Diffusional kurtosis imaging using a fast heuristic constrained linear least squares algorithm: a plugin for OsiriX

Diffusion Kurtosis Imaging (DKI) is a fairly new magnetic resonance imag-ing (MRI) technique that tackles the non-gaussian motion of water in biological tissues by taking into account the restrictions imposed by tissue microstructure, which are not considered in Diffusion Tensor Imaging (DTI), where the water diffusion is considered purely gaussian. As a result DKI provides more accurate information on biological structures and is able to detect important abnormalities which are not visible in standard DTI analysis. This work regards the development of a tool for DKI computation to be implemented as an OsiriX plugin. Thus, as OsiriX runs under Mac OS X, the pro-gram is written in Objective-C and also makes use of Apple’s Cocoa framework. The whole program is developed in the Xcode integrated development environ-ment (IDE). The plugin implements a fast heuristic constrained linear least squares al-gorithm (CLLS-H) for estimating the diffusion and kurtosis tensors, and offers the user the possibility to choose which maps are to be generated for not only standard DTI quantities such as Mean Diffusion (MD), Radial Diffusion (RD), Axial Diffusion (AD) and Fractional Anisotropy (FA), but also DKI metrics, Mean Kurtosis (MK), Radial Kurtosis (RK) and Axial Kurtosis (AK).The plugin was subjected to both a qualitative and a semi-quantitative analysis which yielded convincing results. A more accurate validation pro-cess is still being developed, after which, and with some few minor adjust-ments the plugin shall become a valid option for DKI computation

Application of different heuristic classes in memory-based and stimulus-based decisions

This paper studies the drivers of heuristic application in different decision types. The study compares differences in frequencies of heuristic classes' such as recognition, one-reason choice and trade-off applied in, respectively, memory-based and stimulus-based choices as well as in high and low involvement decisions. The study has been conducted online among 205 participants from 28 countries.

Professions and inter-disciplinary teamwork in socially embedded bureaucracies: Synthesis and hypotheses on the impact of informal and formal organization

In order to maximize their productivity, inter-disciplinary multi-occupation teams of professionals need to maximize inter-occupational cooperation in team decision making. Cooperation, however, is challenged by status anxiety over organizational careers and identity politics among team members who differ by ethnicity-race, gender, religion, nativity, citizenship status, etc. The purpose of this paper is to develop hypotheses about how informal and formal features of bureaucracy influence the level of inter-occupation cooperation achieved by socially diverse, multi-occupation work teams of professionals in bureaucratic work organizations. The 18 hypotheses, which are developed with the heuristic empirical case of National Science Foundation-sponsored university school partnerships in math and science curriculum innovation in the United States, culminate in the argument that cooperation can be realized as a synthesis of tensions between informal and formal features of bureaucracy in the form of participatory, high performance work systems.

Competência intercultural: conteúdos culturais na aquisição da língua estrangeira e sua integração didáctica no ensino do alemão

Dissertação apresentada à Faculdade de Ciências Sociais e Humanas da Universidade Nova de Lisboa para obtenção do grau de Doutor em Cultura Alemã.

Liderança e estratégia em contexto de inovação nas organizações de saúde : estudos de caso

