Effects of a Shortage of Imiglucerase on Three Patients with Type I Gaucher Disease

Background: Children with Gaucher disease type I (GD1) are usually treated with enzyme replacement therapy (ERT) at a dose of 30-60U/Kg/2W. Recently, due to an acute shortage supply of imiglucerase, a reduced dose or a reduced infusion frequency was recommended. Objective: To evaluate the effects of a reduced infusion frequency of imiglucerase over 15 months of follow-up. Patients and Methods: Three patients (1M:2F) were treated with ERT since a median age of 7 years (range 5-12). Only one had bone crisis and Erlenmeyer deformations. Median duration of treatment before dose reduction was 3 years (range 1-8). ERT resulted in total regression of symptoms, normalization of hematological parameters and progressive improvement of chitotriosidase in all patients. In August 2009 infusion schedule was changed from a media 45U/Kg every two weeks to every four weeks. Results: All patients remained asymptomatic and with no major change on hematological parameters except for the patient with bone crisis who presented subnormal platelet count. All patients showed an upward trend in chitotriosidase values. Comments: Although a longer follow-up is needed, is probable that even children completely stabilized can probably not be kept on lower doses even though the reduction of frequency of the infusions represent a lower social burden.

Análise de estabilidade e fundações de equipamentos de sinalização vertical rodoviária

O presente projeto foi realizado no âmbito da unidade curricular Dissertação/Estágio/Projeto, e desenvolve um estudo sobre as estruturas porticadas de sinalização vertical em Autoestradas, ao nível da estrutura metálica e das fundações, com o objetivo de analisar três casos diferentes com características distintas. Dois dos casos em estudo são modelos comuns que se encontram facilmente nas autoestradas. O terceiro tem uma configuração diferente, mais gravoso que o habitual. Com estes três casos obtém-se um estudo completo e abrangente deste tipo de estrutura porticada. Ao longo do projeto é seguida a norma EC3 (Eurocódigo 3 – Projeto de estruturas de aço). Dimensionaram-se as estruturas utilizando secções tubulares, mas é também realizado o dimensionamento de uma solução estrutural alternativa recorrendo a perfis laminados I ou H. As estruturas foram modeladas com recurso ao software de cálculo Autodesk Robot Structural Analysis Professional, obtendo-se os esforços e deformações nos vários pontos da estrutura, que permitem realizar o dimensionamento manual das secções dos perfis estruturais, chumbadouros, chapas de fundação e fundações propriamente ditas. Na parte final do projeto apresenta-se uma apreciação global do mesmo, conclusões gerais sobre os resultados obtidos e possíveis desenvolvimentos futuros.

Image processing for displacement measurements

Since the invention of photography humans have been using images to capture, store and analyse the act that they are interested in. With the developments in this field, assisted by better computers, it is possible to use image processing technology as an accurate method of analysis and measurement. Image processing's principal qualities are flexibility, adaptability and the ability to easily and quickly process a large amount of information. Successful examples of applications can be seen in several areas of human life, such as biomedical, industry, surveillance, military and mapping. This is so true that there are several Nobel prizes related to imaging. The accurate measurement of deformations, displacements, strain fields and surface defects are challenging in many material tests in Civil Engineering because traditionally these measurements require complex and expensive equipment, plus time consuming calibration. Image processing can be an inexpensive and effective tool for load displacement measurements. Using an adequate image acquisition system and taking advantage of the computation power of modern computers it is possible to accurately measure very small displacements with high precision. On the market there are already several commercial software packages. However they are commercialized at high cost. In this work block-matching algorithms will be used in order to compare the results from image processing with the data obtained with physical transducers during laboratory load tests. In order to test the proposed solutions several load tests were carried out in partnership with researchers from the Civil Engineering Department at Universidade Nova de Lisboa (UNL).

