Design, implementation, and performance of a distributed and scalable sensor system for critical distance measurements in the CMS detector at LHC

The “CMS Safety Closing Sensors System” (SCSS, or CSS for brevity) is a remote monitoring system design to control safety clearance and tight mechanical movements of parts of the CMS detector, especially during CMS assembly phases. We present the different systems that makes SCSS: its sensor technologies, the readout system, the data acquisition and control software. We also report on calibration and installation details, which determine the resolution and limits of the system. We present as well our experience from the operation of the system and the analysis of the data collected since 2008. Special emphasis is given to study positioning reproducibility during detector assembly and understanding how the magnetic fields influence the detector structure.

Produção de matrizes porosas 3D baseadas em réplicas invertidas de cristais coloidais

A Engenharia de Tecidos surge da necessidade recorrente de regenerar ou recriar órgãos e tecidos danificados devido a vários tipos de trauma. A carência de funcionalidades resultante pode ser resolvida através da implantação de substitutos bio-sintéticos. O presente trabalho consiste na produção de matrizes porosas 3D baseadas em réplicas invertidas de cristais coloidais com futura aplicação em substituintes ósseos sintéticos para fraturas de não-união. O substituinte ósseo consiste numa estrutura denominada Inverse colloidal crystal (ICC), em que a sua organização singular resulta numa homogénea proliferação celular e num aumento das propriedades mecânicas, quando comparada com outros substituintes. O primeiro passo para a obtenção desta estrutura é a produção de microesferas de poliestireno, por uma técnica baseada em microfluídica. Posteriormente as microesferas são empacotadas resultando numa estrutura coesa com ligações entre microesferas vizinhas. O preenchimento dos espaços vazios entre microesferas pelo biomaterial pretendido e posterior remoção das microesferas dá origem à estrutura porosa do ICC. ICCs poliméricos (ϕCs = 1,00) e compósitos (ϕCs = 0,86 e ϕHA = 0,14; ϕCs = 0,67 e ϕHA = 0,33; ϕCs = ϕHA = 0,50) são produzidos e as suas propriedades mecânicas são testadas através de ensaios de compressão e comparadas com outros substituintes sintéticos. Para avaliação do comportamento dos materiais em contacto com meio biológico, foram realizados testes de citotoxicidade que revelaram uma viabilidade celular acima dos 80% em todos os ICCs.

Development of 3D in vitro models for prediction of hepatic metabolism and toxicity

The development of human cell models that recapitulate hepatic functionality allows the study of metabolic pathways involved in toxicity and disease. The increased biological relevance, cost-effectiveness and high-throughput of cell models can contribute to increase the efficiency of drug development in the pharmaceutical industry. Recapitulation of liver functionality in vitro requires the development of advanced culture strategies to mimic in vivo complexity, such as 3D culture, co-cultures or biomaterials. However, complex 3D models are typically associated with poor robustness, limited scalability and compatibility with screening methods. In this work, several strategies were used to develop highly functional and reproducible spheroid-based in vitro models of human hepatocytes and HepaRG cells using stirred culture systems. In chapter 2, the isolation of human hepatocytes from resected liver tissue was implemented and a liver tissue perfusion method was optimized towards the improvement of hepatocyte isolation and aggregation efficiency, resulting in an isolation protocol compatible with 3D culture. In chapter 3, human hepatocytes were co-cultivated with mesenchymal stem cells (MSC) and the phenotype of both cell types was characterized, showing that MSC acquire a supportive stromal function and hepatocytes retain differentiated hepatic functions, stability of drug metabolism enzymes and higher viability in co-cultures. In chapter 4, a 3D alginate microencapsulation strategy for the differentiation of HepaRG cells was evaluated and compared with the standard 2D DMSO-dependent differentiation, yielding higher differentiation efficiency, comparable levels of drug metabolism activity and significantly improved biosynthetic activity. The work developed in this thesis provides novel strategies for 3D culture of human hepatic cell models, which are reproducible, scalable and compatible with screening platforms. The phenotypic and functional characterization of the in vitro systems performed contributes to the state of the art of human hepatic cell models and can be applied to the improvement of pre-clinical drug development efficiency of the process, model disease and ultimately, development of cell-based therapeutic strategies for liver failure.

