Galactokinase promiscuity: a question of flexibility?

Galactokinase catalyses the first committed step of the Leloir pathway, i.e. the ATP-dependent phosphorylation of α-D-galactose at C1-OH. Reduced galactokinase activity results in the inherited metabolic disease type II galactosaemia. However, inhibition of galactokinase is considered a viable approach to treating more severe forms of galactosaemia (types I and III). Considerable progress has been made in the identification of high affinity, selective inhibitors. Although the structure of galactokinase from a variety of species is known, its catalytic mechanism remains uncertain. Although the bulk of evidence suggests that the reaction proceeds via an active site base mechanism, some experimental and theoretical studies contradict this. The enzyme has potential as a biocatalyst in the production of sugar 1-phosphates. This potential is limited by its high specificity. A variety of approaches have been taken to identify galactokinase variants which are more promiscuous. These have broadened galactokinase's specificity to include a wide range of D- and L-sugars. Initial studies suggest that some of these alterations result in increased flexibility at the active site. It is suggested that modulation of protein flexibility is at least as important as structural modifications in determining the success or failure of enzyme engineering.

An Evaluation of the Dual Diagnosis (substance use and mental health )Strategy in the South Eastern Trust Workers and Service Users Perceptions of Dual Diagnosis Issues

In the UK it is estimated that over 33% of psychiatric patients with enduring mental illness have a substance misuse problem, whilst over 50 % of clients currently accessing drug and alcohol services have a mental health problem. Between 2003 and 2013 in Northern Ireland, there were 741 recorded suicides by patients who were in contact with mental health services. Of this number, 68% (n=501) had a history of either alcohol or drug misuse or both, resulting in an average of 46 patient suicides per year associated with dual diagnosis (University of Manchester 2015).
The current evaluation examined staff attitudes towards working with dual diagnosis (co-existing difficulties) issues, staff confidence in working with clients with dual diagnosis, workers’ perceptions of the South Eastern dual diagnosis strategy and service user perspectives of dual diagnosis service provision.
The purpose of the evaluation was to provide evidence regarding the following in accordance with the current dual diagnosis strategy;
Staff understanding of the concept of dual diagnosis,
Staff attitudes towards working with dual diagnosis,
Staff confidence in working with individuals, who present with dual diagnosis,
Service users’ perspectives of SE Trust provision for dual diagnosis.
Staff views on the South Eastern Trust Dual Diagnosis Strategy.

Assessing the evidence: Student response system versus computer based testing for undertaking multiple choice question assessment in undergraduate nursing education

There is a dearth of evidence focusing on student preferences for computer-based testing versus
testing via student response systems for summative assessment in undergraduate education.
This quantitative study compared the preference and acceptability of computer-based testing
and a student response system for completing multiple choice questions in undergraduate
nursing education. After using both computer-based testing and a student response system to
complete multiple choice questions, 192 first year undergraduate nursing students rated their
preferences and attitudes towards using computer-based testing and a student response system.
Results indicated that seventy four percent felt the student response system was easy to use.
Fifty six percent felt the student response system took more time than the computer-based testing
to become familiar with. Sixty Percent felt computer-based testing was more users friendly.
Seventy Percent of students would prefer to take a multiple choice question summative exam
via computer-based testing, although Fifty percent would be happy to take using student response
system. Results are useful for undergraduate educators in relation to student’s preference
for using computer-based testing or student response system to undertake a summative
multiple choice question exam

Multi-scale dynamics on the Eastern Brazilian margin

Este trabalho combina esforços de simulação numérica e de análise de dados para investigar a dinâmica em diversos compartimentos (oceano aberto, plataforma continental e zona costeira-estuarina) e, em multiplas escalas, na Margem Continental Leste Brasileira (MCLB). A circulação de largo e mesoescala espacial e a propagação da maré barotrópica são investigadas através de uma configuração aninhada do modelo numérico ROMS. O estudo da dinâmica regional da Baía de Camamu (CMB) baseia-se na análise de dados locais. A MCLB, localizada a SW do Atlântico Sul entre 8±S e 20±S, possui plataforma estreita, batimetria complexa, e baixa produtividade primária. A sua dinâmica é influenciada pela divergência da Corrente Sul Equatorial (CSE). As simulações refletem as conexões sazonais e espaciais entre a Corrente do Brasil e a Contra Corrente Norte do Brasil , em conexão com a dinâmica da CSE. As simulações revelam atividades vorticais nas proximidades da costa e interações com a dinâmica costeira, cujos padrões são descritos. A validação do modelo em mesoescala é baseada em cálculos de energia cinética turbulenta e em dados históricos de transporte. A CMB, localizada a 13±400S, abriga uma comunidade piscatória tradicional e extenso de manguezal. Situa-se porém sobre uma bacia sedimentar com grande reservas de óleo e gás, estando em tensão permanente de impacto ambiental. Neste trabalho sumarizamos as condições físicas regionais e investigamos sua dinâmica interna, focando sua variabilidade em amostragens realizadas sob condições de seca (Setembro de 2004) e de chuva (Julho de 2005). Finalmente, o modelo numérico ROMS é forçado com o sinal de maré, empregando-se uma configuração simples (com coeficientes de atrito de fundo constantes e condições hidrográficas homogéneas), com o intuito de avaliar sua resposta e investigar a natureza da propagação da maré barotrópica na MCLB, convergindo na CMB. A análise da resposta do modelo à maré basea-se em séries históricas do nível do mar para a MCLB e dados recentes da CMB.

