Regulation of histone H2A.Z expression is mediated by sirtuin 1 in prostate cancer

Histone variants seem to play a major role in gene expression regulation. In prostate cancer, H2A.Z and its acetylated form are implicated in oncogenes’ upregulation. SIRT1, which may act either as tumor suppressor or oncogene, reduces H2A.Z levels in cardiomyocytes, via proteasome-mediated degradation, and this mechanism might be impaired in prostate cancer cells due to sirtuin 1 downregulation. Thus, we aimed to characterize the mechanisms underlying H2A.Z and SIRT1 deregulation in prostate carcinogenesis and how they interact. We found that H2AFZ and SIRT1 were up- and downregulated, respectively, at transcript level in primary prostate cancer and high-grade prostatic intraepithelial neoplasia compared to normal prostatic tissues. Induced SIRT1 overexpression in prostate cancer cell lines resulted in almost complete absence of H2A.Z. Inhibition of mTOR had a modest effect on H2A.Z levels, but proteasome inhibition prevented the marked reduction of H2A.Z due to sirtuin 1 overexpression. Prostate cancer cells exposed to epigenetic modifying drugs trichostatin A, alone or combined with 5-aza-2’-deoxycytidine, increased H2AFZ transcript, although with a concomitant decrease in protein levels. Conversely, SIRT1 transcript and protein levels increased after exposure. ChIP revealed an increase of activation marks within the TSS region for both genes. Remarkably, inhibition of sirtuin 1 with nicotinamide, increased H2A.Z levels, whereas activation of sirtuin 1 by resveratrol led to an abrupt decrease in H2A.Z. Finally, protein-ligation assay showed that exposure to epigenetic modifying drugs fostered the interaction between sirtuin 1 and H2A.Z. We concluded that sirtuin 1 and H2A.Z deregulation in prostate cancer are reciprocally related. Epigenetic mechanisms, mostly histone post-translational modifications, are likely involved and impair sirtuin 1-mediated downregulation of H2A.Z via proteasome-mediated degradation. Epigenetic modifying drugs in conjunction with enzymatic modulators are able to restore the normal functions of sirtuin 1 and might constitute relevant tools for targeted therapy of prostate cancer patients

Protective effect of C. sativa leaf extract against UV mediated-DNA damage in a human keratinocyte cell line

Toxic effects of ultraviolet (UV) radiation on skin include protein and lipid oxidation, and DNA damage. The latter is known to play a major role in photocarcinogenesis and photoaging. Many plant extracts and natural compounds are emerging as photoprotective agents. Castanea sativa leaf extract is able to scavenge several reactive species that have been associated to UV-induced oxidative stress. The aim of this work was to analyze the protective effect of C. sativa extract (ECS) at different concentrations (0.001, 0.01, 0.05 and 0.1 μg/mL) against the UV mediated-DNA damage in a human keratinocyte cell line (HaCaT). For this purpose, the cytokinesis-block micronucleus assay was used. Elucidation of the protective mechanism was undertaken regarding UV absorption, influence on 1O2 mediated effects or NRF2 activation. ECS presented a concentration-dependent protective effect against UV-mediated DNA damage in HaCaT cells. The maximum protection afforded (66.4%) was achieved with the concentration of 0.1 μg/mL. This effect was found to be related to a direct antioxidant effect (involving 1O2) rather than activation of the endogenous antioxidant response coordinated by NRF2. Electrochemical studies showed that the good antioxidant capacity of the ECS can be ascribed to the presence of a pool of different phenolic antioxidants. No genotoxic or phototoxic effects were observed after incubation of HaCaT cells with ECS (up to 0.1 μg/mL). Taken together these results reinforce the putative application of this plant extract in the prevention/minimization of UV deleterious effects on skin.

N.C.R.F. 3: adopção pela primeira vez das Normas Contabilísticas e de Relato Financeiro

Dissertação para obtenção do Grau de Mestre em Auditoria

O Contributo do sistema SAP R/3 no controlo interno na REFER

Dissertação apresentada ao Instituto Superior de Contabilidade para a obtenção do Grau de Mestre em Auditoria Orientador: Mestre Agostinho Sousa Pinto

Informal learning recognition through a cloud ecosystem

Learning and teaching processes, like all human activities, can be mediated through the use of tools. Information and communication technologies are now widespread within education. Their use in the daily life of teachers and learners affords engagement with educational activities at any place and time and not necessarily linked to an institution or a certificate. In the absence of formal certification, learning under these circumstances is known as informal learning. Despite the lack of certification, learning with technology in this way presents opportunities to gather information about and present new ways of exploiting an individual’s learning. Cloud technologies provide ways to achieve this through new architectures, methodologies, and workflows that facilitate semantic tagging, recognition, and acknowledgment of informal learning activities. The transparency and accessibility of cloud services mean that institutions and learners can exploit existing knowledge to their mutual benefit. The TRAILER project facilitates this aim by providing a technological framework using cloud services, a workflow, and a methodology. The services facilitate the exchange of information and knowledge associated with informal learning activities ranging from the use of social software through widgets, computer gaming, and remote laboratory experiments. Data from these activities are shared among institutions, learners, and workers. The project demonstrates the possibility of gathering information related to informal learning activities independently of the context or tools used to carry them out.