RESUMO - A presente investigação procura descrever e compreender como a estratégia influencia a liderança e como esta por sua vez interage nos processos de inovação e mudança, em organizações de saúde. Desconhecem-se estudos anteriores, em Portugal, sobre este problema de investigação e da respectiva problemática teórica. Trata-se de um estudo exploratório e descritivo que envolveu 5 organizações de saúde, 4 portuguesas e 1 espanhola, 4 hospitais (dois privados e uma unidade local de saúde). Utilizou-se uma abordagem mista de investigação (qualitativa e quantitativa), que permitiu compreender, através do estudo de caso, como se articulam a estratégia, a liderança e a inovação nessas cinco organizações de saúde. Os resultados do estudo empírico foram provenientes da recolha de dados efectuada através de observação directa e estruturada, entrevistas com actores-chave, documentos em suporte de papel e digital, e ainda inquérito por questionário de auto-resposta a uma amostra (n=165) de actores do line e do staff (Administradores, Directores de Serviço/Departamento, Enfermeiros Chefe e Técnicos Coordenadores) das cinco organizações de saúde. Tanto o modelo de Miles & Snow (estratégia organizacional), como o modelo dos valores contrastantes de Quinn (cultura organizacional e liderança), devidamente adaptados, mostram-se heurísticos e provam poder aplicar-se às organizações de saúde, apesar a sua complexidade e especificidade. Tanto as organizações do sector público como do sector privado e organizações públicas concessionadas (parcerias público privadas) podem ser acompanhadas e monitorizadas nos seus processos de inovação e mudança, associados aos tipos de cultura, liderança ou estratégia organizacionais adoptadas. As organizações de saúde coabitam num continuum, onde o ambiente (quer interno quer externo) e o tempo são factores decisivos que condicionam a estratégia a adoptar. Também aqui, em função da realidade dinâmica e complexa onde a organização se move, não há tipologias puras. Há, sim, uma grande plasticidade e flexibilidade organizacionais. Quanto aos líderes, exercem habitualmente a autoridade formal, pela via da circular normativa. Não são pares (nem primi inter pares), colocam-se por vezes numa posição de superioridade, quando o mais adequado seria a relação de parceria, cooperação e procura de consensos, com todos os colaboradores, afim de serem eles os verdadeiros protagonistas e facilitadores da mudança e das inovações. Como factores facilitadores da inovação e da mudança, encontrámos nas organizações de saúde estudadas o seguinte: facilidade de aprender; visão/missão adequadas; ausência de medo de falhar; e como factores inibidores: falta de articulação entre serviços/departamentos; estrutura organizacional (no sector público muito verticalizada e no sector privado mais horizontalizada); resistência à mudança; falta de tempo; falha no tempo de reacção (o tempo útil para a tomada de decisão é, por vezes, ultrapassado). --------ABSTRACT - The present research seeks to describe and understand how strategy influences leadership and how this in turn interacts in the process of innovation and change in health organizations. Previous studies on these topics are unknown in Portugal, about this research problem and its theoretical problem. This is an exploratory and descriptive study that involved 5 health organizations, 4 Portuguese and 1 Spanish. We used a mixed approach of research (qualitative and quantitative), which enabled us to understand, through case study, how strategy and leadership were articulated with innovation in these five health organizations. The results of the empirical study came from data collection through direct observation, interviews with key actors, documents and survey questionnaire answered by 165 participants of line and staff (Administrators, Medical Directors of Service /Department, Head Nurses and Technical Coordinators) of the five health organizations. Despite their complexity and specificity, both the model of Miles & Snow (organizational strategy) and the model of the Competing Values Framework of Quinn (organizational culture and leadership), suitably adapted, have proven heuristic power and able to be apply to healthcare organizations. Both public sector organizations, private and public organizations licensed (public-private partnerships) can be tracked and monitored in their processes of innovation and change in order to understand its kind of culture, leadership or organizational strategy adopted. Health organizations coexist in a continuum, where the environment (internal and external) and time are key factors which determine the strategy to adopt. Here too depending on the dynamic and complex reality where the organization moves, there are no pure types. There is indeed a great organizational plasticity and flexibility. Leaders usually carry the formal authority by circular normative. They are not pairs (or primi inter pares). Instead they are, sometimes, in a position of superiority, when the best thing is partnership, collaboration, cooperation, building consensus and cooperation with all stakeholders, in order that they are the real protagonists and facilitators of change and innovation. As factors that facilitate innovation and change, we found in health organizations studied, the following: ease of learning; vision / mission appropriate; absence of fear of failure, and as inhibiting factors: lack of coordination between agencies / departments; organizational structure (in the public sector it is too vertical and in the private sector it is more horizontal); resistance to change; lack of time and failure in the reaction time (the time for decision making is sometimes exceeded).

Reducing the number of membership functions in linguistic variables

Dissertation presented at Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia in fulfilment of the requirements for the Masters degree in Mathematics and Applications, specialization in Actuarial Sciences, Statistics and Operations Research

Expression of the human carboxylesterase 2 enzyme (CES2) in mammalian cells

Dissertation to obtain a Master Degree in Biotechnology

Landslide susceptibility assessment in Karanganyar regency - Indonesia - Comparison of knowledge-based and Data-driven Models

Dissertation submitted in partial fulfillment of the requirements for the Degree of Master of Science in Geospatial Technologies.

