Attenuation of monocyte chemotaxis--a novel anti-inflammatory mechanism of action for the cardio-protective hormone B-type natriuretic peptide

B-type natriuretic peptide (BNP) is a prognostic and diagnostic marker for heart failure (HF). An anti-inflammatory, cardio-protective role for BNP was proposed. In cardiovascular diseases including pressure overload-induced HF, perivascular inflammation and cardiac fibrosis are, in part, mediated by monocyte chemoattractant protein (MCP)1-driven monocyte migration. We aimed to determine the role of BNP in monocyte motility to MCP1. A functional BNP receptor, natriuretic peptide receptor-A (NPRA) was identified in human monocytes. BNP treatment inhibited MCP1-induced THP1 (monocytic leukemia cells) and primary monocyte chemotaxis (70 and 50 %, respectively). BNP did not interfere with MCP1 receptor expression or with calcium. BNP inhibited activation of the cytoskeletal protein RhoA in MCP1-stimulated THP1 (70 %). Finally, BNP failed to inhibit MCP1-directed motility of monocytes from patients with hypertension (n = 10) and HF (n = 6) suggesting attenuation of this anti-inflammatory mechanism in chronic heart disease. We provide novel evidence for a direct role of BNP/NPRA in opposing human monocyte migration and support a role for BNP as a cardio-protective hormone up-regulated as part of an adaptive compensatory response to combat excess inflammation.

Enabling Provenance on the Web: Standardization and Research Questions

Provenance is a record that describes the people, institutions, entities, and activities, involved in producing, influencing, or delivering a piece of data or a thing in the world. Some 10 years after beginning research on the topic of provenance, I co-chaired the provenance working group at the World Wide Web Consortium. The working group published the PROV standard for provenance in 2013. In this talk, I will present some use cases for provenance, the PROV standard and some flagship examples of adoption. I will then move on to our current research area aiming to exploit provenance, in the context of the Sociam, SmartSociety, ORCHID projects. Doing so, I will present techniques to deal with large scale provenance, to build predictive models based on provenance, and to analyse provenance.

Web Knowledge and Web Governance: WAIS PhD Research Reports

Abstract This seminar consists of two very different research reports by PhD students in WAIS. Hypertext Engineering, Fettling or Tinkering (Mark Anderson): Contributors to a public hypertext such as Wikipedia do not necessarily record their maintenance activities, but some specific hypertext features - such transclusion - could indicate deliberate editing with a mind to the hypertext’s long-term use. The MediaWiki software used to create Wikipedia supports transclusion, a deliberately hypertextual form of content creation which aids long terms consistency. This discusses the evidence of the use of hypertext transclusion in Wikipedia, and its implications for the coherence and stability of Wikipedia. Designing a Public Intervention - Towards a Sociotechnical Approach to Web Governance (Faranak Hardcastle): In this talk I introduce a critical and speculative design for a socio-technical intervention -called TATE (Transparency and Accountability Tracking Extension)- that aims to enhance transparency and accountability in Online Behavioural Tracking and Advertising mechanisms and practices.

Nature-based solutions to climate change mitigation and adaptation in urban areas: perspectives on indicators, knowledge gaps, barriers, and opportunities for action

Nature-based solutions promoting green and blue urban areas have significant potential to decrease the vulnerability and enhance the resilience of cities in light of climatic change. They can thereby help to mitigate climate change-induced impacts and serve as proactive adaptation options for municipalities. We explore the various contexts in which nature-based solutions are relevant for climate mitigation and adaptation in urban areas, identify indicators for assessing the effectiveness of nature-based solutions and related knowledge gaps. In addition, we explore existing barriers and potential opportunities for increasing the scale and effectiveness of nature-based solution implementation. The results were derived from an inter- and transdisciplinary workshop with experts from research, municipalities, policy, and society. As an outcome of the workshop discussions and building on existing evidence, we highlight three main needs for future science and policy agendas when dealing with nature-based solutions: (i) produce stronger evidence on nature-based solutions for climate change adaptation and mitigation and raise awareness by increasing implementation; (ii) adapt for governance challenges in implementing nature-based solutions by using reflexive approaches, which implies bringing together new networks of society, nature-based solution ambassadors, and practitioners; (iii) consider socio-environmental justice and social cohesion when implementing nature-based solutions by using integrated governance approaches that take into account an integrative and transdisciplinary participation of diverse actors. Taking these needs into account, nature-based solutions can serve as climate mitigation and adaptation tools that produce additional cobenefits for societal well-being, thereby serving as strong investment options for sustainable urban planning.

