Modes of action of antibacterial agents

This chapter describes the modes of action of the major antibiotics and synthetic agents used to treat bacterial infections. Particular attention is given to the biochemical mechanisms by which the agents interfere with biosynthetic processes and the basis for their selective antibacterial action. Interference with the biosynthesis and assembly of structural components of the bacterial cell wall provides the basis for many important groups of antibiotics, including the agents targeting steps in peptidoglycan synthesis. Other agents exploit more subtle differences between bacteria and mammalian cells in fundamental processes such as DNA, RNA and protein synthesis.

A domain specific modeling approach for coordinating user-centric communication services

Rapid advances in electronic communication devices and technologies have resulted in a shift in the way communication applications are being developed. These new development strategies provide abstract views of the underlying communication technologies and lead to the so-called user-centric communication applications. One user-centric communication (UCC) initiative is the Communication Virtual Machine (CVM) technology, which uses the Communication Modeling Language (CML) for modeling communication services and the CVM for realizing these services. In communication-intensive domains such as telemedicine and disaster management, there is an increasing need for user-centric communication applications that are domain-specific and that support the dynamic coordination of communication services commonly found in collaborative communication scenarios. However, UCC approaches like the CVM offer little support for the dynamic coordination of communication services resulting from inherent dependencies between individual steps of a collaboration task. Users either have to manually coordinate communication services, or reply on a process modeling technique to build customized solutions for services in a specific domain that are usually costly, rigidly defined and technology specific. ^ This dissertation proposes a domain-specific modeling approach to address this problem by extending the CVM technology with communication-specific abstractions of workflow concepts commonly found in business processes. The extension involves (1) the definition of the Workflow Communication Modeling Language (WF-CML), a superset of CML, and (2) the extension of the functionality of CVM to process communication-specific workflows. The definition of WF-CML includes the meta-model and the dynamic semantics for control constructs and concurrency. We also extended the CVM prototype to handle the modeling and realization of WF-CML models. A comparative study of the proposed approach with other workflow environments validates the claimed benefits of WF-CML and CVM.^

Decision-making under extreme *uncertainty: Rethinking hazard -related perceptions and action

Understanding who evacuates and who does not has been one of the cornerstones of research on the pre-impact phase of both natural and technological hazards. Its history is rich in descriptive illustrations focusing on lists of characteristics of those who flee to safety. Early models of evacuation focused almost exclusively on the relationship between whether warnings were heard and ultimately believed and evacuation behavior. How people came to believe these warnings and even how they interpreted the warnings were not incorporated. In fact, the individual seemed almost removed from the picture with analysis focusing exclusively on external measures. ^ This study built and tested a more comprehensive model of evacuation that centers on the decision-making process, rather than decision outcomes. The model focused on three important factors that alter and shape the evacuation decision-making landscape. These factors are: individual level indicators which exist independently of the hazard itself and act as cultural lenses through which information is heard, processed and interpreted; hazard specific variables that directly relate to the specific hazard threat; and risk perception. The ultimate goal is to determine what factors influence the evacuation decision-making process. Using data collected for 1998's Hurricane Georges, logistic regression models were used to evaluate how well the three main factors help our understanding of how individuals come to their decisions to either flee to safety during a hurricane or remain in their homes. ^ The results of the logistic regression were significant emphasizing that the three broad types of factors tested in the model influence the decision making process. Conclusions drawn from the data analysis focus on how decision-making frames are different for those who can be designated “evacuators” and for those in evacuation zones. ^

A inserção da família no processo socioeducativo de adolescentes em privação de liberdade

