On the origins of Mendelian disease genes in man: the impact of gene duplication

Over 3,000 human diseases are known to be linked to heritable genetic variation, mapping to over 1,700 unique genes. Dating of the evolutionary age of these disease-associated genes has suggested that they have a tendency to be ancient, specifically coming into existence with early metazoa. The approach taken by past studies, however, assumes that the age of a disease is the same as the age of its common ancestor, ignoring the fundamental contribution of duplication events in the evolution of new genes and function. Here, we date both the common ancestor and the duplication history of known human disease-associated genes. We find that the majority of disease genes (80%) are genes that have been duplicated in their evolutionary history. Periods for which there are more disease-associated genes, for example, at the origins of bony vertebrates, are explained by the emergence of more genes at that time, and the majority of these are duplicates inferred to have arisen by whole-genome duplication. These relationships are similar for different disease types and the disease-associated gene's cellular function. This indicates that the emergence of duplication-associated diseases has been ongoing and approximately constant (relative to the retention of duplicate genes) throughout the evolution of life. This continued until approximately 390 Ma from which time relatively fewer novel genes came into existence on the human lineage, let alone disease genes. For single-copy genes associated with disease, we find that the numbers of disease genes decreases with recency. For the majority of duplicates, the disease-associated mutation is associated with just one of the duplicate copies. A universal explanation for heritable disease is, thus, that it is merely a by-product of the evolutionary process; the evolution of new genes (de novo or by duplication) results in the potential for new diseases to emerge

Observations of road safety behaviours and practices of motorcycle rickshaw drivers in Lahore, Pakistan

Motorcycle Rickshaws (MRs) are an informal paratransit mode in Pakistan. They are locally manufactured and very popular but there are concerns about their crash involvement and overall safety. The first study of the current PhD program revealed that rickshaws (both MRs and auto-rickshaws) were involved in 51,992 road crashes attended by emergency ambulances in Punjab province, Pakistan between 2011-2013. This study aims to examine the road safety behaviours and practices of Motorcycle Rickshaw Drivers (MRDs) that may be contributing to these crashes. MRDs were observed at 12 major signalised intersections in Lahore. Vehicle characteristics and driver behaviours were recorded using a paper-based survey between 9am-7pm for a full week in May 2015. Of the 500 MRDs observed, about 23.4% appeared to be younger than the minimum driver licensing age of 18 years. More than half (52.6%) of the MRDs entered on the red light and 17.4% crossed when the signal was turning from yellow to green or red. MR traffic conflicts were observed in 62.8% of cases and one crash and 15 near-miss crashes were witnessed. Additionally, about half of MRs were overloaded, no MRD wore a helmet, and 3.8% were using a mobile phone while driving. This study provides the first scientific evidence to substantiate public concerns regarding the safety of MRs. It demonstrates that about a quarter of MRDs are underage,almost half of MRs are overloaded and more than half disobey traffic signals. This research could inform authorities to manage MR related transport and road safety issues

Market Risk Disclosures and Investment Efficiency: International Evidence from the Gulf Cooperation Council Financial Firms

This study examines the association between market risk disclosures (MRDs) and the investment efficiency of financial firms from six emerging markets in the Gulf Cooperation Council (GCC) region. Based on a sample of 553 firm-year observations over the 2007-2011 period, we find that MRDs are significantly and negatively associated with both under-investment and over-investment and that this association is more pronounced for larger firms. We also find that the association between MRDs and under-investment is moderated during periods of economic distress such as the Global Financial Crisis of 2008 and that the association between MRDs and over-investment is magnified during periods of reduced financial distress. Our results are consistent with the idea that MRDs reduce information asymmetry, which ultimately improves investment efficiency. We contribute to the literature in an emerging market context by providing empirical evidence on the association between MRDs and investment efficiency across six emerging GCC capital markets. This study also fills a gap in the literature by providing evidence on the factors affecting the investment efficiency of financial firms

How Can Speech Recognisers Help Applied Research in the Civil Engineering, Transport and Related Industries

BACKGROUND Speech recognition technology is rapidly advancing to the point here it can be usefully applied in a wide range of mtexts. For applications within the SERC Environment Committee's area of interest -civil engineering; construction; building; transport; water resources there are a number of kinds of recording situation in which one needs to keep one's eyes on the situation being studied; or in which the recording conditions (eg moving around with instruments) are unfavourable. The limitations of conventional pen and paper recording for these situations are obvious; and the limitations of hand-held data capture devices are also becoming apparent. Speech is therefore an easier medium to use; and a tape recorder a convenient means of recording the observations. For well defined recording tasks; speech recognisers might be a helpful way of transcribing the record. This seminar was convened to enable those who are potentially interested in such an application of information technology to hear of the latest developnents and assessments of the suitability of the technology

AltURI: a thin middleware for simulated robot vision applications

Fast software performance is often the focus when developing real-time vision-based control applications for robot simulators. In this paper we have developed a thin, high performance middleware for USARSim and other simulators designed for real-time vision-based control applications. It includes a fast image server providing images in OpenCV, Matlab or web formats and a simple command/sensor processor. The interface has been tested in USARSim with an Unmanned Aerial Vehicle using two control applications; landing using a reinforcement learning algorithm and altitude control using elementary motion detection. The middleware has been found to be fast enough to control the flying robot as well as very easy to set up and use

Trends. An Implosion of Ideology: Bosnia, Kosovo, Northern Ireland, Palestine, the Soviet Union, and Beyond

The article discusses multiethnic, representative democracies (MRDs) that often promulgate and effect foreign policies that are founded on the ideological premise that instilling MRDs throughout the world is necessarily the optimal road to Good