Regulation of PLK4 levels and activity to ensure centriole number control

Dissertation presented to obtain a Ph.D degree in Cellular Biology

User-centered design of the interface prototype of a business intelligence mobile application

Dissertação para obtenção do Grau de Mestre em Engenharia e Gestão Industrial

A cross-cultural study on the effect of decimal separator on price perception

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

Old cellulose for new multifunctional networks

Dissertação para obtenção do Grau de Doutor em Ciência e Engenharia de Materiais

Cellulose micro/nano fibers conformational effects probed by nematic liquid crystal droplets

Probing micro-/nano-sized surface conformations, which are ubiquitous in biological systems, by using liquid crystal droplets, which change their ordering and optical appearance in response to the presence of more than ten times smaller cellulose based micro/nano fibers, might find new uses in a range of biological environments and sensors. Previous studies indicate that electrospun micro/nano cellulosic fibers produced from liquid crystalline solutions could present a twisted form [1]. In this work, we study the structures of nematic liquid crystal droplets threaded by cellulose fibers prepared from liquid crystalline and isotropic solutions as well as droplets pierced by spider-made fibers [2]. Planar anchoring at the fibers and planar and homeotropic at the drop surfaces allowed probing cellulose fibers different helical structures as well as aligned filaments.

Transcriptional regulation of the mannosyltransferase-encoding gene pigm in inherited glycosylphosphatidylinositol (GPI) deficiency