This master thesis has the main goal investigate how families are inserted in the socioeducational process of teenagers who are undergoing social measures of liberty deprivation. The specific objectives are: to characterize the family´s living together of adolescents deprived of their freedom and their families, from the actions and routines of the socio-educational system; to assess the professional working links in the context of socio-education, in order to care and strengthening families of the adolescents; to investigate how families evaluate the operation of socio-educational process in which adolescents are met. Method: to achieve the proposed objectives, data collection occurred in complementary steps: the first phase took place from visits to socioeducational units of liberty deprivation of RN, and dialogues with professionals working in socio-education. Subsequently, action research stage was carried out, from the insertion of the researcher in the extension project Family and the struggle for the effectiveness of the National Socio Service System, that aimed to strengthen monitoring the adolescents socio-education by their families, and had as methodology the conversation circles and thematic workshops. Lastly, were performed reading and analysis of the references to the family in the Individual Care Plans (PIAs) for adolescents. The information gathered was recorded in field diaries and subjected to thematic content analysis. This research was guided by the Marxist theoretical framework, structured on the understanding of the involvement of adolescents with illegal acts as a development and expression of the social question. From this theoretical framework, the prevailing view in the capitalist society of adolescents in conflict with the law as individuals who are treated by means of repression and segregation and the weakness of social policies is questioned, both in the execution of their own socioeducational measures as the articulation of network services for adolescent protection and strengthening your family. Results: in relation to the operation of the socioeducational system in RN in general, it was observed a state of unhealthy physical spaces and institutional practices that violate human rights, idleness and lack of access to social rights, and criminalization and institutionalization of poor young people and their families. With regard to family´s living together, it was noticed great distance between principles and guidelines recommended by the SINASE, about acquaintanceship and family strengthening, and every day practices of socio-education in RN: serious violations were observed that undermine the family´s living together, as the distance between the socio-educational units of deprivation of liberty and the cities where families live; absence, irregularity and poor conditions in carrying out the family visits; lack of conjugal visits; restricted and unarticulated actions for the care and strengthening of the families of adolescents, most of whom live in poverty or extreme poverty. Finally, it was found a number of blamefully and punishments to the family, including practices such as inward inspection (visual inspection while naked and squant), plus a series of violence and omissions care that sick family members and weaken the links between adolescents and their families.

Caracterização funcional da BaltMTx, uma miotoxina isolada da peçonha de Bothrops alternatus

CHAPTER II: Snake venoms are a complex mixture of organic and inorganic compounds, proteins and peptides such as aminotransferases, acetylcholinesterase, hyaluronidases, L-amino acid oxidase, phospholipase A2, metalloproteases, serine proteases, lectins, disintegrins, and others. Phospholipase A2 directly or indirectly influence the pathophysiological effect on envenomation, as well as their participation in the digestion of the prey. They have several other activities such as hemolytic indirect action, cardiotoxicity, aggregating of platelets, anticoagulant, edema, myotoxic and inflammatory activities. In this work, we describe the functional characterization of BaltMTx, a PLA2 from Bothrops alternatus that inhibits platelet aggregation and present bactericidal effect. The purification of BaltMTx was carried out through three chromatographic steps (ion-exchange on a DEAE-Sephacel column, followed by hydrophobic chromatography on Phenyl–Sepharose and affinity chromatography on HiTrap™ Heparin HP). The protein was purified to homogeneity as judged by its migration profile in SDS–PAGE stained with coomassie blue, and showed a molecular mass of about 15 kDa under reducing conditions and approximately 25 kDa in non-reducing conditions. BaltMTx showed a rather specific inhibitory effect on platelet aggregation induced by epinephrine in human platelet-rich plasma in a dose-dependent manner, whereas it had little or no effect on platelet aggregation induced by collagen or adenosine diphosphate. BaltMTx also showed antibacterial activity against Staphylococcus aureus and Escherichia coli. High concentrations of BatlMTx stimulated the proliferation of Leishmania (Leishmania) infantum and Leishmania (Viania) braziliensis. BaltMTx induced production of inflammatory mediators such as IL-10, IL-12, TNF-α and NO. BaltMTx could be of medical interest as a new tool for the development of novel therapeutic agents for the prevention and treatment of thrombotic disorders as well as bactericidal agent.

