Investigating the Diabetic Brain: The Effects of Pioglitazone and Insulin on the Cellular Processes and Pathology of Alzheimer's Disease

Alzheimer’s disease (AD) is the sixth leading cause of death in the US. Some researchers refer to AD as “Type III Diabetes” because of reported glucose metabolism dysfunction. Preclinical studies suggest increasing insulin decreases AD pathology, although the mechanism remains unclear. To sensitize insulin signaling, this study activated Peroxisome Proliferator-Activated Receptor Gamma using intranasal co-administration of pioglitazone (PGZ) and insulin. This method targeted the site of action to reduce peripheral effects and to maximize impact in transgenic mice expressing AD pathology. Data from GC-MS fluxomics analysis suggested that PGZ+Insulin increased glucose metabolism in the brain. Immunohistochemistry with relevant antibodies was used to identify AD pathological markers in the subiculum, indicating that PGZ+Insulin decreased pathology compared to Insulin and Saline. This suggests that increasing glucose uptake in the brain alleviated AD pathology, further clarifying the role of insulin signaling in AD pathology.Gemstone

Strategic Management of Resources for International Business Operations in Small Consulting Firms - People, Processes and Tools in Managing International operations

Research on strategic management of resources for small consulting firms which are international or planning to operate internationally is scarce or not existing at all. It is however important to start generating the theories that will support managers in their decision making and planning. This thesis investigates how do small management consulting firms manage their internal and external resources while operating in international markets. Throughout the study, aspects related to internal and external resources management as well as management strategies in these firms have been examined in relations to firm’s internationalisation activities. A qualitative analysis was carried out whereby four small consulting firms in Export Management Consulting, Integration Services Consulting-, Software Development Consulting- and Business Solutions Consulting companies were interviewed. In order to generate the holistic understanding of the study, the thesis writer selected Value Enhanced Collaborative Working (VECW) model as an analysis framework. The model focuses on people, processes and tools as key elements that small consulting firms consider when thinking about managing their international operations. The findings of the thesis reveal that, internal and external resources in the interviewed consulting firms are viewed similarly, but managed differently depending on the nature and size of the firm. Firm’s management strategies concentrate on the adequate utilisation of the employees' motivation and experiences, effective stakeholders' management, various administrative evaluation processes and tools, the ability to realise useful networks, constant improvement through employee trainings, employees and customers’ feedbacks as well as enhanced freedom in order to support employees’ creativity. Further research to examine functional administrative tools and tools that small consulting firms could use to assess their resource capabilities when planning to become international would benefit the smaller businesses in terms of resources management and certainty in planning.

Development of business processes and sales reporting - Case recovered paper

The purpose of this research is to discover development points for business processes and sales reporting in the recovered paper sourcing organization. The processes under development are both sales and sourcing processes that were determined by the commissioning company. All of these processes have in common that there are used sales orders to organize the money flows correctly. Although the main objective is to source only recovered paper, the sourcing also brings by-products that cannot be utilized and are thus sold. As the purpose of the sales function is to only support the sourcing strategy, it should be organized as efficiently as possible. Investigating the current status of the processes and finding development points help in building proposals for enhanced process descriptions. In order that sales function could be analyzed, should the sales reporting be accurate and present the needed key figures. The current status of the processes as well as the possible problems and development ideas were researched with the help of interviews. Best practices could also be brought from other business lines in the commissioning company. The theory part was build according to relevant literature and scientific articles. The research indicates, that processes have shaped differently in sourcing organization’s business units. Local infrastructure and legislation sets certain limitations to the sourcing of recovered paper, and these circumstances cannot be changed. Customer-supplier power relations also affect to the formulation of business processes. In order to steer the processes, there has to be more internal controls. Still, the enterprise resource planning system also sets boundaries how the processes can be made more efficient.