The role of arl13b in cilia length regulation and in zebrafish development

RESUMO: Arl13b é uma importante proteína ciliar, presente em cílios primários e cílios móveis. Ratinhos mutantes para Arl13b têm comprimento dos cílios reduzido e defeitos nos B-túbulos dos cílios. Como consequência destes fenótipos, deficiências na Arl13b originam, em modelos animais, várias doenças congénitas, incluindo problemas no estabelecimento do eixo esquerda-direita, malformações cerebrais e deformações corporais. Nos seres humanos, deficiências na Arl13b levam a uma doença crónica congénita chamada Síndrome de Joubert. Por outro lado, a sobreexpressão de Arl13b origina cílios mais longos, no entanto existe uma ausência da caracterização dos fenótipos celulares e durante o desenvolvimento embrionário. Neste trabalho, quisemos explorar o efeito da sobre-expressão de Arl13b em embriões de peixezebra. Descobrimos que, ao nível ciliar, a sobre-expressão de Arl13b nas células aumenta o comprimento ciliar em cílios primários e móveis, no entanto, a esses cílios falta adequada acetilação da alfa-tubulina no citoesqueleto feito por microtúbulos. Os nossos resultados mostraram que esse efeito é específico de Arl13b sobre-expressão e quando se manipularam as enzimas responsáveis pela acetilação (Mec17) e pela de-acetilação (HDAC6) encontrámos uma sinergia potencial com ambas. Testámos ainda, que o aumento no comprimento ciliar não estava causalmente relacionado com a falta de acetilação, ou seja, os cílios com menos acetilação não eram necessariamente os mais longos. Também mostrámos que a sobre-expressão de Arl13b é capaz de restaurar o comprimento dos cílios em mutantes com cílios curtos e como isso pode ser explorado para um futuro potencial papel terapêutico para Arl13b. Em seguida, foi avaliado o impacto do aumento da quantidade de Arl13b no desenvolvimento embrionário do peixe-zebra. Observou-se que a sobre-expressão de Arl13b apresentava fenótipos muito fracos, quando comparados com a perda de função dos mutantes de Arl13b. Focados no inesperado fenótipo leve no estabelecimento do eixo esquerda-direita abordámos a questão através do estabelecimento de uma colaboração com matemáticos, descobrimos que os cílios mais longos que potencialmente têm a capacidade de movimentar mais fluido são atenuados por amplitudes de batimento menores, e, como resultado, estes longos cílios não prejudicam o movimento do fluido e consequentemente não afetam o estabelecimento dos padrões de esquerda-direita. Sugerimos assim que a Arl13b é um regulador chave, do comprimento ciliar. Descobrimos uma nova interação com as enzimas de acetilação/de-acetilação e levantamos novas hipóteses quanto aos mecanismos moleculares da função da Arl13b. Propomos um novo modelo para o mecanismo molecular da Arl13b na regulação do comprimento dos cílios onde podemos integrar os nossos resultados com os relatados na literatura. Este trabalho adiciona mais conhecimento para o mecanismo de ação da Arl13b e, portanto, fornece uma importante contribuição para o campo da investigação em cílios.---------------------------------------------------------------------------------------------------------------------- ABSTRACT: Arl13b is an important ciliary protein, present in primary and motile cilia. arl13b-/- mouse mutants have reduced cilia length and cilia B-tubule defects. As a consequence of these phenotypes, Arl13b loss of function animal models suffer from several congenital disorders including left-right problems, brain malformations and body deformations. In humans Arl13b depletion leads to a congenital chronic disease called Joubert Syndrome. On the other hand, overexpressing Arl13b leads to longer cilia but the characterization of the cellular and developmental phenotypes was missing. In this work we explore the effect of Arl13b overexpression in zebrafish embryos. We found that, at the ciliary level, Arl13b overexpression from 1 cell stage produces longer primary and motile cilia, but these cilia lack proper alpha tubulin acetylation of their microtubule cytoskeleton. Our results showed that this effect is specific from Arl13b overexpression and when we manipulated the enzymes responsible for acetylation, Mec17, and de-acetylation, HDAC6, we found a potential synergy of both mec17 knockdown and HDAC6 activity with Arl13b overexpression. We tested that the ciliary increase in length was not causally related to the lack of acetylation, meaning the more de-acetylated cilia were not necessarily the longer ones. We also showed that Arl13b overexpression is able to restore cilia length in short cilia mutants and how that may be explored to a potential future therapeutic role for Arl13b. Next, we evaluated the impact of increasing the amount of Arl13b in zebrafish embryonic development. We observed that Arl13b overexpression presented very mild phenotypes when compared to the loss of function mutants. We focused on the unexpected left-right mild phenotype and by establishing a mathematical modeling collaboration, we found out that the longer cilia generated force was attenuated by smaller beating amplitudes, and as a result, these long cilia were not impairing the cilia generated flow and the establishment of left-right patterning. We suggest that Arl13b is one key cilia length regulator. We disclosed a novel interaction with the acetylation / de-acetylation enzymes and raised new hypothesis as to the mechanisms of Arl13b function. We propose a new model for the Arl13b molecular mechanism of cilia length regulation where we integrate our findings with those reported in the literature. This work adds more knowledge to the Arl13b mechanism of action and therefore provides an important contribution to the cilia research field.

Análisis mecánico de albañilería arqueológica de adobe bajo cargas de compresión uniaxial: El caso de Huaca de la Luna

This article presents an experimental and numerical study for the mechanical characterization under uniaxial compressive loading of the adobe masonry of one of the most emblematic archaeological complex in Peru, 'Huaca de la Luna' (100-650AD). Compression tests of prisms were carried out with original material brought to the laboratory. For measuring local deformations in the tests, displacement transducers were used which were complemented by a digital image correlation system which allowed a better understanding of the failure mechanism. The tests were then numerically simulated by modelling the masonry as a continuum media. Several approaches were considered concerning the geometrical modelling, namely 2D and 3D simplified models, and 3D refined models based on a photogrammetric reconstruction. The results showed a good approximation between the numerical prediction and the experimental response in all cases. However, the 3D models with irregular geometries seem to reproduce better the cracking pattern observed in the tests.