Evaluation of Tottenham Thinking Space Pilot: Final Report. Research Report 11.

This reports summarises research that began in March 2014 and was completed in October 2015 by an experienced inter-disciplinary research team from the Centre for Social Justice and Change and Psycho-Social Research Group, School of Social Sciences, the University of East London (UEL) and included Dr Yang Li from the Centre for Geo-Information Studies, UEL, for the first phase of the study. Tottenham ‘Thinking Space’ (TTS) was a pilot therapeutic initiative based in local communities and delivered by the Tavistock & Portman NHS Foundation Trust and funded by the London Borough of Haringey Directorate of Public Health. TTS aimed to improve mental health and enable and empower local communities. TTS was situated within a mental health agenda that was integral to Haringey’s Health and Wellbeing Strategy 2012-2015 and aimed to encourage people to help themselves and each other and develop confident communities. On the one hand TTS was well-suited to this agenda, but, on the other, participants were resistant to, and were trying to free themselves from labelling that implied ‘mental health difficulties’. A total of 243 meetings were held and 351 people attended 1,716 times. The majority of participants attended four times or less, and 33 people attended between 5 and 10 times and 39 people attended over 10 times. Attending a small number of times does not necessarily mean that the attendee was not helped. Attendees reflected the ethnic diversity of Tottenham; 29 different ethnic groups attended. The opportunity to meet with people from different cultural backgrounds in a safe space was highly valued by attendees. Similarly, participants valued the wide age range represented and felt that they benefited from listening to inter-generational experiences. The majority of participants were women (72%) and they were instrumental in initiating further Thinking Spaces, topic specific meetings, the summer programme of activities for mothers and young children and training to meet their needs. The community development worker had a key role in implementing the initiative and sustaining its growth throughout the pilot period. We observed that TTS attracted those whose life experiences were marked by personal struggle and trauma. Many participants felt safe enough to disclose mental health difficulties (85% of those who completed a questionnaire). Participants also came seeking a stronger sense of community in their local area. Key features of the meetings are that they are democratic, non-judgemental, respectful, and focussed on encouraging everyone to listen and to try to understand. We found that the therapeutic method was put in place by high quality facilitators and health and personal outcomes for participants were consistent with those predicted by the underpinning psychoanalytical and systemic theories. Outcomes included a reduction in anxieties and improved personal and social functioning; approximately two thirds of those who completed a questionnaire felt better understood, felt more motivated and more hopeful for the future. The overwhelming majority of survey respondents also felt good about contributing to their community, said that they were more able to cooperate with others and accepting of other cultures, and had made new friends. Participants typically had a better understanding of their current situation and how to take positive action; of those who completed a questionnaire, over half felt more confident to seek support for a personal issue and to contact services. Members of TTS supported each other and instilled hope and build community-mindedness that reduced social isolation.

Oncology research and clinical decisions based on immunohistochemistry: the importance of the technical aspects that support a complex method

Immunohistochemistry (IHC) is the group of techniques that use antibodies as specific reagents to identify and demonstrate several cell and tissue components that are antigens. This linking allows locating and identifying the in situ presence of various substances by means of color that is associated with the formed antigen-antibody complexes. The practical value of this biotechnology area, widely used in Pathology and Oncology, in diagnostic, prognostic, theranostic and research context, results from the possibility of combining a colour marker with an antibody without causing any damage to specific binding established between antibody and antigen. This provides the microscopic observation of the target locations where the antibody and hence the antigen are present. IHC is presented as a powerful means for identification of several cellular and tissue structures that can be associated with pathologies, and of the consequences, at functional and morphological level, of these same elements action.

