Next generation approaches to polysaccharide preparation for Burkholderia pseudomallei vaccine development.

Burkholderia pseudomallei is the aetiological agent of melioidosis and a potential bioterror threat. Infections are difficult to treat due to extensive antibiotic resistance and there is no prophylactic vaccine available. Studies have shown that the capsular polysaccharide (CPS) of B. pseudomallei is a virulence factor, immunogen and candidate antigen for a glycoconjugate vaccine. However, polysaccharides are complex to synthesise. One approach is to genetically engineer Escherichia coli to express the CPS; however, previous attempts at cloning the CPS coding locus from B. pseudomallei into E. coli were unsuccessful. This project proposes to clone only the essential genes from B. pseudomallei and to use native E. coli mechanisms to complete CPS synthesis. This would contribute to development of a new platform for the expression of any bespoke polysaccharide in E. coli. Six biosynthetic genes for the nucleotide sugar precursor were successfully expressed in E. coli. The structure of the precursor was verified by mass spectrometry. Precursor synthesis was also performed in an in vitro microfluidics system. This minimised the quantity of substrates and enzymes required, in preparation for the characterisation of glycosyltransferases required for CPS assembly. A novel assay for characterising glycosyltransferase activity was also developed, as current available options are prohibitively expensive and require significant quantities of glycosyltransferase which are difficult to purify. Finally, plasmids for the expression of additional glycosyltransferases to link the nascent B. pseudomallei CPS to truncated polysaccharides in E. coli were constructed. The aim of this project was to contribute to the development of a platform for the expression of bespoke polysaccharides in E. coli. The CPS of B. pseudomallei was chosen as the model polysaccharide as it has a simple structure and its manufacture is desirable for use in a vaccine against melioidosis.EPSRC with CASE awardDst

'Look for the truth and tell it': politics and Harold Pinter

For more than two decades, Pinter had been most passionately engaged with world politics as a citizen; as an artist he has often sought to reflect this political engagement through his representation of the relationship between an oppressive totalitarian state and the dissenting individual. In interviews he claims that he was always a ‘political playwright’. Yet it is not Pinter’s overt political plays which interest me here. This thesis seeks to explore how Pinter was ‘political’ throughout his career, both in the plays that seem to separate art from politics, and the political activism he was engaged in right up until his death. Firstly, I will focus on the politics of personal relationships, relationships that are consumed with a battle for power between man and woman. Secondly, I will examine his symbolic response to world politics using such relationships as he had become famous for. Thirdly, I will look at his political writings, his poetry, journalism and public speeches which see his increasingly public role as political activist

Factors influencing the uptake of memory compensations following acquired brain injury

The use of memory strategies can promote independence in people who have an acquired brain injury but people often do not take readily to using such strategies. Certain demographic variables have been associated with the use of memory strategies these variables cannot be changed through therapeutic interventions. The aim of this thesis is to explore variables that may be modifiable through rehabilitation e.g. health beliefs and perceptions of aids, to see whether they help us understand factors influencing the uptake of memory strategies. The thesis consists of three studies. The first uses Interpretative Phenomenological Analysis to explore how people feel about using memory strategies. The second is a cross sectional questionnaire design exploring the predictive power of variables identified in the first study to predict the use of strategies together with demographic variables. The third is a single case study utilising findings from the first two studies to help an individual use a mobile phone and Google calendar as a memory aid. A key factor in the use of memory compensations is the need to ‘fit’ the aid to an individual’s lifestyle. Consequently, there is greater optimism for those who may otherwise be regarded as unlikely to use aids

Creating Interest in Reading in the Cedar Bayou School

My purpose of study is to find methods of motivating interest in reading for information as well as establishing good reading habits. I have observed primary instructors such as Mrs. Wheeler at the Horace Mann School at Goose Creek, Texas, Pauline Watkins at Prairie View, Texas, Prairie View State College teaching primary methods. Other methods or means of securing material were by reading bulletins, journals, periodicals and reference books. Books on reading and education texts were used also. This study covers grades 1st. to the eighth in a one-teacher school from 1933-1937

Google Calendar : a single case experimental design study of a man with severe memory problems

A single case experimental design across behaviours was utilised to explore the effectiveness of Google Calendar text alerts delivered to a mobile phone as a memory aid. The participant was a 43-year-old man (JA) with severe memory problems and executive difficulties caused by a traumatic brain injury (TBI). JA was initially very unwilling to use any memory aid and so a detailed assessment of his beliefs about memory aids, his cognitive difficulties and his social context was performed and a set of specifications for an aid was produced collaboratively. Six weeks of baseline data and six weeks of intervention data were collected for three target memory behaviours and three control memory behaviours. Results were analysed using nonoverlap of all pairs (NAP) analysis which showed a reduction in forgetting in the three target behaviours and no change in two of the three control behaviours. A subjective measure (the revised Everyday Memory Questionnaire) also suggested improvement. This study illustrates that Google Calendar is a highly effective memory aid and emphasises the importance of choosing a memory aid to suit the person's lifestyle and beliefs

Linguistic triage: Documentary linguistics and language revitalisation

There has been considerable discussion of the question as to whether a linguist engaged in language documentation should also be involved in language maintenance and revitalisation projects. This begs the question of what qualifications are needed to meaningfully engage in revitalisation and maintenance, and whether a linguist should participate even if they lack them. The relationship of the linguist to the language community has altered significantly in recent years, and yet outdated perceptions of the linguist’s role persist. Simultaneously, a new paradigm has emerged wherein there is an expectation on field-working linguists to engage with and contribute to language communities in ways that some fear may interfere with the goal of rigorous linguistic scholarship. This paper will explore the changing expectations of linguistic fieldwork, who is really qualified for revitalisation and maintenance, and how the relationship and responsibilities of the linguist to the community in which they work may impact the way in which language documentation is carried out

Psychosurgery: A History from Prefrontal Lobotomy to Deep Brain Stimulation

Neurosurgical treatment for psychiatric disorders features a long and controversial history. This article explores a ‘spectrum of psychosurgery,’ describing how old-fashioned and controversial prefrontal lobotomy gradually evolved into modern day, mainstream scientific deep brain stimulation (DBS). We focus on the rise, fall and possible re-emergence of psychosurgery as a therapeutic intervention today.We journey through historic indiscriminate use of prefrontal lobotomy, which evoked stern criticism from both public and professionals, through to the development of modern day DBS - performed for patients suffering from severe, treatment resistant symptoms of obsessive-compulsive disorder (OCD), epilepsy and movement disorders.We hope this article will provide a basis for understanding the availability of existing treatment options and potential future opportunities, whilst simultaneously challenging any public/professional preconceptions of psychosurgery, which may indirectly be obstructing patient care.Additionally, we carried out a qualitative survey displayed in WordCloud Format, capturing the intellection of 38 mental health professionals working for North West Boroughs NHS Healthcare Foundation Trust, on ‘psychosurgery,’ ‘prefrontal lobotomy’ and ‘DBS’, which may well reflect wider public opinion.In summary, the article provides a brief, yet comprehensive overview of the controversial history of psychosurgery, present-day practice, and future trends of neurosurgery for psychiatric disorders