Forward - Green Virtual Enterprises and Their Breeding Environments: Sustainable Manufacturing, Logistics and Consumption

Part 9: Innovation Networks

Phylogeography of the Atlanto-Mediterranean sea cucumber Holothuria (Holothuria) mammata: the combined effects of historical processes and current oceanographical pattern

We assessed the genetic structure of populations of the widely distributed sea cucumber Holothuria (Holothuria) mammata Grube, 1840, and investigated the effects of marine barriers to gene flow and historical processes. Several potential genetic breaks were considered, which would separate the Atlantic and Mediterranean basins, the isolated Macaronesian Islands from the other locations analysed, and the Western Mediterranean and Aegean Sea (Eastern Mediterranean). We analysed mitochondrial 16S and COI gene sequences from 177 individuals from four Atlantic locations and four Mediterranean locations. Haplotype diversity was high (H = 0.9307 for 16S and 0.9203 for COI), and the haplotypes were closely related (p = 0.0058 for 16S and 0.0071 for COI). The lowest genetic diversities were found in the Aegean Sea population. Our results showed that the COI gene was more variable and more useful for the detection of population structure than the 16S gene. The distribution of mtDNA haplotypes, the pairwise FST values and the results of exact tests and AMOVA revealed: (i) a significant genetic break between the population in the Aegean Sea and those in the other locations, as supported by both mitochondrial genes, and (ii) weak differentiation of the Canary and Azores Islands from the other populations; however, the populations from the Macaronesian Islands, Algarve and West Mediterranean could be considered to be a panmictic metapopulation. Isolation by distance was not identified in H. (H.) mammata. Historical events behind the observed findings, together with the current oceanographic patterns, were proposed and discussed as the main factors that determine the population structure and genetic signature of H. (H.) mammata

Volcanic processes and human exposure as elements to build a risk model for Volcan de Fuego, Guatemala

The activity of Fuego volcano during the 1999 - 2013 eruptive episode is studied through field, remote sensing and observatory records. Mapping of the deposits allows quantifying the erupted volumes and areas affected by the largest eruptions during this period. A wide range of volcanic processes results in a diversity of products and associated deposits, including minor airfall tephra, rockfall avalanches, lava flows, and pyroclastic flows. The activity can be characterized by long term, low level background activity, and sporadic larger explosive eruptions. Although the background activity erupts lava and ash at a low rate (~ 0.1 m3/s), the persistence of such activity over time results in a significant contribution (~ 30%) to the eruption budget during the studied period. Larger eruptions produced the majority of the volume of products during the studied period, mainly during three large events (May 21, 1999, June 29, 2003, and September 13, 2012), mostly in the form of pyroclastic flows. A total volume of ~ 1.4 x 108 m3 was estimated from the mapped deposits and the estimated background eruption rate. Posterior remobilization of pyroclastic flow material by stream erosion in the highly confined Barranca channels leads to lahar generation, either by normal rainfall, or by extreme rainfall events. A reassessment of the types of products and volumes erupted during the decade of 1970's allows comparing the activity happening since 1999 with the older activity, and suggests that many of the eruptive phenomena at Fuego may have similar mechanisms, despite the differences in scale between. The deposits of large pyroclastic flows erupted during the 1970's are remarkably similar in appearance to the deposit of pyroclastic flows from the 1999 - 2013 period, despite their much larger volume; this is also the case for prehistoric eruptions. Radiocarbon dating of pyroclastic flow deposits suggests that Fuego has produced large eruptions many times during the last ~ 2 ka, including larger eruptions during the last 500 years, which has important hazard implications. A survey was conducted among the local residents living near to the volcano, about their expectations of possible future crises. The results show that people are aware of the risk they could face in case of a large eruption, and therefore they are willing to evacuate in such case. However, their decision to evacuate may also be influenced by the conditions in which the evacuation could take place. If the evacuation represents a potential loss of their livelihood or property they will be more hesitant to leave their villages during a large eruption. The prospect of facing hardship conditions during the evacuation and in the shelters may further cause reluctance to evacuate. A short discussion on some of the issues regarding risk assessment and management through an early warning system is presented in the last chapter.