Developmental TVET rhetoric in-action: the White Paper for post-school education and training in South Africa

This paper explores the extent to which latest developments in the Technical and Vocational Education and Training System in South Africa respond to key principles espoused for a developmental, democratic and inclusionary ideal. The White Paper for post school education and training approved by Cabinet in November, 2013 is referred to by the Minister as the “definitive statement of the governments vision for the post school system” and as such represents a crucial strategy document intended to chart the TVET direction to 2030. Using key theoretical constructs from development theory, this paper provides an assessment of the TVET strategy contained is the paper and explores the extent to which it does respond to the agenda defined by the promise. It is argued that the challenges outlined are not yet able to provide the blueprint for a TVET transformative vision. It is concluded that while the development rhetoric contained in the paper is plausible, the creative tinkering of the system is unlikely to lead to the radical revisioning necessary for a truly transformative TVET system. The underlying assumptions regarding purpose, impact and outcome will need to be carefully reconsidered if the system is to be responsive to the promises of the democratic developmental ideal to which the government is committed. (DIPF/Orig.)

Motivation in action: A process model of L2 motivation

As part of a long-term project aimed at designing classroom interventions to motivate language learners, we have searched for a motivation model that could serve as a theoretical basis for the methodological applications. We have found that none of the existing models we considered were entirely adequate for our purpose for three reasons: (1) they did not provide a sufficiently comprehensive and detailed summary of all the relevant motivational influences on classroom behaviour; (2) they tended to focus on how and why people choose certain courses of action, while ignoring or playing down the importance of motivational sources of executing goal-directed behaviour; and (3) they did not do justice to the fact that motivation is not static but dynamically evolving and changing in time, making it necessary for motivation constructs to contain a featured temporal axis. Consequently, partly inspired by Heckhausen and Kuhl's 'Action Control Theory', we have developed a new 'Process Model of L2 Motivation', which is intended both to account for the dynamics of motivational change in time and to synthesise many of the most important motivational conceptualisations to date. In this paper we describe the main components of this model, also listing a number of its limitations which need to be resolved in future research.

A novel mechanism of action of HER2 targeted immunotherapy is explained by inhibition of NRF2 function in ovarian cancer cells

Nuclear erythroid related factor-2 (NRF2) is known to promote cancer therapeutic detoxification and crosstalk with growth promoting pathways. HER2 receptor tyrosine kinase is frequently overexpressed in cancers leading to uncontrolled receptor activation and signaling. A combination of HER2 targeting monoclonal antibodies shows greater anticancer efficacy than the single targeting antibodies, however, its mechanism of action is largely unclear. Here we report novel actions of anti-HER2 drugs, Trastuzumab and Pertuzumab, involving NRF2. HER2 targeting by antibodies inhibited growth in association with persistent generation of reactive oxygen species (ROS), glutathione (GSH) depletion, reduction in NRF2 levels and inhibition of NRF2 function in ovarian cancer cell lines. The combination of antibodies produced more potent effects than single alone; downregulated NRF2 substrates by repressing the Antioxidant Response (AR) pathway with concomitant transcriptional inhibition of NRF2. We showed the antibody combination produced increased methylation at the NRF2 promoter consistent with repression of NRF2 antioxidant function, as HDAC and methylation inhibitors reversed such produced transcriptional effects. These findings demonstrate a novel mechanism and role for NRF2 in mediating the response of cancer cells to the combination of Trastuzumab and Pertuzumab and reinforce the importance of NRF2 in drug resistance and as a key anticancer target.

Action-Emotion Style, Learning Approach and Coping Strategies, in Undergraduate University Students

Action-Emotion Style (AES) is an affective-motivational construct that describes the achievement motivation that is characteristic of students in their interaction with stressful situations. Using elements from the Type-A Behavior Pattern (TABP), characteristics of competitiveness and overwork occur in different combinations with emotions of impatience and hostility, leading to a classification containing five categories of action-emotion style (Type B, Impatient-hostile type, Medium type, Competitive-Overworking type and Type A). The objective of the present research is to establish how characteristics of action-emotion style relate to learning approach (deep and surface approaches) and to coping strategies (emotion-focused and problem-focused). The sample was composed of 225 students from the Psychology degree program. Pearson correlation analyses, ANOVAs and MANOVAs were used. Results showed that competitiveness-overwork characteristics have a significant positive association with the deep approach and with problem-focused strategies, while impatience-hostility is thus related to surface approach and emotion-focused strategies. The level of action-emotion style had a significant main effect. The results verified our hypotheses with reference to the relationships between action-emotion style, learning approaches and coping strategies.