Produção e caracterização de espumas 3D obtidas por electrofiação para aplicação em engenharia de tecidos

A produção de estruturas tridimensionais poliméricas tem sido foco de estudo por parte da Engenharia de Células e Tecidos, pelo que mimetizam melhor as condições in vivo dos tecidos. A conjugação das propriedades eléctricas com arquitectura 3D permite uma regeneração tecidual mais eficaz. Desta forma este estudo incidiu na construção de scaffolds, que conjugasse as propriedades mecânicas, eléctricas e biológicas num só suporte. O processo utilizado para produção de scaffolds baseou-se na electrofiação de soluções poliméricas de PCL (8% m/m) com incorporação de óxido de grafeno em diferentes concentrações: 0.01%, 0.1% e 0.25% (m/V). Foram avaliados os parâmetros de electrofiação que permitiram a organização tridimensional. A composição química e a morfologia das membranas foram avaliadas por FTIR-ATR e por microscopia electrónica de varrimento (MEV), respectivamente. Através de ensaios de tracção e de permeabilidade estudou-se a influência de óido de grafeno na matriz polimérica. Foram feitas experiências de redução de óxido de grafeno nas fibras electrofiadas, tanto nas membranas como das espumas, através do uso de vapores de hidrazina. Este mecanismo mostrou-se ineficaz, uma vez que afectou a sua morfologia. As espumas foram avaliadas quanto à sua bioactividade e propriedades mecânicas (ensaios de compressão). Também foram realizados testes de viabilidade celular nas membranas e de adesão celular nas espumas, de forma a avaliar o seu potencial para aplicação biomédica. Os resultados destes ensaios revelaram que óxido de grafeno não apresenta efeitos citotóxicos para o organismo e a sua presença promove a adesão celular ao scaffold.

Jogo 3D online para reabilitação de pacientes afásicos

Esta plataforma foi projetada como auxílio complementar ao processo de reabilitação de doentes afásicos lusófonos. Uma gama de exercícios são disponibilizados de forma a induzir diferentes estímulos (compreensão escrita e auditiva e expressão escrita) sendo a grande maioria destes realizados dentro de um ambiente virtual em três dimensões onde o utilizador (dependendo da tarefa) pode interagir com objetos presentes dentro de uma casa. A principal particularidade desta plataforma reside no facto desta estar alojada online, dispensando instalações e permitindo um acompanhamento mais próximo por parte do terapeuta da fala do progresso feito pelo paciente. A ferramenta desenvolvida está disponível para visualização e teste no endereço www.weblisling.net.

Antioxidant extraction process for Andean Oca by a photodiode array detector using response surface methodology

Application of Experimental Design techniques has proven to be essential in various research fields, due to its statistical capability of processing the effect of interactions among independent variables, known as factors, in a system’s response. Advantages of this methodology can be summarized in more resource and time efficient experimentations while providing more accurate results. This research emphasizes the quantification of 4 antioxidants extraction, at two different concentration, prepared according to an experimental procedure and measured by a Photodiode Array Detector. Experimental planning was made following a Central Composite Design, which is a type of DoE that allows to consider the quadratic component in Response Surfaces, a component that includes pure curvature studies on the model produced. This work was executed with the intention of analyzing responses, peak areas obtained from chromatograms plotted by the Detector’s system, and comprehending if the factors considered – acquired from an extensive literary review – produced the expected effect in response. Completion of this work will allow to take conclusions regarding what factors should be considered for the optimization studies of antioxidants extraction in a Oca (Oxalis tuberosa) matrix.

Building 3D City Models: Testing and Comparing Laser Scanning and Low-Cost UAV Data Using FOSS Technologies

Contém resumo

Development of human central nervous system 3D in vitro models for preclinical research