WHEN INTERACTING ONLINE LEADS TO TAKING ACTION OFFLINE: EXAMINING THE EFFECTS OF ONLINE PERSUASION ON IS USERS’ PRO-ENVIRONMENTAL BEHAVIOURS

With the increasing attention towards the role of information systems (IS) as a vehicle to address environmental issues, IS researchers and practitioners have strived to leverage advanced Green IS innovations to persuade people to engage in environmentally responsible practices and support pro-environmental initiatives. Yet, existing research reveals that the persuasion effects of Green IS designs remain equivocal. In particular, many design characteristics advocated in Green IS research can produce bi-directional changes in IS users’ attitudes and behaviours. To address this issue, this thesis drew upon the circumplex model of social values (S.H. Schwartz, 1992) to explain when and how online persuasion designs come to affect people’s judgements on resource conservation and environmental protection. Three sets of working propositions and specific hypotheses were developed. Specifically, this research suggests that the use of an IS application can elicit different value primes and draw IS users’ attentions to different motivational functions of engaging in suggested behavioural changes. It is expected that matching online persuasion appeals with IS users’ personal value priorities can increase users’ acceptance of online behavioural suggestions. Second, it is hypothesized that the persuasion effect tends to be weakened, as the system users become aware of the valuematching design in a given IS application. Third, it is proposed that different value primes presented in an IS application can result in different unintended effects on IS users’ global pro-environmental attitudes and motivations. The hypotheses were tested in the two pilot studies and two full-scale online experiments. The study findings generally support the main predictions of the hypotheses. On the one hand, this thesis providesiii empirical evidence that IS design for online persuasion can be instrumental in influencing IS users’ judgements on a range of resource conservation practices. On the other hand, this work explains why the effectiveness of IS-enabled online persuasion attempts needs to be measured not only in terms of the intended changes in a target behavioural domain but also in terms of unintended changes in people’s general environmental orientations. Findings in this research may bring a different perspective on understanding and assessing the influence of Green IS applications on IS users’ judgements and behaviou

Small Steps or Giant Leaps? Defining Reconciliation in the Transition from Conflict in Northern Ireland

The context of Northern Ireland in the transition of conflict has produced a range of efforts to bring about reconciliation. However, definitions and understandings of the nature of reconciliation differ. This paper draws together how reconciliation has been defined in theory in Northern Ireland and elsewhere, examines some models of practice in the light of that theory and illustrates the process of reconciliation through general initiatives in Northern Ireland and specific projects seeking to reconcile at community level. It is concluded that, while political and public processes can set a context and space for engagement to take place, reconciliation is fundamentally about personal encounter and relationship, which have to take place in a range of settings and at all levels of a society that has experienced conflict.

L'apport de la théorie des systèmes dynamiques complexes à l'ontologie du droit international dans la crise- Analyse de l'action normative du Conseil de sécurité

Cette thèse est une réflexion originale sur le droit international dans la crise, car elle aborde le droit international grâce à une théorie peu connue en droit, celle des systèmes dynamiques complexes. L’étude du cas particulier de la gestion normative de la crise par le Conseil de sécurité illustre les intérêts de l’utilisation d’une théorie novatrice en droit. La théorie des systèmes dynamiques complexes offre les outils d’une réflexion sur le droit, fondée sur les interactions du droit avec le contexte particulier dans lequel il intervient, la crise, et ses acteurs. La mise en lumière de ces interactions favorise une lecture critique du droit international dans la crise et permet de renouveler l’ontologie de ce droit. Les dynamiques complexes appréhendées et définies par cette théorie sont utiles lorsqu’il s’agit d’expliquer les atouts et les limites de l’action normative du Conseil. Par ailleurs en renouvellant l’ontologie du droit, la théorie des systèmes dynamiques complexes facilite une lecture prospective de l’action normative du Conseil et insiste sur le rôle institutionnel du droit.

Site-specific e vídeo-dança: a perceção espacial, corporal e sensorial evidenciada nas disciplinas de Composição Coreográfica e Projeto Coreográfico da ADCS

Relatório Final de Estágio apresentado à Escola Superior de Dança, com vista à obtenção do grau de Mestre em Ensino de Dança.

Contributos para a promoção da igualdade de género no contexto da aula de Técnica de Dança Contemporânea com os alunos do 6º ano da Escola de Dança do Conservatório Nacional

Relatório Final de Estágio apresentado à Escola Superior de Dança, com vista à obtenção do grau de Mestre em Ensino de Dança.

