elephants (PIKE) calculated that more elephant carcasses were found in 2011 than any other year, which resulted in more shipments of ivory leaving Africa and the price of ivory tripling in China. MIKE and PIKE data are analyzed in order to evaluate the crime of elephant poaching and its role in the illegal trade in endangered species.https://ir.library.illinoisstate.edu/urscjs/1000/thumbnail.jp