The Impact of Social Comparison Processes on Hoped-For Possible Selves, Self-Regulatory Processes, and Mental Health Outcomes in Young Adults

In exploring the role of social influences in the development of the self, the current study evaluated whether young adults use social comparisons in developing their hoped-for possible selves and, if so, whether their developmental process correlates with self-regulatory processes and positive mental health outcomes. The current study found the following: (1) the domains of hoped-for possible selves among young adults were related to the gender of the social comparison target, (2) the direction of young adults’ social comparison processes (upward or downward) did not significantly influence self-regulatory processes (self-efficacy and outcome expectancy) toward achieving their hoped-for possible selves, (3) strong masculine gender identification related to greater outcome expectancy, while strong feminine gender identification related to both greater self-efficacy and outcome expectancy, and (4) self-efficacy related to less state anxiety, trait anxiety, and depression, while outcome expectancy related only to less trait anxiety. Males and females were found to use traditional gender role identification in forming their hoped-for possible selves.

Systems 1 and 2 thinking processes and cognitive reflection testing in medical students

Background: Diagnostic decision-making is made through a combination of Systems 1 (intuition or pattern-recognition) and Systems 2 (analytic) thinking. The purpose of this study was to use the Cognitive Reflection Test (CRT) to evaluate and compare the level of Systems 1 and 2 thinking among medical students in pre-clinical and clinical programs. Methods: The CRT is a three-question test designed to measure the ability of respondents to activate metacognitive processes and switch to System 2 (analytic) thinking where System 1 (intuitive) thinking would lead them astray. Each CRT question has a correct analytical (System 2) answer and an incorrect intuitive (System 1) answer. A group of medical students in Years 2 & 3 (pre-clinical) and Years 4 (in clinical practice) of a 5-year medical degree were studied. Results: Ten percent (13/128) of students had the intuitive answers to the three questions (suggesting they generally relied on System 1 thinking) while almost half (44%) answered all three correctly (indicating full analytical, System 2 thinking). Only 3-13% had incorrect answers (i.e. that were neither the analytical nor the intuitive responses). Non-native English speaking students (n = 11) had a lower mean number of correct answers compared to native English speakers (n = 117: 1.0 s 2.12 respectfully: p < 0.01). As students progressed through questions 1 to 3, the percentage of correct System 2 answers increased and the percentage of intuitive answers decreased in both the pre-clinical and clinical students. Conclusions: Up to half of the medical students demonstrated full or partial reliance on System 1 (intuitive) thinking in response to these analytical questions. While their CRT performance has no claims to make as to their future expertise as clinicians, the test may be used in helping students to understand the importance of awareness and regulation of their thinking processes in clinical practice.

Powertrain Architectures and Technologies for New Emission and Fuel Consumption Standards

New powertrain design is highly influenced by CO2 and pollutant limits defined by legislations, the demand of fuel economy in for real conditions, high performances and acceptable cost. To reach the requirements coming from both end-users and legislations, several powertrain architectures and engine technologies are possible (e.g. SI or CI engines), with many new technologies, new fuels, and different degree of electrification. The benefits and costs given by the possible architectures and technology mix must be accurately evaluated by means of objective procedures and tools in order to choose among the best alternatives. This work presents a basic design methodology and a comparison at concept level of the main powertrain architectures and technologies that are currently being developed, considering technical benefits and their cost effectiveness. The analysis is carried out on the basis of studies from the technical literature, integrating missing data with evaluations performed by means of powertrain-vehicle simplified models, considering the most important powertrain architectures. Technology pathways for passenger cars up to 2025 and beyond have been defined. After that, with support of more detailed models and experimentations, the investigation has been focused on the more promising technologies to improve internal combustion engine, such as: water injection, low temperature combustions and heat recovery systems.

Exploiting the environment for structural health monitoring: Strategies, algorithms, and technologies