Maintenance and destrcution of R&D leadership

In the standard Schumpeterian-growth models only follower firms invest in R&D activities and larger economies grow faster. Since these results are counterfactual, this paper reveals that leader firms often support R&D activities and economic growth can be independent of the market size. In particular, the maintenance of R&D leadership increases with: (i) the technological-knowledge gap between leader and followers, since a firm-specific learning effect of accumulated technological knowledge from past R&D is considered, (ii) the leaders’ strategies that delay the next successful R&D supported by some follower firm, (iii) the market size, and (iv) the up-grade of each innovation.

CrimsonHex: a learning objects repository for programming exercises

A repository of learning objects is a system that stores electronic resources in a technology-mediated learning process. The need for this kind of repository is growing as more educators become eager to use digital educa- tional contents and more of it becomes available. The sharing and use of these resources relies on the use of content and communication standards as a means to describe and exchange educational resources, commonly known as learning objects. This paper presents the design and implementation of a service-oriented reposi- tory of learning objects called crimsonHex. This repository supports new definitions of learning objects for specialized domains and we illustrate this feature with the definition of programming exercises as learning objects and its validation by the repository. The repository is also fully compliant with existing commu- nication standards and we propose extensions by adding new functions, formalizing message interchange and providing a REST interface. To validate the interoperability features of the repository, we developed a repository plug-in for Moodle that is expected to be included in the next release of this popular learning management system.

Supporting conceptualisation processes in collaborative networks: a case study on an R&D project

The development of new products or processes involves the creation, re-creation and integration of conceptual models from the related scientific and technical domains. Particularly, in the context of collaborative networks of organisations (CNO) (e.g. a multi-partner, international project) such developments can be seriously hindered by conceptual misunderstandings and misalignments, resulting from participants with different backgrounds or organisational cultures, for example. The research described in this article addresses this problem by proposing a method and the tools to support the collaborative development of shared conceptualisations in the context of a collaborative network of organisations. The theoretical model is based on a socio-semantic perspective, while the method is inspired by the conceptual integration theory from the cognitive semantics field. The modelling environment is built upon a semantic wiki platform. The majority of the article is devoted to developing an informal ontology in the context of a European R&D project, studied using action research. The case study results validated the logical structure of the method and showed the utility of the method.

A 12*(1+|R|/(4m))-speed algorithm for scheduling constrained-deadline sporadic real-time tasks on a multiprocessor comprising m processors where a task may request one of |R| sequentially-reusable shared resources

We present a 12*(1+|R|/(4m))-speed algorithm for scheduling constrained-deadline sporadic real-time tasks on a multiprocessor comprising m processors where a task may request one of |R| sequentially-reusable shared resources.

Phytoplankton analysis of portuguese reservoirs: a cluster analysis with R

In this work, cluster analysis is applied to a real dataset of biological features of several Portuguese reservoirs. All the statistical analysis is done using R statistical software. Several metrics and methods were explored, as well as the combination of Euclidean metric and the hierarchical Ward method. Although it did not present the best combination in terms of internal and stability validation, it was still a good solution and presented good results in terms of interpretation of the problem at hand.

Atividade tradutológica: a (r)evolução dos últimos 20 anos

Trabalho de natureza profissional para a atribuição do Título de Especialista do Instituto Politécnico do Porto, na área de Línguas e Cuturas - Línguas e Literaturas Estrangeiras, defendido a 11-11-2015.

Stochasticity favoring the effects of the R&D strategies of the firms

We present stochastic dynamics on the production costs of Cournot competitions, based on perfect Nash equilibria of nonlinear R&D investment strategies to reduce the production costs of the firms at every period of the game. We analyse the effects that the R&D investment strategies can have in the profits of the firms along the time. We observe that, in certain cases, the uncertainty can improve the effects of the R&D strategies in the profits of the firms due to the non-linearity of the profit functions and also of the R&D parameters.

Cournot duopoly with competition in the R&D expenditures

We present a new R&D investment in a Cournot Duopoly model and we analyze the different possible types of Nash R&D investments. We observe that the new production costs region can be decomposed in three economical regions, depending on the Nash R&D investment, showing the relevance of the use of patents in new technologies.