Neurological disorders are a major concern in modern societies, with increasing prevalence mainly related with the higher life expectancy. Most of the current available therapeutic options can only control and ameliorate the patients’ symptoms, often be-coming refractory over time. Therapeutic breakthroughs and advances have been hampered by the lack of accurate central nervous system (CNS) models. The develop-ment of these models allows the study of the disease onset/progression mechanisms and the preclinical evaluation of novel therapeutics. This has traditionally relied on genetically engineered animal models that often diverge considerably from the human phenotype (developmentally, anatomically and physiologically) and 2D in vitro cell models, which fail to recapitulate the characteristics of the target tissue (cell-cell and cell-matrix interactions, cell polarity). The in vitro recapitulation of CNS phenotypic and functional features requires the implementation of advanced culture strategies that enable to mimic the in vivo struc-tural and molecular complexity. Models based on differentiation of human neural stem cells (hNSC) in 3D cultures have great potential as complementary tools in preclinical research, bridging the gap between human clinical studies and animal models. This thesis aimed at the development of novel human 3D in vitro CNS models by integrat-ing agitation-based culture systems and a wide array of characterization tools. Neural differentiation of hNSC as 3D neurospheres was explored in Chapter 2. Here, it was demonstrated that human midbrain-derived neural progenitor cells from fetal origin (hmNPC) can generate complex tissue-like structures containing functional dopaminergic neurons, as well as astrocytes and oligodendrocytes. Chapter 3 focused on the development of cellular characterization assays for cell aggregates based on light-sheet fluorescence imaging systems, which resulted in increased spatial resolu-tion both for fixed samples or live imaging. The applicability of the developed human 3D cell model for preclinical research was explored in Chapter 4, evaluating the poten-tial of a viral vector candidate for gene therapy. The efficacy and safety of helper-dependent CAV-2 (hd-CAV-2) for gene delivery in human neurons was evaluated, demonstrating increased neuronal tropism, efficient transgene expression and minimal toxicity. The potential of human 3D in vitro CNS models to mimic brain functions was further addressed in Chapter 5. Exploring the use of 13C-labeled substrates and Nucle-ar Magnetic Resonance (NMR) spectroscopy tools, neural metabolic signatures were evaluated showing lineage-specific metabolic specialization and establishment of neu-ron-astrocytic shuttles upon differentiation. Chapter 6 focused on transferring the knowledge and strategies described in the previous chapters for the implementation of a scalable and robust process for the 3D differentiation of hNSC derived from human induced pluripotent stem cells (hiPSC). Here, software-controlled perfusion stirred-tank bioreactors were used as technological system to sustain cell aggregation and dif-ferentiation. The work developed in this thesis provides practical and versatile new in vitro ap-proaches to model the human brain. Furthermore, the culture strategies described herein can be further extended to other sources of neural phenotypes, including pa-tient-derived hiPSC. The combination of this 3D culture strategy with the implemented characterization methods represents a powerful complementary tool applicable in the drug discovery, toxicology and disease modeling.

PHB-HV 3D Scaffold supports osteoblast growth

Bone tissue engineering requires a biocompatible scaffold that supports cell growth and enhances the native repair process. Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHB-HV) is a biodegradable 3D scaffold with 88.1 â 0.3% porosity and pore size of 163.5 â 0.1 mm. Previous studies demonstrated the potential of PHB-HV as a scaffold in spinal cord repair. The aim of this study was to evaluate PHB-HV as a scaffold for bone regeneration by assessing the cytocompatability of this scaffold.

Cell encapsulated hydrogel microspheres as "building blocks" for producing 3D constructs

Cell encapsulation within hydrogel microspheres shows great promise in the field of tissue engineering and regenerative medicine (TERM). However, the assembling of microspheres as building blocks to produce complex tissues is a hard task because of their inability to place along length scales in space. We propose a proof-of-concept strategy to produce 3D constructs using cell encapsulated as building blocks by perfusion based LbL technique. This technique exploits the â bindingâ potential of multilayers apart from coating

Evaluating ubiquitous computing environments using 3D simulation

Human activity is very dynamic and subtle, and most physical environments are also highly dynamic and support a vast range of social practices that do not map directly into any immediate ubiquitous computing functionally. Identifying what is valuable to people is very hard and obviously leads to great uncertainty regarding the type of support needed and the type of resources needed to create such support. We have addressed the issues of system development through the adoption of a Crowdsourced software development model [13]. We have designed and developed Anywhere places, an open and flexible system support infrastructure for Ubiquitous Computing that is based on a balanced combination between global services and applications and situated devices. Evaluation, however, is still an open problem. The characteristics of ubiquitous computing environments make their evaluation very complex: there are no globally accepted metrics and it is very difficult to evaluate large-scale and long-term environments in real contexts. In this paper, we describe a first proposal of an hybrid 3D simulated prototype of Anywhere places that combines simulated and real components to generate a mixed reality which can be used to assess the envisaged ubiquitous computing environments [17].

Development of a new 3D OpenFOAM® solver to model the cooling stage in profile extrusion

[Excerpt] The advantages resulting from the use of numerical modelling tools to support the design of processing equipment are almost consensual. The design of calibration systems in profile extrusion is not an exception . H owever , the complex geome tries and heat exchange phenomena involved in this process require the use of numerical solvers able to model the heat exchange in more than one domain ( calibrator and polymer), the compatibilization of the heat transfer at the profile - calibrator interface and with the ability to deal with complex geometries. The combination of all these features is usually hard to find in commercial software. Moreover , the dimension of the meshes required to ob tain accurate results, result in computational times prohibitive for industrial application. (...)

