The role of succinate dehydrogenase in the Drosophila melanogaster intestinal stem cells and tissue homeostasis

Adult stem cells maintain tissue homeostasis and act in response to challenges such as infection or mechanical damage. The fruit fly Drosophila melanogaster has emerged as a powerful model to study adult stem cells due to its conserved pathways and the existence of different stem cell systems, particularly a stem cell niche in the intestine. Intestinal stem cells (ISCs) have a major role in maintaining tissue homeostasis and improvements in their function result in refined tissue function in aged or damaged organs. Metabolism plays an important role in regulating stem cell activity, influencing cellular events such as differentiation and proliferation. However, several aspects remain unraveled, particularly the role of different subunits of the mitochondrial electron transport chain (ETC) — end players in the oxidative phosphorylation process. Given the importance of metabolism in regulating stem cell activity, we hypothesized that ETC subunits also have a role in regulating ISC activity and tissue homeostasis. To test our hypothesis, we performed a candidate screen to knock down individual subunits of the ETC specifically in ISCs and their direct progeny — enteroblasts — in the adult fly and studied their requirements for normal cell division, differentiation, survival and impact in surrounding differentiated cells. Subunits of the ETC complex II, which converts succinate to fumarate in the Krebs cycle, particularly subunit D (SdhD), emerged from the screen as strong candidates required for normal ISC activity. Knockdown of SdhD in ISCs resulted in inhibition of cell division, hypertrophy with polyploidy, and ultimately, cell death. At a tissue level, evidence of a differentiation bias towards secretory enteroendocrine cells in lieu of absorptive enterocytes was observed upon SdhD knockdown in progenitor cells. Further experiments showed that knockdown of SdhD causes succinate to accumulate, possibly due to a decrease in the function of succinate dehydrogenase activity. Succinate is a known ligand for the GPR91 receptor in mammals which is known to be involved in cellular hypertrophy and death via apoptosis. Further studies need to be performed to determine the existence of a succinate receptor in Drosophila. This work has unveiled a direct relationship between inhibition of complex II subunits and stem cell hypertrophy and death, with succinate as a possible intermediate, and provides a suitable model for the study of the molecular pathways underlying cellular hypertrophy and death in metabolic-deficiency backgrounds. These insights may contribute to the understanding of hypertrophic pathologies, or proliferative diseases, such as cancer

Using ontologies in database preservation

This paper addresses the problematic Digital Preservation and focuses on the conceptual model within a specific class of digital objects: Relational Databases. Previously, a neutral format was adopted to pursue the goal of platform independence and to achieve a standard format in the digital preservation of relational databases, both data and structure (logical model). Currently, in this project, we intend to address the preservation of relational databases by focusing on the conceptual model of the database, considering the database semantics as an impor- tant preservation ”property”. For the representation of this higher level of abstraction present in databases we use an ontology based approach. At this higher abstraction level exists inherent Knowledge associated to the database semantics that we tentatively represent using ”Web Ontol- ogy Language” (OWL). We developed a prototype (supported by case study) and define a mapping algorithm for the conversion between the database and OWL. The ontology approach is adopted to formalize the knowledge associated to the conceptual model of the database and also a methodology to create an abstract representation of it

Relational databases digital preservation

Digital preservation is emerging as an area of work and research that tries to provide answers that will ensure a continued and long-term access to information stored digitally. IT Platforms are constantly changing and evolving and nothing can guarantee the continuity of access to digital artifacts in their absence. This paper focuses on a speci c family of digital objects: Relational Databases; they are the most frequent type of databases used by organizations worldwide. A neutral format that is hardware and software independent is the key to achieve a standard format to use in digital preservation of relational databases. XML for its neutrality was chosen for this representation of the database. The presented solution o ers a possibility to achieve relational databases preservation. The prototype follows the "Reference Model for an Open Archival Information System" (OAIS)

Significant properties in the preservation of relational databases

Relational Databases are the most frequent type of databases used by organizations worldwide and are the base of several information systems. As in all digital objects, and concerning the digital preservation of them, the signi cant properties (signi cant characteristics) must be de ned so that adopted strategies are appropriate. In previous work a neutral format (hardware and software independent) | DBML | was adopted to achieve a standard format used in the digital preservation of the relational databases data and structure. In this paper we walk further in the de nition of the signi cant properties by considering the database semantics as an important characteristic that should be also preserved. For the representation of this higher level of abstraction we are going to use an ontology based approach. We will extract the entityrelationship model from the DBML representation and we will represent it as an ontology

