Active site labeling of cysteine cathepsins by a straightforward diazomethylketone probe derived from the N-terminus of human cystatin C

We designed a straightforward biotinylated probe using the N-terminal substrate-like region of the inhibitory site of human cystatin C as a scaffold, linked to the thiol-specific reagent diazomethylketone group as a covalent warhead (i.e. Biot-(PEG)2-Ahx-LeuValGly-DMK). The irreversible activity-based probe bound readily to cysteine cathepsins B, L, S and K. Moreover affinity labeling is sensitive since active cathepsins were detected in the nM range using an ExtrAvidin®-peroxidase conjugate for disclosure. Biot-(PEG)2-Ahx-LeuValGly-DMK allowed a slightly more pronounced labeling for cathepsin S with a compelling second-order rate constant for association (kass = 2,320,000 M−1 s−1). Labeling of the active site is dose-dependent as observed using 6-cyclohexylamine-4-piperazinyl-1,3,5-triazine-2-carbonitrile, as competitive inhibitor of cathepsins. Finally we showed that Biot-(PEG)2-Ahx-LeuValGly-DMK may be a simple and convenient tool to label secreted and intracellular active cathepsins using a myelomonocytic cell line (THP-1 cells) as model.

Stability in a Network Economy: The Role of Institutions

We consider an economy in which agents are embedded in a network of potential value-generating relationships. Agents are assumed to be able to participate in three types of economic interactions: Autarkic self-provision; bilateral interaction; and multilateral collaboration through endogenously provided platforms.
We introduce two stability concepts and provide sufficient and necessary conditions on the network structure that guarantee existence, in cases of the absence of externalities, link-based externalities and crowding externalities. We show that institutional arrangements based on socioeconomic roles and leadership guarantee stability. In particular, the stability of more complex economic outcomes requires more strict and complex institutional rules to govern economic interactions. We investigate strict social hierarchies, tiered leadership structures and global market places.

Socialized credit and the working-class family economy: a comparative history of Britain and France 1900-2000

This paper provides a comparative analysis of working class consumer credit in Britain and France from the early twentieth century through to the 1980s. It indicates a number of similarities between the two nations in the earlier part of the period: in particular, in the operation of doorstep credit systems. For the British case study, we explore consumer finance offered by credit drapers (sometimes known as tallymen) whilst in France the paper explores a similar system that functioned in the coalmining communities around the city of Lens. Both methods operated on highly socialised relationships that established the trust on which credit was offered and long-term creditor/borrower relationships established. In the second part of the paper, we analyse the different trajectories taken in post-war France and Britain in this area of working class credit. In France this form of socialized credit gradually dwindled due to factors such as ‘Bancarisation’, which saw the major banks emerge as modern bureaucratized providers of credit for workers and their families. In contrast, in Britain the tallymen (and other related forms of doorstep credit providers) were offered a new lease of life in the 1960s and 1970s. This was a period during which British credit providers utilised multiple methods to evade the hire purchase controls put in place by post-war governments. Thus, whilst the British experience was one of fragmented consumer loan types (including the continuation of doorstep credit), the French experience (like elsewhere in Europe) was one of greater consolidation. The paper concludes by reflecting on the role of these developments in the creation of differential experiences of credit inclusion/exclusion in the two nations and the impact of this on financial inequality.

Does childhood bullying lead to the development of psychotic symptoms? A meta-analysis and review of prospective studies

Purpose: Researchers have demonstrated associations between trauma and psychosis. Childhood trauma, in particular, appears to be an important determinant. Recently, bullying has become considered a traumatic experience in its own right. This review aims to analyse research with prospective designs, which will enable conclusions about whether or not bullying causes psychosis.

Methods: A systematic review of the literature was carried out independently by two reviewers. Eligibility and quality assessment criteria were applied. A meta-analysis and narrative synthesis were then completed.

Results: Ten studies met inclusion criteria. Four used data from the same large database, and were combined as one. The majority provided confirmation that bullying appears to cause later development of psychosis. A meta-analysis yielded an unadjusted odds ratio (OR) of 2.148 [95% confidence interval (CI) 1.140–4.044].

Conclusions: The studies reviewed here suggest that bullying does predict the later development of psychotic symptoms. What is lacking from the literature is adequate investigation into other potential mediating factors. The current review highlights the significant role of bullying within this complex interaction. Potential mediating variables are explored, including a dose–response effect for the severity and frequency of victimization. Suggestions for targeting intervention are also suggested alongside clinical implications and recommendations for future research.

Clostridium difficile Ribotype 023 Lacks the Ability To Hydrolyze Esculin, Leading to False-Negative Results on Chromogenic Agar

41.Connor, M.C., Fairley, D.J. Marks, N.J. McGrath, J.W. (2016) Clostridium difficile Ribotype 023 lacks the ability to hydrolyse esculin, leading to false negative results on chromogenic agar. Letters in Applied Microbiology

On the Ontological Quality and Logical Quality of Conceptual-Modeling Grammars: The Need for a Dual Perspective

A core activity in information systems development involves building a conceptual model of the domain that an information system is intended to support. Such models are created using a conceptual-modeling (CM) grammar. Just as high-quality conceptual models facilitate high-quality systems development, high-quality CM grammars facilitate high-quality conceptual modeling. This paper provides a new perspective on ways to improve the quality of the semantics of CM grammars. For many years, the leading approach to this topic has relied on ontological theory. We show, however, that the ontological approach captures only half the story. It needs to be coupled with a logical approach. We explain how the ontological quality and logical quality of CM grammars interrelate. Furthermore, we outline three contributions that a logical approach can make to evaluating the quality of CM grammars: a means of seeing some familiar conceptual-modeling problems in simpler ways; the illumination of new problems; and the ability to prove the benefit of modifying existing CM grammars in particular ways. We demonstrate these benefits in the context of the Entity-Relationship grammar. More generally, our paper opens up a new area of research with many opportunities for future research and practice.