A densely built environment is a complex system of infrastructure, nature, and people closely interconnected and interacting. Vehicles, public transport, weather action, and sports activities constitute a manifold set of excitation and degradation sources for civil structures. In this context, operators should consider different factors in a holistic approach for assessing the structural health state. Vibration-based structural health monitoring (SHM) has demonstrated great potential as a decision-supporting tool to schedule maintenance interventions. However, most excitation sources are considered an issue for practical SHM applications since traditional methods are typically based on strict assumptions on input stationarity. Last-generation low-cost sensors present limitations related to a modest sensitivity and high noise floor compared to traditional instrumentation. If these devices are used for SHM in urban scenarios, short vibration recordings collected during high-intensity events and vehicle passage may be the only available datasets with a sufficient signal-to-noise ratio. While researchers have spent efforts to mitigate the effects of short-term phenomena in vibration-based SHM, the ultimate goal of this thesis is to exploit them and obtain valuable information on the structural health state. First, this thesis proposes strategies and algorithms for smart sensors operating individually or in a distributed computing framework to identify damage-sensitive features based on instantaneous modal parameters and influence lines. Ordinary traffic and people activities become essential sources of excitation, while human-powered vehicles, instrumented with smartphones, take the role of roving sensors in crowdsourced monitoring strategies. The technical and computational apparatus is optimized using in-memory computing technologies. Moreover, identifying additional local features can be particularly useful to support the damage assessment of complex structures. Thereby, smart coatings are studied to enable the self-sensing properties of ordinary structural elements. In this context, a machine-learning-aided tomography method is proposed to interpret the data provided by a nanocomposite paint interrogated electrically.

Acculturation processes and intergroup relations of adolescents in multicultural societies: the role of family, peer, and school contexts

Acculturation processes and intergroup relations lie at the heart of developing more inclusive social attitudes. Notably, these endeavors are embedded in primary socialization contexts of adolescents, as indicated by developmental and socio-psychological theoretical models reviewed in Chapter 1. Hence, this dissertation investigated how adolescents' acculturation processes and intergroup contact are embedded in family, peer, and school contexts. Accordingly, Chapter 2 indicated the combined effects of the perceived parents' acculturation orientations and classmates' acculturation preferences on adolescents' own acculturation orientations in Italy and Turkey. Chapter 3 showed that adolescents could be classified into one of four latent growth trajectory classes (i.e., ethnic-oriented, national-oriented, dual, and marginalized identities), which could be predicted by social identification with family and classmates. Chapter 4 highlighted that adolescents' cross-ethnic friendships mediated the positive associations of parents' cross-ethnic friendships with adolescents' psychological and social adjustment beyond the positive relationships between parents' and adolescents' friendships. Multiple studies conducted in Chapter 5 confirmed that a newly developed questionnaire (i.e., ICIS-Short Version) is a reliable tool to measure positive and negative contact among ethnic minority and majority adolescents. Chapter 6 revealed that teachers' equal treatment increased positive and decreased negative contact among ethnic minority and majority adolescents. Moreover, Chapter 7 indicated that adolescents’ positive and negative contact in the school context were related over time to higher corresponding positive and negative contact in out-of-school contexts and vice versa, while their positive contact in the school context was linked over time to lower levels of negative contact in the out-of-school contexts. Eventually, Chapter 8 strived to summarize and discuss these findings in light of social inclusivity. Overall, this dissertation tapped into the paramount importance of family, peer, and school contexts to provide a unique resource for adolescents to cope with acculturative challenges that go beyond the normative developmental tasks of adolescence.

Data-driven and data-oriented methods for materials science and technologies

The discovery of new materials and their functions has always been a fundamental component of technological progress. Nowadays, the quest for new materials is stronger than ever: sustainability, medicine, robotics and electronics are all key assets which depend on the ability to create specifically tailored materials. However, designing materials with desired properties is a difficult task, and the complexity of the discipline makes it difficult to identify general criteria. While scientists developed a set of best practices (often based on experience and expertise), this is still a trial-and-error process. This becomes even more complex when dealing with advanced functional materials. Their properties depend on structural and morphological features, which in turn depend on fabrication procedures and environment, and subtle alterations leads to dramatically different results. Because of this, materials modeling and design is one of the most prolific research fields. Many techniques and instruments are continuously developed to enable new possibilities, both in the experimental and computational realms. Scientists strive to enforce cutting-edge technologies in order to make progress. However, the field is strongly affected by unorganized file management, proliferation of custom data formats and storage procedures, both in experimental and computational research. Results are difficult to find, interpret and re-use, and a huge amount of time is spent interpreting and re-organizing data. This also strongly limit the application of data-driven and machine learning techniques. This work introduces possible solutions to the problems described above. Specifically, it talks about developing features for specific classes of advanced materials and use them to train machine learning models and accelerate computational predictions for molecular compounds; developing method for organizing non homogeneous materials data; automate the process of using devices simulations to train machine learning models; dealing with scattered experimental data and use them to discover new patterns.