New dimension in relational database preservation : raising the abstraction level

The work addressed in this paper focuses on the preserva- tion of the conceptual model within a specific class of dig- ital objects: Relational Databases. Previously, a neutral format was adopted to pursue the goal of platform inde- pendence and to achieve a standard format in the digital preservation of relational databases, both data and struc- ture (logical model). Currently, in this project, we address the preservation of relational databases by focusing on the conceptual model of the database, considering the database semantics as an important preservation ”property”. For the representation of this higher layer of abstraction present in databases we use an ontology based approach. At this higher abstraction level exists inherent Knowledge associated to the database semantics that we tentatively represent using ”Web Ontology Language” (OWL). We developed a proto- type (supported by case study) and define a mapping algo- rithm for the conversion between the database and OWL. The ontology approach is adopted to formalize the knowl- edge associated to the conceptual model of the database and also a methodology to create an abstract representation of it

Using ontologies to abstract relational databases conceptual model

This paper addresses the problematic Digital Preservation and focuses on the conceptual model within a specific class of digital objects: Relational Databases. Previously, a neutral format was adopted to pursue the goal of platform independence and to achieve a standard format in the digital preservation of relational databases, both data and structure (logical model). Currently, in this project, we intend to address the preservation of relational databases by focusing on the conceptual model of the database, considering the database semantics as an impor- tant preservation ”property”. For the representation of this higher level of abstraction present in databases we use an ontology based approach. At this higher abstraction level exists inherent Knowledge associated to the database semantics that we tentatively represent using ”Web Ontol- ogy Language” (OWL). We developed a prototype (supported by case study) and define a mapping algorithm for the conversion between the database and OWL. The ontology approach is adopted to formalize the knowledge associated to the conceptual model of the database and also a methodology to create an abstract representation of it

Relational databases conceptual preservation

Previously, a neutral format was adopted to pursue the goal of platform independence and to achieve a standard format in the digital preservation of relational databases, both data and structure (logical model). Currently, we intend to address the preservation of relational databases by focusing on the conceptual model of the database, considering the database semantics as an important preservation ”property”. For the representation of this higher level of abstraction present in databases we use an ontology based approach. At this higher abstraction level exists inherent Knowledge associated to the database semantics that we tentatively represent using ”Web Ontology Language” (OWL). We developed a prototype (supported by case study) and define a mapping algorithm for the conversion between the database and OWL

