Upon accounting for the impact of isoenzyme loss, gene deletion costs anticorrelate with their evolutionary rates

System-level metabolic network models enable the computation of growth and metabolic phenotypes from an organism’s genome. In particular, flux balance approaches have been used to estimate the contribution of individual metabolic genes to organismal fitness, offering the opportunity to test whether such contributions carry information about the evolutionary pressure on the corresponding genes. Previous failure to identify the expected negative correlation between such computed gene-loss cost and sequence-derived evolutionary rates in Saccharomyces cerevisiae has been ascribed to a real biological gap between a gene’s fitness contribution to an organism “here and now” and the same gene’s historical importance as evidenced by its accumulated mutations over millions of years of evolution. Here we show that this negative correlation does exist, and can be exposed by revisiting a broadly employed assumption of flux balance models. In particular, we introduce a new metric that we call “function-loss cost”, which estimates the cost of a gene loss event as the total potential functional impairment caused by that loss. This new metric displays significant negative correlation with evolutionary rate, across several thousand minimal environments. We demonstrate that the improvement gained using function-loss cost over gene-loss cost is explained by replacing the base assumption that isoenzymes provide unlimited capacity for backup with the assumption that isoenzymes are completely non-redundant. We further show that this change of the assumption regarding isoenzymes increases the recall of epistatic interactions predicted by the flux balance model at the cost of a reduction in the precision of the predictions. In addition to suggesting that the gene-to-reaction mapping in genome-scale flux balance models should be used with caution, our analysis provides new evidence that evolutionary gene importance captures much more than strict essentiality.This work was supported by the National Science Foundation, grant CCF-1219007 to YX; the Natural Sciences and Engineering Research Council of Canada, grant RGPIN-2014-03892 to YX; the National Institute of Health, grants 5R01GM089978 and 5R01GM103502 to DS; the Army Research Office - Multidisciplinary University Research Initiative, grant W911NF-12-1-0390 to DS; the US Department of Energy, grant DE-SC0012627 to DS; and by the Canada Research Chairs Program (YX). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. (CCF-1219007 - National Science Foundation; RGPIN-2014-03892 - Natural Sciences and Engineering Research Council of Canada; 5R01GM089978 - National Institute of Health; 5R01GM103502 - National Institute of Health; W911NF-12-1-0390 - Army Research Office - Multidisciplinary University Research Initiative; DE-SC0012627 - US Department of Energy; Canada Research Chairs Program)Published versio

The Khmer Rouge Tribunal: Justice for Genocide in Cambodia?

After 30 years a tribunal has finally been established to try those responsible for the mass human rights violations perpetrated against the Cambodian people by the former Khmer Rouge regime. Popularly known as the Khmer Rouge Tribunal (KRT), the Extraordinary Chambers of the Criminal Court of Cambodia (ECCC) is one of the first so-called ‘hybrid’ tribunals to be established by the United Nations in collaboration with local courts to try international crimes such as genocide. This paper will assess the KRT as a transitional justice mechanism in terms of its ability to provide Cambodians with a sense of justice for the past as well as its potential impact on human rights and justice in Cambodia in the future. The cultural specificity and local conflict conditions that affect responses to different types of transitional justice approaches will be interrogated, asking who chose this mechanism and how does it meet the needs and expectations of Cambodians.This conference has been generously sponsored by the School of Social and Political Sciences and the Sydney Law School, University of Sydney, in collaboration with the School of Law, University of Western Sydne

Working Memory Capacity, Temporal Discounting, and Exercise Rates

During decision-making, an individual must weigh the value of the outcomes involved while also considering the amount of time until the outcomes will occur. Discounting occurs when a smaller, immediately available reward is chosen over a larger, more delayed reward. Discounting rates are likely related to working memory capacity, because working memory stores and processes the value of the outcomes. The purpose of this study was to examine the relationship between working memory, temporal discounting, and the decision to engage in physical activity. The results showed that working memory capacity was related to the physical activity rates. Discounting rates from a money task and a health task were not related to activity rates. However, in the subsample of individuals who reported that their primary motive to exercise was health, working memory and discounting rates from the money task were both statistically significant predictors of physical activity

Methods of mission: The ordering of space and time, land and labour on Methodist mission stations in Caffraria, 1823-1835

African Studies Seminar series. Paper presented 24 August 1992The methodist missionary enterprise in the period, 1816 to 1835, formed part of a broader process of colonial intrusion into the lands and lives of African people beyond the Cape colony. This paper examines the everyday activities of missionaries beyond the Eastern Cape in the first quarter of the nineteenth century. It takes as a theme their attempts to structure the pockets of land around mission stations into orderly settlements, and to order the lives of station residents according to the rhythms of industrialising England. The paper describes and analyses the ways in which the aims of the Methodist mission were translated into everyday practices. While focusing on missionary interactions with Africans beyond the Colony, the narrative traverses the web spun, by missionaries, from bases in the Colony across the interior

Ameliorating the quality issues in live subtitling

Access services have evolved significantly over the past 30 years, and optional subtitles are widely available on mainstream channels in the UK and Europe. Live subtitles now routinely accompany news, sports and chat-shows. The production and consumption of live subtitles both impose heavy cognitive loads, not helped by the constraints of time, practical limitations and the inevitability of errors. Live subtitles of broadcast quality are normally created by real-time transcription of phonetic key strokes or re-spoken text produced by a human intermediary. If the subject matter and vocabulary of the content is not known in advance, transcription errors are very likely. Such errors are distracting or confusing – regulators deprecate them, the press mocks them, but producers have to risk them to deliver the service. Less obvious quality issues also arise to do with the timing lag and the style and position of subtitle text. Recent studies into audience perceptions of live subtitle quality are reviewed, and the results of a pilot study in classifying apparent errors according to likely cause are used to illustrate possible opportunities for mitigation. This suggests that aspects of re-speaking style may be adjusted to enhance accuracy, and that there may be opportunities for new approaches to underpin further quality improvements in future

Socialisation problems of entrants into the legal profession during articles of clerkship

Bibliography: leaves 110-121.The aim of the study was to identify perceptions of problems in the effective integration of entrants into the South African legal profession. Two types of problems were investigated. Firstly, typical entrant problems; that is, problems which typically are experienced by newcomers into organisations. Secondly, problems which are specifically related to the race and/or gender of organisational entrants

Biotechnical options

Discusses biological options available for improvement in the productivity of pastoral systems, particularly referring to problems arising from aridity and under-nutrition, and problems of particular systems such as mortality of young stock, bush encroachment, epidemic diseases and management systems

The Multimedia in Physics Teaching and Learning community

The Multimedia in Physics Teaching and Learning community share a keen interest in pedagogical approaches to physics education. A major part of this concerns the development of software and hardware tools to enhance the experience of students and teachers. In September 2017 around 60 colleagues from across the globe came to The Open University campus for three days of networking and sharing of ideas. In plenary sessions John Belcher spoke about the MIT's TEAL project on learning environments for electromagnetism, Eileen scanlon spoke on Learning and Teaching physics 'in the open' and Bruce Mason reviewed Mobile technology. There were general contributions by participants in sessions on Virtual and remote labs, Developments in schools, Simulations and representation, IT/arduino projects, Game based learning, and Use of smart phone technology. There were also workshop activities on Jupyter Notebooks, Remote and Robotic Observatories and on the OpenSTEM labs facilities of the Open University. The abstracts of contributions are archived at this URL https://bit.ly/2SKtoKF. Formal reports based on some of the presentations are included here for future reference. These have been edited together to form a coherent record of those contributions that were ready for publication in a print format. Robert Lambourne and Nicholas Braithwaite</p