RESUMO:O glicosilfosfatidilinositol (GPI) é um complexo glicolipídico utlizado por dezenas de proteínas, o qual medeia a sua ancoragem à superfície da célula. Proteínas de superfície celular ancoradas a GPI apresentam várias funções essenciais para a manutenção celular. A deficiência na síntese de GPI é o que caracteriza principalmente a deficiência hereditária em GPI, um grupo de doenças autossómicas raras que resultam de mutações nos genes PIGA, PIGL, PIGM, PIGV, PIGN, PIGO e PIGT, os quais sao indispensáveis para a biossíntese do GPI. Uma mutação pontual no motivo rico em GC -270 no promotor de PIGM impede a ligação do factor de transcrição (FT) Sp1 à sua sequência de reconhecimento, impondo a compactação da cromatina, associada à hipoacetilação de histonas, e consequentemente, impedindo a transcrição de PIGM. Desta forma, a adição da primeira manose ao GPI é comprometida, a síntese de GPI diminui assim como as proteínas ligadas a GPI à superficie das células. Pacientes com Deficiência Hereditária em GPI-associada a PIGM apresentam trombose e epilesia, e ausência de hemólise intravascular e anemia, sendo que estas duas últimas características definem a Hemoglobinúria Paroxística Nocturna (HPN), uma doença rara causada por mutações no gene PIGA. Embora a mutação que causa IGD seja constitutiva e esteja presente em todos os tecidos, o grau de deficiência em GPI varia entre células do mesmo tecido e entre células de tecidos diferentes. Por exemplo nos granulócitos e linfócitos B a deficiência em GPI é muito acentuada mas nos linfócitos T, fibroblastos, plaquetas e eritrócitos é aproximadamente normal, daí a ausência de hemólise intravascular. Os eventos transcricionais que estão na base da expressão diferencial da âncora GPI nas células hematopoiéticas são desconhecidos e constituem o objectivo geral desta tese. Em primeiro lugar, os resultados demonstraram que os níveis de PIGM mRNA variam entre células primárias hematopoiéticas normais. Adicionalmente, a configuração dos nucleossomas no promotor de PIGM é mais compacta em células B do que em células eritróides e tal está correlacionado com os níveis de expressão de PIGM, isto é, inferior nas células B. A presença de vários motivos de ligação para o FT específico da linhagem megacariocítica-eritróide GATA-1 no promotor de PIGM sugeriu que GATA-1 desempenha um papel regulador na sua transcrição. Os resultados mostraram que muito possivelmente GATA-1 desempenha um papel repressor em vez de activador da expressão de PIGM. Resultados preliminares sugerem que KLF1, um factor de transcrição restritamente eritróide, regula a transcrição de PIGM independentemente do motivo -270GC. Em segundo lugar, a investigação do papel dos FTs Sp demonstrou que Sp1 medeia directamente a transcrição de PIGM em ambas as células B e eritróide. Curiosamente, ao contrário do que acontece nas células B, em que a transcrição de PIGM requer a ligação do FT geral Sp1 ao motivo -270GC, nas células eritróides Sp1 regula a transcrição de PIGM ao ligar-se a montante e não ao motivo -270GC. Para além disso, demonstrou-se que Sp2 não é um regulador directo da transcrição de PIGM quer nas células B quer nas células eritróides. Estes resultados explicam a ausência de hemólise intravascular nos doentes com IGD associada a PIGM, uma das principais características que define a HPN. Por último, resultados preliminares mostraram que a repressão da transcrição de PIGM devida à mutação patogénica -270C>G está associada com a diminuição da frequência de interacções genómicas em cis entre PIGM e os seus genes “vizinhos”, sugerindo adicionalmente que a regulação de PIGM e desses genes é partilhada. No seu conjunto, os resultados apresentados nesta tese contribuem para o conhecimento do controlo transcricional de um gene housekeeping, específico-detecido, por meio de FTs genéricos e específicos de linhagem.-------------ABSTRACTC: Glycosylphosphatidylinositol (GPI) is a complex glycolipid used by dozens of proteins for cell surface anchoring. GPI-anchored proteins have various functions that are essential for the cellular maintenance. Defective GPI biosynthesis is the hallmark of inherited GPI deficiency (IGD), a group of rare autosomal diseases caused by mutations in PIGA, PIGL, PIGM, PIGV, PIGN, PIGO and PIGT, all genes indispensable for GPI biosynthesis. A point mutation in the -270GC-rich box in the core promoter of PIGM disrupts binding of the transcription factor (TF) Sp1 to it, imposing nucleosome compaction associated with histone hypoacetylation, thus abrogating transcription of PIGM. As a consequence of PIGM transcriptional repression, addition of the first mannose residue onto the GPI core and thus GPI production are impaired; and expression of GPI-anchored proteins on the surface of cells is severely impaired. Patients with PIGM-associated IGD suffer from life-threatening thrombosis and epilepsy but not intravascular haemolysis and anaemia, two defining features of paroxysmal nocturnal haemoglobinuria (PNH), a rare disease caused by somatic mutations in PIGA. Although the disease-causing mutation in IGD is constitutional and present in all tissues, the degree of GPI deficiency is variable and differs between cells of the same and of different tissues. Accordingly, GPI deficiency is severe in granulocytes and B cells but mild in T cells, fibroblasts, platelets and erythrocytes, hence the lack of intravascular haemolysis.The transcriptional events underlying differential expression of GPI in the haematopoietic cells of PIG-M-associated IGD are not known and constitute the general aim of this thesis. Firstly, I found that PIGM mRNA levels are variable amongst normal primary haematopoietic cells. In addition, the nucleosome configuration in the promoter of PIGM is more compacted in B cells than in erythroid cells and this correlated with the levels of PIGM mRNA expression, i.e., lower in B cells. The presence of several binding sites for GATA-1, a mega-erythroid lineage-specific transcription factor (TF), at the PIGM promoter suggested that GATA-1 has a role on PIGM transcription. My results showed that GATA-1 in erythroid cells is most likely a repressor rather than an activator of PIGM expression. Preliminary data suggested that KLF1, an erythroid-specific TF, regulates PIGM transcription but independently of the -270GC motif. Secondly, investigation of the role of the Sp TFs showed that Sp1 directly mediates PIGM transcriptional regulation in both B and erythroid cells. However, unlike in B cells in which active PIGM transcription requires binding of the generic TF Sp1 to the -270GC-rich box, in erythroid cells, Sp1 regulates PIGM transcription by binding upstream of but not to the -270GC-rich motif. Additionally, I showed that Sp2 is not a direct regulator of PIGM transcription in B and erythroid cells. These findings explain lack of intravascular haemolysis in PIGM-associated IGD, a defining feature of PNH. Lastly, preliminary work shows that transcriptional repression of PIG-M by the pathogenic -270C>G mutation is associated with reduced frequency of in cis genomic interactions between PIGM and its neighbouring genes, suggesting a shared regulatory link between these genes and PIGM. Altogether, the results presented in this thesis provide novel insights into tissuespecific transcriptional control of a housekeeping gene by lineage-specific and generic TFs.