Relational databases digital preservation

Tese doutoramento - Programa Doutoral em InformáticaWith the expansion and growth of information technologies, much of human knowledge is now recorded on digital media. It began in the 20th century, it has been occurring continuously and it seems that there is no turning back. This paradigm brings scenarios where humans need mediators to understand digital information { computer platforms. These platforms are constantly changing and evolving and nothing can guarantee the continuity of access to digital artifacts in their absence. A new problem in the digital universe arises: Digital Preservation. There are huge volumes of information stored digitally and there are also a panoply of di erent classes, formats and types of digital objects. Our work addresses the problematic Digital Preservation and focuses on the logic and conceptual models within a speci c class of digital objects: Relational Databases. This family of digital objects is used by organizations to record their data produced on daily basis by information systems at operational levels or others. This structures are complex and the relational databases software support may di er from one organization to another. It can be proprietary, free or open source. Previously, a neutral format { Database Markup Language (DBML) { was adopted to pursue the goal of platform independence and to achieve standardization concerning the format in the digital preservation of relational databases. This format is able to describe both data and structure (logical model). The key strategies we are adopting are migration and normalization with refreshment. From our rst approach, we evolved the work to address the preservation of relational databases and we focused on the conceptual model of the database. The conceptual model of the database corresponds to the ideas and concepts that in the basis of the designed and/or modeled database, conceived to support a certain information system. We are referring to the semantics of the database and considering it as an important preservation "property". For the representation of this higher layer of abstraction present in databases we use an ontology based approach. At this higher abstraction level exists inherent Knowledge associated to the database semantics that we tentatively represent using Web Ontology Language (OWL). From the initial prototype, we developed a framework (supported by case studies) and establish a mapping algorithm for the conversion between the database and OWL. The ontology approach is adopted to formalize the knowledge associated to the conceptual model of the database and also a methodology to create an abstract representation of it. The system is based on the functional axes (ingestion, administration, dissemination and preservation) of the Open Archival Information System (OAIS) reference model and its information packages, where we include the two levels/layers of abstraction within the digital objects that are the subject of our research: Relational Databases. The framework o ers a set of web interfaces where it is possible to migrate a database into normalized and neutral formats (DBML + OWL) and perform some minor administration tasks on the repository. The system also enables the navigation or browsing through the database (concepts) without loosing technical details on the database relational model. The end consumers will have at their disposal a broad overview of the preserved object: a) the lower level data and structure of the relational database logical model and b) the higher level semantics and knowledge of the database conceptual model! Considering the unpredicted future access to a preserved database content and structure, our preservation policy tries to capture the signi cant properties of databases that should enable the future interpretability and understanding of the digital object.Através do crescimento das tecnologias de informação, grande parte do conhecimento humano passou a ser armazenado em suportes digitais. Esta transformação iniciou-se no seculo XX, tem vido a ocorrer de forma contínua, e tudo indica que fora já ultrapassado o "ponto-sem-retorno". Este novo paradigma implica cenários substancialmente diferentes, cenários estes onde os seres humanos necessitam de mediadores para compreender a informação digital { plataformas computacionais. Estas plataformas estão em constante evolução e não existe nada que nos possa garantir a continuidade de acesso aos artefactos digitais na sua ausência. Surge um novo problema associado ao mundo digital: Preservação Digital. Grandes quantidades de informação estão armazenadas digitalmente numa panóplia de diferentes classes, formatos e tipos. O nosso trabalho concentra-se na problemática da preservação digital, focando concretamente os modelos lógico e conceptual de uma classe específica de objectos digitais: as Bases de Dados Relacionais. Esta família de objectos digitais é amplamente usada pelas organizações para guardar os dados produzidos diariamente pelos seus sistemas de informação, tanto ao nível operacional como a outros níveis. Falamos de estruturas complexas em que os Sistemas Gestores de Bases de Dados que as suportam podem variar de organização para organização. Os sistemas podem ser proprietários, livres e ou de código aberto ("open source"). Inicialmente, um formato neutro { Database Markup Language (DBML) { foi adotado no sentido de garantir a independência de plataformas, e com o objectivo de conseguir estabelecer um formato normalizado para a preservação de bases de dados relacionais; isto tanto para os dados como para a estrutura (modelo lógico). As estratégias que adoptamos são a migração e normalização com refrescamento. A partir da abordagem inicial, evoluímos o nosso trabalho no que concerne à preservação digital de bases de dados relacionais, focando o estudo também no modelo conceptual da base de dados. O modelo conceptual corresponde às ideias e conceitos na base do desenho e/ou modelação de uma determinada base de dados, e concebido para dar suporte a um determinado cenário "real", i.e., a um determinado sistema de informação. Referimo-nos à semântica da base de dados considerando-a como uma importante "propriedade" na preservação. Para a representação desta camada de abstração mais elevada que estão presente nas bases de dados, utilizamos uma abordagem baseada em ontologias. A este nível mais elevado de abstração existe informação e conhecimento intrínseco que estão associados à semântica da base de dados que se pretende representar através de Web Ontology Language (OWL). A partir do protótipo inicial, desenvolvemos uma plataforma aplicacional (suportada por casos de estudo) e estabelecemos um algoritmo de mapeamento para a conversão entre bases de dados e OWL. A abordagem através da ontologia foi adoptada para formalizar o conhecimento associado ao modelo conceptual da base de dados e também foi usada como uma metodologia para criar uma representação abstracta da base de dados. O sistema baseia-se nos eixos funcionais (ingestão, administração, disseminação e preservação) do modelo de referência Open Archival Information System (OAIS) assim como nos seus pacotes de informação (information packages) onde são incluídos dois níveis/camadas de abstração, relativamente aos objectos digitais que são objecto de preservação neste estudo: Bases de Dados Relacionais. O sistema (framework) fornece um conjunto de interfaces web, onde é possível migrar a base de dados para formatos neutros e normalizados (DBML + OWL), e permitem também executar algumas tarefas de administração do repositório. O sistema possibilita ainda a navegação e pesquisa pelas bases de dados (conceitos), sem que se perca aspectos técnicos associados ao modelo relacional das mesmas. Os consumidores finais têm ao seu dispor uma visão global do objecto preservado: a) a um nível inferior os dados e estrutura do modelo relacional lógico e b) a um nível mais elevado a semântica e conhecimento associado ao modelo conceptual da base de dados! Considerando a imprevisibilidade no acesso futuro ao conteúdo e estrutura de bases de dados preservadas, a nossa política de preservação pretende capturar as propriedades significativas das bases de dados capazes de possibilitar futuramente a interpretação e compreensão do objecto digital