Papel do educador na avaliação e intervenção de crianças com necessidades educativas especiais

Relátorio de estágio apresentado para obtenção do grau de Mestre na especialidade de Educação Pré-escolar

‘A true feeling of authentic portuguese golf'? The discursive construction of the Algarve region in portuguese golf websites

In an increasingly competitive global marketplace, the need for golf destinations to differentiate themselves from competitors has become more critical than ever. This paper raises questions about the promotional strategies employed by the golf sector in the Algarve, focusing on internet communication strategies, since this medium has become the biggest driving force towards the commoditisation of all aspects of the tourism experience. By offering a complementary perspective to the field of (critical) tourism studies, and drawing on a qualitative, multi-modal discourse analysis, this work-in-progress looks at the particular ways that representations and images presented on the Algarve golf websites constitute and frame identities (of people and places) and socio-spatial relationships. This paper analyses a corpus of 45 texts collected from official websites of the 40 Algarve golf courses and from five entities which promote the Algarve as a golf destination, along with the golf images that are displayed alongside them. Findings point to salient discursive and visual representations of a global setting enjoyed by the global elite. Whereas the courses‟ positioning in relation to their regional competitors draws on similar discursive strategies which reflect those used in tourism advertising discourses in general – e.g. reiteration of explicit comparisons, superlatives and hyperbolic statements -, representations of local emplacedness are not salient; in some cases local place seems to have been almost intentionally suppressed.

Visuoperceptual deficits and participation in older adults after stroke

Introduction: Visuoperceptual deficits frequently occur after a stroke but little is known about how they evolve over time. These deficits may have an impact on participation in daily activities and social roles. Objectives: The aims were to 1) track changes over six months in the visual perception of older adults with persistent visuoperceptual deficits after a stroke; 2) examine if these changes differed between participants who had and had not received rehabilitation services; and 3) verify if participation differed between participants with and without visuoperceptual deficits. Methods: Visual perception as well as participation of 189 older adults who had had a stroke were evaluated in the first month (T1) after being discharged home from an acute care hospital (NO REHAB group) or rehabilitation unit (REHAB group). For visual perception, only participants presenting deficits at T1 were re-evaluated at 3 months (T2; n=93), and those with deficits at T2 were re-evaluated at 6 months (T3; n=61). Results: A total of 57 people (30.2%) had visuoperceptual deficits six months after discharge home. Despite persistent deficits, approximately 45% of the participants in the two groups improved while 50% of the NO REHAB group and 24.3% of the REHAB group deteriorated. Changes in the mean scores on the MVPT-V were similar in the two groups. Participation, and especially participation in social roles, was more restricted in participants with visuoperceptual deficits (p<0.001), whatever the severity of the stroke. Conclusion: Visuoperceptual deficits are common post-stroke. However, they evolve differently in different people and are associated with a reduction in participation.

The First Year Experience of Occupational Therapy Students at an Australian Regional University: Promoting Student Retention and Developing a Regional and Remote Workforce

Abstract Objective: Student retention at regional universities is important in addressing regional and remote workforce shortages. Students attending regional universities are more likely to work in regional areas. First year experience at university plays a key role in student retention. This study aimed to explore factors influencing the first year experience of occupational therapy students at a regional Australian university. Design: Surveys were administered to 58 second year occupational therapy students in the first week of second year. Data were analysed using descriptive statistics, inferential statistics (Pearson χ2; Spearman rho) and summarising descriptive responses. Setting: An Australian regional university. Participants: Second year undergraduate occupational therapy students. Main outcome measures: Factors influencing students’ decisions to study and continue studying occupational therapy; factors enhancing first year experience of university. Results: Fifty-four students completed the survey (93.1%). A quarter (25.9%) of students considered leaving the course during the first year. The primary influence for continuing was the teaching and learning experience. Most valued supports were orientation week (36.7%) and the first year coordinator (36.7%). Conclusion: The importance of the first year experience in retaining occupational therapy students is highlighted. Engagement with other students and staff and academic support are important factors in facilitating student retention. It is important to understand the unique factors influencing students’ decisions, particularly those from regional and remote areas, to enter and continue in tertiary education to assist in implementing supports and strategies to improve student retention.

Senior Managers’ Perspectives of Leading and Managing Effective, Sustainable and Successful Partnerships

Formal and informal partnerships have become key features of education policy and practice in many countries and managing such collaborative arrangements is an important dimension of the role(s) of leaders of educational organizations. Recent research has shown both the tensions and conflict that can develop in partnerships as well as the opportunities and benefits of partnership working for organizations and individuals. This article focuses on the characteristics of partnerships that contribute to their effectiveness, sustainability and success, filling a gap in the literature on educational partnerships. The research data emanate from a qualitative study of partnership working in England. The study used a grounded approach and inductively linked characteristics of partnerships found in the partnership literature with empirical data from a case study of a subregional partnership of education and training organizations. This combined evidence is used to conceptualize partnership as a continuum of weak to strong forms of partnership and to develop a table of characteristics which underpin such partnerships. The findings reveal the extent to which trust, networks, norms and values support effective, sustained and successful partnerships. These characteristics are differentiated and may fluctuate during the lifecourse of a partnership but remain fundamental features of partnership working and significantly contribute to the strength and effectiveness of partnerships.

Play it Again

Tese de doutoramento, Belas-Artes (Pintura), Universidade de Lisboa, Faculdade de Belas-Artes, 2016