High performance electromechanical actuators based on ionic liquid/poly(vinylidene fluoride)

Due to the increasing need of low voltage actuators, independent from electrochemical processes, electroactive actuators based on poly(vinylidene fluoride) composites with 10, 25 and 40 % of 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, [C2mim] [NTf2], ionic liquid are prepared by solvent casting and melting. We show that the charge structure of [C2mim] [NTf2] induces the complete piezoelectric -phase crystallization of the PVDF within the composite and decreases its crystallinity fraction significantly. [C2mim] [NTf2] also works as a plasticizer of PVDF, reducing the elastic modulus down to 12 % of the initial value. Moreover, the composites show significant displacement and bending under applied voltages of 2, 5 and 10 Vpp. The displacement and bending of the composite membranes are also evaluated as a function of [C2mim] [NTf2] content and sample thickness. Increasing amounts of ionic liquid result in larger deformations independently of the applied voltage.

Assessment of the mechanical performance of recycled unbound materials for pavement subbase layers

The cyclic load triaxial test is a laboratory test that allows studying the mechanical behaviour of unbound granular materials used in base/subbase layers of road pavements. The resilient modulus and permanent strains are required as inputs in structural pavement design. This paper presents some results obtained for recycled materials (crushed concrete aggregate and blended crushed waste aggregate), with a view to promoting their use in pavement structures. Results relating to a reference material (limestone) are also presented, for comparison. All the test results discussed in this paper were obtained in variable cyclic radial pressure (VCP) tests. The tests performed (VCP) aim to study the influence of water content on the resilient modulus of recycled materials, as well as on the resistance to permanent deformation. Using the experimental data as a basis, further modelling work was carried out to establish the stresses developing in base/capping layers in typical Belgian road pavements. These numerical results allow to propose some simplifications of the stress paths applied in the testing procedures and to establish a new test protocol that also considers compaction during construction works. The results of this research work provide an excellent set of findings for the mechanical characterization of unbound base materials through the cyclic triaxial test, and contribute to a better understanding and correct application of recycled materials under geotechnical engineering background

Quantum field theory approach to the optical conductivity of strained and deformed graphene

The computation of the optical conductivity of strained and deformed graphene is discussed within the framework of quantum field theory in curved spaces. The analytical solutions of the Dirac equation in an arbitrary static background geometry for one dimensional periodic deformations are computed, together with the corresponding Dirac propagator. Analytical expressions are given for the optical conductivity of strained and deformed graphene associated with both intra and interbrand transitions. The special case of small deformations is discussed and the result compared to the prediction of the tight-binding model.

Nonlinear behavior of gelatin networks reveals a hierarchical structure

We investigate the strain hardening behavior of various gelatin networks-namely physical gelatin gel, chemically cross-linked gelatin gel, and a hybrid gel made of a combination of the former two-under large shear deformations using the pre-stress, strain ramp, and large amplitude oscillations shear protocols. Further, the internal structures of physical gelatin gels and chemically cross-linked gelatin gels were characterized by small angle neutron scattering (SANS) to enable their internal structures to be correlated with their nonlinear rheology. The Kratky plots of SANS data demonstrate the presence of small cross-linked aggregates within the chemically cross-linked network whereas, in the physical gelatin gels, a relatively homogeneous structure is observed. Through model fitting to the scattering data, we were able to obtain structural parameters, such as the correlation length (ξ), the cross-sectional polymer chain radius (Rc) and the fractal dimension (df) of the gel networks. The fractal dimension df obtained from the SANS data of the physical and chemically cross-linked gels is 1.31 and 1.53, respectively. These values are in excellent agreement with the ones obtained from a generalized nonlinear elastic theory that has been used to fit the stress-strain curves. The chemical cross-linking that generates coils and aggregates hinders the free stretching of the triple helix bundles in the physical gels.

Análise estrutural e dimensionamento de estruturas de membrana

Dissertação de mestrado integrado em Engenharia Civil

A multi–physics approach applied to masonry structures with non–hydraulic lime mortars

Tese de Doutoramento em Engenharia Civil (área de especialização em Engenharia de Estruturas).