Preservação digital de bases de dados relacionais

Dissertação de mestrado em informáticaO ser humano sempre teve a necessidade de exteriorizar as aprendizagens adquiridas, sendo a linguagem um dos veículos para atingir esse fim. Desde o momento em que a informação deixa de ser transmitida apenas por meio de gestos ou sons voláteis e passa a ser esculpida no mundo que nos rodeia, a informação não mais se encontra presa à mente humana. Segundo reza a História, os primeiros registos de informação ancestral são as gravuras rupestres. Surge a forma, que ainda hoje vigora, de transmissão de conhecimento por intermédio de documentos escritos diversificados. A possibilidade de registar o conhecimento ou a informação fora de nossos cérebros é uma capacidade fundamental para a perpetuação da mesma. Durante muitos séculos, senão milénios, a informação era registada por forma que o ser humano a pudesse entender sem a necessidade de intermediários. Actualmente e devido à recente expansão das tecnologias de informação muito do conhecimento humano passa a estar registado em suportes informáticos. Este paradigma remete-nos para um cenário bem diferente. Passa a existir a necessidade do uso de intermediários – plataformas informáticas – para que a informação nos seja inteligível. O problema prende-se exactamente com os intermediários, ou seja, com as plataformas informáticas. Estas estão em constante evolução e nada nos garante a continuidade de acesso aos artefactos digitais na sua ausência. Irrompe uma nova problemática no universo digital: a Preservação Digital. O nosso estudo aborda esta problemática da preservação digital e centra-se numa classe de objectos digitais específicos: Base de Dados Relacionais. As bases de dados relacionais desempenham um papel relevante no contexto global da informação digital e, por conseguinte, será fundamental não comprometer a sua longevidade, integridade e autenticidade. Este tipo de arquivos são de especial importância para as organizações uma vez que justificam as suas actividades e podem também fornecer uma imagem acerca da própria organização. Os objectos digitais são estruturas complexas que implicam o uso de hardware e software específico para que os seres humanos os possam interpretar e compreender. Das diferentes abordagens e estratégias reiteradas por diversos investigadores coube-nos escolher as que mais se adaptam ao nosso caso concreto. Um formato neutro que seja independente das plataformas de hardware e de software é a chave para alcançar um modelo normalizado a usar na preservação digital de bases de dados relacionais. O XML pela sua neutralidade foi escolhido para essa representação da base de dados. Assim sendo procede-se à migração da base de dados original para uma linguagem definida a partir do XML, o DBML (Database Markup Language). O DBML foi definido de forma a permitir representar tanto a estrutura como os próprios dados existentes na base de dados. O estudo desta temática foi realizado tendo como um dos objectivos a implementação de um protótipo para preservação digital de bases de dados relacionais. O modelo conceptual para o repositório segue as orientações do modelo de referência OAIS (Open Archival Information System). Este modelo define uma série de recomendações e assenta quatro eixos funcionais: Ingestão, Administração, Disseminação e Preservação. A fase final dos trabalhos passou então pela implementação de um sistema capaz de ingerir bases de dados, sob a forma de pacotes de informação (DBML + meta-informação), para uma desejada preservação. O sistema desenvolvido teve por base uma aplicação Web com várias interfaces de forma a possibilitar, além da ingestão da informação, a sua administração, preservação e disseminação.The human being always had the need to exteriorize the learning acquired, and starts doing that using the language. When the information no is longer transmitted only through gestures or volatile sounds and starts being sculpted in the world around us, the information is no longer locked inside the human mind. According to the History, the earliest records of ancestral information were rock carvings. It emerge a form of knowledge transmission through a diversity of written documents. The possibility of registering knowledge or information out of our minds is a key capability to achieve its perpetuation. For many centuries the information was recorded so that human beings could understand it without the need of any mediators. Today, and due to the recent expansion of technologies, much of human knowledge is now recorded on computer media. This paradigm brings us to a very different scenario. We now need to use intermediaries – computing platforms – to understand the information. The main problem concerns exactly with the computing platforms. These are constantly changing and evolving and nothing can guarantee the continuity of access to digital artefacts in their absence. A new problem in the digital universe arises: Digital Preservation. Our study addresses this issue of Digital Preservation and focuses on a specific family of digital objects: Relational Databases. Relational databases are a very important piece in the global context of digital information and therefore it is fundamental not to compromise its longevity (life cycle) and also its integrity, liability and authenticity. These kind of archives are especially important to organizations because they can justify their activities and give us a glimpse about the organization it self. Digital archives are complex structures that without the software and hardware – which they depend on – the human being, or others, will certainly be unable to experience or understand them. Of the different approaches and strategies repeated by several researchers we have to choose those that are best suited to our case. A neutral format that is hardware and software independent is the key to achieve a standard format to use in digital preservation of relational databases. XML for its neutrality was chosen for this representation of the database. We carried a migration of the database from its original form to a new format – DBML (Database Markup Language) – which is defined from the XML. DBML was established to enable representation of both structure and data of the database. The study was conducted having as one of the objectives the implementation of a prototype for digital preservation of relational databases. The conceptual model for the repository follows the guidelines of the reference model OAIS (Open Archival Information System). This model defines a series of recommendations and builds four functional axes: Ingestion, Administration, Dissemination and Preservation. The final phase of our work was the implementation of a system capable of ingest databases, in the form of information packages (DBML + metadata) for preservation. The developed system is based on a Web application and has multiple interfaces that allow not only the ingestion of information, but also its administration, preservation and dissemination

