Mixture models of nucleotide sequence evolution that account for heterogeneity in the substitution process across sites and across lineages

Molecular phylogenetic studies of homologous sequences of nucleotides often assume that the underlying evolutionary process was globally stationary, reversible, and homogeneous (SRH), and that a model of evolution with one or more site-specific and time-reversible rate matrices (e.g., the GTR rate matrix) is enough to accurately model the evolution of data over the whole tree. However, an increasing body of data suggests that evolution under these conditions is an exception, rather than the norm. To address this issue, several non-SRH models of molecular evolution have been proposed, but they either ignore heterogeneity in the substitution process across sites (HAS) or assume it can be modeled accurately using the distribution. As an alternative to these models of evolution, we introduce a family of mixture models that approximate HAS without the assumption of an underlying predefined statistical distribution. This family of mixture models is combined with non-SRH models of evolution that account for heterogeneity in the substitution process across lineages (HAL). We also present two algorithms for searching model space and identifying an optimal model of evolution that is less likely to over- or underparameterize the data. The performance of the two new algorithms was evaluated using alignments of nucleotides with 10 000 sites simulated under complex non-SRH conditions on a 25-tipped tree. The algorithms were found to be very successful, identifying the correct HAL model with a 75% success rate (the average success rate for assigning rate matrices to the tree's 48 edges was 99.25%) and, for the correct HAL model, identifying the correct HAS model with a 98% success rate. Finally, parameter estimates obtained under the correct HAL-HAS model were found to be accurate and precise. The merits of our new algorithms were illustrated with an analysis of 42 337 second codon sites extracted from a concatenation of 106 alignments of orthologous genes encoded by the nuclear genomes of Saccharomyces cerevisiae, S. paradoxus, S. mikatae, S. kudriavzevii, S. castellii, S. kluyveri, S. bayanus, and Candida albicans. Our results show that second codon sites in the ancestral genome of these species contained 49.1% invariable sites, 39.6% variable sites belonging to one rate category (V1), and 11.3% variable sites belonging to a second rate category (V2). The ancestral nucleotide content was found to differ markedly across these three sets of sites, and the evolutionary processes operating at the variable sites were found to be non-SRH and best modeled by a combination of eight edge-specific rate matrices (four for V1 and four for V2). The number of substitutions per site at the variable sites also differed markedly, with sites belonging to V1 evolving slower than those belonging to V2 along the lineages separating the seven species of Saccharomyces. Finally, sites belonging to V1 appeared to have ceased evolving along the lineages separating S. cerevisiae, S. paradoxus, S. mikatae, S. kudriavzevii, and S. bayanus, implying that they might have become so selectively constrained that they could be considered invariable sites in these species.

John Frazer

John Frazer, Professor, trained at the Architectural Association, taught first at Cambridge University and then the AA in the 1970s and again in the '90s. He was Head of School of Design Research History and Criticism at the University of Ulster in the 1980s, he also ran a systems and design consultancy with his wife Julia (including projects for Cedric Price and Walter Segal) and was founder and chairman of Autographics software. He is currently Swire Chair Professor and Head of School of Design in Hong Kong.----- This is a very personal perspective on a concept of universal and future significance. It is personal, both is the sense that it is an unashamedly biased view of both the significance of the project, and the nature of that significance and because the author was personally involved as one of the consultants on GENERATOR and subsequently involved Cedric Price in its educational application at the Architectural Association. GENERATOR is still very much alive and was still developing whilst this chapter was being written.

Concerning the house museum and the picturesque landscape in the work of Sir John Soane : with raw hints for post-heritage museum space

The picturesque aesthetic in the work of Sir John Soane, architect and collector, resonates in the major work of his very personal practice – the development of his house museum, now the Soane Museum in Lincoln’s Inn Fields in London. Soane was actively involved with the debates, practices and proponents of picturesque and classical practices in architecture and landscape and his lectures reveal these influences in the making of The Soane, which was built to contain and present diverse collections of classical and contemporary art and architecture alongside scavenged curiosities. The Soane Museum has been described as a picturesque landscape, where a pictorial style, together with a carefully defined itinerary, has resulted in the ‘apotheosis of the Picturesque interior’. Soane also experimented with making mock ruinscapes within gardens, which led him to construct faux architectures alluding to archaeological practices based upon the ruin and the fragment. These ideas framed the making of interior landscapes expressed through spatial juxtapositions of room and corridor furnished with the collected object that characterise The Soane Museum. This paper is a personal journey through the Museum which describes and then reviews aspects of Soane’s work in the context of contemporary theories on ‘new’ museology. It describes the underpinning picturesque practices that Soane employed to exceed the boundaries between interior and exterior landscapes and the collection. It then applies particular picturesque principles drawn from visiting The Soane to a speculative project for a house/landscape museum for the Oratunga historic property in outback South Australia, where the often, normalising effects of conservation practices are reviewed using minimal architectural intervention through a celebration of ruinous states.