Исследование деформаций земли, регистрируемых кварцевым экстензометром, вызванных локальными флюктуациями атмосферного давления

დედამიწის მყარ ტანში მიმოქცევითი მოვლენების შესასწავლად გამოყენებული ექსტენზომეტრული დაკვირვებების შედეგები შესაძლებელია გამოყენებულ იქნეს დედამიწის ქერქის ნელი და სეისმური დეფორმაციების გასაზომად. დედამიწის ზედაპირის საუკუნოვანი, მიმოქცევითი და სეისმური დეფორმაციების დაკვირვებისათვის საქართველოს მეცნიერთა აკადემიის გეოფიზიკის ინსტიტუტის მიწისქვეშა მიმოქცევით ლაბორატორიაში გამოიყენება ორკომპონენტიანი კვარცის ექსტენზომეტრი. ნაშრომში მოყვანილი მაგალითები გვიჩვენებენ რომ ექსტენზომეტრის დრეიფი კარგ კორელაციაშია ატმოსფერული წნევის არაპერიოდულ ვარიაციებთან.

Terrestrial laser scanning for landslides deformation monitoring

Within last few years a new type of instruments called Terrestrial Laser Scanners (TLS) entered to the commercial market. These devices brought a possibility to obtain completely new type of spatial, three dimensional data describing the object of interest. TLS instruments are generating a type of data that needs a special treatment. Appearance of this technique made possible to monitor deformations of very large objects, like investigated here landslides, with new quality level. This change is visible especially with relation to the size and number of the details that can be observed with this new method. Taking into account this context presented here work is oriented on recognition and characterization of raw data received from the TLS instruments as well as processing phases, tools and techniques to do them. Main objective are definition and recognition of the problems related with usage of the TLS data, characterization of the quality single point generated by TLS, description and investigation of the TLS processing approach for landslides deformation measurements allowing to obtain 3D deformation characteristic and finally validation of the obtained results. The above objectives are based on the bibliography studies and research work followed by several experiments that will prove the conclusions.

The Teggiolo zone: a key to the Helvetic-Penninic connection (stratigraphy and tectonics in the Val Bavona, Ticino, Central Alps)

The Teggiolo zone is the sedimentary cover of the Antigorio nappe, one of the lowest tectonic units of the Penninic Central Alps. Detailed mapping, stratigraphic and structural analyses, and comparisons with less metamorphic series in several well-studied domains of the Alps, provide a new stratigraphic interpretation. The Teggiolo zone is comprised of several sedimentary cycles, separated by erosive surfaces and large stratigraphic gaps, which cover the time span from Triassic to Eocene. At Mid-Jurassic times it appears as an uplifted, partially emergent block, marking the southern limit of the main Helvetic basin (the Limiting South-Helvetic Rise LSHR). The main mass of the Teggiolo calcschists, whose base truncates the Triassic-Jurassic cycles and can erode the Antigorio basement, consists of fine-grained clastic sediments analogous to the deep-water flyschoid deposits of Late Cretaceous to Eocene age in the North-Penninic (or Valais s.l.) basins. Thus the Antigorio-Teggiolo domain occupies a crucial paleogeographic position, on the boundary between the Helvetic and Penninic realms: from Triassic to Early Cretaceous its affinity is with the Helvetic; at the end of Cretaceous it is incorporated into the North-Penninic basins. An unexpected result is the discovery of the important role played by complex formations of wildflysch type at the top of the Teggiolo zone. They contain blocks of various sizes. According to their nature, three different associations are distinguished that have specific vertical and lateral distributions. These blocks give clues to the existence of territories that have disappeared from the present-day level of observation and impose constraints on the kinematics of early folding and embryonic nappe emplacement. Tectonics produced several phases of superimposed folds and schistosities, more in the metasediments than in the gneissic basement. Older deformations that predate the amplification of the frontal hinge of the nappe generated the dominant schistosity and the km-wide Vanzèla isoclinal fold.

Complex landslide behaviour and structural controlled by the structures: A 3D conceptual model example of Åknes rockslide, Norway

Åknes is an active complex large rockslide of approximately 30?40 Mm3 located within the Proterozoic gneisses of western Norway. The observed surface displacements indicate that this rockslide is divided into several blocks moving in different directions at velocities of between 3 and 10 cm year?1. Because of regional safety issues and economic interests this rockslide has been extensively monitored since 2004. The understanding of the deformation mechanism is crucial for the implementation of a viable monitoring system. Detailed field investigations and the analysis of a digital elevation model (DEM) indicate that the movements and the block geometry are controlled by the main schistosity (S1) in gneisses, folds, joints and regional faults. Such complex slope deformations use pre-existing structures, but also result in new failure surfaces and deformation zones, like preferential rupture in fold-hinge zones. Our interpretation provides a consistent conceptual three-dimensional (3D) model for the movements measured by various methods that is crucial for numerical stability modelling. In addition, this reinterpretation of the morphology confirms that in the past several rockslides occurred from the Åknes slope. They may be related to scars propagating along the vertical foliation in folds hinges. Finally, a model of the evolution of the Åknes slope is presented.