Virtual Research Environments The Next Steps workshop

The main aim of the workshop was to extend international dialogue and promote the development of VREs led by researcher needs. On the first day principal investigators and project managers of a great variety of projects provided an insight in the current state of development regarding technical innovation, disciplinary specific solutions, and impact on the research community. A series of short presentations of selected projects were followed by an extensive poster session that functioned as a "trade fair" of current trends in the field of VRE development and implementation. The second day was dedicated to the discussion of the "next steps" to improve and advance the development of VREs and to foster ideas for future engagement. The results of landscape studies funded by Jisc and the SURFfoundation were presented as Key Notes and impulse for the following discussions in four sub-groups. The sub-groups concentrated on the following four key themes: technological challenges organisation & concepts researcher needs strategic issues The outcomes of the separate discussions consisted of recommendations to the Knowledge Exchange initiative itself, for the Knowledge Exchange partner organisations and beyond.

Relatório de estágio de qualificação profissional

Relatório EPE - Relatório de estágio em Educação Pré-Escolar: O presente Relatório de Estágio de Qualificação Profissional situa-se no contexto de Educação Pré-Escolar, tendo como propósito revelar o que foi sendo realizado no Centro Social da Paróquia Nossa Senhora da Ajuda ao longo de quatro meses em contexto de creche. A prática educativa sustentou-se num quadro teórico-concetual de referência, com vista à construção de saberes para a Educação de Infância, pelo compromisso e responsabilização progressiva da ação docente, tendo sido encarado como um momento de singular importância. O contexto de formação assumiu-se, portanto, como um lugar privilegiado de articulação entre teoria e prática, onde o processo de ensino e aprendizagem ficou pautado por intencionalidades educativas com vista ao desenvolvimento integral de cada criança, bem como para a construção de saberes e competências profissionais. No âmbito da investigação-ação e associada à observação, à planificação, à avaliação e à ação propriamente dita, esteve sempre presente a comunicação e a articulação, pois são estas etapas interligadas que revelam a intencionalidade do processo educativo que carateriza a intervenção profissional do educador. A reflexão evidenciou-se também fulcral, pois só mediante uma reflexão na ação e sobre a ação é possível uma introspeção pessoal, despoletando uma compreensão mais sustentada da ação, facilitando a tomada de decisões conscientes. Salienta-se, ainda, a importância de uma formação profissional ao longo da vida, de modo a potenciar o desenvolvimento de uma atitude perante a Educação cada vez mais crítica, indagadora e reflexiva, em prol do desenvolvimento de cada criança.