Joint Action CHRODIS Work Package 5 - Good practices in the field of health promotion and chronic disease prevention across the life cycle: outcomes at a glance

Associated Partners in the Work Package 5: National Health Institute Doutor Ricardo Jorge (INSA), Portugal (Luciana Costa)

Design as a critical research

Historically the imaginary and the hegemonic thinking, in the Western globe north, has been marked by the epistemology and capitalists archetypes. Notwithstanding the design seem as a practice and discipline shielded on a simplistic discourse of functional / communicative efficiency, wandering through by multiple aestheticism apparently neutral in relation to the symbolic, but in fact they never are, because what really hapens is that the aesthetic appearance of the generated forms will always be a review of the powers ruling. We start from the understanding that the act of creating an aesthetic artifact, will also be a movement of inscription in a discursive platform (that precedes it), is in itself an narrative act and that fact represent a certain take place in relation to certain symbolic reality. On reflection shown if it sees design as a discipline and / or an instrument of action, whose operational relevance tends to question and simultaneously rehearsing a response, in which more than why interests answer to why. Apparently the design is a content mediator, but also, it is structure, is body, is idea. We think a design praxis as discipline and enrollment tool of critical thought and social transformation. For guiding research in this text, we propose the following question: Can the Design want for themselves an engagement with the symbolic in order to be an active part in the production of critical thinking in the place where it belongs? Methodologically our argument will be present in two differents moments: 1. a first, exploratory nature where we rescue the draw issues in the practice of design and 2. a second analytical nature concerning the subject issues (graphic and / or utility ) design and how it incorporates formal rites, political events and social practices of contemporary everyday life. We consider the praxis of design as a discipline and critical thinking enrollment tool as agents of social transformation. With this study we seek for contribute phenomenology design by studying the artifacts of configuration as well as the possible messages they convey and what impact they may have on the social network.

Action and perception: Neural indices of learning in infants

Early human development offers a unique perspective in investigating the potential cognitive and social implications of action and perception. Specifically, during infancy, action production and action perception undergo foundational developments. One essential component to examine developments in action processing is the analysis of others’ actions as meaningful and goal-directed. Little research, however, has examined the underlying neural systems that may be associated with emerging action and perception abilities, and infants’ learning of goal-directed actions. The current study examines the mu rhythm—a brain oscillation found in the electroencephalogram (EEG)—that has been associated with action and perception. Specifically, the present work investigates whether the mu signal is related to 9-month-olds’ learning of a novel goal-directed means-end task. The findings of this study demonstrate a relation between variations in mu rhythm activity and infants’ ability to learn a novel goal-directed means-end action task (compared to a visual pattern learning task used as a comparison task). Additionally, we examined the relations between standardized assessments of early motor competence, infants’ ability to learn a novel goal-directed task, and mu rhythm activity. We found that: 1a) mu rhythm activity during observation of a grasp uniquely predicted infants’ learning on the cane training task, 1b) mu rhythm activity during observation and execution of a grasp did not uniquely predict infants’ learning on the visual pattern learning task (comparison learning task), 2) infants’ motor competence did not predict infants’ learning on the cane training task, 3) mu rhythm activity during observation and execution was not related to infants’ measure of motor competence, and 4) mu rhythm activity did not predict infants’ learning on the cane task above and beyond infants’ motor competence. The results from this study demonstrate that mu rhythm activity is a sensitive measure to detect individual differences in infants’ action and perception abilities, specifically their learning of a novel goal-directed action.

Analysing intention and action in mobile banking services

Technological advances at the level of mobile devices are transforming the world. Banking users are able to conduct banking services at any place, and at any time, with m-banking. The purpose of this research is to analyse intention and action in m-banking services. A research model was developed and PLS was used to test the causalities in the proposed model. Our proposal extends the existing models with an assessment of the actual usage of m-banking and of how behavioural intention translates into action. This study found that the main determinants of behavioural intention for m-banking are social influence and relative advantage. Furthermore, perceived risk, lack of information and usage barriers have a negative effect on m- banking behavioural intention. Perceived risks, e-banking use, and behaviour intention are found to be significant antecedents of m-banking use. Gender has a positive and significant influence on m-banking usage, but not on the construction of behavioural intention.