Análise de risco associado a quebras de serviço

Tese de mestrado, Segurança Informática, Universidade de Lisboa, Faculdade de Ciências, 2015O conceito de “risco” tem-se tornado cada vez mais presente na vida das organizações. Desde sempre que o Gestor de topo tem presente na sua consciência que gerir a vida da sua organização ou do seu sistema implica também a gestão do risco. Nos dias de hoje, o risco é universalmente entendido como um conceito que incorpora uma parte negativa que pode impedir as organizações de atingirem os seus objectivos mas também uma parte positiva que é a oportunidade de estas obterem ganhos. Este documento descreve um trabalho autónomo que aborda um problema concreto a que uma determinada instituição bancária pretende dar resposta. Este problema prende-se com a necessidade de, por um lado, melhorar a estimativa de risco associado a possíveis quebras de serviço que possam ocorrer no futuro e, por outro, quantificar perdas associadas a quebras de serviço ocorridas no passado. Este trabalho teve como objectivo valorar as perdas que uma determinada organização pode sofrer em consequência de um funcionamento deficiente, ou mesmo indisponibilidade, dos serviços que oferece aos seus clientes. Este mau funcionamento pode resultar de ataques bem-sucedidos à sua infra-estrutura informática ou de outros eventos que provoquem quebras de serviço. Foi feito um levantamento das interacções entre os vários subsistemas e dos vários eventos que podem conduzir a estados de operação irregular, de forma a estabelecer relações de causalidade entre eles. Por outro lado, foi feita uma análise do histórico de eventos e suas repercussões de forma a estimar custos. Foi desenvolvida uma aplicação para auxiliar o processo de análise de risco associado à falha da infra-estrutura. Esta aplicação permite efectuar a modelação de sistemas, recolher métricas indicadoras do valor e desempenho dos processos que lhes estão associados e, com base nesta informação, estimar riscos relacionados com potenciais falhas, assim como, apurar perdas associadas a quebras de serviço efectivamente ocorridas. Procedeu-se à avaliação da utilidade e usabilidade da aplicação junto de decisores de alto nível de gestão que serão os seus futuros utilizadores na referida instituição.The concept of "risk" has become increasingly present in the life of organizations. Senior managers have always had the notion that the effective organizational life has to deal with risk. Nowadays risk is universally known as a concept that incorporates both positive and negative aspects. The negative aspect of risk is what prevents the organization of achieving its goal while the positive are opportunities that can be explored to achieve more earnings. This document describes an autonomous work addressing a concrete problem that a certain bank aims to deal with. This problem is related to the need of improving the estimation of risk associated with service failures that may occur in the future as well as quantifying losses due to service failures occurred in the past. The current work aimed to assess the losses of value that an organization may suffer as a result of a malfunction or even unavailability of the services it offers to its customers. This malfunction can result from successful attacks on their IT infrastructure or other events that cause service breaks. A survey was taken on the interactions between the several subsystems and the various events that can lead to irregular operating states, in order to establish causal relationships between them. An analysis of historical events and their effects was made in order to estimate costs. An application was developed to assist the risk analysis process associated with infrastructure failure. It allows to model systems and collect metrics about the value and performance of processes associated with these systems. Based on this information, it is possible to estimate risk related with potential failures as well as determining losses from a failure that has occurred in the past. The application was then evaluated for its utility and usability by senior managers to be used by the above organization