Duggaibah, or 'place of whiteness' : Australian feminist and race

Our society operates in such a way as to put whiteness at the center of everything, including individual consciousness--so much so that we seldom question the centrality of white- ness, and most people, on hearing 'race', hear 'black'. That is, whiteness is treated as the norm, against which all differences are measured. 1 Race shapes white women's lives. In the same way that both men's and women's lives are shaped by their gender, and that both heterosexual and lesbian women's experiences in the world are marked by their sexuality, white people and people of color live racially structured lives. In other words, any system of differentiation shapes those on whom it bestows privi- lege as well as those it oppresses. White people are 'raced' just as men are 'gendered'. 2

Art, popular culture and cultural policy: variations on a theme of John Carey

The article presents a criticism of the accounts of John Carey in his book entitled "The Intellectuals and the Masses." The author focuses on Carey's argument that the art is not an eternal category but an invention of the late eighteenth century and it no longer has any intellectual legitimacy other than that of provoking feelings which are no more and no less valuable than those provoked by any other form of entertainment or physical activity

Sir Neville Howse (VC), Private John Simpson Kirkpatrick and Private Martin O’Meara (VC) and their contributions to Australian military medicine

Medical personnel serving with the Defence Forces have contributed to the evolution of trauma treatment and the advancement of prehospital care within the military environment. This paper investigates the stories of an Australian Medical Officer, Sir Neville Howse, and two stretcher bearers, Private John Simpson (Kirkpatrick) and Private Martin O’Meara, In particular it describes the gruelling conditions under which they performed their roles, and reflects on the legacy that they have left behind in Australian society. While it is widely acknowledged that conflicts such as World War One should never have happened, as civilian and defence force paramedics, we should never forget the service and sacrifice of defence force medical personnel and their contribution to the body of knowledge on the treatment of trauma. These men and women bravely provided emergency care in the most harrowing conditions possible. However, men like Martin O’Meara may not have been given the same status in society today as Sir Neville Howse or Simpson and his donkey, due to the public’s lack of awareness and acceptance of war neurosis and conditions such as post traumatic stress disorder, reactive psychosis and somatoform disorders which were suffered by many soldiers during their wartime service and on their return home after fighting in war.

A quite unreasonable state of affairs : corporate social responsibility and the John Lewis Partnership

On the surface the subjects of Corporate Social Responsibility (CSR) and Critical Management Studies (CMS) seem to be closely related. Both are concerned with reflecting on the impact of management and organisation on employees, the wider community and the environment. Both suggest that there may be a need for organisations to take responsibility for and account of people other than shareholders and both have used the concept of accountability to suggest that organisations may need to do more than just comply with the legal framework.

Kava and St. John's wort : current evidence for use in mood and anxiety disorders

Background: Mood and anxiety disorders pose significant health burdens on the community. Kava and St John’s wort (SJW) are the most commonly used herbal medicines in the treatment of anxiety and depressive disorders, respectively. Objectives: To conduct a comprehensive review of kava and SJW, to review any evidence of efficacy, mode of action, pharmacokinetics, safety and use in Major Depressive Disorder (MDD), Bipolar Disorder (BP), Seasonal Affective Disorder (SAD), Generalized Anxiety Disorder (GAD), Social Phobia (SP), Panic Disorder (PD), Obsessive-Compulsive Disorder (OCD), and Post Traumatic Stress Disorder (PTSD). Methods: A systematic review was conducted using the electronic databases MEDLINE, CINAHL, and The Cochrane Library during late 2008. The search criteria involved mood and anxiety disorder search terms in combination with kava, Piper methysticum, kavalactones, St John’s wort, Hypericum perforatum, hypericin and hyperforin. Additional search criteria for safety, pharmacodynamics , and pharmacokinetics was employed. A subsequent forward search was conducted of the papers using Web of Science cited reference search. Results: Current evidence supports the use of SJW in treating mild-moderate depression, and for kava in treatment of generalized anxiety. In respect to the other disorders, only weak preliminary evidence exists for use of SJW in SAD. Currently there is no published human trial on use of kava in affective disorders, or in OCD, PTSD, PD or SP. These disorders constitute potential applications that warrant exploration. Conclusions: Current evidence for herbal medicines in the treatment of depression and anxiety only supports the use of Hypericum perforatum for depression, and Piper methysticum for generalized anxiety.

Is it possible to dissociate ‘liking’ and ‘wanting’ for foods in humans? A novel experimental procedure

Berridge's model (e.g. [Berridge KC. Food reward: Brain substrates of wanting and liking. Neurosci Biobehav Rev 1996;20:1–25.; Berridge KC, Robinson T E. Parsing reward. Trends Neurosci 2003;26:507–513.; Berridge KC. Motivation concepts in behavioral neuroscience. Physiol Behav 2004;81:179–209]) outlines the brain substrates thought to mediate food reward with distinct ‘liking’ (hedonic/affective) and ‘wanting’ (incentive salience/motivation) components. Understanding the dual aspects of food reward could throw light on food choice, appetite control and overconsumption. The present study reports the development of a procedure to measure these processes in humans. A computer-based paradigm was used to assess ‘liking’ (through pleasantness ratings) and ‘wanting’ (through forced-choice photographic procedure) for foods that varied in fat (high or low) and taste (savoury or sweet). 60 participants completed the program when hungry and after an ad libitum meal. Findings indicate a state (hungry–satiated)-dependent, partial dissociation between ‘liking’ and ‘wanting’ for generic food categories. In the hungry state, participants ‘wanted’ high-fat savoury > low-fat savoury with no corresponding difference in ‘liking’, and ‘liked’ high-fat sweet > low-fat sweet but did not differ in ‘wanting’ for these foods. In the satiated state, participants ‘liked’, but did not ‘want’, high-fat savoury > low-fat savoury, and ‘wanted’ but did not ‘like’ low-fat sweet > high-fat sweet. More differences in ‘liking’ and ‘wanting’ were observed when hungry than when satiated. This procedure provides the first step in proof of concept that ‘liking’ and ‘wanting’ can be dissociated in humans and can be further developed for foods varying along different dimensions. Other experimental procedures may also be devised to separate ‘liking’ and ‘wanting’.