Alcohol gel ingestion amongst homeless Eastern and Central Europeans in London: assessing the effects on cognitive functioning and psychological health

Background: Intentional consumption of alcohol based hand gels has been reported especially amongst non-UK national, alcohol dependent, homeless individuals in London. Whilst alcohol misuse is known to be associated with impaired cognitive functioning and mental health problems, the effects of additional ingestion of alcohol gel are unknown. Objectives: To explore cognitive and psychological functioning in users who intentionally ingest alcohol gel compared with ethyl-alcohol only misusers and controls. Methods: Male, Central and Eastern European alcohol only misusers, (n=14; mean age 39 years), alcohol gel users (n=14; mean age 43 years) and controls (n=12; mean age 31 years) were recruited from a London Homeless Service during 2013/14. Alcohol misusers, alcohol gel users and controls were compared on the Forwards and Backwards Digit Span Test; Block Design test; Retrospective and Prospective Memory Questionnaire (PRMQ) and the Hospital and Anxiety Depression Scale (HADS). Results: Alcohol gel users performed significantly worse on the Block Design task (p<0.01) and PRMQ (p<0.01) relative to both alcohol only and control groups, and significantly worse on the digit span relative to controls (p=0.01). Both alcohol misusing groups scored comparatively on digit span backwards (p<0.01), with both groups performing significantly worse than controls. The alcohol gel group reported significantly higher levels of anxiety relative to controls (p=0.02). Conclusions: Whilst there could be constitutional differences between alcohol misusers who additionally abuse alcohol gel, the findings suggest that alcohol gel ingestion may have a greater impact on psychological functioning than traditional alcohol misuse.

Application of DPSIR framework integrated with multiple regression model to simulate Guadiana catchment - estuary continuum, south eastern Iberia

Dissertação de Mestrado, Gestão da Água e da Costa, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2010

Beach quality assessment and management in the Sotavento (Eastern) Algarve, Portugal

The purpose of this study on beach quality assessment and management was to evaluate the quality of five beaches in the Algarve Sotavento region of Portugal and to identify beach users’ preferences and priorities regarding their visit to a beach. The Algarve is one of the country’s most internationally known regions and it is generally perceived as a major tourist destination. Because of the increasing level of tourists, there is a specific need to address beach quality, as overcrowding can result in excessive litter, reduce water quality and consequently reduce the socio-economic value of the area. The main methodology for the evaluation of the beach quality in this pilot project was the Bathing Area Registration and Evaluation framework (BARE), which recognizes five beach types (rural, remote, resort, urban and village) through five main priority issues of concern to beach users (water quality, scenery, litter, safety, facilities) and evaluates the beach quality, ranging from one (low) to five (high) stars. After overall bathing area classification, Quarteira-Vilamoura, Ilha do Farol, Ilha Deserta and Ilha da Armona received three-star rating and Quinta do Lago site obtained a one-star rating. The quantitative research data on beach users’ preferences and priorities was obtained through administration of 50 questionnaires per beach and showed that beach users at all sites expressed the need for improved cleanliness, safety and facilities on the beach. The BARE framework, together with the questionnaire surveys, allowed the identification of management priorities required to improve the quality of individual beaches and therefore increase income from tourism.

Morphological variation in eight species sparidae of the eastern atlantic and mediterranean sea

Tese de Doutoramento, Ciências do Mar especialidade Zoologia Marinha, Faculdade de Ciências do Mar e do Ambiente, Universidade do Algarve, 2002

Speech of Mr. C. G. Memminger, on the question of rechartering the bank of the state of South Carolina: delivered in the House of Representatives, December 9, 1848

This speech by Mr. Memminger offers resolutions on the issue of rechartering the bank of the state of South Carolina. The issues presented are the Bank of the State is founded on an erroneous policy, unwise for a state to engage in banking, not practical to recharter the Bank of the State and a special committee of each house should be appointed to advise how to carry out these resolutions at the next session.

Speech of Mr. Calhoun, of South Carolina, on the slavery question. Delivered in the Senate of the United States, March 4, 1850

The speech addresses the question, how can the union be preserved? He goes on to explain the threats to the union and give suggestions for how the threats can be handled.

Open-domain web-based multiple document : question answering for list questions with support for temporal restrictors

Tese de doutoramento, Informática (Ciências da Computação), Universidade de Lisboa, Faculdade de Ciências, 2015

A question of tomorrow: Blanchot, surrealism and the time of the fragment

This article offers a close critical reading of Blanchot's essay on Surrealism, 'Tomorrow at Stake', raising a series of questions concerning the time of 'Surrealist experience' and its relation to those temporal structures inscribed within the concepts of modernity, the avant-garde, and (art) history itself. It is argued, through a posited connection to Romantic conceptions of the fragment, that those 'reflexes of the future' which for Surrealism determine the value of the present, may be understood, philosophically, in relation to diverse conceptions of the 'openness' of the question, in turn suggesting a more complex understanding of Surrealism's 'avant-garde' character.

How does globalization affect the tax burden on labour income, capital income and consumption in different welfare regimes? The case of Western and Eastern EU Member States

This article analyzes the effects of globalization on implicit tax rates (ITRs) on labor income, capital income, and consumption in the EU15 and Central and Eastern European New Member States (CEE NMS). We find supportive evidence for an increase in the ITR on labor income in the EU15, but no effect on the ITR on capital income. There is evidence of convergence in terms of the ITR on consumption, as countries with higher than average ITR on consumption respond to globalization by decreasing their tax rates. There are important differences among the welfare regimes within the EU15. Social-democratic countries have decreased the tax burden on capital, but increased that on labor due to globalization. Globalization exerts a pressure to increase taxes on labor income in the conservative and liberal regimes as well. Taxes on consumption decrease in response to globalization in the conservative and social-democratic regimes. In the CEE NMS, there is no effect of globalization on the ITR on labor and capital income, but we find a negative impact on the ITR on consumption in the CEE NMS with higher than average ITR on consumption. (JEL H23, H24, H25, F19, F21)