Gestão de processos e operações

Esta dissertação de Mestrado pretende, numa primeira fase, identificar as condições gerais e os pressupostos da aplicação da ferramenta Análise do Valor (AV) e integrá-la nos Sistemas de Gestão da Qualidade. Pretende-se demonstrar a técnica e aumentar o seu conhecimento, assim como as várias abordagens do processo, as vantagens e os constrangimentos no seu uso, conduzir à ideia que poderá ser útil proceder a uma análise organizada e sistemática dos produtos/serviços existentes nas organizações, abrindo a hipótese a novas soluções para o produto/serviço de mais fácil produção/realização e ensaio ao menor custo. É realçada a importância do conceito da Análise do Valor demonstrando que se pode tornar numa ferramenta eficaz na melhoria dos produtos mas também de processos de fabrico e até em processos administrativos. Sendo a Qualidade entendida como um conjunto de características que um bem, produto ou serviço possui que o tornam apto para satisfazer na plenitude uma dada necessidade do seu utilizador, este trabalho também faz a ligação com os Sistemas de Gestão da Qualidade comparando dois referenciais, a Norma NP EN 12973 e a ISO 9001:2008. Numa segunda fase é realizada uma profunda abordagem à ferramenta QFD – Quality Function Deployment – como uma técnica complementar à aplicação prática da técnica AV e é realizado um estudo a um serviço pós-venda que inclui muitos dos seus conceitos e princípios. O trabalho foi realizado na empresa onde sou colaborador há cerca de 10 anos exercendo o cargo de “Service Manager Press/Post Press” ao departamento de serviço técnico e apoio ao cliente. Foi muito útil a demonstração prática para entendimento das dificuldades sentidas e dos obstáculos a ultrapassar. O trabalho termina com as conclusões do caso prático e as conclusões gerais, mencionando as definições dos aceleradores / obstáculos da aplicação da AV.

Aplicação da técnica Análise do Valor (AV) a um determinado porduto/serviço

Mestrado em Engenharia Mecânica - Gestão de Processos e Operações

Projeto da estrutura e sistema de movimentação robotizado de linha automática de corte de chapa

Os robots de movimentação de chapa são bastantes úteis para as empresas de metalomecânica. De facto, cada vez mais existem máquinas de corte por jato de água, laser ou outros processos, nos quais os robots apresentam um papel importante na carga e descarga do material. O trabalho realizado apresenta novas soluções aos sistemas de movimentação existentes no mercado, e permite reduzir os custos na movimentação do material. Este projeto serve essencialmente para chapas em trajetória retilínea, e efetuar o seu levantamento do equipamento e deposição em estrutura de suporte (ou viceversa). A vantagem a ter em conta é a diminuição dos custos de movimentação do material. Neste trabalho apresentou-se a metodologia de dimensionamento de um robot automatizado que transporta chapas com um peso máximo de 3500 kg, tendo por base as normas do EC3-P1.8 e o Método de Elementos Finitos (MEF). No decurso do projeto foram abordadas os seguintes temas: Abordagem inicial da geometria através do Solidworks; Dimensionamento da estrutura por software de Elementos Finitos, o Solidworks; Dimensionamento das correntes, carretos/discos ou coroas e rolamentos; Dimensionamento e seleção dos moto-redutores, bomba de vácuo e ventosas; Cálculo das solicitações em cada membro da estrutura por software de análise estrutural, o Multiframe3D, e respetivo dimensionamento das ligações aparafusadas e soldadas; Elaboração dos desenhos de projeto finais, processos de fabrico e custos; Dimensionamento do acionamento, MG e disposição dos dispositivos no quadro elétrico. Como conclusão refere-se que se conseguiu realizar o projeto e obter uma solução final otimizada, com a ajuda de ferramentas importantes, como sejam o MEF, resultando num equipamento cujas solicitações para a estrutura e sistema de movimentação foram otimizadas, resultando num equipamento eficiente, robusto, seguro e de custo reduzido.