Jet energy measurement and its systematic uncertainty in proton-proton collisions at s√=7 TeV with the ATLAS detector

The jet energy scale (JES) and its systematic uncertainty are determined for jets measured with the ATLAS detector using proton–proton collision data with a centre-of-mass energy of s√=7 TeV corresponding to an integrated luminosity of 4.7 fb −1 . Jets are reconstructed from energy deposits forming topological clusters of calorimeter cells using the anti- kt algorithm with distance parameters R=0.4 or R=0.6 , and are calibrated using MC simulations. A residual JES correction is applied to account for differences between data and MC simulations. This correction and its systematic uncertainty are estimated using a combination of in situ techniques exploiting the transverse momentum balance between a jet and a reference object such as a photon or a Z boson, for 20≤pjetT<1000 GeV and pseudorapidities |η|<4.5 . The effect of multiple proton–proton interactions is corrected for, and an uncertainty is evaluated using in situ techniques. The smallest JES uncertainty of less than 1 % is found in the central calorimeter region ( |η|<1.2 ) for jets with 55≤pjetT<500 GeV . For central jets at lower pT , the uncertainty is about 3 %. A consistent JES estimate is found using measurements of the calorimeter response of single hadrons in proton–proton collisions and test-beam data, which also provide the estimate for pjetT>1 TeV. The calibration of forward jets is derived from dijet pT balance measurements. The resulting uncertainty reaches its largest value of 6 % for low- pT jets at |η|=4.5 . Additional JES uncertainties due to specific event topologies, such as close-by jets or selections of event samples with an enhanced content of jets originating from light quarks or gluons, are also discussed. The magnitude of these uncertainties depends on the event sample used in a given physics analysis, but typically amounts to 0.5–3 %.

Centrality and rapidity dependence of inclusive jet production in sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Measurements of the centrality and rapidity dependence of inclusive jet production in sNN−−−√=5.02 TeV proton--lead (p+Pb) collisions and the jet cross-section in s√=2.76 TeV proton--proton collisions are presented. These quantities are measured in datasets corresponding to an integrated luminosity of 27.8 nb−1 and 4.0 pb−1, respectively, recorded with the ATLAS detector at the Large Hadron Collider in 2013. The p+Pb collision centrality was characterised using the total transverse energy measured in the pseudorapidity interval −4.9<η<−3.2 in the direction of the lead beam. Results are presented for the double-differential per-collision yields as a function of jet rapidity and transverse momentum (pT) for minimum-bias and centrality-selected p+Pb collisions, and are compared to the jet rate from the geometric expectation. The total jet yield in minimum-bias events is slightly enhanced above the expectation in a pT-dependent manner but is consistent with the expectation within uncertainties. The ratios of jet spectra from different centrality selections show a strong modification of jet production at all pT at forward rapidities and for large pT at mid-rapidity, which manifests as a suppression of the jet yield in central events and an enhancement in peripheral events. These effects imply that the factorisation between hard and soft processes is violated at an unexpected level in proton--nucleus collisions. Furthermore, the modifications at forward rapidities are found to be a function of the total jet energy only, implying that the violations may have a simple dependence on the hard parton--parton kinematics.

Differential top-antitop cross-section measurements as a function of observables constructed from final-state particles using pp collisions at s√=7 TeV in the ATLAS detector

Various differential cross-sections are measured in top-quark pair (tt¯) events produced in proton--proton collisions at a centre-of-mass energy of s√=7 TeV at the LHC with the ATLAS detector. These differential cross-sections are presented in a data set corresponding to an integrated luminosity of 4.6 fb−1. The differential cross-sections are presented in terms of kinematic variables of a top-quark proxy referred to as the pseudo-top-quark whose dependence on theoretical models is minimal. The pseudo-top-quark can be defined in terms of either reconstructed detector objects or stable particles in an analogous way. The measurements are performed on tt¯ events in the lepton+jets channel, requiring exactly one charged lepton and at least four jets with at least two of them tagged as originating from a b-quark. The hadronic and leptonic pseudo-top-quarks are defined via the leptonic or hadronic decay mode of the W boson produced by the top-quark decay in events with a single charged lepton.The cross-section is measured as a function of the transverse momentum and rapidity of both the hadronic and leptonic pseudo-top-quark as well as the transverse momentum, rapidity and invariant mass of the pseudo-top-quark pair system. The measurements are corrected for detector effects and are presented within a kinematic range that closely matches the detector acceptance. Differential cross-section measurements of the pseudo-top-quark variables are compared with several Monte Carlo models that implement next-to-leading order or leading-order multi-leg matrix-element calculations.