Comparison of the modes of action of Apremilast and Roflumilast

The phosphodiesterase 4 (PDE4) family are cAMP specific phosphodiesterases that play an important role in the inflammatory response and is the major PDE type found in inflammatory cells. A significant number of PDE4 specific inhibitors have been developed and are currently being investigated for use as therapeutic agents. Apremilast, a small molecule inhibitor of PDE 4 is in development for chronic inflammatory disorders and has shown promise for the treatment of psoriasis, psoriatic arthritis as well as other inflammatory diseases. It has been found to be safe and well tolerated in humans and in March 2014 it was approved by the US food and drug administration for the treatment of adult patients with active psoriatic arthritis. The only other PDE4 inhibitor on the market is Roflumilast and it is used for treatment of respiratory disease. Roflumilast is approved in the EU for the treatment of COPD and was recently approved in the US for treatment to reduce the risk of COPD exacerbations. Roflumilast is also a selective PDE4 inhibitor, administered as an oral tablet once daily, and is thought to act by increasing cAMP within lung cells. As both (Apremilast and Roflumilast) compounds selectively inhibit PDE4 but are targeted at different diseases, there is a need for a clear understanding of their mechanism of action (MOA). Differences and similarity of MOA should be defined for the purposes of labelling, for communication to the scientific community, physicians, and patients, and for an extension of utility to other diseases and therapeutic areas. In order to obtain a complete comparative picture of the MOA of both inhibitors, additional molecular and cellular biology studies are required to more fully elucidate the signalling mediators downstream of PDE4 inhibition which result in alterations in pro- and anti-inflammatory gene expression. My studies were conducted to directly compare Apremilast with Roflumilast, in order to substantiate the differences observed in the molecular and cellular effects of these compounds, and to search for other possible differentiating effects. Therefore the main aim of this thesis was to utilise cutting-edge biochemical techniques to discover whether Apremilast and Roflumilast work with different modes of action. In the first part of my thesis I used novel genetically encoded FRET based cAMP sensors targeted to different intracellular compartments, in order to monitor cAMP levels within specific microdomains of cells as a consequence of challenge with Apremilast and Roflumilast, which revealed that Apremilast and Roflumilast do regulate different pools of cAMP in cells. In the second part of my thesis I focussed on assessing whether Apremilast and Roflumilast cause differential effects on the PKA phosphorylation state of proteins in cells. I used various biochemical techniques (Western blotting, Substrate kinase arrays and Reverse Phase Protein array and found that Apremilast and Roflumilast do lead to differential PKA substrate phosphorylation. For example I found that Apremilast increases the phosphorylation of Ribosomal Protein S6 at Ser240/244 and Fyn Y530 in the S6 Ribosomal pathway of Rheumatoid Arthritis Synovial fibroblast and HEK293 cells, whereas Roflumilast does not. This data suggests that Apremilast has distinct biological effects from that of Roflumilast and could represent a new therapeutic role for Apremilast in other diseases. In the final part of my thesis, Phage display technology was employed in order to identify any novel binding motifs that associate with PDE4 and to identify sequences that were differentially regulated by the inhibitors in an attempt to find binding motifs that may exist in previously characterised signalling proteins. Petide array technology was then used to confirm binding of specific peptide sequences or motifs. Results showed that Apremilast and Roflumilast can either enhance or decrease the binding of PDE4A4 to specific peptide sequences or motifs that are found in a variety of proteins in the human proteome, most interestingly Ubiquitin-related proteins. The data from this chapter is preliminary but may be used in the discovery of novel binding partners for PDE4 or to provide a new role for PDE inhibition in disease. Therefore the work in this thesis provides a unique snapshot of the complexity of the cAMP signalling system and is the first to directly compare action of the two approved PDE4 inhibitors in a detailed way.

Culture change in a museum: An action research analysis

The move of a museum in the western United States to larger quarters resulted in an increase in visitors and requests for tours. To respond to the greater number of tours, new volunteers (docents) were recruited and trained. But conflicts arose between the old and new docents. As Docent Chair, one of the authors worked with the Curator of Education to understand the culture change faced by the old docent group and integrate the old and new docent groups. This paper analyzes the culture change using Lewin’s Action Research model. The success of the culture integration was demonstrated when the old and new docents moved away from «this is how it should be done…» to «this is what I see…» in speaking about an event or problem. The language and perception changes were steps toward building a common meaning.

Factors influencing Nigerian men's decision to undergo prostate specific antigen testing.

Background: Prostate cancer is a major cause of cancer death in Nigerian men. Attempts to reduce mortality from prostate cancer have focused mainly on early detection of the disease by the use of PSA testing. As a result of the increased incidence of prostate cancer in Nigeria despite the widespread availability of testing facilities, it became pertinent to understand the salient factors that prompt Nigerian men to go for prostate cancer testing. Objective: This study explores the factors that influence a group of Nigerian men’s decision to go for Prostate Specific Antigen (PSA) testing. Methods: Following ethical approval, semi structured interviews were conducted with a group of 10 men who had PSA test following consultation with their doctor with signs and symptoms at the University of Benin Teaching Hospital from July to August, 2010. Interview transcripts were analysed by employing steps proposed by Collaizi (1978). Results: Five themes were identified: the symptoms experienced, the influence of friends and relatives, older age associated with increased awareness, accessibility to testing services and the knowledge of the PSA test. Conclusion: The study revealed that there continues to be a considerable lack of awareness and knowledge about prostate cancer and screening.